key: cord- -dyjpfvvf authors: gardner, anthony luzzatto title: foreign aid and humanitarian assistance date: - - journal: stars with stripes doi: . / - - - - _ sha: doc_id: cord_uid: dyjpfvvf together the us and eu provide two-thirds of global humanitarian assistance for the alleviation of emergencies arising from natural and man-made disasters and % of global foreign aid for longer-term development assistance programs. it is therefore vital that they continue their close partnership to ensure their dollars and euros are spent as effectively as possible in an era of increasingly tight budgetary constraints. the outbreak of ebola in west africa in is a good example of how the us and the eu successfully addressed (albeit belatedly) a major health crisis that could have turned into a global pandemic. in many areas in africa, they are collaborating closely on the foundation of shared priorities, including on food security, resilience, and electrification. they are also among the largest donors to the global fund to fight hiv/aids, tuberculosis, and malaria and to the global alliance for vaccines and immunisation. us and the eu to undertake repeatedly costly emergency measures to respond to disaster. indeed, some short-term solutions can be counterproductive: the dumping of food aid in local markets to address urgent food needs, for example, can undermine the ability of poor countries to develop sustainable farms and functioning markets. during my diplomatic post, i witnessed first-hand how the us and the eu work together in several areas of both humanitarian assistance and foreign aid. there are notable differences in how they pursue their agenda, including their degree of willingness to partner with the private sector and the military, but these have not prevented frequent and deep collaboration. in the fall of , my wife and i found ourselves in a large, abandoned field in downtown brussels to visit the training site of médecins sans frontières (msf), also known as doctors without borders, a non-profit and non-governmental international medical organization of french origin best known for its projects in conflict zones and in countries affected by endemic diseases. we were impressed by the explanations about how the modular kits in the large containers lying in a storeroom could be rapidly shipped to humanitarian disaster zones around the world and assembled on site within hours to provide functioning power generators, water purification, lodging for aid workers, medical treatment, and waste disposal. the logistical know-how and deep experience of msf made it the first, and sometimes most significant, responder to major medical emergencies. although the logistics were interesting, what really grabbed our attention was the sight of several of the organization's instructors training staff on how to put on and take off protective clothing to avoid contamination. the eight-piece clothing, entirely covering the human body, looked like a space suit but was more ominous because it was being worn on land to respond to the outbreak of the ebola virus in west africa in march . the scene reminded me of outbreak, a film released in starring many hollywood icons, including dustin hoffman, kevin spacey and morgan freeman. the film was about the public panic and response by military and civilian agencies in the wake of a fictional outbreak of an ebola-like virus in zaire, and later in a small town in california. a reallife outbreak of the ebola virus was ongoing in zaire when the film was released. the film contained exaggerations to enhance its shock value but wasn't too far from fact. we were transfixed by the demonstration. our guide told us that medical staff could only wear the space suit for several hours in real-world conditions on the ground because temperatures inside the suits can easily reach up to degrees centigrade (nearly degrees fahrenheit). the suit takes a long time to put on in order to ensure that the body is entirely protected from contamination. taking off soiled suits requires even longer (up to twenty minutes) because of a meticulous and rigorous twelve-step process that healthcare workers must repeat three or more times per day. it was clear that there is no margin for error. we were also shown disinfection routines, sample containment wards for infected patients, and the incineration units for soiled clothing and used equipment. during the first months following the detection of an ebola outbreak in march, msf was the most effective response of the developed world. msf remained on the ground throughout the crisis, even when staff members contracted the virus and died. on top of this risk of infection, msf workers also faced angry opposition from villagers suspecting that the treatment facilities were spreading the disease. msf had to close one facility in southern guinea after being attacked in april by a stone-throwing mob. villagers later killed eight african members of an msf team trying to raise awareness of ebola in the region. despite these risks, msf had nearly international workers and local employees fighting the outbreak by the time my wife and i were touring the facility in brussels. by contrast, the eu and its member states struggled to come up with a coherent and decisive response in the early months of the crisis. this was disappointing in light of the eu's deep partnership with africa, europe's proximity to the continent and greater vulnerability to a spread of ebola, and the history of france and britain as former colonial powers in guinea and sierra leone. similarly, the initial us response was slow and focused on domestic preparations. it took until the fall of for the us and the eu to respond in a coordinated fashion. our joint response should have been more effective. as i toured the msf facility i recalled how, as a young director for european affairs in the white house in - , i had played a role in the us-eu new transatlantic agenda that had specifically flagged the importance of transatlantic cooperation on infectious diseases: we are committed to develop and implement an effective global early warning system and response network for new and re-emerging communicable diseases such as aids and the ebola virus, and to increase training and professional exchanges in this area. together, we call on other nations to join us in more effectively combating such diseases. we did not make as much progress on this key challenge as we would have liked in the subsequent twenty years. our msf guide explained that an ebola outbreak starts when a human has direct contact with the blood, body fluids, or organs of infected animals, such as bats, chimpanzees, monkeys, or gorillas. the transmission of the virus from that human to other humans occurs through personal direct contact either with the patient's blood or other body fluids (including sweat and saliva) or through contact with objects, such as needles and syringes, that contain these fluids. transmission of the virus often occurs through caregivers such as family members or medical personnel in homes or healthcare environments where infection-control practices are weak. ebola crises, such as the one in zaire that occurred when outbreak was playing in movie theaters, can be amplified by the transmission of the virus in overcrowded hospitals and burial practices in which highly infectious corpses are washed or touched by family and members of the community in a sign of love for the deceased. ebola is a disease from one of the deeper circles of dante's hell. fortunately, it is not transmitted through the air, like influenza or tuberculosis, or transmitted before symptoms appear, like measles or hiv. nonetheless, it can result in terrible consequences for its victims and can spread quickly if not brought under control. in its early phase, victims of ebola can be misdiagnosed because it is relatively rare and because some of the symptoms, including fever, fatigue, muscle pain, and headache, are difficult to distinguish from those of other infectious diseases, such as malaria and typhoid fever. victims often subsequently experience vomiting, diarrhea, rashes, and hemorrhages resulting in internal and/or external bleeding. the dysfunction or collapse of multiple body organs leads to severe injury and often death. the fatality rate varies from to %, depending on the strain. the ebola outbreak in west africa in was first reported by the world health organization on march in a remote, forested region of south-eastern guinea bordering liberia and sierra leone. multiple chains of transmission of the virus had gone unrecognized for months. by the end of the year, the virus had claimed lives and had infected , persons; by march , the numbers were dead and , sick; and by the time the crisis had been brought under control in march , the dead numbered , . the number of infections and deaths far exceeded those in approximately twenty previous outbreaks since the s in central and eastern africa; in each of those outbreaks, the number of reported cases never exceeded . there were many reasons for the severity of the crisis. like the remote areas of central and eastern africa where prior outbreaks occurred, the virus appeared in a remote area of guinea. normally, this might have helped contain the disease, but in an unfortunate twist of geographic fate the region lay at the junction of guinea with sierra leone and liberia where people regularly move across borders. the region's lack of rudimentary public health infrastructure, partly because of its recent history of civil war and violence, and its lack of experience with a previous outbreak of the virus compounded the problem. as the virus spread to urban areas and expanded into an epidemic, the number of cases quickly overwhelmed the capacity of diagnostic and other healthcare facilities. at the onset of the outbreak, there was a very small number of experienced healthcare workers to deal with it, including in europe and the united states. even at msf, involved in most of the prior outbreaks, there were only "veterans." medical teams were simply not prepared to deal with a disease that kills at least % of its patients and for which no treatments existed. had ebola been a first world disease, there would have been a vaccine. but there wasn't because, in the eyes of the major pharmaceutical companies, the numbers of patients are small, and nearly exclusively in the third world. the business case for the recovery of significant upfront research and production costs had simply not been present. some ebola treatment units (etus) were filled beyond capacity, requiring the facilities to turn away people suspected of having the disease, thereby fostering new chains of transmission. one of the critical factors in bringing an ebola outbreak under control-an exhaustive tracing of contacts between victims and others with whom they had been in contact-was absent. moreover, poor infection control in hospitals led to many infections and deaths among healthcare workers and a rapid collapse of the region's healthcare system. the control of other devastating viruses, such as malaria, and even the provision of routine medical services declined. i had seen reports from our embassies that people who collapsed from heart attacks were sometimes left to die because no one wanted to touch them for fear that they had contracted ebola. children started missing out on education because of school closures. generalized fear and even panic threatened to devastate the region's economies, especially by reducing agricultural output and trade, while driving up prices. my friend and former colleague samantha power, us ambassador to the united nations during president obama's second term, visited brussels several times to brief and coordinate with eu officials on the ebola crisis after her trips to the infected region. on one of those trips, she relayed reports that farming communities were "eating their seeds," indicating not only that current harvests were poor but warning that future harvests and even food security were in danger. a total collapse of civil society was imminent as governments lost control of the situation. in the early days of the crisis, the eu allocated extra emergency funding to msf and other humanitarian organizations, such as the red cross and red crescent, the international medical corps, save the children and the international rescue committee. the aid contributed to the faster deployment of doctors and nurses and the purchase of diagnostic equipment and medical supplies. disaster assistance response teams of the us agency for international development (usaid) and teams from the atlanta-based centers for disease control and protection (cdc) were deployed to the region to carry out an assessment of what needed to be done. the us airlifted significant amounts of personal protective gear, generators, and medical equipment. by early summer, it seemed that wiring funds and providing assistance from a distance would be enough as the number of reported cases leveled off and then dropped, suggesting the outbreak could be contained as in the previously reported outbreaks in africa since . instead, the virus spread. by late july it reached, for the first time in history, densely populated metropolitan areas, not only in the three countries of origin but further afield. a traveler with ebola had flown from monrovia, liberia, to lagos, nigeria, africa's most populous city (with million inhabitants) where he had contact with multiple people who later contracted the illness. a massive effort by the nigerian government, assisted by the cdc, managed to contain the outbreak to just cases in two cities. by early august, the world health organization categorized the outbreak as a "public health emergency of international concern," a declaration that caught media headlines and unlocked significant new funding. claus sorensen, an old friend and the director-general of european civil protection and humanitarian aid operations (echo), conceded that in an ebola crisis "speed is of the essence, and there is a feeling that all of us have been behind the curve." the decisive factor in galvanizing action in the eu and the us was a series of shocking announcements regarding the ebola infections outside africa. in late july and early august, two us citizens, including a doctor with samaritan's purse, were repatriated to atlanta, where they (successfully) underwent treatment for ebola in a specialized isolation ward in emory university hospital. they were the first two patients ever to receive such treatment in the united states. in early october, two spanish priests died in madrid after contracting the virus in sierra leone; a nurse who had treated them also tested positive (but later recovered), the first person to have been infected outside of west africa. shortly thereafter a liberian national who had recently returned from liberia to the united states died of ebola in a dallas hospital. the nurses who had cared for him contracted the virus but recovered. on top of the shock of ebola infections appearing in europe and the united states, public health authorities on both sides of the atlantic conducted modeling about the potential spread of the virus. the results were sobering: in september, the cdc estimated that approximately , ebola cases ( . million cases when corrected for under-reporting) could occur in west africa by january , , if approximately % of all persons with new cases were not effectively isolated. the world health organization projected that new ebola cases could reach , per week by december. when respondents to a telephone poll were asked in october whether they were concerned that there would be a large outbreak of ebola in the united states within the next months, % reported that they were "very" or "somewhat" concerned. the initial us response (before october) was largely domestic because the country was not prepared for an epidemic of this magnitude. when the crisis broke out, only one facility in the united states (the cdc laboratory in atlanta) was qualified to test for ebola and there were only three facilities that could treat ebola patients; by january there were laboratories in states that could do so and by october there were treatment centers in states. during that period, , healthcare workers received instruction on how to identify, isolate, diagnose, and care for patients under investigation for ebola. the cdc and customs and border protection implemented intensive screening of air passengers arriving from west africa. there was significant public support for cutting off all air links with west africa and quarantining anyone who had recently been in the region. while generalized measures of this kind were avoided, the defense department did impose a -day quarantine for all personnel returning from ebola-affected areas, regardless of risk, because of political rather than scientific considerations. the presidential commission established to review the government's response to the ebola crisis was scathing in its final report. it criticized federal, state, and local unpreparedness to cope with the threat of an epidemic and the government's focus on the political implications of public reactions rather than on the underlying health concerns. by the end of the year, the us government's response started shifting decisively toward attacking ebola at its source. president obama was clear about the stakes: this is an epidemic that is not just a threat to regional security -it's a potential threat to global security if these countries break down, if their economies break down, if people panic. that has profound effects on all of us, even if we are not directly contracting the disease. the united states and the eu (as well as its member states), together and in parallel, supported by the african union and several african countries, finally undertook a major and highly successful effort to bring the crisis under control. washington focused on liberia, while paris focused on guinea and london on sierra leone. speaking at the cdc in mid-september, president obama announced that the us military had recently dispatched personnel to monrovia to establish a base under the control of us africa command. its main objectives were to build etus, including new isolation spaces and more than beds, and to recruit and train more than medical personnel to staff them. the department of defense built seven mobile laboratories in west africa that cut turn-around times for testing blood samples from five to seven days to between three and five hours, thereby freeing up bed space in overcrowded clinics and hospitals. the uk and france quickly followed the us example with similar military missions of their own to sierra leone and guinea to build hospitals and diagnostic centers; our experts often singled out the uk effort as being rapid and effective in bringing down new infection rates. in addition to these efforts, thousands of cdc employees and government-supported civilians were deployed in all of west africa, partnering with national governments to train healthcare workers, treat patients, staff field laboratories, trace contacts of patients to identify chains of transmission, develop border and airport-screening programs, promote safe burials, and educate communities. the united states was to airlift more than metric tons of personal protective equipment and other medical and relief supplies during the subsequent months. in the fall of , the white house announced major efforts to accelerate the development of vaccines (to prevent new infections) and therapeutics (to treat those already infected). and in december the us congress overwhelmingly supported legislation providing $ . billion in emergency funding for the cdc and other health services, the state department, and usaid; much of this funding was earmarked for the prevention, detection, and response to the ebola crisis in west africa, as well for efforts to assist in the region's recovery. the eu made an important contribution as a coordinator and donor. the european centre for disease prevention and control, headquartered in sweden, coordinates the work of health experts in different countries but does not have its own emergency-response teams. similarly, eu member states, rather than the european commission, dispose of their own medical personnel, hospitals, labs, and stock of specialized equipment. but as the only european body with a global picture of the fast-moving epidemic, the european commission successfully played the role of "traffic cop" to ensure that europe's response was consistent and effective. that role included the identification of the type and destination of emergency supplies for west africa, providing a clearinghouse of information about the crisis and the disease, and the creation of a list of available member state assets relevant for the treatment of ebola in europe. the european commission also played a key role in identifying european assets and trained personnel that could be deployed for the medical evacuation of patients back to europe and in negotiating a us-eu agreement about when us and european patients could call on their respective emergency medivac "air bridges." ensuring that international healthcare workers could be airlifted to equipped facilities in europe within hours was critical to the ability of the us and eu to recruit such workers. in october, the eu appointed christos stylianides, commissioner for humanitarian aid and crisis management, as eu ebola coordinator to ensure that the eu institutions and member states acted in a coordinated manner with each other and with international partners. in addition to the directorate-general for humanitarian aid, other commission departments were involved in the response to the ebola crisis: these were principally the directorate-general for international cooperation and development (devco), the counterpart to usaid and responsible for foreign aid, and the european external action service (the eu's diplomatic service with delegations in most countries around the world). the role of other departments also had to be coordinated: the directorate-general for health identified facilities in member states that were willing and able to accept ebola patients; the directorate-general for internal affairs (including justice and law enforcement) coordinated entry and exit procedures at airports in case of travelers suspected of having ebola; and the directorategeneral for research worked to promote vaccines and therapies. the eu was also an important donor to help combat ebola in west africa. the european commission and eu member states contributed almost e billion (without counting the value of in-kind contributions from many member states such as personal protective equipment, vehicles, and field hospitals). of this total, the european commission contributed e million out of the eu budget for emergency measures, financial support for the african union's own medical mission to the region, and long-term relief (such as budgetary support for the restoration of vital public services and the strengthening of food security). moreover, the european commission announced substantial funding from the eu budget to promote projects on ebola research, including immediate largescale clinical trials of potential vaccines and tests of existing and novel compounds to treat ebola. the european commission also partnered with the european pharmaceutical industry in launching a e million longer-term research program involving clinical trials of new ebola vaccines, the development of fast diagnostic tests, and new approaches to manufacture, store and transport vaccines. in summary, while the us and eu were both slow in responding to the ebola crisis, by the fall of they had significantly scaled up their efforts and were working very closely together to provide an effective series of measures that brought the crisis under control by the summer of . the lessons learned from that dramatic experience-including european commission coordination of eu member state activities and intensive us-eu coordination to combat epidemics-are important for coping with future humanitarian disasters. the lessons enabled the us and eu to respond to an outbreak of ebola in the democratic republic of congo (drc) in may , the second worst in history and the longest and deadliest of the nation's nine previous outbreaks. us-eu cooperation will be equally important in dealing with the outbreak of coronavirus. while ebola and other epidemics are just one area where the us and eu have worked well in humanitarian assistance, they are emblematic of the many other examples of how they are indispensable partners in alleviating suffering around the globe. one example is their delivery of aid to those suffering from the syrian civil war that has displaced over million people and killed , . the war has been catastrophic, but it would have been far worse without us and eu efforts. under the eu's - multi-annual financial plan, the european commission's annual humanitarian assistance budget averaged e billion per year and is projected to rise under the - budget cycle. in addition to the formal budget, the eu has drawn from other sources to spend hundreds of millions of euros annually to respond to unforeseen events and major crises, including the humanitarian disaster caused by the syrian civil war and the refugee crisis in - . several eu member states-especially the uk, germany, and sweden-are generous donors of humanitarian assistance as well. together with the eu, they provide roughly the same amount of funding as the united states ($ billion per year as of ). us funding, largely administered through a specific bureau within usaid (the office of us foreign disaster assistance), has responded to the same emergencies as the eu-not only the ebola outbreak, but also the syrian civil war and many other crises concentrated in the middle east and africa. both the us and the eu contribute significant amounts through united nations agencies such as the un high commission for refugees, unicef, and other non-governmental organizations such as the world food program and the international red cross. the predominance of the us and the eu as humanitarian assistance actors means that their practices shape those of other donors, including states, ngos, and multilateral organizations. when we join forces to minimize overlaps or inconsistent approaches, we ensure that our dollars and euros have maximum impact, leading to real improvements in the lives of millions of people affected by humanitarian assistance. as one study rightly pointed out: failure by these two parties to enhance their cooperation…would result in additional, yet avoidable, human death and suffering…and could lead to increased insecurity and instability across the globe., threatening us and eu strategic interests. us administrations of both political parties have recognized the importance of this partnership and for good reason. the george h. w. bush administration launched an annual strategic dialogue on humanitarian assistance with the eu at senior levels in usaid, the state department and echo, supplemented with regular contacts on the ground among field officers. in the new transatlantic agenda concluded in under the clinton administration, the us and the eu set forth an extensive list of areas where they should work closely, including improving the effectiveness of international humanitarian relief agencies, and urged the creation of joint missions whenever possible, greater operational coordination, staff exchanges, and information sharing. close dialogue has continued since then, despite the turbulence of us-eu relations during the presidency of donald trump. the us and the eu provide an even larger share of total foreign aid than they provide of total humanitarian assistance. the united states is the largest single provider of foreign aid, accounting for one-quarter of the $ billion disbursed worldwide every year. but the eu, together with its member states (especially germany, the united kingdom, and france), provides over half the total foreign aid disbursed. while the us contribution appears generous, it represents only slightly more than % of the us federal budget and about . % of us gdp, far below the equivalent percentages of many eu member states. the us-eu partnership on foreign aid has worked well, in part because the two are the biggest players globally. an even bigger reason for the successful partnership is that they share values and objectives such as the promotion of human rights, democracy, good governance, gender equality, and open markets. nonetheless, their policies occasionally reflect different outlooks and priorities. us foreign aid policy is often shaped by national security concerns, especially during major wars, and devotes significant resources to military and non-military security assistance (concentrated in afghanistan, israel, egypt, and iraq). moreover, us foreign aid is sometimes used as a tool to open global markets to us exports and is often tied to the purchase of us the united nations has urged countries to spend at least . % of their gdp on foreign aid, a target met by sweden, luxembourg, norway, denmark, the netherlands, and the united kingdom. according to an opinion poll conducted in the united states in , americans on average think that % of the federal budget is spent on foreign aid; given this misconception, many believe that the us should reduce its spending (unlike their european counterparts who support giving generously). see bianca dijulio, jamie firth, and mollyann brodie, "data note: americans' views on the u.s. role in global health," kaiser family foundation, january , . https://www.kff.org/globalhealth-policy/poll-finding/data-note-americans-views-on-the-u-s-role-in-global-health/. goods and services (especially food). some us aid is explicitly made conditional on the recipients' agreement to take certain actions. for example, the millennium challenge corporation, a foreign aid agency established by but independent from the us government, provides large five-year grants to countries that meet certain political and economic criteria and sign up to "compacts" detailing the domestic policies they will pursue. by contrast, the eu's commitment to development assistance is grounded in a widely shared feeling among the european public that the eradication of extreme poverty is a moral obligation and an investment in europe's long-term security. unlike the united states, that has the luxury of large oceans on either side, europe is far more exposed to instability on its borders. without development assistance, significant migration flows into europe from northern africa and the eastern mediterranean are certain. while the eu's development assistance is not shaped by military considerations or the desire to promote exports, the eu has recently moved closer to the us view that aid should be subject to strict conditions about the behavior of recipients, especially their willingness to undertake economic reforms. most us presidents have considered foreign aid as an investment in global and us security and prosperity, and a significant pillar of us foreign policy, rather than a gift to undeserving foreign countries. president trump has departed from that consensus by considering foreign aid wasteful and ineffective unless given to allies. in his speech before the un general assembly, president trump made the latter point in stark terms: "moving forward, we are only going to give foreign aid to those who respect us and, frankly, are our friends." his white house now appears to see africa largely as a playground of big-power rivalry, where chinese and russian influence is on the rise. other than as a destination for growing us exports and investment, africa appears to be of little inherent interest. the president's budgets have regularly proposed massive cuts in foreign aid. his budget has called for % cuts in the foreign aid budget-a target that is not only immoral but geo-politically nonsensical in light of the growing influence of china and russia in africa and other parts of the developing world. fortunately, congress has maintained most of the programs, partly in sympathy with the argument that deploying diplomats and development experts today is cheaper than deploying troops tomorrow. in an open letter to congress in , more than retired admirals and generals argued cogently: we know from our service in uniform that many of the crises our nation faces do not have military solutions alone…[the] state department, usaid…and other development agencies are critical to preventing conflict and reducing the need to put our men and women in uniform in harm's way…the military will lead the fight against terrorism on the battlefield, but it needs strong civilian partners in the battle against the drivers of extremism -lack of opportunity, insecurity, injustice and hopelessness. as with humanitarian assistance, the new transatlantic agenda also tried to introduce greater structure around us-eu cooperation on foreign aid, especially in their joint efforts to "help developing countries by all appropriate means in their efforts towards political and economic reforms." but efforts at a structured dialogue suffered from disagreements in other areas and were only revived when the us and eu launched a development dialogue in . although the annual meetings at ministerial level have not always occurred as envisioned by the dialogue, regular meetings at senior levels and continuous technical exchanges between staff, at headquarters and especially in the field, have enabled the parties to exchange information on policies and programs, as well as to promote greater policy consensus and coordination. the us-eu annual summit in that i attended several weeks after i arrived in brussels issued an ambitious set of targets for the parties' development agenda. some of the objectives were aspirational, such as delivering on the "unfinished business" of the millennium development goals, a set of eight extremely ambitious international development goals for (including the eradication of extreme poverty and hunger) that had been established by the united nations in . these goals have been replaced by the un's global goals for sustainable development, an agenda of social and economic development objectives for that the us and the eu support. us-eu cooperation on foreign aid is not always easy because each party has different budgetary cycles, implementation systems, and measures to ensure accountability. much of the "real" day-to-day work occurs in the field in dozens of countries, making coordination from headquarters in washington and brussels rather complex. even when coordination is successful, moreover, it can be overtaken by fast-moving events. representatives of usaid often observed to me that they preferred to deal with eu member states-such as the uk, the netherlands, sweden, and denmark-because they were less bureaucratic and nimbler than the eu. nonetheless, the constant dialogue between the us and the eu has enhanced their mutual trust and the effectiveness of their foreign aid programs. one example is how each party has increasingly relied on the other's geographic expertise: usaid relies on france and the eu in francophone africa where the us has a relatively more modest presence; the eu relies on the united states in the horn of africa where the former lacks the latter's resources and expertise. during my diplomatic mission, usaid and devco evidenced their mutual trust and intent to specialize by signing an agreement enabling each to fund the other's projects. an important by-product of the us-eu dialogue on development is that it has forced each side to coordinate better among its own government departments. in the case of the eu, that means devco, the european external action service and also the directorate-general for neighbourhood and enlargement negotiations (that implements assistance programs in the western balkans, turkey, the former soviet union, and the maghreb). in the case of the united states, that means not only usaid, but also includes the state department and even the defense department, the department of health and human services, the us treasury, and the department of agriculture. this internal coordination can sometimes be more challenging than transatlantic coordination, as i witnessed many times. the us and the eu development dialogue has covered a wide range of topics. one of the areas of focus has been the challenge of how to improve the "resilience" of developing countries. in the development context "resilience" means the ability of people, households, communities, countries, and systems to mitigate, adapt to and recover from shocks and stresses in a manner that reduces chronic vulnerability and facilitates economic growth that is fairly distributed across society. resilience can be strengthened in many ways: for example, with cash transfer programs to provide a safety net to the poorest households in drought-prone areas; by vaccinating livestock and planting crops that are more resistant to pests and drought; through early warning systems and insurance against extreme weather, plagues, and earthquakes; and with budget support for countries to maintain vital state functions, including policing and health care services. the dialogue has also covered topics such as the effectiveness of aid in achieving economic or human development, adaptation to climate change (especially developing countries' implementation of low-carbon growth strategies and adaptation to harsher weather), improving the availability and accessibility of food ("food security"), the interplay between security and development, electrification (with a focus on rural areas in sub-saharan africa), and health. the last four areas merit further elaboration. at the g- summit in l'aquila, italy, members of the g- and other donors, including the eu, pledged $ billion to support food security over a three-year period. that initiative led to the launch at the g- summit at camp david in may of a new alliance for food security and nutrition between the donors and ten african countries suffering chronic food shortages. the purpose of the initiative is to attract private investment in agriculture, to complement public investment and create the right conditions for the recipient countries to increase agricultural productivity, adopt improved production technologies (including improved seed varieties), and improve their post-harvest management practices to reduce their dependency on food imports and food aid. under the "cooperation frameworks" signed with the donor countries, the recipients agree to implement reforms in a wide variety of areas, including infrastructure improvements, regulatory and tax reforms, and easier conditions for the marketing and trade in farm products. another important example of us-eu cooperation to promote food security in the developing world was the agreement by the bill and melinda gates foundation and the european commission to provide $ million each to fund agricultural and climate-change research during - to assist farmers with crop improvement, protection, and management. the us and the eu have both focused on the importance of providing security as a precondition for effective long-term development. their common views have translated into practical consequences on the ground. for example, the eu and the us ambassadors to south sudan, working with the united nations, averted a military confrontation between two tribes a few years after the country achieved its independence in . the lou nuer and murle tribes had been fighting each other for decades over cattle, with revenge killings occurring frequently. the ambassadors traveled together by helicopter to remote and dangerous areas to negotiate with the tribe's leadership and local elders to mediate an end to the impending conflict. as major providers of aid, the eu and especially the us were successful because they insisted that peace was a precondition for continued aid. electrification is another focus of us-eu cooperation on development. two-thirds of the population of sub-saharan africa, around million people, lacks access to power. that number is growing as rapid population growth creates demand that outstrips increased supply from investments in electrification. the remaining one-third cannot consume as much power as it would like because of blackouts and brownouts. in rural areas, the average electrification rate is only %. the main reasons for this situation include droughts that affect hydropower capacity, aging infrastructure and poor maintenance, unreliable fuel supply and inadequate transmission and distribution capacity. lack of electricity has numerous dramatic effects: for example, it stunts industrial growth and agricultural yields, hurts healthcare services (such as hospital care and the delivery of drugs requiring refrigeration), impedes digital connectivity that is increasingly essential to participate in the knowledge economy, and increases the number of premature deaths, especially among women and children, because of household air pollution caused by the use of solid biomass for cooking and of candles and kerosene lamps for indoor lighting. electrifying africa, especially sub-saharan africa, is therefore crucial to progress; at the same time, electrification using cleaner fuel sources, such as natural gas and renewable energies, will be key to avoid major harm to the environment from meeting the energy needs of a rapidly growing population with dirty coal or oil. ensuring that all people in sub-saharan africa have access to electricity by , one of the un's sustainable development goals, will require a major effort by the region's governments and the international community, above all the united states and the european union. according to various estimates, the region will need to increase its electrical capacity by about gigawatts and invest at least $ billion per year to achieve this goal. attracting that investment from the private sector is a huge challenge because almost none of sub-saharan electric utilities are currently financially sustainable due to artificially low tariffs, low operational efficiency due to losses during transmission and distribution, and poor bill collection. wasteful subsidies incentivize inefficient forms of energy, disincentivize maintenance and investment, and overwhelmingly benefit higher income groups. political patronage, corruption, and a poor regulatory environment present further challenges. investments in the electricity sector are overwhelmingly in the traditional fossil fuel sector generating power on the grid rather than in the renewables sector generating power off the grid. the latter, especially in the form of solar photovoltaic, small hydropower and small wind turbines, are especially relevant for the three-fifths of the population that lives in rural areas. even despite ongoing technological improvements that increase efficiency, renewable energy projects require significant upfront capital commitments and high transaction costs relative to the amount of power produced and the return on investment. sub-saharan africa will only be able to substantially increase electrification rates, especially with renewable energy projects in rural areas, through energy sector reform and international public-private partnerships that mobilize private capital. there are dozens of international initiatives originating in asia, the middle east, europe, and the americas to improve access to power in africa. china is increasingly active, including in sub-saharan africa where chinese contractors (the vast majority of them state-owned) were responsible for % of new electrical capacity between and . the us and the eu are working closely to align their initiatives to promote electrification in sub-saharan africa. in , they signed a memorandum of understanding that outlined their cooperation to reduce energy poverty and increase energy access in sub-saharan africa. although the mou is non-binding and does not require either party to make financial commitments, it establishes a structure for cooperation in several areas, including joint financial support, stimulating private sector investment, and the alignment of technical assistance and reform efforts. as of , there were separate initiatives originating from the member states and the eu institutions. while it is understandable that various member states wish to have separate initiatives to promote national political and commercial interests, it appears rather inefficient for the eu institutions (the european commission and the european investment bank) to have numerous ones as well. nonetheless, during the five years ending in , the eu budget alone allocated more than e . billion in grants to support sustainable energy in sub-saharan africa; those grants enabled the private sector to commit several times that amount in equity and debt capital as well. together with the member states, the eu has supported projects that have brought electricity to more than million people in the region. one of the key projects is the european commission's electrification financing initiative (electrifi) to support the adoption of renewable energy, with an emphasis on decentralized energy solutions in rural areas around the developing world, principally in sub-saharan africa. usaid not only assisted the european commission to structure the program but also approved a us investment of e million in electrifi. that investment represented a crucial "seal of approval" that enabled the european commission to access a far larger pool of capital than would otherwise have been possible. electrifi provides financing and technical support, even at an early stage and in partnership with other funders, to enable projects to overcome gaps in available market financing and achieve maturity in order to attract private long-term capital. the united states has also been active in promoting the electrification of sub-saharan africa. power africa, announced by president obama in , is the largest public-private partnership in history, involving many agencies of the us government, african governments, more than memorandum of understanding between the united states and the european union for reducing energy poverty and increasing energy access in sub-saharan africa, signed july , . https://www.usaid.gov/sites/default/files/documents/ /eu% signed% mou% from% july% % .pdf. private sector partners and international organizations like the african development bank and the world bank. power africa was underpinned by the us electrify africa act of , passed with overwhelming bipartisan support to promote african developments, as well as to assist us exports and counter chinese influence. power africa was one of the few obama-era executive decisions that president trump did not cancel upon entering office; indeed, his administration supported it as a model for how governments can leverage private capital to build infrastructure. the aim of the initiative has been to finance by gigawatts of electricity capacity and million new domestic electricity connections, especially from renewable projects in rural areas, by unlocking sub-saharan africa's substantial wind, solar, hydropower, natural gas, and geothermal resources. by the end of , power africa had attracted over $ billion in commitments and had catalyzed about $ billion in investment into power projects and over gigawatts of capacity. these projects connected about million homes and million people. most of these connections are from solar lanterns that power a single light and enable the charging of a mobile phone. as basic as that may sound, even such connections can result in dramatic improvements in livelihood. power africa is moving beyond these connections to include larger, more on-grid power projects using non-renewable sources. in addition to the power sector, both the us and the eu are actively engaged in the promotion of global health. for example, they are the main contributors to the global fund to fight hiv/aids, tuberculosis and malaria and to the global alliance for vaccines and immunisation (gavi). they sit on the governing boards and closely align their policies. founded in as a partnership among governments, nongovernmental organizations, and the private sector, the global fund raises and invests the world's money-about $ billion per year-to support programs in more than countries that combat the three deadliest infectious diseases. the eu (the european commission and eu member states combined) and the united states provide roughly and % of the global fund's financing, respectively. the health programs supported with this money have reduced the number of deaths caused by hiv/aids, tb, and malaria by one-third since and have saved million lives, the majority of these in sub-saharan africa, as of the end of . the global fund has enabled millions to be on antiretroviral therapy and therefore to be spared the death sentence that hiv/aids used to represent. of the million people living with hiv, million are on antiretroviral therapy ( . million of these thanks to the global fund). improved access to hiv treatment has cut the number of aids-related deaths in half since the peak in , from . million to under million in . however, hiv infections remain very high and especially among adolescent girls and young women who are up to eight times more likely to be hiv positive than young men in some african countries. on the current trajectory, the global fund is unlikely to meet its goal of reducing new infections to , globally by . in addition to the terrible human cost of the disease, the economic impact of hiv/aids is estimated to be over $ billion in lost earnings in . the global fund provides more than % of all international financing to combat tb. the global fund has disbursed about $ billion in the fight against tb by the end of . much of this has focused on expanding molecular diagnostic technology which delivers faster and more accurate results, supporting programs that identify those living with the disease without treatment, and enabling millions to be treated. progress is being made: the mortality rate for tb fell by % between and . but tb remains a serious threat to global health security because it is highly contagious, airborne and increasingly drug resistant. it remains the leading cause of death from infectious disease, with . million deaths per year, not including hiv co-infections. deaths from drug-resistant tb are responsible for about one-third of all deaths due to antimicrobial resistance worldwide; if trends continue, . million people will die of drug-resistant tb by , costing the global economy trillions of dollars in lost output. the global fund is also the leading provider of funding to combat malaria, a disease transmitted to humans by mosquitoes. malaria is a major killer: in , there were million infections and , deaths from malaria (most of them children under age ). in africa alone the economic impact of malaria is estimated to be $ billion per year, including the costs of healthcare, absenteeism, days lost in education, decreased productivity, and loss of investment. but thanks to the support of the global fund, hundreds of millions of insecticide-treated mosquito nets have been distributed and over million cases of malaria have been treated by . as a result, global malaria deaths have dropped by % since . unfortunately, progress has stalled in the past few years due to drug and insecticide resistance. some countries are even losing ground to the disease. launched in with the help of a $ million five-year pledge from the bill and melinda gates foundation, gavi is an international organization that brings together the public and private sectors in the shared goal of creating access to new and underused vaccines for children living in the world's poorest countries. the us and the eu are among gavi's six original donor countries; as with the global fund, they are the largest donors, providing roughly $ million each per year. gavi estimates that it has helped treat over million children and has prevented more than million future deaths in the first years of its existence. looking to the future demands on foreign aid and humanitarian assistance are certain to grow in the future, principally because of population growth and climate change, causing extreme weather patterns (including heat and drought), pests, disease, and rising oceans. some studies predict that of the . billion increase in world population between and . billion will be in africa. the oecd estimates that by half a billion people may be living in "fragile states," defined as countries that are incapable of exercising basic functions, because of climate change and conflict. every year hundreds of millions of people require humanitarian assistance, largely because of natural disasters and conflicts. hunger is one of the main urgent challenges: the food and agriculture organization estimates that over million people suffer from food insecurity, of which over million (roughly half of them children) face acute hunger, even starvation. only one-fifth of children affected by severely acute malnutrition receive adequate care, with the result that many become ill and suffer impaired growth and cognitive development. there are nearly million people around the globe-principally in syria, turkey, lebanon, palestine, yemen, afghanistan, south sudan, somalia, and myanmar-requiring protection, shelter, food, and other basic services due to forced displacement, often lasting a decade or more. very often these people lack access to water, sanitation, and hygiene, resulting in heightened risk of epidemic outbreaks. the world bank estimates that % of land area worldwide, home to approximately % of the world's population, is exposed to drought. at the same time, rapid population growth and urbanization are contributing to a steady increase in the demand for water. as a result, the number of people without access to safe drinking water is expected to double by to billion. in light of increasing demand for urgent humanitarian assistance and longer-term development aid, the us and the eu, including its member states, need to build on their cooperation as the world's leading donors to coordinate more frequently and deeply than ever before. this coordination is not only necessary to make the dollars and euros stretch further, but also to ensure that their common values shape the global development agenda despite the rapid rise of new state donors (especially china) that are focused almost exclusively on the expansion of political power and economic ties, rather than the promotion of democracy, human rights, and good governance. the us and the eu also need to work together to ensure that their activities in foreign aid and humanitarian assistance are consistent with the growing role of private development assistance coming from ngos, foundations, and corporations in the oecd. it will be more challenging, but important, for the us and eu to reconsider some of their policies that undermine their joint objectives to promote more stable economic and political conditions in the poorest countries. in the case of the us, that means its practice of tying aid to the purchase of us agricultural commodities. in the case of the eu, that means its practice of dumping into african markets the cheap surplus food that results from generous european production subsidies; and it also means its opposition to genetically modified food and feed that prevents african countries from accepting some food aid and planting more resilient crops. the signature of a cooperation agreement between the us and the eu in on the sharing of data received from the eu's copernicus constellation of earth observation satellites will assist joint efforts to manage and mitigate natural disasters the new alliance for food security and nutrition in africa the invaluable assistance of dr. emmanuel de groof in the preparation of this chapter is gratefully acknowledged. key: cord- -bm jqqf authors: mokgolodi, neo c.; hu, yan; shi, ling-ling; liu, yu-jun title: ziziphus mucronata: an underutilized traditional medicinal plant in africa date: - - journal: for doi: . /s - - - sha: doc_id: cord_uid: bm jqqf in africa, rural people depend heavily, if not exclusively, on medicinal plants and indigenous healthcare knowledge to meet their medical needs. over flowering plant species are used medicinally worldwide. amongst them are the underutilized ziziphus species in the rhamnaceae family. in terms of abundance and economic value, z. jujuba and z. mauritiana are currently the most important, especially in china and india where they are cultivated and exploited for medicinal use and their edible fruits. we examined a related common species widely distributed in africa, z. mucronata, whose economic value has not, as yet, been explored. local people in various african countries use its different parts to cure a large number of diseases, many of which are similar to those treated with z. jujuba and z. mauritiana. several studies have shown that z. mucronata has cyclopeptide alkaloids, i.e., mucronines f, g and h, with antibacterial properties. conservation strategies to sustain and maximize the benefits of z. mucronata to people are proposed. medicinal plants contain inherent active ingredients used to cure diseases or relieve pain (okigbo et al., ) . traditional remedies made from these plants play an important role in maintaining the health of %- % of people in rural and indigenous communities throughout africa (cunningham, ) . in fact, in some african countries, the number of traditional healers far outnumbers that of modern, westerneducated doctors (table ). even where modern medical services are available, use of medicinal plants has remained a more feasible option. this is due to their affordable prices, relative accessibility, local availability, trust in their effi cacy, given the emergence of new and incurable diseases, such as hiv/aids, cancer, malaria and diabetes (aumeeruddy-thomas, ) . for example, both china and mongolia are pursuing health care systems based on the practice of traditional medicine. in china, health care professionals use medicinal plants to treat and prevent diseases as well as to foster primary health of % of their patients (brown, ; zhang, ) . after the discovery of the fi rst infl uenza a virus (the subtype h n ) in may , for example, the chinese government recommended a combination of western medicine and traditional chinese medicine (tcm) as the primary course of treatment. in , the sars outbreak was also combated in the same way in china, resulting in % proven effi cacy among more than patients treated (shan, ) . china has at least manufacturers of herbal products, with an output worth about $ . billion per annum. moreover, on a total planted area of ha for medicinal herbs, central farms specialize in the production for traditional medicine and farmers cultivate medicinal plants (who, ) . one of the medicinal plants used in china to cure diseases is ziziphus jujuba mill. (chinese date or chinese jujube) of the family rhamnaceae. over time, interest in expanding the use of underutilized crops, i.e., ziziphus species, has been sporadic, especially in relation to rural development initiatives. in india, z. mauritiana lam. has already been included in the national program on underutilized crops (pareek, ) . similarly, azerbaijan also recognized the underutilization of ziziphus species and thus gave chinese jujube a priority in its national programs (pareek, ) . different ziziphus species, especially z. mucronata in africa, z. mauritiana in india and z. joazeiro in south america, are also valuable sources of traditional african, indian and south american medicines, respectively. our primary focus is on z. mucronata. the objectives are: ) to present an overview of traditional medicinal use of z. mucronata in the african continent using available literature, ) to outline briefl y similar medicinal use of z. mucronata with other ziziphus species and their economic value, ) to highlight the potential economic importance of z. mucronata in relation to other vital ziziphus species and subsequently ) to suggest some possible conservation measures necessary to ensure its lasting supply to the communities it serves. description of z. mucronata ziziphus mucronata willd. subsp. mucronata belongs to the buckthorn family (rhamnaceae) in the order rhamnales. it is a plant species in the genus ziziphus tourn. ex l. (azam-ali et al., ) . the latin name 'ziziphus' means thorny and 'mucronata' refers to the pointed leaves of this species (world agroforestry, ) . ziziphus is a generic name derived from the arabic word zizoufo (world agroforestry, ) used for z. lotus (l.) desf., but also related to the ancient persian words zizfum or zizafun; ancient greeks used the word ziziphon for the jujube (azam-ali et al., ) . the genus ziziphus is of some historical importance. it is believed that christ's crown was made from z. spina-christi willd., a species which closely resembles z. mucronata but grows from central africa northwards (palmer and pitman, ) . nevertheless, this is not certain, since paliurus spina-christi mill., synonym p. aculeatus, has also been proposed (azam-ali et al., ) . generally, there is a consensus that the genus ziziphus consists of approximately species (johnston, ; hyde and wursten, ) . bhansali ( ) suggested that there could be up to species and studies by some authors (liu and cheng, ; islam and simmons, ; liu and zhao, ) showed that there could be up to species. a major factor contributing to this complexity may be that, in some cases, the same specifi c epithet has been used by different authors for different species. for example, z. mauritiana lam. has had the specifi c epithet of jujuba applied as z. jujuba (l.) lam. and z. jujuba (l.) gaertn. (azam-ali et al., ) . moreover, inter-regional comparisons are sometimes not taken into consideration when naming the species. for instance, johnston ( ) proposed possible affi nities between z. lotus of mauritania and the sahara and also between z. hamer of east africa and z. leucodermis (baki) o. schwartz of arabia and as such suggested a more detailed study of the genus; but up to date no literature has been found to show that this has been done. synonyms of z. mucronata include z. adelensis del., z. mitis a. rich, z. mucronata willd. var. glabrata sonder, z. mucronata willd. var. glauca schinz, z. mucronata willd. var. inermis engl. and z. mucronata willd. var. pubescens sonder (world agroforestry, ). the common english name of z. mucronata is buffalo thorn. alternative names include cape thorn, shiny leaf and wait-a-bit. apart from z. mucronata, other ziziphus species widely found in africa include z. abyssinica hochst. ex a. rich. and z. spina-christi willd. (azam-ali et al., ) . gelfand et al., ; world bank, ; cunningham, note: tmp * , traditional medical practitioners; ** , region; *** , city; na, data not available. z. mucronata is a common, drought resistant species distributed throughout the summer rainfall areas of sub-saharan africa, extending from south africa northwards to countries such as eritrea, ethiopia, ghana and senegal (schmidt et al., ) . it also occurs in yemen in the arabian peninsula (united states department of agriculture, ). figure shows its overall distribution. z. mucronata regenerates naturally from seeds in various habitats with a mean annual temperature of - °c and a mean annual rainfall of - mm (orwa et al., ; world agroforestry, ) . however, it is more common on fl at and open woodlands, in alluvial soils along rivers, around pans as well as on termite mounds (palgrave et al., ; azam-ali et al., ) . z. mucronata occurs both in coastal regions and inland, up to m above the sea level (orwa et al., ; world agroforestry, ) . in addition, z. mucronata can be propagated in nurseries, where it grows reasonably quickly from seeds or cuttings in any soil type and reaches to m in - years (orwa et al., ; world agroforestry, ). z. mucronata is a shrub to medium-sized deciduous tree, up to m in height, with an irregular spiky canopy (shackleton et al., ) . it has a single trunk that is often crooked; its branches spread and droop, branching above ground or sometimes near the base (world agroforestry, ). z. mucronata has distinctive angular zigzag branchlets and twigs, together with the hooked and straight thorns. the thorns of this species, usually present at the base of the leaf, are often in pairs, reddish brown, one straight (up to cm; world agroforestry, ) and the other shorter, stronger and hooked. leaves of z. mucronata are shiny and light green, simple ( - mm × - mm), alternate or in tufts, with blade prominently - veined from their base (schmidt et al., ) . the small (± mm in diameter), yellowish-green star-shaped flowers are borne in dense clusters above each leaf during october and november (shackleton et al., ) . the normally round fruits always appear thereafter from january to july (shackleton et al., ) , which often stay attached to the plant long after the leaves have fallen. the fruits of z. mucronata are green when young, usually up to . cm in diameter and turn to reddishbrown when ripe (maundu et al., ) . they contain a large stone inside and as such have relatively little pulp which is usually dry and mealy. the seeds are usually solitary, elliptic and compressed. mature trees produce about - kg of seeds (orwa et al., ; world agroforestry, ). the bark of z. mucronata is normally red-brown and smooth but only on young stems. in older trees, it is roughly mottled grey and often cracked in small rectangular blocks, revealing a stringy red under-bark. the main stem of z. mucronata is green and hairy when young (schmidt et al., ) . modern scientific medicine is a highly regulated social and economic activity. however, most people, particularly in the developing countries, still rely on various forms of traditional medicine (akerele, ) . in africa, traditional healing systems exist in almost all countries. table shows medicinal roles of z. mucronata in healing various health conditions in several african countries. medicines, obtained from its roots, bark, leaves and/or fruits, are applied in various ways, usually as drinks, food and even as poultice. common ailments treated using z. mucronata include chronic cough, boils, toothache, rheumatism and swellings (roodt, ; iwalewa et al., ; orwa et al., ). as noted by pareek ( ) , most parts of the ziziphus plants have medicinal value due to their inherent constituents. in particular, the traditional medicinal use of z. mucronata can be attributed to the various cyclopeptide alkaloids it contains (table ) (auvin et al., ; pareek, ) . these include mucronines a -h (moloto, ) , the recently discovered mucronine j (auvin et al., ) , abyssenine a and frangufoline (sanjoinine a) which are isolated from the bark of its stem, root bark, roots and leaves (auvin et al., ; tan and zhou, ) . the frangufoline (sanjoinine a), possessing a strong sedative property, has attracted increasing attention in chemical investigations of natural products since the mid 's (tan and zhou, ) . together with mucronines f-h found in the bark of z. mucronata stem, they give this traditional medicinal plant its antibacterial properties (tan and zhou, ) . mcgaw et al. ( ) also support the antibacterial activity of z. mucronata in a study using escherichia coli, enterococcus faecalis, pseudomonas aeruginosa and staphylococcus aureus bacterial strains in leaf extracts. the average antibacterial activities for these bacterial strains, expressed in minimum inhibitory concentration in mg·ml − , were > . in methane, > . in hexane and > . in water. for p. aeruginosa and e. coli, the antibacterial activity was more than . mg·ml − in all three extracts, while e. faecalis and s. aureus recorded . mg·ml − in water and . mg·ml − in hexane . a study by moloto ( ) provides similar support for the use by traditional medical practitioners to treat bacterial infections such as gonorrhea, syphilis, cholera, dysentery and boils using z. mucronata extracts, as shown in table . in addition, z. mucronata has antifungal and antiplasmodial properties, probably due to the tetracyclic triterpenoid saponins and flavonoids in its fruits (prozesky et al., ; pillay et al., ) . the species is reported to have a high antisickling activity as well. based on mpiana et al. ( ) , the antisickling property arises from anthocyanins, extracted from its roots and bark. the bark of z. mucronata has %- % tannin (orwa et al., ) , an astringent often used to treat diarrhea. moreover, ziziphus species, z. mucronata included, commonly have a lot of vitamin c. its concentration ranges from to mg per g (bal and mann, ) , which is beyond the mg daily intake recommended by passmore et al. ( ) for adults. while some cyclopeptide alkaloids in the rhamnaceae family, including the ones specifi ed for z. mucronata, have shown antibacterial, antifungal, antiplasmodial and sedative activities, there have not been any potential applications of cyclopeptide alkaloids in new drug research and development (tan and zhou, ) . therefore, this remains to be explored in the future. due to its abundance, z. mucronata is also a valuable source of food for all browsers such as giraffe, springboks, antelopes, black rhinos and elephants (setshogo and venter, ; shackleton et al., ; orwa et al., ). its highly nutritious fruits are usually eaten by monkeys, baboons, warthog and birds. the fruits can be made into porridge and flour once they are dried and grounded (roodt, ) . sometimes the fruits are sucked by children and are reportedly sold in rural markets in zimbabwe (van wyk and gericke, ) . if fermented properly, the fruits can also be made into a traditional beer (setshogo and venter, ) . though rarely practiced, the seeds can be used as a coffee substitute (maundu et al., ; shackleton et al., ) . the leaves are edible and young ones can be cooked and eaten as spinach. they play a central role in the nutrition of larval caterpillars, such as tuxentius melaena, t. calice calice and zintha hintza (orwa et al., ) . z. mucronata are also used in kerharo and adam, syphilis, gonorrhea bark of underground parts, sap bark powdered and locally applied, sap applied locally kerharo and adam, urogenital infection, bilharzia, schistosomiasis fruits infusion taken orally kerharo and adam, (to be continued) gelfand et al., arthritis, cramp, kidney pain, lameness, rheumatism, muscular infl ammation bark, branches, roots infusion applied on scarifi cations, infusion taken orally gelfand et al., diarrhea, tape worms, malaria, hypertension, syphilis, gonorrhea, urinary, gynecological complaints bark, leaves, roots ns* palmer and pitman, ; who/danida, note: ns*, not specifi ed. connection with burial rites by the zulu tribe in south africa and the swazi tribe in swaziland (shackleton et al., ) . in botswana as well as in most parts of south africa, it is believed that z. mucronata is immune against lightning, so anyone sheltering under it in a storm is considered to be safe. in rural areas, the termite resistant timber from z. mucronata trees is used for a variety of household items such as tables, chairs, spoons and dishes (palmer and pitman, ) . the wood of z. mucronata is fairly dense and can be used to make long burning fi rewood and charcoal. z. mucronata is also commonly used as a live fence, for instance in schools and gardens, as well as a form of protection against animals in fi elds, homesteads and kraals, at least for years before the crown is too high off the ground to act as a barrier (world agroforestry, ). moreover, z. mucronata is considered to be a good indicator of underground water in areas where it naturally occurs (setshogo and venter, ) as well as a valuable source of nectar by beekeepers (orwa et al., ) . species in the genus ziziphus are increasingly becoming popular due to their outstanding advantages, such as early bearing, high fruit yield, rich nutrition, multiple uses, long flowering season and high tolerance to drought and barren soils (international centre for underutilized crops, ; liu and zhao, ). in addition to z. mucronata, several other ziziphus species are exploited for medicinal use in other parts of the world as well. examples include z. jujuba, z. mauritiana and z. spina-christi. medicinal uses of these three species are generally similar to those of z. mucronata in africa. the fruits, leaves and seeds of z. jujuba are commonly used in china to treat illnesses, such as irritability, insomnia, heart palpitations, constipation, lack of appetite, inflammation, sore throat and shortness of breath (zhu, ; azam-ali et al., ; jiang et al., ; naftali et al., ) . similar diseases treated with z. mucronata in africa cover psychiatric cases in mali, rheumatism in kenya and south africa as well as measles in botswana. just like z. mucronata, z. jujuba possesses saponins which have some sedative effects. the saponins in z. jujuba are ziziphin and jujubosides a and b, acetyljujuboside b and protojujubosides a, b and b (azam-ali et al., ) . in addition, this species also contains triterpenoic acids (e.g. oleanolic acid, betulonic acid, oleanonic acid and colubrinic acid) and some phospholipids (lee et al., ; jiang et al., ) . some medicinal uses of z. mauritiana in india are similar to those of z. mucronata in africa. these include the treatment of diarrhea, dysentery, nausea, vomiting, mental retardation, rheumatism, ulcers, wounds and fever (ara et al., ) . the plant parts used in treatments are leaves, roots, seeds, bark and in some instances, fl owers. alkaloids, such as mauritines a-h and j, amphibines b and d-f, frangufoline, hysodricanin a, scutianin f and aralionin c, are examples of cyclopeptide alkaloids found in z. mauritiana (jossang et al., ) . moreover, traditional medicinal uses of z. mucronata are comparable to those of z. spina-christi. for instance, based on dafni et al. ( ) , z. spina-christi in morocco is similarly used in snake bite treatments as z. mucronata in benin, tanzania and zimbabwe (table ) . other ailments, such as arthritis, muscle pains, chest pains, headache, colds, measles, swollen organs and liver problems, treated with z. spinachristi (dafni et al., ) , are in certain african countries cured using z. mucronata ( table ). the active components of z. spina-christi include zizyphine f, auvin et al., ; tan and zhou, . jubanine a, amphibine h and spinanine a (shappira et al., ) . therefore, in view of these similarities, z. mucronata is an equally potential source of medicine. the -ali et al., ) . in south korea, it has become a commercially cultivated fruit tree. in , it was grown on roughly million ha of land in china, with production of . million tons on a fresh weight basis, accounting for % of world production (liu and zhao, ) . chinese date (jujube) is eaten as fresh fruit, or dried and soaked in water before use in savory and sweet dishes. a wine made from z. jujuba fruits called "hong zao jiu" is also produced in china. in korea, jujubes are called "daechu" and used in teas to help cure the common cold. similar to z. jujuba, z. mauritiana (indian jujube) is mainly cultivated for its fruits in india (pareek, ) . it is one of the ziziphus species found in india (ara et al., ) . z. mauritiana is native from yunnan province, china, to afghanistan, malaysia and australia (kaaria, ) . it is also found in the bahamas, fiji, colombia, philippines and venezuela. in , six trees from malaysia were introduced into israel and fl ourished there. the usa has also imported germplasm of z. mauritiana and a small number of trees are cultivated in southern florida (azam-ali et al., ) . between and , . million tons of z. mauritiana fruits were produced in india from an area of ha. z. mauritiana can produce an annual fruit yield of - kg·tree − and is relatively easy and inexpensive to cultivate (international centre for underutilized crops, ). among india, thailand and pakistan, only thailand exports z. mauritiana fruits to the middle east, malaysia and the far east throughout the year. about tons of z. mauritiana fruits have been produced in thailand between (international centre for underutilized crops, . the ripe fruits of z. mauritiana contain large amounts of vitamins a and c and are mostly eaten raw in india and sometimes stewed. in indonesia, young leaves are cooked and eaten while in venezuela, a jujube liqueur is made and sold. z. mauritiana is also a source of fodder for cattle, sheep and goats. plants have long provided mankind with herbal remedies for many infectious diseases and even today, they continue to contribute immensely as primary health remedies in developing countries. from a research and development point of view, many ziziphus species have not received any major emphasis from governments and as such, they remain underutilized (azam-ali et al., ) . nonetheless, we have shown that they serve valuable medicinal and cultural roles to millions of people. z. mucronata helps in the treatment of diseases such as diarrhea, syphilis and gastric ulcers. it also helps heal boils, wounds and hypertension in many african countries. moreover, it provides food to animals as well as material for handicrafts to local people in various african countries. as such, there is a need to preserve this species in order to ensure its lasting supply to local communities. some possible conservation strategies are mentioned below. if z. mucronata is to be maintained as a renewable resource, more domestication initiatives such as those taken for z. jujuba and z. mauritiana can be employed. this will likely take pressure off the existing wild stocks. additionally, z. jujuba, z. spina-christi and z. mauritiana have been successfully introduced in areas outside their natural habitats. they widely occur in almost all continents. attempts can be made to introduce z. mucronata to other continents as well, since it can tolerate various environmental conditions, just like the ziziphus species mentioned earlier. presently, the distribution of z. mucronata is mainly restricted to africa. furthermore, to maximize the use of z. mucronata, collaboration among nations is crucial in enhancing scientific research on the pharmacological potential of this species in the global market. a number of the traditional medicinal uses of z. mucronata in various african countries are similar to those of the widely recognized z. jujuba and z. mauritiana. this indicates that with more research, z. mucronata can be economically valuable as well. compared to india and china, many african countries still have much to do in terms of effectively inte-grating medicinal plants and the associated indigenous healthcare knowledge in modern healthcare systems. to achieve this, the preservation and documentation of indigenous medicinal knowledge related to medicinal plants, i.e., z. mucronata, with the involvement of traditional medical practitioners is vital. plantes médicinales hausa de l'ader (république du niger) contribution aux Études ethnobotaniques et floristiques en république populaire du bénin. paris: agence de coopération culturelle et technique (acct) version . . pretoria: conservatoire et jardin botaniques de la villle de genève and south african national biodiversity institute medicinal plants and primary health care: an agenda for action availability, accessibility, acceptability and adaptability: four attributes of african ethnomedicine ethnobotanical study of plants used for the treatment of diarrhea in the eastern cape, south africa taxonomic study of the genus ziziphus mill. 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mcclinton appollis, tracy; jonas, kim; maruping, kealeboga; dietrich, janan; lovette, ashleigh; kuo, caroline; vanleeuw, lieve; mathews, catherine title: “as a young pregnant girl… the challenges you face”: exploring the intersection between mental health and sexual and reproductive health amongst adolescent girls and young women in south africa date: - - journal: aids behav doi: . /s - - - sha: doc_id: cord_uid: zqt vu d in south africa, adolescent girls and young women (agyw) are at risk of poor mental health, hiv infection and early pregnancy. poor mental health in agyw is associated with increased sexual risk behaviours, and impeded hiv testing and care. using in-depth interviews and focus group discussions, we explored subjective experiences of mental health and sexual and reproductive health (srh) amongst agyw aged – years in five south african districts. respondents shared narratives of stress, emotional isolation, feelings of depression, and suicidal ideation, interconnected with hiv, pregnancy and violence in relationships. findings show that agyw in south africa face a range of mental health stressors and lack sufficient support, which intersect with srh challenges to heighten their vulnerability. framed within the syndemic theory, our findings suggest that south african agyw’s vulnerability towards early pregnancy, hiv infection and poor mental health are bidirectional and interconnected. considering the overlaps and interactions between mental health and srh amongst agyw, it is critical that mental health components are integrated into srh interventions. poor mental health, including depressive disorders and stress, contributes significantly to the burden of disease in south africa, and other parts of sub-saharan africa, and is also associated with negative sexual and reproductive health (srh) outcomes for women, such as 'unintended' or early pregnancy, and increased risk behaviours for hiv [ ] [ ] [ ] . researchers in the field of women's health have highlighted the need to further explore the syndemic interactions between psychosocial vulnerability, mental health, hiv infection, and poor srh outcomes [ ] . in south africa's hiv epidemic, the largest in the world, a quarter of all new infections occur amongst adolescent girls and young women (agyw) aged - , three times as high as their male counterparts [ ] . as with hiv, south africa also has high rates of teenage pregnancy; in , % of females aged - years had begun childbearing [ ] . agyw in south africa are more susceptible to depressive symptoms than their male counterparts, and are likely to remain underdiagnosed and untreated [ ] [ ] [ ] . thus, their vulnerability lies at a biological, social, and environmental nexus. the onset of depression in particular, but other mental health problems as well, can coincide with other developmental milestones such as sexual debut and escalated risks for hiv infection. estimates suggest that approximately three quarters of mental health comorbidities that affect adults across the life course emerge during adolescence and young adulthood [ ] . adolescents' mental health status can have profound impacts on their future health, social, and economic circumstances as adults, particularly in contexts of poverty and vulnerability [ ] . the development of poor mental health outcomes during this period is influenced by neurological, hormonal, and physical changes associated with puberty, combined with changes in adolescents' social environments [ ] . evidence from south africa and other countries in the sub-saharan african region show that age-specific risk factors for depression and anxiety disorders include lower socio-economic status, lack of social capital and support, substance use, and exposure to violence and traumatic events [ ] . adolescents growing up in the context of socio-economically adverse communities are faced with a range of additional psychosocial and health risks that may evoke stress and negatively affect their mental health; these risks include exposure to hiv, substance use, violence, and other stressors [ ] . poverty has been shown to be associated with heightened vulnerability to experiencing poor mental health, including mood and anxiety disorders [ ] . in addition to age-related factors and socio-economic factors, gender-related factors, including sexual and reproductive biology, also play a role in contributing to mental health risks. adolescent pregnancy poses a significant mental health burden, predisposing agyw to adverse mental health outcomes, with depression and anxiety being the most common [ ] . in resource-deprived settings in sub-saharan africa, pregnancy amongst agyw is associated with adverse mental health outcomes and psychosocial stresses including stigma and discrimination [ ] . in the south african context, pregnancy may exacerbate existing social and contextual stressors, adding additional stressors such as interpersonal relationship challenges, regret around 'unintended' pregnancies, and depression [ ] . globally, suicide is the second leading cause of mortality among females aged - years; with low and middle income countries accounting for over % of global suicide deaths [ ] . rates of suicidal ideation, defined as the thought of killing oneself, are highest among adolescents on the african continent, with hiv as a contributing factor [ ] . the syndemic theory of health refers to the clustering of risk factors, or co-occurring and intersecting epidemics embedded in the particular social context in which an individual is situated, which combine and interact to create vulnerability to health outcomes that are worse than any one risk factor alone would cause [ , ] . by focusing on the 'biosocial complex', the interconnected and cooccurring health issues, as well as the social and environmental factors that promote and enhance negative health outcomes, the syndemic theory can help to explain the way in which risk behaviours which lead to negative srh outcomes, namely hiv infection and 'unintended' pregnancy, are situated within co-occurring and interacting psychosocial health conditions, including psychological distress and poor mental health [ , , ] . the immense physical, neurocognitive, mental, and social changes that occur during adolescence not only affect mental health, but also influence sexual behaviour; during this period of transitioning to adulthood, adolescents are at increased risk of hiv infection [ ] . the association between depressive symptoms and decreased sexual agency and decision-making power in agyw are compounded by low self-esteem; in turn these are associated with increased risk behaviours, including increased susceptibility to pressure to have sex, comfort seeking, condomless sex, transactional sex, trans-generational sex, substance use, and 'unintended' pregnancy [ , , [ ] [ ] [ ] . some of the mechanisms through which poor mental health symptoms influence sexual risk include substance use, maladaptive coping mechanisms to deal with stress, and impaired decision-making, indicating poor mental health as a prospective predictor of sexual risk [ ] . depressive symptoms in agyw have also been correlated with a lack of ability to withstand social pressure, including peer pressure to engage in risky behaviours, a tendency to be more subservient and less assertive in sexual relationships, as well as with being more vulnerable to intimate partner violence and abuse [ , ] . in addition to the links between depression and increased sexual risk taking, depression is also associated with impeded health seeking behaviour, including hiv testing [ ] . considering the overlaps and interactions between mental health and srh amongst agyw is critical. greater insight into the lived subjective experience of depression and stress, and how these are linked to srh outcomes is needed. there appears to be a gap in the literature pertaining to the ways in which mental health and psychosocial risks, including depression and stress, intersect and overlap with srh related factors such as distress caused by 'unintended' pregnancy, material/emotional stressors of having a child, or social stigma [ ] . various studies explore depression amongst hiv positive women, but there has been little exploration of mental health issues that arise due to, or co-occur with, srh outcomes. although mental health was not an initial focus of the research, upon qualitative enquiry, the significance of poor mental health outcomes impacting on sexual and reproductive health practices emerged as a salient theme, warranting closer examination. we examined agyw's narratives and conceptualizations of their own mental health, that of peers, and of the surrounding emotional and psychosocial support context in order to explore the ways in which these factors might interact with sexual health outcomes. this research formed part of the herstory study, which evaluated a comprehensive combination hiv prevention intervention for agyw implemented in ten priority districts in south africa from to , funded by the global fund (https ://www.samrc .ac.za/intra mural -resea rch-units /healt hsyst ems-herst ory). included in the analysis for this paper are qualitative data from in-depth interviews (idis) and focus group discussions (fgds) conducted between august and march in five south african districts, with a total of agyw aged - years. of the agyw, were from the western cape (wc), from kwazulu-natal (kzn), from mpumalanga (mpu), from the north west (nw), and from the eastern cape (ec). participant recruitment took place in selected schools and communities through liaising with school staff and/or intervention implementers in order to identify eligible participants, arrange interviews, and secure appropriate venues. a brief demographic questionnaire was also administered. idis ( - min) and fgds ( - min) were conducted in english, isizulu, isixhosa, setswana, or siswati, by one of two lead interviewers, accompanied by a research assistant, all female, and all of whom had received training on the study protocol, design, research tools, and human subject research ethics. semi-structured topic guides comprised of open-ended questions and probes guided discussions. included in the topic guides were questions relating to sources of social/emotional support; agyw were asked who they talk to or seek support from when experiencing emotional/relationship/school/health/srh concerns or challenges. mental health was not a specific focus of the study but arose in response to these. the research team engaged in an on-going reflective process of note-taking and debriefing discussions, which formed part of the collaborative interpretation discussions and analysis process. informed consent was obtained from all participants years and older. written assent with written guardian consent was obtained for those younger than years. participants were provided with a zar . (approximately us$ . ) supermarket voucher, transport reimbursement, and refreshments. the study protocol and research tools were approved by the south african medical research council research ethics committee, and by the associate director for science in the center for global health in the centers for disease control and prevention. the research team received training on the study protocol and procedures for reporting and managing social harms and adverse events, as outlined in human subject research ethical guidelines. during data collection, private-sector social workers were procured to assist with ensuring access to social support services for participants who needed psychosocial support. audio recordings of idis and fgds were transcribed verbatim into their original language, reviewed by the researcher who conducted the interviewer for accuracy, translated into english and re-reviewed by the interviewer. data analysis followed a thematic approach, in which a pre-determined deductive codebook underwent cyclical review and refinement [ ] [ ] [ ] . collaborative interpretation by the research team, comprising the two interviewers who were also co-investigators, along with four other co-investigators, included individual data immersion and familiarisation, repeated deep readings of transcripts, documentation of reflective thoughts, and sharing growing insights about the research topic during regular team discussions. the codebook was entered into nvivo software, which was used to organise and label relevant text from the transcripts. as concepts and themes emerged, the team collaboratively reviewed them, returning to the data, and refining themes. weekly research meetings were held throughout the data collection and analysis phases allowing for team debriefing and examination of how thoughts and ideas were evolving as they engaged with the data. three feedback workshops were held with agyw aged - at three of the study sites, some of whom had previously participated in idis and fgds, and some who had not. the objective of these workshops was to review and discuss the preliminary analysis and interpretations, ensure accurate and appropriate interpretation of the data, clarify misunderstandings, and confirm findings and interpretations. during the workshops, the research team summarised and presented key themes and findings to the participants, who were then invited to give feedback, discuss their interpretation of the findings, and expand or elaborate on themes. facilitated discussions on each theme were captured through notes and audio recordings, transcribed and reviewed, and included in the overall analysis. amongst the agyw respondents aged - , the mean age was . years. of these, % (n = / ) selfreported to have been assigned female at birth. amongst the agyw respondents, % (n = / ) self-identified their gender as female, with two identifying as transgender, and three as gender-variant. most, % (n = / ) of agyw self-identified as heterosexual/straight, % (n = ) as homosexual/gay/lesbian, and % (n = ) as bisexual. for reporting of language spoken at home, the top three languages were isixhosa ( %, n = / ), isizulu ( %, n = / ), and siswati ( %, n = / ). overall, % (n = / ) of the agyw reported to have had a pregnancy. emergent themes in the qualitative data included agyw narratives and perceptions of depression, stress, and suicide. in the accounts of agyw, poor mental health, including depression and suicidal risk were linked to sexual/ romantic relationship challenges, early pregnancy and child-bearing, parenting responsibilities, experiences of violence/abuse, hiv status, and lack of emotional support. suicide risk emerged as a salient theme and was associated with discovery of pregnancy or an hiv positive status, low self-esteem, and a lack of anyone to trust or confide in. in general, agyw voiced a need for increased access to support, and additional information on mental health. the findings presented below are arranged into key thematic areas that emerged during analysis. illustrative quotations are excerpts from english transcripts or translations; in brackets are details of the respondents' site and sample group. in selected excerpts, original language terms/words have been included in italicised brackets for the purpose of illustrating the exact words/language used by participants relating to key concepts associated with mental health. the rationale for this is that often concepts such as "depression" have been framed in a universal/western way, without attention to contextual specificity. where qualitative research uses translations, there is a danger of the original meaning and concept getting lost in the translation process, as translators seek to find 'equivalent' terms [ ] . suicidal ideation emerged as salient theme across provinces, despite there being no specific question probes relating to suicide. according to agyw, issues such as self-harm and having suicidal tendencies were common amongst their peers. one participant expressed hesitancy using the diagnosis of 'depression', but described self-harming and suicidal ideation: "there are girls, i don't want to say 'depressed', but who do things like self-harming, some attempt suicide" ( ) ( ) ( ) ( ) ec) . agyw made links between low self-esteem and self-worth, and lacking a sense of belonging, with suicidal ideation: "most girls… have a low self-esteem… feel as though they don't belong in this world. that's why people commit suicide. i used to have that… mentality… suicidal thoughts because of people" ( ) ( ) ( ) ( ) ( ) ( ) nw) . illustrating the link between srh and mental health, feelings of emotional isolation leading to suicidal ideation were exacerbated in the case of hiv positive or pregnant agyw who feel unable to access support: "this thing of suicide is becoming popular now, even here at school… especially when girls are pregnant or hiv positive, because they can't share it with anyone, they don't trust anyone" ( - years, wc). the sense of having no one to trust or confide in, and seek emotional support from, resulted in agyw feeling emotionally isolated, fostering suicidal ideation: "we don't share our sexual and personal life things… we keep it to ourselves, then some of us commit suicide (sizigcinia kuthi, abanye bethu ke baphela sebezibulala)" ( - years, wc, isixhosa). suicide was linked to feelings of isolation after an hiv positive diagnosis: "(when) the nurse told her that is she is hiv positive, she didn't know who to tell… so she took a rope and hanged herself because she had no one to talk to" ( - years, wc). the discovery of being pregnant was also described as a difficult emotional event. agyw in the older age group, - years, described personal experiences with suicidal ideation in this situation: "when i found out i was preg-nant… that was very difficult, i even thought about sui-cide… it was tough (kwabanzima kakhulu, ngangicabanga ngisho ukuyibulala, ya kwaku tough)" ( - years, kzn, isizulu). additional links between mental health and srh were apparent in the narratives of suicidal ideation in relation to the stress of teenage pregnancy, compounded by fear of hiv: "as a young pregnant girl… the challenges you face… maybe you will find out that he (baby's father) is hiv-positive… those are challenges that can be a problem and you end up committing suicide… a better solution is to kill yourself (yizona ngqinamba lezo ezingaba inkinga ugcine usu… usuzibula… i solutions kuncono ukuthi uzibulale)" ( - years, kzn, isizulu). respondents suggested that due to social stigma attached to teenage pregnancy, pregnant agyw fear being judged and gossiped about: "pregnant girls feel sad… some even contemplate suicide (azive efuna ukuzibulala)… because of hearing unpleasant things about their life being spoken by other people. ( - years, wc, isixhosa); "pregnant girls are teased, and then they drop out of school, they don't fin-ish… here at school… we gossip about each other in the toilets" ( - years, wc). parents' attitudes towards their daughters' romantic and sexual behaviour prevented agyw from accessing support: "like most girls, i got pregnant at an early age. some girls resort to committing suicide (ezibulala) or just run away from home because they cannot face their parents" ( - years, wc, isixhosa). getting involved in transactional relationships, compounded by a sense of shame and fear of social judgement, also led to depression and suicidal ideation: "most girls in the community, they get into those (transactional) relationships, to a point that it damages them… they end up being depressed… 'why are you doing this and that to me in front of people?'… they end up like that and they end up trying to commit suicide… 'he embarrassed me in front of people, tomorrow how will people look at me?'" ( - years, nw). the emotional 'burden' of teenage pregnancy was described as a key contributing factor to poor mental health: "they say having a child is a good thing, but as a teenager it is a burden, it's difficult to cope" ( - years, ec). financial, material and relationship insecurity added stress to pregnancy: "the baby's father has denied the baby, there will be stress of how you are going to support the baby, because the (social) grant is not enough" ( - years, kzn). those agyw who had experienced unexpected discovery of pregnancies described their stress related to being rejected by families, kicked out of school or from home. one participant described her concerns after finding out she was pregnant in grade : "i was confused and didn't know what to do… (i told my boyfriend) my dad is strict… i will be chased away from home" ( - years, kzn). those agyw who became pregnant with casual sex partners, or who were not in committed relationships described the stress and unhappiness they experienced. one young woman described how she wanted to terminate her pregnancy but was told it was already too late to do so, and how this unwanted pregnancy caused her stress: "i had stress… i only realised when i was months days that i was pregnant… if i had realised this earlier, i was going to do an abortion… then i asked the doctor 'is there any other way i can do an abortion?'… he then said 'it's either you die… i will not allow you to risk an abortion'…[sigh] i was not ready to have a child at that time… i knew how my situation was… the guy i was dating, i was just dating him for fun. i did not see myself having a child with him, or to have future with him… that was why i was going to abort this baby… i did not want the child… everything failed… i did not eat, i had stress… the one who impregnated me was staying in a shack" ( - years, nw). a lack of emotional support from partners/fathers of children also contributed to stress and depression amongst young mothers: "where does the stress go? …to me… i'm always watching this child, he cries the whole day and i don't know why… i'm holding him, gave him his bottle, he continues to cry, i don't know why he is crying… you call him (baby's father)… (but) he doesn't take any action… i become depressed and it affects the child" ( - years, nw). being a single parent was described as difficult and stressful: "if you are a single mother, there is nothing nice… (you) have love for your baby but that's it. everything else is not nice… it's difficult to raise the child" ( - years, nw). the feeling that former dreams and aspirations for the future were shattered by unexpected pregnancies heightened feelings of hopelessness and depression: "it's not going to be dark forever, things will be right… but what i can say? …to be pregnant unexpectedly is not good at all… life is not good… especially if… you had plans and maybe life does not go the way you had planned… i am speechless… for me now, life is not good… it's not good… tough times…" ( - years, nw). lacking a supportive social environment negatively impacted on mental health and self-esteem: "when people are discouraging me… i get very sad… i'm trying… i'm telling them that… and they say 'you cannot do that… you're weak'… it makes me angry, but… i don't defend myself" ( - years, nw). some agyw suggested that they tried to cope without sharing their problems with anyone: "i keep my problems to myself… i talk to no one… i keep to myself and own it, i don't make my problem someone else's… if ever i have something troubling me i will keep it to myself… eventually i will be fine (ndizade ndibe right)" ( - years, ec, isixhosa). the lack of emotional support for dealing with traumatic life events, including grief over the death of a loved one, was present in agyw narratives: "when i think about something that happened in the past my heart becomes sore (intliziyo yam ibabuhlungu)… (like) when i think about my mother… she passed away… there is nobody (i talk to at home)… i don't feel free talking to them… i don't speak to anyone at school (either)" ( - years, ec, isixhosa). a minority of agyw were vocal about receiving emotional support at home: "i know i am loved at home and they show me that they love me because they care for me and stuff" ( - years, ec). sexual and romantic relationships with violent and controlling partners were also described by some of the agyw, who ended up living in a state of fear: "if i have made friends… and we want to go out as girls, then he (boyfriend) will refuse and beat you. even when you make a minor mis-take… he will beat you, and you end up afraid… you now live in fear… when happy, it doesn't last for long… sometimes he will take out his anger on you even when you did nothing… but you continue to love him even when friends try to talk some sense to you, but you will continue staying and loving him because you are afraid of him and not at liberty to do your own things" ( - years, mpu). refusal to have sex with a partner also led to violence: "sometimes, it happens that he wants to sleep with you, and you don't want to, then he gets angry and he beats you" ( - years, kzn). those agyw who had experienced intimate partner violence explained their reluctance to disclose to her family and friends: "in most times, you keep quiet and when they ask you 'what happened, why are you hurt?' you just tell them that you got hurt, you turned and bumped into a wall" ( - years, kzn) . experiencing violence negatively impacted agyw self-esteem and self-worth: "it has to do with how you perceive yourself, he sees me as not good enough then maybe you will find that boyfriend that hits you, he is the one that you want to stay with because you think where else will you find another boyfriend? …when he hits you that means this person does not see any value on you he beats you, abuses you… physically you will be injured obviously because that will hurt you… and she will think that she is not good enough" ( - years, ec). pregnancy increased agyw dependence on partners, even when they are violent: "my friend is pregnant… (her boyfriend) beats her… in her pregnancy the guy did not care for her and he was beating her saying the child is not his" ( - years, ec). our study did not initially set out to examine mental health amongst agyw, but narratives around depression, stress and suicide became salient, as did evidence of their interconnection with sexual and reproductive health. feelings of stress, anxiety and not being able to cope, even to the point of suicide ideation, were associated with hiv status, unexpected discovery of pregnancy, and parenting responsibilities. violence in relationships, a lack of emotional support from family and partners, and financial insecurity interact to exacerbate agyw vulnerability to poor mental health and srh outcomes. agyw in our study who had been pregnant, shared narratives of negative emotions they had experienced on discovering their pregnancy, leading to depression and suicidal ideation. the social causation hypothesis theory posits that stressful circumstances or events increase an individual's susceptibility to manifesting or experiencing mental health problems [ ] . it would therefore make sense that the emotional aspects related to the discovery of an unexpected pregnancy or an hiv positive status would act as a stressor and have potentially negative mental health outcomes [ ] . it is likely that after encountering a stressor, adolescents will experience stress and symptoms of depression and anxiety [ ] . the stress related to the discovery of an unexpected pregnancy is compounded by the shame and social stigmatisation of teenage pregnancy, and the ensuring social isolation from family and community increases the risk for psychological distress [ ] . the framing of pregnancy during adolescence as a social problem means that pregnant teens receive limited social support, which in turn is linked to poor mental health outcomes [ ] . the stress related to the discovery of an unexpected pregnancy is heightened further in the case of a dual discovery of being hiv positive [ ] . the presence of depression, anxiety, and post-traumatic stress disorder in hiv-positive individuals is related to diagnosis and disclosure, and hiv-positive women experiencing 'unintended' pregnancy are at high risk for antenatal depression [ , ] . agyw in our study described a worrying trend of suicidal ideation. thoughts about suicide narrated by agyw were related to unexpected discovery of pregnancy and its consequences, hiv diagnosis, and feelings of emotional isolation. suicide was described as "the best solution" to situations of stress created by the discovery of unexpected discovery of pregnancy or hiv positive status, lack of material/financial or emotional support for young mothers, and feelings of victimisation as a result of gossip or judgement. adolescents faced with multiple stressors may experience a sense of being overwhelmed and unable to cope, and view suicide as an escape [ ] . agyw in our study associated low self-esteem and low self-worth with depression and suicidal ideation. negative self-cognitions and low self-worth are associated with depression, and positive self-esteem is a critical component of emotional well-being [ ] . adolescents' ability to manage their stress symptoms or address the stressor they encounter may be pivotal to protecting their mental health state, as it may buffer the impact of experienced stress on mental health [ ] . additionally, self-esteem and social support are amongst the 'protective assets' associated with improved srh outcomes [ ] . in our study, agyw expressed feeling emotionally isolated, lacking people who they felt they could trust and confide in without fear of judgement or recrimination. emotional isolation and lack of support, especially when faced with stressors such as the discovery of an unexpected pregnancy or an hiv diagnosis, negatively impacts mental health. the emotionally distressing aspects of unexpected discovery of pregnancy, or an hiv diagnosis, combined with a lack of social support, contribute to the high rates of depression amongst agyw [ ] . agyw in our study described additional stress related to teenage pregnancy and child-bearing relating to concern around the ability to support a baby financially, especially when there was a lack of material and/or emotional support from the father of the child. agyw in south africa, particularly those in resource-constrained or violent households, face a variety of personal and structural challenges, linked to disempowerment and psychological distress more broadly; an 'unintended' pregnancy can compound pre-existing social and economic vulnerabilities, and result in heightened feelings of stress and unhappiness [ ] . socio-economic disadvantage compounds other stressors in an adolescents' life, and when co-occurring with pregnancy or hiv, can lead to poor mental health outcomes and a lack of utilisation of health care services [ , ] . one limitation of this study was that the framing and concept of 'unintended' pregnancy was not investigated in more depth. for this reason, we avoid using the term 'unintended', and instead use the words of agyw respondents themselves when describing their unexpected discovery of a pregnancy, rather than objectively categorising the pregnancies as 'unintended'. in addition, social desirability bias relating to the stigma and shame around mental health may have resulted in a lack of disclosure from agyw regarding their own feelings of depression or suicide ideation. interpreting our findings within a syndemic theory framework is helpful, in order to describe the integration of sociocultural, psychological, and physiological factors that combine to shape agyw vulnerabilities and experiences [ ] . our findings suggest that south african adolescent girls and young women's vulnerability towards early pregnancy, hiv infection and poor mental health are bidirectional and interconnected. the social context in which south african agyw are situated, as described by respondents in our study, is characterised by a lack of social support, economic insecurity, and stigma, and serves to exacerbate the gendered and age-related vulnerabilities of this population. this interaction of socio-cultural, economic, structural, gendered, age-related and biological factors increase south african agyw's heightened risk of negative srh outcomes, cooccurring with psychological distress and poor mental health [ ] . in line with the syndemic theory suggesting synergistic interactions between epidemics, and the interconnectedness and clustering of psychosocial conditions such as 'unintended' pregnancies, psychosocial distress, and hiv infection in agyw, there is a need for comprehensive hiv prevention programming inclusive of mental health support [ ] . it is clear that interventions aiming to reduce rates of teenage pregnancy and reduce hiv acquisition amongst agyw in south africa, need to incorporate mental health components [ ] . recommendations have been made for integrating mental health care into care for patients with chronic non-communicable diseases, as well as communicable diseases such as hiv [ ] , but few recommendations for integrating mental health into srh delivery exist [ ] . the links between mental health, hiv status, and 'unintended' pregnancy, exacerbate the need to strengthen the integration of routine mental health screening in srh and hiv programming in order to enhance the health outcomes amongst agyw [ ] . addressing underlying mental health risks may be an important additional strategy to promote sexual risk reduction, and behavioural interventions which are able to improve mental health are also more effective in preventing negative sexual health outcomes such as hiv infection [ ] . the indication of a dual burden of psychological distress and sexual risk behaviours suggests that screening for mental health disorders should be integrated into srh services [ ] . despite the evidence of intersecting epidemics, mental health screening is not standard in hiv prevention and care settings and has not been added to the hiv care cascade. combination interventions inclusive of psychological and behavioural components may be able to achieve greater reductions in sexual risk behaviour among adolescents, as incorporating psychological health interventions appears to be a critical part of any comprehensive strategy for mitigating hiv risk [ ] . mental health services targeted at agyw, especially those that are hiv positive and/or pregnant, need to be integrated into srh services, especially those that aim to be "youth-friendly"; prevention, diagnosis and management of depressive symptoms should also be included in the package of comprehensive services [ , ] . early mental health screening could help catch agyw who might not yet be diagnostically clinical depressed. given the evidence, it is likely that agyw have overlapping epidemics that are clinically significant. practical recommendations for improving mental health care delivery to agyw include improving mental health, advocacy, decentralization of services, taskshifting and on-the-job training [ , ] . the way in which mental health issues, such as stress and depression, are defined and conceptualised differs across settings and socio-cultural contexts, and interventions needs to be contextually relevant [ ] . in addition to contextual and conceptual equivalence, linguistic equivalence of terms related to mental health should be taken into account. the words "depression" and "anxiety" do not have direct equivalents in some south african languages, with psychological distress, including depression, described behaviourally rather than cognitively, and expressed and/or experienced somatically, or situated within the relational domain [ , ] . in addition, the term "unintended pregnancy" is problematic, with traditional measurements dichotomously classifying pregnancies as intended or not, based on a woman's intentions before she became pregnant [ , ] . "unplanned pregnancies" likewise have been defined as pregnancies which occur when a woman is using contraception or did not desire pregnancy as an outcome [ ] . the key problem with these binary classifications of pregnancies as unintended/intended, planned/unplanned, is that they fail to consider the complexity of intention, motivation and desire [ ] . the construct of 'pregnancy acceptability' may be a more useful way to taking into account the complexity of pregnancy intentions, in the context of women's lived experiences, emotions, relationships, and socio-economic circumstances [ ] . a woman's emotions, levels of preparedness, and acceptance of a pregnancy are likely to change in reaction to external factors, which in turn influence health outcomes [ ] . the biomedical/clinical understandings and definitions of "depression" and "unintended pregnancy" may not always capture an individual's subjective experiences and articulation of these states [ ] , and in order for any intervention to be successful, there is a need to be sensitive and reflective of the reality of people's lives, with an understanding of the language that agyw use to describe their lived experiences of depression and pregnancy, which is why qualitative research such as the findings we present here, is much needed [ ] . indeed, agyw in south africa construct "depression" and pregnancy is a complex phenomenon manifesting in a variety of emotions, thoughts, and behaviours; finding ways to surface contextually congruent understandings of sexual and reproductive health, and mental health can inform the development of interventions that are contextually and population relevant [ ] . mental health and srh interventions and services need to be contextually appropriate and reflective of the reality of people's lives. screening tools need to take into account the diversity of understandings of emotional suffering and distress, using appropriate terms, language and concepts. it is evident that agyw in south africa face substantial social adversities and related mental health challenges due to a range of srh, social, economic, environmental, physiological and interpersonal factors. building on previous research that has found associations between depressive symptoms and psychological distress related to pregnancy, combined with a lack of social support amongst south african women [ ] , our findings provide rich descriptive data on the lived reality of the interconnected psychosocial risks including stress, emotional isolation, feelings of depression and suicidal ideation, with 'unintended' pregnancy and hiv that agyw in south africa face, from their own perspectives. framing these interconnections within the syndemic framework can help to inform interventions that seek to address agyw risk. as psychological distress is associated with increased risk behaviours, it is critical that efforts to address early pregnancy and hiv infection amongst agyw incorporate mental health components. interventions to improve emotional wellbeing and coping mechanisms for agyw are needed in order to improve sexual and reproductive health outcomes; indeed, in a context where hiv, stis, early pregnancy are common, it is all the more important to have such interventions integrated into srh services and part of largescale programmes for agyw. understanding the context of mental health is crucial in order to design and implement effective mental health programming, and to provide appropriate psycho-social support to young women, and in turn, address sexual and reproductive health challenges. open access this article is licensed under a creative commons attribution . international license, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the creative commons licence, and indicate if changes were made. the images or other third party 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inside yourself": lowincome adolescent south african girls' subjective experience of depression mentoring interventions and the impact of protective assets on the reproductive health of adolescent girls and young women this baby came up and then he said, 'i give up!': the interplay between unintended pregnancy, sexual partnership dynamics and social support and the impact on women's well-being in beyond comorbidity: a critical perspective of syndemic depression and diabetes in cross-cultural contexts syndemics and the biosocial conception of health a syndemic of psychosocial and mental health problems in liberia: examining the link to transactional sex among young pregnant women mental health system costs, resources and constraints in south africa: a national survey integrating mental health into south africa's health system: current status and way forward umthente uhlaba usamila-the rd south african national youth risk behaviour survey measuring depression and anxiety in sub-saharan africa the measurement and meaning of unintended pregnancy it's not planned, but is it okay? the acceptability of unplanned pregnancy among young people. women's health issues a feminist phenomenological description of depression in low-income south african women we would like to acknowledge and thank the adolescent girls and young women, and other participants who agreed to make themselves available to take part in this research, and share their views, opinions and experiences with us. the combination hiv prevention interventions were funded by the global fund to fight aids, tb and malaria, and implemented in districts in south africa by a range of government departments and civil society organisations that were appointed by the organisations responsible for the management of the agyw programme: western cape department of health, kwazulu-natal treasury, kheth'impilo, soul city institute for social justice, and the networking hiv and aids community of southern africa (nacosa). the programme was aligned with the she conquers campaign and was implemented with support from the south african national aids council (sanac) through the country coordinating mechanism (ccm) and the ccm secretariat. key: cord- -pxryt wn authors: leroy, eric; gonzalez, jean paul title: filovirus research in gabon and equatorial africa: the experience of a research center in the heart of africa date: - - journal: viruses doi: . /v sha: doc_id: cord_uid: pxryt wn health research programs targeting the population of gabon and equatorial africa at the international center for medical research in franceville (cirmf), gabon, have evolved during the years since its inception in in accordance with emerging diseases. since the reemergence of ebola virus in central africa, the cirmf “emerging viral disease unit” developed diagnostic tools and epidemiologic strategies and transfers of such technology to support the response of the national public health system and the world health organization to epidemics of ebola virus disease. the unit carries out a unique investigation program on the natural history of the filoviruses, emergence of epidemics, and ebola virus pathogenesis. in addition, academic training is provided at all levels to regional and international students covering emerging conditions (host factors, molecular biology, genetics) that favor the spread of viral diseases. the international centre for medical researches of franceville (cirmf) was founded in by his excellency el hadj omar bongo ondimba, president of the gabonese republic, and mr. pierre guillaumat, the chairman of the petroleum company, total gabon. the centre was inaugurated on december th, with the participation of numerous internationally eminent scientists (figure ) . in the s, viral hemorrhagic fevers became a focus of attention in equatorial. the decision to develop a high security laboratory for the study of ebola virus disease came after a ebola virus disease outbreak in mayibout area, gabon. the main objective was to develop the potential for rapid and specific diagnosis on viral hemorrhagic fevers and to have a backup for field investigation of severe viral hemorrhagic fever epidemics. because the unique expertise and interaction of the cirmf team along with the international world health organization (who) teams for ebola virus disease, the gabonese government agreed to such a project. the first bsl + (including negative pressure and glove box) laboratory was built in , mostly financed by the foreign ministry of france ( figure ). this laboratory was built in a period of quasi "emergence" of successive ebola virus disease outbreaks in gabon, and the plans to upgrade the bsl + laboratory were not efficient. a specific research unit was founded in to study emerging infectious diseases: the emerging viral disease unit (umve). thanks to work done between and , both in the field and in research, cirmf became a national reference laboratory and a who collaborating center in the equatorial african region. a second high security laboratory for risk group / agents, mostly funded by the total gabon oil company and the gabonese government, was built between and on cirmf campus ( figure ). this bsl- laboratory was commissioned by a combined team of experts from the pasteur institute of paris, national institute of health and medical research, france, and jean mérieux p laboratory of lyon. on hectares, the cirmf campus has a working space of , square meters composed of a main building, laboratories, service buildings, and living accommodations (figure ). the present high containment and high security laboratory, operated by the emerging viral diseases unit (umve), is one of laboratories in africa that can manipulate risk group / agents (i.e., ebola, marburg, and crimean-congo hemorrhagic fever viruses). research, including isolation and characterization of these highly pathogenic viruses is performed in accordance with international rules defined by who on the handling risk group / agents updated equipment includes a double door autoclave, thermo regulated cabinet, a high security centrifuge system, a conventional photonic microscope, a virus isolation unit, and two independent rooms the can be shut down alternatively after decontamination when necessary. an uninterruptable controlled electrical supply for refrigeration, computer systems, and other systems is ensured by two back-up power plants. the telecommunication network consists of mobile phones and the internet through a dedicated satellite antenna. other service units consist of a primate center, the gorilla and chimpanzee study station in lopé national park, and the dienga health observatory. investigators from this observatory conduct field studies on the prevalence of viral and parasitic diseases and their implications for public health [ ] dedicated to medical research, the primate center houses more than primates belonging to ten different african species (e.g., chimpanzees (pan troglodytes), gorillas (gorilla sp), mandrills (mandrillus sphinx), guenons (cercopithecus sp.), collared mangabeys (cercocebus torquatus), greater spot-nosed monkeys (cercopithecus nictitans), vervet monkeys (chlorocebus pygerythrus) and an asian macaque (macaca sp.) colony. one of the largest primate centers in africa, the primate center is equipped with level a and a animal facilities for scientific research protocols. the great apes are housed in large open-air facilities. semi-free living colony of twelve forested hectares harbor about half of the primates at the primate center. at the gorillas and chimpanzee study station, researchers study ecological approaches to the emergence of zoonotic diseases, inter-species transmission of pathogens, and disease outbreaks in humans and wild animals [ ] . running costs are funded by the ministry of economy, gabon, the national petroleum company of total-gabon, and the ministry of foreign and european affairs, france. several international agencies participate in a variety of financial supports including scientists' salaries, equipment, research projects, and academic grants (e.g., ird, who, united states agency for international development, national center for scientific research, france). technical laboratory training support of gabonese teams and other african countries has been one of the major aims of cirmf. the umve actively participates in the academic training at the regional graduate school and the different state universities of equatorial africa. a special relationship with the "health sciences university" of libreville and the "sciences and technology university" of masuku in franceville encourages collaborative research projects with teachers and supports students of the faculties of medicine and sciences in the preparation of doctoral theses. cirmf receives doctoral and post-doctoral scientists from other universities of developed countries (e.g., bonn, marseille, montpellier, and tübingen universities). continuing medical education in the form of post-doctoral workshops are held at the cirmf for discussion and demonstration of modern techniques. as a national reference laboratory, cirmf has the following roles: diagnosis of suspected cases during outbreaks of viral hemorrhagic fevers or severe clinical infectious syndromes; development of new methods for diagnosing such infections; surveillance of animal fatalities in reservoir or intermediate hosts; and intervention during outbreaks of unknown etiology. cirmf diagnosed infections of more than pathogens that could not be identified in other biology laboratories throughout the country. cirmf maintains close ties to several components of the national healthcare system, such as amissa bongo regional hospital in franceville or the sino-gabonese friendship hospital. in order to facilitate national and international scientific exchanges including scientists, equipment, biological specimens, the capital of gabon, libreville, is part of cirmf operational system. hosted by the university of health sciences, libreville, one laboratory is now operational. tight connections with other scientific teams in libreville are under development (i.e.,: military hospital, libreville; general hospital, libreville; a. schweitzer lambarene foundation). the emerging viral diseases unit, cirmf, proposes forming a research partnership to study infectious diseases transmitted by animals of the tropical rain forests regions of equatorial africa. the proposed partnership builds on such existing collaborations of several years between the major research centers of other french speaking equatorial african countries, namely the national public health laboratory in brazzaville, republic of the congo, and the institute for biomedical research in kinshasa, democratic republic of congo. an international partnership with the ird, marseille, france, and the institute of virology, bonn, germany, will assist in the development of this regional partnership. with the who regional office, brazzaville, republic of the congo, the umve-cirmf field team participates along with other international partners (e.g., centers for disease control and prevention, usa; laboratory centre for disease control and national microbiology laboratory, winnipeg, canada; p laboratory of the national institute for communicable diseases, south africa) to respond to all ebola virus disease epidemics in africa. cirmf aims to use laboratory and field expertise be a regional focal resource in conjunction with local health authorities to organize epidemic responses. cirmf expertise is also offered from by entering into laboratory-to-laboratory agreements. also, an informal international laboratory network for the diagnosis and surveillance of severe infectious clinical syndromes includes: the institut national de recherche biomédicale, democratic republic of the congo; laboratoire national de santé publique de brazzaville, republic of the congo; metabiota/laboratoire des maladies emergentes, yaoundé, cameroon; pasteur institute, bangui, central african republic; institute of virology, bonn university, germany; and p jean mérieux lyon, france. exchange of materials, equipment, and personnel is facilitated through memorandums of understanding. cirmf holds more than , samples of various origins in a biological repository, which is accessible to the international scientific community. the uvme assists the national public health system in consolidating and formalizing microbiological monitoring of the equatorial african sub-region. ultimately, cirmf will be positioned as a center of excellence for microbiological surveillance and research in a global network. developing diagnostic tools and strategies is the main driver to improve surveillance and research of emerging viral diseases. a strategic choice was made to link syndromes to an etiological agent, including hemorrhagic syndromes. to isolate and diagnose highly pathogenic viruses, a progressive and diversified methodology was applied. the first approach used real-time virus-specific pcr (qrt-pcr). if the first approach was not successful, conventional rt-pcr was implemented using degenerate consensus primers targeting conserved regions of the genome. ultimately, random amplification of nucleotide sequences was directly applied to the original biological material (dna chip re-sequencing, meta-genomic pyrosequencing ( life sciences, branford, ct)). umve studied the factors implicated in the three steps that led to ebola virus and marburg virus diseases emergence in humans. these steps include: the identification of reservoir species, the circulation within the natural host, the crossing to intermediary animal species, and finally the direct transmission to humans from great apes and fruit bats. antibodies and nucleotide sequences specific for ebola virus were detected in the liver and spleen of fruit bat belonging to three species (hypsignathus monstrosus, epomops franqueti, myonycteris torquata) in gabon and republic of the congo (figure ). antibodies and nucleotide sequences specific for marburg virus were found in the egyptian fruit bat (rousettus aegyptiacus) in gabon, suggesting that bats might be reservoirs for filoviruses [ ] [ ] [ ] . we showed that ebola virus caused extensive epizootics among gorillas and chimpanzees, killing thousands of animals during the last decade in parts of gabon and republic of the congo [ ] . we characterized the viral variants associated with all ebola virus disease outbreaks that occurred between and and developed new epidemiological models of ebola virus disease epidemics, based on the identification of several independent epidemic chains. the identification of multiple variants during the gabon/republic of congo outbreak and two phylogenetically divergent lineages suggest independent introductions into great ape and human populations following multiple viral spillovers from a reservoir host [ ] [ ] . in this "multi-emergence" hypothesis, ebola virus disease outbreaks would occur episodically during certain ecological conditions caused by habitat disturbances or climatic phenomena. this hypothesis also implicitly assumes that ebola virus was present in equatorial africa long before the first documented disease outbreak in , as supported by various serological surveys. furthermore, we recently showed that the luebo outbreak in the democratic republic of the congo was linked to massive fruit bat migration, strongly suggesting that humans could be infected directly by bats or by consumption of bats [ ] . in the study of immunological mechanisms of ebola virus disease humans, we showed that fatal infection is associated with aberrant innate immunity and global suppression of adaptive immunity [, [ ] [ ] [ ] [ ] . the innate immune reaction is characterized by a 'cytokine storm', with a hyper secretion of numerous pro-inflammatory cytokines, chemokines and growth factors, and by the noteworthy absence of antiviral interferon (ifn)-α [ , , ] . immunosuppression of adaptive immunity is characterized by very low levels of circulating cytokines produced by t lymphocytes and by massive loss of peripheral cd and cd lymphocytes, probably through fas/fasl-mediated apoptosis. finally, we hypothesized that a viral protein with super-antigen activity might be involved in the massive t cell apoptosis [ ] . in striking contrast with fatal outcome, effective control of ebola virus infection is associated with balanced immune responses in survivors. asymptomatic ebola virus infection was demonstrated in humans during the - disease outbreak in gabon [ ] . asymptomatic infection was associated with an early strong inflammatory response that may be involved in the early inhibition of viral replication [ , ] . consistent with this discovery, we showed a decade later that a large fraction of the human population living in forested areas of gabon has both humoral and cellular immunity to ebola virus [ ] . in the absence of identified risk factors, the high prevalence of 'immune' individuals suggests a common source of human exposure such as fruits contaminated by bat saliva. initially focused on ebola virus disease, umve science policy was redirected since by expanding the main research themes to other emerging viral diseases that could threaten public health in the congo basin (table ) [ ] [ ] [ ] [ ] . cirmf is geographically isolated from the capital of gabon, libreville. the libreville office is essential to the franceville headquarters as it coordinates visits from staff on field missions, and forwards imported equipment to headquarters. the capital is accessible by a -hour ride in a four-wheel drive vehicle or in a train (three times/week schedule) covering km. due to tropical weather, four weekly domestic plane rotations often fly on an inconsistent schedule. ultimately cirmf needs to be largely autonomous in term of electrical power (i.e.,: unexpected fuel supply disruption), cold chain with the necessity to maintain in situ a unit of liquid nitrogen production (repository), and purified water supply. cirmf is uniquely suited to study infectious diseases of the congolese tropical rain forest, the second world's largest rain forest. as a central point of a north-south transect of the rain forest, the center is able to study the biodiversity of africa including animal species, microbes, and parasites. cirmf is dedicated to conduct medical research of the highest standard, and is the only facility of its type in equatorial africa. with unrivalled infrastructure, multiple sites, and multidisciplinary teams, the center promotes a modern healthcare system in gabon. cirmf teams are engaged in trans-disciplinary projects bringing together specialists from the health sciences, biological sciences, veterinary medicine, conservation, the humanities, and environmental sciences. the center welcomes partnerships from around the world to work on global human health issues. coronaviridae coronavirus/hcov nl /gabon - human + coronavirus/hcov hku /gabon - human + coronavirus/hcov oc /gabon - human + available online fruit bats as reservoirs of ebola virus spatial and temporal patterns of zaire ebolavirus antibody prevalence in the possible reservoir bat species marburg virus infection detected in a common african bat multiple ebola virus transmission events and rapid decline of central african wildlife isolates of zaire ebolavirus from wild apes reveal genetic lineage and recombinants human ebola outbreak resulting from direct exposure to fruit bats in luebo, democratic republic of congo defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in ebola virus-infected patients apoptosis in fatal ebola infection. does the virus toll the bell for the immune system human fatal zaire ebola virus infection is associated with an aberrant innate immunity and massive lymphocyte apoptosis association of kir ds and kir ds with fatal outcome in ebola virus infection lansoud-soukate, j. inflammatory responses in ebola virus-infected patients the acute phase of chikungunya virus infection in humans is associated with strong innate immunity and t cd cell activation evidence for ebola virus superantigen activity human asymptomatic ebola infection and strong inflammatory response early immune responses accompanying human asymptomatic ebola infections high prevalence of both humoral and cellular immunity to zaire ebolavirus among rural populations in gabon recent introduction and rapid dissemination of chikungunya virus and dengue virus serotype associated with human and mosquito co-infections in re-emergence of crimean-congo hemorrhagic fever virus in central africa type wild poliovirus and putative enterovirus in an outbreak of acute flaccid paralysis in congo concurrent chikungunya and dengue virus infections during simultaneous outbreaks this article is an open access article distributed under the terms and conditions of the creative commons attribution license we would like to thank all the umve-cirmf and the health ecology research unit of cirmf work teams. we acknowledge the support and funding of the gabonese government and the oil company total-gabon. we acknowledge foreign agencies that largely contributed to the success of the "cirmf filovirus program": the french ministry of foreign and european affairs through the french embassy in gabon; metabiota and global viral (alias gvfi) for technical and equipment support; and the institute for research development, for funding research teams and providing high performance equipment. pneumovirus/hrsv /gabon - human +/- the authors declare no conflict of interest. key: cord- -f y vh authors: nelson, martha i.; njouom, richard; viboud, cecile; niang, mbayame n. d.; kadjo, hervé; ampofo, william; adebayo, adedeji; tarnagda, zekiba; miller, mark a.; holmes, edward c.; diop, ousmane m. title: multiyear persistence of pandemic a/h n influenza virus lineages in west africa date: - - journal: j infect dis doi: . /infdis/jiu sha: doc_id: cord_uid: f y vh our understanding of the global ecology of influenza viruses is impeded by historically low levels of viral surveillance in africa. increased genetic sequencing of african a/h n pandemic influenza viruses during – revealed multiyear persistence of viral lineages within west africa, raising questions about the roles of reduced air traffic and the asynchrony of seasonal influenza epidemics among west african countries in the evolution of independent lineages. the potential for novel influenza virus lineages to evolve within africa warrants intensified influenza surveillance in africa and other understudied areas. our understanding of the global ecology of influenza viruses is impeded by historically low levels of viral surveillance in africa. increased genetic sequencing of african a/h n pandemic influenza viruses during - revealed multiyear persistence of viral lineages within west africa, raising questions about the roles of reduced air traffic and the asynchrony of seasonal influenza epidemics among west african countries in the evolution of independent lineages. the potential for novel influenza virus lineages to evolve within africa warrants intensified influenza surveillance in africa and other understudied areas. keywords. human influenza a virus; pandemic; phylogenetic analysis; africa. despite strong seasonal bottlenecks, influenza a viruses (iavs) persist in humans through continual global migration, which repeatedly reseeds viral diversity on local scales [ , ] . it has been proposed that southeast asian countries are the most important global sources of antigenically novel iavs, supplying europe, north america, africa, latin america, and oceania with novel variants on a continual basis [ ] . subsequent studies added complexity to this model, including roles for north america and other regions in the genesis of novel diversity [ ] that are more consistent with a shifting meta-population model [ ] . however, the lack of viral sequence data from a number of global regions, including latin america, south asia, and africa, remains a major barrier to understanding the complex global ecology and evolution of iavs. the emergence of novel pandemic a/h n ( ph n ) viruses in early resulted in a global expansion in iav sequencing. currently, > full-length sequences of the main antigenic protein, the hemagglutinin (ha), are available through the global initiative on sharing all influenza data (gisaid; www.gisaid.org). notably, influenza surveillance increased in a number of african countries during - in response to the pandemic and as part of a larger trend of increased recognition of the seasonal influenza virus burden in africa (see reviews [ , ] ). to elucidate the evolution of influenza viruses in africa, we conducted a large-scale phylogenetic analysis of global ph n influenza virus diversity during - , including ph n ha sequences collected in african countries. our analysis identified well-supported clades of ph n viruses that each persisted for > . years in west africa, highlighting the need to further understand the ecology and evolution of iavs in this understudied and relatively geographically isolated region. table ; genbank accession numbers kj -kj ). because cameroon shares a long border with nigeria and no other central african countries had viral sequence data available that met the criteria for this study, for simplicity cameroon was considered to be within west africa in this analysis. the entire data set of ph n ha (h ) sequences was aligned using muscle alignment software (version . . ) [ ] , with manual correction. a maximum likelihood (ml) tree of these data was inferred by using raxml software (version . . ) [ ] and a general time-reversible (gtr) model of nucleotide substitution with a gamma-distributed (Γ) rate variation among sites (data available on request). given the extremely large size of the data set, bootstrap replicates were generated using raxml software, with the same gtr + Γ model of nucleotide substitution, to assess the robustness of individual nodes. the resulting phylogeny was visualized and midpoint rooted using figtree software (version . . ; available at: http://tree. bio.ed.ac.uk/software/figtree/), and amino acid substitutions were identified using a customized r script. similarly, an ml phylogeny also was inferred for full-length ( nt) ph n na (n ) sequences that were obtained and analyzed using identical methods (supplementary figure ) . for the purposes of visualization ( figure ), an ml tree also was inferred from a subset of the ha sequence data ( ha sequences) that included all african viruses, viruses identified within west african clades i and ii (described below), and ha sequences randomly sampled from each year during - (all sequences from were used because < sequences were available). the full tree used for figure , including tip labels, is available in supplementary figure . the majority of ph n influenza viruses collected in africa during - ( of ; %) are phylogenetically interspersed with viruses collected from other continents, as expected given the ability of influenza viruses to rapidly disseminate between continents. however, african ph n viruses ( %) are positioned within phylogenetically distinct clades that comprised viruses collected predominantly in west africa (labeled as west african clades i and ii in figure ). both west african clades i and ii are defined by high bootstrap values (≥ %) and separated by long branch lengths on the ha tree, indicating that the lineages have evolved independently. a monophyletic cluster of kenyan viruses also was identified that contains viruses collected from march (a/nairobi/ / ) through november (a/kenya/ / ), indicative of months of persistence ( figure ). however, this cluster was not supported by high bootstrap values and therefore was not considered in our analysis. both west african clades i and ii are relatively small- and isolates, respectively. however, the small size of these clades is more likely to be explained by the sparse sampling of influenza viruses in west africa than by their low prevalence (table ) . west african clade i comprises isolates collected from west african countries (côte d'ivoire, ghana, and senegal) figure ) . otherwise, the s t and r k substitutions were observed globally at extremely low levels, at < % among the other pandemic h sequences. all west african clade i isolates also clustered together on the na global phylogeny, and of isolates in this cluster also were highly bootstrap supported ( %) (supplementary figure ) . west african clade ii is larger ( isolates) and more diverse than clade i, containing isolates from west african countries (burkina faso, cameroon, côte d'ivoire, ghana, and nigeria), from ethiopia in east africa, and from non-african countries in europe (france, italy, norway, and sweden) and the united states (minnesota). within west africa, clade ii has persisted for ≥ . (table ). in contrast, the east african isolates were collected during , and all non-african isolates were collected from november to january . critically, of the non-west african isolates (except for a single outlier from france: a/paris/ / ) cluster together within a highly supported subclade (bootstrap, %), consistent with migration event of this lineage out of west africa. although the majority of west african isolates from clade ii also cluster together on the na phylogeny ( supplementary figure ) , the non-west african isolates from ethiopia, europe, and the united states are positioned together in a different part of the na tree, indicative of reassortment. four amino acid substitutions in the h sequences were observed among / clade ii viruses: a t, n d, t k, and v a ( supplementary figure ) . the a t, n d, and t k substitutions were observed globally at extremely low levels: < % among the other pandemic h sequences. a central question in influenza virus epidemiology and evolution is whether viral lineages can persist at low levels of circulation on local and regional scales, or whether new viruses must be reseeded continually from a globally sustained gene pool. in the past years, large-scale phylogenetic analyses of global influenza virus sequence data have provided important insights into viral migration and persistence [ ] [ ] [ ] [ ] [ ] . the great intensification of iav sequencing that occurred during the h n pandemic provided the best opportunity to identify viral persistence on local scales, including low-frequency variants. heightened influenza surveillance during new york state's first pandemic wave revealed that a/h n seasonal influenza viruses persisted into the early summer, although this persistent lineage did not give rise to the state's subsequent fall epidemic virus [ ] . in the united kingdom, baillie et al [ ] detected united kingdom-specific ph n lineages that persisted between the first and second pandemic waves of , although the close timing of the waves meant that the lineages persisted for < months in the united kingdom. our analysis of viral evolution in west africa revealed the sustained persistence of ph n clades over a nearly -year period, although increased sampling is required to confirm that isolates from other localities are not interspersed within these clades. the intensity of global sampling of pandemic a/h n influenza viruses during this time (> full-length ha sequences were included in this analysis) reduces the likelihood that the persistence observed here is an artifact of unsampled diversity. in fact, the relative sparseness of sampling in west africa compared to other regions ( of global sequences, . %) means that our data are strongly biased against the detection of clades comprised solely of west african viruses. that air traffic volume within west africa is lower than in other global regions further supports the plausibility of influenza virus lineage persistence for several years without widespread dissemination to other continents. the delayed appearance of the pandemic h n virus in west africa months after the emergence of the virus in north america in march further supports the possibility that influenza virus evolution in west africa is less strongly linked to other continents owing to reduced international air traffic [ ] . the lack of synchrony among the variable seasonal patterns of geographically linked african countries may also facilitate the persistence of influenza viruses within west africa. in contrast to temperate areas where influenza virus epidemics are strongly synchronized during winter and undergo strong bottlenecks during summertime, the virus may persist through continual migration among seasonally variable and asynchronous west african localities, similar to what is thought to occur within the southeast asian network [ ] . in senegal, which has been conducting influenza surveillance for more than a decade, peaks in influenza activity coincide with the rainy season during july through september [ ] . nigeria, côte d'ivoire, and cameroon exhibit more variable patterns of influenza virus seasonality, although longer time series of data are required [ , ] . the phylogenies indicate that both west african clades, clades i and ii, evolved within multiple west african countries, with no evidence of long-term persistence within a single country, which is consistent with a role for viral migration between west african countries in the persistence of the virus. high levels of bootstrap support for a subclade within clade ii that contains isolates from ethiopia, europe, and the united states indicates that clade ii viruses may have disseminated from west africa to east africa and from east africa to europe and the united states around . additionally, the detection of a singleton virus from france within both clade i (a/lyon/ chu/ . / ) and clade ii (a/paris/ / ) could relate to the frequency of air traffic between francophone west africa and france. the lack of detection of either west african clades i or ii in north or southern africa may also reflect low human mobility between these regions and west africa. further understanding of influenza virus migration within africa and between africa and other continents will require additional sequence data. although the intensity of influenza surveillance in africa still lags behind that of other continents, these findings suggest that substantial viral diversity circulates within africa, including viral lineages that are unique to the region but capable of disseminating to other continents. small sample sizes at country levels necessitate cautious inference of clade prevalence, and it remains unknown whether clades i and ii comprised substantial proportions of the h n diversity in west african countries. the possibility of minor variants evolving locally within west africa undermines the assumption that a vaccine matched to globally dominant lineages will necessarily protect against these local lineages, although more data is clearly required. further knowledge of the viral lineages that circulate within africa, including antigenic characterization, is required to understand the full diversity and global ecology of influenza viruses in humans and to inform vaccination strategies within africa. supplementary materials are available at the journal of infectious diseases online (http://jid.oxfordjournals.org/). supplementary materials consist of data provided by the author that are published to benefit the reader. the posted materials are not copyedited. the contents of all supplementary data are the sole responsibility of the authors. questions or messages regarding errors should be addressed to the author. phylogenetic analysis reveals the global migration of seasonal influenza a viruses the genomic and epidemiological dynamics of human influenza a virus the global circulation of seasonal influenza a (h n ) viruses global migration dynamics underlie evolution and persistence of human influenza a (h n ) temporally structured metapopulation dynamics and persistence of influenza a h n virus in humans influenza in africa: uncovering the epidemiology of a long-overlooked disease influenza in africa muscle: multiple sequence alignment with high accuracy and high throughput maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models unseasonal transmission of h n influenza a virus during the swine-origin h n pandemic evolutionary dynamics of local pandemic h n / influenza virus lineages revealed by whole-genome analysis delayed pandemic influenza a virus subtype h n circulation in west africa sentinel surveillance for influenza in senegal influenza viruses in nigeria, - : results from the first months of a national influenza sentinel surveillance system spatiotemporal circulation of influenza viruses in african countries during - : a collaborative study of the institut pasteur international network acknowledgments. we thank dr workenesh ayele, phd at ethiopian health and nutrition research institute for providing a/h n ha sequences from ethiopia, east africa, for comparison with sequences from west africa.financial support. this work was supported by the multinational influenza seasonal mortality study, an ongoing international collaborative effort to understand influenza epidemiology and evolution, led by the fogarty international center, national institutes of health, with funding from the office of global affairs at the department of health and human services (c. v. and m. i. n.). e. c. h. is supported by an national health and medical research council (nhmrc) australia fellowship.potential conflicts of interest. all authors: no reported conflicts. all authors have submitted the icmje form for disclosure of potential conflicts of interest. conflicts that the editors consider relevant to the content of the manuscript have been disclosed. key: cord- - vetk jd authors: shayo, elizabeth; van hout, marie claire; birungi, josephine; garrib, anupam; kivuyo, sokoine; mfinanga, sayoki; nyrienda, moffat j; namakoola, ivan; okebe, joseph; ramaiya, kaushik; bachmann, max oscar; cullen, walter; lazarus, jeffrey; gill, geoff; shiri, tinevimbo; bukenya, dominic; snell, hazel; nanfuka, mastula; cuevas, luis e; shimwela, meshack; mutungi, gerald; musinguzi, joshua; mghamba, janneth; mugisha, kenneth; jaffar, shabbar; smith, peter g; sewankambo, nelson kaulukusi title: ethical issues in intervention studies on the prevention and management of diabetes and hypertension in sub-saharan africa date: - - journal: bmj glob health doi: . /bmjgh- - sha: doc_id: cord_uid: vetk jd nan the incidence of diabetes and hypertension has risen sharply in sub-saharan africa alongside a continuing high burden of hiv infection. in many settings, the prevalence figures among adults are %- % for diabetes, above % for hypertension and %- % for hiv infection. [ ] [ ] [ ] all these conditions require lifelong treatment, and they have increased substantially the demand for chronic care services in africa, where health systems have, until recently, focused on tackling acute infectious diseases. there is considerable inequity in service provision for chronic diseases. hiv services, including antiretroviral therapy, are available widely for free and are organised typically in stand-alone clinics. over % of people estimated to be living with hiv infection are in regular care. in contrast, this figure is only about %- % for people living with diabetes or hypertension. a major challenge is that medicines for diabetes and hypertension are generally not provided free of charge and have to be purchased by patients. even in those countries that do provide free medicines for hypertension and diabetes, shortages are common and patients then have to purchase the medicines from private suppliers. our research collaboration is evaluating a biomedical diabetes preventive intervention in people living with hiv infection in a placebocontrolled randomised trial and, separately, evaluating integrated healthcare provision compared with standard care for people living with hiv, diabetes or hypertension in a clusterrandomised controlled trial. there are no data on the effectiveness of these approaches from africa. therefore, these trials have clinical and health economic endpoints and the research is underpinned by an implementation research approach, which, for example, requires strong engagement with health policy makers . [ ] [ ] [ ] [ ] we discuss the implications of a limited supply of medicines and potential solutions to track the equity of medicine supply. in particular, we consider what should the ethical approach be for a research programme in terms of provision of a steady and sustainable supply of medicines for patients with diabetes and hypertension when alternative affordable and accessible supplies are unavailable? possible solutions and lessons from other contexts should the research be conducted in realworld conditions where medicines supply for hypertension and diabetes is patchy? if we conduct the research within the context of real-world conditions, then, under the ► conducting intervention studies in africa, where medicines supply for chronic conditions is inequitable and patchy, raises major ethical issues. ► here we discuss what should the ethical approach be for a research programme in terms of provision of a steady and sustainable supply of medicines for patients with diabetes and hypertension. integrated care model that we are testing, patients with different conditions would sit together in the same clinic and have consultations with the same healthcare providers. it will be morally challenging for clinical staff and researchers to turn away one group of patients because of a lack of medicines while for others, with hiv infection, treatment is available freely. in the past, in the vertical stand-alone models of care, the ethical dilemma was less stark because hiv and diabetes/hypertension clinics operated at different locations, sometimes on different days and involved different clinicians. as well as the issue of inequity, observing people living with diabetes and hypertension unable to access medicines, which are both low-cost and effective, could break the ethical principle of beneficence, which states that researchers should have the welfare of the participants as a goal. also, if the research is conducted to real-world conditions, it may be of limited relevance by the time it is completed. this is because the provision of medicines for chronic disease management in africa is likely to increase in the next few years with the increased pressure that is now on donors and governments to support these treatment programmes. if drug shortages decrease, then the findings of our research programme, which would be available in a few years' time, would be of very limited relevance when they are published. thus, in our view, there are both moral and scientific reasons for ensuring patients entering such intervention studies have access to uninterrupted supplies of medicines for the duration of the research. should the research programme purchase the medicines for participants to enable the research to run smoothly? if the study identifies a model of care that is costeffective, it could give impetus to government health services to strengthen their medicine supply chains. on the contrary, by carrying the cost that should be met by governments and donors, it could potentially reduce the pressure on health authorities to find solutions, weaken the advocacy for patients' rights and inhibit the public from demanding their rights to access treatments. advocacy for the right to access antiretroviral therapy was crucial in hiv control in africa and will likely play a major role in enhancing access to medicines for diabetes and hypertension. if the research programme provides the medicines for study participants, it would not be sustainable beyond the duration of the research programme and would mean that patients who access treatment services today may have to stop taking their medicines when the study finishes. while the study is running, provision of free drugs would be a strong incentive for participants to join the study. patients will have the right to decline and to receive the care they would otherwise have received, but if this means a less reliable supply of medicines (than in the research programme), then patients are very likely to join the research. the issue is whether or not this is undue coercion. in our view, the ideal situation here is that access to medicines is strengthened for all, ideally by ministries of health. for this to happen, researchers must work in partnership with policy makers and disease control managers, that is, policy makers and disease control managers must have ownership of the research. researchers should be prepared to purchase medicines for short-term use to cover any gaps that might occur. where ministries of health cannot achieve a reliable supply, even with the support of research programmes, then research in those settings may not be feasible. is there an obligation to provide medicines to non-trial participants? another ethical dilemma arises because the research programme will include only a fraction of all the patients with the target conditions attending the clinics and patients not in the research studies will not have access to any enhanced treatment. although the costs of treatment for diabetes and hypertension are relatively low, it is most unlikely that a research programme could bear the costs of treating large numbers of non-study participants and a requirement to do so would make the research nonviable. not providing medicines to non-study participants will cause inequity between patients in the trial and those who are not. it could compromise outcomes if participants share their medicines to spread the benefits, for example, with relatives with chronic conditions not in the study. it may also endanger community support for the study if this sends the message that we do not care about family members. there is no precedence with provision of drugs to large numbers of non-study participants. when combination antiretroviral therapy for hiv was introduced in high-income countries, it was not available in public health clinics in africa because of its high cost. research in africa at that time will have faced similar dilemmas but wide-scale provision only occurred more recently. at that time, there were also some calls that the standards in clinical trials around treatment and access to medicines should be the same in africa as in high-income countries. however, the standardisation would have inhibited hiv research in africa and was opposed by global health researchers. this enabled the research to be conducted quickly and at relatively low cost, and research on the prevention and management of diabetes and hypertension may need similar considerations. thus, although not ideal, priority of medicines for research subjects will be essential in some settings where the supply of medicines cannot be strengthened for all. should the health facilities be encouraged to procure a greater supply of medicines to facilitate the research? in some circumstances, health facilities might be able to procure a greater supply of medicines to facilitate the bmj global health research. in countries such as tanzania and uganda, under district fiscal decentralised systems, health facilities have flexibility in how they spend their resources. however, if the supply of medicines for diabetes and hypertension was augmented in this way, this could be at the expense of service provision for other conditions, raising further ethical concerns. moreover, there are clear ethical issues if health facilities procure medicines to support a research programme without ensuring that this supply will be maintained after the study. the ideal solution here is that health facilities are supported to strengthen all medicines supply, not just for diabetes and hypertension. research to inform strategies for the prevention and management of diabetes and hypertension is vital in africa. however, such research raises complex ethical issues relating to the limited supply of medicines and a pragmatic approach specific to the african context is needed. it is clear that the research would likely produce meaningless results if the supply of medicines was erratic, but equally, the research programme cannot just purchase the necessary drugs for its trial participants. a solution to this conundrum has to be through discussion and working in partnership with the key stakeholders: the policy makers, disease control managers, healthcare providers, patient groups and community representatives. indeed, a fundamental ethical requirement is meaningful engagement with the key stakeholders. similar issues arose in the early years of research on hiv treatment in africa when antiretroviral therapy was prohibitively expensive and not available widely. the research that was conducted in these situations precipitated later pressure on the international community to ensure that life-saving medicines were made freely available to people living with hiv. hiv care and prevention would not have reached its current level without overcoming the initial obstacles to research on treatment. there is a pressing need to take on board the lessons from the progress made with hiv control to develop and expand research on diabetes and hypertension control. we have used our studies on three specific diseases-hiv infection, diabetes and hypertension-to highlight the ethical dilemmas, but the ethical challenges are likely to be common to other diseases. global, regional, and national age-sex specific mortality for causes of death, - : a systematic analysis for the global burden of disease study unaids. global hiv and aids statistics diabetes in sub-saharan africa: from clinical care to health policy world health organisation. global health observatory data: raised blood pressure redesigning primary care to tackle the global epidemic of noncommunicable disease world health organisation. global health observatory data. antiretroviral therapy coverage among all age groups hypertension in sub-saharan africa: a systematic review integrated care for human immunodeficiency virus, diabetes and hypertension in africa developing the ethics of implementation research in health implementation research: what it is and how to do it implementation research: new imperatives and opportunities in global health world health organisation. ethical considerations for health policy and systems research. geneva: world health organization the history of aids exceptionalism the ethics of clinical research in the third world ethics of hiv trials provenance and peer review not commissioned; externally peer reviewed. open access this is an open access article distributed in accordance with the creative commons attribution non commercial (cc by-nc . ) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. see: http:// creativecommons. org/ licenses/ by-nc/ . /. marie claire van hout http:// orcid. org/ - - - max oscar bachmann http:// orcid. org/ - - - jeffrey lazarus http:// orcid. org/ - - - luis e cuevas http:// orcid. org/ - - - shabbar jaffar http:// orcid. org/ - - - contributors es, ag, jb and sj wrote the first draft. mcvh made substantial contributions following the review by the journal. all the authors contributed to many iterations.disclaimer the views expressed in this publication are those of the author(s) and not necessarily those of the nihr or the uk department of health and social care or the european union.competing interests none declared.patient consent for publication not required. key: cord- -asclastg authors: kenmoe, sebastien; bigna, jean joel; modiyinji, abdou fatawou; simo, fredy brice n.; njouom, richard title: epidemiology of respiratory viral infections in people with acute respiratory tract infections in africa: the variafrica systematic review and meta-analysis protocol date: - - journal: syst rev doi: . /s - - - sha: doc_id: cord_uid: asclastg introduction: better characterisation of the epidemiological data on respiratory viral infections among people with acute respiratory tract infection (arti) can help to implement efficient strategies to curb the burden of arti in africa. we will conduct a systematic review and meta-analysis to determine the prevalence and factors associated with respiratory viral infection in people of all ages with arti residing in africa. methods: this work will include cross-sectional studies published between january , and december , , without any language restriction, on populations residing in african countries. we will consider studies that reported the prevalence of respiratory viruses in people with arti confirmed by a polymerase chain reaction technique. we will be searching pubmed, embase, african journals online, web of science, and global index medicus. the selection of relevant studies, extraction of data, and evaluation of the quality of the articles will be carried out independently by two review authors, and the discrepancies will be resolved by consensus or intervention of a third author. the heterogeneity of the studies will be assessed using the χ( ) test on cochrane’s q statistic. publication bias will be assessed by the egger test. studies will be pooled using a random-effect meta-analysis model. results will be presented by age group and sub-region of africa. using meta-regression models, we will identify factors associated with viral infections in people with arti. discussion: this systematic review and meta-analysis is based on published data and therefore does not require ethical approval. this work will serve as a basis for the development of strategies for prevention and control arti in africa and will also serve to identify data gaps and guide future investigations. the final report will be published in peer-reviewed journals as a scientific article and presented in workshops, conferences, and scientific conferences. systematic review registration: prospero, crd . electronic supplementary material: the online version of this article ( . /s - - - ) contains supplementary material, which is available to authorized users. data on people of all ages from a meta-analysis show that about million deaths were caused by acute lower respiratory infections in [ ] . the burden of these infections is essentially supported by sub-saharan africa which recorded about a quarter of all deaths ( . million death) [ ] . several viruses have been identified as etiologic agents responsible for arti. the clinically most important are classified into families which include paramyxoviridae (human respirovirus and , human rubulavirus and previously named parainfluenza virus - ), pneumoviridae (respiratory syncytial virus a and b and human metapneumovirus a and b), picornaviridae (enterovirus a to j and rhinovirus a to c), coronaviridae (human coronavirus: hcov- e, hcov-oc , hcov-nl , hcov-hku , sars-cov and hcov-emc), orthomyxoviridae (influenza a, b, and c), and adenoviridae (human adenovirus a to g) [ ] . the ecology of africa can give to this continent a specific epidemiological profile for arti. to date and to the best of our knowledge, one systematic review of data published between and on the prevalence of respiratory pathogens only in children under living in africa has been reported [ ] . this systematic review considered only data from sub-saharan africa did not perform a meta-analysis and quality assessment of the included articles. in the present systematic review with meta-analysis, we will include population regardless of age and from the entire african continent including northern africa. we will therefore able to compare the epidemiology of viral aetiologies of acute respiratory tract infections among age groups and among geographical regions of the continent. to address this gap of knowledge, we will conduct a systematic review and meta-analysis of the viral aetiology of acute respiratory infections in africa (var-iafrica) on people of all age groups to describe the epidemiology of respiratory viral infections (human respiratory syncytial virus, metapneumovirus, influenza virus, rhinovirus, adenovirus, bocavirus, parainfluenzavirus, coronavirus, and enterovirus). specifically, we will report prevalence and factors associated with high prevalence. this work is done to provide accurate data to guide health decision makers and to identify information gaps to guide future research on the burden of viral infections in arti africa. design this systematic review and meta-analysis will be conducted in accordance with centre for reviews and dissemination guidelines [ ] . this protocol has been reported following the recommendations for preferred reporting items for systematic reviews and meta-analyses for protocol (additional file : table s ) [ ] . this review has been registered with prospero, crd . this study will include the following: table s . this search strategy will be adapted to fit other databases. the references of the eligible articles and relevant reviews will be manually searched to identify additional studies. duplicates will be removed using endnote . two reviews authors will independently assess the titles and/ or abstracts of eligible articles according to the inclusion and exclusion criteria using rayyan online application. studies in a language different from english, french, or spanish will be translated using google translate and considered for eligibility. two review authors will independently evaluate the full text of the selected records. discrepancies will be resolved by consensus or will involve a third review author as an arbitrator. the agreement between the two authors will be estimated by cohen's kappa coefficient [ ] . the risk of bias tool developed for prevalence studies by hoy et al. will be used to assess the risk of bias of finally included studies [ ] . the defined items will be scored with for 'no' and for 'yes.' the total score of each article will be calculated by the sum of its items. the studies will be ranked according to their total score as low risk, moderate risk, and high risk for scores of - , - , and - , respectively. two review authors will assess the risk of bias and disagreements will be solved through a consensus or by arbitration of a third review author. a preconceived and tested questionnaire will be used to collect data (name of the first author, year of publication, design of the study, location, sampling method, period of study, timing of sample collection, number of viruses searched, country, city, latitude, longitude, altitude, clinical presentation, number of patients tested for respiratory viral infections, number of patients infected with viruses, diagnostic technique used, and male proportion).the countries will be grouped into regions according to the united nations statistics division. arti will be classified as severe infections (severe acute respiratory infections, acute lower respiratory infections, bronchitis, bronchiolitis and pneumonia) and benign infections (upper respiratory tract infections and influenza-like illness). two review authors will independently extract data. discrepancies between the two review authors will be resolved by consensus or by a third review author if necessary. authors of included studies will be contacted to request information in case of missing data. data will be analysed using the 'meta' packages of the statistical software r (version . . , the r foundation for statistical computing, vienna, austria). unadjusted prevalence will be recalculated based on the information of crude numerators and denominators provided by individual studies. prevalence will be reported with their % confidence interval and prediction interval. to keep the effect of studies with extremely small or extremely large prevalence estimates on the overall estimate to a minimum, the variance of the study -specific prevalence will be stabilised with the freeman-tukey double arcsine transformation before pooling the data with the random-effects meta-analysis model [ ] . egger's test will serve to assess the presence of publication bias [ ] . a p value < . on egger test will be considered indicative of statistically significant publication bias. heterogeneity will be evaluated by the χ test on cochrane's q statistic [ ] , which will be quantified by h and i values. the i statistic estimates the percentage of total variation across studies due to true between-study differences rather than chance. in general, i values greater than - % indicate the presence of substantial heterogeneity [ ] . subgroup analyses will be performed for the following subgroups: age groups ( - years versus > years), population (children [≤ years] versus adults), clinical presentation (severe versus benign forms), and unsd african regions. univariable meta-regression will be used to test for an effect of study and participants' characteristics (year of publication, seasonality, number of screened viruses, clinical presentation, age groups, population, unsd of regions, absolute latitude [distance to equator], latitude, longitude, and altitude). following crude overall prevalence, we will conduct two sensitivity analyses to assess the robustness of our findings. the first one will include only studies with low risk of bias and the second only studies reporting data of a full year(s) period (complete season(s)). we do not plan to make any changes to this protocol. however, if substantial changes occur during the review process, they will be reported in the published results. this work is based on published data and therefore does not require an ethical approval. this systematic review and meta-analysis should serve as a basis for designing preventive and control strategies for arti in africa, and serve as a guide for future research based on the identification of the remaining gaps. the results of this study, in the form of scientific article, will be published in a peer-reviewed journal. these results will also be presented at conferences and submitted to relevant public health authorities. we also plan to update the review in the future to monitor changes and guide solutions for health services and policies. the overall objective of this systematic review is to inform public health stakeholders about the burden of respiratory viral infections in people with arti in africa and to provide information that can support actions to optimise their decisions. we hope that this work will serve as a sink for the consideration of this major public health concern and to identify the priorities for future research in the field. to the best of our knowledge, this will be the first systematic review and meta-analysis that will report the prevalence of viral aetiologies of arti in africa including children and estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory tract infections in countries: a systematic analysis for the global burden of disease study viral pneumonia systematic review of articles on etiologies of acute respiratory infections in children aged less than five years in sub-saharan africa centers for reviews and dissemination. crd's guidance for undertaking reviews in healthcare: centers for reviews and dissemination preferred reporting items for systematic review and meta-analysis protocols (prisma-p) statement understanding interobserver agreement: the kappa statistic assessing risk of bias in prevalence studies: modification of an existing tool and evidence of interrater agreement meta-analysis of prevalence bias in meta-analysis detected by a simple, graphical test the combination of estimates from different experiments quantifying heterogeneity in a meta-analysis none. this work received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.availability of data and materials not applicable. adults. there would be some heterogeneity in the definition of cases of arti according to studies. additional file : prisma-p (preferred reporting items for systematic review and meta-analysis protocols) checklist: recommended items to address in a systematic review protocol*. (pdf kb) additional file : table s . search strategy in pubmed. (pdf kb)abbreviations arti: acute respiratory tract infection; variafrica: viral aetiology of acute respiratory infections in africa.authors' contributions jjb, sk, and rn have conceived and designed the protocol. jjb and sk drafted the manuscript. all authors revised the manuscript and approved its final version. rn is the guarantor of the review.ethics approval and consent to participate not applicable. not applicable. the authors declare that they have no competing interests. key: cord- -upwe cpj authors: sullivan, kathleen e.; bassiri, hamid; bousfiha, ahmed a.; costa-carvalho, beatriz t.; freeman, alexandra f.; hagin, david; lau, yu l.; lionakis, michail s.; moreira, ileana; pinto, jorge a.; de moraes-pinto, m. isabel; rawat, amit; reda, shereen m.; reyes, saul oswaldo lugo; seppänen, mikko; tang, mimi l. k. title: emerging infections and pertinent infections related to travel for patients with primary immunodeficiencies date: - - journal: j clin immunol doi: . /s - - - sha: doc_id: cord_uid: upwe cpj in today’s global economy and affordable vacation travel, it is increasingly important that visitors to another country and their physician be familiar with emerging infections, infections unique to a specific geographic region, and risks related to the process of travel. this is never more important than for patients with primary immunodeficiency disorders (pidd). a recent review addressing common causes of fever in travelers provides important information for the general population thwaites and day (n engl j med : - , ). this review covers critical infectious and management concerns specifically related to travel for patients with pidd. this review will discuss the context of the changing landscape of infections, highlight specific infections of concern, and profile distinct infection phenotypes in patients who are immune compromised. the organization of this review will address the environment driving emerging infections and several concerns unique to patients with pidd. the first section addresses general considerations, the second section profiles specific infections organized according to mechanism of transmission, and the third section focuses on unique phenotypes and unique susceptibilities in patients with pidds. this review does not address most parasitic diseases. reference tables provide easily accessible information on a broader range of infections than is described in the text. . this review covers critical infectious and management concerns specifically related to travel for patients with pidd. this review will discuss the context of the changing landscape of infections, highlight specific infections of concern, and profile distinct infection phenotypes in patients who are immune compromised. the organization of this review will address the environment driving emerging infections and several concerns unique to patients with pidd. the first section addresses general considerations, the second section profiles specific infections organized according to mechanism of transmission, and the third section focuses on unique phenotypes and unique susceptibilities in patients with pidds. this review does not address most parasitic diseases. reference tables provide easily accessible information on a broader range of infections than is described in the text. physician be familiar with emerging infections, infections unique to a specific geographic region, and risks related to the process of travel. this is never more important than for patients with primary immunodeficiency disorders (pidd). a recent review addressing common causes of fever in travelers provides important information for the general population [ ] . this review covers critical infectious and management concerns specifically related to travel for patients with pidd. this review will discuss the context of the changing landscape of infections, highlight specific infections of concern, and profile distinct infection phenotypes in patients who are immune compromised. the organization of this review will address the environment driving emerging infections and several concerns unique to patients with pidd. the first section addresses general considerations, the second section profiles specific infections organized according to mechanism of transmission, and the third section focuses on unique phenotypes and unique susceptibilities in patients with pidds. this review does not address most parasitic diseases. reference tables provide easily accessible information on a broader range of infections than is described in the text. emerging infectious diseases are a result of a convergence of numerous factors and comprise complex interactions among multiple variables. some of those factors are human movement, land use change, encroachment and wildlife translocation, rapid transport, and climate change. several studies demonstrate that for a pathogen to persist in a population, a minimal host population size that is specific for the type of pathogen and host population. of particular relevance to emerging infections is the pattern of rapid population growth. in the tropics, before wwii, most regional ecosystems consisted of few large cities and scattered human settlements separated by large areas of cropland, pastureland, or undisturbed forest. today, the pattern is the opposite: many large cities have developed with only patches of undisturbed forest or grassland. domestic vectors have therefore expanded their population with increasing urbanization and this markedly impacts the interactions between vectors and pathogens [ ] . human activities such as deforestation, use of pesticides, pollution, etc. lead to the loss of predators that naturally regulate rodent and insect populations. this contributes to emerging zoonotic diseases and explains why they occur more frequently in areas recently settled. in today's global economy and affordable vacation travel, it is increasingly important that visitors to another country and their the southern, with a reduction in the number of cold days per year, changes in rainfall (more winter precipitation and summer droughts) [ ] , and together these changes increase the risk of several vector-borne diseases in new areas. climate change involves not only global warming but also changes in precipitation, wind, humidity, and the location and frequency of extreme weather events like floods, droughts, or heat waves. changes in climate produce changes in pathogens, vectors, hosts, and their living environment. increases in precipitation can increase mosquitoes for example, but heavy rainfalls may cause flooding that temporarily eliminates larval habitats and decreases mosquitoes. flooding may force rodents to look for new habitats in houses and increase the opportunities of vector-human interactions, as occurs for example in the case of epidemic leptospirosis. humidity is another very important factor of climate change in the development of vector-borne diseases. mosquitoes and ticks do not survive well in dry conditions. therefore, weather impacts infectious pathogen distribution in complex ways that are not predictable by the forecast. extreme weather events can precipitate outbreaks of infection. an increase in the frequency and intensity of natural disasters like hurricanes and tsunamis, in relation to the el niño/southern oscillation phenomenon, may result in more flooded grasslands, which favor the breeding of aedes and culex mosquitoes [ ] , and impact water sanitation fostering outbreaks such as cholera. flooded areas can displace rodents leading to plague. tornados and other severe weather can stir up soil leading to infections with soil fungi leading to episodic outbreaks of invasive fungal disease such as mucormycosis such as apophysomyces trapeziformis [ ] . malaria is a common disease that can vary dramatically depending on weather, and extreme weather can alter the very landscape, providing new bodies of water to support larval development. if the melting of glaciers and the polar ice caps bring coastal cities underwater, or if overpopulation and waste cause drinkable water shortages in certain regions of the world, we can expect mass migrations. these could change the patterns of infection and drive outbreaks. migrants traversing tropical forests, or feeding with meat from game or carcasses, are but two scenarios that could be envisioned for the emergence of zoonotic infectious diseases [ ] . several predictive models have been developed to evaluate the impact of climate change on the emerging infectious diseases: climex, dymex, miasma models. nevertheless, it remains difficult to predict when and where pathogen behavior will deviate from its typical pattern. climate change primarily affects vector-borne diseases by increasing rates of reproduction and biting and by shortening the incubation period of the pathogen they carry. ticks have gained spread from the mediterranean basin to northern and eastern europe, as well as appearing at higher altitudes. increased survival, density, and activity have also been reported following shorter, milder winters. climate change has also resulted in more days of activity per year for mosquitoes. as temperatures rise, more parasites are viable within regions ranging from the mediterranean and tropical zones, up to the balkans, russia, scandinavia, and the uk. for some ticks and fleas, temperatures over °c with relative humidity of over % are optimal for their proliferation and activity throughout the year [ , , ] . for example, dengue fever is usually limited to a tropical latitude and a low altitude, since mosquito eggs and larvae lose viability with sustained low temperatures. during unusually warm summers, however, dengue has been reported as high up as m above sea level. warmer temperatures also result in smaller adult mosquitoes, which need to bite more frequently to feed themselves and be able to lay eggs, thus increasing the rate of transmission [ ] . in contrast, the incidence of malaria has followed mixed patterns of increase and decrease along recent decades, and computer models have failed to predict the spread. the explanation for this is, in part, that climate change also results in diminished survival of the vectors (warming over °c affects the survival of both parasites and vectors), and in part, that the effect of climate change is non-linear and complex [ ] . the frequency of emerging vector-borne infections varies per changes in land use, human activity, intervention maneuvers to eradicate the vector or prevent transmission to humans, drug treatment, and vaccines. both ecologic and economic changes may bring together rodents and humans. hunting activities may change vector distribution and large-scale animal movements can impact disease distribution. impoverishment of cities and overcrowding in slums, but also reforestation, golf club development, and the urbanization of rural suburbs facilitate exposure to ticks and rodents [ ] . many patients with pidd require immunoglobulin replacement. immunoglobulin products have been demonstrated to improve outcomes in hepatitis a and measles [ , ] . at least some neutralizing antibody is present directed to rsv and group b streptococci [ , ] . this raises three distinct issues for patients: ( ) difficulty in the diagnosis of infections in travelers because locally produced immunoglobulin may have antibody titers to local infections that are not typical for other countries, ( ) safety concerns about locally produced immunoglobulin, if the patient resides in the location long enough to require immunoglobulin from a local provider, ( ) the decision to use locally produced immunoglobulin products to provide superior prevention of infection compared to the patient's usual product. there are limited data on each of these subjects. serologic diagnostic testing in patients on immunoglobulin therapy will be addressed below in terms of issues related to lack of specific antibody produced by the patient (potentially) after infection. the converse can also be an issue. patients arriving from countries with significant occurrences of infections unusual in their current country may have igg antibodies to those infections simply through their immunoglobulin product and not reflecting a true infectious event in the patient. this can lead to diagnostic confusion when serologic testing demonstrates the presence of antibodies due to the infusion product. patients will often ask if immunoglobulin products from other countries are held to the same rigorous standards as their home country. today, commercially produced immunoglobulin is safe and tightly regulated. all commercially produced immunoglobulin around the world has one of the time-tested viral inactivation procedures such as nanofiltration, caprylate absorption, pasteurization, solvent/detergent, vapor heating, and low ph treatment. these procedures uniformly inactivate enveloped viruses. many emerging viruses are specifically tested for their ability to withstand the purification process. much has been learned since the transmission of hepatitis c viruses through immunoglobulin products in the early s [ ] . nevertheless, vigilance is important. in , counterfeit immunoglobulin was identified. therefore, patients should ensure that they receive only brand name products while traveling. the subject of whether a patient's interests would be best served by using a local immunoglobulin product, with antibodies to pathogens that are prevalent in the community, or have their home physician ship their usual product, for which the patient has a known tolerance is hotly debated. patients with a history of intolerance to immunoglobulin products should not switch unless necessary. however, there are compelling reasons to consider a locally produced product when patients are in a foreign country for an extended period. it is known that antibodies to west nile virus have tracked with the distribution of the virus as it has emerged in several areas [ , ] . titers in products using donors from the usa have higher neutralizing titers to west nile virus than those using donors from europe, although there is a -fold difference in titers between lots from the usa [ ] . similarly, protective antibodies to concerning pathogens may be optimal in locally produced immunoglobulin. it is critical to inquire where the plasma source is derived. in most countries, the utilized immunoglobulin is produced in europe or the usa. having a different name does not ensure that the plasma pool comes from a different country. most lots of immunoglobulin are produced from to , plasma donors. the infrastructure to support such an endeavor is not easy to establish in each geographic area. serologic testing is commonly used for the diagnosis of infection. this approach relies upon detection or quantitation of antibodies made by the host against specific pathogens. the presence of igm antibodies against a specific pathogen indicates recent infection, while igg antibodies against a specific pathogen indicate past infection. importantly, serologic testing can only be applied for the diagnosis of infection if the host can mount a specific antibody response to the pathogen. conversely, serology cannot be relied upon to diagnose infection in the setting of immune deficiency where there is impairment of the specific antibody response, such as in the case of primary antibody deficiencies, cellular immune deficiencies, combined immune deficiencies, and other secondary immune deficiencies affecting t and/or b cell function. in these situations, the causative pathogen must be identified by alternate means such as culture of the organism, antigen detection, or molecular approaches (nucleic acid hybridization, nucleic acid sequencing, or oligonucleotide probe arrays). molecular approaches are particularly relevant for the diagnosis of infection in patients with pidd. signal and target amplification techniques can be coupled with nucleic acid hybridization or probe assays to allow detection of pathogen dna or rna that is present in very small amounts in clinical samples. in patients with pidd, vaccines could play an important role in preventing infections with vaccine-preventable diseases. even pidd patients may generate some protective responses [ , ] . the decision to immunize such patients or not depends on the type and severity of pidd as well as the type of vaccine to be administered (live or inactivated) ( table ). in general, inactivated vaccines are safe for pidd patients while immunization with live attenuated vaccines is a known hazard to patients with serious immunodeficiencies of t cell, b cell, and phagocytic cell origin (table ). in less severe pidd, the vaccine can induce adequate protection as in healthy individuals or the efficacy may be reduced [ ] [ ] [ ] . of note, immunoglobulin replacement therapy induces passive immune protection to some vaccine-preventable infections, such as measles, mumps, rubella (mmr), and varicella. in addition, live viral vaccines have greatly reduced efficacy while on immunoglobulin replacement. therefore, vaccine administration in patients receiving regular immunoglobulin replacement treatment should be withheld until at least to months (depending on dose) after cessation of such treatment, if cessation and vaccination are safe. in addition, pidd patients who have received hematopoietic stem cell transplantation but have incomplete immune reconstitution or are under immunosuppression should not receive live attenuated vaccines. in general, the decision of administering live viral vaccines should be made by clinical immunology experts [ ] . in developing countries where polio is still endemic and oral polio vaccine is essential for eradicating the disease, it is of utmost importance that all pidd patients and family members should not receive live oral polio (opv) because of the reported prolonged excretion of the virus for months and even years [ ] . in addition, vaccine-associated paralytic polio is a real risk for some with pidd. these patients and family members should receive inactivated polio vaccine (ipv) instead of opv. similarly, the hazards of administering bacillus calmette-guerin (bcg) vaccine to pidd patients have been documented. in a series of bcg, vaccinated severe combined immunodeficiency (scid) patients from centers in countries, % of scid patients developed disseminated bcg infection and had the worst outcome [ ] . patients with chronic granulomatous disease vaccinated with bcg also developed local and disseminated bcg infection. recently, vaccine strains of rubella virus were found to be associated with skin granulomas in pidd patients [ ] [ ] [ ] . siblings and household contacts of patients with suspected or diagnosed pidds should receive all the national immunization scheduled vaccines. ipv should be substituted for op in families where an antibody-deficient patient exists. yearly influenza vaccination of family members is recommended in order to reduce the risk of household-social transmission [ , , ] . diseases where routine vaccination has reduced incidence can occasionally experience a resurgence in times of economic hardship with reduced attention to vaccination. diphtheria is currently seen in venezuela for this reason. war and disruption of health infrastructure are other common reasons for resurgence in vaccine-preventable diseases. in other settings, antivaccination sentiment has led to outbreaks of diphtheria, measles, and mumps. an additional consideration is that not all countries provide the same level of vaccination, and therefore, vaccine-preventable illness can still be seen regionally. these outbreaks represent a significant risk to patients with pidd. a universal consideration for patients with pidd is the concern about antibiotic resistance, which varies dramatically around the world. for certain high impact infections, the emerging antibiotic resistance patterns will be discussed below. antimicrobial resistance occurs naturally, but misuse and overuse of antimicrobials are accelerating this process. in nearly every country, antibiotics are overused and misused in people and animals leading to antibiotic resistance in every country. key resistance patterns to common bacteria include emergence of carbapenem-resistant klebsiella pneumoniae around the world with high frequency of resistance (due to different mechanisms) in the mediterranean, with greece, italy, and turkey having endemic spread of this pathogen [ ] . carbapenem-resistant strains among other genera of enterobacteriaceae have also been recognized. they are particularly common in greece, but have been found widely distributed [ ] . the new delhi metallo-beta-lactamasemediated resistance, which is endemic in the indian subcontinent but becoming increasingly spread worldwide, is a growing concern [ , ] . as a common cause of urinary tract infections, colistin is the only recourse when carbapenemresistant enterobacteriaceae, and colistin resistance has recently emerged in small outbreaks throughout the world [ ] . in these cases, the infection is essentially untreatable. fluoroquinolone-resistant escherichia coli, a common cause of urinary tract infections, now accounts for over half of the isolates in some asian countries [ , ] . t he emergence of resistance to antibiotics in grampositive pathogens has become a major international problem as there are fewer, or even sometimes no effective, antimicrobial agents available for infections caused by these bacteria. methicillin-resistant staphylococcus aureus is common in many countries and in fact has spawned a nomenclature recognized by the general public: mrsa. several studies have reported resistance to the newer antimicrobial agents like linezolid, vancomycin, teicoplanin, and daptomycin [ ] . thus far, these isolates appear to be uncommon and have been found in < % of isolates in brazil, china, ireland, and italy, with nearly undetectable rates elsewhere. vancomycinresistant enterococcus (vre) is growing in frequency and can now be a cause of primary bacteremia in immunocompromised individuals [ ] . a key message is that antibiotic resistance is increasing (generally) and travelers should be alerted to resistance to commonly encountered organisms, and if antibiotic prophylaxis is required, their prophylaxis is adjusted. neisseria gonorrhoeae is a specific organism for which resistance has become especially problematic. it has progressively developed resistance to virtually all antimicrobial agents since introduction of sulfonamides in mid- s. the current treatment guidelines recommend dual antimicrobial therapy (ceftriaxone - mg × plus azithromycin - g × ) as first-line regimen [ , ] . although dual therapy is very effective, development of concomitant ceftriaxone and azithromycin resistance is likely to emerge [ ] . the risk of untreatable n. gonorrhoeae demands better global antimicrobial surveillance system, clinical trials on combined therapy of existing drugs as well as novel agents in monotherapy, and development of a gonococcal vaccine. for pidd patients, guidance on barrier methods for the prevention of sexually transmitted diseases should be a part of any pre-travel counseling. mycobacteria tuberculosis (mtb) is an age-old pathogen with emerging resistance. drug-resistant tb, fueled by the hiv epidemic, is a global threat. in , who estimated , new cases of multidrug-resistant tb (mdr-tb) and an additional , new cases of rifampin-resistant tb (rr-tb) who would also require mdr-tb treatment. treatment of mdr-tb and mycobacterium bovis disease is beyond the scope of this text and reader is referred to recent who mdr treatment guidelines [ ] . regions of the world with > % mdr tb include regions of azerbaijan, kazakhstan, russia, uzbekistan, china, georgia, and eastern europe. extensively drug-resistant tb (xdr tb) refers to mtb resistant to isoniazid, rifampin, any fluoroquinolone and at least one second-line drug. xdr tb has been reported in countries. on average, % of patients with mdr tb have xdr tb. as is true for all types of mtb, xdr tb is contagious and small outbreaks related to person-person transmission have been reported. non-tuberculous mycobacteria (ntm) cause significant systemic infections in patients with defects of the il- / ifnγ/stat axis as well as in gata deficiency and can cause significant pulmonary infections in pidd patients with bronchiectasis. compared to tb, ntm is acquired from the environment and not from person-to-person transmission; therefore, acquisition of antibiotic-resistant strains is less common. however, in these individuals with pidd, ntm disease is often chronic and can be difficult to eradicate, and resistance can then easily develop during therapy. using combination of antibiotics is essential, and consultation with those familiar with treatment of treatment refractory ntm disease is recommended. aspergillus species are ubiquitous inhaled molds with worldwide distribution that cause opportunistic infections in immunocompromised patients [ ] . aspergillosis also occurs in pidds associated with quantitative and/or qualitative phagocyte defects; it develops most frequently in chronic granulomatous disease (cgd) patients (prevalence,~ %), while it is seen less often in patients with gata deficiency, card deficiency, and congenital neutropenia syndromes [ , ] . upon inhalation, aspergillus species cause invasive pulmonary disease in susceptible hosts with the exception of card deficiency, where aspergillosis has a predilection for extrapulmonary tissues with sparing of the lungs [ ] . diagnosis is established by fungal culture and/or histopathology showing acute-angle septate hyphae and/or detection of galactomannan, an aspergillus cell wall component released during invasive infection, in serum or bronchoalveolar lavage fluid [ ] . while azole-susceptible aspergillus fumigatus is still the most common infecting species in pidd patients, the emergence of azole-resistant a. fumigatus and nonfumigatus aspergillus species underscores the importance of a high index of suspicion in patients who do not respond to front-line voriconazole treatment [ ] . the advent of fungal molecular diagnostics has demonstrated that patients with pidds are more prone to infections by uncommon low-virulence aspergillus species with intrinsic resistance to azole antifungal agents that do not infect patients with iatrogenic immunosuppression. these primarily include aspergillus viridinutans, aspergillus tanneri, and neosartorya udagawae, which pose major diagnostic and therapeutic challenges due to their impaired sporulation and propensity for contiguous and distant tissue spread, respectively. in addition, acquired azole resistance in a. fumigatus can be seen in patients on long-term exposure to azole drugs used as treatment and/or prophylaxis [ ] . azole resistance in these strains is predominantly caused by point mutations in the lanosterol α-demethylase gene that encodes the cyp a protein, the primary target of azole drugs. importantly, infection by azole-resistant a. fumigatus strains without prior exposure of patients to azole antifungals has recently emerged as an important global health concern due to the widespread use of sterol demethylase inhibitor fungicides in agriculture that results in cross-resistance with the triazole antifungals used in clinical practice [ ] [ ] [ ] . fungicide-driven azole-resistant environmental aspergillus strains were first observed in the netherlands in and have since then been documented in other parts of europe, south and north america, the middle east, australia, africa, and asia. the prevalence of these azole-resistant aspergillus strains among clinical aspergillus strains recovered from patients in european countries was reported to be . %, while alarmingly in some areas > % of recovered strains exhibited azole resistance [ ] . the emergence of such aspergillus environmental strains poses serious threats to the treatment of immunosuppressed patients. mortality rates as high as % have been seen due to delays in diagnosis and suboptimal treatment with azole antifungals [ ] . although no prospective data exist for the treatment of patients with such resistant fungi, the use of amphotericin b-and echinocandin-based regimens are preferred over azoles [ ] . in the absence of azoles, the lack of alternative oral antifungal agents is particularly challenging for pidd patients such as those with cgd who require long-term suppressive antifungal treatment. candida species are commensal yeast fungi that colonize the mucosal surfaces of~ % of healthy individuals [ ] . when perturbations in immunity and/or microbiota occur, candida causes opportunistic mucosal or systemic infections that depend on clearly segregated immune responses for host defense. specifically, t cells of the th program are critical for mucosal and phagocytes for systemic immunity [ ] . indeed, a proportion of patients with cgd and complete myeloperoxidase deficiency develop systemic, but not mucosal candidiasis [ ] , whereas patients with monogenic syndromes of chronic mucocutaneous candidiasis due to mutations in the il- signaling pathway (il ra, il rc, il f, act ) or in other genes that adversely affect th differentiation (rorc, stat , stat , aire, dock , stk , irf ) do not develop systemic candidiasis. the only known pidd to date that results in combined mucosal and systemic candida infection susceptibility is card deficiency. systemic candidiasis in card -deficient patients has a predilection for the central nervous system, associated with brain-specific impaired recruitment and effector function of neutrophils [ ] [ ] [ ] . diagnosis of candida infections is established by culture. azole-susceptible candida albicans is still the most common infecting species in pidd patients; however, emergence of azole-resistant c. albicans is not uncommon during chronic azole use, making long-term therapy challenging due to lack of alternative oral antifungal treatment options [ ] . beyond c. albicans, non-albicans candida species can rarely infect pidd patients, some of which have intrinsic resistance to azole antifungals, including candida glabrata and candida krusei [ ] . most recently, candida auris has emerged as a global public health concern due to its resistance to antifungal drugs, high virulence potential, propensity for health careassociated horizontal transmission and outbreaks in health care settings, persistence in the human skin and hospital environment, inherent resilience to antiseptics, and misidentification by routine biochemical methods as other yeasts (most often candida haemulonii, but also candida famata, rhodotorula glutinis, or saccharomyces cerevisiae). c. auris was first recovered from the ear canal of a patient in japan in and has since then been reported to cause life-threatening infections and hospital outbreaks in europe, asia, africa, the middle east, and south and north america [ ] [ ] [ ] [ ] . most of the reported strains of c. auris have intrinsic resistance to fluconazole and other triazole antifungal agents, while a significant proportion of strains has elevated minimum inhibitory concentrations to amphotericin b and echinocandins, with some strains reportedly resistant to all three classes of azoles, polyenes, and echinocandins [ ] . avoidance of azole antifungals is important in c. auris-infected patients, and echinocandinor amphotericin b-based regimens are preferred, guided by strain-specific in vitro susceptibility patterns. this section on vector-borne infections is a major focus of this review because the infections are often more severe in immunocompromised individuals and because there are mitigation strategies that should be considered even in the absence of defined medical treatments for infection. prevention of mosquito bites depends somewhat on the endemic species but there are generalizations. the use of a mosquito repellant such as deet, oil of lemon eucalyptus, ir , or picaridin is as important as using long sleeves and long pants while in an affected area. deet and picaridin are safe in pregnancy, and some data support their greater efficacy [ ] . air conditioning and fans tend to keep mosquitoes away but netting at night is essential in mosquito-prone areas. light-colored clothing is less attractive to mosquitoes than dark clothing, and scented detergents and use of dryer sheets tend to attract mosquitoes, hence should be avoided. aedes species prefer to bite indoors and thrive in urban areas with small puddles of water. they bite most frequently around dawn and dusk. anopheles species have very similar behaviors. culex mosquitoes, in contrast, bite primarily at night. tick and fly bite prevention is focused on physical and chemical prevention. for ticks, physical inspection for biting ticks should also be incorporated. arthropod-borne viruses (arboviruses) are transmitted to humans through the bites of infected insects: mosquitoes, ticks, sand flies, or midges. some arboviruses can be transmitted through blood transfusion, organ transplantation, perinatal transmission, consumption of unpasteurized dairy products, or breastfeeding. there are > arboviruses causing human disease. most arboviral infections are asymptomatic. infectious manifestations range from mild febrile illness to severe encephalitis. arboviral infections are often categorized into two primary groups: neuroinvasive disease and non-neuroinvasive disease. tables and list the encephalitigenic viruses and the febrile/hemorrhagic disease causing viruses. in this section, we will highlight west nile virus, the most common of the encephalitogenic arboviruses. west nile virus is a single-stranded mosquito-borne rna virus of the family flaviviridae. the natural transmission cycle of the virus occurs in culex mosquitoes and birds. humans and horses are dead-end hosts for the virus. the most common mode of transmission to humans is through the bite of infected mosquitoes. other less common modes of transmission include blood transfusions, organ transplantations, occupational exposure in laboratories and mother-to-child transmission during pregnancy, childbirth, and breastfeeding. west nile virus has been diagnosed in > people in the usa with slightly more than half having neuroinvasive disease. since , > , people in the usa have been infected. it is also common in africa, europe, and asia [ ] . infection with west nile virus is asymptomatic in most individuals [ , ] . the incubation period lasts for to days. however, it can be significantly longer in immunocompromised hosts. clinical manifestations following infection develop in - % of those infected and include fever, headache, myalgia, arthralgia, vomiting, and rash. severe neuroinvasive disease leading to meningitis, encephalitis, and flaccid paralysis develops in less than % of infected individuals. the overall case fatality is approximately % which is a disproportionately high mortality in patients with encephalitis and myelitis. diagnosis of west nile virus rests on demonstration of specific antibody responses especially specific igm antibodies in the serum or csf of infected individuals by enzyme immunoassays. plaque reduction neutralization tests can differentiate cross-reactive antibodies. detection of virus in csf, blood, or tissue specimens by culture or pcr is particularly useful in immunosuppressed individuals who may have impaired serological responses. west nile virus has been reported in the context of both primary and secondary immunodeficiency. severe neurological manifestations have been reported in hiv-positive individuals, individuals receiving immunosuppressive therapy including rituximab, and individuals with pidd. infection with wnv has been reported in individuals with common variable immunodeficiency, idiopathic cd lymphopenia, gata deficiency, and a case of probable good's syndrome [ ] [ ] [ ] . individuals with antibody defects, neutropenias, and impaired t cell responses are potentially at an increased risk of severe manifestations of wnv disease including severe neurological involvement. this section highlights the four important non-neuroinvasive arboviruses based on current geographical distribution: dengue, yellow fever, zika, and chikungunya (table ) . approximately countries/territories have reported local transmission for both chikungunya and dengue viruses [ ] . dengue is due to infection with one of four dengue virus serotypes, transmitted by a mosquito (typically aedes aegypti). this febrile illness affects all ages with symptoms appearing - days after the infective bite. symptoms range from mild to high fever, with severe headache, musculoskeletal pain, and rash. severe dengue (also known as dengue hemorrhagic fever) occurs in . - % of cases and is characterized by fever, abdominal pain, persistent vomiting, bleeding, and breathing difficulty and is a potentially lethal complication [ ] . paradoxically, the main risk factor for dengue hemorrhagic fever is pre-existing antibodies. early clinical diagnosis and comprehensive management by experienced clinicians increase survival. dengue is ubiquitous throughout the tropics with the highest infection rates in the americas and asia. dengue is now endemic in countries, causing up to million infections a year and , deaths, mainly among children. over half of the world's population inhabits areas at risk for dengue infection [ ] . the presence of a. aegypti in over countries potentially puts almost the whole world at risk of becoming infected with this virus. pcr is widely used as serologic methods to diagnose dengue. immunity to one serotype does not confer protection against the other three serotypes, and heterologous antibody may be a risk factor for hemorrhagic dengue [ ] . the natural history of dengue has been studied in hiv patients where hiv did not appear to increase severity. there have been no reports of patients with pidd having dengue; however, dengue infection after solid transplantation has been reported [ ] [ ] [ ] [ ] with some patients having severe complications suggesting that t cell compromise in pidd could be a risk for severe disease. there are no antiviral medications utilized for dengue virus. care of patients with hemorrhagic disease requires meticulous approach to fluids and coagulation status. one dengue vaccine has been registered in several countries (cyd-tdv) for individuals from to (or ) years old. it is a live attenuated recombinant tetravalent vaccine with backbone of the attenuated yellow fever d virus genome with the prm and e genes that encode the proteins from the four wild-type dengue viruses. the who has suggested its use in regions where seroprevalence of dengue virus of any serotype is % or greater, but has not recommended it to hiv-infected, immunocompromised individuals, nor pregnant or lactating women [ ] . most people infected with the yellow fever virus have no illness. symptoms of yellow fever include sudden onset of fever, chills, headache, musculoskeletal pain, nausea, vomiting, fatigue, and weakness. the incubation period is typically - days, and symptoms may appear after return from travel. most people improve after the initial presentation, but % of cases progress to develop a more severe form of the disease, usually after a day of presumed recovery. the severe form is characterized by high fever, jaundice, bleeding, and eventually shock and failure of multiple organs [ ] . yellow fever virus is an rna virus that belongs to the genus flavivirus. it is transmitted from mosquitoes after biting an infected primate. it is widely distributed in the equatorial tropics [ ] . aedes species of mosquitoes are primarily responsible for transmission. large epidemics of yellow fever occur when the infection enters heavily populated areas with a high mosquito density and where most people have little or no immunity. west africa has undergone a large-scale vaccination campaign with impressive results and yellow fever is now uncommon in west africa [ ] . serologic testing for yellow fever is the diagnostic standard. pcr can be performed on tissue samples. there are no published studies of yellow fever in immunocompromised people, but the elderly, very young, people with autoimmune disease, or who are post-thymectomy are at risk from the attenuated vaccine strain. thus, it seems likely that any immunodeficiency would be associated with more severe wildtype disease. currently, no specific antiviral drug for yellow fever exists. treatment of dehydration, liver and kidney failure, and fever improves outcomes. the yellow fever vaccine is highly effective; however, immunodeficient patients should not receive it. infection with zika virus is often asymptomatic. it represents a mild infection for those who have any symptoms [ ] . the zika virus has been detected in urine, semen, and saliva of infected individuals, and transmission from transfusion and sexual relations has been reported. it is also detectable in breast milk, but breastfeeding-associated transmission has not been reported so far [ ] [ ] [ ] . contact with highly infectious body fluids from patients with severe zika infection has also been suggested as a possible mode of transmission [ ] . of tremendous importance is the presence of prolonged shedding of zika virus in a congenitally infected newborn [ ] . the main public health risk of zika virus is microcephaly in newborns from infected mothers [ ] . zika virus is capable of infecting human neural progenitor cells in vitro. infection results in disruption of cell cycle, increased cell death, and attenuated neuron growth [ ] . zika is not thought to be a major risk for people with pidd (based on the experience with hiv patients, but our recognition of zika is very recent. there is no known specific treatment for zika; however, there is an important effort to develop a vaccine. chikungunya fever is an acute febrile illness caused by the alphavirus, chikungunya virus. the incubation period is usually - days after the bite of an infected aedes mosquito. there is abrupt onset of high fever, and the fevers can be biphasic [ , ] . severe polyarthraligias develop after the onset of fever. the joint pains can affect any joint, but the pattern is usually symmetric and a true acute arthritis is not uncommon. the proportion of infected people with rash has varied across studies. when seen, the rash appears after the fever as a truncal maculopapular type of rash [ ] . cervical adenopathy is another common feature of infection. death is uncommon in chikungunya, but serious complications such as myocarditis have been seen. over half of the patients report continued joint symptoms year after acute illness and % have long-term joint symptoms [ ] . chikungunya originated in central/east africa. in forests, the virus circulates in aedes mosquitoes and non-human primates. in urban centers, the virus circulates between humans and mosquitoes similar to the pattern of dengue. there have been periodic urban outbreaks in asia and africa since with an acceleration in spread since [ ] . an important consideration is the periodic outbreaks with high attack rates in naïve populations. areas at risk currently are east africa, central africa, la reunion, india, and southeast asia. diagnostic testing utilizes pcr or serology. the threat to immunodeficient patients is not entirely clear. there are a few provocative cases where the immunocompromised appears to have been associated with fewer joint symptoms, but there were two patients, medically immune compromised, who had very severe disease [ , ] . this suggests that the presentation may be atypical and the course may be severe in immunodeficient people. treatment is supportive, although chloroquine, acyclovir, ribavirin, interferon-ɑ, and steroids have limited preclinical data to support clinical trials. babesia microti (the main species in the usa) infection can be asymptomatic, but many people develop fever, chills, headache, myalgias, anorexia, nausea, or fatigue [ ] . babesiosis often causes hemolytic anemia. b. microti is spread by ixodes scapularis ticks in the usa and babesia divergens (the main species in europe) is spread by ixodes ricinus. symptoms begin - weeks after a bite from an infected tick with b. divergens having a higher mortality rate and greater symptomatology compared to b. microti. the main geographic areas involved are the coastal eastern usa and cattle breeding areas throughout europe. the diagnosis is usually by inspection of a blood smear or through serology. a pcr test has just been developed. immunodeficiency, asplenia, and older age are recognized risk factors for severe disease and even death [ ] [ ] [ ] . thus, congenital asplenia would be considered a major risk for severe disease. a combination of atovaquone and azithromycin is generally used for therapy, although clindamycin and quinine have been used with success. patients with severe illness have been treated with exchange transfusions. five different types of plasmodium (plasmodium falciparum, plasmodium vivax, plasmodium ovale, plasmodium malariae, and plasmodium knowelsi) infect humans. malaria is transmitted primarily by female anopheles mosquitoes. symptoms vary depending on the type of plasmodium involved but usually include high fever, chills, and headache. in some cases, the illness can progress to severe anemia, kidney and respiratory failure, and death. the incubation period typically ranges from to days for p. falciparum, to days for p. vivax and p. ovale, and to days for p. malariae. in p. vivax and p. ovale infections, relapses can occur months or even years without symptoms. p. vivax and p. ovale have dormant liver stage parasites that must be specifically eradicated through medical therapy. malaria has been a global health concern throughout history and is a leading cause of death and disease across many tropical and subtropical countries. over the last years, new control measures have reduced malaria by over half [ ] . the democratic republic of the congo and nigeria account for over % of the estimated total of malaria deaths globally. high rates of malaria are seen in india as well. nevertheless, malaria exists in most tropical regions of the americas, africa, and asia [ ] . the diagnosis of malaria depends on the demonstration of parasites in the blood, usually by microscopy. the threat to immunodeficient patients is not entirely clear, but patients with hiv seem to have no additional burden of disease other than an increase in placental malaria, suggesting that t cells are not central to the defense of malaria [ , ] . asplenia is a known risk factor for severe malaria [ ] . antibodies appear to be both protective and pathologic [ , ] . treatment and prophylaxis depend on the region of the world because the parasites and resistance are highly variable and highly dynamic. therefore, it is best to consult an infectious disease specialist familiar with the prophylaxis before travel and for treatment of acute cases. leishmaniasis is due to infection with an obligate macrophage intracellular protozoa of the genus leishmania. it causes a spectrum of disease ranging from a cutaneous ulcer to mucosal disease and the most severe form, visceral leishmaniasis (vl). the liver, spleen, and bone marrow are major sites of parasite growth and disease pathology in vl [ ] . purely cutaneous leishmaniasis is most often caused by leishmania major, leishmania. tropica, leishmania aethiopica, leishmania infantum, and parasites belonging to the leishmania mexicana complex, the leishmania braziliensis complex, and the leishmania guyanensis complex. mucocutaneous disease is most often due to l. braziliensis complex, leishmania panamensis, leishmania amazonensis, and rarely by leishmania guyanensis. vl is most often caused by leishmania donovani and leishmania infantum (previously l. chagasi) [ ] . cutaneous leishmaniasis can have many variations but is most often an ulcer that develops after an indolent papule. the incubation period ranges from weeks to months. the ulcer usually heals within months to years, and there can be mild adenopathy. mucocutaneous leishmaniasis follows a cutaneous ulcer and is only caused by l. braziliensis parasites. oral and respiratory mucosa are most often involved with granulomatous lesions that may be extremely destructive. vl is associated with fever, lymphadenopathy, hepatosplenomegaly, wasting, hypoalbuminemia, and pancytopenia. this picture evolves over months to years. there can be secondary immune deficiency due to the pancytopenia. the epidemiology has changed dramatically and has been impacted by climate change [ ] . the sand flies that spread the parasite are affected by temperature and rainfall. in most endemic regions, leishmania has a patchy distribution due to micro-ecologic factors. poverty has been demonstrated to be a major risk factor for leishmaniasis [ ] . it has been estimated that up to half a million new cases of vl occur every year, but the majority are in resource-poor countries such as bangladesh, nepal, india, sudan, ethiopia, and brazil. emergence of resistance to antimony-based drugs has also led to a major resurgence of disease. the primary reservoir for leishmania is forest rodents, but dogs are increasingly important. the growing spread of leishmania is due to a combination of factors, and now countries have reported cases. immunodeficient patients are more susceptible to infection, and relapse occurs more frequently [ ] . the risk of developing vl is estimated to be between and times higher in hiv-infected than in non-hiv-infected individuals [ ] , and these patients have higher rates of treatment failure with the illness often taking a prolonged chronic course and higher mortality rates [ ] . a similar picture has been seen in patients with vl-infected post-kidney transplantation [ ] . dendritic cells, t cells, and the generation of reactive oxygen species have been shown to be essential for parasite control [ ] [ ] [ ] . pidd with impaired il- production have been associated with severe disease [ ] . a patient with cd l deficiency, associated with poor il- production, had chronic leishmania and died in spite of aggressive treatment. vl has been reported in cgd patients [ ] . six cgd patients were infected by leishmania, and they developed hemophagocytic syndrome with a poor outcome for one of them [ ] . the diagnosis of leishmaniasis is usually by visual inspection for parasites. immunofluorescence microscopy, direct agglutination, skin test, and pcr have been used. treatment is long-term and difficult. emerging resistance to first-line treatment is increasingly problematic. pentavalent antimonials are the mainstay of treatment in most countries, but liposomal amphotericin is widely used where resistance occurs. newer drugs with more favorable side effect profiles have been used in certain geographic settings: miltefosine, paromycin, and sitamaquine. rickettsiae are small gram-negative bacteria. they are obligate intracellular parasites, and the primary target in humans appears to be endothelial cells with subsequent thrombosis and clinical presentation of vasculitis [ ] . the rickettsiaceae family, originally defined by non-specific phenotypic characteristics, was reclassified into different strains and subspecies based on gene sequencing and genetic phylogeny ( table ). the clinical presentation of rickettsial disease can vary, but the classic triad of fever, rash, and headache still provides major clues for the diagnosis [ ] [ ] [ ] . however, rash is not an obligatory sign, and the incidence of rash can range between % for rickettsia conorii infection,~ % for rickettsia rickettsii, % for rickettsia africae, and less than % in the case of anaplasma phagocytophilum infection. therefore, fever in patients with exposure to a potential vector should raise a concern for a rickettsial disease, especially if there is also evidence of rash, inoculation eschar, or localized lymphadenopathy. additional supporting laboratory findings can include neutropenia, thrombocytopenia, and increase in liver transaminases. the geographic distributions of rickettsioses and ehrlichioses are mostly dependent on their vector distribution [ ] . as such, louse-borne and flea-borne are worldwide, reflecting the worldwide distribution of lice and fleas, with a tendency to parasite poor people in cold places and, characteristically, during wars. ticks, on the other hand, depend on their environment and most do not have a worldwide distribution. with the exception of the dog tick, vector for r. conorii in asia and north africa, r. rickettsii in the usa, rickettsia massiiae and erhlichia canis worldwide, most other tick-borne diseases are restricted to areas of the world correlating with the distribution of their vector [ ] . for that reason, it should be anticipated that climate and environmental changes will affect vector distribution and its reservoir host and, hence, the geography and epidemiology of tick-borne diseases [ , , ] . diagnosis presents a challenge, as it is extremely difficult to grow these organisms in culture. immunohistochemistry and pcr can be helpful. the severity of rickettsial disease varies with the causative agent and the host. r. rickettsii, rickettsia prowazekii, and orienta tsutsugamushi are considered most pathogenic. as for host factors, although severe and fatal cases have been described in healthy immunocompetent hosts [ , ] , there is evidence to suggest that children under the age of [ ] and immunocompromised hosts either secondary to hematologic malignancies, immunosuppressant treatment for organ transplantation, or hiv infection are at a greater risk to develop more severe disease with higher case fatality rates [ , ] . all rickettsiaceae are intracellular pathogens, and one could expect an increased risk for severe disease in pidds with abnormal t cell function. five to days of doxycycline is the preferred treatment for non-pregnant adults and children. treatment should not be delayed while awaiting diagnostic testing [ ] and can be given to children despite a minimal risk for dental staining. alternative treatments include azithromycin for mild disease [ ] and chloramphenicol for pregnant women. anaplasma is an intracellular bacterium that infects wild and domestic mammals, including man. a. phagocytophilum was formerly known as human granulocytotropic ehrlighiosis but is now known as human granulocytotropic anaplasmosis [ ] . e. chaffeensis infects monocytes and causes human monocytic ehrlichiosis [ ] . anaplasma and ehrlichia have historically cycled within non-human enzootic hosts, and man has become infected through increasing interactions with the environment. ehrlichia and anaplasma are transmitted by ixodes species of ticks, and their ranges include the eastern usa, south central usa, and scattered regions of europe, as far north as sweden. these infections have not been seen in humans in the southern hemisphere, but there are reports of organisms being identified [ ] . a less common mode of transmission is through transfusions. the symptoms of ehrlichia and anaplasma infections are similar [ ] . abrupt onset of an influenza-like illness occurs about days after a tick bite. ehrlichia can cause a mild rash ( % of adults and % of children), but rash is uncommon in anaplasma infections. highly suggestive laboratory features are leukopenia and thrombocytopenia. mortality in the general populations appears to be < %, but icu admission is not uncommon. hemophagocytosis has been described with anaplasma [ ] and ehrlichia [ ] . both infections are more severe in any setting of immune compromised, including asplenia [ , ] . the diagnosis is typically made by pcr, and doxycycline is the recommended treatment. intracellular inclusions can be seen on cbc smears (more often in anaplasma than ehrlichia). an uncommon but well described facet of these infections is that the tick vector can also transmit borrelia burgdorferi and babesia microti, and simultaneous infection with multiple organisms can occur. c. burnetii is a highly pleomorphic gram-negative coccobacillus and the causative agent of q fever. q fever is a zoonosis, and the most common reservoirs are cattle, sheep, and goats but many other animals can be infected by c. burnetii [ , ] . when infected, these domestic animals can shed the organism in urine, feces, milk, and especially birth products. the pathogen survives within the phagolysosome of host cells, and a spore stage has been described. this spore stage explains the ability of c. burnetii to survive in unfavorable environmental conditions, and it can be an environmental risk for months to years after shedding from an infected animal. q fever is considered an occupational disease affecting people with direct contact with infected animals; however, indirect contact through exposure to contaminated animal products has also been described to cause disease outbreaks. humans are infected by inhalation of contaminated aerosols. following an average incubation period of days, infected patients can present with severe headache, fever, chills, fatigue, and myalgia. other signs and symptoms depend on the organs involved. in contrast to rickettsial diseases described above, rash rarely occurs in the early stages of the disease. c. burnetii can cause a range of clinical symptoms. a self-limited febrile illness is probably the most common form of q fever. pneumonia, either atypical or severe, is also common and can be a part of acute q fever syndrome. in contrast, a variety of manifestations can be recognized in chronic q fever, including endocarditis, endovascular infection, osteomyelitis, hepatitis, interstitial pulmonary fibrosis, prolonged fever, and purpuric vasculitic rash. q fever diagnosis is based on serologic testing with indirect immunofluorescence being the best for differentiating between acute and chronic q fever (high antiphase i antigen titer). the treatment of choice for acute q fever is doxycycline, with co-trimoxazole, chloramphenicol, or rifampin being an accepted alternative. there is no agreement on the treatment for q fever endocarditis, and a combination of doxycycline with either fluoroquinolone or hydroxychloroquine is recommended. there is also controversy regarding the duration of treatment, ranging from years to indefinite treatment. old evidence suggests that q fever is more common in immunocompromised patients. a french study showed higher incidence of antibodies to c. burnetii in hiv positive compared to hiv-negative patients ( . vs . %). in addition, out of hospitalized patients were hiv positive ( . %), suggesting a more frequent symptomatic disease [ ] . a smaller similar study performed in central africa failed to show increased incidence of seropositivity in hivpositive patients [ ] . two case reports describe severe disease in immunocompromised patients. the first was a case of fatal q fever disease in an -year-old male with cgd [ ] . the patient was treated with broad spectrum antibiotics, but without coverage for q fever. the second case was a -yearold asplenic male who presented with fever, jaundice, and encephalopathy and was diagnosed with acute q fever [ ] . the patient was successfully treated, but the two case reports could suggest susceptibility in cases of phagocytic disorders. the bartonellaceae are fastidious, facultative intracellular gram-negative bacilli (table ). most species infect primarily non-human animals, and in most cases, human are considered incidental hosts. the documented common human pathogens include bartonella bacilliformis, bartonella henselae, and bartonella quintana, and it is believed that humans are the primary mammalian reservoir of b. quintana. infection occurs through inoculation of bartonella-infected arthropod feces into breaks in the skin. the epidemiology of bartonella infection in humans follows the distribution of the vector. as such, infection with b. bacilliformis follows the distribution of the sand fly vector (lutzomya) and is confined to the andes mountain in peru, ecuador, and colombia at heights of between and m. the human body louse pediculus humanus is the vector of b. quintana, which explains the global distribution of this pathogen and worldwide outbreaks of trench fever, mostly in conditions of poor sanitation and upon exposure to body lice. trench fever was responsible for over a million infections during world war i. fever, either abrupt or indolent in onset, with a maculopapular rash, conjunctivitis, headache, myalgias (most often affecting legs), and splenomegaly was described. urban b. quintana infections occur most often among homeless and have a distinct clinical picture with fever as the most common manifestation. endocarditis occurs in many [ ] . bartonella henselae is globally endemic, and domestic cats are a major reservoir. the major arthropod vector of b. henselae is the cat flea, which is responsible for cat-to-cat transmission. human infection, called cat scratch disease, is assumed to involve inoculation of bartonella-infected flea feces into the skin during a cat scratch. b. henselae causes primarily adenopathy and neurologic symptoms [ ] . b. bacilliformis causes a condition with two phases: the acute phase with fever, anemia, and transient immunosuppression followed by nodular dermal eruption [ ] . recently appreciated are the ongoing systemic features during the eruptive phase such as arthralgias, adenopathy, and anorexia [ ] . diagnosis of bartonella-associated diseases can be achieved by direct examination of clinical material, bacteriologic culture methods, serologic and immunocytochemical studies, pcr-based assay, or combination of these methods. bartonella infection can present differently in immunocompromised hosts [ ] . in addition to higher prevalence of bartonella infection in hiv patients [ ] , both b. quintana and b. henselae can induce neovascular proliferation which might involve the skin, lymph nodes, and a variety of internal organs including the liver, spleen, bone, brain, lung, bowels, etc. these neovascular lesions, known as bacillary angiomatosis/peliosis (ba/bp), were initially described in hiv-infected patients with advanced disease and was later described in other immunocompromised hosts secondary to immunosuppressant treatment for solid organ transplantation or hematologic malignancy [ ] [ ] [ ] [ ] . cutaneous ba lesions can vary in presentation and can be subcutaneous, dermal nodules, single or multiple papule that can be flesh colored, red, or purple. lesions may ulcerate and bleed. they can change in number and size (millimeters to centimeters; few to hundreds) and can involve mucosal surfaces or deeper soft tissues. similar variation can be seen with visceral involvement. histologically, lesions consist of lobular proliferation of small blood vessels and neutrophilic predominant cell infiltration. the term bacilliary peliosis is used to describe bloodfilled cystic spaces mostly involving the liver, spleen, and lymph node. pathogenic bacteria can be isolated from vascular lesions. while both pathogens were associated with cutaneous lesions, only b. henselae was associated with visceral bp [ ] . based on hiv literature, it is reasonable to expect an unusual presentation of bartonella infection especially in pidds involving t cell dysfunction. bartonella infection was described as a cause for hepatitis in a single cd l deficiency patient [ ] . in addition, since cases of granulomatous disease due to bartonella infection [ ] [ ] [ ] have been described, it should be considered in the differential diagnosis of pidd with granulomatous inflammation. borrelia spp. the genus borrelia belongs to the spirochaetaceae family. it includes b. burgdorferi which causes lyme disease and species that cause relapsing fever. the latter are further divided into tick-borne species and louse-borne species. louse-borne relapsing fever (lbrf) is caused only by borrelia recurrentis and is spread by human body louse. the disease was epidemic in the early twentieth century, and it is estimated that more than , died of lbrf during world war ii. with sanitation improvement lbrf is now found only in the horn of africa and among homeless people in europe. more recently, cases of lbrf in refugees and migrants were described [ , ] . tick-borne relapsing fever (tbrf) is caused by a group of pathogens which are maintained by and survive in softticks (orinthodoros genus). each tbrf borrelia species depends on one specific species of soft-body tick. except for australia and antarctica, tbrf species can be found in all continents. the animal reservoir includes small animals and rodents. since the spirochetes persist in the tick salivary gland, disease transmission occurs when humans intrude the tick's environment. tick bites are painless, and history of a tick bite is often missing. therefore, a history of potential exposure can be valuable. the major clinical symptom is relapsing fever. after a median incubation period of days, patients present with febrile episode that can last - days, followed by afebrile period of - days. patients with tbrf can have up to febrile relapses, while lbrf is usually associated with only one relapse. other symptoms include myalgia, arthralgia headaches, and vomiting, and physical findings include lymphadenopathy and splenomegaly with rash occurring only in third of the patients. a range of neurologic complications as well as systemic inflammatory response syndrome also have been described [ ] . diagnosis is based on identifying the spirochetes on blood smear. sensitivity of blood smear is higher during febrile period (about %), and a negative blood smear does not exclude rf. in lbrf, the spirochete load can be low and specific stains can be helpful. other diagnostic methods include serologic testing, pcr, and mouse inoculation. doxycycline, tetracycline, and penicillin are the preferred treatment, with most patients treated with - days of doxycycline. jarisch-herxheimer reactions with high fever and leukopenia occur in half of the patients following the first antibiotic dose and can develop into a severe reaction with hypotension, respiratory distress, and death [ ] . without treatment, tbrf carries a mortality rate of up to % with even higher % mortality rate for untreated lbrf. two cases of meningoencephalitis with borrelia miyamotoi in heavily treated immunocompromised patients have been described [ , ] . lyme borreliosis is the most common vector-borne disease in the northern hemisphere caused by a group of at least genospecies. lyme disease is a multisystem illness affecting the skin, joints, nervous system, and heart. human infection is caused mainly by three species: b. burgdorferi is the most common cause in north america but also found in europe, and borrelia afzelii and borrelia garinii which cause the disease in europe and asia. emerging infections in the mid-western usa with borrelia mayonii cause a condition similar to lyme disease. most tick species do not carry borrelia species. the vectors of all borrelia species are the ixodid tick species; this includes the deer tick, i. scapularis, in the northeast and midwest of the usa, ixodes pacificus in the west, the sheep tick, ixodes ricinus, in europe and the taiga tick, ixodes persulcatus, in asia. the ixodid tick demonstrates a complex vector ecology with preferences for different hosts in different geographical regions and at different stages of its development. more than different species, including deer, rodents, birds, and reptiles, have been described. infection rates also show seasonal variation with highest rates during lyme disease follows several stages starting with localized disease at the site of inoculation, followed by dissemination stage and, later, persistent infection [ ] . however, an individual patient can show highly variable disease progression with different patterns of organ involvement and disease severity. erythema migrans (em) is often seen at the site of the tick bite after - days of incubation. regional lymphadenopathy can be seen. secondary skin lesions represent hematogenous dissemination. at this stage, constitutional symptoms of general fatigue, fever and headaches, migratory musculoskeletal pain, conjunctivitis, and cardiac involvement occur. in total, % of untreated patients can develop frank neurologic manifestations of meningitis, encephalitis, and variable forms of neuritis with fluctuating symptoms. persistence can occur in untreated (on inadequately) patients. antibiotic refractory arthritis is well described. however, even without treatment, intermittent or persistent attacks usually resolve completely within several years. co-infection with a. phagocytophilum and b. microti can cause diagnostic confusion [ , ] . the diagnosis of lyme disease is established based on clinical symptoms, history of potential exposure, and serologic studies. although positive culture can confirm the diagnosis, it can usually be obtained only from early em lesions. pcr testing is superior to cultures and can be performed on joint fluid samples [ ] . cdc recommendations for the diagnosis of lyme disease are based on serology which might be impossible in pidd patients with abnormal humoral response. cdc guidelines require both an elisa (or comparable test) to be positive and a western blot ( out of bands ( , , or kd) on the igm or out of bands on the igg ( , , , , , , , , , kd) . most lyme manifestations can be treated with oral antibiotics, while patients with neurologic abnormalities and some patient with lyme arthritis require intravenous therapy [ ] . doxycycline is the treatment of choice for early and disseminated disease, with amoxicillin as the second-line choice. jarisch-herxheimer-like reactions can appear in the first h in about % of the patients. for patients with clear neurologic symptoms, - weeks of iv ceftriaxone is the most commonly used therapy. few cases of neuroborreliosis and hiv have been described with a good response to treatment. descriptions of lyme disease in pidd patients are lacking. zoonoses are infectious diseases that pass between animals and humans and span the spectrum of pathogens including viruses, bacteria, fungi, and parasites. zoonoses are very common and range from mild such as certain forms of tinea to lifethreatening infections such as rabies. some of the zoonoses that are vector-borne will be covered in other sections. risk mitigation strategies for zoonoses include patient education, proactive advice about risk scenarios, and avoidance of infected animals. several zoonoses are associated with contact with mammals such as rodents or domestic farm animals through direct contact or through contact with their feces. for instance, hantavirus infections are often associated with exposures to mouse droppings when staying in cabins in the western usa. occupational exposures can occur with buffalopox or parapoxvirus (causing orf infection) through direct contact with buffalo and goats/sheep, respectively [ ] [ ] [ ] [ ] . in general, there are very few cases of pidd with zoonotic infections acquired from mammals. however, there are a few special considerations. for instance, lymphocytic choriomeningitis virus is acquired through exposure to house mice primarily, with hamsters being a less common source of infection. both domestic and wild mice can carry the infection without exhibiting symptoms. although infection is rare, there have been severe cases in patients with t/ nk cell dysfunction, such as a case in xlp and cases in solid organ transplant recipients [ ] . therefore, in patients with severe t/nk defects, consideration should be given to whether small rodents are appropriate household pets. tularemia is a disease of animals and humans caused by the bacterium francisella tularensis. rabbits, hares, and rodents are the main reservoirs. humans become infected through direct contact, ingestion of contaminated water, or inhalation of organisms. ticks and deer flies can also transmit the disease through bites. fever is universal, but other features depend on the mode of transmission. a patient with cgd had a complex course suggesting myeloid defects are a risk for more severe disease [ ] . rabies is an almost universally fatal infection caused by contact with oral secretions from infected mammals, typically raccoons, bats, or foxes, and there is no suggestion that pidd or immune compromised modifies the prognosis. for individuals with high-risk exposures, such as those working with wildlife or traveling in endemic areas, pre-exposure prophylaxis is given with vaccination, and if an exposure occurs, rabiesspecific immunoglobulin is provided as well as vaccination. however, for those with humoral immunodeficiencies who cannot respond to the typical pre-exposure vaccination, there needs to be counsel on the additional risk without vaccination. in table , several of the bacterial and viral zoonoses are summarized with their typical endemic areas, which is somewhat limited by diagnostic abilities and reporting, as well as the typical clinical scenarios, known cases in immunodeficiency and an approach to diagnosis and therapy. nipah virus causes a range of infectious phenotypes ranging from asymptomatic infection to acute respiratory distress and encephalitis. nipah virus was identified in on pig farms in malaysia, leading to identification of human cases, including human deaths and the culling of one million pigs [ ] . the natural host is the fruit bat: pteropodidae pteropus. symptoms of infection from the malaysian outbreak were primarily encephalitic in humans, but later, outbreaks have caused respiratory illness, increasing the likelihood of human-to-human transmission. fever, headache, cough, abdominal pain, nausea, vomiting, weakness, problems with swallowing, and blurred vision were common. seizures were seen in % and coma in %. relapses of encephalitis have been described [ ] . increasing infections due to nipah virus is thought to be due to an increasing overlap between bat habitats and pig sties in malaysia. all outbreaks thus far have been in india, bangladesh, or malaysia. the diagnosis of nipah virus relies on pcr of fluid samples, serology in convalescent samples, and immunofluorescence of tissue. there have been no infections of immune compromised patients reported. therapy is largely supportive, although preliminary reports of ribavirin use have been encouraging. a vaccine is under development. severe acute respiratory syndrome coronavirus (sars-cov) and the middle east respiratory syndrome coronavirus (mers-cov) are two zoonotic coronaviruses. the sars pandemic in - resulted in reported cases in countries. no further sars cases were reported after the pandemic except isolated cases linked to laboratory accidents. patients usually presented with fever and respiratory symptoms, but occasionally had diarrhea and vomiting. about - % of sars patients required mechanical ventilation, with a case fatality rate of about % [ ] [ ] [ ] . mers was first noted in saudi arabia in , and countries around the arabian peninsula are now endemic for mers-cov. patients usually present with fever, cough, chills, sore throat, myalgia, and arthralgia rapidly progressing to pneumonia with over % of patients requiring intensive care. about one-third of patients present with diarrhea and vomiting, and acute renal impairment is a striking feature of mers. risk factors for poor outcome include diabetes, hypertension, and renal and lung disease. cases have been exported to at least countries with travel occasionally causing cluster of secondary outbreaks. one such example is the mers-cov outbreak involving patients in south korea, and the median incubation period was estimated to be days with a range of to days [ ] . at the end of , there were confirmed mers with a % mortality rate [ ] [ ] [ ] . bats are the natural reservoirs of both sars-cov and mers-cov. sars-cov crossed the species barrier into palm civets and other animals in live animal markets in china, which then infected human, while a mers-cov ancestral virus crossed species barrier into dromedary camels. abundant circulation of mers-cov in camels results in continuous zoonotic transmission of this virus to human, while sars-cov was not found to circulate in the intermediate reservoirs, explaining sars being a one-off outbreak and mers a continuing zoonotic disease [ ] . aerosolgenerating procedures such as intubation were associated with increased viral transmission of both covs resulting in nosocomial outbreaks [ ] . super-spreaders are responsible for large and prolonged outbreaks [ ] . the diagnosis for sars and mers include both serological tests and pcr assays that can quantify viral loads [ ] . functional genetic polymorphisms leading to low serum mannose binding lectin (mbl) are associated with susceptibility to but not severity of sars in both southern and northern chinese [ ] [ ] [ ] . mbl was shown to bind to sars-cov and inhibit the infectivity [ ] , suggesting its role as first-line defense against sars-cov. although no patients with primary immunodeficiency infected with sars-cov or mers-cov were identified, likely due to the limited number of such infections, patients with t cell defect and type interferon pathway defects could suffer a more severe disease course [ , ] . virus-based and host-based treatment strategies are largely experimental with uncertain benefits. ribavirin, type interferons, small molecules, and monoclonal antibodies that block covs entry have been explored [ ] . passive immunotherapy and multiple candidate vaccines have been tested in various animal models. convalescent plasma immunotherapy has been considered, but clinical trials are lacking in mers [ ] , while for sars a systematic review concluded convalescent serum may reduce mortality and appear safe [ ] . the filoviridae family contains three known genera, the ebolaviruses, marburgviruses, and cuevavirus. ebolavirus and marburgvirus cause hemorrhagic fever syndromes in primates and humans, with high fatality rates. cuevavirus infects only bats. the ebolavirus genus contains five species, with two of the species (zaire ebolavirus and sudan ebolavirus) being responsible for the majority of cases of human disease, while marburgviruses contain two species (marburg virus and ravn virus). filoviruses are capable of replicating in a number of cell types (with the exception of neurons and lymphocytes). upon entry into the body of the host (via breaks in the skin, parenterally, or through mucosal surfaces), filoviruses employ a variety of mechanisms to evade the activity of the immune system [ ] . the incubation period (interval from infection to onset of symptoms) varies from to days. symptoms begin abruptly, with high fever, severe headache, malaise, myalgia, diarrhea, nausea, and vomiting. a rash can occur between and days after onset of symptoms. hemorrhagic manifestations occur between and days, and fatal cases usually have some form of active bleeding. in an outbreak setting, the symptoms are unmistakable but confusion with malaria can occur early in the disease or in sporadic cases. since their original descriptions in and , respectively, for marburg and ebola, there have been a number of sporadic cases and several major outbreaks. the largest marburg virus outbreak occurred in angola in (with a fatality rate of > %), while the largest ebola epidemic happened between and in west africa (sierra leone, guinea, and liberia) and claiming over , lives (fatality rate > %). although not definitively proven in the case of ebola, bats are believed to be the natural animal reservoir for these viruses [ , ] . these viruses are transmitted via contact with blood or body fluids from an infected host; notably, certain body fluids can harbor virus for weeks to months after resolution of disease. given the recent outbreak in west africa, there has been renewed interest in understanding the pathogenesis of filovirus infections and possible therapies. literature regarding how the pathogenesis of disease may be altered in patients with pidd is lacking. however, the assumption is that in the absence of an intact cellular and/or humoral immune response, the patient with a pidd may be at increased risk of mortality in the setting where mortality is already high. these viruses induce apoptosis of lymphocytes and macrophages, and there is therefore a profound secondary immune compromised [ , ] . filoviruses can be detected in multiple body fluids via pcr. although practiced for decades, a study in guinea in failed to show a decrease in mortality among patients receiving convalescent plasma from previously infected donors [ ] . a number of additional compounds (e.g., tkm-ebola, bcx , and gs- ) and biologics (zmapp) have been shown to offer protection in animal models of ebola, but to date, no controlled and appropriately powered clinical trials have addressed their efficacy in humans. finally, a number of vaccines for ebola are undergoing clinical studies (including four in phase iii trials). importantly, in late , the rvsv-zebov vaccine was shown to have displayed high efficacy in protecting immunized adults during the guinea ebola outbreak, and the data also suggested that the vaccine may even offer bherd immunity^to unimmunized persons in proximity to recipients of the vaccine [ , ] . hepatitis e virus is a single-strand rna virus of the hepeviridae family. it is an important zoonotic disease in asia and africa, and fecal-oral spread is the usual route of transmission [ ] . handling of pig or boar meat is a risk factor, and - % of pig livers sold in grocery stores in japan and the usa are infected [ , ] . swine represent the major reservoir, although antibodies to the virus have been found in many species [ ] . the incubation period is weeks to months, and viremia disappears with the onset of symptoms. the mortality rate is - % and can reach % in pregnancy [ ] . acute hepatitis usually resolves but can lead to liver failure in severe cases. patients with hepatitis e posttransplant have had severe courses in some cases [ ] . in immune compromised patients, the course can become chronic [ ] [ ] [ ] . in these cases, cirrhosis develops. the diagnosis is by serology or pcr, and the treatment is supportive. prevention modalities for infections transmitted by humans are conceptually different than infection prevention for vector-borne infections. hand hygiene is extremely important, and avoidance of clearly infected people can be helpful. recognition of infections with fecal-oral transmission and the importance of water purity are critical for patients with pidd. in contrast, infections transmitted by aerosols require prevention strategies related to droplet precautions. in outbreak scenarios, if the risk to the patient is high, specific chemoprophylaxis may be considered. influenza viruses type a and b cause annual epidemic influenza, while type c causes sporadic mild influenza-like illness. patients present with sudden onset of fever, chills, and myalgia, followed by sore throat and cough. other less common features include diarrhea, acute myositis, and encephalopathy [ , ] . co-infection with bacteria such as pneumococci results in more severe disease [ , ] . influenza pandemics occur yearly around the world. influenza viruses infect to % of the global population, resulting in~ , deaths annually [ ] . the viruses circulate in asia continuously and seed the temperate zones, beginning with oceania, north america, and europe, then later seeding into south america [ ] . diagnosis of influenza includes direct/ indirect immunofluorescent antibody staining for antigens in nasopharyngeal aspirates and pcr. a patient with compound heterozygous null mutations of the gene encoding irf , a transcription factor for amplifying ifn-α/β, was reported to have life-threatening influenza during primary infection [ ] . fatal influenza-associated encephalopathy in both chinese and japanese children has been reported to be associated with genetic variants of thermolabile carnitine palmitoyltransferase ii [ ] . patients with scid will have prolonged viral shedding [ ] . severe pandemic influenza a virus (h n ) infection has been associated with igg and igg subclass deficiency [ , ] . in addition, influenza infection can be more severe in pidd patients with underlying lung disease, such as bronchiectasis, and antibiotic coverage of chronic colonizing bacteria (such as pseudomonas) in this setting may be helpful. inactivated seasonal influenza vaccine should be given to pidd patients even those with humoral deficiencies as their t cell response to influenza could be normal and offer protective immunity against severe influenza [ , ] . antiviral drugs include neuraminidase inhibitors (oseltamivir and zanamir) and adamantanes (amantadine and rimantadine), but resistance to adamantanes is widespread. measles is a single-stranded, negative-sense, enveloped (nonsegmented) rna virus of the genus morbillivirus. measles is highly communicable, transmitted by droplets, and less commonly by airborne spread. patients present with fever, cough, coryza conjunctivitis rash, and koplik spots. complications include pneumonia, acute encephalitis, and subacute sclerosing panencephalitis (sspe) [ ] . diagnosis of measles includes serological tests, virus isolation, and pcr. in an outbreak, the clinical features may be sufficient for diagnosis. measles vaccine has caused severe measles in children with stat and ifn-α/β receptor deficiency [ , ] , demonstrating the importance of type interferon pathway in controlling measles. immune compromised of nearly any type is associated with severe disease and higher mortality [ ] . t cell deficiency states are the most strongly associated with the development of giant cell pneumonia and inclusion body encephalitis, the most feared complications of measles. sspe is a slow encephalitis due to persistence of replication defective measles virus in the cns. it is most frequently seen when young infants are infected with measles and - years later, sspe becomes evident. there are case reports supporting the immune compromised as increasing the risk of sspe [ ] . treatment of sspe with ribavirin has shown some improvement, but the prognosis in general with sspe is very grave. patients with cgd have defective memory b cell compartment, resulting in lower measle-specific antibody levels and antibody-secreting cell numbers, but severe disease has not been reported [ ] . pidd patients may harbor the virus latently for longer than usual, leading to complications at the time of transplant [ ] . specific antiviral therapy is lacking, but ribavirin has been given to severely ill and immunocompromised children. for measles post-exposure prophylaxis, intravenous immunoglobulin (ivig) is recommended for severely immunocompromised patients without evidence of measles immunity [ ] . this would likely include patients with scid and hypogammaglobulinemia who are not yet on regular ivig. measles vaccine, given in a two-dose regimen, has brought down incidence enormously worldwide and the who is planning for eradication globally. enteroviruses (evs) are among the most common viruses infecting humans worldwide. evs are small non-enveloped, single-stranded rna viruses of the picornaviridae family. human evs are categorized into seven species that include hundreds of serotypes, such as polioviruses (pv), coxsackie viruses a, and b (cv-a and b), echoviruses, and human rhinoviruses (hrvs). of these species, many important serotypes are known to infect human such as pv - , cv-a , cv-b , ev-a , ev-d , and hrv (table ) . non-polio enteroviruses (npevs) have a worldwide distribution. infants and young children have higher incidence of infection and a more severe course of illness than adults. the mode of transmission is mainly through fecal-oral and respiratory routes. infection occurs all around the year in tropical and subtropical regions, while in temperate climates the peak incidence of infection is during summer and fall months [ ] . npevs are associated with diverse clinical manifestations ranging from mild febrile illness to severe, potentially fatal conditions. most cases are asymptomatic or have mild symptoms including fever with or without rash; symptoms of hand, foot, and mouth disease; herpangina; acute hemorrhagic conjunctivitis; upper respiratory infection; and gastroenteritis. more severe symptoms occur in infants and young children [ , ] . acute flaccid paralysis [ ] , neonatal enteroviral sepsis [ ] , myocarditis/pericarditis [ , ] , hepatitis, pancreatitis, pneumonia, and atypical hemolytic uremic syndrome [ ] are severe manifestations seen in immunocompetent people. chronic infections have been seen in immunocompromised patients [ ] . each virus may produce one or more of the aforementioned manifestations; however, some serotypes are often associated with particular features ( table ) . the definitive diagnosis of npev infection relies on pcr or virus isolation from the cerebrospinal fluid, blood, stools, urine, or throat swab [ , ] . treatment of npevs is mainly supportive since most infections are self-limited. high doses of intravenous immunoglobulin (ivig) are recommended in patients with severe symptoms. the efficacy of some new antiviral drugs (pleconaril, vapendavir, and pocapavir) is still under investigation [ ] . no vaccine has been licensed yet for npevs. however, phase clinical trials of inactivated monovalent ev-a vaccines manufactured in china showed high efficacy against ev-a in infants and young children [ ] . patients with a variety of pidds are unusually susceptible to ev [ ] . the most susceptible groups are patients with primary antibody deficiency such as xla, cvid, and hyper-igm syndrome (higms) as well as those having scid and major histocompatibility class ii deficiency [ , ] . the most severe form of infection has been described in patients with xla due to the profound deficiency of immunoglobulins essential for viral neutralization during infection. affected patients usually present with indolent but relentlessly progressive non-necrotizing meningoencephalitis. regression of cognitive skills, flaccid quadriplegia, and deafness has been described. the reported non-neurologic presentations in xla include septicemia, dermatomyositis-like disease, hepatitis, and/or arthritis [ , ] . the incidence of npev meningoencephalitis in large registries of xla cases is - % [ ] . unpublished data from the kuwait national pidd registry, which includes pidd patients, showed that nine patients had documented npev infections and two died from these infections. the two deaths were seen in scid patients (personal communication with prof. waleed al-herz, md). in addition, npev meningoencephalitis and/or septicemia were reported in few cases with either primary b cell deficiency such as b cell linker (blink) protein deficiency [ ] or acquired b cell deficiency following the administration of anti-cd (rituximab) [ , ] . in all reports, better outcome was attributed to the early administration of high doses of ivig during npev viremia [ ] . npev infection in pidd diseases remains a major threat to patients. also, the possible prolonged viral excretion and the emergence of resistant strains runs the risk of spreading infection to the surrounding community. oral polio vaccine (opv) consists of a mixture of three live attenuated poliovirus serotypes. opv induces production of neutralizing antibodies against all three serotypes, in addition to a local intestinal immune response. opv can result in vaccine-associated paralysis (vap) secondary to reversion of the vaccine strain to the neurovirulent wild-type strain. an example for such an event was demonstrated by the - outbreak in the dominican republic and haiti [ ] , believed to be driven at least in part by undervaccination of the population, which allowed the spread of the reverted vaccine strain [ ] . although rare, patients with pidd have a higher risk to develop vap. reports have shown that pidd patients with antibody deficiency can have prolonged viral replication which can persist for years and therefore theoretically increase the risk for a spontaneous reversion within the immunodeficient host [ ] [ ] [ ] [ ] . cases of vap were shown in patients with antibody deficiency and combined immunodeficiency syndromes [ , , ] . therefore, opv is contraindicated in patients with pidd, and this contraindication extends to their household contacts [ ] . beyond the obvious risk for the pidd patient, prolonged virus shedding also increase the risk for spreading vaccine-derived paralytic strain in the general population. bacterial infections have molded human behavior and altered societies over human history. today, largely ignored due to antibiotic susceptibility, they continue to cause misery and disease around the world. three infections are highlighted, and additional commonly encountered infections are listed in table . pertussis is a respiratory infection caused by bordetella pertussis that begins after a -to -day incubation period as a minor upper respiratory infection that progresses with cough. initially intermittent, it evolves into paroxysmal coughing spells usually followed by vomiting in infants and young children. it lasts to weeks and can have many complications such as syncope, weight loss, rib fracture, and pneumonia. infants under months are more severely affected, developing pneumonia, pulmonary hypertension, hypoxia, subdural bleeding, and seizures. death can occur, especially in young infants [ , ] . adults typically have a prolonged cough with fewer complications [ ] . it is transmitted via aerosolized droplets during close contact. people are most contagious during the catarrhal stage and the first half of the paroxysmal phase, totaling to weeks [ ] . the introduction of whole-cell pertussis vaccine (dpt) in the s in the usa reduced the incidence of the disease from , cases to around cases per year in the s. a resurgence in was associated with the substitution of the whole-cell vaccine by the acellular pertussis vaccine (dtap) [ ] . new strategies such as boosters with acellular pertussis for adolescents and adults with tdap and use of tdap during pregnancy seem to be effective in partially reducing the incidence of the disease [ ] ; however, pertussis cases in the usa remain higher than the s. the lack of persistence of antibody in the adult population means adults not only represent a reservoir for the disease but also do not provide sufficient titers to immunoglobulin products prepared from adult plasma pools. a relatively recent requirement in some countries is vaccination of adults every years to maintain immunity. this should, over time, improve titers in immunoglobulin products. culture of specimens obtained by nasopharyngeal swabs is the gold standard of laboratory diagnosis due to the % specificity, but polymerase chain reaction (pcr) is gaining prominence due to its higher sensitivity and speed of results; serodiagnosis can be used in the late stages of the disease [ ] . filamentous hemagglutinin (fha) and pertussis toxin (pt) antibodies were detected at peak measurements in pidd patients on regular ivig, although some of them had pt antibodies below the protective level as trough measurements [ ] . severe pertussis cases have not been reported in pidd patients, but severe disease has been seen in malignancies [ ] . antimicrobials such as azithromycin, erythromycin, and clarithromycin, if given during the catarrhal stage, may ameliorate the disease and shorten the contagious period. to avoid cases of pertussis, it is also worth emphasizing the importance of good vaccine coverage rate among the whole population, but especially among healthcare workers and family members of patients with pidd. neisseria meningitidis the onset of neisserial meningitis is associated with sore throat, headache, drowsiness, fever, irritability, and neck stiffness [ , ] . purpuric lesions are very characteristic. this pathogen can also present with sepsis which has a % mortality rate as opposed to % mortality with a meningitic presentation. this bacterium can also cause a chronic condition referred to as chronic meningococcemia. this condition is characterized by intermittent fevers lasting week to - months [ ] . a non-purpuric rash is common which may evolve into purpura. arthritis, similar to that seen with gonococcus, is common. meningococcal disease primarily affects children under years of age. n. meningitidis is a global pathogen [ ] . there are serogroups, but the majority of invasive meningococcal infections are caused by organisms from the a, b, c, x, y, or w serogroups. the annual number of invasive disease cases worldwide is estimated to be at least . million, with , deaths related to invasive meningococcal disease. serogroups b and c are responsible for most infections in europe. serogroup a has historically been the major organism in africa; mass vaccination has led to some improvement, but the emergence of group x disease is worrisome. the hajj in the middle east has seen epidemics of w- , and vaccination is now required for hajj travelers. b and c serogroups are the most common through the americas. n. meningitidis cases occur at a rate of about case per , people throughout the world [ ] , but across the sahel of africa and in china, epidemics can lead to case rates of per , [ ] . the bacterium is a natural human commensal, with carriage rates of about %. diagnosis can be by clinical examination in epidemics or by gram stain and culture. complement-deficient individuals have an increased risk of neisserial disease, but not necessarily increased mortality. hiv is associated with increased disease, suggesting that t cells are also important for defense. thirdgeneration cephalosporins are typically used for treatment. penicillin, ampicillin, aztreonam, and chloramphenicol are alternatives. there is great inter-individual variability in the development of tb disease. roughly, % of infected individuals develop clinical disease within years of infection (mostly during childhood). about % became latently infected without clinical disease, and the remaining to % develop pulmonary tb later in life, either from reactivation of latent infection or reinfection. molecular epidemiology studies from high burden areas suggest more disease results from recent transmission than from reactivation of latent tb, particularly in people living with hiv [ ] . acquired or inherited host factors may at least partially account for the variable disease course, resulting in increased susceptibility to mycobacteria infections [ ] . pidd associated with tb and ntm infections include t cell deficiencies, gata deficiency, cgd, anhidrotic ectodermal dysplasia with immunodeficiency, x-linked (xl) recessive cd ligand deficiency, autosomal recessive (ar) stat deficiency, ar irf deficiency, and ar tyk deficiency. in addition, a group of disorders with a strong susceptibility to ntm, named mendelian susceptibility to mycobacterial diseases (msmd), have been recognized since the s. these are rare inborn errors of ifn-γ signaling pathway that present with isolated predisposition to infections caused by weakly virulent mycobacteria such as bcg vaccine and environmental ntm, in otherwise healthy patients. the genetic defects involve impairment in the production of interferons (ar il rβ , ar il p , autosomal dominant (ad) irf , ar isg , xl recessive nemo) or response to interferons (ifn-γr, ad stat , ad irf , cgd) [ ] . an acquired form exits: adults with ntm infection in thailand and taiwan were found to have high-titer anti-interferongamma antibody [ ] . these individuals from southeast asia were found to have hla-drb * / : and dqb * : / : . patients suspected of having pulmonary tb should have acid-fast bacilli (afb) smear microscopy and culture performed in three sputum samples. pcr for mtb can be performed [ ] . the use of rapid tests facilitates early diagnosis, and the who has recently recommended their use. the only recommended rapid test for detection of tb with and without rifampicin resistance is the xpert mtb/rif assay (cepheid, sunnyvale, ca). the who recommends the xpert test for those suspected of having drug-resistant tb or in hiv; however, culture is still the mainstay and is not replaced by the xpert test. tb skin testing (mantoux testing) uses a purified protein derivative injected under the skin. its advantages are that it can be used for large-scale screening and it is cost effective. skin testing does have several disadvantages when used as a diagnostic test. reading the induration requires training and immunodeficiencies can alter the magnitude of the induration. immunosuppressed patients (hiv, organ transplant) are considered positive if the induration is ≥ mm. some immunodeficiencies may completely ablate the response. other causes of false-negative tests are malnutrition, concurrent infection, recent live viral vaccine administration, renal failure, malignancy, medical stress, very elderly, young infants, or with a very recent infection with mtb. conversely, the results may be falsely positive if bcg has been administered. interferon gamma release assays can be used in any setting where skin testing would be done but are considered superior in settings where the patient has had bcg vaccination and, in some cases, where skin testing has been sown to have high false-negative rates. in general, tb treatment for patients with impaired immune response, including pidd, hiv infection, and immunosuppressive therapy, is based on the standard -month regimen consisting of a -month intensive phase of isoniazid, rifampin, pyrazinamide, and ethambutol, followed by months of isoniazid and rifampin. decisions regarding treatment duration can be individualized, taking into account disease severity, organs involved, and response to treatment. significant pharmacological interaction can occur between rifampin-based mtb regimens and immunosuppressive drugs, such as calcineurin inhibitors or rapamycin, requiring strict monitoring of drug plasma concentrations [ ] . therapy for ntm is complex with highly variable drug resistance patterns and a need for biological augmentation to effectively clear the organism. aspergillus fumigatus (see above), cryptococcus gattii, histoplasma capsulatum, coccidioides immitis (or c. posadasii), blastomyces dermatitidis, paracoccidioides brasiliensis, emmonsia pasteuriana, and penicillium (talaromyces) marneffei are environmental fungi that are endemic in certain parts of the world (table ). with the exception of penicillium marneffei and emmonsia pasteuriana that only cause disease in profoundly immune compromised individuals, these fungi can cause infection in healthy individuals, ranging from mild, self-limited pulmonary disease to infection that requires antifungal therapy for eradication. on the other hand, patients with acquired defects in cell-mediated immunity such as those infected with hiv, and patients with specific monogenic disorders, particularly those involving the il- / ifn-γ/stat signaling pathways, scid, and gata depends on underlying state of immunosuppression and magnitude of environmental exposure icl idiopathic cd lymphocytopenia, aids acquired immune deficiency syndrome, stat signal transducer and activator of transcription , gata gata binding protein , scid severe combined immunodeficiency, cvid common variable immune deficiency, pidd primary immunodeficiency, il rb , interleukin- receptor subunit beta , ifngr gamma interferon receptor deficiency, are at high risk of developing life-threatening disseminated infections by these endemic fungi following environmental exposure [ , [ ] [ ] [ ] [ ] [ ] . diagnosis relies on culture of the corresponding fungus, histopathological demonstration of the fungus-specific characteristic morphologies, and/or surrogate serological and fungal antigen tests. treatment of clinical disease (as opposed to colonization) typically involves an initial induction phase with amphotericin b, followed by long-term azole maintenance therapy and secondary prophylaxis, and prognosis varies significantly depending on the fungal pathogen and underlying pidd. melioidosis is caused by b. pseudomallei, a gram-negative bacteria found in soil and water, in tropical climates of southeast asia and northern australia [ , ] . melioidosis is an emerging, potentially fatal disease ( % mortality). b. pseudomallei can be transmitted by inhalation, ingestion, or direct contact (through open skin) with contaminated soil or water. animals (sheep, goats, swine, horses, cats, dogs, and cattle) are also susceptible to infection and cases of zoonotic transmission through direct contact of skin lesions with infected animal meat or milk have been described [ ] . b. pseudomallei infections are endemic in northern australia and southeast asia. approximately % of reported infections occur during the rainy seasons. cases have also been reported in south pacific, africa, india, and the middle east. in temperate areas, infection is extremely rare and is predominantly imported by travellers or immigrants [ ] . the incubation period of melioidosis is variable from day to years, although common symptoms develop between and weeks after exposure. melioidosis presents most frequently in adults - years of age, but can occur in all ages, with one study reporting % of cases occurred in children [ ] . in australia, the average annual incidence in - was reported as . cases per , people [ ] . the incidence in indigenous australians was higher at . cases per , . a case-cluster in an australian community was associated with post-cyclonic flooding. a recent review suggests that b. pseudomallei is increasingly prevalent in the americas, with a mortality rate of % [ ] . infection in healthy individuals is uncommon, and more than % of cases occur in the setting of underlying conditions such as chronic renal disease, diabetes, chronic lung disease, and alcoholism. a recent review of melioidosis in travelers found that % of cases were acquired in thailand. symptoms usually started at days (range - days) after leaving the endemic area. traveller infections were less often associated with predisposing risk factors ( . %), diabetes mellitus being the most common ( %). melioidosis in travelers had lower mortality ( %) than infection in autochthonous cases in southeast asia [ ] . pneumonia (~ - %) is the most common presentation in adults. there is usually high fever, headache, anorexia, and myalgia. b. pseudomallei infection may also present as localized skin infection, septicemia, or disseminated infection. localized infection results in an ulcer, nodule, or skin abscess. this usually occurs from the bacterium breaching through a break in the skin. patients with renal disease and diabetes are more susceptible to sepsis. in disseminated infection, abscesses may develop in the liver, spleen, lung, and prostate. in children, primary cutaneous melioidosis is the commonest presentation ( %). bacteremia is less common in children than in adults, but brainstem encephalitis has been reported [ ] . difficulties in laboratory diagnosis of melioidosis may delay treatment and affect disease outcomes [ ] . diagnosis of melioidosis is primarily by isolation of the organism. identification of b. pseudomallei can be difficult in clinical microbiology laboratories, especially in non-endemic areas where clinical suspicion is low. although various serological tests have been developed, they are generally unstandardized bin house^assays with low sensitivities and specificities. pcr assays have been applied to clinical and environmental specimens but are not widely available and sensitivity remains to be evaluated. cases of melioidosis have been reported in patients with acquired or inherited immune deficiency. melioidosis was the presenting complaint in several patients with cgd. bacteremic melioidosis was recently reported in two patients with prolonged neutropenia, who succumbed despite appropriate antibiotics [ ] . it is likely that there is increased susceptibility in situations where innate or adaptive immunity is compromised. treatment is with intravenous antimicrobial therapy for - days, followed by - months of oral antimicrobial therapy. intravenous therapy with ceftazidime or meropenem is usually effective. oral therapy may continue with trimethoprim-sulfamethoxazole or doxycycline. free-living amoebas (fla) are protozoa found worldwide that do not require hosts to survive. fla do not employ vectors for transmission and are not well adapted to parasitism in humans. however, there are four genera/species that can cause human disease: naegleria (n. fowleri), acanthamoeba (multiple species), balamuthia (b. mandrillaris), and sappinia (s. pedata). all of these amoebae are capable of inducing cns disease in humans, but acanthamoeba species also cause various extra-cns infections, especially in immunocompromised hosts. the fla that are pathogenic in humans are reviewed below. naegleria are a diverse group of fla flagellate protozoans with a large number of distinct species. only one species, n. fowleri, has been shown to cause infection in humans. n. fowleri has a multi-stage life cycle with amoeboid and trophozoite-infective forms as well as a cyst form [ ] . n. fowleri is found commonly in warm freshwater around the world including lakes, rivers, and hot springs. humans become can become infected when swimming or diving in contaminated water. in rare circumstances, infections have also been attributed to exposure from contaminated tap water sources when utilized for religious cleansing of the nose or irrigation of the sinuses. thus, tap water should not be used for nasal and sinus irrigation. it is not possible to become infected from drinking contaminated water or from contact with an infected person, and the amoeba is not found in salt water. after entry to the nasal cavity, the amoeba travels through the cribiform plate to the olfactory bulbs and migrates to the cerebellum, resulting in primary amoebic meningoencephalitis (pam), a rapidly fatal brain infection characterized by the destruction of brain tissue. in its initial presentation, pam can mimic bacterial meningitis, further delaying accurate diagnosis and initiation of therapies that may save the patient. overall, n. fowleri infections are rare. worldwide, most cases are reported in the usa, australia, and europe; however, in developing countries, it is suspected that a large number of cases go unreported. between and , there were only infections reported in the usa with of the cases attributed to contaminated recreational water, infections following nasal irrigation with contaminated tap water, and case where a person was infected following use of a backyard slipn-slide utilizing contaminated tap water [ ] . the fatality rate associated with n. fowleri infection is over %, and between and , only of the infected persons in the usa have survived infection. initial symptoms of pam start to days after infection and can include headache, fever, nausea, or vomiting [ ] . progressive symptoms can include stiff neck, confusion, lack of attention, loss of balance, seizures, and hallucinations. cardiac arrhythmias have also been observed. the infection progresses rapidly after initial onset and causes death within to days after exposure (mean of . days). since infection often progresses rapidly to death, there is often insufficient time to mount a robust immune response. however, both the innate (neutrophils, macrophages, and complement system) and the adaptive (both t and b cells) arms of the immune system have been shown to participate in the immune response to n. fowleri [ ] . patients with pam have csf with elevated pressure that is often cloudy or hemorrhagic, with neutrophil-predominant pleiocytosis, elevated protein levels, and very low glucose. wet mounts from centrifuged csf will show motile mono-nucleated trophozoites measuring~ - μm in size. additionally, trophozoites can be identified with giemsa and wright stains of csf smears combined with an enflagellation test [ ] . confirmation can be achieved via a variety of timeconsuming methods including an immunofluorescence assay [ ] , culture of csf [ ] , or pcr-based methods [ ] . the optimal therapy for n. fowleri pam is still debated. the use of intravenous amphotericin b and fluconazole followed by oral administration of rifampin resulted in survival of a year-old child with pam [ ] . another child was shown to survive following intravenous and intrathecal amphotericin b and miconazole as well as oral rifampin [ ] . most recently, an adolescent girl was successfully treated with the combination of azithromycin, rifampin, fluconazole, and miltefosine [ ] . prevention is critical for this highly fatal infection and warning pidd patients not to use tap water for nasal irrigation is important. since its original description in , over cases of b. mandrillaris infections have been described worldwidewith most cases occurring in south america and the usa. balamuthia are found in soil, and acquisition of disease has been associated with agricultural activities, dirt-biking, gardening, and swimming in contaminated water sources. b. mandrillaris is thought to enter the body of the host through breaks in the skin and or via inhalation. the organism is believed to access the cns through hematogenous spread, resulting in a chronic, insidious, but often fatal granulomatous amoebic encephalitis (gae), which has been documented in both immunocompetent and immunocompromised hosts [ , ] . the incubation period from exposure to development of clinical symptoms is not well established and experts believe that this may occur between months and years. finally, an alternative mode of transmission via solid organ transplantation has also gained attention [ ] [ ] [ ] . in many cases, gae is diagnosed post-mortem, due to delayed diagnosis or unawareness of the clinical entity. following infection by b. mandrillaris, two clinical patterns of presentation have been described. in the first pattern, patients initially develop a skin lesion that may resemble a painless plaque that may evolve into subcutaneous nodules and rarely ulcerations [ ] . these patients may develop neurologic manifestations weeks to months later. histopathologic examination of these lesions typically reveals granulomatous reactions in the reticular dermis, associated with lymphocytic and plasma cell infiltrates as well as multinucleated giant cells, without distinct epidermal changes. skin lesions will harbor trophozoites, but these are scarce and often easily overlooked as they resemble histiocytes. it is believed that early diagnosis of b. mandrillaris infections in those presenting with skin lesions may prevent subsequent development of cns disease, but there have also been cases in which patients presenting with skin lesions have progressed to developing gae despite treatment. in the second pattern, patients present with cns involvement without a previously recognized skin lesion. patients presenting with gae may initially display fever, malaise, headache, nausea and vomiting, and frank lethargy. later, these symptoms evolve into visual abnormalities, cranial nerve palsies, seizures, focal paresis; as intracranial pressure builds, coma, and eventually death with tonsilar or uncal herniation ensue within - weeks [ ] . upon infection with b. mandrillaris, brain endothelial cells produce the proinflammatory cytokine il- , thereby initiating an inflammatory response [ ] . moreover, the amoebic trophozoites infiltrate blood vessel walls. degradative enzymes, vessel wall infiltration, and the host inflammatory responses result in tissue necrosis and infarctions in the cerebral hemispheres, cerebellum, and the brainstem. in a mouse model of b. mandrillaris infection, cd + t cells were shown to be protective [ ] , suggesting that patients with lowered number or dysfunction in cd + t cells may be more susceptible to disease by this amoeba. however, b. mandrillaris infections have been described in a variety of human hosts [ ] , ranging from the young, healthy, and presumably immunocompetent to the elderly, and those with hiv, chronic corticosteroid exposure, on post-transplant immunosuppression and even patients with cvid. as such, further research is necessary to fully delineate the susceptibility of pidd patients. in patients who develop the characteristic skin lesions, recognition, testing, and treatment for b. mandrillaris may prevent subsequent gae. as such, obtaining tissue and looking for granulomas and trophozoites is quite helpful. skin biopsies can be stained via immunofluorescence or immunoperoxidase techniques to identify b. mandrillaris [ ] . additionally, a pcr technique that identifies mitochondrial s ribosomal rna from b. mandrillaris is also available through the cdc [ ] . in patients in whom the diagnosis is confirmed via skin biopsy, wide resection and medical treatment appears to prevent development of cns disease in at least a proportion of patients. in patients presenting with cns involvement, lumbar punctures reveal csf with lymphocytic pleiocytosis, low-to-normal glucose, and mildly to significantly elevated protein levels. trophozoites are not typically found in the csf, but pcr analysis may be performed. ct or mr imaging may show multiple nodules with ring enhancement; some of these nodules may also contain focal areas of hemorrhage. biopsies of brain tissues typically reveal granulomas and foamy macrophages and multinucleated giant cells surrounded by lymphocytic infiltrates. additionally, there will be areas of necrosis filled with neutrophils, multinucleated giant cells, and lymphocytes, with balamuthia trophozoites and cysts interspersed with macrophages [ ] . as with the skin biopsies, immunofluorescent and immunoperoxidase stains may aid diagnosis and should be performed. unfortunately, the optimal medical management of cns disease is unknown. in the usa, a few patients have been successfully treated with a combination of fluconazole, flucytosine, pentamidine, a macrolide antibiotic (either clarithromycin or azithromycin), and one of the following agents: liposomal amphotericin b, miltefosine, sulfadiazine, or thoridazine [ ] [ ] [ ] ; others in peru have been treated successfully with fluconazole (or itraconazole), albendazole, and miltefosine [ ] . based on these case reports, most experts recommend treatment with a combination of medications (along with partial or complete resection of nodules) for a prolonged period of time to prevent further deterioration and death [ ] [ ] [ ] [ ] . acanthamoeba spp. the genus acanthamoeba contains at least morphologically distinct species that live in a diverse array of habitats, including soil, salt, brackish, and fresh water. acanthamoeba spp. have also been found in humidifiers, heating and cooling unit components, jacuzzis, hot water tanks, bathrooms and drains, eye wash stations and dentistry irrigation systems, and more. acanthamoeba spp. have been isolated from reptiles, birds, and other non-human mammals, suggesting a broad distribution in the environment. acanthamoeba trophozoites feed on bacteria, but have also recently been shown to harbor a number of bacteria (including legionella and burkholderia spp., e. coli, listeria monocytogenes, vibrio cholerae, mycobacteria spp., chlamydophila, and others) and at least one virus (mimivirus) as endosymbionts. acanthamoeba infections in humans can present in a variety of ways. of primary importance are cns infections. like b. mandrillaris, acanthamoeba spp. can induce gae (described above). there is a high predilection for gae in those with hiv/aids, patients on chemotherapy, and those receiving broad spectrum antibiotics [ ] . acanthamoeba are rarely found in csf, but some case reports indicate isolation of amoebae by culturing csf on bacterized agar plates. similar to gae seen with b. mandrillaris, cns histopathology may reveal edema, multiple areas of necrosis and hemorrhage, and occasional findings of angitis and blood vessel cuffing by inflammatory cells, as well as occasional trophozoites or cysts. cns disease treatment is not standardized, but several patients have been successfully treated with pentamidine, fluconazole, flucytosine, sulfadiazine, as well as miltefosine. acanthamoeba can rarely cause cutaneous infections; these lesions, like gae, are also predominantly seen in immunocompromised hosts. these lesions can start as nodules or papules on the lower extremities and develop into necrotic ulcers. histopathologic examination may reveal granulomatous dermal lesions in immunocompetent hosts, with histiocytes, as well as neutrophils and plasmacytes; trophozoites are typically visible [ , ] . the optimal management of cutaneous disease is not known, but typically involves combinational therapy with topical (e.g., chlorhexidine, gluconate, or ketoconazole) and systemic (miltefosine, sulfadiazine, flucytosine, liposomal amphotericin b, azole antifungals, etc.) drugs. additionally, nasopharyngeal and sinus infections have been seen in people with severe compromise in immunity [ , ] . patients typically present with purulent nasal discharge, and examination may reveal erosion of the nasal septum. nasopharyngeal disease can present concomitantly with cutaneous disease. treatment of nasopharyngeal or sinus disease is difficult and involves surgical debridement and combinations of systemic drugs. disseminated disease is also seen in immunocompromised hosts and typically involves concomitant pulmonary and cutaneous disease in the presence or absence of cns infection. keratitis readily occurs in immunocompetent hosts-with the major risk factor being contact lens wearing without proper adherence to recommended cleansing protocols. this infection less commonly presents as a result of direct inoculation with trauma. one of the most common reasons for contact lens wearers to acquire disease is due to the use of non-sterile tap water in preparing contact lens saline solutions [ ] , although contaminated solutions from manufacturers have also been identified. patients will have pain and photophobia. physical exam reveals conjunctival injection and epithelial abnormalities (including pseudodendritic lesions) and stromal infiltrates [ ] . the proper diagnosis can be made by staining corneal scrapings with calcofluor or wright-giemsa stains and examined by confocal microscopy, culture, or pcr analysis. prompt therapy with a combination of polyhexamethylene biguanide (or biguanide-chlorhexidine) and propamidine or hexamidine [ , ] is indicated, but misdiagnosis and delayed therapy are common. more severe cases may also require debridement. the use of topical steroids before administration of combinational therapy may result in worse outcomes and should be avoided; however, if scleritis ensues, it may be necessary to use immunosuppressants to reduce the need for enucleation. severe and/or refractory cases may result in the need for cornea transplantation. phenotypes seen in pidd like hsv- and candida [ ] . patients with ifnar deficiency seem highly susceptible to cns disease caused by mmr vaccine, an otherwise extremely rare phenomenon [ ] . recently, a case of noroviral cns disease was described associated with a novel, yet unpublished pidd, suggesting that some pidds may lead to susceptibility of the cns to viruses that normally do not exhibit neurotropism (casanova jl, personal communication) . this again favors metagenomic approaches in the study of cns sequelae in pidd patients. in pidds, the cns is also more vulnerable to virally induced immunodysregulation [ ] . conditions like primary hemophagocytic lymphohistiocytosis (hlh) may present as isolated cns disease or relapse only in the cns [ ] [ ] [ ] . almost % all human malignancies are associated with chronic infections by hbv, hcv, hpv, ebv, hhv /kshv, htlv-i, hiv- , hiv- , jcv, merkel cell polyomavirus (mcpv), helicobacter pylori, schistosomes, or liver flukes [ ] . accordingly, pidd patients' malignancies are often associated with chronic infections. mcpv-associated merkel cell carcinoma has now been described in gata and tmc (ever ) deficiencies as well as other forms of pidd [ , [ ] [ ] [ ] [ ] [ ] . large follow-up cohorts are needed to refute or confirm associations between novel pidds and malignancies, such as hyperactivating pik cd and ovarian dysgerminoma or gata deficiency and leiomyosarcoma [ , ] . recently, hymenolepis nana was found to have driven malignant transformation in an hiv patient. likely, other novel pidd-and pathogen-associated malignancies will be found in the future by those with an open and inquisitive mind [ ] . understanding the specific infection susceptibility for each pidd allows not only a better understanding of host defense, but also allows the clinician to collaborate with the microbiology laboratory to make definitive diagnoses and provide the best therapy. reviewing all of the infections for each pidd is not within the scope of this article, but there are several infections that are unique for specific pidds and require special attention from the microbiology laboratory. three examples are provided below. g. bethesdensis is a gram-negative bacterium that was identified to cause disease in patients with cgd in [ ] . g. bethesdensis is a member of the methylotroph group of bacteria, which are able to use single-carbon organic compounds as their only source of energy. they are widespread in the environment, but are rare human pathogens, and infections with g. bethesdensis have been limited thus far to patients with cgd. the organism was first detected in an adult patient with indolent and recurrent necrotizing lymphadenitis [ ] . subsequently, g. bethesdensis was isolated from nine patients with cgd, primarily causing lymphadenitis, but there have been two fatalities [ ] . treatment has been most effective with intravenous ceftriaxone. the microbiology laboratory should be alerted when there is concern for g. bethesdensis infection to allow for proper culture media. charcoal yeast extract (cye) agar and lowenstein jensen (lj) media are appropriate culture media. mycoplasma and ureaplasma spp. as molecular techniques are becoming more widely used to detect pathogens, the spectrum of infections that were previously only detected through serologic assays and research laboratories will increase. this is important especially for patients with pidd who have unique susceptibility to infection and may not have the ability to mount a serologic response. examples of infections in this group are those caused by mycoplasma and ureaplasma [ , ] . these pathogens have been known to cause osteoarticular infections for those with antibody deficiency, such as xla and cvid. recently, mycoplasma orale, typically an oral commensal, has been isolated from two patients with defects in the activated pi k delta syndrome, as chronic lymphadenitis in one and chronic splenic abscess in the other (sm holland personal communication). defects in pi kcd and pi kr are frequently associated with hypogammaglobulinemia and therefore would fit in the pattern of mycoplasma infections in those with humoral immunodeficiency. mycoplasma orale has also previously been reported as causing bone disease in a patient with cvid [ ] . in patients with xla, helicobacter, camplyobacter, and the related flexispira bacteria that are typically isolated to the gi tract can disseminate and often lead to chronic bacteremia, ulcers, and bone infections [ ] [ ] [ ] . xla patients have higher susceptibility than other humoral pidd and are thought to be due to the role that igm is playing in controlling the dissemination of these pathogens and potentially iga in providing mucosal immunity. these bacteria can be fastidious to grow, and therefore, when there is suspicion, identification needs collaboration with the microbiology laboratory. for instance, the blood culture media may allow growth (although with a longer incubation period), but then the organisms may need molecular techniques for identification, such as s sequencing, as they will not grow on the agar plates. treatment is often difficult, requiring combination antimicrobials for prolonged periods (such as year), and relapse is common. this review provides an important perspective for practicing immunologists, namely that we are a part of a global community as are our patients. this overview of emerging infections and infectious concerns for travelers serves as a foundation for practical considerations for clinicians and patients. using prevalence data, an estimation of the number of infected patients with pidd (table ) can be developed [ , , [ ] [ ] [ ] [ ] . thus, the concerns addressed in this review are not theoretical but impact a considerable number of patients already. the landscape of emerging infections is by its nature highly 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spotted fever in israel over years complications of bacille calmette-guerin (bcg) vaccination and immunotherapy and their management acknowledgements the authors would like to thank thomas krell for information regarding ivig safety and david peden for recognizing global warming as central to medical knowledge. conflict of interest the authors declared that they have no conflict of interest. pidds display wide genetic and phenotypic heterogeneity [ ] . similar disease phenotypes may be caused by multiple genes, while patients' phenotypes caused by the same gene and even by the same mutations vary between individuals. importantly, after a novel pidd has been described, subsequent reports often reveal a wider variation in associated infections and cellular findings, often without clear genotype-phenotype correlations [ ] [ ] [ ] [ ] [ ] . variation may be caused by mechanisms such as other contributing genes or geographical variation in infectious exposures. geographic differences seem most pronounced in intracellular and often chronic infections. while the numbers of described pidd patients increase, at first seemingly rarely pidd-associated infections turn out to be found in a significant subset of pidd patients [ ] [ ] [ ] . for example, patients with cd l deficiency living in endemic areas display susceptibility to bartonellosis and paracoccidioidomycosis, infections not described in european and us cohorts [ , , ] .often, an infectious phenotype previously only described in secondary immunodeficiencies may reveal the possibility of an underlying primary immunodeficiency [ , , ] . increasing numbers of genetic defects causing early-onset, severe, and recurrent susceptibility to commonly circulating pathogens like pneumococci, tuberculosis, herpes simplex, and influenza viruses as well as endemic protozoans like trypanosomes and fungi are being recognized, and thus, infections with unusual pathogens require a high index of suspicion for pidd [ ] . in contrast, pidds may also manifest as suspected infection but sterile inflammation. for example, in inflammatory lesions like granulomas and necrotizing fasciitis where no clear pathogens are found, one needs to rule out aberrant host responses due to pidd [ ] .chronic viral and fungal infections may also display novel phenotypes never or rarely seen in secondary immunodefic i e n c i e s . i n f e c t i o n s l i k e d e r m a t o p h y t o s i s a n d phaeohyphomycosis deeply infiltrating the skin and lymph nodes, occasionally extending to bones and central nervous system (cns) as well as predisposition to primary cns candidiasis and extrapulmonary aspergillus slowly revealed the full phenotypic spectrum of card deficiency [ , , ] . chronic skin ulcers caused by hsv- and severe molluscum contagiosum suggest dock deficiency or gain-of-function mutations of stat [ , ] . chronic mucocutaneous candidiasis has revealed a large group of monogenic diseases (il ra, il rc, il f, stat (gof), rorx, act ), which may also be associated with recurrent bacterial infections or syndromic features [ ] . while novel diseases by newly described viruses are being discovered, one needs awareness to suspect these in pidd patients [ ] .interestingly, most novel forms of infectious disease in pidd patients have been described either in easily accessible sites like the skin or in immunologically privileged, normally sterile sites like the cns. this suggests that with the increasing use of invasive sampling and sensitive metagenomic approaches, we might find more novel infectious phenotypes. pathogens highly suggestive of certain pidds, like chronic enteroviral cns infections in xla patients are reviewed above. in hypomorphic mutations, cns seems to be especially vulnerable to chronically active and/or recurrent novel infectious bsmoldering^focal encephalitis lesions by pathogens key: cord- -u zjzqbr authors: demos, terrence c.; webala, paul w.; goodman, steven m.; kerbis peterhans, julian c.; bartonjo, michael; patterson, bruce d. title: molecular phylogenetics of the african horseshoe bats (chiroptera: rhinolophidae): expanded geographic and taxonomic sampling of the afrotropics date: - - journal: bmc evol biol doi: . /s - - - sha: doc_id: cord_uid: u zjzqbr background: the old world insectivorous bat genus rhinolophus is highly speciose. over the last years, the number of its recognized species has grown from to , but knowledge of their interrelationships has not kept pace. species limits and phylogenetic relationships of this morphologically conservative group remain problematic due both to poor sampling across the afrotropics and to repeated instances of mitochondrial-nuclear discordance. recent intensive surveys in east africa and neighboring regions, coupled with parallel studies by others in west africa and in southern africa, offer a new basis for understanding its evolutionary history. results: we investigated phylogenetic relationships and intraspecific genetic variation in the afro-palearctic clade of rhinolophidae using broad sampling. we sequenced mitochondrial cytochrome-b ( bp) and four independent and informative nuclear introns ( bp) for individuals and incorporated sequence data from additional individuals on genbank that together represent of the currently recognized afrotropical rhinolophus species. we addressed the widespread occurrence of mito-nuclear discordance in rhinolophus by inferring concatenated and species tree phylogenies using only the nuclear data. well resolved mitochondrial, concatenated nuclear, and species trees revealed phylogenetic relationships and population structure of the afrotropical species and species groups. conclusions: multiple well-supported and deeply divergent lineages were resolved in each of the six african rhinolophus species groups analyzed, suggesting as many as undescribed cryptic species; these include several instances of sympatry among close relatives. coalescent lineage delimitation offered support for new undescribed lineages in four of the six african groups in this study. on the other hand, two to five currently recognized species may be invalid based on combined mitochondrial and/or nuclear phylogenetic analyses. validation of these cryptic lineages as species and formal relegation of current names to synonymy will require integrative taxonomic assessments involving morphology, ecology, acoustics, distribution, and behavior. the resulting phylogenetic framework offers a powerful basis for addressing questions regarding their ecology and evolution. electronic supplementary material: the online version of this article ( . /s - - - ) contains supplementary material, which is available to authorized users. we remain in an era of biological discovery [ ] , even for supposedly well-known vertebrate groups such as mammals. in the last years alone, the total number of mammal species has grown by fully %, while the accumulation of new bat species ( . %), especially in tropical regions, has grown even faster [ , ] . the discovery of new bat species in the afrotropics (africa south of the sahara, including madagascar and continental shelf islands) has paralleled these global trends, buoyed by continuing geographic and taxonomic surveys of bats across the region, a growing number of systematic investigations using molecular phylogenetic and integrative taxonomic approaches, and the use of more powerful and objective means of assessing species boundaries. the species limits of morphologically conservative or cryptic lineages of bats have been greatly clarified by an integrative approach using multi-locus genetic delimitation methods as a starting point for identifying candidate species and then testing them using additional, corroborative data from behavioral, morphological, distributional, and/or ecological information ( [ ] , cf. [ ] ). new species have also come to light via collecting in previously unsampled regions and through genetic analysis of ancient dna using new methods [ ] [ ] [ ] [ ] . the genus rhinolophus offers an instructive example. the sole living genus of the paleotropical (and southern palearctic) family rhinolophidae, rhinolophus is the second-most speciose genus of bat (after myotis). over the last years, the number of its recognized species has grown from ( of them afrotropical; [ ] ) to (with afrotropical; [ , ] , an enormous % increase. in this study, recent intensive surveys in east africa and neighboring regions of africa, coupled with parallel studies by others in west africa and in southern africa, permit a new region-wide multi-locus phylogenetic study of the genus.. rhinolophidae has been arranged taxonomically on the basis of molecular and morphological data into subgenera by csorba et al. [ ] . of these subgenera, the subgenus rhinolophus is restricted to africa and the palearctic; it includes species groups whose names represent the nomenclatural framework for this study: ( ) r. landeri group (landeri, alcyone, guineensis, lobatus); ( ) r. euryale group (euryale, blasii, mehelyi); ( ) r. capensis group (capensis, denti, gorongosae, rhodesiae, simulator, swinnyi); ( ) r. adami group (adami, maendeleo); ( ) r. ferrumequinum group (ferrumequinum, bocharicus, clivosus, damarensis, deckenii, hillorum, horaceki, nippon, sakejiensis, silvestris); ( ) r. maclaudi group (maclaudi, hilli, kahuzi, ruwenzorii, willardi, ziama); ( ) r. fumigatus group (cohenae, fumigatus, darlingi, eloquens, hildebrandtii, mabuensis, mossambicus, smithersi). of the currently recognized afrotropical rhinolophus species [ , ] , our study includes at least named taxa (fig. ) . multiple well-supported and deeply diverged clades are also revealed by our phylogenetic analyses. coalescent species delimitation methods incorporate phylogenetic uncertainty in gene trees and jointly infer species limits and species phylogenies. they have been shown to be conservative in that high delimitation posterior probabilities are consistent indicators of species status ( [ ] and references therein). briefly, methods such as the software bpp [ , ] infer statistical support for genetic isolation on an evolutionary timescale. however, species delimitation based exclusively on molecular data is controversial. it has been shown that multispecies multilocus coalescent delimitation methods can confound species-level and population-level processes and delimit population structure rather than species when the speciation process is protracted ( [ ] but see also, [ , ] ). however these debates on the status of delimited lineages are resolved, the multispecies coalescent remains a powerful method for inferring the evolutionary independence of lineages that can be subsequently tested with independent data (e.g., morphology, and bioacoustics data in bats) to assess species status in an integrative taxonomy [ ] . in this study we carry out lineage delimitation as a foundation for subsequent taxonomic revisions (see [ ] ). we do not claim that lineages distinguished by our analyses substantiate the boundaries of species; for this reason, we do not formally name these delimited lineages pending integrative taxonomic revision. the goals of this study are to identify evolutionary lineages among the afrotropical rhinolophus and to assess their phylogenetic relationships. lineages for which we were unable to assign confident names (here considered putative species) are considered hypotheses for later testing via integrative taxonomy. more than half of the sequence data used in this study are newly generated, extending the multi-locus analysis of dool et al. [ ] with substantial new material obtained in bat surveys of western, central, eastern, and southern africa. our expanded geographic, taxonomic, and population level sampling enables a more robust assessment of phylogenetic relationships and population structure among afrotropical rhinolophus. the intron data set used here has strong advantages over using mitochondrial loci alone and offers independent representation of the nuclear genome as each of the four introns are found on different chromosomes [ ] . incorporating independent genomic regions into phylogenetic analysis of this monogeneric family [ , ] and assessment of species relationships and limits is crucial because several instances of mitochondrial introgression have been documented within rhinolophidae [ , [ ] [ ] [ ] . other instances of possible mitochondrial introgression were investigated via comparisons between our intron phylogenies and those generated with mitochondrial sequences. finally, using our well resolved nuclear gene tree and species tree, we assess support for broad biogeographic patterns in a comparative context to studies of other afrotropical bats [ , , , , ] . all new genetic data from tissue samples used in this study (n = ) were obtained from specimens previously catalogued and part of the permanent collections of the following natural history museums: field museum of natural history, chicago, usa; biodiversity research and teaching collections, texas a&m university, college station, usa; royal ontario museum, toronto, canada; national museums of kenya, nairobi, kenya; and durban natural science museum, durban, south africa. no animals were collected in this study; all tissues were parts of permanent research collections. tissue samples available from kenya and tanzania was especially dense (fig. ) . initial assignments to species were based on the bats of east africa key in [ ] . an additional cytochrome-b (cyt-b) sequences and nuclear intron sequences for each of the introns acox , cops a, rogdi, and stat a of rhinolophus were downloaded from genbank from a total of individuals. a species in the recently resurrected genus macronycteris [ ] , m. vittatus (hipposideridae) was used as an outgroup. in total, individuals with - genes were analyzed for our study (see additional file for voucher numbers, locality data, and genbank accession numbers). to avoid adding to taxonomic confusion in rhinolophus, we purposefully took a conservative approach to the nomenclatural consequences of our analyses. where an apparent group's taxonomic identity is unknown or fig. type localities for recognized species of rhinolophus (black circles), as well as subspecies and synonyms (white circles); label names represent the specific epithets of currently recognized species. biomes of africa and neighboring regions indicated by color shading, dark yellow: tropical and subtropical moist broadleaf forests; orange: flooded grasslands and savannas; gray: tropical and subtropical grasslands, savannas, and shrublands; olive brown: deserts and xeric shrublands; gray-green: tropical and subtropical moist broadleaf forests; peach: mangroves; ochre: mediterranean forests, woodlands, and shrub; dark tan: tropical and subtropical dry broadleaf forests [ ] ambiguous, we refer to it as a numbered clade. this approach was applied to specimens provisionally assigned to combined rhinolophus fumigatus and r. eloquens clades that are labeled fumigatus/eloquens. these names are used as explicit labels for our analysis but cannot vouch for their validity with respect to other taxa that might have nomenclatural priority. morphological assessment of the clades supported by our analyses will be necessary to determine which existing names can be applied to them. we generally used the methodology previously described by demos et al. ( ) and patterson et al. ( ) in the generation and analyses of genetic data for this study. whole genomic dna was extracted using the wizard sv genomic dna purification system (promega corporation, wi, usa). specimens were sequenced for mitochondrial cytochrome-b (cyt-b), using the primer pair lgl f and lgl r [ , ] , and four unlinked autosomal nuclear introns: acox intron (acox ), cops a intron (cops a), and rogdi intron (acox , cops a, rogdi; [ ] ); and stat a intron (stat a; [ ] ; table , supplemental material). internal primers were designed for the cyt-b gene to amplify degraded dna from a museum skin of putative rhinolophus landeri from cameroon, the nearest topotype available from a voucher specimen (additional file ). pcr amplifications were carried out using the same thermocycler protocols as in [ ] . amplified products were purified using exosap-it (thermo scientific, ma, usa). sequencing was performed on an abi prior distributions on τ represent two relative divergence depths (deep and shallow) and on θ represent two relative mutation-rate-scaled effective population sizes (large and small) thermocycler (applied biosystems, ca, usa) at the pritzker laboratory for molecular systematics and evolution, field museum of natural history (fmnh). sequences were assembled and edited using gen-eious pro v. . . (biomatters ltd.). sequences were aligned using muscle [ ] with default settings in geneious. protein coding data from cyt-b were translated to amino acids to set codon positions and confirm the absence of premature stop codons, deletions, and insertions. several gaps were incorporated in the alignments of the nuclear introns, but their positions were unambiguous. gene trees, species trees, and summary statistics jmodeltest [ ] on cipres science gateway v. . [ ] was used to determine the sequence substitution models that best fit the data using the bayesian information criterion (bic) for cyt-b and the four nuclear introns. uncorrected sequence divergences (p-distances) between and within species/clades were calculated for cyt-b using mega x . . [ ] . maximum likelihood estimates of cyt-b gene trees and a concatenated alignment of the four partitioned introns were made using the program iq-tree version . . [ ] on the cipres portal. we conducted analyses using the ultrafast bootstrap algorithm to search for the bestscoring ml tree algorithm [ ] with bootstrap and topology replicates. bayesian gene-tree analyses were carried out in mrbayes v. . . [ ] on the cipres portal to infer individual gene trees for cyt-b, the four individual nuclear introns, and the concatenated partitioned alignment of four nuclear introns. two replicates were run to assist proper mixing. nucleotide substitution models were unlinked across partitions and then allowed to evolve at individual rates for each locus in the concatenated alignment. four markov chains with default heating values were run for × generations and sampled every th generation. stationarity of mrbayes results was assessed using tracer v. . [ ] . majority-rule consensus trees were inferred for each bayesian analysis. african taxa assigned to species or clades and named based on support for such clades in the bayesian and ml analyses of the cyt-b and nuclear intron datasets. thus, results from gene-tree analyses were used to define populations to be used as 'candidate species' (as in [ ] ) in a coalescent-based species-tree approach implemented in starbeast [ ] , an extension of beast v. . . [ , ] . species-tree analysis was conducted using the four nuclear intron alignments. substitution, clock, and tree models were unlinked across all loci. a lognormal relaxed-clock model was applied to each locus with a yule tree prior and a linear with constant root population size model. analyses were replicated four times with random starting seeds and chain lengths of × generations, with parameters sampled every , steps. for the starbeast analyses, evidence for convergence and stationarity of the posterior distribution of model parameters was assessed based on ess values > and examination of trace files in tracer v. . . burn-in was set at %, and separate runs were assembled using logcombiner v. . . and treean-notator v. . . [ ] . we conducted joint independent lineage delimitation and species-tree estimation using the program bpp v. . [ , ] . this analysis was carried out to guide future investigations of the lineages inferred here, using an integrative species taxonomic approach to include fixed differences in phenotypic characters, acoustics, ectoparasitic associations, and geographic distributions. bpp analyses were carried on those populations obtained from the concatenated gene-tree analyses and were identical to specimens assigned to lineages in the species-tree analyses. each population was designated as a putative independent lineage to be evaluated under the multispecies coalescent model [ and references therein]. separate analyses were carried out for lineages within each of four different rhinolophus species groups: capensis group, six lineages; ferrumequinum group, six lineages; fumigatus/eloquens group, eight lineages; and landeri group, four lineages. the validity of our assignment of specimens to populations was tested using the guide-tree-free algorithm (a ) in bpp. two replicates were run for each of four different combinations of priors on divergence depth and effective population sizes (τ and θ, respectively; table ), as the probability of delimitation by bpp is sensitive to these two parameters [ , ] . all bpp analyses were run for × generations, with a burn-in of generations and samples drawn every th generation. in total, eight bpp runs were carried out for each of the aforementioned species groups using nuclear intron loci (n = ). lineages were considered to be statistically well supported when the delimitation posterior probabilities generated were ≥ . under all four prior combinations. all newly generated sequences were deposited in genbank with accession numbers mn -mn ; (see also additional file ). sequence alignments used in this study have been made available on the figshare data repository (doi: https://doi. org/ . /m .figshare. ). the alignment of cyt-b sequences used in the ml and bi gene-tree analyses had a total number of base pairs (bp) ranging from to , and averaged % coverage of the complete cyt-b gene ( bp). to aid in visualizing the phylogenies inferred from this matrix, we reduced a matrix of individuals to a set of mostly unique sequences, resulting in a final alignment of individuals. the number of base pairs for the sequence alignments used in individual ml and bi gene trees and bayesian species tree analyses were: acox (n = ml and bi, species tree), - bp; cops a (n = ml and bi, species tree), - bp; rogdi (n = ml and bi, species tree), - bp; stat a (n = ml and bi, species tree), - bp; and intron concatenated alignment (n = ), - bp. the best supported substitution models for each locus estimated by jmodelt-est were: sequence cyt-b = gtr + i + g; acox = k + g; cops a = hky + i; rogdi and stat a = hky + g. uncorrected cyt-b p-distances for african rhinolophus in the sequence cyt-b alignment (removing eurasian sequences except for r. hipposideros and r. xinanzhongguoensis) ranged from . to . between species/clades, while within species/clade distances ranged from . to . (additional file ). maximum likelihood (ml) and bayesian inference (bi) inferred trees with similar topologies; the ml gene tree is shown for the sequence cyt-b alignment of rhinolophus species/clades ( fig. ; see also additional file for the phylogeny with all terminals labeled). in the cyt-b gene tree, a majority of sub-saharan taxa were strongly supported as monophyletic (i.e., maximum likelihood bootstrap support [bs] ≥ %, bayesian posterior probability [pp] ≥ . ), with several exceptions detailed here. for sub-saharan african rhinolophus, there were four major well-supported monophyletic endemic haplogroups: a) the fumigatus species group that includes eight r. fumigatus/eloquens clades, two r. hildebrandtii clades, and r. darlingi; b) the maclaudi species group that includes r. ruwenzorii and r. willardi, whose phylogenetic position is unresolved; c) the capensis species group that includes two r. simulator clades, r. denti, r. capensis, r. swinnyi, and two clades provisionally labeled as cf. denti/simulator and cf. simulator distributed widely south of the sahara; and d) the landeri species group consisting of two r. landeri clades, r. lobatus, and r. alcyone. the phylogenetic position [ ] of r. damarensis, recently elevated because it rendered r. darlingi paraphyletic [ ] , is uncertain. rhinolophus damarensis as currently known is associated with arid southern african habitats. however, a newly available specimen collected in western democratic republic of congo (drc; guineo-congolian rainforest in [ ] ) is unexpectedly nested within the r. damarensis cyt-b clade. of the two species groups whose members include both african and palearctic species, the ferrumequinum species group is strongly supported as sister to fumigatus + maclaudi + damarensis while the monophyly and position of the euryale species group is poorly supported. species from eastern eurasia + australasia cluster outside of african clades in the cyt-b tree with two notable exceptions. first, r. nippon [formerly r. ferrumequinum; ]) from eastern eurasia is strongly supported as sister to four endemic afrotropical r. clivosus clades specific epithets in parentheses following clade names indicate sequences from specimens used in recent species descriptions that were not supported as monophyletic and are subordinate to other clades and would render them paraphyletic. branch colors indicate individual clade membership; species groups are from [ ] and two r. ferrumequinum + r. clivosus clades whose distributions include north africa, europe, and the middle east. second, eastern eurasian r. xinanzhongguoensis [ ] has mixed support as sister to taxa in the fumigatus, maclaudi, and ferrumequinum groups (bs = %, pp = . ). finally, within the euryale group, r. blasii includes a clade distributed in eastern and southern africa that is sister to a north african + middle eastern clade. a majority of the deeper nodes are strongly supported ( of ). several currently recognized species scarcely differ genetically (~ % or less cyt-b uncorrected p-distances); and render other species paraphyletic (see additional file for a detailed cyt-b tree that depicts all labeled terminal branches). in the maclaudi species group, r. kahuzi is genetically identical to three sequences of r. ruwenzorii. in the fumigatus species group, r. smithersi, r. cohenae, and r. mabuensis all differ by < % in cyt-b from r. hildebrandtii clade and, if they are valid, would render that species paraphyletic (cf. [ ] ). in the capensis species group, five newly sequenced r. gorongosae specimens and three r. rhodesiae specimens differed from r. simulator clade by only . and %, respectively, in cyt-b. moreover, they are not reciprocally monophyletic and likewise would render r. simulator paraphyletic [cf. , where r. gorongosae is . % cyt-b distant from r. simulator; also see fig. , supplemental material]. we resequenced a specimen assigned to r. landeri by taylor et al. [ ; dm , genbank mg ], along with another newly obtained specimen from the same locality in liberia, and found that they nest deeply within r. blasii clade (fig. and additional file ) . finally, a monophyletic clade of three specimens from three separate countries in the central african guineo-congolian rainforest region (cf. denti) was unexpectedly inferred as nested within the capensis group, otherwise distributed in eastern and southern africa. all other members of the capensis group are considered to be savanna/woodland species [ ] with the exception of the subspecies r. simulator alticolus (see discussion). the ml gene tree inferred from concatenation of the nuclear genes acox , cops a, rogdi, and stat a ( individuals; matrix > % complete) is shown in fig. (individual intron gene trees from ml and bayesian analyses are depicted in additional file ). this tree was very similar to the bi tree with most nodes recovered as well supported. topological differences with the cyt-b gene tree exist, including the indeterminate placement of r. hildebrandtii within the fumigatus/eloquens group and strong support for r. landeri from mali as sister to r. cf. landeri + r. lobatus + r. alcyone. incomplete lineage sorting and/or gene flow between recently diverged sisters may account for the lack of monophyly for a) r. fumigatus/eloquens clades + + , r. fumigatus/eloquens clades + , r. fumigatus/eloquens clades + , r. hildebrandtii clades + , and r. ferrumequinum clades + . the remaining clades supported as monophyletic in the cyt-b gene tree are moderately or strongly supported as monophyletic in the concatenated nuclear gene tree with the exception of r. alcyone which is not supported as monophyletic. rhinolophus gorongosae is not monophyletic and is nested among minimally diverged specimens identified as r. simulator by [ ; sequences, ; sequence], and in this study as r. simulator . this simulator clade is distributed in tanzania, malawi, zambia, mozambique, and south africa. rhinolophus rhodesiae is likewise nested within r. simulator clade that includes sequences from drc, botswana, zambia, malawi, mozambique, zimbabwe, and south africa. there is no indication of mitochondrial introgression involving either r. gorongosae or r. rhodesiae. rhinolophus cf. denti/simulator is a deeply diverged, monophyletic clade from southeast africa with uncertain relationships to r. denti (southern africa) and sympatric r. simulator + . the membership of r. deckenii in the ferrumequinum group is challenged by its well supported sister relationship to the fumigatus group, rather than to r. clivosus + r. ferrumequinum (fig. ) . the position of r. ruwenzorii and r. willardi (maclaudi group) is uncertain, although r. ruwenzorii + r. willardi + r. deckenii are strongly supported as sister to members of the fumigatus group. the four starbeast runs in the multilocus coalescent species tree analyses converged within × generations. we discarded the first % of each run, resulting in , trees in the posterior distributions. ess values for all posterior parameters were greater than in the combined species tree analysis of , trees. the species tree (fig. ) is largely in agreement with the concatenated nuclear tree (fig. ) in the following respects: a) strongly supports r. hipposideros as sister to all other rhinolophus species in the tree; (b) strongly supports the sister relationship of the r. landeri group to the remaining african groups in the tree; c) strongly supports r. landeri as sister to r. alcyone + r. lobatus + r. cf. landeri; and d) strongly supports all the species group assignments made by csorba et al. , with the exception of r. deckenii (which had been uncertainly placed in ferrumequinum group) and r. ruwenzorii and r. willardi (maclaudi group), but here recovered in the fumigatus group. in contrast to the concatenated analysis, r. alcyone is poorly supported as sister to r. lobatus + r. cf. landeri clade. r. gorongosae and r. rhodesiae are respectively members of well supported monophyletic clades that also include specimens assigned to simulator and simulator in the cyt-b tree ( fig. and additional file ), although r. simulator clades and in the species tree analysis (fig. ) have different memberships than the two clades in the mitochondrial gene tree (fig. ) with the same labels. the clades labeled simulator and simulator in the species tree analysis (fig. ) have largely overlapping distributions although simulator also includes specimens from drc and gabon that were provisionally assigned to r. cf. denti in the cyt-b gene tree (fig. ) . the enigmatic placement of these guineo-congolian rainforest [ ] specimens within r. simulator , otherwise distributed in savanna/ woodland, warrants further investigation. results from the replicated bpp analyses show that prior choice had minimal effect on delimitation probabilities for most of the tested species/clades (table ) . however, for the four clades whose mean pp in the four summed partition schemes (see table for prior scheme definitions) fell below a threshold of . , ps and had the most influence. the clades that were not delimited all had pp ≤ . but ≥ . and thus had marginal support. most of the unsupported clades had short branches and weak node support in the species tree analysis (fig. ) . distinguishing robustly defined lineages by congruence across all prior schemes, evolutionarily independent lineages are delimited including all six lineages analyzed in the capensis group (these include two possibly new species; three of five lineages in the ferrumequinum group, including possibly new species; two of four lineages in the landeri group, including strong support for recently recognized r. lobatus (distinct from r. landeri [ ] and the newly sequenced r. cf. denti/ simulator; and finally of lineages in the fumigatus group, including three possibly new species as well as support for the recent recognition of r. damarensis as a valid species [ ] . however, there was no pp support for alternative delimitations of clades; that is, all alternate delimitations that statistically tested the merger of two or more putative species had pp ≤ . ). the eight strongly delimited clades that could not be confidently named are candidates to be evaluated as potentially valid species using independent datasets. this is the broadest phylogenetic study of afrotropical species in the genus rhinolophus published to date. multiple phylogenetic studies have confirmed the monophyly of rhinolophus and the rhinolophidae [ , , ] . csorba et al. [ ] presented a phylogenetic hypothesis for the monophyly of african rhinolophus, with r. blasii and r. clivosus extending from the afrotropics to the western palearctic, and r. euryale, r. ferrumequinum, and r. hipposideros having distributions in both north africa and the western palearctic. several studies have placed the most recent common ancestor of rhinolophus at~ mya [ , ] ; cf. ([ ] , at mya). it has long been considered that rhinolophidae originated in the african or asian tropics, although csorba et al. [ ] presented data supporting a european origin of the family when tropical conditions prevailed in southern europe during the miocene. however, dool et al. [ ] argued instead for a middle eastern origin for the basal lineage r. hipposideros. owing to poor resolution of basal nodes in their multi-locus phylogeny [ ] , they refrained from speculating on the ancestral origin of rhinolophidae but, did find support for accelerated diversification within afrotropical rhinolophus over the last mya. subsequently, the new species r. xinanzhongguoensis, described from southwestern china [ ] , was strongly supported as having affinities to the ferrumequinum, fumigatus, and maclaudi groups. this eastern palearctic/indomalayan species is phylogenetically nested deeply within the african rhinolophus radiation (fig. ) ; it has mixed support (bs = %, pp = . ) as sister to the african fumigatus and maclaudi species groups plus the afro-palearctic ferrumequinum group that includes another eastern palearctic species, r. nippon [ ] . both of these eurasian species are closer to the endemic african groups fumigatus and maclaudi than to the endemic afrotropical capensis and landeri groups. thus, the membership of r. xinanzhongguoensis and r. nippon in a predominantly african clade seems to indicate a complex historical biogeographical relationship between the afrotropics and eastern eurasia, terminal tips in the tree that are statistically well-supported (pp ≥ . ) from bpp are indicated by "*" preceding the clade name, and terminal tips that had pp < . are indicated by "?" preceding the clade name. species groups are from [ ] possibly supporting additional dispersal events between the continents. however, it should be noted that data is still lacking from independent nuclear loci for r. xinanzhongguoensis and r. nippon. the phylogenetic relationships of afrotropical rhinolophus species inferred here are in broad agreement with the study of dool et al. [ ] , based on six introns. to extend their findings, we sampled four of their introns for vouchered specimens representing eight monophyletic cyt-b clades not present in their study. we also sequenced members of nine clades represented in their study with samples from new afrotropical localities. our expanded data set is the largest yet for afrotropical rhinolophus, and infers support for up to independent evolutionary lineages as candidate species for future assessment with corroborative data. results from coalescent delimitation and species tree analysis suggest three named species may be synonyms (r. kahuzi and either r. gorongosae or r. rhodesiae). although we did not have access to tissue samples from r. smithersi, r. cohenae, and r. mabuensis, and so lack intron data, cyt-b sequences from genbank indicate that these recently described taxa are minimally divergent from r. hildebrandtii (< % in cyt-b), and their recognition would render it paraphyletic. taylor et al. [ ] recently argued for species status for two african rhinolophus names long regarded as synonyms: r. lobatus (peters, ) from r. landeri and r. rhodesiae (roberts, ) from r. swinnyi. they described the new species r. gorongosae on the basis of integrative data that included a suite of morphological variables, but their molecular phylogenetic analyses relied solely on cytochrome-b. their putative r. gorongosae (dm , dm ) had anomalously long branches (p-distance . and . % from r. simulator and putative r. rhodesiae, respectively; see their fig. ) and nested within r. simulator, which motivated us to re-examine these deeply diverged specimens. in addition, the sister relationship they determined of r. landeri and r. gorongosae ( % p-distance), instead of with alcyone and lobatus [other members of the landeri group; ], led us to compare this sequence to genbank accessions using blastn. the blastn query showed % identity of their r. landeri (genbank accession mg , dm , liberia) with bos taurus. when tissue from this voucher specimen and another (dm ), also from liberia, was extracted and new sequence data generated, those individuals were found to nest deeply within the r. blasii clade (additional file ). we extracted and sequenced five samples identified as r. gorongosae from the durban museum, including dm from [ ] , and found them to be - . % cyt-b diverged from r. simulator and r. rhodesiae. this strongly suggests that the genetic arguments in [ ] for the newly described r. gorongosae and for elevation of r. swinnyi rhodesiae to species rank were based on sequencing error (see additional file for comparison of genbank sequences versus newly sequenced material). several studies have demonstrated instances of mitochondrial introgression (i.e. mitochondrial capture) among populations of r. ferrumequinum and r. clivosus [ ] ; r. sinicus, r. rouxii, r. pearsonii pearsonii, and r. p. chinensis, restricted to eastern eurasia (mao et al. [ , ] , and the r. macrotis species complex in china [ ] . potential mitochondrial introgression is apparent in our study in the cyt-b gene tree for ferrumequinum clades and and clivosus clade as discussed in [ ] . taylor et al. [ ] suggested historical genetic introgression might account for the discrepancy between the morphological disparity of r. simulator and r. rhodesiae and their lack of genetic differentiation ( . %). however, they did not test this hypothesis with genetic data. in this study, mitochondrial, concatenated nuclear loci, and the species tree (also inferred with nuclear data only) all strongly infer the very close relationship of r. rhodesiae to r. simulator clade . although the cyt-b tree recovers both gorongosae and rhodesiae as paraphyletic, the concatenated nuclear phylogeny recovers them in two separate monophyletic clades (simulator and ; fig. ). to understand these conflicting signals, and to determine which of these clades actually represents true r. simulator, a geographically expanded integrative taxonomic assessment will be necessary. the broad phylogenetic and geographic sampling in our study uncovered a number of range extensions for described species and also suggests possible niche divergences of putative undescribed species based on their genetic and geographic relationships. in the capensis group, a clade from cameroon (rom ), gabon (fmnh ), and western drc (fmnh ) is strongly supported in the cyt-b gene tree (fig. ) as sister to r. denti, otherwise known from savanna and woodlands of southern (r. denti) and western (r. denti knorri) africa. the specimens from drc and gabon were included in the concatenated nuclear intron tree and found to nest well within r. simulator, which is sister to r. denti. rhinolophus alcyone alticolus sanborn, [ ] was allocated to r. simulator by koopman [ ] , who was followed by subsequent authors, but csorba et al. [ ] suggested that r. simulator alticolus might prove to be a separate species. the type specimen (which is now lost) was from mt. cameroon, and western cameroon is the only lowland rainforest distribution for the savanna woodland simulator [ ] . the specimen we sequenced from mt. cameroon was from a~ -year-old skin and nuclear genes were not successfully amplified. nonetheless, the strong support for the drc and gabon specimens (from the same clade as the mt. cameroon specimen in the cyt-b tree) with r. simulator suggests that our cf. denti clade may be introgressed r. simulator whose range now extends well into the western african rainforest habitat [ ] . independent nuclear data from additional specimens are needed to confirm the status of this clade. also within the capensis group, all analyses in our study strongly support the existence of an undescribed species provisionally designated cf. denti/ simulator. at present, populations are known from tanzania, mozambique, and malawi where they are sympatric with its close relative r. simulator and presumably differ from it ecologically. in the euryale group, two newly sequenced individuals from liberia are strongly supported as sisters of populations identified as r. blasii populations from southeastern africa. this extends the range of sub-saharan populations clade > km west of their current distribution. however, r. blasii has a highly disjunct distribution, and individuals from southern europe (its type locality is italy) were not included in our analysis; if conspecific with moroccan populations of r. blasii, the liberian records document a km range extension. both specimens had been identified as r. landeri; if mitochondrial introgression was responsible, it is unclear where contact may have occurred. in the maclaudi group, the range of r. ruwenzorii is now extended to the mountains west of lake kivu in kahuzi-biega np, as strong support from mitochondrial and nuclear data indicate that r. kahuzi [ ] is a synonym of r. ruwenzorii. as in csorba et al. [ ] and dool et al. [ ] , the most basal lineage within the african radiation is the landeri group (alcyone, landeri, and lobatus), whose partial distribution in rainforest habitats has been hypothesized to be indicative of the habitat affinities of early colonizers [ ] . however, this hypothesis has not been tested with ancestral-area reconstruction analyses. as in [ ] , resolution of deeper nodes in our analysis was inconsistent, weakening any attempts at ancestral reconstructions. also, uneven geographic sampling in our nuclear dataset indicates that additional populations should be incorporated before carrying out quantitative analysis. as in the bat genus scotophilus [ ] , the populationlevel phylogenetic analyses presented here document repeated patterns of clade replacements between eastern and southern africa. in the fumigatus group, paired clades support replacement between eastern and southern africa (fig. ; fumigatus/eloquens + + vs. fumigatus/eloquens and fumigatus/eloquens + vs. fumigatus/eloquens ). this relationship is also supported by one clade-pair (clivosus vs. clivosus ) in the ferrumequinum group, and one pair (cf. landeri vs. lobatus) in the landeri group. in the capensis group, phylogeographic patterns appear more complex (probably owing to better sampling) and multiple lineages exhibit sympatry. at least one is a putative but undescribed species in sympatry with its sisters in the capensis group (cf. denti/simulator; figs. and ). sampling is still limited in the rain forests of central and west africa, but an enigmatic relationship is apparent in the cyt-b tree (fig. ) , where three newly sequenced specimens from the western guineo-congolian rain forest (cf. denti in fig. ) are sister to arid-land r. denti. the concatenated nuclear tree recovers two members of this clade from drc and gabon as nested within r. simulator. in both datasets an unexpectedly close relationship is inferred for a savanna/woodland habitat species with poorly surveyed populations living in humid rainforest. additional insights to afrotropical rhinolophus are now possible with this greater phylogenetic understanding. the genus is interesting from a public health standpoint owing to various associated viral pathogens [ , [ ] [ ] [ ] . its constant-frequency echolocation calls have been widely studied for their value in communication [ , ] , adaptation and speciation [ ] [ ] [ ] , and resource subdivision [ , ] . their noseleaves, cranial morphology, dentition, and bacula are all richly diversified morphological systems [ , ] hardly studied from developmental or evolutionary perspectives. continued efforts to characterize these newly documented lineages across all of these phenotypic dimensions will offer greater understanding of their evolutionary development and diversification. additional file : maximum likelihood gene tree inferred for cyt-b using iq-tree that includes two sequences of r. gorongosae deposited in genbank [ ; indicated by red font] and five specimens newly sequenced for cyt-b in this study (indicated by blue font). dm is included twice in the tree (both the genbank sequence and a newly generated sequence from this study). nodal support is indicated above branches. our analysis was strengthened with samples collected by the late w. t. (bill) stanley, and this paper is dedicated in his memory. we acknowledge with special thanks the assistance of peter taylor (university of venda) and leigh richards (durban natural science museum) in loaning samples of taxa included in [ ] , and jessica light and duane schlitter (texas a&m university), jacqui miller and burton lim (royal ontario museum), leigh richards (durban natural science museum), and simon musila (national museums of kenya) for tissue loans. carl dick, ruth makena, david wechuli, richard yego, and aziza zuhura all helped collect museum vouchers. new genetic data were generated in the fmnh pritzker laboratory, managed by kevin feldheim. the efforts of curators and collection managers in all the institutions cited in additional file are acknowledged for maintaining the museum voucher specimens that enable follow-up studies, sometimes on different datasets, keeping our science verifiable and our errors correctable. authors' contributions bp, td conceived the project; td, bp analyzed the data; td, bp, pw, jkp, smg, mb contributed samples and provided interpretation of their context; td, bp, pw, jkp, smg, mb participated in discussion and interpretation of the results; td, bp wrote the paper with input from all authors. all authors have read and approved the manuscript. collections in east and southern africa were funded by a variety of agencies in cooperation with the field museum, especially the jrs biodiversity foundation. field museum's council on africa, marshall field iii fund, and barbara e. brown fund for mammal research. we thank the generous support of bud and onnolee trapp and walt and ellen newsom. publication costs were paid by the integrative research center. thanks to the john d. and catherine t. macarthur foundation, fulbright program of us department of state, wildlife conservation society, and the centers for disease control and prevention who sponsored and assisted in obtaining vouchers from drc, malawi, and uganda for accession to fmnh. we thank wwf gabon and partenariat mozambique-réunion dans la recherche en santé: pour une approche intégrée d'étude des maladies infectieuses à risque épidémique (mozar; fond européen de développement régional, programme opérationnel de coopération territoriale) for funding support. the dna sequence data generated for this article are available on genbank with the following accession numbers: mn -mn . the dna sequence alignments used in the analyses for this article have been deposited on figshare under accession doi: https://doi.org/ . /m . figshare. ). ethics approval and consent to participate no animals were used in this study. not applicable. a new age of discovery mammal species of the world: a taxonomic and geographic reference how many species of mammals are there? coalescent-based species delimitation in an integrative taxonomy a genomic evaluation of taxonomic trends through time in coast horned lizards (genus phrynosoma) nuclear introns outperform 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with regard to jurisdictional claims in published maps and institutional affiliations the authors declare that they have no competing interests.author details key: cord- -dhdyxnr authors: den boon, saskia; vallenas, constanza; ferri, mauricio; norris, susan l. title: incorporating health workers’ perspectives into a who guideline on personal protective equipment developed during an ebola virus disease outbreak date: - - journal: f res doi: . /f research. . sha: doc_id: cord_uid: dhdyxnr background: ebola virus disease (evd) health facility transmission can result in infection and death of health workers. the world health organization (who) supports countries in preparing for and responding to public health emergencies, which often require developing new guidance in short timelines with scarce evidence. the objective of this study was to understand frontline physicians’ and nurses’ perspectives about personal protective equipment (ppe) use during the - evd outbreak in west africa and to incorporate these findings into the development process of a who rapid advice guideline. methods : we surveyed frontline physicians and nurses deployed to west africa between march and september of . results: we developed the protocol, obtained ethics approval, delivered the survey, analysed the data and presented the findings as part of the evidence-to-decision tables at the expert panel meeting where the recommendations were formulated within eight weeks. forty-four physicians and nurses responded to the survey. they generally felt at low or extremely low risk of virus transmission with all types of ppe used. eye protection reduced the ability to provide care, mainly due to impaired visibility because of fogging. heat and dehydration were a major issue for % of the participants using goggles and for % using a hood. both gowns and coveralls were associated with significant heat stress and dehydration. most participants ( %) were very confident that they were using ppe correctly. conclusion : our study demonstrated that it was possible to incorporate primary data on end-users’ preferences into a rapid advice guideline for a public health emergency in difficult field conditions. health workers perceived a balance between transmission protection and ability to care for patients effectively while wearing ppe. these findings were used by the guideline development expert panel to formulate who recommendations on ppe for frontline providers caring for evd patients in outbreak conditions. health facility transmission is a hallmark of early ebola virus disease (evd) outbreaks and usually results in infection and death of health workers particularly before the identification of ebola virus as responsible for the clinical presentation of one or a cluster of patients [ ] [ ] [ ] . contributing factors include nonspecific clinical presentation, lack of local advanced diagnostic capabilities and suboptimal infection prevention and control (ipc) practices, amplified by poor surveillance in struggling health systems. the epidemiological pattern of the - evd outbreak in west africa revealed a similar story, but this time with an unprecedented scale and geographic spread, resulting in a record number of affected health workers, with cases and deaths by late . health workers are more likely than non-health workers to be infected: depending on the profession, the risk can be to times higher . the correct use of personal protective equipment (ppe) as part of comprehensive ipc measures contributes to the prevention of evd transmission in healthcare settings by providing a protective barrier from contaminated fluids. however, the characteristics of the material and the configuration of the equipment may lead to health worker discomfort, overheating, and concerns about dexterity and safety to perform clinical tasks when ppe is used in the typical conditions of high heat and humidity present in west african evd treatment centers , . as the united nations' international health agency, the world health organization (who) has the mandate to support member states in preparing for and responding to a wide range of public health emergencies that often require that new technical guidance is developed in short timelines with scarce evidence base. following an urgent request from affected member states, who started the production of a ppe guideline for evd outbreaks in july , shortly before declaring the evd outbreak in west africa a public health emergency of international concern. a rapid review of the efficacy and comparative effectiveness of various components of ppe was commissioned in preparation for an expert panel meeting to develop recommendations on optimal ppe for health workers in ebola treatment units (etus) in outbreak settings. it became clear very early in the process that high quality efficacy and comparative effectiveness studies addressing the use of specific ppe items for evd in outbreak settings were lacking . in addition to the paucity of data, it was critically important to gather and include the perspectives of health workers who had "real-life" experience in etus in west africa. early reports of the local conditions indicated that broader clinical questions than ppe performance as a transmission barrier were as important: usability, comfort, dexterity and impact on communication with patients, for example. the underlying principle was that evidence from efficacy and comparative effectiveness studies was necessary but insufficient for contextualization and adequate decision-making. this approach highlights the importance of understanding the way individuals exercise judgement (values and preferences) when selecting options with potential benefits, harms, and inconveniences in real life and is current best-practice in who standard guidelines . values and preferences are often informed mainly by the opinion of guideline expert panel members, however such proxies for persons affected by the recommendations in a guideline are often inadequate or even inaccurate. thus, in the early stages of the - evd outbreak in west africa, in the context of time constraints and the absence of published data, it was crucial to incorporate the values and preferences of health workers into the guideline development process. the purpose of this study was to support the development process of a who rapid advice guideline on ppe for evd care in outbreaks. the specific objectives were to understand and describe frontline physician and nurses' perspectives about ppe use, while providing direct care for evd patients in the unprecedented conditions of the - evd outbreak in west africa and to incorporate these findings into the rapid advice guideline development process. in september , we electronically surveyed international frontline physicians and nurses who participated in foreign medical teams deployed to the affected countries in early stages of the evd outbreak. the pragmatic approach was necessary given that this survey was developed and delivered at the height of outbreak and that who had very limited time available in which to produce guidance. the online, -item survey was developed specifically for this study (supplementary file ). the first section consisted of multiple-choice questions examining participant demographic characteristics, role, and experience with ppe in west africa. the next section addressed health worker exposure to the following specific components of ppe: eye protection (goggles/face shields), nose and mouth protection (medical mask/particulate respirator), gloves (single/double gloves), body covering (gowns/ coveralls), foot wear (boots/closed shoes), and head covering (hair cover/hoods). in subsequent sections, we used a four or five-point likert-scale to examine participants' perceptions about the impact of each ppe item on the following domains: safety, communication, ability to provide patient care, personal wellbeing (heat and we have made changes to the text based on the referees' comments, in particular emphasizing the connection to oxidative stress in the abstract and expanding the discussion. in response to the suggestions and comments from the reviewers we have made several edits to our research paper. first of all, we have revised table by adding categories that were previously omitted from the table. for example, in version we only presented in the table the number health workers that indicated they felt at extremely low or low risk, but in version we have added a column indicating the number of health workers feeling at high or extremely high risk. we have also added a foot note explaining how the denominator in each cell reflects missing values for that particular question. we hope that this has improved the readability of the table. second, we have added some additional references to the literature on ppe in the discussion. finally, we have added a few small clarifications and moved some text to other sections in the paper. revised dehydration), and comfort. in addition, for each of the items, participants could provide free-text comments on open-ended questions to describe any difficulties or to provide suggestions on how ppe could be improved. the final section explored specific training needs and confidence in ppe. the last question asked participants to compare two sets of ppe available in west africa shown side-by-side in a picture: one was composed of lighter items and the other had more robust components. five experts reviewed the study protocol and questionnaire during the development phase. subsequently, three clinicians with experience in the evd outbreak in west africa similar to that of the sampling frame field-tested the survey for consistency, readability, completeness, and question sequencing. the final version of the online survey incorporated all relevant feedback and comments. we obtained expedited approval of the study protocol and survey from the who ethics review committee (rpc ). we contacted potential participants via email. the first email explained the objectives, expected time commitment, and provided a link to the informed consent form and online survey on survey monkey ® . participation was voluntary and implied informed consent. a follow-up email in days reminded potential participants of the deadline ( days after launching). participants could withdraw from the study at any time without providing any justification. the study population consisted of international frontline physicians and nurses with direct field experience caring for evd patients in west africa. our sampling frame targeted international physicians and nurses deployed by who and médecins sans frontières (msf) to west africa between march and september . we used maximum variation purposeful sampling, a non-probability sampling strategy, to capture a wide range of health worker perspectives and experiences in two organizations and four different countries affected by the evd outbreak. health workers were reached through a contact individual in each organization (msf and who) who directly emailed potential participants. physicians and nurses from the affected countries and from other international organizations were not included for pragmatic reasons given the extreme time constraints and infeasibility of obtaining additional organizational approvals in the available timeline. an initial communication error led to the participation of other groups of health workers that did not have frontline clinical experience. the perspectives of these workers were considered for who quality improvement efforts, but were excluded from this analysis as these groups were not part of the approved sampling frame for this study. participants could indicate their experience with more than one item for each ppe component (e.g., both goggles and face shields for eye protection). for the purpose of statistical analysis, we considered each participant's experience with a ppe item unique and independent (i.e. we did not account for the fact that the experience came from one and the same health worker). we analysed closed-ended questions with stata (statacorp. . college station, tx) using counts, proportions, and the chi-square test when comparisons were appropriate. two independent researchers analysed the answers to the openended questions using an iterative and reflexive process. this encompassed close reading and re-reading of the answers using constant comparison within and across different participants to identify key topics. the researchers then grouped the interpretations and understanding of the participants' ideas and selected quotes to represent these findings, discussing discrepancies to achieve agreement. immediately after data collection with the survey monkey ® instrument, all information was downloaded to an anonymized spreadsheet and removed from the online database. all analyses were performed on de-identified data. informing rapid advice guideline recommendations the rapid advice guideline was developed using the grading of recommendations assessment, development and evaluation (grade) approach , . with this approach, clinical and public health recommendations are based on a systematic review and critical appraisal of the evidence on benefits and harms of an intervention, and an assessment of the balance between the two. other considerations are also taken into account when an expert panel formulates recommendations, including feasibility, acceptability and resource implications of the intervention options, and the effects on equity across subpopulations. the relative value of the potential outcomes of the intervention options and the values and preferences of persons affected by the intervention are also important considerations. the findings of the survey were presented at the guideline development meeting and incorporated into evidence-to-decision tables (supplementary file ) to inform the formulation of recommendations for ppe components in the context of an evd outbreak. evidence-to-decision tables followed the grade-decide approach and were populated by the who guideline development team in preparation for the expert panel meeting. these tables were key instruments used to present multiple sources of information to the guideline expert panel, helping to structure the discussion and to document the final judgements and decisions that underpin each recommendation. we developed the study protocol, obtained who ethics approval, contacted the participants, delivered the survey, analysed the data, and presented the findings as part of the evidence-to-decision tables at the expert panel meeting where the recommendations were formulated in a period of weeks. we invited health workers ( from msf and from who) to participate in the survey and ( %) responded. respondents from msf included logisticians and water, sanitation and hygiene experts who were excluded because they were not part of the sampling frame. thus participants ( physicians and nurses) were included in the final analysis and their characteristics are described in table . for each of the different components of ppe, one item was used by the majority of survey participants (table ) . for example, ( %) of participants had experience using goggles, while only seven ( %) had used a face shield (some participants had experience with both types of eye protection). generally, health workers felt at low or extremely low risk regardless of the type of ppe used. ppe, particularly goggles, particulate respirators, and medical masks or hoods, impaired communication (table ) . a reduction in the ability to provide care was predominantly related to eye protection equipment -both face shields and goggles. heat and dehydration were a significant or major issue for participants using goggles ( %) compared to two ( %) using a face shield (p= . ), and for ( %) using a hood compared to none using a hair cover (p= . ). heat and dehydration also were a significant or major issue for the majority of individuals using a gown (n= , %) or coverall (n= , %); however, there was no significant difference between the two groups (p= . ). goggles were considered more uncomfortable (n= , %) than face shields (n= , %, p= . ) ( table ) . participants indicated that fogging of goggles or face shields was a major issue, affecting visibility and potentially creating a hazard for health workers as well as patients. there was some indication that fogging was a bigger issue with goggles and a few participants indicated that they would have preferred a face shield. two participants indicated that the goggles caused pain after using them for extended periods. a number of participants noted that goggles did not cover sufficient skin of the face and there were requests for larger goggles, which would have the added advantage of greater visibility. other issues were the poor quality of face shield and goggles, poor fit of goggles, and the logistical challenges of waiting to clean and dry re-usable goggles. one respondent summarized it as follows: "the goggles (are) not so comfortable and (they) felt like the "unsafe" part of the ppe. they move easily, hurt on the head, and affect vision in a negative way due to sweat, etc.". medical mask and the particulate respirator were reported to cause difficulty breathing when wet (due to sweat or condensation). one participant doubted the mask's effectiveness when wet. two participants were of the opinion that respirators were excessive since evd is not airborne. the main problem regarding gloves was the risk of having them slip down, allowing fluids to contact the skin as illustrated by the following respondent: "some people found using tape over gloves (the second pair) useful as sometimes they did roll down during arduous patient care activity and in the end i also did this". other participants also attempted to solve this problem by taping gloves to the coverall, however this occasionally resulted in the tearing of gloves or the coverall. it was also mentioned that gloves were not long enough and that they tore easily. difficulties included finding the right size coverall -in several instances the available coveralls were too small, leaving the health worker to opt for a coverall of lesser quality or have difficulties removing the coverall. a number of health workers indicated that they had difficulty taking off the coverall. specific issues included having to remove the face shield first, leaving the eyes and face unprotected while undressing from the coverall, and problems taking off the coverall over large rubber boots. one respondent mentioned that coveralls with attached shoe covers could increase the risk of tripping. one respondent commented that boots were too big causing difficulty walking on irregular ground. as for reusable items (goggles and boots), it was mentioned that the time required to fully decontaminate and dry them sometimes brought challenges and put pressure on the team. training on ppe use a third of survey participants had received formal training over to days (n= , %) and four ( %) reported training duration of more than days. on the other hand, % (n= ) had received no formal or on-the-job training and another % (n= ) reported training for hours or less. the remaining % of study participants (n= ) had training of one day or less. a number of participants commented that they would have liked to have had training, more formal training, or longer training. others indicated that they would have liked to receive training before their departure, or before arriving at the treatment centre. the training topics that the survey participants would have liked included were the removal of ppe, and, how to manage eye glasses. one health worker recommended weekly refresher training, especially in the light of frequent equipment changes, which may impact the order items are put on and taken off. another health worker commented: "i believe that only experienced people can teach about ebola. teaching on the use of ppe is not about dressing and undressing. it is about using a set of behaviours with it and the understanding of all the underlying water and sanitation principles and applying them". regarding hand hygiene, alcohol-based hand-rub was not always available and there was conflicting information in different settings about which product to use. the majority of participants (n= , %) were very confident that they were using ppe correctly, ( %) were reasonably confident and ( %) was not very confident. generally, participants were least confident about goggles (fogging, moving/displacing), medical masks and particulate respirators (difficulty breathing, becoming uncomfortable), and gloves (rolling down, tearing). removing ppe was also an area that people felt less confident about (e.g., taking arms and feet out of a coverall, lack of face protection during undressing if the face shield was worn outside the hood). as one health worker illustrated: "taking off the (tyvek suit) coverall was difficult due to my height; it required me to wiggle out of it more than the average person". a respondent also mentioned feeling less confident working in the screening area where much lighter ppe was worn, while possibly also being exposed to infectious patients. when asked to indicate their preference regarding two sets of ppe depicted in a picture, ( %) participants preferred the ppe that was composed of lighter items, ( %) participants preferred the more robust components, ( %) did not have a preference and one participant did not respond to the question. the - evd outbreak in west africa required extensive local and international response and for the first time since evd was described in , a large number of organizations were directly involved in clinical and laboratory activities in the field. these interactions highlighted differences in the selection and use of ppe across the organizations. early on in the outbreak, when the cases of health worker transmission were numerous and confusion about the best available equipment was wide-spread, who was asked to provide technical guidance in a short period of time. when a public health emergency involves a new disease, or a known disease with a different presentation, there may be scarce or no evidence on the benefits and harms of potential interventions. indirect evidence (e.g., from related diseases such as other blood-borne pathogens and simulation), expert opinion, and data acquired and analysed in real-time may become the best available evidence for the guideline panel. in addition, factors other than the effectiveness of interventions may have a significant influence on the direction and strength of the recommendations. such was the situation in during the height of the evd outbreak in west africa; a rapid review of the effectiveness of different types of ppe for protecting health workers revealed insufficient evidence upon which to draw conclusions about optimal ppe . in this context and within a period of weeks, we developed and executed a survey, the results of which formed a critical part of the evidence upon which the recommendations developed by the expert panel were based . to the best of our knowledge, this approach of collecting primary data regarding the values and preferences of persons affected by clinical or public health recommendations in a guideline is novel in the extremely challenging setting of a public health emergency. overall, our findings showed that health workers perceive a balance between transmission protection and the ability to effectively care for complex patients while using ppe. health workers accept a certain degree of discomfort in return for the protection provided by ppe. the survey highlighted a slight preference of health workers for face shields compared to goggles because of less fogging, easier communication and better fit. there was no strong preference for one item of ppe over the other for all other ppe components. given the variation in preferences for different components of ppe and the absence of data on comparative effectiveness, it may be important to provide a choice for health workers. this was, in fact, a guiding principle during the development of the ppe guidelines. several issues raised by survey participants should be relatively straightforward to address, making a major contribution to health worker safety and comfort, such as providing a sufficient range of sizes, choice of equipment, and adequate training on how to put on and take off ppe in the conditions that will be faced in the field. active training, in which health workers receive face-to-face training has been shown to improve doffing procedures . we experienced a number of challenges planning and executing this study. we had to develop a survey questionnaire de novo with limited time for field testing. although this likely had a minimal impact on the results, we noted two questions that participants appeared to have difficulty comprehending (questions and ; see supplementary file ); if we had had more time for field testing we could have revised the questionnaire before formal data collection began. while our aim was to include only health workers who had provided direct patient care, such as nurses and physicians, given a communication error early in the study, we invited to participate and consequently received responses from workers without direct clinical experience who had been deployed to the evd outbreak. because these workers were not part of our pre-defined sampling frame, we excluded their responses from the analysis. similarly, our survey failed to take into account the fact that ppe consists of different components such as eye protection, nose and mouth protection, gloves and body coverings that work together to protect the health worker from the risk of infection. in the first part of our questionnaire we asked how the survey participant experienced individual components of ppe (e.g., goggles or face mask). however, it is difficult to review these components as isolated items, separate from the rest of the ppe. as one survey participant noted: "it is the combination of the respirator and the face shield which is difficult. one or the other would be manageable but both together meant major impairment". another survey participant commented: "the coverall would probably be better tolerated if we could breathe easier and see without problems". in addition, although we compared gowns and coveralls, we did not specify or ask about the materials the body coverings were made of, its level of fluid resistance, or whether the head cover was attached or not. such issues can have a significant impact on health workers' experiences. for example, a simulation study carried out in hong kong in response to the outbreak of severe acute respiratory syndrome (sars) found that ppe made of more breathable material did not lead to a significant difference in contamination but did have greater user satisfaction , . it also became clear that solutions to an issue with one component of ppe could compromise the safety of another element of ppe. for example, participants mentioned that they would improvise and tape gloves to the coverall in order to prevent them from slipping down, but then the coverall would tear when removing the tape. finally, the combination of different components of ppe may change the order in which ppe items are put on and taken off, thus end-users may perform donning and doffing procedures that are different than the training they received. this is particularly relevant if there are frequent changes in the availability of specific types of ppe, as was the case early in the outbreak response. most of the limitations of this study were caused by pragmatic decisions the research team had to make in order to complete the study in the available time. this was in and of itself an invaluable learning experience for undertaking similar projects in the future. specifically, we had to include only international health workers deployed by who and msf in our study; therefore, we did not collect information on the values and preferences of local health workers and health workers deployed by other organizations. there were two important reasons as to why we selected our sampling frame. first, we carried out the survey at the height of the evd epidemic when local doctors and nurses were fully engaged in the response efforts and we refrained from removing them from their primary work. internationally recruited health workers on the other hand, were usually deployed for shorter periods and could thus participate when they returned home. second, we had little time in which to execute the survey before the guideline meeting and we anticipated that it would be a lengthier and more complex process to identify and recruit local health workers. thus, the findings of this survey may not be applicable to local health workers. in addition, generalizability of our findings to other international health workers involved in the ebola response may be limited due to the small size of our purposive sample. in the context of the most challenging of research settings, our study proceeded very efficiently and effectively in several regards. peer reviewers for both the study protocol and draft survey made very helpful comments within to days. the who ethics review committee approved the survey in less than two weeks. by reaching out to several key managers and opinion leaders from the two organizations, we were quickly able to identify frontline clinicians that were part of the sampling frame. the online format of the survey allowed us to quickly reach a larger number of health workers in different countries who had recent personal experience with different types of ppe in the evd outbreak. the combination of different types of questions in our survey also worked well. closed and likert-scale questions made analysis of trade-offs and comparisons of health workers' preferences possible while open-ended questions allowed the survey participants to share additional thoughts and perspectives in more depth. our study highlights some of the challenges and potential limitations and demonstrates the feasibility of generating and incorporating primary data on end-users' values and preferences into a rapid advice guideline developed during the height of a public health emergency with extreme field conditions. our survey showed that health workers perceive a balance between transmission protection and their ability to effectively care for patients while wearing ppe. these findings were a critical part of the information used by the guideline development expert panel when formulating recommendations on ppe for frontline health workers caring for evd patients in outbreak conditions. we obtained expedited approval of the study protocol and survey from the world health organization ethics review committee (rpc ). as approved by the ethics committee, we provided a link to the informed consent form with the survey. participation was voluntary and implied informed consent. supplementary file : study questionnaire. click here to access the data. supplementary file : evidence-to-decision tables used in the formulation of recommendations for the who rapid advice guideline: personal protective equipment in the context of filovirus disease outbreak response. click here to access the data. author response mar , world health organization, switzerland saskia den boon i had difficulty reading the tables in the article. i thought maybe it was the way they were displaying on my computer, but nothing seemed to change when i clicked on them. please make these charts simple to read and clear. i need to see the tables to make sure your findings are adequately described. thank you for reviewing and approving our paper. we assume that you are author's response: referring to table . we have revised the table by adding the categories that were previously omitted from the table. for example, in version we only presented in the table the number health workers that indicated they felt at extremely low or low risk, but in version we have added a column indicating the number of health workers feeling at high or extremely high risk. we have also added a foot note explaining how the denominator in each cell reflects missing values for that particular question. we hope that this has improved the readability of the tables. the article is really well written. i was very pleased with the quality of the writing and the honesty of the authors about their challenges. this is important work in the area of ppe use. thanks for these kind words about our study. author's response: while i know that this was quick work in a difficulty setting, i still feel like the article needs to do justice to personal protective equipment research of the past years (at least since sars). the major section that needs more referencing is the discussion section. how do your findings compare to what we have found in epidemiological studies, simulation studies, and others on ppe. even if these studies were not done in the context of an outbreak of evd in africa, they should still be discussed. there is literature on some of these areas that would bring worthwhile context to your findings. thanks for this suggestion. we have added a number of references to the author's response: literature to our discussion section. well written paper on an important and largely ignored subject: 'health workers perspectives for guidelines'; also on top global health issue 'ebola virus disease'. study process was speedy and appropriate for the urgency needed for guidelines to be developed making this a good learning experience. however, there are a few points of attention listed below. i have also highlighted the sections relevant to my comments . here 'the - evd outbreak in west africa was initially declared a public health emergency of international concern in early august , coinciding with the decision to develop a who rapid advice guideline on the selection and use of ppe for evd care in outbreaks.' this statement will fit more within the background section, consider moving into background. 'we electronically surveyed international frontline physicians and nurses who participated in foreign medical teams deployed to the affected countries in early stages of the evd outbreak.' clearly stating time frame in the methods section within which survey was done will also be helpful for readers, although a time frame is given later under participants, it is not clear if this was for survey or the sampling. this time frame is also very early in the outbreak aq : settings is not well described, consider discussing setting in more detail under a separate title. clinicians express discomfort and safety, it may be interesting to know if at some point in the interviews they weighed in on safety versus comfort e.g. will the feeling of safety make them cope with discomfort? or does discomfort make safety inconsequential? i have answered 'partly' to the question "is the work clearly and accurately presented and does it cite the current literature?" as a small part of the methods may benefit clarity if texts are moved around. i have answered 'partly' to the question "are the conclusions drawn adequately supported by the results?" as it will be important to discuss discomfort versus safety of risk or clearly state if this was not evaluated by the study. this is an interesting piece and important in the context of infectious diseases. i will like to appreciate the authors for taking the initiative during such an emergency to collect such data. i will recommend the paper to be considered for indexing especially as it contributes towards developing guidelines for ppe which was more of a challenge to health workers during the outbreak. understanding their challenges and experiences especially in very humid temperatures is important. most importantly, the outbreak was a remarkable and most catastrophic outbreak. thus, using the outbreak as a point of focus adds value to the work considering that it pulled health workers from various countries. the work considering that it pulled health workers from various countries. why only physicians and nurses perspectives regarding ppe? i understand the relative risk for physicians and nurses as frontline workers is high, but other health workers are involved, and have recorded fatality rates, their experiences with ppe may also add value especially in the context of developing guidelines. maybe the authors should consider adding this to limitations. four or five likert is not explicit; it does not tell which questions were measured using scales of four and which used five and how they way categorize for-example., indicating low or high? agree or somewhat agree? understand the sample size was small and is actually mentioned as a limitation, however, any data on number of nurses and physicians that were deployed by who and msf during the period of data collection for background purposes and to justify the limitation? the sentence under data analysis is not clear to me, maybe rephrasing to better explain to the audience "for the purpose of statistical analysis, we considered each participant's experience with a ppe item unique and independent." the survey assumes that all the participants speak and write english? language characteristic not mentioned considering that these affected countries some are french countries. if all participants were not english speaking how was it translated? especially as the authors mentioned that respondents could not comprehend some questions due to time constraint. the literature highlights some gender differences for ppe amongst physicians and nurses especially in african context-assuming nurses are mostly women and physicians men--it would have been good to explore differences between nurses and physicians with regards to the specific ppe used. were physicians exposed to more sophisticated ppe than nurses? other comments that may be of interest to the authors: i understand the limitation of the paper is focused on participants in ebola treatment centers and only foreign deployed. however, guidelines should take into consideration local reality in terms of culture? based on previous outbreaks, most families prefer to care for patient at home and given the limited resources in this context; local materials were used at home in as ppe . http://www.cnn.com/ / / /health/ebola-fatu-family/index.html given the reality of limited resources, and the fact that most families prefer to care for patient at home it would add more value also to consider experiences of those who cared for patient at home, the type of ppe used and opportunities in incorporating local reality into evidence-based guidelines for ppe. if applicable, is the statistical analysis and its interpretation appropriate? yes settings is not well described, consider discussing setting in more detail under a separate title. we are not sure how to respond to this question of the reviewer. we did an author's response: online survey among health workers who were deployed by msf or who to respond to the ebola outbreak in west africa early on in the epidemic. health workers worked in local hospitals, clinics or ebola treatment centers, but because we did not ask further information about these settings we cannot provide a more detailed description. clinicians express discomfort and safety, it may be interesting to know if at some point in the interviews they weighed in on safety versus comfort e.g. will the feeling of safety make them cope with discomfort? or does discomfort make safety inconsequential? we assume that the reviewer is referring to question which asked, "please author's response: indicate how safe you felt by ticking a box for each aspect of personal protective equipment". as we have stated in the discussion, survey participants had difficulty answering this question because of the way the answer categories were phrased, e.g. "extremely low risk, i felt comfortable". in this answer category we wanted comfortable to mean "i am not worried about safety", but this was sometimes interpreted as "i am physically comfortable (e.g. not overheated, etc.)". if we had had more time for piloting, we would have been able to pick this up before sending out the survey. however, through comments from health workers it became clear that they indeed cope with discomfort because the ppe makes them feel safe and we have added the following sentence to the discussion: "health workers accept a certain degree of discomfort in return for the protection provided by ppe". i have answered 'partly' to the question "is the work clearly and accurately presented and does it cite the current literature?" as a small part of the methods may benefit clarity if texts are moved around. we hope that our amendments have improved the methods section. author's response: i have answered 'partly' to the question "are the conclusions drawn adequately supported by the results?" as it will be important to discuss discomfort versus safety of risk or clearly state if this was not evaluated by the study. we hope that our amendment has taken away the concern of the reviewer. author's response: this is an interesting piece and important in the context of infectious diseases. i will like to appreciate the authors for taking the initiative during such an emergency to collect such data. i will recommend the paper to be considered for indexing especially as it contributes towards developing guidelines for ppe which was more of a challenge to health workers during the outbreak. understanding their challenges and experiences especially in very humid temperatures is important. most importantly, the outbreak was a remarkable and most catastrophic outbreak. thus, using the outbreak as a point of focus adds value to the work considering that it pulled health workers from various countries. thank you for reviewing our paper and for making helpful comments and author's response: thank you for reviewing our paper and for making helpful comments and author's response: suggestions. see below our responses. why only physicians and nurses perspectives regarding ppe? i understand the relative risk for physicians and nurses as frontline workers is high, but other health workers are involved, and have recorded fatality rates, their experiences with ppe may also add value especially in the context of developing guidelines. maybe the authors should consider adding this to limitations. we agree with the reviewer about the importance of ppe for other health author's response: workers, for example cleaners, laboratory workers, burial teams and other workers. however, the focus of the who guideline which our study aimed to inform, was on healthcare workers and therefore we also focused our survey on this group. four or five likert is not explicit; it does not tell which questions were measured using scales of four and which used five and how they way categorize for-example., indicating low or high? agree or somewhat agree? we agree with the reviewer that it would have been better to have used a author's response: comparable (e.g. -point scale) for all the questions. if we had more time for piloting, we may have picked this up before sending out the survey. now, the questions on safety and comfort had a -point scale and questions on communication, ability to provide care, and heat and dehydration had a -point scale. as can be seen in the questionnaire which is included in the supplementary material, we did not use coding in the answer categories. understand the sample size was small and is actually mentioned as a limitation, however, any data on number of nurses and physicians that were deployed by who and msf during the period of data collection for background purposes and to justify the limitation? as stated in the results section, we invited health workers ( from msf author's response: and from who) to participate in the survey, but this included health workers outside the sampling frame (e.g. logisticians and water, sanitation and hygiene experts). unfortunately we do not have more detailed information on numbers deployed. the sentence under data analysis is not clear to me, maybe rephrasing to better explain to the audience "for the purpose of statistical analysis, we considered each participant's experience with a ppe item unique and independent." we have now added the following clarification to the methods section: "i.e. we author's response: did not account for the fact that the experience came from one and the same health worker". the survey assumes that all the participants speak and write english? language characteristic not mentioned considering that these affected countries some are french countries. if all participants were not english speaking how was it translated? especially as the authors mentioned that respondents could not comprehend some questions due to time constraint. yes, this is correct. we assumed that all participants could speak and write author's response: english and we did not translate the questionnaire. the miscomprehension was due to the fact that two questions were not phrased clearly, rather than the language skills of the survey participants. the literature highlights some gender differences for ppe amongst physicians and nurses especially in african context-assuming nurses are mostly women and physicians men--it would have been good to explore differences between nurses and physicians with regards to the specific ppe used. were physicians exposed to more sophisticated ppe than nurses? ppe used. were physicians exposed to more sophisticated ppe than nurses? this is a very interesting question. although our study was not designed to author's response: answer this question and the number of participants was too small to do any stratified analysis, i had a brief look at the data. we indeed found a higher proportion of physicians among males ( %) than among females ( %), but there were no obvious differences in robustness of ppe, when i compared gown or coverall use between males and females, or between physicians and nurses (varying between - % using a gown). other comments that may be of interest to the authors: i understand the limitation of the paper is focused on participants in ebola treatment centers and only foreign deployed. however, guidelines should take into consideration local reality in terms of culture? based on previous outbreaks, most families prefer to care for patient at home and given the limited resources in this context; local materials were used at home in as ppe . http://www.cnn.com/ / / /health/ebola-fatu-family/index.html given the reality of limited resources, and the fact that most families prefer to care for patient at home it would add more value also to consider experiences of those who cared for patient at home, the type of ppe used and opportunities in incorporating local reality into evidence-based guidelines for ppe. we acknowledge the importance of this issue brought up by the reviewer but it author's response: fell outside the scope of the study and the who guideline that we were aiming to inform. the benefits of publishing with f research: your article is published within days, with no editorial bias you can publish traditional articles, null/negative results, case reports, data notes and more the peer review process is transparent and collaborative your article is indexed in pubmed after passing peer review dedicated customer support at every stage for pre-submission enquiries, contact research@f .com report of a who/international study team we thank the following people for providing invaluable comments on the project proposal and questionnaire: patricia hudelson, gordon guyatt, martine verwey, doris bacalzo and elie akl. we are grateful to armand sprecher from médecins sans frontières for sending the questionnaire to his staff during the peak of the outbreak response. we are also grateful to the survey participants for making this study possible. participants could withdraw from the study at any time without providing any justification. due to the small number of survey participants, the detailed information collected, and the terms in the consent form approved by the who ethics review committee, which guaranteed participant anonymity, the individual-level data cannot be made available. requests for raw data can be dealt with on a case-by-case basis by contacting the corresponding author dr den boon, who will facilitate enquiries to the who ethics review committee.competing interests sdb and cv declare no competing interests. mf declares that his spouse is an employee at bristol myers squibb and owns company stock as part of her remuneration plan. sln declares that she is a member of the grading of recommendations assessment, development and evaluation (grade) working group, has published numerous papers related to grade, and that her career has benefited from this relationship. grade is the guideline process used by her employer, the world health organization, to develop guidelines. this study was funded by who core funds. no external funding was obtained.the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. i had difficulty reading the tables in the article. i thought maybe it was the way they were displaying on my computer, but nothing seemed to change when i clicked on them. please make these charts simple to read and clear. i need to see the tables to make sure your findings are adequately described. the article is really well written. i was very pleased with the quality of the writing and the honesty of the authors about their challenges. this is important work in the area of ppe use.while i know that this was quick work in a difficulty setting, i still feel like the article needs to do justice to personal protective equipment research of the past years (at least since sars). the major section that needs more referencing is the discussion section. how do your findings compare to what we have found in epidemiological studies, simulation studies, and others on ppe. even if these studies were not done in the context of an outbreak of evd in africa, they should still be discussed. there is literature on some of these areas that would bring worthwhile context to your findings. are all the source data underlying the results available to ensure full reproducibility? yes no competing interests were disclosed. are all the source data underlying the results available to ensure full reproducibility? yes no competing interests were disclosed. competing interests: we have read this submission. we believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. well written paper on an important and largely ignored subject: 'health workers perspectives for guidelines'; also on top global health issue 'ebola virus disease'. study process was speedy and appropriate for the urgency needed for guidelines to be developed making this a good learning experience. however, there are a few points of attention listed below. i have also highlighted the sections relevant to my comments . here thank you for reviewing and approving our paper. see below our responses to author's response: your comments. we have made a number of changes in the text in response to your comments. 'the - evd outbreak in west africa was initially declared a public health emergency of international concern in early august , coinciding with the decision to develop a who rapid advice guideline on the selection and use of ppe for evd care in outbreaks.' this statement will fit more within the background section, consider moving into background.we removed this sentence from the methods section and have added it, author's response: slightly modified, to the background section. 'we electronically surveyed international frontline physicians and nurses who participated in foreign medical teams deployed to the affected countries in early stages of the evd outbreak.' clearly stating time frame in the methods section within which survey was done will also be helpful for readers, although a time frame is given later under participants, it is not clear if this was for survey or the sampling. this time frame is also very early in the outbreak we send out the request for participation in september and have added author's response: this to the methods section. later we indicate that the survey was open for a -day period. the health workers eligible for participation were those who were deployed to west africa between march and september which was already stated in the methods section under participants. settings is not well described, consider discussing setting in more detail under a separate title. key: cord- -f moopcc authors: eggermont, hilde; verschuren, dirk title: original article: taxonomy and diversity of afroalpine chironomidae (insecta: diptera) on mount kenya and the rwenzori mountains, east africa date: - - journal: j biogeogr doi: . /j. - . . .x sha: doc_id: cord_uid: f moopcc aim anthropogenic climate change is expected to result in the complete loss of glaciers from the high mountains of tropical africa, with profound impacts on the hydrology and ecology of unique tropical cold‐water lakes located downstream from them. this study examines the biodiversity of chironomidae (insecta: diptera) communities in these scarce afroalpine lake systems, in order to determine their uniqueness in relation to lowland african lakes and alpine lakes in temperate regions, and to evaluate the potential of afroalpine chironomidae as biological indicators to monitor future changes in the ecological integrity of their habitat. location mount kenya (kenya) and rwenzori mountains (uganda). methods the species composition of afroalpine chironomid communities was assessed using recent larval death assemblages extracted from the surface sediments of high‐mountain lakes between and m. results were compared with similar faunal data from east african lakes at low and middle elevation ( – m), and with literature records of chironomidae species distribution in sub‐saharan africa, the palaearctic region and elsewhere. all recovered taxa were fully described and illustrated. results the ‐lake analysis yielded subfossil chironomid larvae belonging to distinct taxa of full‐grown larvae, and three taxa of less differentiated juveniles. eleven of these are not known to occur in african lakes at lower elevation, and eight taxa (or % of total species richness) appear restricted to the specific habitat of cold lakes above m, where night‐time freezing is frequent year‐round. the faunal transition zone coincides broadly with the ericaceous zone of terrestrial vegetation (c. – m). snowline depression during the quaternary ice ages must have facilitated dispersion of cold‐stenothermous species among the high mountains of equatorial east africa, but less so from or to the palaearctic region via the ethiopian highlands. main conclusions chironomid communities in glacier‐fed lakes on africa's highest mountains are highly distinct from those of lowland african lakes, and potentially unique on a continental scale. by virtue of excellent preservation and their spatial and temporal integration of local community dynamics, chironomid larval death assemblages extracted from surface sediments are powerful biological indicators for monitoring the hydrological and ecological changes associated with the current retreat and loss of africa's glaciers. concerns about the environmental effects of anthropogenic climate change are motivating considerable effort to model and predict the impact of global warming on regional ecosystems. this is particularly true for the high-mountain regions of tropical africa, where climate change is expected to result in complete loss of ice caps and glaciers. on mount kilimanjaro (tanzania), the ice cap covering its western (kibo) top has shrunk by % in the last century; at this rate, all 'eternal' snow will disappear within two decades (thompson et al., ) . glaciers on mount kenya (kenya) have shrunk by % since (hastenrath, ) . likewise, in the rwenzori mountains (uganda, democratic republic of the congo) the ice field of elena glacier is thinning, and its front has retreated several hundreds of metres in the last years (kaser & osmaston, ; mölg et al., ) . this rapid retreat is consistent with warming of the tropical middle troposphere in recent decades (hastenrath & kruss, ; gaffen et al., ) , though a longer-time decrease of precipitation and air humidity may be the principal cause of the near-continuous retreat of the african glaciers since (hastenrath, ; kaser et al., ) . clearly, loss of permanent ice from the tops of africa's highest mountains will have profound effects on the hydrology and temperature regime of alpine lakes located downstream from those glaciers. this by itself may have a severe impact on the integrity and function of these scarce afroalpine aquatic ecosystems, and add to the direct effects of a regional rise in air temperature. consequently, there is an urgent need to characterize the aquatic fauna and flora of these (still relatively) undamaged afroalpine lakes, to determine their uniqueness in relation to both african lowland lakes and alpine lakes in temperate regions, and to find adequate means to monitor future changes in their biological diversity. chironomid larvae (insecta: diptera, non-biting midges) are a dominant component of bottom-dwelling invertebrate communities in lakes and streams around the world (armitage et al., ) . previous surveys of the chironomid fauna of african highland regions have mainly focused on flowing waters in the montane forest zone, e.g. mountain streams and rivers in ethiopia (harrison & hynes, ; harrison, harrison, , harrison, , , democratic republic of the congo (lehmann, (lehmann, , , south africa (scott, ; harrison & agnew, ; harrison, a,b) and north-eastern tanzania (saether & wang, ; , a saether, ; stur & ekrem, ) . with the exception of a few streams at - m a.s.l. (above sea level) in ethiopia (harrison, (harrison, , (harrison, , , most chironomid habitats studied so far are actually cool forest streams at modest elevations of c. - m. standing waters within this altitude range in tropical africa are still quite warm (surface temperatures of - °c), and their chironomid fauna is similar to that of low-elevation lakes (eggermont & verschuren, a,b) . little information is available on the chironomid fauna in africa's true high-mountain lakes, which occur above the tree line within the afroalpine zone of the few sizeable mountain massifs higher than m. their unique, perennially cold tropical standing-water habitat (löffler, ) may well be reflected in a distinct and vulnerable aquatic fauna. in this context we conducted a study of larval chironomidae in lakes situated between and m a.s.l. on mount kenya and the uganda side of the rwenzori mountains. this paper presents diagnoses, illustrations and biogeographical notes for all encountered taxa, followed by an evaluation of species diversity compared to other groups of aquatic biota in these lakes, and of the uniqueness of this afroalpine chironomid fauna compared with that of african lakes at low and middle elevations. instead of studying collections of the living larval communities, we examined their remains preserved in recently deposited lake sediments. in the small lakes considered here, recent death assemblages yield a spatially and seasonally integrated picture of present-day species diversity (frey, ) , which would otherwise require intensive live collecting that in these remote locations is challenging to realize. ls cm ) , ph from . to . and water depth from . to . m (table ) . for comparison we also analysed sediment samples from two lakes on the lower slopes of mount kenya, i.e. in the cultivation and basal plateau belt (c. - m, dominated by grasses and agricultural crops: rurie swamp and lake nkunga). their surface-water conductivities are . and ls cm ) , respectively, their ph is . and . , and they are . and . m deep. the rwenzori mountains are a group of six glaciated massifs stretching from lake edward to lake albert on the border between uganda and the democratic republic of the congo (fig. ) . the high massifs (reaching between and m a.s.l.) are all topped with glaciers, and dissected by deep glacier-eroded valleys. vegetation distribution is largely similar to that on mount kenya with some difference in altitudinal extent of the vegetation belts, and in the plant species present (hedberg, ) . the rwenzori mountains are wetter than mount kenya because of heavier and more regular rainfall, with main rainy periods from mid-march to may, and from september to mid-december. an estimated glacier-fed lakes and tarns occur on the ugandan side, and another or so on the democratic republic of the congo side of the range. we studied samples (authors' own collection, july ) from five highly dilute lakes (surface-water conductivity between and ls cm ) ) situated in the alpine zone (bujuku, lower kitandara, upper kitandara and josephat's pool; with mosses, giant heather, lobelias and groundsels around the lakes) and the nival zone (green pool; an isolated permanent pool surrounded by rocks with lichens, no real vegetation), spanning elevations between and m. due to logistic constraints at the time of sampling, data on lake depth and temperature are currently not available for these rwenzori lakes; their ph ranges between . and . (table ) . in contrast to the study sites on mount kenya, where bottomsediment samples were collected from a boat, larval chironomid communities in the rwenzori lakes were studied using journal of biogeography , - bottom sediments collected nearshore. we cannot assume that these present a fully integrated picture of faunal diversity in these lakes (frey, ) . however, cold polymixis (frequent mixing) and lack of submerged littoral vegetation (löffler, ) creates similar well-oxygenated bottom habitat in both deepwater and nearshore environments. consequently, recently deposited chironomid death assemblages are probably fairly homogeneous lake-wide. surface-sediment samples ( - cm) were prepared by dispersing the sediment in warm % koh (walker & paterson, ) , and rinsing through -and -lm mesh sieves. retained residues were scanned at · magnification under transmitted light. all chironomid head capsules were picked and mounted in glycerine on microscope slides; cover slips were sealed with a synthetic epoxy. identification was done at - ·, by comparison with reference collections from lake tanganyika (eggermont & verschuren, a,b) and about other low-and mid-elevation lakes in east africa (verschuren, ; eggermont & verschuren, a,b) , alpha-taxonomic literature (see eggermont & verschuren, a) , and general works on holarctic and nearctic chironomidae (wiederholm, ; moller-pillot, a,b; epler, epler, , . representative specimens were photographed with a nikon coolpix digital camera. the illustrations presented here are adobe photoshopÒ collages of stacked partial images, each with certain skeletal elements in focus. to ensure consistency of identification throughout the collection, all fossils were looked at several times until all specimens possessing a minimum set of diagnostic characters could be assigned to a distinct morphotype. differences in diagnostic characters between these taxa resemble differences at the species level in live material from the holarctic region, so we regard most of our fossil morphotypes to be equivalent to morphospecies. morphological terminology follows saether ( ) , supplemented by kowalyk ( ) , rieradevall & brooks ( ) and webb & scholl ( ) for the relevant taxa. species attribution of the subfossil morphotypes follows criteria set out by eggermont & verschuren ( a) , using both morphological and biogeographical considerations. specimens were attributed to a known morphotype when the minimum set of required diagnostic characters were recorded at least once per site. morphotypes bearing no explicit resemblance with known african or holarctic species and larval types are designated by their genus or tribe name followed by the name of the lake in which the most complete specimen was found, e.g. 'larsia type kitandara'. if no single diagnostically complete specimen was found, we used the name of a lake in which the taxon was sufficiently abundant to construct a composite diagnosis. species richness was evaluated using the raw number of taxa present, and the number of taxa expected with constant sample size (es ) using hurlburt's rarefaction method (magurran, ) ; species diversity was evaluated using hill's ( ) diversity measure n ; the two latter values were calculated using primerÒ version . . (primer-e ltd, ) . the significance of differences in sample size between lakes and in taxonomic diversity between regions was assessed with the student's t-test and mann-whitney u-test using statistica . (statsoft inc., ) . analysis of the surface-sediment samples from highelevation lakes (> m a.s.l.) yielded subfossil remains of chironomid larvae, of which ( . %) could be assigned to different taxa of full-grown larvae, and three morphotypes of less differentiated juveniles. the faunal inventory of full-grown larvae includes one species of diamesinae, two tanypodinae, six orthocladiinae and seven chironominae (four chironomini and three tanytarsini) ( table ). all taxa are diagnosed and illustrated below. a further taxa were encountered only in the two mid-elevation lakes on mount kenya (nkunga and rurie swamp) studied here for comparison. for completeness these are listed in table , but not treated in the taxonomic section of this paper; we refer to verschuren ( ) and eggermont & verschuren ( a ,b, a for a taxonomic diagnosis. head capsule heavily sclerotized. mentum with simple median tooth flanked by four pairs of well-developed lateral teeth, and another three to four pairs of smaller lateral teeth steeply sloping back on the curved lateral portions of the mentum. ventromental plates inconspicuous, vestigial. there are three known species of diamesa in africa, of which diamesa kenyae freeman and diamesa freemani willassen and cranston have been described as larvae (both from mount kenya; willassen & cranston, ) . the present morphotype differs from d. freemani in having a mentum with only about eight pairs of lateral teeth (not ), and from d. kenyae in the more steeply sloping arrangement of the outer teeth. our species designation is based on the reported occurrence of diamesa rwenzoriensis at lake bujuku in the rwenzori (freeman, ) . we did not find this species in lake bujuku but recovered it from two other rwenzori lakes in the alpine and nival zone, above m. procladius brevipetiolatus goetghebuer (figs & ) . ligula with concave row of five black, straight-pointed teeth, median tooth distinctly shorter and narrower than the lateral teeth. paraligula with a tall apical point, barbed on both sides (about four to six teeth on the outer side and two or three points on the inner side). dorsomentum with two rows of seven or eight teeth on either side of the median, but always fewer in early instars (usually about five). mandible with a uniformly curved apical tooth about a third of the length of the mandible, a large pale basal tooth with blunt apex pointing distally, and a small pale accessory basal tooth lodged between them on the inner mandibular margin. pecten hypopharyngis well-developed with a strong medial tooth and about more teeth of equal length. basal segment of the antenna stout about four to five times its basal width, ring organ about a third from the distal end. cephalic setation as for the genus, with dp present, s and s in an angulated line, and s anteromesial to s (not illustrated). first-instar larvae of this type (fig. ) have a ligula with constricted base, and four teeth, of which the outer darkcoloured pair are distinctly swollen and point outward, while the median teeth are very small and pale; dorsomentum with at least three teeth on either side of the median; mandible with indication of a developing basal tooth; basal segment of antenna short, about three times its basal width. there are seven known procladius species in sub-saharan africa, of which at least two species (procladius brevipetiolatus goetghebuer and procladius shibrui harrison) have been collected at high-elevation sites (freeman, ; harrison, harrison, , a . this particular fossil type is identical to larval p. brevipetiolatus described from various east african lakes and reservoirs (chrispeels, ; mclachlan, ; harrison, ) , and widely distributed in lakes at low and middle elevations (verschuren, ; eggermont & verschuren, a) . here we found it to be common at two lakes in the ericaceous zone of mount kenya (fig. ) ; it also occurs lower down on the mountain (table ) . larsia type kitandara (figs - ). head capsule yellowish brown, with two longitudinal grooves positioned symmetrically above the ventrobasal margin (fig. ) . ligula with weakly concave row of five teeth, three central teeth roughly equal in size with apices pointing forward, middle section moderately narrowed, and shallow stripe-like muscleattachment area. paraligula bifid, about half the length of the ligula, outer point about two and a half times the length of the inner point, inner point arising from immediately above a weakly thickened base. mandible narrow and strongly curved, table chironomidae recovered from the african high-elevation lakes (> m a.s.l.) studied, with number of lakes where each taxon was recorded, number of specimens analysed and the slide-collection codes of illustrated specimens with a large basal tooth, a smaller accessory tooth, and a pronounced projection at its base. pecten hypopharyngis with about pointed teeth, the innermost corner tooth larger than the remaining teeth. dorsomentum a sclerotized complex without teeth, extending by ridges to the ventral region of the premento-hypopharyngeal complex, and apically ending in a blunt process, with a large, apically directed dorsal tooth. basal segment of the maxillary palp undivided, with ring organ at about a quarter of the distance from the distal end. basal segment of the antenna relatively long, about nine to ten times its basal width, with ring organ at about a third of the distance from the distal end. cephalic setation as typical for the genus, with seta (s ) posterolateral to seta (s ), ventral pore (vp) posterolateral to s , closer to s than s , and greater than the setal sockets; dorsally, seta (s ) anterior to the dorsal pore (dp), close grouping of seta (s ) and seta (s ) (fig. ) . some six species of larsia are known to occur in sub-saharan africa (freeman & cranston, ) , but none have been described as larva. this morphotype was found in three alpine lakes in the rwenzori (fig. ) , comprising up to . % of the recovered local fauna. pentaneurini spp. larvula (fig. ) . ligula slightly concave, with four teeth, of which the outer lateral teeth are wide and the median teeth narrower and smaller. paraligula bifid, but very small and usually unclear in fossil specimens. mandible with a pointed apical tooth, otherwise no other details visible. pecten hypopharyngis with about four or five teeth. basal segment of the antenna up to six times its basal width. this morphotype groups first instar larvae of various pentaneurini taxa. in east african low-elevation lakes it most likely represents larvae of ablabesmyia and paramerina species (eggermont & verschuren, a) . in this collection, a specimen found at lake bujuku (rwenzori) is possibly larsia; and a specimen from lake nkunga (mount kenya) is possibly paramerina near ababae or pentaneurini indet. type naivasha. table chironomidae recovered from rurie swamp ( m a.s.l.) and lake nkunga ( m a.s.l.) on mt. kenya, with primary reference(s) for the taxonomic diagnosis ( , verschuren, ; , , eggermont & verschuren, a,b; , , eggermont & verschuren, a,b; , this study) . taxa also recovered from the high-elevation sites are marked by an asterisk chaetocladius melaleucus (meigen) . head capsule strongly sclerotized. mentum with a double median tooth and five pairs of pointed lateral teeth with apices in slightly convex alignment; median tooth about two and a half to three times as wide as the first laterals, and two small nipples in unworn specimens; in early (first and second) instars, the incision between the first and second laterals is sometimes deeper than adjacent incisions; setae submenti located near the posterior margin of the ventromental plates, below the second laterals. ventromental plates well developed, with a strongly sclerotized triangular plate extending scarcely beyond the basal margin of the mentum. apical tooth of mandible shorter than the combined width of the three inner teeth; mola nearly as dark as the inner teeth; seta subdentalis stubby, placed well below the mola; seta interna with at least six strong branches, all toothed at one side of distal quarter (fig. ) ; dorsal surface of the mandible with flanged inside margin, coloured light brown (fig. ). pre-mandible with two apical, and one blunt subapical tooth (fig. ). pecten epipharyngis with three teeth; about six pairs of chaetulae laterales present; s i toothed at both sides. antenna with five segments; first antennal segment about twice its basal width; third and fourth segment subequal; blade shorter than flagellum ( fig. ). at least two chaetocladius species occur in east africa (freeman & cranston, ; harrison, ) , but their larvae are unknown. our species designation is based on adult chaetocladius melaleucus having been netted in the vicinity of lake bujuku (freeman, ) , where this morphotype occurs. it appears restricted to the alpine and nival zones, but is fairly common both in the rwenzori (five lakes) and on mount kenya (two lakes). the other east african species, chaetocladius awasae harrison, has been recorded only from the ethiopian rift valley and south africa (harrison, (harrison, , a . limnophyes minimus group (epler) (figs - ). mentum uniformly pale brown with double median tooth and five pairs of lateral teeth; median tooth about two and a half times as wide as the first laterals; lateral portions of the mentum concave, with second to fourth laterals gradually diminishing journal of biogeography , - in size; fifth laterals small. ventromental plates narrow anteriorly, widened and sclerotized posterolaterally into a rounded plate extending beyond the basal margin of the mentum. mandible with apical tooth much shorter than the combined width of the three inner teeth; seta subdentalis stout, not extending beyond the third inner tooth (fig. ). premandible with two rounded apical, and two subapical teeth. antenna with five segments; fourth segment longer than third segment; blade about as long as the flagellum (fig. ) . saether ( ) recognized four african species of limnophyes, of which limnophyes bubo saether, limnophyes lobiscus saether and limnophyes minimus (meigen) appear to be restricted to high-elevation sites in east africa (including the rwenzori and mount kenya; saether, ) , whereas limnophyes natalensis (kieffer) is also widely distributed in lowland lakes and streams throughout eastern and southern africa. all four african limnophyes species belong to the l. minimus group as defined by epler ( ), but their larvae cannot reliably be separated without associated adults (saether, ; epler, ) . this morphotype matches larval l. minimus described from the kerguelen islands (saether, ) , but also l. natalensis (saether, ; eggermont & verschuren, a) . given the possible occurrence of all four african limnophyes species in the study area, we attribute this morphotype to the species group. it occurs at all altitudes ( fig. ) both in the rwenzori and on mount kenya, most abundantly in the alpine and nival zones (making up . % of the fauna in green pool). near paraphaenocladius type ol bolossat (fig. ) . mentum with a broad single median tooth, and five pairs of lateral teeth pointing inward; median tooth about two and a half to three times as wide as first laterals, nippled in unworn specimens but the small point is often broken off; first and second laterals large and pointed; fourth and fifth laterals small and pointing inwards; lateral margin of the mentum with indentation below the fifth laterals; setae submenti positioned below the incision between the median tooth and first laterals. ventromental plate conspicuous, laterally extending beyond the mentum. mandible with apical tooth shorter than the combined width of the four inner teeth, and wide mola extending to behind the second inner tooth; seta subdentalis short and pointed. mentum, ventromental plates and mandible of this taxon resemble paraphaenocladius, which has two african represent- atives (freeman & cranston, ) , but skeletal elements that would permit definitive generic assignment (labro-epipharyngeal region, antenna) were missing in our material. this morphotype also occurs in both fresh and saline waters in the lowlands of kenya and uganda, suggesting it may group a number of sibling species (eggermont & verschuren, a) . here we recovered it from the alpine upper kitandara lake (rwenzori), and from the mid-elevation lake nkunga (mount kenya). paratrichocladius type hausburg tarn (figs - ) . head capsule strongly sclerotized. mentum with a simple median tooth and first two pairs of lateral teeth pale brown, separated from the rest of the mentum by a deep incision; median tooth broadly domed, about two to two and a half times as wide as the first laterals; first laterals with rounded apex; second laterals pointed and smaller than both first and third laterals, leaning against the first laterals, but still clearly separated from them; third to sixth laterals about equal in size, dark brown with pointed apices; setae submenti located below the lateral margin of the mentum. ventromental plates conspicuous and sclerotized, starting from below the second laterals. mandible with a narrow apical tooth shorter than the combined width of the three inner teeth, inner teeth gradually decreasing in size; outer margin always smooth; seta subdentalis short and pointed, placed below a well-developed mola (fig. ) . premandible with one apical tooth (fig. ) . antenna with five segments gradually becoming smaller; ring organ at basal third of first antennal segment. the genus paratrichocladius includes three known african species, of which paratrichocladius micans (freeman) and paratrichocladius pretorians (freeman) are known to occur in the highlands (lehmann, ; freeman & cranston, ) . this morphotype was fairly common in hausburg tarn, large hall tarn (both mount kenya), and lower kitandara (rwenzori), all situated in the alpine zone. paratrichocladius type simba tarn (figs & ) . this morphotype closely resembles paratrichocladius type hausburg tarn as described above, but the median tooth is only about as wide as a first lateral tooth, and scarcely protruding them; second laterals pointing forwards, separate from the first laterals in unworn specimens but frequently worn down to nothing more than a rounded shoulder on the side of the first laterals. this species was fairly common throughout the study region (four lakes in the rwenzori and two on mount kenya), but it appears to be restricted to the alpine and nival zone (up to % of the fauna in simba tarn, mount kenya). in hausburg tarn (mount kenya) and lower kitandara (rwenzori), it occurs together with paratrichocladius type hausburg tarn. pseudosmittia type tanganyika (fig. ) . mentum with a single domed median tooth which sometimes has a central nipple, and four pairs of lateral teeth; first laterals protruding, pointing outwards in unworn specimens, second to fourth laterals about equal in size; lateral margin of mentum constricted below the fourth laterals. ventromental plates distinct, also a second plate is present and extends beyond the mentum laterally but the latter is often worn down. mandible with apical tooth shorter than the combined width of the three inner teeth. pseudosmittia occurs with at least four species in equatorial africa (harrison, (harrison, , a , but their larvae are unknown. one species, pseudosmittia rectilobus (freeman) is known from highland regions (freeman, ; harrison, ) . specimens in the present material are indistinguishable from pseudosmittia sp. diagnosed from lake tanganyika (eggermont & verschuren, a) and reported from various other african lakes (eggermont & verschuren, a) . we found it in alpine lakes both on mount kenya and the rwenzori, and in the mid-elevation lakes nkunga and rurie swamp (mount kenya). chironomus type kibos (figs & ) . mentum with trifid median tooth and six pairs of lateral teeth; the central median tooth accounts for distinctly less than half the total width of the median, and the lateral median teeth reaching at least half the height of the central median tooth; their apices point forward; lateral median teeth separate from the central tooth and well-developed, but always less than half the height of the central tooth (unlike chironomus near imicola, see below); the first and second pair of the lateral teeth stand close together but are not fused; the configuration of the fourth to sixth laterals is usually according to mentum type i of webb & scholl ( ) , i.e. with apices of the third to fifth laterals placed in line (fig. ) . ventromental plates fan-shaped, . - . times the width of the mentum, anterior margin smooth. mandible with row of radially arranged grooves on the ventral surface as characteristic for chironomus, and with an apical, one dorsal, and three inner teeth; third inner tooth small and slightly paler than the remaining teeth, i.e. chironomus mandible type ii of webb & scholl ( ) ; seta interna with four plumose branches; inner mandibular margin with about three spines in the basal quarter; seta subdentalis with broad base, stout and pointed. pre-mandible bifid with outer tooth stiliform, narrower than the inner tooth. pecten epipharyngis with around - subequal teeth. some chironomus species are reported to occur in equatorial africa (freeman & cranston, ) , six of which have been described as larvae (dejoux, (dejoux, , mclachlan, ; petr, ; harrison, ) but none of these is similar to the present morphotype, which was first described from kibos swamp in lake victoria (eggermont & verschuren, b ) and found to be widespread throughout uganda and kenya. the specimens here were recovered from five lakes distributed across the altitudinal gradient on mount kenya. chironomus near imicola (kieffer) (figs & ) . head capsule of full-grown larvae mostly dark brown, with pigmentation often extending forward beyond halfway to the gula; early instars scarcely pigmented. mentum with trifid median tooth of which the central median tooth is prominent, almost half the total width of the median tooth; lateral median teeth separate from the central tooth and well-developed, but always less than half the height of the central tooth (unlike chironomus type kibos, see above), and pointing slightly inward; first and second laterals strongly protruding and fused over much of their length, incision between second and third laterals distinctly deeper and wider than adjacent incisions; fourth laterals always smaller and less wide than fifth laterals, and placed as in chironomus mentum type ii (i.e. with apex of fourth laterals clearly below the line connecting the apices of the third and fifth laterals, and the line connecting the apices of the fourth and fifth laterals nearly horizontal relative to the axis of symmetry), chironomus mentum type iii (having the fifth laterals slightly higher than the fourth laterals), or an intermediate configuration. ventromental plates, mandible and pre-mandible as in chironomus type kibos. pecten epipharyngis with at least - teeth of irregular length. this taxon was previously described from low-elevation lakes in east africa (eggermont & verschuren, b) . here it was found only on mount kenya, but fairly commonly at all altitudes (seven lakes, spanning elevations between and m a.s.l.). in the alpine lakes it was more common than chironomus type kibos, discussed above. dicrotendipes pilosimanus (kieffer) (figs - ) . mentum very dark brown to black, with single median tooth and six pairs of lateral teeth; median tooth not protruding beyond the first laterals, and with barely noticeable lateral incisions; second laterals small, fully fused with the first laterals so as to form no more than a notch on the side of the first laterals just below the apex of the third laterals; third to sixth laterals normally developed, gradually diminishing in size. ventromental plates compact fan-shaped, about . times the width of the mentum, with about - strial ridges, and a mostly smooth or very finely crenulated anterior margin. mandible with pointed apical tooth, a pale dorsal tooth at the base of which a small accessory dorsal tooth is sometimes visible, three inner teeth of equal size, and a weakly developed mola; seta subdentalis spatulate but pointed, extending just beyond the apex of the third inner tooth (fig. ) . premandible with two teeth of which the inner tooth is the largest, and some two rounded subapical teeth. pecten epipharyngis with about five robust, blunt teeth. anterior margin of the frontal apotome without irregular crenulation (figs & ) ; labral sclerite smooth. antenna with five segments of which the fourth segment is slightly shorter than the second, but distinctly longer than both third and fifth segments; antennal blade slightly longer than the flagellum; ring organ in proximal third of the basal segment. the present morphotype matches the larva of dicrotendipes pilosimanus described from kebena river (ethiopia) and lake noordhoek (south africa; harrison, ) . it differs from larvae of the related dicrotendipes septemmaculatus (becker) mainly in having ventromental plates with more striae (c. - rather than c. - ), and a frontal apotome with smooth anterior margin, not displaying the irregular tubercles present in d. septemmaculatus (contreras-lichtenberg, ; epler, ; harrison, ) . records of d. pilosimanus are restricted to south africa and cool montane streams and ponds in east africa (harrison, (harrison, , a , whereas d. septemmaculatus seems to occur in warm low-and mid-elevation lakes throughout east and north africa (freeman, ; epler, ) . also dicrotendipes collarti (goetghebuer) has been reported from the east african mountains (nyandarua range in kenya; freeman, ) , but its larva is unknown. we found d. pilosimanus only on mount kenya, at all elevations (seven lakes between and m a.s.l.) but most abundantly in lakes below tree line. as its frontal apotome is not always preserved and the ventromental striae often difficult to count, we are aware that our material may include some d. septemmaculatus, especially in the mid-elevation lakes nkunga and rurie swamp. lake nkunga dicrotendipes include at least three true d. pilosimanus specimens, but some others are more likely to belong to d. septemmaculatus. also some incomplete dicrotendipes from mid-elevation kenya lakes such as ol bolossat (c. m a.s.l.) and narasha (c. m a.s.l.) which eggermont & verschuren ( b) assigned to d. septemmaculatus may actually be d. pilosimanus, yet none of the several dicrotendipes specimens recovered from these and other lakes could be unambiguously assigned to it. polypedilum type bandasa (fig. ). mentum uniformly brown or black with four median teeth of which the outer pair are small, and six pairs of lateral teeth; two central median teeth wide with slightly outward pointing apices; first laterals as tall as central median teeth; third laterals often set slightly forward, and taller than the fourth laterals; fourth to sixth laterals small, with apices somewhat turned outward; lateral sides of mentum slanted. ventromental plates fan-shaped, in some cases nearly trapezoidal, about . - . times as wide as the mentum, with smooth anterior margin, medial margin with a distinct corner halfway, pointed posterolateral ends, and pointed anteromedian ends directed towards each other or slightly upturned, with well-expressed but fine striation running over their entire surface. mandible with apical tooth, a strong dorsal tooth, and two inner teeth. at least polypedilum species have been reported from equatorial africa, and nine of these were (partly) described as larvae (mclachlan, ; dejoux, ; lehmann, ; oyewo & saether, ) , but no one particularly resembles the present morphotype. our material closely resembles subfossil polypedilum type narasha from mid-elevation lake narasha ( m a.s.l.) on the western shoulder of the kenya rift valley (eggermont & verschuren, b ), but small differences in the shape of the ventromental plates (p. type narasha never has the anteromedian ends upturned, and striation is less well expressed) and the mentum (in polypedilum type narasha the fourth laterals are not taller the third laterals) warrants separating the two morphotypes. nine other polypedilum species have been found as fossils in lowland african lakes (eggermont & verschuren, b) , but these are all unambiguously distinguishable from the present morphotype. it was recovered from four lakes on mount kenya, all located below m a.s.l.; in lake bandasa, it represented . % of the recovered fauna. chironomini larvula type (fig. ) . mentum not greater than c. lm, pale brown with clearly trifid median tooth, and six pairs of lateral teeth gradually diminishing in size; all laterals clearly separated from each other, or first and second laterals pressed against each other. ventromental plates fanshaped, less wide than the mentum, their anteromedian ends pointing up towards central part of the mentum, and their posteromedian corners tapering backward; anterior margin very finely crenulated. mandible with apical, one dorsal, and three inner teeth. pre-mandible with at least two teeth. pecten epipharyngis with at least seven teeth. antenna with five segments. this previously described morphotype (eggermont & verschuren, b) here most probably groups first-instar larvae of chironomus type kibos and chironomus near imicola. it was only encountered on mount kenya (seven lakes, spanning elevations between and m a.s.l.), most abundantly in lakes above m a.s.l. chironomini larvula type (fig. ) . mentum not greater than about lm, laterally compressed, with laterally notched median tooth and six pairs of lateral teeth; median tooth protruding beyond first laterals, first to sixth laterals gradually decreasing in size. ventromental plates, mandible and pre-mandible as in chironomini larvula type ; pecten epipharyngis not clearly recorded. s i toothed; s ii simple. antenna with five segments, fourth segment longer than both third and fifth segment, but smaller than the second segment. in low-elevation african lakes this morphotype includes first-instar larvae of nilodorum, dicrotendipes and other closely related chironomini (eggermont & verschuren, b ). here we found it almost exclusively in two mount kenya lakes rheotanytarsus type kitandara (fig. ) . mentum with weakly notched median tooth (probably because of wear) and five pairs of lateral teeth gradually decreasing in size; median tooth about twice as wide as the first laterals. ventromental plates compact, only c. . times as wide as the mentum, and about two and a half times as long as wide; anterior margin strongly curved, with behind it a narrow zone without striae, a band of square surface sculpturing, and then a band of striae taking up the middle third; the plates touch each other medially with their upper anteromedian ends only. antennal pedestal tubular and curved, about as wide as long. three rheotanytarsus species have been reported from african mountain streams (rheotanytarsus bufemoratus kyrematen and saether, rheotanytarsus guineensis (kieffer), rheotanytarsus montanus lehmann), but the associated larvae are unknown. this morphotype mainly differs from larvae of the african lake species rheotanytarsus ceratophylli (dejoux, ) in having more compact ventromental plates, and a mentum with wider, scarcely notched median tooth. in this respect, it resembles the nearctic rheotanytarsus sp. a (epler, ) . only a few partial specimens of this type were recovered, from the alpine upper kitandara lake (rwenzori). tanytarsini indet. type ellis (figs & ) . head capsule of older instars with circular gula pigmentation, ventrobasal margin well-sclerotized, sclerotization extending forward in two y-shaped thickened ridges (fig. ) . mentum dark brown, with single median tooth and five pairs of lateral teeth; median tooth and first laterals separated from the rest of the mentum by a deep incision, and set backward; lateral teeth gradually decreasing in size, fifth laterals small and pressed against the fourth laterals; mentum somewhat constricted towards its base; setae submenti inserted below the fifth laterals. ventromental plates rectangular, with a curved anterior margin, c. . - . times as wide as the mentum, clearly striated, anteromedian part of the posterior margin often more sclerotized. mandible with one dorsal, an apical, and three inner teeth, all dark brown; seta subdentalis long and curved; pecten mandibularis well-developed, with one or more setae quite stiff and extending beyond the dorsal tooth. premandible with at least four teeth, the outermost being stiliform, other teeth more or less spatulate and decreasing in size; brush present. labral lamella well-developed, with about teeth. pecten epipharyngis consisting of three serrated platelets. antennal pedestal tubular, broadening towards the base, about as high as wide, with irregular surface and short distal spur. antenna consisting of five segments; first antennal segment about six times its basal width, with ring organ twofifths from its base; second antennal segment cylindrical, about a quarter of the length of the first antennal segment. attribution of this morphotype to the genus tanytarsus s.s. is uncertain because of the lack of a complete antenna. this taxon differs from tanytarsini indet. type large hall tarn (below) in having a mentum which is not constricted at its base, and with first laterals gradually decreasing in size (not smaller than both the median and second laterals). all tanytarsini morphotypes previously described from lake tanganyika (eggermont & verschuren, b) and african lakes at lower elevation (eggermont & verschuren, b) can be distinguished from tanytarsini indet. type ellis by details in mental teeth configuration, shape of the antennal pedestal, and/or the mandible. this morphotype was found in three alpine lakes on mount kenya. in lake ellis, it made up . % of the recovered fauna. tanytarsini indet. type large hall tarn (figs & ) . mentum with broad median tooth and five pairs of robust lateral teeth; median tooth about twice as wide as the first laterals, and slightly notched in unworn specimens; first laterals pointing outward, smaller than both the median tooth and second laterals, and separated from them by a deep incision; second to fifth laterals gradually diminishing in size and slightly turned outward; mentum constricted towards its base. ventromental plates relatively high rectangular, about as wide as the mentum, with a curved anterior margin. mandible with one dorsal, an apical, and three well-developed inner teeth. antennal pedestal tubular, c. . - . times as high as wide, and with a short distal spur. generic attribution to tanytarsus s.s. remains uncertain since the examined material lacks essential skeletal components, such as pre-mandible, pecten epipharyngis, and antenna. it mainly differs from tanytarsini indet. type ellis (above) by having a mentum with constricted base (lateral margins not straight) and first laterals smaller than both the median and second laterals (laterals not gradually decreasing in size). this morphotype was found in two alpine tarns (hausburg tarn and large hall tarn) on mount kenya, being most abundant in large hall tarn ( . % of the recovered fauna). the altitudinal distribution of the chironomid taxa inhabiting high-elevation lakes (> m a.s.l.) on mount kenya and the rwenzori displays the following trends: . eight taxa appear restricted to the alpine and nival zones (> m a.s.l.): the diamesinae species diamesa type kitandara, one tanypodinae (larsia type kitandara), three orthocladiinae (chaetocladius melaleucus, paratrichocladius type hausburg tarn and paratrichocladius type simba tarn) and three tanytarsini (rheotanytarsus type kitandara, tanytarsini indet. type ellis, and tanytarsini indet. type large hall tarn); . two taxa occur at low and middle elevations up to the ericaceous zone, but are excluded from the alpine and nival zones: procladius brevipetiolatus and polypedilum type bandasa; . four taxa occur at all elevations from the basal plateau belt to the alpine zone: limnophyes minimus group, chironomus type kibos, chironomus near imicola and dicrotendipes pilosimanus; . two taxa appear to occur both in low-and mid-elevation lakes and in the alpine zone but not at intermediate altitudes: pseudosmittia type tanganyika and near paraphaenocladius type ol bolossat. combination of this east african mountain data set with similar chironomid death-assemblage data from east african lakes (uganda-kenya-ethiopia) at low to intermediate elevations ( - m a.s.l.; eggermont & verschuren, a,b) reveals the highly distinct character of african highmountain chironomid communities. this is illustrated in fig. , where the altitudinal distributions of the taxa recorded in this study are shown together with those of eight chironomid taxa widely distributed in east african freshwater lakes, along a combined altitudinal gradient ranging from to m a.s.l. these eight common taxa each occur in at least % of the freshwater lakes (conductivity < ls cm ) ) at low and middle elevations sampled to date (eggermont et al., ; lake nkunga and rurie swamp in this study), but are lacking in the high-mountain lakes studied here. among the chironomid taxa recorded to date in low-and midelevation east african lakes, only six (procladius brevipetiolatus, polypedilum type bandasa, pseudosmittia type tanganyika, near paraphaenocladius type ol bolossat, chironomus type kibos and chironomus near imicola) are here recorded from lakes above m, and only the latter four appear to penetrate into the afroalpine zone (but see discussion below). consequently a marked faunal transition occurs in lakes between c. and m a.s.l., i.e. broadly corresponding with the ericaceous zone of terrestrial vegetation. chironomid species diversity in the sampled high-mountain lakes (table : . taxa on average; es ¼ . ; n ¼ . ) is significantly lower than that in the two mid-elevation lakes on mount kenya (mean . taxa; es ¼ . ; n ¼ . ) or in the east african low-and mid-elevation lakes (mean . taxa; es ¼ . ; n ¼ . ). the biodiversity and biogeography of afroalpine ecosystems have long attracted interest from both botanists and zoologists. today these ecosystems occur on seven mountain ranges in equatorial africa (mount kenya, the nyandarua (aberdare) range, mount kilimanjaro, mount meru, mount elgon, the rwenzori mountains and the virunga mountains) and three mountain massifs in ethiopia (simien, arsi and bale), which are typically treated as a separate biogeographical region. the origins of afroalpine biota are predominantly local (tropical african) or palaearctic depending on the group, with typically smaller contributions from temperate south africa and other distant sources (harmsen et al., ) . in poorly dispersing terrestrial biota such as vascular plants (hedberg, ; harmsen et al., ) , mosses (spence & pocs, ) , flightless insects (brühl, ) and spiders (scharff, ) , each mountain has a significant component of locally endemic species. in plants and mosses, this component ranges from c. % on the aberdares and mount meru to c. % in the rwenzori, with a positive relationship to the area occupied, age and isolation from other mountains (harmsen et al., ) . in flightless insects, genera can be distributed widely over the different mountains but at the species level local endemism is the rule rather then the exception (brühl, ) . in contrast, highly mobile terrestrial biota such as mammals, birds and butterflies are mostly represented by eurytopic lowland species, and species diversity above the tree line is typically unimpressive. the occurrence of standing-water aquatic ecosystems in the afroalpine zone depends on present or past glacial activity carving out lake depressions or forming barriers to drainage, and on a positive water balance to fill those basins. consequently they are not evenly distributed across africa's highest mountains. the large majority occur on mount kenya and in the rwenzori. mount kilimanjaro (tanzania, fig. ), africa's highest mountain, is a relatively young intact volcano with only one known lake at high elevation (mawenzi tarn; m). on mount elgon (eastern uganda) and the nyandarua range (central kenya) only bogs and shallow swamps occur, and on the dry mount meru (northern tanzania) nothing more than a few seasonal ponds. in the ethiopian highlands, high-altitude depressions are mostly occupied by bogs, with the exception of lake garba guratch in the bale mountains (umer et al., ) . individual afroalpine lakes are ephemeral on geological time scales, as during quaternary ice ages most of their basins have repeatedly been occupied by glaciers. consequently, aquatic biota were not necessarily favoured by the larger and more contiguous afroalpine zone which occurred when the snowline was depressed (between and m on individual mountains; osmaston & harrison, ) and vegetation belts shifted downslope: their local persistence would have depended on the presence of alternative suitable lake habitat at intermediate elevations. this long-term instability of tropical cold-water habitat together with harsh abiotic table mean taxon richness, es and hill's n diversity (mean and standard deviation) for high-elevation african lakes (this study), east african low-and mid-elevation lakes (eggermont & verschuren, a,b) and lakes nkunga and rurie swamp on the lower slopes of mount kenya (this study) high elevation low and mid-elevation nkunga and rurie swamp no. of taxa . ( . ) . ( . ) . ( ) es . ( . ) . ( . ) . ( . ) n . ( . ) . ( . ) . ( . ) no. of lakes r u r i e s w a m p ( m ) * h y e n a d a m ( m ) o l b o l o s a t ( m ) n k u g u t e ( m ) k i f u r u k a ( m ) k a t a l i n ( m ) r u t u n d u ( m ) * b u j u k u ( m ) * u p p e r k i t a n d a r a ( m ) * l a r g e h a l l t a r n ( m ) * h a u s b u r g t a r n ( m ) * k i b e n g o ( m ) k y a s u n d u k a ( m ) k a r o l e r o ( m ) k y e r b w a t o ( m ) k a y i h a r a ( m ) n a i v a s h a ( m ) n k u n g a ( m ) * n a r a s h a ( ) b a n d a s a ( m ) * e l l i s ( m ) * l o w e r k i t a n d a r a ( m ) * j o s e p h a t ' s p o o l ( m ) * g r e e n ' s p o o l ( m ) * s i m b a t a r n ( m ) * chironomus near imicola ( conditions has resulted in low species diversity and endemicity in most groups of aquatic biota. for example, afroalpine phytoplankton communities are mainly composed of easily dispersing (aerophilic) cosmopolitan species, complemented by eurytopic tropical species (löffler, ) . zooplankton communities (cladocera, rotifera) appear to have modest species diversity and a mix of biogeographical affinities (löffler, (löffler, , lens, ) ; however, the often exceedingly low population abundances have so far complicated comprehensive sampling and a proper biodiversity assessment. the same being true for aquatic insects (löffler, ) , quantitative faunistic and ecological monitoring of afroalpine aquatic ecosystems is logistically challenging. our present dataset of chironomid communities in african high-mountain lakes (> m a.s.l.) permits distinction between: ( ) (eggermont & verschuren, a,b) ; consequently they must be cold-stenothermal species which are adapted to, and require, the harsh climatic conditions prevailing at the top of africa's highest mountains. night-time freezing can occur from c. m a.s.l. (i.e. the present-day tree line between bamboo forest and the ericaceous zone), but at m (transition between ericaceous zone and alpine zone) nocturnal frosts occur on - % of the nights and almost throughout the year (rundel, ) . the equatorial position of these mountain ranges creates daily oscillations in air temperature between ) and °c in the alpine and nival zones, an order of magnitude greater than the seasonal change in maximum daytime temperature. in the deeper lakes, night-time water-surface cooling and convection creates bottom temperatures approaching °c, as in seasonally stratified lakes in coldtemperate regions. shallow lakes often freeze over at night, and with the exception of the shallowest tarns, daytime warming heats up surface waters to, at most, - °c (table ) . as almost all life processes in holometabolous insects (egg survival and hatching rate, larval growth and feeding, pupation, emergence, flight and fecundity) are under temperature control (pinder, ) , african chironomidae whose larvae are restricted to these alpine lakes and tarns must evidently be cold-stenothermal. all but one of the eight recorded cold-adapted taxa are relatively small forms belonging to the subfamilies diamesinae, orthocladiinae and tanytarsini, which also dominate the chironomid fauna of alpine lakes and tarns in north-temperate regions (walker & mathewes, ; lotter et al., ) . the diamesinae in particular are a characteristic component of alpine chironomid faunas in the holarctic region (north america and eurasia). the three known east african diamesinae species are restricted to the ultra-oligotrophic waters of glacial tarns and streams on mount kenya, mount kilimanjaro and the rwenzori (freeman & cranston, ; willassen & cranston, ) . a handful of african orthocladiinae (cricotopus scottae, cricotopus albitibia, limnophyes natalensis, nanocladius saetheri, psectrocladius viridescens) are widely distributed in warm and productive lowland lakes (tudorancea et al., ; eggermont & verschuren, a) , but as a group the orthocladiinae contribute significantly to chironomid faunal diversity only in well-oxygenated waters of fast-flowing streams (harrison & hynes, ) , cool forest rivers (lehmann, ) and the rare unproductive african lakes at low elevation (e.g. lake tanganyika; eggermont & verschuren, a) . here in cold, unproductive mountain lakes we find orthocladiinae to be common both in number of taxa ( of , or . %) and absolute abundance ( . % of total yield). of the eight taxa constituting groups ( ) to ( ), i.e. those not restricted to the afroalpine ecosystem, six have previously been found in lowland african lakes. the group ( ) species procladius brevipetiolatus and polypedilum type bandasa can be considered warm-adapted tropical elements, as also are the majority of tanypodinae and chironomini which we only encountered in rurie swamp and/or lake nkunga (table ; fig. ). group ( ) includes at least two distinct, well-defined species that can be considered as positively eurythermic: chironomus type kibos and chironomus near imicola. their known distribution in equatorial east africa now encompasses both alpine tarns of °c and lowland tropical lakes with (bottom-water) temperatures of up to °c (fig. ) . the other two morphotaxa of group ( ) may include more than one biological species, therefore their apparent altitudinal distribution may be an artefact of inadequate discrimination of subfossil remains. the disjunct distribution of group ( ) taxa similarly indicate that their high-mountain populations actually represent a different species, which at present cannot be separated consistently on the basis of morphological features on the larval head and mouthparts. we found that the chironomid communities in african highmountain lakes are comparatively poor in species: their mean local species richness is significantly lower than that in the two mid-elevation lakes on mount kenya studied here or east african low-and mid-elevation lakes in general (table ). this is also typical of cold, ultra-oligotrophic alpine lakes elsewhere (bretschko, ) . however, the combined chironomid species diversity of taxa now recorded is high compared with that of other groups of resident aquatic insects and crustacean zooplankton (löffler, (löffler, , , especially taking into account that this study covers only c. % of present-day afroalpine lake ecosystems. in the present data set, % of this diversity are cold-stenothermal taxa restricted to these systems. these chironomidae, and their diagnostic remains preserved in lake-sediment records, thus constitute valuable biological indicators to monitor past and future environmental change affecting the hydrology and temperature regime of scarce glacier-fed aquatic ecosystems in tropical africa. our exploratory data set currently lacks the coverage to address conclusively the question of endemism among afroalpine chironomidae, either local (individual mountain ranges), regional (e.g. equatorial east african mountains vs. the ethiopian highlands) or continental (e.g. afrotropical vs. palaearctic). given efficient long-distance dispersal of adult midges (armitage et al., ) , there is no reason to expect a high proportion of local endemics (i.e. restricted to just one mountain range) among the chironomidae inhabiting africa's high-mountain lakes, unlike the situation in less mobile afroalpine biota such as vascular plants, mosses and flightless insects. among the eight cold-stenothermous taxa encountered only chaetocladius melaleucus, paratrichocladius type hausburg tarn and paratrichocladius type simba tarn were found both on mount kenya and in the rwenzori, but with only c. % of potential habitat on the two mountains sampled, this small proportion of shared species is not likely to be a true reflection of the shared fauna. afrotropical diamesa do show species differentiation between mountains (d. kenyae and d. freemani on mount kenya, d. rwenzoriensis in the rwenzori; diamesa has not yet been recorded on mount kilimanjaro: freeman, ; willassen & cranston, ) , but with the caveat that distribution records for the adult midges are as fragmentary as they are for larvae. the chironomid fauna of ethiopian mountain streams ( sites between and m a.s.l.) is strongly linked with those of east and south african counterparts (harrison & hynes, ) . likewise, inventory of the forest river kalengo in the democratic republic of congo (c. m a.s.l.; lehmann, ) yielded several species with continent-wide african distribution. part of this pattern of widespread species distribution may be credited to the occurrence of cool forest-river systems over large contiguous areas in east and central africa. by contrast, true cold-water lakes with (bottom) temperatures of - °c or less are restricted to the few isolated islands of africa's highest mountain ranges, which are separated by large expanses of warm lowlands (fig. ) . still, regional endemism in afroalpine chironomidae between the group of seven equatorial east african mountain ranges and other african highland regions is not likely to be substantial, if only because of the general lack of afroalpine standing-water ecosystems outside of equatorial east africa, with the exception of one lake and a handful of bogs in the ethiopian arsi and bale mountains. similarity of cold-stenothermal chironomid faunas among africa's mountain ranges, and between tropical africa and the palaearctic region may, in addition to present-day dispersal, also reflect improved conditions for long-distance dispersal in the past (kingdom, ) . willassen & cranston ( ) suggested a more or less continuous dispersal route for alpine aquatic biota between the east african mountains and eurasia during the mid-tertiary period. this route would have stretched from the caucasus through the near east to the ethiopian highlands, and allowed colonization of east africa by strictly cold-stenothermal taxa. prominent among these are diamesa and african montane orthocladiinae such as chaetocladius melaleucus (meigen) that are considered to have a palaearctic or nearctic origin (willassen & cranston, ) . limnophyes minimus (meigen) and l. natalensis (kieffer), here combined into epler's ( ) limnophyes minimus group, are both widely distributed throughout europe and north america, and even occur on some sub-antarctic islands (saether, ) . african chironominae with montane distribution patterns are proposed to have used the same route but in either direction (harrison & hynes, ) . one example is dicrotendipes pilosimanus (kieffer), which besides africa's eastern and southern highlands also occurs throughout the middle east, the balkans and the oriental region (epler, ) . although the reality of intercontinental dispersal of coldadapted biota between eurasia and africa is unquestioned, improved knowledge of africa's tectonic and palaeoclimatic history argues against a prominent role of mid-tertiary faunal exchange. first, the oligocene period of world-wide cooling [ - million years ago (ma)], which is supposed to have created a stepping-stone corridor of cold mountain environments from eurasia to east africa, was most probably still as warm or warmer than today (zachos et al., ) , and was followed by myr of late oligocene and miocene warming ( - ma), at which time no glaciers can have existed at tropical latitudes. second, although eocene volcanic activity in the incipient east african rift system (c. - ma) extruded sequences of flood basalt up to . km thick in present-day ethiopia, northern kenya and southern arabia (ebinger et al., ; tiercelin & lezzar, ) , there is no evidence for temporal continuity of high-mountain environments in east africa between this period of early rifting in the north, and the main uplift of the aberdares in the late miocene, the rwenzori in the pliocene or the formation of mount kenya c. ma (barker et al., ; pickford et al., ; ebinger et al., ) . abundant palaeoclimatic evidence shows that over the entire period from ma to the present global cooling was most extreme during late quaternary glaciation (zachos et al., ) , the major ice ages which occurred at roughly , year intervals over the past , years (e.g. raymo, ) . during this period, global cooling relative to the present has been the rule rather than the exception: interglacial climate conditions similar to those of the current holocene epoch prevailed during c. % of the time (epica, ) . therefore, faunal exchange between africa's high-mountain environments and eurasia has almost certainly been most prominent not during the mid tertiary but during late quaternary glacial episodes, and as recently as , - , years ago. it is commonly assumed that afroalpine ecosystems persisted continuously since the late pliocene (axelrod & raven, ; harmsen et al., ) , but probably not much longer. the oldest concrete evidence for mountain glaciation in equatorial east africa is in fact decidedly younger: c. , years on mount kilimanjaro (downie, ) , c. , years on mount kenya (shanahan & zreda, ) and > , years in the rwenzori (osmaston & kaser, ) . besides the three currently snow-capped mountains, extensive field evidence for late quaternary glaciation, and by implication the existence of glacier-fed lakes and streams, exists in the ethiopian highlands (umer et al., ) and on most other east african massifs higher than m (reviewed in osmaston & harrison, ) . at that time, mean annual temperature in mountainous regions was reduced by - °c (porter, ) , and snowlines were depressed by - m (kaser & osmaston, ) . vegetation belts shifted downslope and contracted, extending the afroalpine zone to c. m a.s.l. (mahaney, ) . the seven current afroalpine enclaves in equatorial east africa must have increased somewhat in size (harmsen et al., ) but not substantially so, and only very few new enclaves with probable afroalpine abiotic conditions were formed in the cherangani hills of northern kenya, the ngorongoro area west of mount meru, and the mitumba range of eastern democratic republic of the congo. only when including the entire faunal transition zone (fig. ) , of which the lower boundary may have extended to c. m, can it be proposed that cold-stenothermal african chironomidae potentially enjoyed significantly more widespread distributions and increased dispersal between individual mountain systems during quaternary glaciation periods. broad swaths of highlands at that elevation lie both among the eastern (mount elgon, mount kenya, nyandarua, mount kilimanjaro, mount meru) and western (rwenzori, virunga) equatorial mountains, and among the three ethiopian massifs, and substantial new stepping stones between these three mountain regions may have occurred in the uganda-sudan border region. for the aquatic midge larvae in question, the true limiting factor on glacial-time distribution would have been the occurrence of permanent open water bodies within the altitude range of suitable abiotic conditions, as is the case today. through study of recent death assemblages of larval remains in surface sediments, we found that the chironomid fauna of high-elevation (> m a.s.l.) lakes and tarns on glaciated mountains of equatorial east africa is diverse in species and highly distinct from that of low-and mid-elevation african lakes. the faunal transition zone coincides broadly with the ericaceous zone of terrestrial vegetation, where night freezing becomes increasingly more common with altitude. eight taxa, or % of total species richness, appear restricted to the specific habitat of cold holomictic lakes in the alpine and nival zones (> m a.s.l.), and can thus be considered true afroalpine elements. the question of endemism among afroalpine chironomidae at either a local, regional or continental scale remains largely unanswered at this time, but taking into account the restricted occurrence of glacier-fed lakes and tarns on africa's highest mountains we surmise that the chironomid fauna of these tropical cold-water ecosystems is potentially unique on a continental scale. by virtue of their excellent preservation and their spatial and temporal integration of local community dynamics, chironomid larval death assemblages extracted from surface sediments are powerful biological proxy indicators to monitor the potentially dramatic hydrological and ecological changes associated with the retreat of africa's alpine glaciers. in north-temperate regions, chironomid palaeoecology is already an established instrument to reconstruct past histories of climate-driven temperature and ecological change (battarbee, ) . initial demonstration, from surface-sediment larval death assemblages, of strong altitudinal and latitudinal gradients in chironomid species distribution (walker & mathewes, ; walker & macdonald, ) resulted in the development of chironomid-based quantitative inference models for reconstruction of past variations of air and water temperature in both north america and europe walker et al., ; larocque et al., ) . reconstruction of africa's climate history from natural climate archives such as lake sediments will be essential to amend the current scarcity of information on natural tropical climate variability and help forecast the fate of afrotropical ecosystems over the next centuries. given the difficulty of separating the effects of changes in temperature and moisture balance on geochemical records of african climate change (gasse, ) , an independent and reliable proxy indicator for past temperature change in africa would be most welcome (verschuren, ) . documentation in this study of the distinct character of chironomid communities inhabiting africa's true cold-water lakes is a first step towards chironomid-based reconstruction of past temperature change in africa, and improved understanding of past and future tropical climate dynamics. hilde eggermont is post-doctoral fellow with the research foundation of flanders (fwo-vlaanderen), belgium. she studies subfossil larval chironomidae preserved in african lake sediments with emphasis on taxonomy, biogeography and their use as quantitative indicators for past environmental changes in lakes. this includes palaeoclimate reconstruction and historical biomonitoring of the various anthropogenic impacts to which african lakes are exposed. dirk verschuren is research professor in ecology at ghent university, belgium. his research interests include african climate history and the long-term dynamics of african lake ecosystems. he exploits multiple proxy indicators preserved in lake-sediment records to reconstruct past climate dynamics at decadal to millennial time scales, and the evolution of human impact on african lakes and their drainage basins. editor: john lambshead lerheimia, a new genus of orthocladiinae from colosmittia clavata gen. n., sp. n., a new orthoclad from the west usambara mountains, tanzania (diptera: chironomidae) usambaromyia nigrala gen. n., sp. n. and usambaromyiinae, a new subfamily among the chironomidae (diptera) the chironomidae: biology and ecology of non-biting midges late cretaceous and tertiary vegetation history of africa stratigraphy, geochronology and volcano-tectonic evolution of the kedong-naivasha-kinangop region palaeolimnological approaches to climate change, with special regard to the biological record the chironomid fauna of a high alpine lake (vorderer firstertaler see), tyrol, austria, m asl flightless insects: a test case for historical relationships of african mountains larves de chironomidae (diptera nematocera) the ecology of the alpine zone of mount kenya zur kenntnis der jugendstadien von dicrotendipes septemmaculatus (becker, ) (diptera, nematocera, chironomidae). zeitschrift arbeitsgem. 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environmental research on east african mountains notes on some larval and pupal chironomids (diptera) from lake kariba, rhodesia the contribution of increased incoming shortwave radiation to the retreat of the rwenzori glaciers, east africa, during the th century de larven der nederlandse chironomidae (diptera) -inleiding, tanypodinae en chironominae de larven der nederlandse chironomidae (diptera) -orthocladiinae sensu lato rwenzori mountains national park the late quaternary glaciation of africa: a regional synthesis uresipedilum sasa et kikuchi, (diptera: chironomidae), with a review of the subgenus benthic fauna of a tropical man-made lake geology and paleobiology of the albertine rift valley the habitats of chironomid larvae. the chironomidae: the biology and ecology of non-biting midges snowline depression in the tropics during the last glaciation primer version . . . roborough, plymouth global climate change: a three million year perspective an identification guide to sub-fossil tanypodinae (insecta: diptera: chironomidae) based on cephalic setation tropical alpine climates. tropical alpine environments. plant form and function glossary of chironomid morphology terminology (diptera: chironomidae). entomologica scandinavica supplement a review of the genus limnophyes eaton from the holarctic and afrotropical regions (diptera: chironomidae, orthocladiinae). entomologica scandinavica supplement afrotropical records of the orthoclad genus mesosmittia brudin (diptera: chironomidae). spixiana lobosmittia, a new genus of orthoclads from tanzania and turkey (diptera: chironomidae) ionthosmittia cudiga n. gen. n. sp., a new orthoclad from the usambara mts, tanzania (diptera: chironomidae) first afrotropical records of doithrix and georthocladius, with notes on the pseudorthocladius group (diptera: chironomidae) euryhapsis fuscipropes sp. n. from china and tokyobrillia anderseni sp. n. from tanzania, with a review of genera near irisobrillia oliver (diptera: chironomidae) the linyphiid fauna of eastern africa (aranea: lyniphiidae) -distribution patterns, diversity and endemism hydrobiological studies on the great berg river, western cape province. part . the chironomidae chronology of quaternary glaciations in east africa distribution patterns in the afroalpine moss flora of east africa. quaternary and environmental research on east african mountains statistica for windows tanytarsus usambarae spec. nov. from west usambara mts kilimanjaro ice-records: evidence of holocene climate change in tropical africa a million year history of rift lakes in central and east africa: an updated broad review a comparitive limnological study of zoobenthic communities in lakes of the ethiopian rift valley. archiv für hydrobiologie supplement quaternary glacial activity on the ethiopian mountains. quaternary glaciations -extent and chronology taxonomy and ecology of sub-fossil chironomidae (insecta: diptera) from rift valley lakes in central kenya lake-based climate reconstruction in africa: progress and challenges distributions of chironomidae (insecta: diptera) and other freshwater midges with respect to treeline chironomid (diptera) remains in surficial lake sediments from the canadian cordillera: analysis of the fauna across an altitutional gradient efficient separation of sub-fossil chironomidae from lake sediments. hydrobiologia an expanded surface-water palaeotemperature inference model for use with fossil midges from eastern canada identification of larvae of european species of chironomus meigen (diptera: chironomidae) by morphological characters chironomidae of the holarctic region -keys and diagnoses afrotropical montane midges (diptera, chironomidae, diamesa) trends, rhythms and aberrations in global climate ma to present fieldwork was conducted under uganda ncst research clearance ec and kenya government research permit moes/ / c, and sponsored by the leopold iii fund and the research foundation of flanders (fwo-vlaanderen), belgium. we thank the uganda wildlife authority and kenya wildlife service for permission to sample lakes in the rwenzori and mount kenya national parks. we also thank wibjorn karlén, daniel olago and bob rumes for field support, and alayne street-perrott and philip barker for providing additional study material. key: cord- -efc msf authors: blumberg, lucille title: severe malaria: manifestations, diagnosis, chemotherapy, and management of severe malaria in adults date: journal: tropical and parasitic infections in the intensive care unit doi: . / - - - _ sha: doc_id: cord_uid: efc msf nan the burden of malaria is increasing, especially in sub-saharan africa, because of drug and insecticide resistance and social and environmental changes ( ). each year an estimated three to four hundred million people will contract malaria globally, resulting in five hundred thousand to two million deaths. ninety percent of the world's malaria, and at least % of malaria-related mortality, occurs in sub-saharan africa, primarily in young children ( ). malaria occurs in every country in sub-saharan africa, with the exception of lesotho, but transmission rates vary within regions and within countries. in parts of africa where endemicity of malaria is high and transmission stable, such as tanzania, malawi, and mozambique, severe malaria is mainly a disease of children under years of age and of pregnant women. it is less common in older children and adults because of the partial immunity acquired as a result of repeated infections. in areas of low endemicity severe malaria occurs in both adults and children. non-immune travellers to malaria areas are always at risk for severe disease ( , ). the majority of malaria cases in africa are due to plasmodium falciparum, the major species associated with mortality and morbidity. the development of parasite resistance to chemotherapeutic agents such as chloroquine has resulted in a significant increase in malaria morbidity and mortality. the demise of chloroquine, an affordable option in resource-poor countries, has major implications for malaria management ( ). in africa resources for management of severe malaria are limited and at least - % of patients with complications of disease will die. in a confidential inquiry into malaria deaths in an area of south africa with limited tertiary care facilities, major contributing factors were delays in diagnosis and initiation of adequate therapy, failure to administer the correct antimalarial at the correct dosage and frequency, inadequate monitoring of severity indicators in complicated cases, and the suboptimal management of complications ( ). key features of malaria are the adherence of infected red blood cells to the endothelium of small blood vessels compromising blood flow through tissues, and the production of pro-inflammatory cytokines ( ). factors that determine whether a patient develops mild or severe disease are complex and multifactorial and are related to both the parasite and the host. parasites causing severe malaria have a greater multiplication potential than those causing uncomplicated infections ( ). the effect of inoculum dose on severity is unclear and difficult to investigate. cyto-adherence of parasitised red cells may be influenced by the virulence of different strains of parasite ( ). the development of immunity to the clinical effects of malaria requires several years of continuous exposure. lack of this protective immunity would be expected to be the major factor determining the severity of a clinical attack of malaria. differences in hla antigens may play a role in host predisposition to severe disease. certain red blood cell abnormalities, including sickle-cell trait, protect against malaria disease. prevalence rates of these abnormalities are high in some parts of africa and may provide some protection against severe malaria ( ). plasma interleukin (il- , il- ) and tumour necrosis and the il- : il- ratio is significantly higher in patients who die than in survivors ( ). symptoms and signs of malaria may present as early as seven days, but more commonly an average of - days after being bitten by an infected mosquito. fever is prominent, but may be absent in some cases. some of the following symptoms may also appear: rigors, headache, myalgia, diarrhoea, vomiting and cough. physical signs may include fever, anaemia, jaundice, hepatosplenomegaly and a variety of cerebral signs. malaria should be suspected in any person presenting with any of the above symptoms or signs with a history of travel to, or residence in a malaria transmission area. presentation is very variable and may mimic other diseases, including influenza, hepatitis, meningitis, septicaemia, typhoid, tickbite fever, viral haemorrhagic fever, trypanosomiasis, hiv seroconversion illness, and relapsing fever ( ). p. falciparum infections may progress rapidly to a lethal, multi-system disease. the diagnosis of malaria is urgent, and complications can develop rapidly within hours of the onset of disease in any non-immune person but especially in young children and pregnant women ( ). the clinical manifestations of severe malaria depend on the age of the patient. in children, hypoglycaemia, convulsions, and severe anaemia are relatively common; acute renal failure, jaundice, and ards are more common in adults. cerebral malaria, shock and acidosis may occur at any age ( ). a number of clinical and laboratory criteria are used to define severe malaria, as shown in table ( , ). patient blood should be examined immediately to confirm or exclude the diagnosis of malaria. in the majority of cases of severe malaria, examination of correctly stained blood smears will reveal malaria parasites, however, a negative smear does not exclude the diagnosis, and repeat smears are indicated. some patients with severe malaria may have a negative smear due to sequestration of parasitised red blood cells, and a decision to treat with antimalarial chemotherapy should be considered if the index of suspicion is very high. in these cases it is imperative to continue to look for alternative diagnoses, especially trypanosomiasis, septicaemia and viral haemorrhagic fever. high levels of parasitaemia are generally predictive of severe malaria in nonimmune patients. importantly, the converse may not be true, with severe disease also occurring with low parasitaemias in the peripheral blood ( , ) . quantification is often inaccurate, peripheral parasitaemia may not reflect the total parasite load and sequestration in the organs, and levels of parasitaemia may vary cyclically. prognosis worsens considerably if p. falciparum schizonts are present in a blood smear, and if more than % of peripheral polymorphonuclear leucocytes contain visible malaria pigment ( ). commercial kits are available that rapidly detect parasite antigen or enzymes. the tests for p. falciparum are highly sensitive, but depend on correct usage, interpretation of results, and the quality of the particular test used. these tests can only be used for diagnosis of acute malaria infections, and not for follow-up, as the test may remain positive for several weeks, even after successful treatment ( ). in a febrile patient where there is no obvious cause of fever, and a recent history of visiting or living in a malaria area is not forthcoming, malaria should still be excluded, as infected mosquitoes have been documented to travel long distances in road, rail and air transport. mortality is high in this group of patients, because of missed diagnosis, but a finding of thrombocytopenia should always stimulate a search for possible malaria parasites ( ). patients should be treated urgently with the most effective treatment regimen available, in a facility with the highest level of care. the choice of chemotherapy for malaria is dependent on the severity of disease, the known or suspected resistance pattern of the parasite in the area where the malaria infection was acquired, the species of parasite, and patient profile (age, pregnancy, comorbidity, allergies, and medications, including any antimalarials recently administered). quinine, the drug of choice for the treatment of severe malaria in africa, is rapidly effective ( , ). in most parts of africa quinine resistance has not developed. in some parts of west africa however, foci of low-level resistance have been documented ( ). an initial loading dose of quinine to rapidly reach a therapeutic level is critical in the management of severe malaria and has a major impact on favourable outcome. the loading dose should be omitted if the patient has definitely received mefloquine, quinine, quinidine or halofantrine in the previous hours, mefloquine in the previous seven days, or mg/kg of quinine in the previous two days. if there is doubt, the loading dose of quinine should be given ( , , ) . the loading dose is given as quinine di-hydrochloride salt, mg/kg body weight diluted in - ml/kg body weight of dextrose water, by slow intravenous infusion over two to four hours. quinine must never be administered by bolus intravenous injection, as this is associated with cardiotoxicity. the loading dose is given strictly according to body weight. the disposition of quinine in very obese patients is not known. it has been suggested that there is a ceiling dose above which quinine should not be given, but there is no evidence to support this ( ). six to eight hours after starting the loading dose, a maintenance dose of quinine di-hydrochloride salt, l mg/kg diluted in - ml/kg body weight of a dextrose-containing solution should be commenced and infused over - hours. intravenous quinine should be administered every eight hours until the patient can take oral medication (usually by hours). for obese patients, the maintenance dose should be calculated according to ideal body weight ( ). males: ibw (kg) = . x height in cm - females: ibw (kg) = . x height in cm - . the dosage of oral quinine is l mg/kg/dose or mg/dose given three times a day. the total duration of quinine therapy is - days. additional drugs, tetracycline (usually as doxycycline mg twice a day x days), or clindamycin (l mg/kg twice a day x days) are recommended to improve cure rates ( , , ). these, however, do not add initial therapeutic benefit, may contribute to drug side effects, and should be introduced only once the patient is improving. quinine can be administered by deep intramuscular injection if intravenous infusion is not possible ( ). quinine has a narrow therapeutic window, although serious side effects are rare. the pharmacokinetic properties of quinine are altered considerably in malaria with a contraction in the volume of distribution and a reduction in clearance that is proportional to the severity of disease ( ). there is significant binding of quinine to acute phase reactants, notably glycoprotein, with reduction in the levels of free quinine. quinine toxicity is, therefore, relatively uncommon ( ). the most frequent side effect of quinine therapy is hypoglycaemia, especially in children and pregnant women ( , ) . although quinine may prolong the qtc-interval, hypotension, heart block, and ventricular arrhythmias are rare ( , , ) . convulsions and visual disturbances have been reported as idiosyncratic responses or with overdosage ( , ). doses should be reduced by - % after the third day of treatment to avoid accumulation of the drug in patients who remain seriously ill, especially those with evidence of renal failure ( ). the measurement of levels of free (not total) quinine may be helpful in patients with severe malaria and renal failure, but accessibility to this test is very limited. the precise level has not been defined but probably lies between . - mg/l ( ). quinidine is more active than quinine, but is also more cardiotoxic and more expensive, is not readily available, and consequently is not used for treating severe malaria in africa ( ). in the early 's chinese scientists identified artemisinin, a sesquiterpene lactone peroxide, as the principal active component of the traditional chinese malaria remedy, qinghaosu. artemisinin and two derivatives, artesunate and artemether are effective against multi-drug resistant p falciparum and clear sensitive parasites from the blood more rapidly than other antimalarial agents due to their broad stage specificity of anti-malarial action. despite administration to over million people, resistance has not emerged, and only rarely has treatment failure been reported. the drugs are well tolerated and despite neurotoxicity in animal studies, serious adverse reactions have included only a few case reports of anaphylaxis. the chemical structure and mode of action of these drugs distinguish them from other currently available antimalarial agents, and render them less vulnerable to cross-resistance. however, when used alone, unacceptably high recrudescence rates are seen ( , , , ). combination therapy, which includes an artemisinin, is the recommended malaria treatment policy to delay the emergence of drug resistance to sequential monotherapy, as well as to improve cure rates. drugs used in combination with the artemisinins include mefloquine, sulfadoxine pyrimethamine, amodiaquine and lumefantrine, and the choice depends on parasite resistance in the geographical area ( ). there are parenteral preparations of the artemisinins, either intramuscular (artemether, arteether, artesunate) or intravenous (artesunate). artemether and arteether are oil-based preparations and absorption from the intramuscular site may be compromised in severe malaria, leading to treatment failures ( ). artesunate is water-based, can be given intravenously, or intramuscularly from where it is well absorbed. although theoretically preferable, there are no large comparative trials to indicate whether artesunate is superior to artemether or quinine ( ). the use of parenteral artemisinins is limited by availability and manufacturing practices, which may not adhere to international standards. a meta-analysis of randomized clinical trials comparing the efficacy of artemether with quinine in the management of severe malaria demonstrated equality, but indicated a trend toward greater effectiveness of artemether in regions where there is recognised quinine resistance. artemether was superior to quinine in terms of overall serious adverse events ( , ). in patients with hyperparasitaemia there may be an advantage of the artemisins over quinine. in south-east asia, where multi-drug-resistant malaria is a major problem and quinine resistance has emerged, the artemisinin drugs are used as first-line therapy for severe malaria ( ). widespread, high-level chloroquine resistance precludes the use of chloroquine in the treatment of both uncomplicated and severe malaria in most parts of the world, including africa. sulfadoxine pyrimethamine, mefloquine and halofantrine are not indicated in the management of severe malaria ( ). anaemia may result from haemolysis or dyserythropoeisis ( ). severe anaemia is defined as a haemoglobin of less than g/dl, or haematocrit < %. severe anaemia is the most important manifestation of severe malaria in areas of high stable transmission and occurs predominantly in children. pregnant women may also present with profound degrees of anaemia. anaemia may manifest as shock, cardiac failure, hypoxia, or confusion and the rate at which anaemia develops is an important determinant of compensatory mechanisms. blood transfusion using packed cells should be considered in patients in whom the haemoglobin is g/dl or less, especially those with cardiovascular decompensation. fluid overload must be avoided. transfused blood has a reduced lifespan in malaria patients ( ). in many parts of the world cerebral malaria is the most common clinical presentation and cause of death in adults with severe malaria. the term cerebral malaria in many published studies is restricted to the syndrome in which altered consciousness associated with a malaria infection could not be attributed to convulsions, sedative drugs or hypoglycaemia alone or to a non-malarial cause. cerebral malaria may be part of multi-system pathology, in which case the outlook is much poorer than if disease was localised only to the central nervous system. clinically, the commonest neurological picture is of a symmetrical upper motor neuron lesion, mild neck stiffness is not uncommon, and muscle tone and tendon reflexes are variable. cerebral malaria can resemble bacterial or viral meningitis and a lumbar puncture should be considered in patients where the diagnosis is not clear. hypoglycaemia, metabolic disturbances, severe anaemia and hypoxia as a result of malaria can all present with signs of central nervous system dysfunction. generalised or focal convulsions may occur as a result of cerebral malaria, or in association with hypoglycaemia ( ). imaging of the brain commonly shows evidence of mild cerebral swelling. oedema is very unusual, and may be an agonal phenomenon ( , ). studies to date with dexamethasone or mannitol have not shown benefit and have been associated with prolongation of coma and gastro-instestinal haemorrhage ( ). anticonvulsants should only be used once convulsions occur, and should not be used prophylactically ( ). the use of ironchelating agents has not been shown to impact on mortality ( ). in adult patients who recover, neurological sequelae are uncommon. renal failure is an early complication of severe malaria in adults. hypovolaemia, sequestration of parasitised red cell in the renal vasculature, intravascular haemolysis and haemoglobinuria are implicated and may lead to acute tubular necrosis. renal failure is generally oligaemic and hypercatabolic. a serum creatinine of greater than or a rapidly rising creatinine and/or a urine output of < ml/day in an adult should be regarded as renal failure. a central venous catheter (cvp) should be inserted and dehydration should be corrected. the cvp should not be above cm of water. the indications for dialysis are the same as for patients with other diseases, but since renal failure in malaria occurs against a background of a hypercatabolic state and non-renal causes of acidosis frequently co-exist, early dialysis is recommended ( ). venovenous haemofiltration is the recommended mode of dialysis and is significantly more efficient than peritoneal dialysis ( ). quinine is not removed by dialysis and in patients with severe malaria and renal failure, the dosage of quinine should be reduced by half to one-third after days of full dosage administration. if the patient survives the acute phase of the disease and has no pre-existing underlying disease, recovery of renal function generally occurs within three weeks ( ). this is a grave complication of severe falciparum malaria in adults, and may present several days after commencing malaria chemotherapy. the cause of this often lethal complication is unknown in falciparum malaria. some cases show evidence of pulmonary oedema while others resemble acute respiratory distress syndrome. pregnant women are particularly at risk. latrogenic overadministration of fluids may contribute to the development of ards or pulmonary oedema and should be avoided. some patients may require ventilatory support ( , , , ) . although a raised indirect bilirubin due to haemolysis is a frequent finding in malaria, the clinical presence of jaundice or the finding of raised hepatic transaminases x normal) should alert the clinician to the probability of severe malaria. the presence of jaundice combined with renal failure and acidosis may indicate a grave prognosis ( ). dic is rare in patients with severe malaria although laboratory evidence of haemostatic abnormalities may be present without bleeding. moderate degrees of thrombocytopenia are noted in the majority of cases of uncomplicated malaria unassociated with other coagulation abnormalities and bleeding is uncommon. possible mechanisms of thrombocytopenia include sequestration in the spleen, decreased production, or reduced survival from intravascular lysis. platelet transfusion should be considered if the platelet count is less than or if there is evidence of bleeding. platelet counts should return to normal within a few days with effective malaria treatment. continuing thrombocytopenia may indicate failed antimalarial therapy, sepsis, or a drug reaction to quinine ( ) secondary bacterial infections may complicate malaria: aspiration pneumonia, urinary tract infections or nosocomial septicaemia. in a significant number of patients, especially children, septicaemia may complicate severe malaria very early. salmonella species and staphylococci are common causes of septicaemia. the syndrome is associated with high mortality. since the features of bacterial sepsis and malaria overlap, empiric treatment using a broad-spectrum antibiotic for gram-positive and gram-negative organisms is recommended ( ). metabolic acidosis is a consistent feature of severe malaria. lactic acidosis is a major cause of death from severe falciparum malaria. the pathophysiology of acidosis is multifactorial and results from tissue hypoxia and anaerobic glycolysis, liver dysfunction and impaired renal handling of bicarbonate. the presence of acidosis is an important predictor of poor outcome ( ). the management of acidosis includes correction of fluid balance, improvement in haemodynamic status, and haemodialysis ( ). the use of dichloracetate has been shown to be beneficial in animal models. the pathogenesis of this rare condition is unknown, and is seen in patients with g- -pd deficiency who receive oxidant drugs. it may also occur in patients without apparent g- -pd deficiency but who have severe malaria and are treated with quinine or artemisinin derivatives. intravascular haemolysis results in anaemia, and the passage of haemoglobinuria. a small minority will develop renal failure, the cause of which is unknown. in patients with malarial haemoglobinuria, quinine chemotherapy should be continued. supportive therapy includes blood transfusions for severe anaemia, maintaining adequate hydration, and renal dialysis where indicated ( , ). hypoglycaemia may result from impaired glycolysis or gluconeogenesis, or as a result of quinine-induced hyperinsulinaemia. it is a particular problem in pregnant women and patients on intravenous quinine. blood glucose should be monitored, as the signs may be very subtle. hypoglycaemia must be excluded in all patients with an altered mental state and in those who present with convulsions ( ). shock may occur as a result of hypovolaemia, massive blood loss from splenic rupture or gastrointestinal haemorrhage, bacterial septicaemia, hypoxia and severe metabolic acidosis. myocardial function is remarkably good in severe falciparum malaria and most patients have an elevated cardiac index ( ). hypovolaemia should be corrected with an appropriate intravenous infusion, usually . % saline initially, followed by a plasma expander. the central venous pressure should not be allowed to exceed cm. if hypotension persists, inotropes should be administered ( ). the placenta acts as a haven for parasites due to upregulation of adhesion receptors. the course of malaria in pregnancy is rapidly progressive and common complications are anaemia, hypoglycaemia and ards. the risk of severe disease extends into the immediate postpartum period. malaria may cause abortion, premature delivery and low birth-weight. the management remains the same as in non-pregnant patients, with emphasis on preventing and managing the complications mentioned. in particular, fluid restriction is important to prevent ards. quinine is the drug of choice but may be associated with intractable hypoglycaemia. the use of the artemisinin drugs is currently not indicated due to a lack of safety data, unless there is evidence of quinine resistance. there is no indication to terminate pregnancy. in areas of high malaria transmission, anaemia is the most common manifestation of severe disease and placental parasitaemia is associated with low birth-weight infants ( ). the non-falciparum malarias are not generally associated with severe disease due to a lack of sequestration of parasitised red cells. rarely plasmodium vivax has been associated with the development of ards and cerebral malaria ( , ) . mixed infections with falciparum malaria occur occasionally and should be managed as for falciparum malaria. malaria and human immunodeficiency virus (hiv) infections are common, widespread and overlapping problems in africa. any interaction between these two pandemics would be of great importance. this interaction could be in either direction, with malaria causing more rapid progression of hiv, and hiv-associated immunosuppression leading to an impaired immune response to malaria. greater parasite densities and rates of clinical malaria have been demonstrated in hiv-positive patients from uganda, an area of high malaria endemicity, where the majority of people would be expected to have developed some malaria immunity ( , ) . in a cohort study of non-immune patients with malaria in south africa, hiv-positive patients had an increased rate of severe malaria compared to hiv-negative patients, and the rate increased as cd + cell count decreased. hiv-positive patients had significantly increased rates of renal failure, severe anaemia and dic ( ). the efficacy of exchange transfusion as adjunctive therapy for severe malaria is controversial. no sufficiently powered, randomized, controlled study has been reported, although anecdotal case reports in the literature indicate benefits in selected groups of patients with hyperparasitaemia and organ failure ( , ). a meta-analysis of eight studies comparing survival rates associated with exchange transfusion to survival rates with antimalarial chemotherapy alone did not show improved survival rates in the former groups of patients. there were significant problems with the comparability of treatment groups in the studies reviewed, with higher levels of parasitaemia and more severe malaria in the group who received transfusions ( ). recent studies suggest that the benefits associated with exchange transfusion result from replacing the rigid, non-deformable parasitised and unparasitised red cells with fresh blood, and not from reducing parasite load or removal of toxins or cytokines ( ). requirements for exchange transfusion include the availability of pathogen-free compatible blood, facilities for adequate clinical monitoring, and a haemodynamically stable patient. exchange transfusion may be considered in a patient who is seriously ill and the parasitaemia exceeds %. exchange should still be considered with parasitaemia in the range of - %, if there are other signs of poor prognosis. there is no consensus of the volume of blood to be exchanged for a given parasitaemia and the volumes have varied from litres to litres. blood may be exchanged using a double-lumen catheter or alternatively via haemodialysis ( , ). successful red blood cell exchange using a cell separator has been reported ( ). in a study conducted in a well-established intensive-care unit in south africa, despite appropriate chemotherapy with quinine, and standard intensive-care support including inotropic agents, ventilatory support and haemodialysis where appropriate, mortality was . % in a group of patients ( adults and children). pregnancy was a major cause of unfavourable outcome. ards was the most important cause of death. high apache ii scores, high arterial lactate, and negative base excess in the first hours of admission correlated with mortality. admission haemoglobin, platelet count, level of parasitaemia and level of glasgow coma scores in the first hours were shown not be predictors of mortality. these parameters may 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severe malaria? predictors of mortality in severe malaria: a two-year experience in a non-endemic area key: cord- - ggw authors: lane, j. m. title: mass vaccination and surveillance/containment in the eradication of smallpox date: journal: mass vaccination: global aspects &#x ; progress and obstacles doi: . / - - - _ sha: doc_id: cord_uid: ggw the smallpox eradication program, initiated by the who in , was originally based on mass vaccination. the program emphasized surveillance from the beginning, largely to track the success of the program and further our understanding of the epidemiology of the disease. early observations in west africa, bolstered by later data from indonesia and the asian subcontinent, showed that smallpox did not spread rapidly, and outbreaks could be quickly controlled by isolation of patients and vaccination of their contacts. contacts were usually easy to find because transmission of smallpox usually required prolonged face-to-face contact. the emphasis therefore shifted to active searches to find cases, coupled with contact tracing, rigorous isolation of patients, and vaccination and surveillance of contacts to contain outbreaks. this shift away from mass vaccination resulted in an acceleration of the program’s success. , the world health organization's smallpox eradication program shifted emphasis from mass vaccination to surveillance and containment. the shift evolved from early field experiences by the center of disease control (cdc) staff who improvised new approaches based on their developing understanding of the epidemiology of smallpox, and the relative ease of its control. this chapter summarizes these data and experiences, and comments on the results of the initial efforts in surveillance and containment. in the world health organization (who) expert committee on smallpox mandated % vaccination coverage to eradicate smallpox, rather than an % level of herd immunity as previously claimed (who ) . these experts assumed that smallpox was highly contagious and would therefore find isolated pockets of susceptible population. the committee emphasized the need to measure levels of immunity by developing methods of rapid and reliable assessment of vaccination coverage. around the same time, jet injector technology was being developed for rapid point-of-collection immunization roberto et al. ; neff et al. ) . coincidentally, trials in the early s, which showed the safety and efficacy of measles vaccine in africa, led many west african public health advocates to request assistance with measles control. (meyer et al. ) these developments set the stage for the west african measles/smallpox campaign. the initial plan for the smallpox eradication/measles control program was to do mass vaccination of the entire population for smallpox, and all children under the age of years for measles. the program used mobile teams going village to village, with collection point vaccination. measles had a high case fatality rate in sub-saharan africa, about %. (morley ) there was therefore considerable interest in the successful trial of measles vaccine in upper volta (now burkina faso). this led usaid to advocate a measles vaccination campaign through west africa (meyer et al. ) . cdc agreed to provide technical assistance to this campaign if smallpox eradication was added to the effort (fenner et al. ). simultaneous childhood measles and universal smallpox vaccination was started in , using collection-point mass vaccination with jet injector guns as the main strategy. collection point mass vaccination utilized the jet guns maximally, and helped the logistics of handling measles vaccine, which required careful refrigeration. the jet guns were cumbersome and made house-to-house visitation awkward. collection point mass immunization and treatment methods had been successfully used throughout much of west africa to control yellow fever and yaws, so that public health authorities were comfortable with mass vaccination concepts (hopkins ; tomori ) . cdc and who were vitally interested in adding disease surveillance to the effort, mostly as a method of assessing the results of the smallpox and measles immunization program. surveillance and outbreak investigations also allowed direct comparison of the epidemiology of measles and smallpox in similar communities. while superficially similar, the epidemiology of measles and smallpox in west africa proved to be quite different. measles in west africa was highly infectious and had about a % case fatality rate (morley ) . the median age of attack was less than years. virtually all children got the disease. transmission was common in gathering places such as markets, schools, or other gathering places. it was difficult to trace chains of transmission. in large urban areas such as the city of dakar, measles would exhaust all susceptibles and require continual re-introductions from outside the city to maintain transmission (rey et al. ). one case often caused six or more new cases. once the disease was introduced into a household or compound, the attack rate among exposed susceptibles was usually nearly %. smallpox was much less infectious. the median age of attack was in the mid-teens or early s (foege et al. ) . chains of transmission were easy to trace. most transmission was to intimate household contacts (henderson and yekpe ) . one case rarely spread the disease to as many as three others. very small tribal groups, as few as or so, often sustained transmission for six or more generations (imperato et al. ) . in individual compounds with extended family groups, the interval between the onset of the first case and the onset of the last case was frequently weeks, and often was weeks (foege et al. ). the two viral exanthems, although superficially similar, behaved very differently in the community. four observations led the cdc to give increased emphasis on surveillance of smallpox and rapid containment of outbreaks. first, in early dr william h. foege, who had agreed to head the smallpox and measles efforts in the eastern state of nigeria, detected a substantial epidemic of smallpox in several communities in ogoja province. the initial shipments of vaccine had not arrived. he called upon a network of friends and medical missionaries in the area, and suggested that they use their very limited supplies of vaccine to vaccinate close contacts of cases and possibly attenuate the outbreak. to his delight the outbreak was rapidly eliminated (foege et al. ). in retrospect dr c.w. dixon had observed similar results in tripolitania shortly after world war ii. he rapidly eliminated a substantial outbreak among the arab population with very limited supplies of glycerinated lymph vaccine. he vaccinated occupants of tents in which cases were found, telling his workers to vaccinate residents of surrounding tents only if there was sufficient vaccine. dixon coined the term 'ring vaccination', which has become synonymous with the vaccination strategy of surveillance/containment (dixon ) . second, shortly after the ogoja province outbreak showed that smallpox was relatively easy to eliminate with vaccination of small numbers of close contacts, dr foege and his colleagues conducted a textbook mass vaccination campaign in the eastern nigerian city of abakaliki. independent field assessment with a carefully drawn sample of the city showed that % of the population had been effectively vaccinated, with the major cutaneous reactions that who used as criteria for 'take'. shortly thereafter there was an outbreak of cases of smallpox in the city (thompson and foege ) . this observation cast doubt on the ability of mass vaccination alone to eliminate the disease. third, while these observations were being made in west africa, data from several studies of the epidemiology and viral shedding of asian variola major became available. these studies showed that the vast majority of spread was to persons with very close prolonged face-to-face contact with obviously sick patients. most transmission occurred during the first or days of the rash when the patient was prostrate and visibly ill. secondary household attack rates among susceptibles were as low as % in the seasonal downswing of the disease, and the highest recorded was only % during the seasonal increase. rarely did any patient spread smallpox to more than three other patients, perhaps in part because they were too sick to be effectively mobile (rao et al. ; mack et al. ; sommer and foster ; heiner et al. ; thomas et al. ) . joint us, uk, and indian researchers used plates of viral culture medium placed near patients in a smallpox hospital to show that viral shedding was detected only within feet of the patient. virus was not shed during the first or days of the prodrome when the patients were very ill, but had not yet developed an enanthem in the back of the nose and throat (downie et al. ) . finally, review of the epidemiology of imported smallpox in europe from to yielded similar data on the relatively slow spread of the disease. there were very few large outbreaks. indeed of importations resulted in no spread at all. the average number of cases per importation was just . over % of cases acquired smallpox in hospital, when undiagnosed very sick patients were not fully isolated (mack ) . in commenting on this study the author wrote "it is my judgment that under contemporary conditions smallpox cannot be said to live up to its reputation. far from being a quick-footed menace, it has appeared as a plodding nuisance with more bark than bite." mack has subsequently pointed out that smallpox probably would have been eliminated in developed nations, even without vaccine, by prompt isolation of patients (mack ) . during the fall of , the cdc program in west africa, led by dr foege, changed its strategy for smallpox eradication. foege and his colleagues reasoned that the relatively slow spread of smallpox, with the ease of aborting outbreaks by vaccination of contacts, made the disease susceptible to control by actively searching for cases and concentrating on vaccinating their household and village contacts. foege was also impressed by the marked seasonality of the disease. he believed that if outbreaks could be found during the west african seasonal low in september through january, and chains of transmission broken by patient isolation and/or vaccination of close contacts, a large decrease in the seasonal high from february through june would result from a fairly small effort. in india less than % of villages were infected at any one time, suggesting that only modest numbers of vaccinations were necessary if reporting could be improved (national institute of communicable diseases of india ). cdc thus laid plans for intensive active surveillance in the fall of and early winter of (foege et al. ). the surveillance and outbreak control strategy is conceptually simple, but required several changes in emphasis from the straightforward mass vaccination technique. improvements in surveillance were central to the effort. passive reporting through the medical care system was very poor in the newly emerging nations of west africa. reporting efficiency in nigeria was only about % of actual cases, and was poor in other areas of west africa (henderson et al. ) . instead of relying on formal medical reports, cdc teams went to markets and schools, and showed pictures of typical cases of smallpox, inquiring whether anyone had seen similar patients in their village in recent weeks. they quickly learned that tribal and civil authorities knew more about the health conditions in the villages than the medical hierarchy. surveillance became an active search, rather than passive reliance on traditional disease notification by medical personnel. a second element is improved isolation of patients. patient isolation can be very effective in controlling smallpox since patients are not infectious during the first days or so of the prodrome, and transmission is usually only to contacts with prolonged direct face-to-face exposure. indeed one experienced observer suggests that in developed countries smallpox could be eradicated by isolation alone (mack ) . many tribes in west africa hid cases because they had learned that isolation in smallpox hospitals was tantamount to a death sentence. medical and nursing care was poor in most african smallpox hospitals, and patients were not given good food and fluids. family members could do a better job of nursing patients, and particularly feeding them, given that there was no actual therapy for smallpox. a system of home isolation with careful education of family members and villagers, coupled with vaccination of caregivers, replaced forced hospitalization. a third element is identification of contacts. this proved easy once contacts realized that being vaccinated might save them from developing smallpox. many of the cdc operations officers in the program had been sexually transmitted disease investigators in the us, and were experienced in interviewing and contact tracing. a fourth element is vaccinating the contacts. the biology and immunology of smallpox allows contacts to be spared the disease if they are vaccinated within about days after contact (massoudi et al. ; kennedy et al. ) . cdc staff quickly realized that vaccinating contacts with the jet injector guns was cumbersome and time consuming, whereas all workers in the program could carry several vials of vaccine and containers of sterile bifurcated needles. they could vaccinate contacts wherever and whenever they were found. fully % of contacts had to be vaccinated, which meant that teams often made multiple visits to infected villages, including staying at night to vaccinate villagers who had gone to markets or were engaged in remote agricultural activities. a fifth element of the new strategy is placing contacts under careful and close surveillance, so that they can be isolated as soon as they develop early prodromal symptoms of smallpox (smallpox is not infectious until or days after the beginning of the febrile prodrome). surveillance could be accomplished by program team members, local health workers, or village officials trained to do the task. the final element of the surveillance/containment strategy is vaccinating the 'second ring', i.e., the contacts of contacts. in practice this often meant vaccinating an entire village once the initial contacts had been carefully identified and vaccinated. the second ring was vaccinated in case there was a vaccine failure in one of the first ring contacts, or a failure to identify a contact already infected. the shift from mass vaccination to surveillance and outbreak containment rapidly accelerated smallpox eradication. figure shows the secular trend of smallpox in the nations of west and central africa, displayed on a semi-log scale as the ratio of observed cases to those expected from the mean of the years from to . this corrects for the sharp seasonal trend observed in the historical data. when active search began in the fall of , there was an immediate increase in cases detected. this was followed by a rapid decline, with smallpox being finally eradicated more than months in advance of the original target date (foege et al. ; foege ) in late , during the tensions leading to, and then the actual conduct of, the biafra civil war, the eastern state of nigeria shifted from mass vaccination to surveillance and containment and interrupted transmission in just months, with only of the state's million population vaccinated (foege et al. ) . sierra leone had the highest incidence of reported smallpox in all of africa in , and started its mass vaccination program a year later than most of the other west african nations. it eradicated smallpox rapidly, and indeed three of its four largest outbreaks, and seven of its administrative districts, cleared smallpox completely before the planned beginning of mass vaccinations (hopkins et al. ) . mali eradicated smallpox with barely % of its population vaccinated (foege et al. ). there were similar success stories in guinea, togo, upper volta, and northern nigeria. the results of the emphasis on surveillance and outbreak control in west africa were sufficiently impressive so that who urged other nations, particularly in asia, to adopt the strategy as a mainstay of their eradication programs. the success of these measures is well documented in the defini-tive history of the who smallpox eradication programme (fenner et al. ). in the indonesian province of west java, a fortuitous experiment took place in which bogor regency did surveillance/containment alone, bandung regency did surveillance/containment combined with mass vaccination efforts aimed at reducing the backlog of unvaccinated population, and tjirebon regency first did mass vaccination to reduce the backlog, followed by surveillance/containment. the outcome convinced indonesian authorities of the superiority of surveillance/containment, and they were instrumental in helping who convince indian program leaders to adopt the strategy. the asian efforts included improvements and extensions of the basic steps in the surveillance/outbreak containment methods. in india increasing rewards were made for reporting bona fide cases of smallpox, with increasing values ( to to rupees) as the final cases were found. in bangladesh family health workers lived for nearly weeks in each infected village to assist with vaccination, and guards were posted at houses where infected patients were isolated. surveillance built in measures of the time from the onset of each patient's illness to the time of report, the time between initiating control measures and the onset of the last case in the outbreak, and similar methods of documenting the speed of finding cases and contacts. the time taken to control outbreaks became the measure most closely monitored, other than the actual decline of cases itself. in concerns about the use of smallpox as a bioterrorist weapon led to planning for handling outbreaks with unnatural sources. kaplan and his colleagues constructed a mathematical model of smallpox outbreaks, and claimed that surveillance and outbreak containment methods did not work as well as mass vaccination. his model included several aspects that are not consistent with historical experience; only % of contacts were found, patients spread the disease during the asymptomatic period of their infection, and quarantine and isolation of patients and contacts was not fully effective (kaplan et al. ) . several other investigators, using a variety of different mathematical modeling methods but employing realistic biological parameters consistent with historical field experience, have found that surveillance and containment methods works better than mass vaccination in virtually all scenarios (meltzer et al. : halloran et al. : bozette et al. eichner ; eubank et al. ; legrand et al. : porco et al. glasser et al. ) . unique biologic and epidemiologic aspects of smallpox allow it to be rapidly eliminated by surveillance and outbreak containment techniques. patients have a characteristic visible rash, which is easy for non-medical personnel to recognize. the disease is not infectious in the early stages of the prodrome, while the patients are very sick. this keeps patients from being mobile and spreading the virus. the vast majority of spread is to very close contacts, who are thus easy to identify. vaccination early in the incubation period is effective in stopping the development of the illness. emphasis on finding cases, isolating them, and vaccinating their contacts accelerated the eradication of smallpox, and allowed de-emphasis of mass vaccination methods. surveillance and careful isolation of patients may be important in other diseases spread by large droplet respiratory secretions, such as sars. in the author's opinion, a terrorist attack in the us using smallpox should not prompt mass vaccination. mass vaccination with current first generation vaccinia strains would cause considerable morbidity and mortality (lane and goldstein ) . it would be unnecessary given the efficiency and ease of surveillance and containment in a nation with sophisticated communications systems (mack ; lane and goldstein ) . if widespread simultaneous releases of large volumes of aerosolized smallpox took place in several cities, mass vaccination might become politically inevitable, but during the campaign contacts of known cases would still be ethically and epidemiologically the most important people to receive vaccination. thus surveillance and containment methods would have to accompany any mass vaccination efforts, and should receive the highest priority. the post / efforts to create a cadre of vaccinated health care workers in the u.s. was not a mass vaccination effort, but rather an attempt to selectively immunize people known to be at high 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in west pakistan i acquired immunity and the distribution of disease effectiveness of postexposure vaccination for the prevention of smallpox: results of a delphi analysis modeling potential responses to smallpox as a bioterrorist weapon response of volta children to live attenuated measles vaccine status of eradication of smallpox (and control of measles) in west and central africa smallpox vaccination by intradermal jet injection. i introduction, background, and results of pilot studies measles in west africa pattern of intrafamilial transmission of smallpox in calcutta smallpox vaccination by intradermal jet injection. iii evaluation in a well vaccinated population logistics of community smallpox control through contact tracing and ring vaccination: a stochastic network model epidemiological studies of smallpox. a study of intrafamilial transmission in a series of infected families lessons of an experimental campaign of vaccination against measles in the urban environment smallpox vaccination by intradermal jet injection. ii cutaneous and serological responses to primary vaccination in children the smallpox outbreak in khulna municipality, bangladesh . methodology and epidemiologic findings endemic smallpox in rural east pakistan. i. methodology, clinical and epidemiological characteristics of cases and intravillage transmission key: cord- -eahx cy authors: fleischack, anne; macleod, catriona; böhmke, werner title: the conundrums of counselling women in violent intimate partner relationships in south africa: implications for practice date: - - journal: int j adv couns doi: . /s - - - sha: doc_id: cord_uid: eahx cy little research focuses on how counsellors experience counselling encounters concerning intimate partner violence. this study reports on narrative research conducted with eight south african non-governmental organisation counsellors. participants spoke of creating productive and caring counselling dynamics, and providing non-directive counselling. however, they also indicated providing moral guidance, particularly in cases where pregnancy or children were involved. success was viewed rather narrowly as the women leaving the relationship, setting up ‘all-or-nothing’ outcomes. such ‘success’ led to counsellor happiness, whilst failure in this regard led to counsellors experiencing anger and burn-out. we conclude that the conundrums evident in these data are grounded in patriarchal systems, limiting the efficacy of counselling based on a bondage and deliverance narrative. implications for practice and training are also outlined. local and international research has shown that counselling for women who have experienced relationships characterised by intimate partner violence (ipv) can have many positive effects. these include women gaining confidence to leave a violent/abusive relationship (hatcher et al. ; jewkes et al. ; rhodes and mckenzie ) , considering options for solving problems within the relationship, and increasing their emotional wellbeing (iverson et al. ; rhodes and mckenzie ) . counselling, however, may also be challenging. for example, research into a latino community in the usa revealed that counsellors sometimes did bnot consider some potentially important personal barriers to reporting^, such as the victim's shame (lewis et al. , p. ) . various models of conducting counselling in relation to ipv have been suggested in the literature. these include: viewing ipv relationships as developing in stages, and modelling therapy based on this perspective; a client-centred approach in which the counsellor facilitates the client in choosing solutions and actions that are compatible and appropriate for themselves (the client) (mchattie ); and a competency framework that focuses on counselling skills, specialist knowledge and specific personal characteristics needed for working with this client group (roddy and gabriel ) . research on the experiences of receiving counselling for ipv has been used to refine recommendations for the counselling encounter (roddy ) . little research has been conducted, however, on how counsellors themselves experience and describe their own positioning within the counselling encounter. given the high level of gender-based violence in many countries (including south africa, the site of this study), and that counsellors tend to be women, how the counsellors experience the counselling encounter in regard to ipv is an important aspect of understanding such counselling. in this paper, we report on a study in which we interviewed counsellors, using narrative interviews, about their understandings of relationships characterised by ipv and how they, as counsellors, worked with ipv in their practice. all of the counsellors interviewed were women. we report, in this paper, on these counsellors' experiences of providing counselling within the context of the study. south africa has one of the highest prevalence rates of ipv in the world (britton ; joyner and mash ; modiba et al. , p. ; ntaganira et al. ) . ipv cuts across all ethnic groups regardless of education or income level, or the victim's or perpetrator's line of employment (modiba et al. ) . south african research reveals that % of women have experienced a lifetime prevalence of domestic victimisation (seedat et al. ) and . % of south african men reported abusing their current or most recent partner (gupta et al. ) . there are many barriers that women face in south africa when reporting ipv, related to resource constraints and social issues. the resource-related barriers include the relative lack of availability of healthcare or service provision facilities in the first place (mbokota and moodley ; modiba et al. ; njuho and davids ) . other reasons include lack of adequate assistance due to problematic interactions with counsellors (rasool bassadien and hochfeld ) . that is, counsellors may sometimes view ipv as a private matter, or that it is a normal phenomenon, possibly leading to lack of action or non-interference (rasool bassadien and hochfeld ); they may misdiagnose ipv (joyner and mash ) , be afraid to intervene on behalf of the community (lewis et al. ) , and may not have received adequate or appropriate primary care training (noted locally, mash et al. , and globally, watts and mayhew ) . in terms of social issues, some women may not report abuse due to conservative gender roles; e.g., the belief that the man is the head of the household and that his authority, and manner in which he runs the household, should not be questioned (sugarman & frankel , cited in jewkes et al. . as a result of the relatively widespread acceptance of such conservative and traditional gender roles within south african society, ipv has, in many respects, become normalised within relationships. women may either accept such violence as an everyday feature of their intimate relationships, or may see themselves as deserving of violent treatment from their partners for failing to adhere to culturally-located gendered expectations regarding their relationship roles (kim and motsei ; wood et al. ) . as a result, many women who experience ipv may feel that their violent partners were justified in their actions or that they did not harm them intentionally (silverman et al. ) . women may also feel reluctant or ashamed about reporting ipv (lewis et al. ) due to the personal, and sometimes sexual nature of the assault (vogelman and eagle ) . cultural and contextually mediated understandings of violence in intimate relationships, as well as subjective interpretations of the relative harm sustained, may also play a role. for example, anthropological research in south africa has described violence in interpersonal relationships as being understood by those involved as a demonstration of love, depth of feeling, or emotional investment in the relationship, with women victims of ipv consequently downplaying the harm caused (wood et al. ) . as noted earlier, ipv is also often not recognized by primary care providers and when it has been identified, the treatment has often been badly coordinated, fragmented, missed important aspects and/or lacked continuity (joyner and mash ) . this may be due to the lack of appropriate or adequate training that healthcare workers receive, both globally (watts and mayhew ) and locally . the south african non-governmental organisation (ngo) sector has played a role in addressing ipv. there are a number of safe houses available for abused women within south africa (kaldine ) often linked to ngos. the south african ngo sector also has many organisations linked to women's movements, examples of which include family welfare society and living hope. these ngos offer various services including counselling for domestic violence, women's upliftment, empowerment programmes, interventions, legal support and shelter services. in essence, these organisations specifically aim to bengage masculinities within 'feminist' frameworks^due to bthe growing institutionalisation and ngo-isation of the south african women's movement^ (britton , p. ) . due to the various problems surrounding access to counselling for ipv as noted above, effective help from counsellors and healthcare professionals is vital when ipv is reported. indeed, b[a]chievement of an efficient healthcare system which enhances respect for women and children is likely to contribute to a reduction of violence in communities and [will] subsequently boost the quality of life in south africa^ (njuho and davids , p. ) . research shows that women who have utilised the services of counselling centres are able to consider options for solving problems within the relationship, increase their emotional wellbeing (iverson et al. ; rhodes and mckenzie ) and also develop an enhanced ability to physically remove themselves from the abuse (hatcher et al. ; jewkes et al. ) . a variety of models for conducting effective counselling for those experiencing ipv have been developed. for example, the care guidelines by miller et al. ( ) outline addressing decision-making, which clinical services should be considered, and timelines for when intervention and assessment should occur. feminist principles proposed by mwau ( ) include helping women to explore options, acknowledging their strengths, assisting them with coping with shame or guilt, educating them about ipv dynamics and validating women's feelings. research conducted on clients' experiences of counselling has been used to enhance counselling dynamics. for example, women have emphasised the need to share their stories with counsellors within a safe and trustworthy environment (mchattie ; roddy ) where there was sufficient time to explore issues (roddy ) . other important factors are clients having their agency supported, being able to complete certain tasks, learning skills, having access to information, the importance of empowerment (mchattie ), and counsellors recognising diversity (e.g., same-sex partnerships) and nuances within relationships (oswald et al. ) . overcoming shame in relation to ipv within a non-judgemental environment was also linked to feelings of acceptance and validation (roddy (roddy , . however, very little research has been conducted on the experiences of counsellors who work with ipv, with research of this kind being useful for enhancing the quality of counselling. exceptions include zust et al.'s ( ) study with evangelical pastors, who indicated that they were ill-prepared to deal with domestic violence, and that counselling focused mainly on keeping the children safe and helping victims/survivors to understand that the violence was not their fault. iliffe and steed ( ) found that counsellors in their study who were involved in ipv issues experienced vicarious trauma, reported changes in their views of safety and gender power issues, as well as feelings of isolation and powerlessness as a result of the involvement. this study used a narrative-oriented inquiry (hiles and Čermák ) , based on the 'lightly-structured biographic-narrative interview structure' by wengraf ( ) see further details belowto investigate the micro-narratives elicited from counsellors when they spoke about their understandings of ipv and their practice in relation to it. narratives are bstories with words and meanings^that are linked to certain social groups and communities and provide information about the experiences and ways of life of these groups and communities (jovchelovitch and bauer , p. ) . micro-narratives can be defined as bshort bursts of narrative interactionally embedded in question-answer sequences: several stories produced often in intricate relations to one another^ (blommaert , p. ) . they often take the form of smaller, personal stories (fok ) and are bprovisional, contingent, temporary, and relative^ (barry , cited in o'donovan . although each person's narrative is idiosyncratic to their life experiences (hiles and Čermák ) , narratives also benable human experiences to be seen as socially positioned and culturally grounded^ (hiles and Čermák , p. ; young and collin ) . thus it is suggested that people construct narratives by drawing upon culturally-available social and discursive resources. data were collected by means of interviewing counsellors, using wengraf's ( ) method, who were based at two ngos, one located in an urban and the other in a peri-urban area in the eastern cape, south africa. these areas were chosen to ensure some diversity in the micronarratives. the clients who approach these ngos are from a lower socio-economic bracket. the agencies offer a variety of services including individual, couple and family counselling, women's empowerment initiatives and working in conjunction with the magistrates' court and the police to process safe house referrals and protection orders, as well as handling divorce and maintenance orders. the counsellors also intermittently enter the local communities to share knowledge and information on human rights. across the two sites, eight counsellors were interviewed for this research; owing to the relative size of the organisations, two were recruited at the peri-urban site and six at the urban site. the participants all had experience counselling people who had experienced ipv. seven of the counsellors were lay counsellors who had received in-house training and the other had a degree in social work. some of the counsellors themselves had been abused by their partners and thus could be seen as 'wounded healers'. counselling by 'wounded healers' may be beneficial as the counsellors are able to identify with the clients' traumatic experiences, and, through self-disclosure, can de-stigmatise the clients' experiences. on the negative side, however, counsellors may become too emotionally involved in their clients' situations, be unable to manage the countertransference set up in the encounter, and suffer from compassion fatigue (zerubavel and wright ) . at both sites, a client-centered, solution-based approach to counselling is adopted. after listening to the clients' stories, the counsellors, in a private, one-on-one setting, probe for more information, offer clients a variety of options for action, provide emotional support for the particular path chosen by the client, and offer to link the clients directly to places where they can get help. the study was granted ethical clearance by the rhodes university psychology department's research projects and ethics review committee. counsellors all provided their consent for the interviews to be conducted, including the fact that the interviews would be digitally recorded. the participants were assured that they would not be asked to divulge sensitive personal issues (e.g. their own histories in relation to ipv), as our research was focused on their experiences of their counselling. locations and names mentioned in the interviews were kept non-specific and the participants were asked to choose pseudonyms so as to ensure that the information could not be linked back to them. all of the participants were women; seven were black and spoke isixhosa as a home language; one was white with english as a home language. all were fluent in english. the first author and a co-researcher together conducted three separate interviews with each of the eight participants, using wengraf's ( ) method. this interview method allows the content of the narratives to guide further questions that the interviewers might ask. during the interviews, the co-researcher took notes, specifically focusing on topics that emerged during the elicitation of counsellors' micro-narratives. in the first interview, the counsellors were asked, using an open-ended narrative-inducing question, to share their understandings of ipv, and their experiences with conducting counselling sessions with clients who were in relationships characterised by ipv. in the second interview, held min after the first one, the researcher asked questions based on topics that had emerged during the first interview. the third and final session was conducted two months later, once the data had been transcribed and after a preliminary analysis had been conducted on the data, so as to determine which topics would be suitable for follow-up questions in the final interview. the data were transcribed verbatim using parker's ( ) transcription conventions (see appendix). these conventions were selected as they provide details of the talk (pauses, interruptions, etc.) without being too technical. the data were analysed using aspects of taylor and littleton's ( ) narrative-discursive method in order to examine the micro-narratives that emerged during the interviews with the counsellors. taylor and littleton's ( ) approach focuses, inter alia, on how micro-narratives enable subject positioning (the depiction of people within particular roles and responsibilities) to take place. the interview recordings were listened to several times and the transcription read at the same time. the transcribed data were imported and coded using qsr nvivo , a qualitative data analysis software program. coding centred on the identification of micro-narratives. in the analysis, we examined common micro-narratives occurring across the interviews and at different times in the same interview, which allowed us to see patterns in the counsellors' micro-narratives. all three authors engaged with the analytical process, and the findings were presented to peers in order to refine the analysis. the following micro-narratives were identified across the interviewees' data: 'we develop good counselling dynamics', 'we use non-directive counselling', 'when things go well, we feel positive', 'counselling ipv victims is emotional labour' and 'we provide moral guidance and suggestions'. with regard to each of these, the subject positions enabled by the micronarratives, and the implications for counselling are discussed below. the counsellors shared that they utilised a variety of session management tools (praise for clients; listening deeply; building trust) in order to create a positive environment and appropriate counsellor-client session relationships/dynamics. in this way they positioned themselves as professional, and as following well-established counselling techniques. some of the counsellors indicated that they praised their clients for coming to see them. this, they explained, formed a positive relationship between the client and counsellor, as can be seen in the following extracts: extract : duvi (p ): ...so the woman straight away she's going to be straight and say that 'enough is enough /hmm/ ja 'when i am looking at myself … i see that i'm going nowhere' /hmm/ hmm …i even congratulate her /mmm/ saying that 'no-one forced you to come here' /mmm::/ meaning that you are ready to take any step. extract : lwando (p ): ...as for us at [name of ngo] (.) once a woman take[s] a step forward =/mmm/ (.) to look at herself =/mmm/ (.) we see that as a survivor person =/mmm/= because once you find that … you need i-advice =/yes/= you need i-solution /mmm/ you need to find out what will work for you /mmm/ so once you take a step (.) we take you … as a great survivor. in the above extracts, duvi spoke of attempting to build a positive relationship with her client by bcongratulat[ing]^her for coming to see her, and lwando by bsee[ing] that [person] as a survivor^. these affirmations are seen as important to the process of taking bsteps^in the right direction; i.e., the women moving towards solving the problem. across the dataset, interventions were viewed by the counsellors as something that should help the women leave their ipv situation. these extracts reveal how a story of bondage and then of deliverance (see haaken ) , or at least the possibility of deliverance (byou are ready to take any step^; bwe take you as a great survivor^), provided a positive framing that counsellors encouraged in the session. the client's movement from victim to survivor through extracting herself from the relationship was viewed by the participants as an essential element of successful counselling. counsellors acknowledged that the movement from victim to survivor requires counselling labour. some of the counsellors mentioned providing a space to listen empathetically and attentively to their clients as an important counselling management tool, seen in the extracts below. intervention. this is because trust and confidentiality are important aspects of effective intervention as they provide the safe space in which the client can share her stories. the counsellors mentioned that they educate their clients about their rights and available intervention options. within this micro-narrative, the participants saw the counsellor's job as being non-directive, simply assisting the client to make the best decision for her amongst the options presented, as exemplified in the extract below. however, this micro-narrative stands in contrast to the counsellors' stated orientation of working towards the client leaving the ipv relationship. certain examples of subject positioning, however, show the slippage from nondirective to directive counselling. shelly (p ): i always tell them (.) it's very good to talk =/mmm/= not to keep inside you mmm/= talk about it so that …when you are talking …you're also getting the answers …because the answer is not coming from people … that you are sharing with (.) it's also coming with from you =/mmm./… you started to do this by yourself =/mmm/= you have to be strong for that. in extract , despite indicating that she does not say bdo these things^, amandisa takes up the subject position of beducator^in relation to her clients, narrating how she informs them of their rights and the options open to them. in this way, she suggests that women are victims of ignorance: they are less knowledgeable than the counsellor or are un(der)educated and in need of information in order to best decide how to manage their ipv situation. as the counsellors are speaking from an institutional space of helping women with ipv situations, they are considered qualified to speak about interventions because of their skills, expertise and knowledge in the field. furthermore, being in an institutional 'space of helping' may reinforce counsellors' narrative of bondage/deliverance of which they see themselves as facilitators. they thus act as facilitators of deliverance by representing apparently neutral options to their clients. this might in turn obscure the contradiction between their stated neutrality and their practice of providing options that follow a restrictive narrative of successful counselling outcomes. nevertheless, these options are presented, according to shelly, in a neutral way, with the client having to make her own decisions, as seen in extract . in this extract, shelly outlines that an element of counselling is women providing their own answers through talking with the counsellor. shelly constructs her clients as having their own agency and responsibility for their futures. interestingly, amandisa initially indicates that she gives badvice^. this is quickly corrected to giving boptions^because telling clients what to do is viewed as problematic. work undertaken to promote the perception of neutrality seems to be a defining feature of the first micro-narrative of 'good practice'. we will take up the slippage between non-directive and directive counselling in a later analytical section. counsellors spoke of positive experiences when reflecting on successful outcomes. examples of these positive reflections can be seen in the following extracts: extract : lwando (p ): women … they (.) becoming brave to report these cases that makes me very happy =/mmm/= and even if the case has been taken to court and then the perpetrator is being sentenced =/yes/= that makes me very happy. shelly's extract above expresses emotional satisfaction (bfeel[ing] good^) at essentially helping clients (to leave relationships characterised by ipv). similarly, lwando expresses happiness at women being 'brave' and reporting cases as well as the outcome of a perpetrator being sentenced in court. importantly, lwando's extract emphasises the view that successful interventions, as mentioned earlier, are those where the women leave relationships characterised by ipv. clients are seen to change from the subject position of victim to survivor in the extracts as the women in these cases have been bbrave^: they have become survivors by taking the cases to court and having the perpetrator sentenced (extract ). it is in these circumstances that the counsellors experience positive emotions and feel that they are successful in their work of helping their clients. a clear micro-narrative that emerged in the interviews concerned the emotional labour that goes into providing counselling for ipv clients. counsellors spoke about the sessions evoking strong emotions in them, the difficulty at times to remain objective as a result and thus the need to look after themselves. this can be seen in the extracts below: extract : shelly (p ): i got angry when … (.) a woman is staying … in an abusive relationship /mmm/ i got angry very angry =/okay/ … because … i stayed (.) but i don't want someone to stay there because i know (.) how it's pain … yho i know that in extract , shelly's struggle to remain objective can be seen in her revealing that she felt angry when her clients chose not to leave relationships characterised by ipv. in constructing this micro-narrative, shelly positioned herself as caring, as she is concerned for her clients and interested in their well-being. this can be seen in her remark that she understood and identified with the bpain^that the woman in this case was going through. the anger shelly felt at her client's inability to see the necessity of leaving the relationship links to work on wounded storytellers; frank ( , p. xv) suggests that anger or bchaos [is] in the claustrophobia of confronting others' inability to see what [one] so clearly feel[s]^. shelly, as the wounded healer, managed, eventually, to accomplish the situation most desired by the counsellorsthat women leave abusive relationships. as such, she feels compelled to assist the client along the same path, and thus experiences the countertransference of anger when this does not occur. while confessing to anger, shelly also positioned herself as knowledgeable (through the experience of not leaving at first). in this way, the woman client is positioned as a victim with little agency. as a result of their work being emotionally taxing, the counsellors spoke about trying to look after themselves and one another in order to continually carry out their work effectively, as can be seen in the following extracts: extract : nomsa (p ): we still have the [weekly] supervision … so each week we bring … all those worrying cases /mmm/ and also we … get … advices from the:: other … colleagues /okay/ …we … present your [our] case [p claps] and all other … colleagues will intervene in your case /that's great/= [we] discuss discuss discuss (.). extract : amanda (p ): i have in the past (.) organised … (.) consultations with:: … a private person or someone =/mmm::/= … to deal with that =/yes/= … to make sure that it doesn't overwhelm [me] . nomsa indicates that she and her colleagues were interested in supporting one another and were concerned about one another's wellbeing in light of the emotionally taxing work that they do. they discuss ball those worrying cases^, providing input and advice. nomsa alluded to the idea that the helper needs help to navigate the bworry^, and suggested that the counsellors take on the burden of their clients' ipv experiences by feeling empathy for the clients. amanda expressed concern over the real possibility of the work overwhelming her emotionally, and pointed, therefore, to the need to consult a person outside of the ngo for professional supervision. as was noted earlier, the counsellors indicated that they provide non-directive counselling, in particular presenting their clients with options for resolving the problems they are facing. however, the counsellors also spoke at times about encouraging their clients to engage in certain practices/behaviours through providing moral guidance or suggestions. this occurred mostly when discussing matters involving pregnancy or children. these moral suggestions included encouraging women to look after themselves during pregnancy and to consider the children: not to leave them behind if the woman was thinking of leaving a relationship characterised by ipv. this stance is opposed to letting the woman freely choose their options without such suggestions. in relation to this, it is important to note that the moral suggestions and guidance offered by the counsellors were largely influenced by culturallylocated and socially-sanctioned constructions of gendered roles and subjectivities, especially those around the concept of motherhood. these ideas can be noted in the extracts below: extract : mrs. x (p ): i always remind them that it's only temporary that your tummy is big. you're going to have your baby in your arms no more in your:: tummy after nine months so for the nine months that the baby is depending on you for survival you need to take better care of yourself . mrs. x (participant's chosen pseudonym) is attempting to reassure her client that the pregnancy is temporary and that her client must btake better care of [her]self^. in this way, mrs. x was positioning the woman as a nurturer with a responsibility towards her children. while not problematic in and of itself, this positioning leads to the moral injunction of self-care. in providing this moral injunction, mrs. x was subtly implying that failure to attend to this self-care could result in damage to the children. preventing damage to the children thus becomes the sole responsibility of the woman; failure to engage in self-care results in the woman being positioned as wilfully refusing to prevent damage. shelly stated that if a woman was thinking of leaving a relationship characterised by ipv, she bmust think about [her] children^. as with mrs. x, shelly was placing herself in a superior subject position as she seemed to feel that she had the status, knowledge and expertise in order to provide this moral guidance. the micro-narratives the counsellors related of their experiences of counselling women in ipv relationships, and the associated subject positions, point to a number of conundrums or double binds. the counsellors positioned themselves as professionals who implement good counselling practices (praise, listening, confidentiality, trust); at the same time, they could not help but feel angry, burnt-out and overwhelmed. when counselling was successful, the counsellors felt positive, but there were often failures, which they reported led to anger. this anger could be viewed as the countertransference of wounded healers, who, having suffered similar abuses, simultaneously empathise with the client, feel righteous anger towards the perpetrator, and dismay at the lack of 'success' (zerubavel and wright ) . throughout the data, 'success' was described by the counsellors as the woman removing herself from the ipv relationship. as such, the classic narrative of women being delivered from bondage formed the foundation of counselling. within this narrative, women who remain are regarded as victims and women who leave are considered survivors. this creates a dichotomy or an 'all-or-nothing' position within the counselling dynamic. the counsellor's emotional investment in the client and relationship building (such as ensuring confidentiality and thus building trust, listening attentively, displaying empathy where possible, promoting strength) was seen as worthwhile when the woman leaves the relationship (see also lewis et al. ) . however, the counsellors indicated becoming discouraged when the woman remained within the relationship. counsellors indicated that they used non-directive counselling, informing women of their rights and options and assisting them in making decisions. in this, however, the counsellors positioned themselves as experts on the options open to women, and regarded the women as experts on their own lives. however, there were limits displayed to simply allowing women to make their own decisions. when it came to matters to do with pregnancy or children, the counsellors felt it imperative to provide moral guidance on the correct form of action; i.e., that women must engage in self-care and take their children with them if they were to leave the relationship characterised by ipv. the fact that these counsellors invested in a narrative of female survivorhood, that implied leaving violent intimate relationships, is perhaps not surprising, given the high rates of abuse in the country and that all counsellors interviewed were women. counsellors who have experienced abuse themselves (some voluntarily revealed this in the interviews, as can be seen in one or two extracts here) may create an emotional weight or responsibility if their female clients choose not to leave the relationship. we argue that the conundrums evident in the counsellors' talk stem from the fact that they counsel the women within already entrenched patriarchal and structural power relations. there is no guarantee that the women will be able to successfully leave their current relationship characterised by ipv, or avoid another one in the future, and the counsellors were painfully aware of this. they nevertheless held onto the narrative of bbondage to deliverance^or bvictimhood to survivorhood^as the only valid outcome of counselling. this singular narrative regarding what constitutes a 'successful' outcome of counselling women who have had experiences of ipv during pregnancy, does not take into account the sometimes very real structural and/or cultural obstacles that frequently prevent women from leaving relationships characterised by ipv (e.g., economic dependency on their partners for survival, or culturally-located customs and traditional practices regarding marriage bonds) (see fleischack et al. ). this 'narrow' view of counselling outcomes may, therefore, be more likely to fail than not. indeed counsellors' insistence on clients' adherence to patriarchal and culturally-entrenched forms of motherhood may unwittingly constitute a barrier to successfully leaving an ipv relationship, thereby undermining their own criterion for a successful outcome (that is, leaving the ipv relationship). the counsellors indicated that they felt overwhelmed, fatigued and disappointed if their clients did not leave the ipv relationship. this emotional cost suggests that the counsellors as well as the clients were victims, working against a patriarchal system. in this tough and challenging environment, the counsellors often turned to one another for help, support and guidance. our research illustrates the importance of studying not only clients' but also counsellors' experiences so as to improve counselling concerning ipv. the conundrums illustrated above point to a number of implications in terms of the counselling process. firstly, to obviate counsellors feeling that their emotional investment has not been worthwhile, a useful perspective would be to see clients as complex beings: somewhere between victim and survivor, slipping between the two depending on circumstances, or as neither. this may also allow the counsellors to see and value small gains in their counselling process. examples include: when the women come to counselling in the first place, because they feel hopeful that they can receive some assistance; valuing women having a comfortable space to share their stories to gain some insight (which also links to moon's idea that story telling is a means to healing); and the notion of women engaging in everyday practices that serve to increase their agency and reduce the ipv, even if it involves remaining in the relationship. thus, secondly, the narrative of bondage and delivery (i.e., being in an ipv relationship followed by leaving) needs to be nuanced to allow for other narratives of success, including changing dynamics within the household or simple mechanisms to reduce the possibility of abuse. this is particularly important in circumstances where, as mentioned earlier, some women feel unable, for a range of reasons (e.g., financial, childcare), to leave the relationship. research into ipv risk factors and reduction interventions have highlighted key risks and aspects that, if addressed, might lower the likelihood of ipv occurring. these include addressing, for example, poor relationship communication and conflict management skills (abrahams et al. ; hatcher et al. ) , as well as economic and social empowerment initiatives (jewkes et al. ; kim et al. ; pronyk et al. ) . these all aim to alter and/ or develop troubling dynamics within relationships to reduce ipv, rather than arguing that women should simply leave situations of ipv. thirdly, recognising that counsellors and clients are both steeped in patriarchal power relations that, in the first place, foster ipv and, in the second place, make resolving the situation very difficult is important. the kind of support received from colleagues that was spoken about by participants is essential. peer support as well as sensitive clinical supervision go a long way in developing growth and self-care in counsellors, as identified by friesema ( ) . equally, though, counselling needs to be supplemented with a focus on accountability or collective responsibility for ipv in communities. this, thus, suggests the need for widerscale interventions and advocacy. running these kinds of interventions alongside counselling may assist counsellors in feeling less burnt-out and despondent about what is and is not achievable in this context. finally, the conundrums evidenced in the 'wounded healer' position need to be taken up in training and clinical supervision. as noted above and in the literature (zerubavel and wright ) , 'wounded healers' have the potential to empathise with clients and to de-stigmatise being the victim of abuse. on the flip side, uncontained emotions such as anger may surface and may interfere with the sessions. this is particularly pertinent when, as in this case, the 'success' of the counselling is narrowly defined. training and supervision, thus, could concentrate on: ( ) allowing the counsellors to reflect on and work through countertransference emotions, and ( ) ensuring that the client's options and choices are taken seriously and supported without the implication that counsellor-led outcomes are better. ian parker's ( ) transcription conventions (adapted) round brackets ( ) indicates doubts arising about the accuracy of material ellipses … to show when material is omitted from the transcript square brackets [ ] to clarify something for the reader forward slashes / / indicates noises, words of assents and others equals sign = indicates the absence of a gap between one speaker and another at the end of one utterance and the beginning of the next utterance round brackets with number inserted, e.g. ( ) indicates pauses in speech with the number of seconds in round brackets round brackets with full stop (.) indicates pauses in speech that last less than a second colon :: indicates an extended sound in the speech underlining ______ indicates emphasis in speech single inverted commas b indicates words or phrases which have been quoted; either the counsellor quoting themselves or quoting their clients, in this research intimate partner violence: prevalence and risk factors for men in cape town applied ethnopoetics. narrative enquiry organising against gender violence in south africa bthe man can use that power^, bshe got courage^and binimba^: discursive 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domestic violence -an antenatal survey at king edward viii hospital what helps, what hinders when counselling women who have experienced intimate partner violence (master's thesis) care pathway guidelines for assessment and counseling for domestic violence pilot survey of domestic abuse amongst pregnant women attending an antenatal clinic in a public hospital in gauteng province in south africa narrating political reconciliation: truth and reconciliation in south africa counselling victims of domestic violence in kenya patterns of physical assaults and the state of healthcare systems in south african communities: findings from a population-based national survey intimate partner violence among pregnant women in rwanda moving away from bfailing boys^and bpassive girls^: gender meta-narratives in gender equity policies for australian schools and why micro-narratives provide a better policy model lesbian mothers' counseling experiences in the context of intimate partner violence discourse dynamics: critical analysis for social and individual psychology effect of a structural intervention for the prevention of intimate-partner violence and hiv in rural south africa: a cluster randomised trial across the public/private boundary: contextualising domestic violence in south africa why do battered women stay?: three decades of research client perspectives: the therapeutic challenge of domestic violence counselling -a pilot study counselling and psychotherapy after domestic violence: a client view of what helps recovery a competency framework for domestic violence counselling life stress and mental disorders in the south african stress and health study dating violence and associated sexual risk and pregnancy among adolescent girls in the united states biographies in talk: a narrative-discursive research approach overcoming endemic violence against women in south africa reproductive health services and intimate partner violence: shaping a pragmatic response in sub-saharan africa qualitative research interviewing bshowing roughness in a beautiful way^: talk about love, coercion, and rape in south african youth sexual culture binjuries are beyond love^: physical violence in young south africans' sexual relationships introduction: constructivism and social constructionism in the career field the dilemma of the wounded healer evangelical christian pastors' lived experience of counseling victims/survivors of domestic violence publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations conflict of interest the authors declare that they have no conflict of interest. key: cord- -b r authors: labrunda, michelle; amin, naushad title: the emerging threat of ebola date: - - journal: global health security doi: . / - - - - _ sha: doc_id: cord_uid: b r ebola is one of the deadliest infectious disease of the modern era. over % of those infected die. prior to , the disease was unknown. no one knows exactly where it came from, but it is postulated that a mutation in an animal virus allowed it to jump species and infect humans. in simultaneous outbreaks of ebola occurred in what is now south sudan and the democratic republic of the congo (drc). for years, only sporadic cases were seen, but in a new outbreak occurred killing hundreds in the drc. since that time the frequency of these outbreaks has been increasing. it is uncertain why this is occurring, but many associate it with increasing human encroachment into forested areas bringing people and animals into more intimate contact and increased mobility of previously remote population. this chapter will navigate ebola in the context of global health and security. there are multiple objectives of this chapter. first is to provide a basic understanding of ebola disease processes and outbreak patterns. second, is to explore the interplay between social determinants of health and ebola. the role of technology in spreading ebola outbreaks will be explained as will ebola’s potential as a bioweapon. readers will gain understanding of the link between environmental degradation and ebola outbreaks. this chapter will be divided into five main sections. these are ( ) a case study; ( ) ebola disease process; ( ) social determinants of health and ebola; ( ) ebola in the modern era, and ( ) the link between ebola and environmental degradation. who contracts ebola. the story will be told from her perspective. she will describe from her why she thinks the outbreak has occurred. her husband has died of ebola despite efforts of traditional healers. she will discuss burial rites in the context of her religious beliefs. the next section looks at the disease itself. the history, epidemiology, transmission, and signs/symptoms will be described. prevention measures including the use of personal protective equipment and vaccination strategies will be discussed. the basics of diagnosis and treatment will be covered. the section will end with a discussion of ebola epidemics. social determents of health play an important role in the epidemiology and transmission of ebola. factors impacting spread include, high population mobility, porous international borders, and ongoing conflict resulting in displaced populations. poverty, cultural beliefs and practices and prior ineffective public health messages have all played a role in the emergence of ebola. the following section will explore ebola in the era of technology. the role of air travel in disease spread and the effectiveness of airport screening measures will be discussed. ebola's potential for use in bioterrorism will also be discussed in this section. the relationship between environmental encroachment and disease emergence will be explored. global warming, and the impact of a growing population in ebola outbreaks will be explored. the chapter will end with a discussion of future directions. in this last section the important of international collaborations for disease prevention and public education programs will be discussed. sia waited nervously in the small one room house where she lives. she was waiting for her brother-in-law to return with the body of her dead husband, saa. he had died yesterday of the bush illness that was killing so many in her community, ebola the outsiders called it. just weeks ago, the world had seemed a different place. sia had sat with the other women of the kissi tribe at church joking and planning for the upcoming rice harvest. yes, they practiced christianity, but also followed the traditions of their ancestors. women in her village prayed to jesus and god, but also to their ancestors. outsiders sometimes questioned how the kissi could follow both christianity and their old traditions, but sia had never seen a problem. ancestors after all, were the ones who communicated with god. when someone in the family died, they were escorted to the realm of the ancestors where they were able to protect the living family and speak to god on their behalf. ancestors continued to live in the village, but in their new form. sia shivered thinking of what happened to those who died and were not escorted to the realm of the ancestors. ceremonies were usually performed by the brother of the deceased. if the ceremonies were not done properly, a loved one would become a wandering ghost instead of an ancestor. wandering ghosts torment the living bringing misfortune to everyone in the village, especially to the family that failed to perform the proper rights. sia did not like to think of such things, but there had been several deaths in a nearby village and she could not help but to wonder if it was the work of a wandering ghost. that was the day it started. saa was fine when he woke up, but while they were at the church, he started to get sick. he got sick so quickly that sia suggested that they return home early so he could rest. it wasn't a far walk, but by the time they arrived home, saa was having chills, headache, nausea, and said his joints hurt. while saa rested, sia prepared a tonic to ease the pain and ward off evil spirits. saa's eyes were red and he felt hot to touch. "a powerful spirit must be involved", sia thought to herself. she couldn't imagine who would have cursed her husband this way. he hadn't argued with anyone that she knew. for days sia cared for her husband with special food, potions, and prayers. she had even sacrificed a chicken, but instead of getting better he started vomiting and having diarrhea. obviously, she needed assistance from someone with greater influence in the spirit realm. kai, a local medicine-man of conservable powerful agreed to help but needed time to make the necessary preparations. by that evening saa had stopped eating altogether and his gums started to bleed. kai belonged to a secret society that added to his powers. sia was not allowed to attend kai's ceremony but was told that saa had cried blood and started to hiccough uncontrollably. kai was notable to defeat the evil spirits even with his most powerful incantations. some of the villagers wanted to take saa to a treatment center set up by some foreigners to see if they could help him. sia was hesitant, but by the next morning saa had developed a yellow color to his skin and was having black diarrhea, so she agreed. after a bunch of questions saa was taken into the camp that the foreigners set up, but they would not let sia or anyone else in the family enter. that was the last time she had seen saa alive. two days later sia was informed that saa had died. he was to be buried in a mass grave and no one was allowed to see his body. saa's brother said that he thinks the foreigners killed him. they weren't really there to help but part of a government plan to destroy the kissi. workers in the camp were removing the internal organs of the sick while they were still alive and selling them. that is why no one was allowed into the camp or to bury the bodies properly. they weren't just attacking the living, but also trying to destroy the ancestors by preventing the death ceremony from happening. luckily saa's brother knew people. it had cost everything that the family owned, but the man driving the truck full of bodies agreed to meet a short distance from the foreigners' camp. he would give them the body there, but there were not to tell anyone. as saa's brother walked into the house carrying saa's body, sia felt an overwhelming sense of relief. all the worry gave her a headache and made her feel weak. now that they had saa's body it will be better. they will do the rituals this evening and burry saa in the morning. he will be able to walk with the ancestors. one of the world's deadliest pathogen, the ebola virus made its first appearance in in not just one but two simultaneous outbreaks. the first of its deadly attacks were in what is now known as nzara, south sudan while the second occurred in a small village community near the ebola river bank in yambuku, democratic republic of congo (drc) [ ] . of the known to be infected, lost their lives. since that time, we have learned much about the ebola virus and the disease it causes. ebola virus is an uncommon virus which infects both human and non-human primates. it belongs to the family filoviridae, a negative stranded rna virus. when magnified, it appears as a filamentous structure fig. . the ebolavirus genus has six known species, zaire, sudan, tai forest (formerly côte d'ivoire ebolavirus), bundibugyo, reston, and the recently described bombali [ ] . reston is highly pathogenic for non-human primates and pigs, and bombali has been discovered in free-tailed bats as part of ongoing research to discover the ebola reservoir. the zaire species was responsible for the first ebola virus outbreak in and is considered to be the deadliest of the six [ ] . initially the disease caused by ebola virus was called ebola hemorrhagic fever, but later studies showed that the hemorrhagic manifestations were less common than initially thought and subsequently the name was changed to ebola virus disease (ebd). until , the ebola virus isolated sporadic outbreaks occurred only in central africa with counts numbering in the hundreds or less, and only lasting days to weeks. however, in march the who confirmed an epidemic of the zaire species of ebola virus emerging in west africa. this outbreak lasted years and grew to be one of the world's deadliest epidemics. there were , case and , fatalities documented by the world health organization (who). the index case of this epidemic is thought to be a -year-old child who became ill in late . the child eventually succumbed to the illness with symptoms of fever, chills, vomiting, and black-tarry stool [ ] . this was in guinea, west africa a country where ebola supposedly did not exist. from here it spread to liberia, sierra leone, nigeria, and mali. the natural reservoir of ebola virus is not known with certainty, although research has suggested that it may be bats. human infection may occur through direct contact with the mystery reservoir or through contact with infected primates. this can occur when hunting and preparing bush-meat or via contact with body fluids from an infected person. ebola is highly transmissible. the disease pattern of evd has shifted over the last years. currently, ebola has been found across central and west africa, with occasional exported cases to other regions. for obscure reasons, outbreaks seem to be occurring with increasing frequency. this may be linked to environmental degradation and increasing mobility of local populations. ebola spread is through contaminated body fluids. unfortunatly, traditional funerary practices across africa put funeral attendees in contact with body fluids from those who have died of ebola. initial international efforts to control ebola spread during outbreaks have often resulted in clashes and conflict as control measures confront tradition. inadequate public health messages, distrust of those providing the health messages, political instability, and regional conflict have allowed ebola to spread and kill thousands when early containment could have been within reach. ebola is one of the most fatal infectious diseases humans have encountered. even with the best medical care the disease is deadly. unfortunatly, the developing countries where evd occurs are not equipped with optimal medical or public health facilities. to complicate the situation further, survivors of evd are not hailed as heroes, but instead may be left with chronic illness and stigmatized in their communities. transmission of ebola disease is still being studied, but it is known that person-toperson contact is the most common form of spread. infection occurs primarily through direct contact with body fluids from infected people or animals (fig. ). viral antigens have been isolated from the skin of those infected suggesting that skin contact alone may be sufficient to spread disease [ ] . it has also been shown that, at least in primates, ebola can be spread through intramuscular injection, and inoculation can occur through contact of the conjunctiva or oral mucosa with infected body fluids [ ] . blood, vomitus, and feces are the body fluid most likely to spread infection because of the frequency with which they are encountered during the course of the illness, but other fluid such as urine, semen, vaginal fluid, tears, sweat, and breast milk also have potential for viral transmission [ , , , , , ] . caring for an infected person with ebola, whether at home or in the hospital has been identified as a high-risk activity for acquiring ebola. household members who provide direct care to an ebola victim are - times more likely to contract ebola than household members who share a residence but do not participate in patient care [ , ] . healthcare workers are also at high risk for acquiring ebola. one study found the risk of developing evd for healthcare workers to be times that of the general community during an outbreak of ebola in sierra leone [ ] . there are many factors contributing to the spread of ebola amongst healthcare workers. the presentation of ebola is non-specific so early on in the disease process it may be diagnosed as malaria, influenza, or other non-specific viral illness. if a patient is initially misdiagnosed, then proper protective measures to limit the spread of ebola will not be initiated. also, the use of personal protective equipment (ppe) including gloves and gowns for routine patient care is less common in developing countries than in more developed countries due to financial restriction. there is a risk of iatrogenic spread of ebola. in the initial outbreak of , health care workers reusing glass syringes and needles in a community clinic may have inadvertently caused spread of infection. the facility consisted of a -bed hospital and a busy outpatient center which treated between and , people per month. at the beginning of each day, nurses were given five syringes each which were reused after a warm water rinse. unfortunatly, this is where ebola made its first appearance. potentially hundreds were exposed from this clinic alone [ , ] . there have been many other instances where hospitals have turned into epicenters for ebola outbreaks [ , ] . early detection and isolation is key to preventing similar incidents in the future. the greatest risk of transmission of evd from human to human occurs when a patient is acutely ill. risk also corelates with severity of illness. the sicker a patient is the more infective she is. in early phase of acute illness, the viral load is relatively low, however it increases exponentially during the latter part of the acute illness, and high viral loads are associated with high mortality rates and infectivity [ ] . those who handle corpses of ebola victims after death also run considerable risk of acquiring the disease. many funerary customs in ebola-prone regions involve extensive physical contact with the dead body. despite the risk of transmission, many still engage in these traditional practices. without these preparations, some local traditions hold that misfortune will plague the living and the dead will not be able to pass into the spirit realm. family who do not engage in expected funerary practice may be viewed negatively in the communities where they live. one funeral ceremony alone has been linked to additional cases of ebola [ ] . transmissibility of ebola virus depends on the phase of infection of the ill-person. the viral load corresponds to the severity of illness [ ] . in other words, the sicker a person is, the higher concentration the concentration viral particles in the blood stream. as an ill person succumbs to ebola, they become more debilitated and require more care. at the same time, the viral load increases as the victim declines. because of this, family caring for the ill are more likely to be infected in the later stages and corpses of those killed by ebola are highly infectious [ ] . even after a person has recovered from ebola and no virus can be isolated from blood, it may still be found in other tissues and able to transmit disease. live virus has been isolated from breastmilk after recovery raising the issue of transmission to mother to infant [ ] . ebola has been isolated from semen up to months after onset of symptoms, in urine for days, sweat for days, aqueous humor of the eye for weeks, and in cerebral spinal fluid for months [ , , , , ] . there has been at least one case where a man who recovered from ebola transmitted the infection to a sexual partner days after his initial illness [ ] . to prevent sexual transmission of ebola, the who recommends systematic testing for ebola virus in semen. for the first months after infection, the semen of male ebola survivors should be assumed to be infectious. three months after the day symptoms started semen testing for ebola should be initiated. if the result is negative, then it should be repeated in week. if the test is positive, then it should be repeated monthly until a negative result is obtained. once two consecutive negative results have been obtained sexual activities can be resumed [ ] . vaginal secretions have been found to contain virus up to days after the initiation of symptoms, but no official testing recommendations exist for vaginal secretions [ , ] . other methods of ebola spread have been postulated, but do not appear to be significant sources of transmission. surfaces contaminated with body fluids produce a theoretical risk of transmission, but no confirmed documented cases of fomite transmission of ebola exist. ebola virus has been shown to persist in the environment supporting the need for close attention to decontamination of surfaces [ , ] . medical procedures can augment disease spread if proper precautions are not taken [ ] . hunting and capturing infected animals for bush meat or for trading in black market as exotic pets can result in exposure and transmission of ebola. there have been numerous instances of human infection resulting from contact with dead primates [ , ] . contact with wild primates, especially those found dead should be avoided to curb the risk of contracting ebola. there is another step in ebola transmission that continues to be elusive. humans and other primates can catch ebola from each other, but they are not the reservoir. the reservoir is not known with certainty, but there is some evidence linking bats to ebola [ ] . the evidence for bats as the ebola reservoir is suggestive but not compelling. antibodies against ebola have been found in bat species, but the significance of this is unclear. antibodies are formed when an organism has been exposed to an infectious organism. this is evidence of exposure and immune response, but not of long-term infection or viral shedding [ ] . only one small study has ever isolated ebola rna from bats [ ] . attempts to infect bats then isolate viral rna or shedding have not met with success [ , ] . as the systematic search for the reservoir continues, negative findings are as important as positive one. plants and arthropods have not been shown to harbor ebola [ , ] . ebola virus disease is an acute febrile illness that has been associated with hemorrhagic manifestations. it has an incubation period of - days, but presentation of symptoms is most common between day and after exposure [ ] . it is unclear whether or not infected people can transmit disease prior to developing symptoms, but those with symptoms should be assumed to be contagious. evd typically begins with abrupt onset of malaise, fever, and chills. it is also common to experience vomiting, headache, diarrhea, and loss of appetite early in the disease course. the diarrhea can be profuse and water losses of up to l per day have been reported [ ] . dehydration and hypovolemic can result. relative bradycardia can also be seen in ebola [ ] . a maculopapular rash commonly develops - days after onset of illness. the rash is not a consistent finding and seems to vary from region to region [ ] . hemorrhage is the most dramatic symptom associated with evd but is not as common as first feared. usually it manifests as gastrointestinal bleeding, but petechia, ecchymosis, bleeding oral mucosa can also be seen [ ] . bleeding is multifactorial and likely due to a combination of thrombocytopenia, coagulopathy from liver involvement, and in some instance disseminated intravascular coagulation (dic). evd can cause involve a number of different organ systems. neurologically, it can cause meningoencephalitis, confusion, chronic cognitive decline, and seizures. neurological symptoms typically occur - days after onset of illness [ , ] . cardiomyopathy and respiratory muscle fatigue have been described [ ] . eye involvement is also common early in the disease course and may persist. patients frequently report blurred vision, photophobia and blindness [ ] . laboratory findings during the course of the infection can include leukopenia, elevated renal profile, abnormal coagulation panel, thrombocytopenia, anemia, and elevated liver function tests [ ] . hiccoughs are common late in the acute phase of illness. symptoms typically abate after weeks of illness. even after the acute illness has resolved, ebola victims can have long term symptoms. these include fatigue, insomnia, headaches, myalgias, arthralgias, cognitive decline, and hair loss. uveitis and hearing loss are both common after recovery from evd [ , ] . even after the resolution of acute evd, new symptoms can develop. in a study looking at early clinical sequela, % of ebola survivors developed arthralgias, % ocular symptoms, % auditory symptoms, and % uveitis [ ] . studies evaluating the long -erm sequela of evd are ongoing. prevention strategies for ebola are numerous, but essentially boils down to avoiding all contact with skin and body fluids that could potentially harbor the ebola virus. of course, this is more easily said than done especially in health care settings, and for families of those infected. health care providers deal with rapidly changing conditions often in limited resource settings and are at high risk for contracting ebola if prevention protocols are not followed. families of ebola victims face similar, but even more daunting challenges. ebola may be found in secretions of those who have recovered for months or even years after the acute illness has resolved. while not common, cases of transmission have occurred months after a person has recovered. active ebola virus can persist in urine, vaginal secretions, breast milk, semen, ocular fluid, and cerebrospinal fluid even after recovery making prevention more challenging. while not heavily researched as an effective prevention strategy, people who eat bushmeat should be encouraged to take precautions to prevent ebola infection. this means avoiding contact with fluids from slaughtered animals as much as possible. ebola virus is inactivated by thorough cooking, so through cooking of bush meat should be encouraged [ ]. ebola is highly pathogenic and easily transmitted. both the who and the center for disease control (cdc) have published detailed guidelines on prevention which are freely available online [ , , ] . the who recommends the following key elements to prevent transmission of ebola virus in the hospital setting: • hand hygiene • gloves • facial protection (covering eyes, nose and mouth) • gowns (or overalls) • sharps safety • respiratory hygiene for both health care providers and patients • environmental cleaning • safe linen transport and cleaning • proper waste disposal • proper sanitation of patient care equipment ebola prevention requires attention to and special training in donning and removing personal protective equipment (ppe). specific instructions and videos for use of this equipment is available at the who prevention cdc websites. health care workers who use ppe equipment properly are safe from ebola infection, but can develop other health issues from the ppe itself. the ppe suits are hot, uncomfortable, and require constant surveillance to ensure that all the equipment remains in place and undamaged. areas prone to ebola outbreaks tend to be hot, humid, and lack resources for air conditioning, wearing ebola suits creates a risk for development of heat related illness and dehydration. the cdc has published guidelines for preventing heat related illness for those providing care to ebola patients in hot african climates [ ] . as previously mentioned, people have survived initial ebola infection may still be able to transmit the disease to others. with proper preventive measures the risk of transmission can be ameliorated. as with other aspects of ebola, both the cdc and who have published extensive guidelines available on their websites. for healthcare workers, no special precautions are needed for basic patient care. the cdc does recommend that additional ppe be used when caring for ebola survivors if contact with testes, urine, breast, breast milk, spinal fluid, or intraocular fluid is anticipated during patient care [ ] . in the home, additional precautions may be needed. cases of transmission through sexual contact and breast milk have been describe in the literature [ , ] . cdc guidelines recommend abstinence from sexual activity of all types including oral, anal, and vaginal. if abstinence is not possible then condoms and avoidance of contact with semen is recommended. the who has recommended that semen be tested months after the onset of disease in men. if the test is negative, then it should be repeated in week. after two negative test sexual activity can be resumed. if the test is positive, it should be repeated every month until a negative test is obtained. once a negative test occurs, it should be repeated in week, and after two negatives sexual activity can be resumed [ ] . maternity issues around ebola are complex. it is unclear when it is safe for a woman to become pregnant after recovering from ebola. some organizations have suggested that a woman wait a few months prior to becoming pregnant, but so far this recommendation has not been supported by clinical data. breastmilk can transmit ebola virus from a mother who has recovered from evd to her child. if feasible, breastfeeding should be avoided. the data on ebola transmission through breasting is limited, and resources in ebola-prone areas make repeat testing of breastmilk impractical. suggested strategies have recommended avoiding breasting feeding for months after recovery [ ] . travel restrictions may occur during ebola outbreaks. it is generally accepted practice that those who have potentially been exposed to ebola virus not travel for days after the last possible day of their exposure. as an alternative for those at low risk, close monitoring with no restrictions on travel may be done. balancing individual rights with community safety creates ethical and regulatory challenges in cases of potential exposure. additional information on monitoring and travel restriction can be found at both the cdc and who websites. vaccination development is in place, but there is currently no federal drug administration (fda) approved vaccination for ebola. currently, there are different clinical trials running with the goal of developing a safe and effective ebola vaccine [ ] . an investigational vaccine called rvsv-zebov is presently being used in drc under "compassionate use". this vaccine is specific for the zaire strain of ebolavirus. this same vaccine was previously administered to , volunteers during an outbreak in . so far, the vaccine appears safe with few side effects, but insufficient data is available for licensing [ ] . preliminary reports suggest an efficacy of %, but duration of protection is currently not known [ ] . even though there are no specific therapies to treat ebola, diagnosis is important to prevent spread and to ensure administration of appropriate supportive care and monitoring. anyone who has had any potential exposure to ebola in the last days should be evaluated if symptoms of ebola develop. while awaiting the result of ebola testing, appropriate infection control practices should be implemented. diagnosis is done by reverse-transcription polymerase chain reaction (rt-pcr). the test should be done days after the onset of symptoms [ ] . false negatives can occur if the lab is collected before h of symptom onset. a positive test confirms ebola virus disease and that the patient is infective. considering repeat testing in patients whose clinical picture is highly suspicious of ebd and have a negative initial test. ebola virus disease has a broad differential, and simultaneous testing for other illnesses should be undertaken as clinically warranted. this differential includes, malaria, lassa fever, typhoid fever, influenza, meningococcal meningitis (neisseria meningitidis), measles, crimean-congo hemorrhagic fever, yellow fever, marburg, and the familiar travelers' diarrhea among many others [ ] . supportive care is the only treatment for ebola. there are no antimicrobial agents proven to be effective in ebd. when possible, care should be provided at a facility familiar with the clinical progression of ebola. supportive care in ebola is no different than for any other critically ill patient. give intravenous fluids to prevent dehydration and shock. patients with ebola suffer from vomiting and diarrhea and may easily dehydrate. if intravenous fluids are unavailable or prohibitively expensive, oral hydration should be undertaken. ebola can lead not only to hypovolemic shock, but also septic shock [ ] so close patient monitoring is warranted. electrolytes will require close monitoring and should be repleted as needed. vasopressors may be required if blood pressure cannot be maintained. ebola can result in significant hematological abnormalities [ , ] . it can also lead to liver failure followed by coagulopathy [ ] . thrombocytopenia, leukopenia, and anemia are all common and treatment should be based on the specific abnormality encountered. other management may include antipyretics, respiratory support, analgesics, antimotility agents for diarrhea, antiemetics for nausea and vomiting, antibiotics, nutritional support and renal replacement therapy. these and other supportive measures must be tailored to the individual patient need. the first reported outbreak of ebola-like illness occurred in in sudan and zaire [ ] [now south sudan and the democratic republic of congo (drc)]. it is probable that sporadic outbreaks happened earlier but were not identified. outbreaks appear to be occurring more frequently than before. this is not only due to improved detection techniques, but also due to environmental encroachment, increasing population mobility, and changing weather patterns. the following section will summarize data on known ebola social determinants of health are the conditions in which a person lives and grows. there is no one list of these factors, but they are generally considered to include influences such as school, (un)employment, the community where one resides, food, and transportation. the factors are driven by forces outside of one's sphere of control such as poverty and war as well as some potentially self-directed choices such as belief system and friend circle. for example, social determinants of health are a way of describing why when a . magnitude earthquake hits haiti buildings collapse and people die and when a . magnitude earthquake and the same earthquake on guam causes no damage. social determinants of health significantly affected how ebola has impacted affected countries. poverty affects every aspect of life for most. according to world bank data, the rate of poverty in sub-sahara africa is trending downwards but is still over % of the population. poverty leads to lack of education, limited medical resources, poor nutrition, and crowded living conditions. people in poverty will eat a dead animal if they find one because it may be all they have to eat. they are unlikely to seek medical care outside of traditional healers because it is all they know and can afford. they may insist on washing the bodies of the dead because their only knowledge of science are traditions passed from generation to generation. all of which contributes to the spread of ebola. anyone who reads the history the countries that make up the peri-equatorial regional of africa will quickly notice that the region has suffered from nearly continuous war since even before the european occupation. there are pockets of stability in the region, but conflict is a way of life for many. conflict leads to destruction of infrastructure, fear, stress, distrust, and population displacement. currently, an ebola outbreak is occurring in drc. refugees from drc continually flee into neighboring countries, especially uganda. conflict driven human movement is a means by which ebola can be spread. no widespread outbreak of ebola has occurred in a refugee camp, but these types of settlements are fertile soil where an outbreak could start and flourish before an alarm is raised. the ugandan government is working with the international federation of the red cross and red crescent societies (ifrc), unicef, and the who collaborating to develop an ebola emergency preparedness plan [ ] . political and economic instability across have resulted in a debilitated medical and public health infrastructure. official data is limited, but media sources have reported that liberia has experienced a severe shortage of trained health workers within the country. media sources list general practitioners, public health specialists, pediatricians, surgeons, obstetrician-gynecologists, ophthalmologists, internists, dentists, psychiatrists, family medicine specialists, orthopedic surgeons, radiologists, pathologist, ear-nose-throat specialist, veterinarian, and dermatologist as comprising the entire formally trained health community (excluding nursing professionals) [ ] . the cia world factbook lists the number of physicians per people to be . for liberia, . for sierra leona, . for guinea, . in drc, and . in uganda [ ] . even some of these numbers are almost years-old making it difficult to assess the actual situation in the region. regardless, it is a safe conclusion that none of these countries are even close to having the recommended physician per residents recommended by the who. each of these countries is unique in the health care challenges it faces, and only are mentioned here because they have all been touched by ebola. infrastructure development is generally associated with improved health and decreased disease burden, but this is not always the case. while lack of infrastructure such as water and sanitation is thought to lead to increased transmission. increased connectivity via road and boat is thought to increase the risk of transmission through increased number of contacts [ ] . one of the most fascinating aspects of ebola occurs at the intersection of culture and public health. for generations, a mixture of traditional beliefs and mainstream religion has served as a cultural foundation in many tribal areas across central and western africa. funerary practices in these tribes are some of the most important in their belief system. it is these practices that have been exploited by the ebola virus allowing it to spread. exposure has been associated with attendance of funerals and contact with dead bodies in multiple countries [ , , ] . as public health and medical personnel tried to curb ebola spread, conflict has occurred. those most at risk for ebola suddenly felt threatened not only by the disease itself, but also by those where were trying to help as their core beliefs were suddenly targeted. from the perspective of the health care workers trying to save lives, the cultural beliefs were generally considered as just another barrier to be surmounted. this lack of understanding between those at risk and the health care workers lead to conflict, distrust, which at times drove ebola victims into hiding rather than seeking care. bribes were made, bodies were stolen, aid workers were attacked, and ebola spread. some of the cultural beliefs common in central and western africa will be discussed here with the goal of fostering cultural understanding of disease. given the diversity of human beliefs, it is likely that future events will again put disease control against traditional beliefs. a good starting point in cultural sensitivity is viewing an idea from the point-ofview of the other party. in the case of ebola, it is important to understand what different groups of people believe to be the etiology of disease. most educated health professionals view disease as an understandable biological process. infections are caused by microbes. in the case of ebola, it is a filovirus. in many traditional african cultures, disease is believed to be due to witchcraft [ ] . consultation with traditional healers is a common practice across africa. in many regions traditional healers are the only locally available medical provider. even if modern medical facilities exist, many will turn to the traditional healers first because they are more trusted, and their beliefs tend to align more closely with those of the community. there are many different traditional healing practices, sometimes traditions are passed down through generations in specific families. one description of a traditional medical ceremony in sudan describes a medicine man and his assistants. first, ritualistic dance and chants are performed. next the medicine man shows his spiritual power by having a large rock placed on his abdomen and broken by an ax while he remains still. once his strength has been established, his attention can be turned to his patient. the medicine man's diagnosis is mental illness caused by evil ancestors who have returned with the purpose of tormenting the patient. incantations are the treatment [ ] . beliefs and practices such as this are common in rural central africa. in these societies, illness is viewed as a disruption in the relationship between god, ancestors, and the person affected. witchcraft, sorcery, angry ancestors, and evil spirits may all be at the root of disease and a powerful medicine man can restore the proper balance in these relationships thus curing disease [ , ] . the individual customs and beliefs associated with the cause and treatment of disease is too long to be included here, but those interested in additional information should read the articles cited in this section for additional details. traditional healers can be a great asset to a community, but there have been unfortunate instances where they actually promoted the spread of ebola. some traditional healers claimed to be able to cure ebola. unfortunatly, their attempts at cure have been known to spread the disease to those in attendance of curative ceremonies as well as to themselves [ ] . traditional healers can also charge a significant amount of money putting a family who is already dealing with the loss of a loved one in additional financial stress [ ] . not all traditional healers seek the good of the community but instead are motivated by personal gain. many societies in central africa practice religious beliefs based on a combination of mainstream religion and ancestor worship. occult ceremonies, secret societies, and rituals are common, and the details of these practices are often covert, only known to a small subpopulation. the ceremonies may be benign such as the one described in the preceding paragraph or may involve animal or human sacrifice [ , ] . while many of these practices involve sacrifice and exposure to blood no studies have been published linking these activities to ebola transmission. it is the traditional funerary practices that have been most closely associated with the spread of ebola. many central and western african cultures view the death ceremony as one of the most important. when people die, they must be guided to the realm of the ancestors. from this realm, ancestors are able to hear the requests and see the needs of the living family and communicate these needs to god. the living family prays directly to the ancestors. if death rights are not done correctly then instead of becoming an ancestor, the deceased may become an angry ghost which torments the family [ ] . a common funerary practice in liberia is for an elder family member to bathe the body of the deceased. it is common for mourners to touch the face and kiss the forehead of the deceased. in some traditions the spouse of the deceased continues to share a bed with the corpse until the time of burial. another tradition involves dance. on the night prior to the funeral, men dance with the dead body while women wail. several traditions involve sacrifice and exposure to the blood of a bull as part of their ceremony [ ] . to prevent the spread of disease the governments in liberia and guinea passed laws requiring safe burial teams or cremation when the number of grave sites was insufficient for the number of bodies. numerous reports of bribing health workers responsible for collecting and properly disposing of the bodies allowed ebola to persist in this region [ ] . people stopped going to the health care facilities, and families would try to hide the cause of death from officials. at the height of the epidemic in sierra leone, the number of ebola care beds was insufficient for the number of patients. many were transferred from facility to facility and their families were not notified. rumors began to spread that the ebola facilities were harvesting organs and killing people [ ] . poor communication resulted in suspicion and distrust. it took thousands of deaths, but finally both sides began to compromise. the government and health care workers started to work with local religious leaders and traditional healers to find solutions that would let the people honor the dead without exposing themselves. many muslim leaders told their followers to abstain from washing bodies until the outbreak ended. bodies were buried with families nearby and although the could not touch the bodies prayers could be said. burial teams started to dress corpses in clothing requested by the family and often placed requested jewelry. once all sides compromised and started working together the epidemic was able to be contained [ ] . even if someone survives ebola the battle is not over. there is poor understanding of disease and disease transmission. survivors may be ostracized and shunned by their communities because there is fear that they can spread disease. survivors have had their houses burned, families attacked, and lost their jobs due to irrational community fear. during the west african ebola outbreak survivors were issued certificates stating that they were no longer contagious in an attempt to combat social stigma. this is not to say that it is all gloom-and-doom in countries that have experienced ebola outbreaks. social determinants of health are not isolated static elements. technology and globalization are bringing health improvements at an unprecedented rate. if one reviews data for the countries where significant ebola outbreaks have occurred, guinea, uganda, drc, south sudan, and liberia. all of these countries have had a decrease in infant mortality rates, decrease in maternal mortality rates, and extreme poverty rate have been steadily dropping over the last years despite the presence of ebola [ ] . anyone interested in additional information on measurable global trends, whether they be economic, or health based is encouraged to visit gapminder (www.gapminder.org). not every country that faces ebola descends into a public health crisis. in july multiple cases of evd were diagnosed in lagos, nigeria. lagos is a densely populated city and the capital of nigeria. the nigerian ministry of health was able to rapidly contain the situation before a full-scale epidemic began. the nigerian government had access to trained health care providers able to do contact tracing, able to mobilize a rapid efficient response, and worked closely in cooperation with the who to implement standardized epidemiologic practices. the epidemic in nigeria was halted before it was able to start [ ] . ebola in the technology era the concept of quarantine was first developed in the fourteenth century to control the spread of plague [ ] . quarantine is a required separation of incoming people or animals prior to mixing with the local population with the goal of preventing the spread of disease. it is one of the oldest and most effective public health measures, but very unpopular with those whose movements are restricted by quarantine. recently, kaci hickcox, a nurse volunteering in sierra leone returned to the us. she possibly had been exposed to the ebola virus. ms. hickcox was placed on a mandatory home quarantine of days, but she defied the quarantine order and proceeded with her day-to-day activities [ ] . in reality, she was at very low risk for developing the disease, and there was essentially no risk for widespread ebola transmission in the us, but her unwillingness to comply with the quarantine brought attention to many public issues surrounding quarantine. specifically, the conflict between individual civil liberty and the well-being of the general public [ ] . since when quarantine laws were first written technology has expanded drastically. surely there exists a technology that allows us to abolish the antiquated quarantine system. whether an intentional act of terrorism or through accidental contagion spread, travelers pose a significant threat to homeland security. various measures have been attempted to try and identify sick travelers with the goal of limiting epidemic spread. the following is a discussion of currently available boarder control measures aimed at preventing the spread of disease, and evaluation of the effectiveness of these measures, and a discussion of technologies that may be of utility in the future in preventing cross-border ebola spread. two-point-five million people fly in or out of the united states every day [ ] and an estimated one-million more per day cross via land and sea [ ] . with millions of border crossings daily, transmission of communicable disease between remote locations is inevitable. the vast majority of communicable diseases spread by travelers are upper respiratory viruses such as the common cold or influenza. generally, these are self-limited illnesses with few long-term consequences. every few years though, something new with greater lethality emerges and threatens the security of the us travelers, their contacts, and the broader population at home. ebola, severe acute respiratory syndrome (sars), and even the relatively benign zika virus have made media headlines with travelers seen as potential harbingers of disease. another factor that must be taken into account is the increasing population density and urbanization. the united nations (un) predicts that % of all people will live in cities by the year [ ] . a megacity is defined as an urban population of over ten million people. the first to reach megacity status was new york city in the 's [ ] . by , the megacity count rose to [ ] . large numbers of people in a small area constitute a vulnerability when looking at epidemic risk assessment. a single ill traveler arriving to a megacity has the potential to start a local chain of infection that could rapidly spread to millions. with the widespread availability and affordability of trains, planes, automobiles, buses, and boats it is easy for microbes as well as humans to travel rapidly across the globe. travel provides individual freedom for pleasure and commerce but, at the expense of national security. small disease outbreaks are continually occurring across the globe. multiple international monitoring systems are in effect and the center for disease control (cdc) has issued official recommendations for travel restrictions for persons with higher-risk exposure to communicable diseases of public health concern [ ] . briefly, these guidelines state that a person who meets the following criteria will have their travel restricted [ ] : be known or likely infectious with, or exposed to, a communicable disease that poses a public health threat and meet one of the following three criteria: . be unaware of diagnosis, noncompliant with public health recommendations, or unable to be located. or . be at risk for traveling on a commercial flight, or internationally by any means. or . travel restrictions are warranted to respond effectively to a communicable disease outbreak or to enforce a federal or local public health order. while the above criteria may be the best legally available option, it leaves a multitude of holes by which a person with a communicable illness could slip into a us city and start a new epidemic. ideally, additional layers of protection would allow potentially ill travelers to be identified and detained prior to entry to the united states. an infectious agent can travel across the globe in h if spread via airplanes [ ] . this has important implications for those trying to prevent disease from spreading. land and boat entry into the united states present other challenges. the sheer number of people crossing by land on a daily basis makes any screening difficult. boat traffic can also present unique screening challenges. a cruise boat, for example, may arrive with thousands of people who all debark within a short period of time. though screens are impractical in these situations. even if screening technology was employed allowing security agents to detect fever there are so many causes of fever that timely interpretation of the data would be difficult. with so much international travel occurring, there is a continual search for ways to improve screening for ill travelers with the goal of preventing importation of disease. many different methods have been tried, most centered around a specific pandemic rather than continual monitoring. none have had great success. these methods have included entry-screens, exit-screens, and post-entry monitoring. the us division of quarantine is not only authorized, but required to identify and detain anyone entering the country with actual or suspected diphtheria, any viral hemorrhagic fever including ebola, cholera, tuberculosis, small pox, plague, novel influenza strains or yellow fever [ , , ] . in theory, this is an excellent regulation, but how can millions of travelers be efficiently screened and detained if needed? after the outbreak of sars in many countries starting using boarder screening to try to identify possibly ill people in hopes of limiting spread of infectious disease, others jumped on board after the h n influenza pandemic. the issue then resurged in the wake of the ebola outbreak in west africa. as with many things, there must be an understanding of the costs, potential benefits and effectiveness of programs aimed at preventing a possible public health disaster. an article by the cdc, published around the same time as the article recommending travel restriction for high-risk individuals, concludes that border screens are expensive and not effective in preventing the spread of disease [ ] . while point-of-care screens are not yet considered an effective means of controlling certain biosecurity threats, progress is being made. temperature screens have been developed with the goal of identifying people with fever. what happens when a fever is detected depends on where a person is traveling to and from, and the current state of outbreaks occurring in the world. there are several types of temperature readers including ear gun thermometers, full body infrared scanners, and hand-held infrared thermometers [ ] . none of these methods is highly effective and most screening devices can be fooled with minimal training and effort. once study found that thermal screens were only about % effective in detecting fever. the authors of this study concluded that temperature screens were ineffective in identifying ill travelers [ ] . the european center for disease control (ecdc) has also investigated the feasibility of using temperature screens to identify ill travelers and came to similar conclusions. this report was done during the ebola of and geared towards diagnosing travelers potentially infected with ebola. they estimate that even under ideal conditions % of symptomatic illness would be missed due to low sensitive of temperature devices [ ] . additionally, it was concluded that those intentionally trying to mask their temperature could easily do so and that those who had not developed symptoms would be missed by the screen. even if fevers screens were accurate and difficult to manipulate that would still be a poor screening measure. first of all, with many illnesses including chicken pox, flu, the common cold and countless others, people can be contagious before a fever starts. it is not yet known if an infected person can spread ebola before symptoms begin. secondly, not all fevers indicate an infectious disease. fevers can be due to drug reactions, blood clots, and even cancer. third, not everyone reacts to an infection the same way. some people naturally tend to have fever and others tend not to. one expression commonly taught in medical schools across the us is, "the older the colder". this is a reminder to students that elderly patients may never have a fever even if they are extremely ill with an infectious disease. lastly, what determines what constitutes a fever? the medical field defines fever as a temperature of degrees celsius ( . f) or higher. are these same numbers valid for travelers or should different cut offs be used? while temperature screens may have their place in emergency settings, they are far from an ideal way of detecting an ill passenger and the day to day use of temperature screens is not generally considered an effective means of identifying ill travelers. when foreign agencies are cooperative screening may be done prior to departure. exit screening was done during the ebola outbreak of for travels from west africa to the united states. the goal of exit screening is to identify those potentially infected with a specific disease and prevent them from departing for the united states until they can be medically cleared. the cdc considers this to be one of the more effective forms of preventing disease importation to the united states [ ] . departure screens are not routinely used except during times of known outbreaks. during the west african ebola outbreak exit screening measures were implemented. the general process used for screening during the outbreak was as follows. travelers were instructed to arrive earlier than they normally would for their travel due to increased processing times. general instructions to travelers instructed them to postpone travel if they were ill. in addition to the regular airport screening, all travelers were required to have their temperature taken and fill out a "traveler public health declaration". travelers who were febrile or considered at risk based on the answers to their health declaration forms were detained and their travel delayed [ ] . during the ebola outbreak the who provided resources for predeparture screening that were detailed yet used easy-to-follow language and including flow charts for those performing the screen. basic information on ebola and its symptoms so that the illness was more well understood and the disease symptoms familiar. directions for using personal protective equipment for those performing the screening. written tools and the public health declaration form were provided. additional resources included a data collection log and a traveler information card that could be distributed to travelers [ ] . the ebola screening was done in two steps, a primary screen and a secondary screen. the primary screen included three questions: ( ) is the traveler febrile?; ( ) is the traveler demonstrating symptoms of ebola?; and ( ) has the traveler marked "yes" to any questions on the health declaration form? an affirmative response to any of these questions resulted in secondary screening. secondary screening involved a public health interview and filling of the secondary health screen form, repeat temperature measurement preferably with an accurate thermometer, and focused medical exam. if the secondary screen found a temperature < . , no risk factors for ebola in the public health interview, and no symptoms of ebola on the public health interview they were allowed to proceed to check-in. if the above criteria were not met, check-in was denied until health clearance could be obtained [ ] . this strategy was considered effective. the limitations include the time and money required to implement the program, frustrating travel delays for travelers, and the inability to identify illnesses other than ebola or similar diseases. its usefulness is limited to known and identified epidemics. this strategy will likely continue to be used in future outbreaks to prevent exportation of disease [ ] . temperature screens have been used during five epidemics to date, dengue, sars, ebola, and influenza during both the entry and exit process. screening for fever in taiwan entry points during a dengue outbreak was reported to be effective. one research study reports that % of imported dengue cases were able to be identified through airport screening [ ] . during the sars outbreak, singapore entry points screened , people and identified no cases, canada entry points screened . million people and identified no cases, and hong kong entry points screened . million people identifying only two cases of sars [ ] . fever screening was used during the - influenza pandemic and even with a low threshold for defining fever was found to have a sensitivity in the . % range. exit screening done in west africa during the ebola outbreak identified fever in out of , travels screened. of these, none had ebola [ ] ). active monitoring is another technique that can be used in preventing disease spread within ebola naive countries such as the united states. it involves allowing a traveler freedom to come into the us, freedom from quarantine, but also allows health authorities to monitor the health status of potentially infected people. if someone begins to develop symptoms then measures can be taken to isolate, diagnose, and treat the ill person. this method is best applied to those who are reliable and at low risk for developing illness. there has not been much experience with widespread use of active monitoring systems with the exception of the western africa ebola outbreak. during this outbreak, travelers from liberia, sierra leone, and guinea to the us were given care (check and report ebola) kits upon arrival to the us [ ] . care kits provided resources to travelers from ebola affected countries. travelers were given information on the signs and symptoms of ebola, educated on the basic pathophysiology of ebola, provided a thermometer with detailed use instructions and given a cell phone to ease the communication process. travelers were allowed to travel freely but were required to check in with public health officials daily. during these check-ins, Àhealth reports were given including the development of any new symptoms, and daily temperature readings for days. ebola has a highly variable incubation period. twenty-one days was the longest interval between exposure and disease presentation to have been reported accounting for its use in both care packages and quarantine [ ] . while the cdc coordinated active monitoring programs, the programs were managed at the state level. all states eventually participated, but with varying start dates. new york, pennsylvania, maryland, virginia, new jersey, and georgia were those to first initiate the program. seventy percent of travelers from west africa enter through these states making them logical starting points for the program [ ] . after much legal debate and unwanted publicity, ms. hickcox mentioned in the introduction, eventually went into active monitoring program which restored most of her personal freedoms while at the same time protecting public interests. currently available technology is considered insufficient to prevent entry of ill individual into ebola naive countries. the general public continues to demand protection of civil liberties that include the freedom to travel and protection of privacy. despite recommendations by the cdc, it is difficult to identify an ill traveler either before a person embarks for the us or at the point-of-entry. post entry monitoring of reliably low risk travels is a socially acceptable alternative to quarantine and considered reliable although not widely tested. screening technologies such as infrared screens may not be considered useful on a daily use basis but may prove of utility under certain circumstances such as an active ebola outbreak. as research continues, technology advances, and better models to study patterns of disease spread are developed, new methods of pointof-entry biosecurity are sure to emerge. bioterrorism is the intentional spread of disease with the goal of destabilizing an opposing group. it is thought to have roots extending back to at least bce when the hittites used infected sheep to spread infection and destabilize their opponents [ ] . since that time, technology has improved and along with it the threat of bioterrorism has augmented. the center for disease control (cdc) divides bioterrorism agents into three separate categories a, b, and c. category a agents are those which are considered to be of highest risk. characteristics group a pathogens are, easy transmission, high mortality rate, protentional for social disruption, and require special action. category b agents are of concern, but considered to have a lower potential for disease than those in group a. this category is comprised of pathogens that are moderately easy to spread, have moderate morbidity, low mortality and require specific diagnostic and surveillance tools. group c are agents of some concern. this group is made of pathogens that are easily available, easy to produce and disseminate, and potentially have significant medical and public health implications. emerging infections also fall within group c pathogens. ebola is considered to be a high threat level a biothreat [ ] . bioweapons are at least as large a threat to homeland security as are traditional weapons. biological weapons are attractive to potential terrorists because they are relatively inexpensive to manufacture, easy to encounter, and easy to distribute [ ] . in the biological weapons convention went into effect. it has been signed by countries and prohibits the development of biological agents for the purpose of warfare. unfortunatly, terrorists fail to abide by this convention, and it is rumored that even some of the countries that signed the convention document continue to engage in clandestine research into biological agents for warfare. characteristics of a pathogen with bioterrorism potential are those with consistent disease induction and progression, high infectivity, are easily transmissible between people, are difficult to diagnose, and have a high mortality rate [ ] . it is also important that the pathogen be stable during production, storage, and distribution [ ] . lack of immunity in the targeted population and diseases that are difficult to diagnoses are also attractive to would-be terrorists. ebola possesses many of these characterizes. ebola possesses many features of an ideal bioterrorism weapon. in the early stages, ebola presents as an acute viral illness. by the time clinical features unique to ebola infection have developed, it is likely that the illness will already have be transmitted to others. particularly vulnerable are those caring for infected patients including family members and health care workers. despite being limited to transmission through body fluids, ebola is highly contagious. ebola has a high mortally rate and is attractive to terrorists because there is already widespread fear associated with ebola infection. reston virus, a non-human pathogen in the ebola family, can be transmitted. there is concern that with genetic manipulation evd could be transformed into an airborne illness and distributed as a bioterrorism weapon [ ] . ebola is one of the many pathogens that could potentially be converted into a biological weapon. preparedness plans at the local, state, and national level all include sections applicable to ebola. all hospitals in the nation have received training on ebola identification and response. continued vigilance and repetitive training sessions are required to ensure that should ebola be used as a biological weapon, it will be rapidly identified and contained. ebola virus is an agent that could be used as a bioterrorism agent. it is deadly, can result in long term infection in survivors, and non-specific clinical presentation make it an attractive choice for would be terrorists. also, for many people, the word ebola creates fear out of proportion to the actual risk of disease. this visceral reaction and exaggerated fear make ebola a tempting agent. on the other hand, the lack of airborne spread and existence of effective vaccine (even if not licensed) are deterrents to its use. it is impossible to know with certainty when the first ebola infection occurred. most likely it was in a remote african jungle and those infected died without a diagnosis other than that provided by the local traditional healer. what can be said with certainty is that the outbreaks are occurring with more frequency. no one knows with certainty why this is. hypothesis tend to center around issues of environmental degradation in association with increased population mobility. increasing population, global warming, and continued human encroachment into forested areas have been put forth as potential contributing factors. increasing population is theorized to be contributing to the increasing frequency of ebola outbreaks. increasing populations, particularly in developing countries, tend to lead to congesting living conditions and rapid disease spread, but this would not explain how the index case in an outbreak becomes infected. experts opinion often lists expanding population as contributing to the ebola outbreak, and intuitively it is credible, but there is little in the way of direct evidence to support this theory. literally hundreds of studies have been conducted on ebola since the outbreak, but none directly addresses the relationship between population growth in africa and increasing frequency of ebola outbreaks. it is likely that the impact of increasing human populations in endemic areas will not be fully understood until the reservoir of ebola has been determined. what we can say with certainty is that once started, ebola spreads more quickly than it did in the past and is killing more people. population level research on ebola has yielded interesting results. for a start, risk of ebola infection has been associated with a higher level of education [ , ] . lower risk for acquisition of ebola at the population level has been associated with urban residence, households with no or low-quality sanitary system, and married men in blue-collar professions in the outbreak in west africa [ ] . other studies have found different results when examining the interplay between population dynamics and the emergence of ebola. for example, in contrast to the study by levy & odoi, ebola transmission has been positively correlated with population density, and proximity to ebola treatment centers in other investigations [ ] . another study found that . % of people who tested positive for ebola cases lived within a -km of roads connecting rural towns and densely populated cities [ ] . basic public health principles hold that increasing population density allows infectious disease to spread more quickly, but it is unclear what the impact is on the emergence of ebola. it is safe that there is a relationship between population density, population distribution, and ebola but the exact nature of that relationship remains elusive. climate change has been cited by mass media sources as the source of emerging disease such as ebola. elevated atmospheric temperature have been associated with the development of evd, but then so have low temperatures [ ] . there does appear to be a relationship between ebola and temperature, but the character of that relationship is not clear. ebola virus is sensitive to high temperatures so intuitively, higher temperatures would not create a more active form of the virus. what may change is the human response to higher temperatures. when it is hot, people sweat more, drink more, and may wear different clothing. it may be that the human response to hot weather is responsible for the noted difference rather than changes in viral activity. it is also possible that temperature changes correlate with other phenomena such as rain storms and that rain, or the response of vegetation to rain somehow impacts the emergence of ebola. climate change, whether due to human activities or natural climatic cycles will change patterns of disease across the globe. how changing weather patterns may affect the distribution and frequency of ebola cases remains to be seen. possibly once the reservoir of ebola virus has been discovered scientists can predict with greater certainty how climate change will impact the emergence of ebola. it is also postulated that ebola is occurring with greater frequency due to increasing human activities within previously untouched natural areas. at least one study has linked deforestation to evd outbreaks [ ] . again, there are limited studies confirming this idea, but logic does suggest that it would be true. expert opinion, and the mass media purport that the increasing frequent outbreaks of ebola are due to environmental encroachment [ ] . as roads are build, forests are cut, and mineral resources exploited humans are in more intimate contact with the forest and its inhabitants including the reservoir for ebola. the reservoir is unknown, but it is probably found in african jungles. a study looking at vegetation cover, population density and incidence of ebola found that vegetation was protective until the population reached people per square km. at this population density vegetation became associated with and increase incidence of evd [ ] . there is a relationship between environmental encroachment and the emergence of ebola, but until the reservoir is found it will be difficult to determine the exact nature of this relationship. the frequency of ebola outbreaks has been increasing. international collaboration is essential to better understand how and why this is occurring. traditional tribal regions do not always follow country lines and both official and unofficial border crossing are common. contact tracing is essential for containment of ebola outbreaks requires countries to coordinate as people cross borders. epidemiological evaluation and experience in treating the disease also require a global rather than country approach. the study of ebola requires systematic evaluation and intercountry coordination to most effectively predict outbreaks and limit their spread once they do occur. the global community would also benefit from international standards for diagnosis, prevention, and treatment. luckily, framework already exists for this collaboration, at least in times of epidemics with pandemic potential. the international health regulations (ihr) agreement is legally binding accord signed by countries. it stipulated that these countries must act to contain the threat if a public health emergency of international concern (pheic) is declared by the who director general. a pheic was declared in august in response to the ebola outbreak in west africa [ ] . the ihr helps to ensure that an appropriate global health response will be made once a public health disaster is well underway. intervention at this level will help curb progression of the disaster. along this same line of thinking, mitigation and preparedness efforts are needed prior to development of a public health disaster. if a pheic is declared, then local measures have failed. improved regional collaboration is needed to help minimize the impact of ebola in the region. many countries at risk for outbreaks of evd would benefit from bolstering of their public health and medical programs. outside assistance is a starting point, but capacity building is required for long term solutions. in countries with weak public health infrastructure international efforts need to focus on programs to develop a sustainable public health system. the challenges are considerable particularly in areas of chronic conflict, but progress has already been made and with continued support will continue into the future. a basic public health infrastructure will help contain ebola as well as whatever threat comes next. when an ebola outbreak hits the general public needs to be educated on how to respond. if ebola preparedness is part of the local education, then lives can be saved. the public can help with surveillance efforts. this would require the population to trust the public health community, believe that their input is useful, and that they be trained to recognize potential ebola in the community. public health education can also assist with limiting spread if an outbreak does occur. this education can be provided through schools, community outreach campaigns, or religious institutions. the education does not need to be complex, just consistent, concise, true, and culturally appropriate. outbreaks of evd have been occurring with increasing frequency. thousands have died and thousands more have been lives have suffered because of the disease. the disease is highly fatal, but even more insipid, it exploits traditional ceremonies and death-rights as a means of spread. poverty, both at personal and national level has resulted in an infrastructure ill-equipped to deal with events such as ebola. overcrowding promotes transmission and lack of financial incentives have delayed vaccine development. despite the barriers, evd is slowing being more well understood, thousands of research articles have been published, and guidelines for every aspect of the disease have been published by the who, cdc, or other government level organizations. progress is being made. esposure patterns driving ebola transmission in west africa: a retrospective observational study assessment of the risk of ebola virus 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interim guidance ebola virus disease: faq: compassionate use of ebola vaccine in the context of the ebola outbreak in north kivu, democratic republic of the congo who: international commission ( ) ebola haemorrhagic fever in zaire who: international study team ( ) ebola haemorrhagic fever in sudan who interim guidance for ebola: exit screening at airports, ports and land crossings november ) who interim guidance for ebola: exit screening at airports, ports and land crossings ebola fact sheet the cdc's new quarantine rule could violate civil liberties. the atlantic a novel immunohistochemical assay for the detection of ebola virus in skin: implications for diagnosis, spread, and surveillance of ebola hemorrhagic fever key: cord- -v r lr authors: vasan, aditya; friend, james title: medical devices for low- and middle-income countries: a review and directions for development date: - - journal: j med device doi: . / . sha: doc_id: cord_uid: v r lr the development of diagnostics and medical devices has historically been concentrated in high-income countries, despite a significant need to expand healthcare services to low- and middle-income countries (lmic). poor quality healthcare extends beyond lmic to underserved communities in developed countries. this paper reviews diseases and conditions that have not received much attention in the past despite imposing a significant burden on healthcare systems in these circumstances. we review the underlying mechanism of action of these conditions and current technology in use for diagnosis or surgical intervention. we aim to identify areas for technological development and review policy considerations that will enable real-world adoption. specifically, this review focuses on diseases prevalent in sub-saharan africa and south asia: melioidosis, infant and maternal mortality, schistosomiasis, and heavy metal and pesticide poisoning. our aim with this review is to identify problems facing the world that require the attention of the medical device community and provide recommendations for research directions for groups interested in this field. a formal search of peer-reviewed articles pertaining to diseases affecting low-and middle-income countries (lmic) was performed using google scholar and pubmed in order to compile this qualitative systematic review. keywords used to identify diseases and technologies included, but were not limited to, the following terms: medical devices, low-cost design, global health, low-income countries, low-and middle-income countries, pointof-care diagnostics, neglected tropical diseases (ntd), neonatal mortality. the names of specific health challenges in conjunction with other keywords were also used in the search. identified conditions were compared based upon the number of affected people, disability adjusted life years, and current research carried out to address the condition. the diseases chosen for this review are melioidosis and neglected tropical diseases such as schistosomiasis. these two diseases combined affect over , people in south asia and sub-saharan africa [ ] . this is a fraction of the number of people affected by mosquito-borne diseases [ ] , but still presents a significant healthcare burden on developing economies. in contrast to, for example, malaria or hiv, these diseases have not received notable attention nor the development of technological solutions toward their treatment. one of the key aims of this review is to expose this unmet need. a section of this review focuses on neonatal mortality, which accounts for over  deaths worldwide and is a significant economic burden due to the number of productive years of life lost [ ] . finally, a section on policy and implementation is provided to aid researchers in identifying useful areas of study. melioidosis (whitmore's disease) is an infection caused by the bacterium burkholderia pseudomallei and is prevalent in south and east asia and northern australia. in major regions where the disease is endemic, the annual incidence rates are up to cases per , people [ ] . it has been classified as a category b bioterrorism agent by the united states and recent reports indicate that the endemic areas have expanded to southern china, hong kong, taiwan, and parts of the americas [ ] . although healthcare facilities have seen significant improvements over the past few years, reports suggest that diagnosis of melioidosis is only possible in large regional referral centers. this could lead to a delay in diagnosis and treatment, and an underestimate of the number of people infected with the disease [ ] . diagnosis of melioidosis can be complicated by the presenting symptoms and their similarity to tuberculosis: abscesses in the lungs, liver, spleen, and brain stem encephalitis. the bacterium typically infects the host by inoculation onto the skin, by inhalation, or by ingestion. inoculation onto the skin can cause subcutaneous abscesses, inhalation can cause pneumonia, and the bacterium can reach internal organs such as the spleen, liver, and the lungs through the blood. the most common presentation of melioidosis is pneumonia, with over % of cases either occurring through lung abscess or due to septicemic spread. an additional challenge with melioidosis is that the bacteria, b. pseudo-mallei, is a difficult organism to kill, with studies showing that it is capable of surviving in triple distilled water for years [ ] . the disease primarily occurs during the rainy season [ ] and people who are in direct contact with wet soil are most vulnerable to the disease. predispositions such as diabetes mellitus, cirrhosis, and alcoholism, or those who are immunosuppressed increase the risk of contracting the bacterium [ ] . over % of patients diagnosed with melioidosis already have diabetes mellitus as a predisposition [ ] . this presents a major problem for south asian countries as the number of patients living with diabetes as an underlying condition is projected to increase by % between and [ ] . an additional risk factor is the age group for contracting diabetes mellitus in these countries is - , with reports showing that incidence of melioidosis peaking in this age group, and most countries of this region exhibiting aging demographics. the recommended treatment of melioidosis involves the intravenous injection of the antibiotic ceftazidime for at least days [ ] . the therapeutic response to the drug is slow and physicians tend to prematurely switch antibiotics in a considerable number of cases, with the assumption that the bacterium has developed antibiotic resistance. the mortality for a -week administration of the drug is % [ ] . although there have been developments over the past years with multiple clinical trials [ ] [ ] [ ] in treating melioidosis, the cost of the antibiotics is still high (from us$ -$ a day [ ] ), imposing a significant economic burden on developing countries. simpson et al. [ ] comment on the price of drug regimens used to treat the disease and cite lack of financial support from pharmaceutical companies for diseases prevalent in rural areas as one of the challenges in developing treatment and diagnostic solutions. melioidosis has been described as "the great imitator" of other tropical diseases such as malaria, typhoid fever, leptospirosis, and tuberculosis [ ] . the varying clinical manifestations of the disease and the multiple affected organs often lead to an incorrect diagnosis. delayed identification results in the administration of antibiotics that are usually unsuitable to treat melioidosis, which has led to high mortality rates as indicated by multiple studies [ , ] . it is critical that rapid diagnostic solutions are developed to reduce mortality rates. the most widely used method to detect b. pseudo-mallei is culturing in a modified ashdown medium with colistin [ ] , but even this technique may yield inaccurate results, especially in nonendemic areas where the clinical suspicion is low. in cases where there is a positive culture, it may be difficult for commercial systems to differentiate between b. pseudo-mallei and phenotypically similar species such as burkholderia thailandensis [ ] . recent reports highlight not only the limitations of bacterial gene amplification and detection but also the development of new screening and amplification techniques [ ] . since the sequencing of the complete genome of b. pseudo-mallei [ ] , several quantitative polymerase chain reaction (pcr) assays have been developed to identify the species [ ] . however, it is still a challenge to identify primers that can differentiate b. pseudo-mallei from closely related species. clinical laboratories have recently started adopting matrixassisted laser desorption/ionization mass spectrometry systems for the identification of bacterium [ ] [ ] [ ] [ ] , with modest clinical success alongside reports that suggest the databases used mass spectrometry require expansion to accurately identify b. pseudomallei. this technique shows great potential to be used as a rapid identification technique but has the limitation of requiring skilled personnel, expensive equipment, and the infrastructure to support them. low-cost molecular profiling and analysis has been a challenge, and advancements in this field would have a significant beneficial impact on healthcare outcomes in endemic areas. surface acoustic wave-based atomization has been proposed to simplify the sample extraction and filtration process [ ] . highfrequency surface acoustic wave-based atomization was used for the formation of micrometer scale droplets of cell lysate, and the purification step was achieved by loading the sample on a porous membrane placed in the direction of propagation of the surface acoustic waves. since the main cause of melioidosis spread is through soil during the rainy season, analyzing soil for the presence of b. pseudomallei would prevent infection and hospitalization. environmental samples are difficult to purify via pcr due to the typical presence of a diverse species of bacteria and fungi. development of better enrichment and purification techniques would enable an increase in the number of relevant dna templates for amplification to occur. an alternative to sampling environmental specimens is the analysis of relevant clinical samples-blood and sputum [ , ] . the sensitivity of pcr-based techniques is high for sputum and pus, but, by contrast, the sensitivity for blood samples is quite low [ , ] . there may be as many as , cases of melioidosis every year with an estimated , deaths [ ] . the most commonly used technique for identification, bacterial culture, is % specific but has low sensitivity. slow or incorrect diagnosis results in a significant burden on healthcare systems and can be fatal. matrix assisted laser desorption/ionization-time of flight mass spectrometry is increasingly being used as a rapid and accurate technique to identify isolates [ , ] , though significant challenges to its adoption remain but likely can be addressed by further research in this field. this section details the risks associated with poisoning due to metals, such as lead and cadmium, and associated detection techniques. additionally, we consider the effects and detection of environmental pollutants arising from intensive agricultural and industrial practices. evidence of the toxicity of lead has been documented in studies conducted as early as [ ] and studies demonstrating the adverse effects of lead on attention, childhood development, and neurological disorders were established in the s [ ] . lead poisoning has been shown to impair cognitive ability and social function [ ] . the toxic properties of lead are partially due to its ability to compete with calcium at a cellular level, for neuronal signaling [ ] and in inhibiting calcium influx into cells [ ] . the neurological effects are due to its inhibitory impact on stimulated neurotransmitter release [ , ] . at high doses, lead can inhibit myelin formation and compromises the integrity of the blood brain barrier. children are more sensitive to lead than adults due to increased hand-to-mouth activity and increased absorption in the gut. the acceptable thresholds for lead in blood have drastically changed since the s in the united states, from lg/dl to essentially recognizing that there is no safe level of lead exposure, with amounts under lg/dl having been shown to adversely impact learning [ ] . significant reduction in lead exposure in the united states has been achieved by eliminating lead in gasoline and paint, but lead contamination of water remains a problem without a commensurate level of attention [ ] . the decision in by the city of flint to change its primary source of water saw lead levels in water rise to as much as lg/dl in some cases [ ] , with lasting healthcare implications. the only medical treatment for lead exposure is chelation [ ] , but chelating drugs may not be available in lmic and in lower income regions of even wealthy countries. in any case, they are not very useful to treat chronic exposure. another heavy metal that has adverse health effects is cadmium, commonly used in the electronics industry in batteries and circuit boards. chronic exposure to cadmium results in accumulation in the kidneys that eventually leads to renal damage [ ] . cadmium can also be absorbed by plants more readily than other heavy metals, presenting another mode of uptake in regions contaminated with industrial waste. the number of people worldwide affected by heavy metal poisoning is difficult to estimate due to the varying sources of poisoning but, given that incidents like the one in flint that occurred in a developed country with safeguards in place to prevent lead poisoning, there is a need to estimate atmospheric and water-based heavy metal exposure risks across the world. the daily per-capita supply of calories has increased by over % over the last years [ ] , and as this demand increases, there has been a push toward maximizing agricultural productivity. increasing agricultural yield has been possible, in part, by the increased use of pesticides. the food and agriculture organization of the united nations defines pesticides as growth regulators and includes substances that can prevent harm to crop during or after harvest [ ] . exposure to pesticides may occur through direct means through occupational exposure or via indirect means through drinking water, dust and food. the world health organization (who) estimates that  severe pesticide poisonings occur annually and that at least , people die as a result of exposure, with % of these cases being from lmics [ ] . the effects of pesticide exposure are wide ranging: chronic diseases such as cancer and developmental disorders [ ] , immunosuppression, hormone disruption, diminished intelligence, and reproductive abnormalities [ ] . of the various classes of pesticides in use today, organophosphate pesticides have been shown to cause substantial morbidity and mortality [ ] but still account for over % of fertilizer produced [ , ] . organophosphates are readily absorbed through the skin, and the gastrointestinal and respiratory tracts. the mechanism of action is by inhibition of acetylcholnesterase, which promotes the production of the neurotransmitter acetylcholine [ ] . overstimulation of nerves due to excess acetylcholine results in autonomic dysfunction, involuntary motor movements, and respiratory depression. long-term exposure has been shown to result in carcinogenicity [ ] . many farmers in developing countries are exposed to pesticides due to unsafe storage and handling practices, a lack of protective equipment during spraying, or chronic exposure to contaminated soil and water. although there have been attempts to implement safe handling practices [ ] and reduce pesticide use, there is a need to develop protective equipment that can be deployed in developing countries to prevent exposure alongside devices that can detect the presence of harmful pesticides in the local environment. there is furthermore a need to monitor the presence of heavy metals and organophosphates in water supplies and in soil, particularly in regions of significant industrial or agricultural output. paper-based microfluidics was first reported by george whitesides' group [ ] and has the advantage of being inexpensive, readily available, and can wick biological fluids without active pumping. a recent point-of-care paper diagnostic assay for the detection of lead and mercury in water was developed by lewis et al. [ ] . the device consists of hydrophobic regions that define where the fluid travels through capillary action. the assay is designed in such a way that the time taken for the fluid to travel from one part of the chip to another is indicative of the concentration of the analyte. this is accomplished by the use of glucose oxidase or streptavidin, which inhibit flow depending on analyte concentration. it has not been determined if time-based assays provide quantitative results for a range of users. more sensitive tests to detect the presence of lead in drinking water have been developed, with one group reporting a fourfold increase in sensitivity over conventional lateral flow assays [ ] . the increased sensitivity was achieved by conjugating gold nanoparticles to a lead-specific monoclonal antibody (anti-pb(ii)-itcbe). organophosphate detection schemes have been considered due to their historical use as chemical warfare agents [ ] , though there has been a lack of development in the detection of trace amounts of organophosphates, despite knowledge they pose a significant health risk. as of , about  babies die in the neonatal period (the first weeks of life) and a similar number of babies are stillborn [ ] . a majority of these deaths are in low-income and middleincome countries in africa and southeast asia [ ] as illustrated in fig. . some estimates show that % of all deaths in children under the age of five occur within the first month of life [ ] . assessment of the cause of death is difficult due to a lack of data collection in lmics, but estimates indicate that complications arising from asphyxia, severe infections, and preterm births are the main causes of death [ ] . the who defines birth asphyxia as the clinical description of a newborn that fails to initiate or maintain regular breathing at birth [ ] . this term applies to a clinical condition and is not a specific cause of death. advanced resuscitation is needed for less than % of babies at birth and babies that typically require advanced resuscitation by intubation typically require a neonatal intensive care unit to recover [ , ] . these are typically not available in regional hospitals in lmics. basic resuscitation, however, which only requires bag-and mask-type ventilators, is easy to implement for cases where intrapartum breathing assistance is required. published guidelines vary on when to provide resuscitation [ ] , but the who recommends resuscitation in cases where the baby does not cry, breathe at all, or is gasping for s [ ] . it is crucial that these guidelines become widely known, as there is potential for adverse effects such as upper airway damage if respiratory support is provided to healthy babies [ ] . existing devices in use in low-resource settings include mucus extractors with one-way valves and rubber bulb suction devices. the key downside of these devices is that they present an infection hazard for both the neonate and the healthcare provider [ ] , alongside the potential risk of hypothermia in prolonged resuscitation of a neonate [ , ] , and asphyxia. however, asphyxia may be overcome with expanded care and improved healthcare provider training, but it is crucial that clear protocols for resuscitation be established first. congenital abnormalities [ ] likewise receive less attention than other medical conditions, especially given that they account for % of all neonatal deaths. one of the most common abnormalities in neonates is spina bifida, which results from the failure of fusion of the caudal neural tube. a large percentage of cases can be prevented by folic acid supplementation as long as the condition is diagnosed [ ] . the underlying cause of the condition is not known but it has been established that women with pregestational diabetes or a high body mass index are at an increased risk of having a child with spina bifida. the protein a-fetoprotein (afp) and ultrasound can each be used to identify fetuses that have the condition [ ] . point-of-care testing of afp would enable screening and potential early detection of spina bifida and allow the patient to seek further medical care in a primary setting. the typical values in maternal serum are under ng/ml until - weeks of gestation [ ] . a quantum-dot-based sensor for the detection of afp has been reported by yang et al. [ ] , with sensitivities to ng/ml. this test, however, relies on comparing the relative fluorescence intensities of the sample with a control, and can be difficult to interpret in the absence of optics and skilled personnel. the who compendium of medical devices and technologies for low-resource settings lists two ultrasound scanners, which are priced at us$ , and us$ , [ ] , still a significant cost in comparison to the annual budget of many hospitals in low-resource settings [ ] . ultrasound is otherwise commonly used to diagnose congenital structural defects during pregnancy. one such condition typically diagnosed using fetal ultrasound is hydrocephalus, a condition where fluid accumulates in the ventricles within the brain. the treatment for this condition involves the implant of a shunt that drains away excess cerebrospinal fluid into the abdominal cavity. the problem with this procedure irrespective of the settingwhether in an lmic or a high-income country-is that implanted shunts fail due to an obstruction caused by glial and inflammatory cells [ ] . a comparison between an inexpensive shunt developed and used in africa and one currently in use in the united states to treat the condition showed that there was no significant difference in clinical outcomes [ ] . the failure rate in the first years for implanted ventriculoperitoneal shunts remains high, at over % [ ] , indicating that there is a need to evaluate failure due to occlusion in greater detail. neglected tropical diseases are a group of thirteen bacterial and parasitic infections that affect around .  people worldwide [ ] as illustrated in fig. . they are highly prevalent in sub-saharan africa and south asia, where over % of the population lives on less than $ a day [ ] . these diseases make it difficult for people affected by them to rise out of poverty as their effects can be chronic or, in some cases, fatal. schistosomiasis is such an ntd, affecting  people in sub-saharan africa alone, accounting for % of the world's cases, and associated with increased human immunodeficiency virus transmission [ ] . about % of the population of sub-saharan africa lives near bodies of water that have been contaminated with schistosomiasis hosts [ ] , with those living near dam reservoirs at higher risk [ ] . the population most affected by schistosomiasis is children and young adults. schistosomiasis can be caused by two strains of bacterium, one of which affects the urinary tract and the second infecting the intestine. schistosoma haematobium is one of the leading causes for urinary tract infections, and around , deaths annually [ ] . schistosoma mansoni causes bowel ulceration and an estimated , deaths [ ] . adult male and female worms can live in the human host for an average of years and the disease spreads by the transmission of eggs to an intermediate snail host typically found in water bodies. the worms feed on glucose present in blood and erythrocytes and excrete waste into the blood stream. biomarkers present in waste may serve as a target for detecting schistosomiasis. the primary treatment for the disease is the drug praziquantel, which is only effective against mature worms [ ] . prolonged treatment for - weeks is required to completely cure the disease. although this drug is being employed in the field to treat schistosomiasis, the mechanism of action is still unknown and side effects include abdominal pain and passage of blood in the stool [ ] . the current diagnostic standard for schistosomiasis is the presence of viable eggs in urine or fecal matter, but the test has a low sensitivity [ ] . the three recommended detection techniques by the who are microscopy, a urine-based dipstick assay [ ] , and the kato-katz fecal examination [ ] . the kato-katz method was developed in the s and uses a cardboard cutout over a glass slide and microscopy to easily count the number of eggs in a sample and quantify the number of eggs per unit weight but this technique, like the others recommended by the who, lack sensitivity. a point-of-care lateral flow assay to detect the presence of circulating cathodic antigen was developed [ ] , addressing the sensitivity limitations of the kato-katz technique, but only for schistosoma mansoni. it did no better than the kato-katz technique when used for stool samples. recent reports on diagnosis of the disease have called for better diagnostic tools [ ] , one of which is pet (positron emission tomography) imaging. this group made use of glucose intake of the worms in vivo to detect and quantify their presence using a pet scanner. with groups starting to develop handheld pet scanners [ ] , this might present a novel research direction for groups looking to develop diagnostic technologies. pcr-based techniques have also been developed to analyze cell-free parasite deoxyribonucleic acid in human plasma [ ] , and the development of microfluidic pcr-based systems [ ] for schistosomiasis could lead to improved detection. control measures against the disease include preventative therapy using praziquantel [ ] , issued by schools screening and treating children for this and other diseases. an additional screening technique that has been attempted in the past is to monitor and eliminate snails that serve as intermediate hosts. the who in pledged to control the morbidity caused by the disease by and eliminate it as a public health problem by , leading to an increased effort in diagnosing and educating the communities most affected by the disease. this has stimulated increased funding and opportunities for novel interventions. there have been significant improvements in healthcare outcomes over the past few decades due to a combination of efforts by public and private organizations, and technological advancements in diagnostics and surgical devices. despite this, there are some limitations to adoption and implementation of technology. in some cases, the underlying disease or condition may not have a device or diagnostic solution. this is common in the case of neglected tropical diseases that are a significant health burden but have seen insufficient investment from the private sector. a point-of-care monoclonal antibody-based dipstick for urinary schistosomiasis was developed by a ghanian group in [ ] but has not been commercialized [ ] . the technology may exist, but other problems such as distribution or energy required to power the devices may not exist [ ] . oxytocin is used to reduce the risk of postpartum hemorrhage but requires refrigeration, unavailable throughout the day in resourcelimited settings. advances in packaging that could extend the shelf life of drugs and vaccines would expand access to available care in these cases. in the case of diagnostics, a more sensitive and specific test may exist but there could be reluctance to adopt it or mistrust in the results it produces due to past misdiagnosis with old technology. rapid diagnostic tests for malaria have been shown to have superior sensitivity and specificity than the current gold standard for malaria detection, microscopy [ ] . but a study found that doctors prescribed antimalarial drugs-even in the case of a negative test result [ , ] . skilled healthcare is crucial to improve surgical outcomes. for example, access to skilled surgeons for delivery is as low as % in sub-saharan africa and less than % in south asia [ ] . designing medical devices for lmic's presents unique challenges not seen in developed markets. the who estimates that % of medical equipment coming from developed countries does not work in hospitals in developing countries [ , ] due to lack of trained personnel, limitations with infrastructure, and the lack of spare parts or support for equipment. it is evident from these examples that research and development of novel diagnostic tools and devices alone is insufficient for adoption. in the context of the conditions presented in this paper, there is a need to develop an effective way to screen for schistosomiasis and melioidosis. the spread of melioidosis starts through soil in the rainy season and the presence of schistosomiasis can easily be detected in fecal matter. a technique to purify samples coupled with existing point-of-care diagnostics would stop the spread of the disease at the source. this can be extended to detect the presence of environmental contaminants such as organophosphates and heavy metals. an increase in sensitivity can be achieved if adequate processing is done prior to point-of-care diagnosis. the un's fourth millennium development goal called for a two-third reduction in neonatal mortality by . although there has been significant progress toward this goal, there are still  neonatal deaths every year, predominantly in south asia and africa. developing medical devices specifically for neonatal care and not having to repurpose devices made for adults would enable easier surgical procedures. better detection schemes for diseases such as spina bifida or hydrocephalus using low-cost ultrasound transducers would prepare doctors better for surgery. it is critical to rethink what low-cost means for such applications, especially considering the annual budget of hospitals in lmic's. frugal technologies that can be used repeatedly can withstand environmental conditions and can be used easily by healthcare workers in target countries should be prioritized. schistosomiasis (primer) clinical review: severe malaria cost effectiveness analysis of strategies for maternal and neonatal health in developing countries melioidosis the global distribution of burkholderia pseudomallei and melioidosis: an update melioidosis: the tip of the iceberg? survival of burkholderia pseudomallei in the absence of nutrients melioidosis: epidemiology, pathophysiology, and management risk factors for melioidosis and bacteremic melioidosis melioidosis global prevalence of diabetes: estimates for the year and projections for 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diseases in low-income countries rapid diagnostic testing for malaria point-of-care diagnostics for global health rapid diagnostic tests compared with malaria microscopy for guiding outpatient treatment of febrile illness in tanzania: randomised trial barriers for medical devices for the developing world technologies for global health key: cord- -n axd bq authors: rusoke-dierich, olaf title: travel medicine date: - - journal: diving medicine doi: . / - - - - _ sha: doc_id: cord_uid: n axd bq before travelling to other countries, thorough travel advice should be provided. not only information about diseases of specific countries but also general advice for travelling should be given on this consultation. before travelling to other countries, thorough travel advice should be provided. not only information about diseases of specific countries but also general advice for travelling should be given on this consultation. the following topics should be included in the travel advice consultation: vaccinations (general and country specific) country-specific diseases malaria prophylaxis mosquito prophylaxis (wearing bright long-sleeved clothes, avoiding perfume, staying in air-conditioned rooms, using a mosquito net, using insect repellents, staying inside at dawn and dusk) food consumption and drinking overseas (no consumption of ice cubes, uncooked meals, salads and food, which is exposed to flies, limited alcohol consumption) uv protection (using sun cream, avoiding sun exposure between . and . o' clock, remaining in shaded areas, wearing a hat and covering skin) fitness assessment for travelling, flying and diving challenges of different climates and their effects on the personal health (dehydration, hyperthermia) medications thrombosis counselling counselling on symptoms on return, which require review (fever, skin changes, abnormal bleeding, lymphadenopathy, diarrhoea) sexual transmitted diseases contraception rabies the following items should be asked to enable to give the appropriate advice: risk assessment of the travel in a particular country (transport, area of stay/ rural or resort, reason for travelling, appropriate conduct overseas, pre-existing diseases and medications) vaccination status accomodation and stopovers duration of the stay the vast majority of up-to-date travel information and information about tropical disease are available on who (world health organization) or cdc (centres for disease control and prevention) websites. information on these websites are frequently updated. before giving appropriate advice based on these online resources, it should be checked, which medications are available in the particular countries. hence, recommendations need to be adjusted individually. usually, a medication record is required at the customs. however, it might be sufficient, if the original medication box has the patients and prescribing doctors details (. table . ). malaria is a tropical disease transmitted by the female anopheles mosquito. the distribution of malaria is primarily in the tropics and subtropics of africa, central and south america, asia, papua new guinea and the western pacific islands. as popular diving spots are located in these areas, malaria prophylaxis and advice should be given. the who (world health organization) estimates the worldwide number of people affected by malaria with about million and , , deaths ( ). the plasmodium parasites need temperatures above °c in order to complete the entire growth cycle. therefore, malaria occurs in some places only seasonal. additionally, there are differences in anopheles species regarding the affinity to the host and their local distribution. some genetic factors are protected against malaria. for example, sickle cell anaemia gives a certain protection against p. falciparum and duffy negative blood group against p. vivax. it appears that after recurrent malaria infections, the body adapts to the disease. this means that an infection is possible, but the symptoms of malaria seem to be reduced. children and pregnant women have an increased risk of being affected by malaria. additionally, children have a high mortality rate. during pregnancy the resistance against malaria is reduced. it also poses an increased risk for the unborn child (low birth weight). anopheles is active especially at sunrise and sunset. different kinds of mosquitoes are rather active during the day and can transmit other diseases such as dengue. especially p. falciparum and p. vivax have resistances against antimalaria drugs. there are different plasmodium pathogens: p. falciparum: worldwide tropical and subtropical distribution, mainly in africa; pathogen of severe malaria causes million deaths per year; rapid growth in the blood with haemolysis and emboli due to cytoadherence of affected erythrocytes; - days of incubation, irregular fever spikes. p. vivax: mainly in asia, latin america and some countries in africa; the disease can be activated after months or years. incubation period of - days; fever spikes every days. p. ovale: mainly west africa and the western pacific islands. similar to the p. vivax, it can also infect people with duffy-negative blood group; incubation period of - days; fever spikes every days. p. malariae: worldwide distribution; typical -day cycle, untreated can lead to lifelong chronic malaria; incubation period - days; fever spikes every days. p. knowlesi: southeast asia, mainly infected animals. after the anopheles mosquito aspirates with gametocytes infected blood, the gametocytes develop to gamete in the mosquito's intestines. in the blood of the mosquito, the microgametes (male) penetrate the macrogametes (female), forming zygotes. then cells are changed to an elongated, motile ookinete. this evolves into an oocyst. after the oocyst bursts, sporozoites are released and get in the saliva of the mosquito. the entire cycle inside the mosquito takes - days. if sporozoites enter the human bloodstream through the saliva of the . symptoms of malaria appear after the incubation period. the incubation period varies depending on the pathogen. it can be between a few weeks and also takes up to several months or even a year (p. vivax or occasionally p. ovale). malaria can be divided in three different forms: malaria tertiana: pathogen: p. vivax and p. ovale; fever every second day with one day without fever, spontaneous remission after max. years malaria quartana: pathogen: p. malaria; fever every third day with days without fever, no spontaneous remission malaria tropica: pathogen: p. falciparum, irregular fevers due to the lack of synchronisation of the parasite reproduction, severe form of malaria (malaria maligna) with high fatality, recurrence up to years the fever has a specific pattern. in the first hour, strong rigors and increasing fever typically develop. the fever can reach °c and more for duration of about h. it is often associated with flushing, vomiting and nausea. the fever stage is followed by an approximately -h stage of severe sweating with decreasing fever. severe forms of malaria can be fatal in within few days. causes of death are cerebral malaria, respiratory failure with adrs and kidney failure. the main reason of these complications is the cyto-adherence ("bonding") of the erythrocytes. it results in a failure of the microcirculation followed by ischaemia of vital organs. . the treatment depends on the severity and the pathogen. in complicated malaria, admission to the intensive care should be considered, if more than one of the following criteria exists: inability of the oral intake of medication parasite load of erythrocytes > % severe symptoms of malaria (see table above) the treatment options of complicated malaria are: artesunate (allowed only in some countries): . mg/kg/bw iv; first dose on admission, repeated after and h, minimum duration of therapy h and then once a day, till oral therapy is tolerated. or combination of quinine + doxycycline or clindamycin. quinine: Ȥ first dose: mg/kg/bw iv over h or mg/kg/bw iv over min with subsequent administration of mg/kg/bw iv over h. Ȥ maintenance therapy: mg/kg/bw iv over h three times a day, beginning h after the completion of the first dose. Ȥ exemption: if the patient received three or more doses of quinine in the last h or had an mefloquine prophylaxis in the last h or received a mefloquine treatment in the last days. + doxycycline: mg iv twice daily for days (iv or oral) or clindamycin: Ȥ initial dose: mg/kg/bw Ȥ maintenance dose: mg/bw every h for days (iv or oral) after clinical improvement medication can be changed to a complete cycle of the oral therapy of an uncomplicated malaria (riamet ® or quinine with doxycycline or clindamycin). uncomplicated malaria can be handled on the normal ward. outpatient therapy with close supervision can be considered under the following conditions: parasite load of erythrocytes < %. age > months. no co-morbidity. pregnancy is excluded. ability of oral medication intake. p. falciparum is excluded. clinically stable under medical therapy for the last h. a daily blood smear is necessary during treatment to follow the process of the disease. the patient can be discharged from the hospital and continue treatment at home; if oral therapy is tolerated, a clinical improvement is achieved and the parasite count decreases. a week and a month after discharge, blood smears should be repeated. primaquine as eradication therapy is approved in some countries. it is the only drug that can be used to eliminate hypnozoites, which are the dormant forms of the malaria parasites that occur with p. ovale and p. vivax. because primaquine causes haemolysis in g- -pd deficiency, g- -pd status prior therapy needs to be established. if an eradication with primaquine is required in patients with g- -pd deficiency, a dose up to mg weekly for weeks, with monitoring for haemolysis, could be considered. in children methaemoglobinaemia can be provoked by giving primaquine. a single dose of primaquine mg for p. falciparum, p malaria and p. knowlesi can be given to sterilise the gametocytes. if malaria caused by p. vivax or p. ovale or co-infection with these parasites is suspected, a -day treatment with mg of primaquine twice a day is recommended. before commencing holidays overseas, medical advice should be given in order to assess the malaria risk of the particular country. in nearly all tropical areas, there is a risk of getting infected with malaria. in some tourist areas, this risk might be small, but infection is still possible. in particular day trips to more remote areas pose a risk. some areas have malaria outbreaks and therefore should be avoided. in general, mosquito bites should be avoided to minimise the risk of any mosquitoborne infections. mosquitoes transmitting malaria are mainly active at night, sunrise and sunset. however, mosquito bites are also possible throughout the day. long-sleeved shirts, long pants and closed shoes cover the skin and provide protection against insect bites. insect repellent for the skin and clothes offer additional protection. higher concentrations offer better and longer protection. the protection period of a normal insect repellent lasts usually only - h. slow release products can prolong the effect. mosquitoes avoid air-conditioned rooms. so staying in air conditioned rooms itself provides certain protection. spraying insecticides in rooms and surroundings can be helpful to repel and minimise the quantities of mosquitoes. the bed should be covered with a mosquito net (. fig. . ). chemoprophylaxis is important, because the main cause of malaria deaths is still inadequate chemoprophylaxis. there are different drugs for chemoprophylaxis available. they are subject to the travel location and the parasite's resistances to certain drugs. in addition, they differ in side effects, dosage and cost. except malarone ® , all other drugs for the chemoprophylaxis against malaria have to be taken weeks after leaving the country as they aren't sufficiently effective against the primary liver stages of malaria. mefloquine (lariam ® ) is the only malaria prophylaxis without absolute contraindication in pregnancy. diving (decrease in vigilance); - weeks (at least week) before entering the malaria-endemic country and weeks after return; lariam ® is a category b medication and is the only medication against malaria without absolute contraindication in pregnancy. the use in the first trimester should only be considered, if the expected benefits justify the potential risk to the foetus. however, recent studies suggest that even in the first trimester this medication is safe to take. the dengue virus is an arbovirus. it has four different serotypes (denv - ). dengue has a worldwide distribution in the tropics and subtropics, especially in asia and south america. approximately - million cases and about , with serious complications per year occur. there is a % mortality, which can be reduced to % with timely diagnosis and appropriate treatment. it has an increased risk for children under years and persons with previous dengue infections. the dengue virus is transmitted by the aedes aegypti mosquitoes. these mosquitoes mainly bite at day and in twilight (. fig. . ). z symptoms the incubation period is - days. there is a wide range in severity of dengue symptoms. the majority of infections cause minor symptoms. but dengue infections can be also quite severe (. table . ). in particular recurrent infections with dengue are associated with complications and severity of the disease. it is important for the treating doctor to remember that after the initial fever, the critical phase follows. therefore, the patient must be monitored closely during this time. the disease goes through three stages: fever phase (day - ): sudden high fever °c occasional associated with bradycardia; myalgia mainly in the spine, arms and legs ("breakbone fever"), headache; retrobulbar pain; rigors; metallic/bitter taste; vomiting; and dehydration. . critical phase (day - ): normal temperature with possible mild fever later on, leucopenia, exanthema, petechiae and lymphadenopathy. severe dengue: abdominal pain, spontaneous bleeding, volume shift in to the peritoneal space ("plasma leak"), pleural effusion, hepatomegaly (≥ cm), rapid increase in haematocrit and decreasing thrombocytes, shock (dengue haemorrhagic shock = dhs or dengue shock syndrome = dss), increased bleeding (dengue haemorrhagic fever = dhf) and organ failure (particularly liver). remission (after days lasting sometimes for weeks): risk of hyperhydration is given when extravascular fluid is reabsorbed without reducing the intravenous fluid administration. in particular in long remissions, fatigue and depression may be present. normally there are no long-term damages after a dengue infection, and the vascular changes recover completely. z treatment there is no medication available to treat dengue directly. the diagnosis of dengue can be demonstrated by pcr in the initial phase and using igm and igg a few days later. due to severe complications, the haematocrit, coagulation parameters, leukocytes and platelets have to be tested daily. thrombocytes < , cells/mm can rise the suspicion of dhf. if pleural effusion is suspected, a cxr should be obtained. by tightening a blood pressure cuff petechiae can be provoked (medium pressure of the systolic and diastolic pressure for min). this can be used as a diagnostic tool. an increase of the haematocrit of > %, pleural effusion, ascites or hypoproteinaemia could be a sign for extravascular fluid loss. the extravascular fluid loss is typically found in the initial phase. hence, fluid replacement therapy is crucial in this phase. as the extravascular fluid loss can come to an end quite quickly, a complication of the fluid replacement therapy is hyperhydration. decrease of haematocrit of > % after fluid administration can represent a fluid excess and hyperhydration. hence, careful monitoring of the fluid balance and weight are necessary. the therapy is adjusted according to its severity. if necessary, dic, blood loss or shock require specific treatment. like dengue, chikungunya is a mosquitoborne disease. the species transmitting the chikungunya virus (chikv) are aedes aegypti in the tropics and subtropics and aedes albopictus in colder regions (. fig. . ). these mosquitoes bite day and night, but mainly in the early morning hours and late afternoon. the incubation period is between and days. the symptoms are similar to that of dengue. patients suffer from sudden fever with headache, skin rash, fatigue, strong limbs and muscle pain. affected joints often are swollen. the symptoms generally last for few days but can persist for weeks and years. the disease has no long-term effects. for diagnosis rt-pcr and virological methods can be used in the initial phase. later, it can be diagnosed by igm and igg. igm peaks after - weeks and can be detected up to months. the treatment requires analgesia only. . yellow fever is a disease transmitted mainly by the aedes aegypti mosquito but also by other mosquitoes or ticks. the pathogen is a rnacontaining flavivirus. it has approximately , infections with approximately , deaths annually. % of cases occur in africa and the remaining % in south america. the risk of getting infected with yellow fever is with : - in africa and higher than : in south america (. fig. . ). the transmission occurs in rainforest areas (jungle or sylvatic cycle), where mosquitoes transfer the virus from monkeys to humans, in endemic areas of the savannah (savannah or intermediate cycle) either transferred from monkeys or human to humans via mosquitoes or in urban areas from human to human via mosquitoes. the incubation period is - days. the disease has two phases. the acute phase comes with fever, headache, myalgia, headand backache, loss of appetite, nausea, vomiting and diarrhoea. the second phase occurs only in approx. % of infected humans within the next h. jaundice, abdominal pain and vomiting are rapidly developing, followed by diffuse bleeding (epistaxis and gi bleeding) and multi-organ failure (mainly kidneys). if symptoms of the more severe second phase develop, % of the patients die within the next - days. patients who survive usually recover without significant organ damage. the diagnosis can be made via a blood or tissue biopsy of the liver. there is no cure for yellow fever and only supportive measures can be taken. however, a very effective life-vaccination (stamaril ® ) is available. only authorised doctors are authorised to prescribe and give the vaccine. severe side effects of these vaccinations are severe allergic reaction ( : ), vaccine-associated neurotropic disease/post-vaccinal encephalopathy ( : ) and vaccine-associated viscerotropic disease/ multi-organ failure ( : ). for travelling into countries where yellow fever is endemic, vaccination is mandatory. the side effects seem to be age-related and occur increasingly with progressive age or in young children. the vaccination is contraindicated in children . · other mosquito-borne diseases below month and during pregnancy. analysis of yellow fever vaccines adverse events demonstrated an increased frequency of serious adverse events in persons age years and older. the risk of viscerotropic side effects in < years is : , in a population of - years of age : and in > years of age : . a failure to be vaccinated or being documented can lead to a refusal of entry into other countries or to a certain time in quarantine when leaving the area where yellow fever occurs. if there is a clinical indication against receiving yellow fever vaccine (e.g. children < month or poor immune status), a written medical exemption can be granted, to enable to travel to these countries without vaccination. absolute contraindications for a yellow fever vaccination are: allergy against the vaccine or egg protein age < months immunodeficiency neoplasia transplantations immunosuppressive therapies relative contraindications for a yellow fever vaccination are: age - months age > asymptomatic hiv infections and cd + t lymphocytes - /mm ( - % of the total in children < years of age) pregnancy lactation aedes aegypti spreads also the zika virus. however, it is also sexually, intrauterine and perinatal transmitted. currently the main distribution is countries in south and north america as well as the caribbean islands, singapore and some countries in south pacific islands. symptoms of zika infection may be fever, rash, arthralgia, myalgia, headache and conjunctivitis. but in most cases, an infection is asymptomatic (~ %). these symptoms are lasting for several days to a week. the incubation period is - days but is likely to be a few days to a week. the diagnosis can be made via pcr or serology. blood pcr can be detected only in the first week of the disease. urine pcr can detect the virus up to weeks. there is no specific treatment available. deaths are unlikely. there is a potential risk during pregnancy, as microcephaly or other birth defects (~ %) may develop. the zina virus cane be also transferred via semen and can affect unborn life. ross river virus (rrv) is transmitted by the bites of culex annulirostris, aedes vigilax, aedes normanensis and aedes notoscriptus in australia, papua new guinea, parts of indonesia and the western pacific islands. the main transmission time is in the humid summer month from december till march. the main symptoms are fever, rash, headache, myalgia, arthralgia and fatigue. the initial symptoms with fever last usually for - weeks. myalgia and arthralgia usually last longer. symptoms of fatigue and depression can be late complications. the incubation time is between days and weeks. the diagnosis is made with igm. there is only symptomatic treatment available. barmah forest virus (bfv) is transmitted by the same species as the rrv. it mainly can be found in australia. many people don't develop any symptoms. the incubation time is - days. if symptoms appear, they are similar to the one of rrv. the initial symptoms last for - weeks, and the arthralgia and myalgia may last for months. the diagnosis is made with igm. there is only symptomatic treatment available. sindbis virus (sinv) is related to the chikungunya virus. it is mainly transmitted via the culex and culiseta mosquitoes. it can be found in europe, africa, asia and oceania. the symptoms and the duration of the symptoms are quite similar to rrv and bfv. the diagnosis is made with igm. there is only symptomatic treatment available. the o'nyong-nyong virus (onnv) is related to the chikungunya virus but is restricted to africa. it has similar symptoms as the chikungunya virus but has additionally mainly cervical lymphadenopathy, and the affected joins rarely show signs of an effusion. most of the gastrointestinal tract infections are caused by poor hygienic conditions of the travel destination. occasionally ingested seawater can cause intestinal infections too. the main transmission routes are either food-borne or by contact. however, the most common cause for gastrointestinal infections is eating contaminated food. old, warmed up food, salads, unpeeled fruits, poorly cooked food, contaminated water (ice and already opened bottles with refilled water) and ice cream often have substantial quantities of pathogens and pose a risk. hence, the best protection against gi infections is avoiding contaminated food or drinks. usually gastrointestinal infections last for a few days and are self-limiting. if diarrhoea contains blood or mucus in combination of high fever for more than days, more thorough assessment is required. blood and mucus without fever are most likely related to a parasitic disease. if fever is present, it's most likely a bacterial or viral disease. but also climate change by itself or dehydration may be caused by autonomic dysregulation gastrointestinal symptoms such as nausea, weakness, vomiting and diarrhoea. with dehydration the dci risk increases. rehydration and supply of certain electrolytes such as sodium, chloride and potassium are the most important treatments for gastroenteritis. fatigue is a common associated symptom. tannins of black tea boiled for more than min might be beneficial for diarrhoea. the consumption of bananas is recommended because of the high content of potassium. but the best options are rehydration preparations in form of drinks, powders or icy poles. loperamide may slow down the peristaltic and give some relief from diarrhoea. probiotics may support recovery. a low fibre diet is rec-ommended in the active phase of diarrhoea. administration of antibiotics is rarely necessary and indicated. it only is used for serious illnesses or symptoms. reservoir: poultry or meals prepared with egg incubation: - h symptoms: fever, vomiting nausea, diarrhoea, occasionally blood and mucous in the stool duration: - days treatment: symptomatic; azithromycin g od for days or ciprofloxacin mg bd for days or ceftriaxone g od reservoir: water and food incubation: - weeks symptoms: headache, myalgia, bradycardia, roseola in the abdominal area, continuous fever - °c, porridge -like diarrhoea, intestinal bleeding and decrease of the fever after weeks treatment: symptomatic; azithromycin g od for days or ciprofloxacin mg bd for days or ceftriaxone g od; vaccination available reservoir: human, flies, food and faeces incubation: - days symptoms: fever, diarrhoea, sometimes with blood and mucus in the stool and severe abdominal pain treatment: symptomatic; ciprofloxacin bd for days, norfloxacin mg bd for days or bactrim / mg bd for days reservoir: food and water incubation: - days symptoms: mild to severe diarrhoea with fever and blood and mucous in the stool, most common cause for diarrhoea overseas treatment: symptomatic; norfloxacin mg od and ciprofloxacin mg od reservoir: food (particular strawberries) and water incubation: - weeks symptoms: diarrhoea like raspberry jelly, no fever! blood and mucous in the stool, risk for developing a liver abscess treatment: symptomatic, asymptomatic carrier, paromomycin mg tds for days; invasive, tinidazole g od for days or metronidazole mg tds for to days . . cholera (vibrio cholerae) reservoir: contaminated food and water incubation: - days symptoms: often mild gi symptoms, - % develop severe symptom with nausea vomiting, rice water-like diarrhoea and severe dehydration, mortality risk of - % treatment: rehydration, electrolyte substitution; vaccination available; azithromycin g single dose, ciprofloxacin g single dose reservoir: food (in particular sea food) and water incubation: - days symptoms: initial phase ( - days)flulike symptoms, gastrointestinal, hepatomegaly; hepatic manifestation ( - weeks), no jaundice (approx. %), jaundice ( %) with dark urine, jaundice, pruritus; hepatitis a has no chronic form, rarely fatal (fatality is age dependent) treatment: symptomatic, bed rest, avoidance of liver toxic substances (alcohol, medication); vaccination available japanese encephalitis is caused by a flavivirus, which is transmitted by mosquitoes (culex particularly c. tritaeniorhynchus). the hosts are usually pigs and water birds. in humans there are usually not sufficiently high concentrations of virus to serve as a host. the distribution is the asia, especially in rural areas. epidemics occur every - years (. fig. . ). the transmission can occur throughout the year but frequently peaks in the rainy season. there are about , cases per year. only about % of the patients are symptomatic. however, if symptoms develop, the mortality rate is - %. approx. - % of patients who survive have long-term neurological or psychiatric complications. mild courses of japanese encephalitis may be accompanied by mild fever and headache. severe cases show high fever, neck stiffness, photophobia, headache, disorientation, coma, convulsions, spastic paralysis or death. consequential damages may be behavioural disorders, convulsions, paralysis and speech disorders. the diagnosis can be established with blood tests and lumbar puncture. there is currently no treatment option. the vaccination is usually well tolerated and available for prophylaxis. there are various tropical diseases, which are present in poorer countries causing more or less severe symptoms. these diseases are termed "neglected tropical diseases" (ntd). the more common ntds are summarised in this chapter. there are three main conditions caused by these pathogens. the african trypanosomiasis (sleeping sickness) is transmitted by the tsetse fly. the distribution is only in some countries of the sub-saharan africa. seventy percent occur in the democratic republic of congo. tsetse flies are mainly found in rural areas. there are two forms causing sleeping sickness, t. brucei rhodesiense and t. brucei gambiense. t. brucei gambiense has an incubation period of months to years and t. brucei rhodesiense weeks to months. the initial phase is the haemolytic-lymphatic phase, in which pathogens replicate in tissues, blood and lymphatic tissues. symptoms are intermittent fever, headache, myalgia and pruritus. additionally, a painless, indurated chancre on the skin - days after the bite and lymphadenopathy (axillary and inguinal) can be associated. in the second phase, the cns affected causes continuous headache, behavioural disorders (mood swings and depression), delirium, sensitivity disorders, coordination problems and disruptions of the sleeping cycle (daytime somnolence). the diagnosis is mainly made clinically. only for the t. b. rhodesiense, a blood test (centrifuged or wet preparation) to data . detect the parasite is available. examination of buffy coat increases sensitivity. a biopsy of the lymph node to detect the pathogens can be diagnostic for t. brunei gambiense or be used for a culture and pcr. the card agglutination test for trypanosomiasis (catt) is a field test suitable for mass population screening in endemic areas for t. b. gambienses but has a low specificity and is hence only used for identifying suspected cases. all diagnosed patients need to have their cerebrospinal fluid examined for staging, which influences treatment options (. table . ). the treatment is dependent on the pathogen and the staging. if untreated, infections of both forms lead to coma and death. leishmaniasis has three forms: visceral, cutaneous and mucosal (kala-azar). there are about different pathogens, from which approx. are held responsible for these diseases. the disease is transmitted by mosquitoes or sandflies (phlebotomus and lutzomyia). the cutaneous form is the most common one, which causes skin ulcerations. typically this form appears weeks to months after the initial mosquito bite. initially papules are formed, which later ulcerate. they can be painful or painless. the visceral form affects organs, especially the liver, spleen and bone marrow. therefore, this form can be quite dangerous. the changes occur within months and years. hepatosplenomegaly and pancytopenia develop. the mucus form is rare. ulcerative changes of the mucous membranes (e.g. nose, mouth and throat) are typical for this. endemic areas for leishmaniasis are east africa, some arabic countries, india, bangladesh, brazil and some other south american countries. historically, the diagnosis was made by taking a biopsy (skin, bone marrow or other tissues) for culture. now pcr or serological testing with high sensitivity replaced biopsies for making diagnosis. as the visceral disease is fatal without treatment, it needs to be treated in any case. all other forms require normally no treatment. following medication is available: pentavalent antimonial (sb v ) compounds ( mg per day iv or im for days) liposomal amphotericin b ( mg od iv on day - , and ) miltefosine (in adults > kg mg times daily for days) azoles (fluconazole mg od for weeks, itraconazole mg bd for days, ketoconazole mg od for at least days) paromomycin (uncommonly used) pentamidine isethionate (uncommonly used) the chagas' disease is transmitted via an insect bite ("kissing bug") or by contaminated food. it occurs in central and south america. it has . an acute and chronic phase. in the acute phase within - weeks after the infection, localised swelling of the area of the insect bite (skin or mucous membranes), lymphadenopathy, bilateral orbital oedema, meningoencephalitis and myocarditis can occur. - % of all infections become chronic, causing arrhythmias with risk of "sudden death", cardiomyopathy and enlargement of the oesophagus (megaoesophagus) or of the colon (megacolon) even after years or decades. the cardiomyopathy consists of fibrosing myocarditis, causing arrhythmia (rbbb, left anterior fascicular block, st changes, premature ventricular beats and bradycardia) and ventricular failure. the diagnosis in the acute phase is made by a blood smear (thick and thin) to visualise the parasite. a serological test is also available. treatment is recommended in the acute phase and in patient up to the age of and no advanced cardiomyopathy with chronic chagas' disease (. table . ). in age groups above , benefits and risk need to be outweighed. worm infections are a major problem in underdeveloped countries. they occur mainly in rural areas. these conditions may cause insignificant symptoms but also lead to serious consequences or even cause death. because some dive sites are located far away from tourist centres, these infections should be discussed before travelling. this kind of roundworm is found in the tropical and subtropical regions of africa and southeast asia. the transfer follows on oral intake of eggs by contaminated food. the larvae are entering the bloodstream after hatching in the intestine. they reach the lungs via the blood and penetrate the lung tissue, and the larvae can be coughed up. if the sputum is swallowed again, the larvae reach the intestine, mature there within the next - months and lay eggs, which are then excreted via the faeces. the adult worms live about - years. infection is usually asymptomatic. however, abdominal pain, flulike symptoms, allergic skin manifestations, malnutrition, productive cough and a stridor can occur. the diagnosis can be made by examining the faeces (eggs, worms) or sputum (larvae). hookworms are found in tropical and subtropical regions of africa and latin america. the transmission is percutaneously or orally by ingestion of contaminated soil. in contaminated soil the larva is able to survive for about - weeks. larvae can penetrate the skin and enter the blood and reach the alveoli in the . lungs. from there they ascend in the airways, are swallowed again and finally get into the intestines. there larvae mature to adult worms. the worms attach themselves to the wall of the intestine and feed on blood. the eggs are excreted in the faeces and reach again the soil. the eggs can survive up to years. common symptoms are pruritus and rash at the entry site, abdominal pain, diarrhoea, weight loss, anaemia and extreme fatigue. the diagnosis can be made of the faeces. z filariasis filariasis has a worldwide distribution in tropical and subtropical regions. it is caused by wuchereria bancrofti and brugia malayi. it is transmitted by mosquitoes. the infective filariform grow inside mosquitoes and enter via its saliva during the bite. they migrate to the lymphatic vessels and lymph nodes where they develop into adults. they can live there for about years. the female worms produce microfila, which are circulating in the blood. absorbed by mosquitoes they develop within - weeks to the infective filariform. initially there are no symptoms. later lymph oedema in extremities or genitals is a common symptom. in men hydrocele can develop. the skin typically swells and hardens ("elephantiasis"). the diagnosis is made via the blood. detection in the blood smear has to be performed at night, as larvae only circulate in the blood at night. there is also a serological detection of anti-filaria igg available for diagnosis. the treatment with dec is the drug of choice. concurrent disease of loa loa or onchocerciasis is a contraindication for dec, because of the serious side effects (encephalopathy and deaths). ivermectin is used as a prophylaxis, but not as a therapy. z schistosomiasis (bilharziose) schistosomiasis can be found in tropical and subtropical regions worldwide. in addition to malaria, it is the most common parasitic disease. the parasite schistosoma is housed in freshwater snails. by being exposed to freshwater in these regions, infections can occur. the eggs are excreted in urine or faeces of the host. they hatch under optimal conditions and release miracidia. these miracidia infect freshwater snails and develop into sporocysts. these develop into cercariae and get released into the water, where they can penetrate the skin of the host. there, they shed their tail and become schistosomulae and migrate to the liver. in the liver they mature into adults. the paired adult worms migrate to the bowel and bladder, where they lay the eggs. a rash ("swimmers itch") may develop at the entry site on the skin. suprapubic pain and haematuria, abdominal pain, myalgia, fever, swelling of the lymph nodes, liver and spleen enlargement and eosinophilia can be additional symptoms. the risk of bladder cancer is increased with schistosomiasis. the diagnosis can be made in the stool and urine. the maximum excretion of eggs in the urine is between and pm. z trichuriasis (whipworm) whipworms have a worldwide distribution in the humid tropics. the eggs are orally absorbed via soil or unwashed vegetables or fruits. the whipworm grows in the large intestine. the eggs are excreted via the faeces. in the soil the eggs pass through various stages before getting absorbed again. the symptoms are abdominal pain, chronic diarrhoea, nausea, vomiting, inflammation of the intestine, anaemia and eosinophilia. the diagnosis is made with a stool sample. the treatment on the infection is dependent on the parasite (. table . ). leptospirae are long, motile spirochetes. they have a worldwide distribution, but infections occur more commonly in tropical and subtropical regions. they spread through infected urine, which enters water or soil. leptospires can survive for several weeks and months. infections can be caused by contact with either direct contact with the urine or other body fluids except saliva as well as with contaminated soil and water. the bacteria enter the body through the skin or mucous membranes. a broken skin increases the risk of infection. increased risk is after heavy rainfall or flooding. the incubation period is usually - days, but can range from - days. symptoms vary greatly. usually sudden onset of headaches, fever, chills, myalgia, nausea and vomiting, diarrhoea, rash and jaundice are common signs of the first phase for - days. if the patient doesn't recover the second phase (weil's disease) develops, with renal failure, ards, hepatomegaly, jaundice, haemorrhage and meningitis. this has a fatality rate of - %. untreated symptoms can persist for several months. treatment is either doxycyclin mg bd or benzylpenicillin . g qid or ceftriaxone g od for days. infections caused by rickettsia, orienta, ehrlichia, neorickettsia, neoehrlichia and anaplasma are summarised as rickettsial infections. rickettsias are divided into the typhus group and the spotted fever group. orienta make up the typhus group. the reservoir is found in mainly animals, like rodents, but some species are found in fish. the vector is commonly ticks. in scrub typhus the vectors are larval mites. others have fleas and lice as a vector. infection occurs either by bites of the vectors or by direct contact, inoculation or inhalation of contaminated fluids or faeces. the clinical presentation varies. mild symptoms are headache, myalgia, abdominal pain, cough and rash. some rickettsial infections, . q-fever is a zoonosis caused by the protozoa coxiella burnetii. the bacterium is quite resilient due to its sporelike life cycle and remains virulent for months even up to more than a year. the primary reservoir is cattle, goats, sheep and other wildlife like kangaroos, rats and cats. rarely is it transmitted by tick bites or by ingestion of unpasteurised milk or dairy products. the incubation time is usually - weeks but can range from days to weeks. the initial acute q-fever comes with sudden onset of high fever up to °c, headache (retrobulbar), myalgia, chills, non-productive cough and sweats. the symptoms settle within - days. % of all infections are however asymptomatic. often thrombocytopenia and abnormal lfts are found. complications are ards, endocarditis and meningoencephalitis. the diagnosis is based on detecting phase ii and phase i antibodies (igg) weeks apart. the initial test (phase ii) should be taken at the end of the first week of illness. igm and igg rise almost at the same time. a fourfold rise is diagnostic. an initial negative titre doesn't rule out q-fever. seroconversion occurs usually between days and but is almost always present by days. pcr testing can be used in the first weeks but before antibiotic administration. however, a negative pcr result doesn't rule out q-fever. chronic q-fever develops in . - %. it can result in endocarditis, aneurysms, osteomyelitis, hepatitis, neurogic (mononeuritis, optic neuritis), pulmonary (interstitial fibrosis, pseudotu-mor) and renal (glomerulonephritis) disease. chronic q-fever usually develops shortly after the infection. however, chronic endocarditis may not come apparent until - years or even longer. chronic fatigue syndrome is described in approx. %. typically in chronic q-fever, the initial igg titre is increasing (> : ). the treatment for acute q-fever is doxycyclin mg bd for days or for at least days after fever subsides and until clinical improvement. as serological confirmation takes time, treatment should not be delayed. early treatment is effective at preventing severe complications. for chronic q-fever, months of doxycyclin mg bd and hydroxychloroquine mg tds is recommended as standard treatment. rabies has an almost worldwide distribution. more than % of deaths occur in africa and asia. about % are children under years of age. dogs are the main vectors. in asia, there is also a risk of transmission through monkeys. in addition to other diseases, like the lyssavirus, bats or flying foxes can transfer rabies. it is transmitted by bites or scratch wounds but also by inoculation of saliva onto mucous membranes or eye of an infected animal. thorough cleaning of the wound and vaccination within hours can prevent the disease. the incubation period is usually - months but can be less than week and more than a year. initial symptoms include paraesthesia in the wound area. the disease can pass in two forms. the hyperactive form ( %) shows up with hyperactivity, manic behaviour, paranoia, hallucinations, delirium, hydrophobicity and occasionally aerophobia (triggered by the extremely painful spasms in the larynx area). the paralytic form ( %) is characterised by a slow but steady increasing paralysis. the paralysis begins in the area of the infection. the diagnostics can be established on the animal that has inflicted the wound. the tissue samples of the animal are taken from the brain (brainstem and cerebel-lum). the diagnosis in humans is difficult and unreliable. investigation of blood (antibodies), saliva (pcr), spinal fluid (antibodies) and skin biopsies (rabies antigen) are available. the vaccine and the immune globulin can be given during pregnancy. typical side effects of the vaccine are headache, myalgia, malaise, fatigue and nausea. treatment after potential infection (postexposure prophylaxis pep) includes: irrigation of the wound for a minimum of min and washing of the wound with water, soap, iodine or other disinfecting substances rabies vaccine rabies immunoglobulin into the wound area within days after the first vaccination following data should be recorded when a rabies vaccine is given overseas: address, email and telephone of the practice or hospital date of vaccinations batch number, name of the vaccine and manufacturer how many vaccinations are given application: subcutaneous or intramuscular injection who recommends the following approach with potential rabies after animal contact: vaccination against rabies is recommended for: travellers, who for more than month in areas, in which rabies is present professions that deal with bats or fruit bats professions, in which might get with rabies in contact (e.g., veterinary surgeon or nurse) laboratory workers who handle objects with rabies or lyssavirus after animal contact category + pre-exposure prophylaxis (prep) includes three vaccinations on day , and - . the dose is . ml intramuscularly or subcutaneously. the vaccination lasts for years. follow-up vaccinations (post-exposure prophylaxis = pep) include four vaccinations on day , , and . the dose is . ml intramuscularly. immunocompromised patients should receive five vaccinations with an additional vaccination on the th day. with previous vaccinations, two vaccinations are recommended on day and after exposure. it is not recommended to change the brand or the manufacturer during the course of vaccinations. however, it is possible, if that particular vaccine is not available. immunoglobulin should be administered with the first vaccination. the dose is iu/kgbw. the immunoglobulin preferably should be given in proximity of the wound. the immunoglobulin can be diluted, if the wounds is large, to enable to cover the entire wound area. the immunoglobulin is not recommended, if the first vaccination was given more than days ago, if prep or pep was completed or if an adequate serologic detection of vnab titres (≥ . iu/ml) is present. to avoid infection, no animals should be fed. bringing your own food or carrying items like handbags, water bottles, etc. should be avoided, if you stay in the range of monkeys. distance should be maintained to stray cats and dogs. the middle east respiratory syndrome (mers) is caused by a corona virus. corona viruses can cause mild flulike symptoms but also severe symptoms like the severe acute respiratory syndrome (sars). the mers-cov occurs . · mers mainly on the arabian peninsula (iran, jordan, kuwait, lebanon, oman, qatar, saudi arabia, united arab emirates and yemen). but through international travel, it can spread worldwide. recently it resulted in some cases in korea. mers has % mortality. the disease is transmitted through droplets or direct contact. the mers-cov also has a wide range of symptoms, from mild common cold symptoms and infections of the upper respiratory tract to a rapidly progressive pneumonitis, respiratory failure, septic shock and multi-organ failure. it seems the mers-cov has a low virulence, since the transmission occurs usually only through close contact by human to human, such as the care of a person suffering from mers. camels seem to be the original reservoir. mild forms with fever and mild respiratory symptoms, mers should be considered, if close contact with infected people existed prior to these symptoms. mers can be asymptomatic but also lead to respiratory failure and death. typical symptoms include fever, cough and shortness of breath. pneumonia or pneumonitis is often associated with mers. sometimes gastrointestinal symptoms such as diarrhoea and vomiting can occur. it has a high mortality of %. the treatment depends on the severity of the disease. caution in contact with camels in affected countries should be taken. eating insufficient heated camel meat and milk should be avoided. a suspicion of mers should be considered in individuals with the following risk profile: fever and pneumonia/pneumonitis and stay in endemic areas or contact with a symptomatic person from an endemic area within days before onset of symptoms fever and pneumonia/pneumonitis and hospitalisation in endemic areas or contact with camels and camel products in an endemic area within days before onset of symptoms fever and pneumonia/pneumonitis and contact with a mers diseased person within days before onset of symptoms cluster of patient (especially medical personnel) with severe respiratory symptoms with unclear aetiology tuberculosis is caused by an acid-resistant mycobacterium. m. tuberculosis is responsible for tuberculosis in more than %. it has global distribution but occurs more frequently in countries with low hygienic standards. tuberculosis spreads around the globe through international travel and immigration. it also shows a rising rate of resistances to conventional therapies. the time between the initial infection and tuberculin conversion takes approx. the diagnosis can be made with the tuberculin skin test (tst/mendel mantoux). days after the strictly intradermal injection of the substance, the induration at the injection site is measured. an induration of > mm may be suggestive of tuberculosis. it is considered a positive test if either the patient has a radiological proof, had close contact with someone with tuberculosis, and has symptoms of tuberculosis, is hiv positive or suffers from immunodeficiency. an induration > mm is considered as positive, when the patient who travelled to a country with high tb prevalence is an iv. drug user, homeless and a resident of nursing home or prison and has diabetes mellitus, silicosis, m. hodgkin's or end-stage renal failure. an induration > mm is considered as evidence of tuberculosis without any risk factors or symptoms. the tst can be negative in the first weeks after an infection as well as in patients suffering from miliary tuberculosis, m. hodgkin, sarcoidosis, viral infections, and lowered immunity, receiving an immunosuppressive therapy or at high age. a false-positive test can occur after multiple tsts, after vaccination against tuberculosis and infection of other mycobacteria. the interferon-γ test (quantiferon ® tb gold) offers an alternative testing method. this test has the same sensitivity as the tst but a higher specificity. moreover, this test is a confirmation test and isn't affected by previous bcg-immunisations. it consists of three parts, the control (to determine the baseline-interferon-γ), mitogen control (determining the ability of an immune response) and antigen detection (detection of prior infections). a cxr may demonstrate caverns or hilar lymph nodes, but is not a diagnostic tool to exclude tuberculosis. the treatment duration of uncomplicated tuberculosis is months, of complicated tuberculosis - months (. table . ). it's a combination treatment of different drugs. medications for the tuberculosis treatment are: isoniazid: mg/kgbw, max. mg /d; side effects: elevated serum transaminases, polyneuropathy, prophylaxis to avoid side effects of pyridoxine - mg/d a vaccination bcg vaccine is not recommended due to its side effects and the lack of efficacy. all vaccinations should be given days before travelling. minimum time for a sufficient protection is weeks (. divers alert network (dan) is a non-profit organisation for divers. they provide medical information and articles, diving insurance, life insurance and travel insurance. they also offer courses, support and research. dan has an international hotline for support and coordination of diving accidents but also for general medical advice overseas. european underwater and baromedical society (eubs) is a european organisation for diving and hyperbaric medicine. they provide guidelines for hyperbaric treatment and training of medical professionals for the hyperbaric medicine. the german organisation for diving and hyperbaric medicine is the "gesellschaft für tauch-und Überdruckmedizin" (getÜm). . . single dose certificate is valid for years, a new vaccination may be required after years to renew the certificate they provide guidelines for hyperbaric treatment and training of medical professionals for the hyperbaric medicine. brazil; office: tel: + - - - , emergency-hotline: + - - - . japan: japan marine recreation association, kowa-ota-machi bldg office: tel: + - - - , f ax southern africa: private bag x , halfway house, midrand eubs: webmaster@eubs.org gtuem: c/o bg-unfallklinik, professor-kuentscher-str. , d- murnau spums: st kilda road uhms: us highway , suite dan: www. diversalertnetwork. org dan europe: www. daneurope. org emedicine yellow fever chikungunya virus middle east respiratory syndrome (mers) parasites -african trypamosiasis (also known as sleeping sickness) parasites -american trypanosomiasis (also known as chagas disease) parasites -trichuriasis (also known as whipworm) air embolism of the brain in rabbits pretreated with mechlorethamine an examination of the critical released gas concept in decompression sickness accessed middle east respiratory syndrome (mers) middle east respiratory syndrome coronavirus (mers-cov) key: cord- -p xjq authors: bindenagel Šehović, annamarie title: introducing ebola (evd): an unnecessary surprise date: - - journal: coordinating global health policy responses doi: . / - - - - _ sha: doc_id: cord_uid: p xjq chapter tackles the ebola (ebola virus disease, evd) pandemic of / . it notes that coming in the wake of the ongoing hiv pandemic, the rights of those infected with ebola to be identified and treated were largely uncontested. the questions of who would be treated, by whom, with what, remained however extremely contentious. the international response to the pandemic also saw, for the first time, not only non-state actors involved in mediating and mitigating a health crisis, but also military intervention. this chapter lays out both the uses and the dilemmas of military response. it explores the impact of these interventions in this ebola pandemic, with a view towards possible future military deployments against health threats, and offers an initial analysis of the consequences thereof on the relationship between individual and state rights and responsibilities. the - outbreak of ebola virus disease (evd) in west africa (again) caught the world off guard. it should not have. one the hand, hiv and aids should have served as a warning of emerging infectious diseases (eids), and on the other, ebola had actually been recorded in west africa before. yet the outbreak still surprised and very quickly overwhelmed all levels of response: local, national and international. by the time it abated (small clusters of cases continue to be identified,), , people had been registered as infected, and , had died. the - ebola pandemic in west africa morphed into a global crisis beyond health. although locally concentrated, it demanded global intervention. the continued spread of the disease is subject to changing prognoses, contradictory reports, and deep angst. fears pertain to medical as well political and economic implications. ebola, and further emerging infectious diseases (eids), are associated with a host of negative consequences in terms of life expectancy and development in affected societies, states and economies, and also pose a threat to peace and security directly and beyond the region of west africa. the three west african countries most affected by the - edv outbreak were guinea, liberia and sierra leone. all three share porous see who ebola situation reports, available at: http://apps.who.int/ebola/ ebola-situation-reports. author's translation of "die ebola-pandemie westafrikas wurde insbesondere in den jahren und zu einer krise globalen ausmaßes und anlass zu weltweiter sorge. räumlich konzentriert, verlangte sie lokale maßnahmen mit weltweiter reichweite. ihr verlauf war und ist thema wechselnder prognosen, widersprüchlicher nachrichten, und auch großer Ängste. besorgnisse richten sich sowohl auf medizinische als auch politische und wirtschafliche implikationen. ebola, sowie weitere sogenannte "emerging infectious diseases" (eid) sind verbunden mit gravierenden folgen für die lebenserwartung und entwicklung der betroffenen gesellschaften, staaten und die Ökonomien sowie eine bedrohung für frieden und sicherheit innerhalb und jenseits der unmittelbar betroffenen regionen westafrika." in Šehović, annamarie bindenagel und stephan klingebiel ( ). "eine funktionsfähigere globale gesundheitspolitik: empfehlungen vor dem hintergrund der ebola-krise," in herdegen, matthias, karl kaiser and james bindenagel (eds). borders; each ranks among the lowest on the human development index (hdi); in addition, all three are still recovering from nearly decade-long civil war(s) that raged throughout the s. however, it is worth noting that from to , numerous outbreaks of evd were recorded throughout the african continent, notably on the borders between bat and human habitats. it should have been no surprise then that the zoonosis evd jumped the bat-human barrier (again) in , leading to infection. the local outbreak became an epidemic and then a regional pandemic as a result not so much of the potency of the infectious agent as the bungled response to it. what is it? how is it transmitted? evd is hosted by pteropodidae bats, who themselves do not fall ill. it belongs to the family of filoviruses. as with hiv transmission, or any zoonosis, the virus jumps the animal-human barrier. in this case it does so when infected saliva, including on fruit, blood, urine or feces mingle with human secretions. as with hiv, this is most likely to happen where animal and human settlements collide: at the borders of cities, in camps lacking hygiene and sanitation facilities, where the human population encroaches upon the forest. evd had been seen in west africa previously. as early as the s, ebola antibodies were detected in the blood of west african patients. these findings were published in a issue of the journal, annals of virology, and further confirmed in . according to these results, liberia should have been included in the so-called "ebola zone." this did not happen. in addition, researchers in the region were themselves unaware of the findings, which were not shared, and subscription to the journal was not affordable. danger, fearing international travel sanctions which could cripple their tourist-dependent economies still struggling to gain ground after the years of civil war. it was a fatal combination of disjointed priorities. west africa has various regional characteristics that exacerbated the challenge. the ratio of doctors to patients is about per . civil war and state-wide turmoil, mainly in the s, still leave footprints in the damage to hospital facilities and to roads, and in a whole cohort of young adults who missed out on schooling and limit their trust in political leaders. but most of all, the populations of west africa are rampantly mobile. to have relatives that need regular visiting in nearby countries is commonplace, and people zip around, unimpeded by porous national borders. "ebola stood still for us in the past, and we could set up an operational machine in one area," explains armand sprecher, a public health specialist with msf who has worked in all three countries during this outbreak. "if you have a contact tracing system, what do you do when your contact picks up and moves km away one morning without telling you? if ebola moves from location a to location b, suddenly you need to duplicate everything." this explains a large part of why the control systems were overrun so quickly. once the virus gained a foothold, which occurred in guinea, it spread like wildfire. it was propelled not only by particular customs, but by porous borders, social mistrust of politicians, and political mistrust among the regional leaders in this fragile post-conflict zone. this intersection of war and recovery, of human and animal, of city and forest, of zoonotic transmission, is precisely where and what happened when the so-called "index case", patient zero, a small boy in guinea, came into contact with a fruit bat, likely eating it or at least injuring it and coming into contact with its bodily fluid(s). the little boy died within a few days in guinea in december . the ebola virus is a simple virus. mimicking sugar, it is absorbed by the human body entering the bloodstream, where it replicates rapidly. once the immune system recognizes the virus not as a sugar molecule but as an infection, it mounts an immune reaction which quickly becomes an overreaction. as the body fights the virus, infection proceeds in two phases. phrase one provokes symptoms of fever and muscle aches/cramps. phrase two elicits the loss of bodily fluids, up to liters a day. while previous ebola outbreaks also featured haemorrhaging, the - pandemic in west africa was characterized more by vomiting, diarrhea and hiccups. the causative mechanism of the last symptom is unknown. an infected person either dies within ca. days of exhibiting symptoms, or lives, taking roughly days (after developing symptoms) to initially recover. the only known antidote, which sometimes helps and sometimes does not, is the provision of fluids. while different ebola strains, during separate outbreaks, have had varying mortality rates, the average appears to be percent. at death, the corpse harbors the highest viral load of the course of infection. touching, or ritually cleansing the body is thus when most transmissions take place. by contrast, hiv and aids remains nearly percent deadly. however, whereas hiv needs to be transmitted intravenously, via sexual contact, or from mother to child, ebola can be transmitted through the skin by contact with contaminated bodily fluids. yet whereas hiv infects on average an additional . people, ebola infects "only" . to . this is largely because unlike hiv, which can take up to years (on average) to reach the stage of aids, without the provision of arvs, ebola reaches its final stage within days. one "advantage" of ebola infection is that those who have become ill, and infectious, are visibly sick. those with hiv are not always so identifiable. when the little boy died, the ebola virus went on to infect his mother and sister and grandmother, all of whom subsequently died. their funerals, aided and abetted by cleaning rituals, served as catalysts for the first transmission chains of the ebola outbreak of - . all this occurred before the cause of the infection, evd, was identified, or confirmed. lacking this first responsive step, no further could reliably follow. the fact that so many of the symptoms of ebola are also those indicative of malaria, which is endemic in the region, delayed initial identification. yet the cluster of dead indicated an infection other than malaria, whose infection pattern is erratic: following mosquitoes' flight rather than human interaction. high death rates and the close clustering pointed away from malaria, but not to the actual culprit. the delay in identification, medically but especially politically, enabled the virus to spread. transmission was all but guaranteed, due to funeral rituals initially, and then through the porous borders between guinea, liberia and sierra leone: as people travelled to and from funerals, as well as to trade and to work, the virus accompanied them. warned that without american assistance the disease could send liberia into the civil chaos that enveloped the country for two decades. . . . "i am being honest with you when i say that at this rate, we will never break the transmission chain and the virus will overwhelm us." she requested , additional beds in new hospitals across the country and urged that the united states military set up and run a -bed ebola hospital in the besieged capital, monrovia. until president johnson sirleaf's request, the head of a sovereign state asking the head of another sovereign state to intervene militarily in order to combat a disease was unheard of. in doing so, the president did two things: first, she acknowledged the security threat to her populationexplicitly citing the physical, economic and political (civil war) threatsand her state (its integrity, especially in the event of a recurrence of ensuing political violence); and second, she voluntarily invited a foreign state violate her state's westphalian (border/ territorial) sovereignty by sending not humanitarian aid workers, but the military. working under the direction of the national government, liberia's domestic sovereignty and its responsibility for security and health (security) remained untouched. september , : building on the precedent set in the global response to the hiv and aids pandemic, the united nation's security council (unsc) passed resolution ( ), in which it called upon immediate measures to respond to the spreading outbreak. resolution ( ) placed the onus for ebola response on the national state. yet president johnson sirleaf's request highlighted the incapacity and inadequacy of many such responses. september , : the un called into being the un mission for ebola emergency response (unmeer). unmeer, like unaids before it, represented a first: the first un emergency health mission. preceding its establishment, beginning on august , the un's ebola emergency response operated under the oversight of the who, under the "direct authority of the who director-general," margaret chan. coming into its own, unmeer was set up as "a temporary measure to meet immediate needs related to the unprecedented fight against ebola," and was responsible for deploying "financial, logistical and human this has caused all kinds of theoretical and practical controversy; the consequences of johnson sirleaf's request are still being grappled with. october , : president obama appointed ronald "ron" klain as ebola "czar." his assignment pointed directly to the concern over security driving the us ebola response: he will report directly to the president's homeland security advisor, lisa monaco, and the president's national security advisor, susan rice, as he ensures that efforts to protect the american people by detecting, isolating and treating ebola patients in this country are properly integrated but do not distract from the aggressive commitment to stopping ebola at the source in west africa. december : treatment centers commence being built in guinea, liberia and, to a lesser extent, sierra leone. however, they are completed only after the epidemic has crested. july , : mission accomplished: unmeer ceased its activities, having achieved its goals. with the dissolution of unmeer, international attention to the ebola pandemic largely dissipated. the pandemic, and especially its aftermath, no longer have policy prioritization. this is despite the mounting clinical evidence that the infection can linger, causing long-term health complications, and can also be transmitted (notably through seminal fluid) months after someone has recovered from the infection. furthermore, the longterm consequences and costs to social cohesion, to economic investment, development and productivity, (including impact on food security, for instance) and to political stability (where one state or subregion (re)gains investment and/or tourism while another does not) remain underacknowledged, underresearched, and underappreciated. with each, the likelihood of a future outbreak-or related crisis-rises. beyond that, the myriad experimental vaccine and treatment initiatives that proliferated during the ebola response illustrated the potential and possibility of conducting high-caliber research and implementation of interventions amidst a crisis. the successful vaccine administration further indicates an ethical standard and an anthropological acceptance that was not foreseeable at the outset of the epidemic (when ebola teams were being attacked). june : in a second attempt, the who declares the end of ebola virus transmission in the republic of guinea and in liberia. even prior to the june declaration of the end of the ebola pandemic in west africa, the world's attention turned elsewhereaway from sustaining the specialized ebola treatment units that were set up to respond to the acute crisis as multipurpose medical centers (as requested by sirleaf johnson, among others). also in peril are long-term commitments to health systems strengthening (hss) initiatives which would invest in and build, literally, the facilities, and from the purchase, maintenance and use of the equipment. the international community has also failed to consider the costs of (not) training and retaining professionals. instead, the private (ngo) sector, and international programs (such as through the uk's national health service, nhs) court have long trained technicians, nurses and doctors, and lured them from local health systems with lucrative contracts abroad. in the case of the nhs this is especially egregious, since the postcolonial structure of many african health systems means that medical staff trained there adhere to uk standards: so staff hired away do not need additional training or certification to be able to practice in the uk. similarly, if intended to be more short-term, the german government has an agreement with the egyptian government: the latter sends doctors to work in german hospitals, their salaries paid by the egyptian government. in both cases, the local (west african or egyptian) health systems are left bereft of medical professionals. the host (national) health systems benefit, but little or no transfer of knowledge takes place. this leads to perverse situations wherein, for instance, there are more malawian doctors practicing medicine in london than in malawi; it is more likely that someone with malaria will be properly diagnosed in london or frankfurt than in east africa because of the concentration of expertise in identifying malaria symptoms. given the high mortality rate for evd in west africa, this is likely to be the case with ebola infection as well: that medical specialists in atlanta and madrid are attuned to ebola, while no doctors are even available in, notably, sierra leone. the world's wandering attention also means waning focus and funding for establishing and monitoring the supply chains of necessary surveillance, and medications necessary to keep ebola, and other diseases, at bay. the myriad systems' failures arising from the world's averted attention to the post-ebola reality of west africa also fails to address the concomitant shortages and medical challenges which undermine effective local and national response to an epidemic /pandemic threat. in addition, from this vantage point-that of the "end" of the ebola pandemic in west africa-it appears that the only epidemics /pandemics to which an international or global response will be mounted are those with resonance in the developed world-including in germany. germany treated three patients infected with ebola during the - pandemic. these were transferred to and isolated in specialized treatment units in frankfurt am main, hamburg and leipzig. despite the fact that evd is relatively difficult to transmit, and only infectious in the last acute phase of the disease trajectory, and then only via direct contact with infected bodily fluids, extraordinary precautions were taken to ensure the virus's containment. thus the transportation alone of the evd patients-via sierra leone lost its one specialist for infectious disease to the ebola outbreak. see "leipziger patient gestorben," süddeutsche zeitung (october , ), available at: http://www.sueddeutsche.de/gesundheit/ebola-leipziger-patientgestorben- . . specialized medical evacuation-made headlines. such medically unnecessary measures, while effectively guaranteeing that the virus could not-and did not-spread, spiked the level of fear felt by the population. this combination of overcaution and fear did a disservice to the tasks of identifying the infectious agent, informing the public about real threats and genuine dangers, and of coordinating an effective, proportionate response. though not much publicly proclaimed-having kept the very presence of evd on german territory more or less hushed (despite the photos of the special transports splashed across newspaper pages)-german clinical teams were able to cure two of the three patients. the level of medical intervention available to respond to evd in germany, as in western europe and the united states and canada is incomparably better than that in west africa. still, it can be counted as progress in the wake of the hiv and aids pandemic that neither local, national and international experts nor publics questioned the right of people infected with evd to be treated and cared for in as comprehensive way as possible. nonetheless, without adequate, timely identification of an infection, and a coordinated response, even the comprehensive german health system would reach a limit in terms of the number of patients it could treat at such a level of care: in isolation, with large medical teams present around the clock, and with plenty of protective suits and other equipment. given growing international connectivity, another infectious disease outbreak is preordained. anticipatory preparation is thus a must. it would benefit all actors involved, especially in high-stakes infectious disease outbreaks, to review and revise the elements of and the decisions involved in response in order to optimize a plan before the next outbreak. as the timeline above indicates, decisions, and non-decisions, reflect multiple elements of health security: the rights of those ill to be treated; the rights of those offering help to be safe; the need for states to protect and provide both of those components to their citizens; and the need for citizens even of states which cannot offer such protection and provision to be met. decision-making reflects all these factors, as well as the pressure to "do something" applied to both affected and aiding states. the decisions taken, or not, also change the relationships between each one of these elements. at moments of epidemic danger, one naturally focuses on the actions of nations to control the outbreak. but turn that question around: what are the likely actions of an epidemic on a nation? epidemics change governments. political leaders could have no clearer signal that it is their responsibility to protect the health of their people (governments, not doctors, defeat epidemics). those leaders understand that their nation's political, economic, and social stability depends on health. liberia's president johnson sirleaf certainly demonstrated this understanding of the state's stability as dependent upon the state of the health of the population. she also understood the limitations of liberia's ability to respond according to its state responsibility to its citizens. msf itself admitted it was overwhelmed with its emergency response to the burgeoning epidemic and called for military intervention to shore up the response. johnson sirleaf herself asked for such intervention. thus, local, including ngo, responses at the acute level try to stem the tide of the outbreak and implement coping mechanisms. where individual cases occur, as is the case now in the post-ebola phase, and contacts can be traced, isolated and monitored, this response is sufficient and rests at this level. where this is not adequate, further response measures are needed. they include the local, national, international and global levels of response. at the national level, this means coordinating response plans and delegating specialists. liberia, for one, wrote a policy plan and collected and coordinated as many medical professionals as possible to be deployed to respond as the epidemic expanded. bridging the gap between local and national level were msf and the ministry of health and social welfare. the exponentially rising infection rates and concomitant mortality rates, especially of frontline medical personnel, raised the alarm at the international level: sounding the siren at the who, the unsc were the president of the country and the president of the much-respected msf. at the international level, the who and the unsc, establishing unmeer, furthered the cause. in addition, the united states, as well as germany, appointed so-called "ebola tsars," charged with identifying needs on the ground, and advocating for and coordinating those country's bilateral and multilateral assistance to the countries who requested help. in keeping with the international system wherein sovereign states have the ultimate decision-making power, supplemented by both ngos (advocacy) and influential external actors (such as peter piot and richard holbrooke for hiv and aids), the decisions on when, and how, to request help in responding to the ebola outbreak lay with the most affected countries themselves. they did not have any prominent international actor to rely on to carry their cause-until president johnson sirleaf stepped into the spotlight. but, reflective of the system, she only pleaded (and only could have pleaded) for assistance for her struggling country. that johnson sirleaf requested help from the united states is itself an interesting political decision. liberia is the result one of the two settlements founded by freed american slaves. the country also received support from the uk. the other such freed slave settlement, which became sierra leone, received support from cuba and the uk. the third west african country, guinea, received some assistance from its former colonial master, france. given these fraught historical relationships, and the lingering mistrust between the three west african countries due to the s civil wars fought there, it is all the more surprising that military aid was requested, both by msf and johnson sirleaf. such military support is also the most contentious of the post-ebola political debates. the ebola pandemic of - illustrates how rapidly an unexpected infectious disease can get out of control. the implications include excessive rates of morbidity and mortality, agricultural losses, food insecurity, productivity losses in everything from mining to production, and those for the tourist industry, as well as political instability. they also include social changes. bonds of trust suffer at all levels of personal interaction. medical burial teams wore protective gear to disinfect and prepare evd infected corpses for burial. these burials, deemed necessary to break the viral transmission chains, violated the cultural practices of the region. failure by external aid workers and/or professionals to adequately explain and support their adoption resulted in mob attacks on these workers. in august a see petherick ( ) . "ebola in west africa: learning the lessons." mob stormed a clinic and accused the foreign medical staff working there of having imported ebola into guinea. hidden burials were common at some times and places, which inevitably resulted in more ebola infections. taking local customs into account is vital for effective disease response. the national response needs to take these social practices into account and to cue both the local populations, for instance by cooperating with local healers, and external actors in order to render any response culturally palatable as well as medically and politically effective. in order to be politically and medically effective in turn, national governments need to realize, invest and negotiate the capabilities and capacities they require in order to anticipate, identify and react to infectious diseases, of which evd is a case in point. this includes, at the national level, investment in the global outbreak alert response network (goarn), the who system which draws on government information sharing, but also allows ngos and social media platforms access in order to report and monitor, in real time, (im)pending disease outbreaks. goarn is meant to operate as an event-management system, the event being an outbreak of potentially international health concern. when it works optimally, it features: • comprehensive databases on epidemic intelligence, verification status, laboratory investigation and operational information. • tracking and recording outbreak history, critical decisions, important actions by who and partners and key documents. • management of logistic support and specialized response equipment, materials and supplies. • integrated database on the skills, experience and availability of international experts for response teams. • profiling of technical institutions in the goarn concentrating on readiness and capacity to support international outbreak response. • standardized information products for member states, public health officials, media and the public. • communications with goarn to enhance operational readiness. at the international /global level, goarn provokes a response by the who, which in turn can issue guidelines and alter, evaluate and if deemed necessary declare a pheic in order to set into motion a cascade of informational support and technical expertise. also at the international level, the international health regulations (ihrs) ideally inform and coordinate global infectious disease response. the latest ihrs, announced in and which came into force in , stipulate the reporting requirements for emerging infections, and outline the necessary measures to be taken in response. however, they have two shortfalls: while a treaty obligation, they rely primarily on voluntary compliance; they have been invoked overwhelmingly with regard to airborne diseases such as avian flu and sars, the subject of the following chapter; and they have no additional, automatic enforcement mechanism(s). the ihrs were of little help in the midst of the ebola pandemic. in the wake of the ebola outbreak in west africa, and in anticipation of future eid outbreaks in particular, the remarks of david nabarro, the un's special envoy on ebola remain undisputed: there will be more: one, because people are moving around more; two, because the contact between humans and the wild is on the increase; and maybe because of climate change. the worry we always have is that there will be a really infectious and beastly bug that comes along. indeed, such a beastly bug might yet emerge from avian flu and sars should their airborne transmissibility become more efficient. ebola clinic in guinea evacuated after attacked: angry mob claims doctors without borders int roduced deadly disease to country ebola: burying the bodies this was done in south africa with regard to hiv and aids. author's professional collaboration with professor ruben in the context of africare in eastern cape province guiding principles for international outbreak alert and response key: cord- -id fjgye authors: djikeng, appolinaire; nelson, barbara jones; nelson, karen e. title: implications of human microbiome research for the developing world date: - - journal: metagenomics of the human body doi: . / - - - - _ sha: doc_id: cord_uid: id fjgye the human microbiome refers to all of the species that inhabit the human body, residing both on and in it. over the past several years, there has been a significantly increased interest directed to the understanding of the microorganisms that reside on and in the human body. these studies of the human microbiome promise to reveal all these species and increase our understanding of the normal inhabitants, those that trigger disease and those that vary in response to disease conditions. it is anticipated that these directed research efforts, coupled with new technological advances, will ultimately allow one to gain a greater understanding of the relationships of these species with their human hosts. the various chapters in this book present a range of aspects of human microbiome research, explain the scientific and technological rationale, and highlight the significant potential that the results from these studies hold. in this chapter, we begin to address the potential and long-term implications of the knowledge gained from human microbiome research (which currently is centered in the developed world) for the developing world, which has often lagged behind in the benefits of these new technologies and their implications to new research areas. new high-throughput sequencing and data analysis approaches (costello et al., ; turnbaugh et al., ) , along with novel diversity screens and even more intrinsic single cell approaches to isolating new species (lasken, ) , have presented the sciences with a unique opportunity to investigate and interrogate the microorganisms that are associated with the human body, all at a greater depth than previously appreciated. from the earliest studies, the greater scientific community has recognized a high level of microbial diversity in nature beyond imaginations. this includes observations on the oceans, soils, and on animals. with respect to humans, it became increasingly apparent that the species on and in our bodies make significant contributions to our health and development. these species maintain normal cell function in the gastrointestinal tract (for example, see eckburg et al., ; bik et al., ; gill et al., ) . we are also dependent on these species for the efficient digestion of food components, such as plant material and xenobiotics , and to ward off certain diseases. in parallel, these microbes have been associated with, and can result in, many common diseases such as cavities, stomach ulcers, bacterial vaginosis (bv), and irritable bowel syndrome (foster et al., ; dorer et al., ) . most of the initial studies on the microbial diversity associated with the human body focused either on traditional culturing approaches or on sequencing and phylogenetic analysis of the s ribosomal (r)rna genes derived from microbial samples taken from the human body (eckburg et al., ; bik et al., ) . the limit to culturing or s rrna sequencing was primarily a reflection of the availability of molecular tools and approaches, and the cost associated with earlier versions of available sequencing technologies. the s rrna sequencing and analysis invariably revealed a higher level of microbial diversity than that seen with conventional culture techniques (gao et al., ; gao et al., ) . from the human stomach, for example, although the highly acidic environment was thought to only contain helicobacter types, bik et al. ( ) used , s rrna sequences obtained from gastric endoscopic biopsy samples to identify phylotypes of bacteria that potentially reside in the human stomach. the majority of these phylotypes was shown to belong to the proteobacteria, firmicutes, actinobacteria, bacteroidetes, and fusobacteria. this work also described that % of the clones represented organisms that were previously uncharacterized. subsequent ongoing studies continue to reveal high levels of diversity from the microbial species that inhabit the human body, with high levels of both intra-and interspecies diversity (costello et al., ; turnbaugh et al., ) . most of these studies that have investigated the diversity of the microbial species associated with the human body have however left important questions unanswered such as the identity of the nondominant community members and their biological roles, and which metabolic processes the populations that are present encode and carry out. in addition, the past years of genomic research have made it clear that closely related species, and even species that are identical at the s rrna level, can have wide variation in gene content (perna et al., ; kudva et al., ) . terms such as pan-genome and core-genome have been coined over the years to address the variations that are apparent in closely related species and have now been applied in a similar fashion to metagenomic populations (callister et al., ; bentley, ) . the initial publication of a shotgun sequencing of the human microbiome focused on the analysis of fecal samples from the human gastrointestinal tract . this study along with subsequent applications of shotgun techniques to the study of the human microbiome again highlighted the extent of microbial diversity associated with the human body (grice et al., ) . gordon and co-workers, for example, investigated the interplay between the gastrointestinal ecology and energy balance of animals on a western diet. here they found that obesity that was induced by the diet resulted in an increased proportion of one class of the firmicutes and that this same population could be reduced by manipulation of the diet. transplantation of the microbial populations from the obese mice to lean germ-free mice resulted in a higher level of the deposition of fat than when these microbial populations were taken from lean donors (turnbaugh et al., ) . more recently, gordon's group presented the results of a monozygotic and dizygotic twin pair study, where twins were concordant for leanness or obesity, and their mothers (turnbaugh et al., ) . the aim of this study was to address how host genotype, environmental exposure, and host adiposity influence the gut microbiome (turnbaugh et al., ) . the comparative analysis of fecal samples that were derived from individuals yielded , near full-length and , , partial bacterial s rrna sequences. in addition, . gb of metagenomic data was obtained from their microbiomes. the results from this analysis suggest that the gastrointestinal microbiome is shared among family members, but variations are present within each individual with respect to the lineages that can be observed. this variation was evident in both the monozygotic and dizygotic twin pairs. the results however suggest that there is a core functional microbiome that can vary depending on physiological states. the genomic era created the possibility of studying the detailed genetics of many microbial species. these include pathogens and nonpathogens and species that have both positive and negative impacts on the environment. the developments in the genomics arena have taken advantage of emerging and improving sequencing technologies, as well as improved assembly algorithms and approaches coupled with reduced costs for generating genomic data. the developments also placed the greater scientific community in positions to ask in-depth gene-based questions and get real answers. the advent of metagenomics was a natural progression of the genomics field, and in particular took advantage of the ability to sequence dna that was derived from a mixed community and assemble this genetic information to reconstitute metabolic and physiological information of any community of choice. metagenomic approaches have by now been successfully applied to environments as diverse as soils, the oceans rusch et al., ; yooseph et al., ; yutin et al., ) , and the human body costello et al., ; turnbaugh et al., ) in an attempt to describe and decipher the microbial species that are present in these niches. entire systems can now be studied with respect to viral, microbial, and fungal diversity, over varying time courses, and before and after perturbation (costello et al., ). on the human side, when coupled with s rrna analyses for detailed estimates of microbial diversity, metagenomics approaches present the perfect opportunity to address questions related to human health and associated problems. this is particularly relevant in the developing world, which presents its own series of challenges, some of which are presented below. one of the most valuable examples to date of the potential benefits from knowledge gained with human microbiome studies comes from a series of studies performed by dore and colleagues at inra. the significance of the studies conducted by this group relates to how the evolution of initial studies focusing on the microbiome can result in recommendations to improve human health conditions. their results evolved from initial metagenomic studies on human gastric samples using fosmid libraries from six healthy patients, and six patients with crohn's disease (cd). the group was able to identify nonredundant ribotypes mainly represented by the phyla bacteroidetes and firmicutes, of which distinct ribotypes were identified in the healthy microbiota, and only in cd. this metagenomic approach that was initially published gave the first insight into the reduced microbial diversity in patients with cd. their work continued to focus on microbiology of cd sokol et al., ; sokol et al., ; seksik et al., ) . they most recently compared fecal samples of patients active for cd (a-cd) patients, cd patients in remission (r-cd), active ulcerative colitis (a-uc) patients, four uc patients in remission (r-uc), eight infectious colitis (ic) patients, and by s pcr and found that members of firmicutes (clostridium leptum and c. coccoides groups in particular) were less represented in a-ibd patients compared to healthy subjects (hs) with faecalibacterium prausnitzii species (a major representative of the c. leptum group) in lower abundance in a-ibd and ic patients compared with hs. as a result of the initial work, the group proposed that f. prausnitzii was important for gut homeostasis. in members of the same group had published on the composition of the mucosa-associated microbiota of cd patients at the time of surgical resection and months following using fish analysis (sokol et al., ) , and again found reduced abundance of f. prausnitzii being correlated with an increased risk of postoperative recurrence of ileal cd. they further studied the anti-inflammatory effects of f. prausnitzii and showed that the bacterium exhibited anti-inflammatory effects on cellular and tnbs colitis models. the us national institutes of health (nih) initiated a roadmap program focused on the human microbiome (peterson et al., ) . the project has been described as a community resource, with overarching aims to help determine the core human microbiome, to understand the changes in the human microbiome that can be correlated with changes in human health, to develop new technological and bioinformatics tools to support these goals, and to address the ethical, legal, and social issues raised by human microbiome research (http://nihroadmap.nih.gov/hmp/). the project has a heavy sequencing and data analysis component that currently is underway at the four large nhgri/niaid-funded sequencing centers (j. craig venter institute (jcvi), baylor college of medicine, the broad institute and washington university). the current sequencing focus includes generating at least reference genomes at various levels of finishing (chain et al., ) , coupled with significant s rrna sequencing and metagenomic sequencing from to body sites on individuals some of which would be repeat sample donors (http://nihroadmap.nih.gov/hmp/). a number of "investigator"-driven demonstration projects have also been awarded. these demonstration projects aim to understand the implications of a number of diseases including cd, bv, psoriasis, and esophageal cancer to name a few (peterson et al., ) . it is anticipated that the results from these demonstration projects will give additional insights into the relationship between human health and disease and changes in the human microbiome. finally, the human microbiome project (hmp) roadmap initiative has awarded funds to investigate new technologies for improving knowledge of the human microbiome, as well as for the development of computational tools that will increase the value of metagenomic data (http://nihroadmap.nih.gov/hmp/fundedresearch.asp), and the ethical, legal, and social implications of this work. in summary, and as captured in the recent publication by peterson et al. ( ) , the goals of the hmp are to demonstrate the characterization of the human microbiome with population, genotype, disease, age, etc., and also catalog the influence of disease. the aim also is to present a standardized data resource and technological benefits. the project will go over years at a funding level of close to million us dollars. since the launch of this roadmap initiative in , a number of other hmps have been described. an overview of available projects as of mid- was presented in an editorial (mullard, ) . projects beyond the large nih usa based human microbiome efforts include work in europe, china, australia, and canada. in , the european commission committed close to million us dollars to a -year initiative called the metagenomics of the human intestinal tract (metahit) where the primary focus is the microorganisms that inhabit the gut, and how they contribute to obesity and inflammatory bowel disease (mullard, ) . a review of this effort is presented in another chapter written by ehrlich and colleagues. we are all cognizant of the fact that age, diet, and geographical location contribute to variations in the human microbiome. consequently, the more initiatives that we have in diverse parts of the world, the better positioned we will be to fully understand the key components of the microbiome and their interactions with the host under various environmental and physiological cues. because of a slow rate of progress in the areas of scientific research, along with low levels of available funding and investment in sciences in most developing countries, there has been very little scientific contribution toward solving major problems that hinder their global development. as coloma and harris ( ) nicely put it, "researchers in many developing countries will not be participating in genomics research, mainly because of their technological isolation and their limited resources and capacity for genomics research combined with the urgency of many other health priorities." areas such as public health, emerging infectious diseases, and agricultural development, which are key to long-lasting and sustainable national development, still lack the funding and innovation required to mitigate their inability to contribute to global development. the global health sector is of particular importance given the increasing number of diseases that plague the developing world (some of which are making a comeback after several years under effective control). examples of some of these are detailed below. consequently, in most developing countries throughout the world, and specifically in sub-saharan africa, south america, and asia, there is a serious need to improve public health. in these countries, communicable diseases caused by known and even unknown pathogens (see below) remain a leading cause of mortality. emerging infectious diseases are a major cause for alarm, and malnutrition and associated effects are also major issues that need to be effectively addressed. if one takes emerging infectious disease as an example, this captures many viral and bacterial agents. severe acute respiratory syndrome (sars) was the first infectious disease to emerge in the st century, and other emerging viral infectious diseases according to the world health organisation (who) include but are not limited to ebola and marburg hemorrhagic fevers. in addition, in an earlier publication by who ("new who office to help developing countries control emerging diseases"; j environ health , ) it was stated that in alone, communicable diseases caused the death of over million people worldwide, mainly among the poorest populations of developing countries. since then, more than new communicable diseases have been identified, and this list includes several diseases that were thought to be almost extinct that apparently have come back into the human population. certain food-borne diseases are also considered to be emerging as they now occur more often, and that list includes outbreaks of salmonellosis, which have increased significantly in the past years. listeria monocytogenes also falls into this category as its major role in food-borne diseases has become more recently appreciated, and some food-borne trematodes are also emerging as a serious public health concern. although food-borne infections with escherichia coli serotype o :h were first described in , it has rapidly emerged to be a leading cause of infections, which in turn result as a major cause of bloody diarrhea and acute renal failure, with an infection that is sometimes fatal. finally, while cholera devastated much of asia and africa for years, its introduction for the first time in almost a century on the south american continent in makes it another example of an emerging infectious disease. in addition, very little to none of the successful metagenomics stories in understanding the human microbiome and its role in aspects of human health have been conducted or duplicated in developing countries. notwithstanding ongoing efforts focusing on vaccines, better diagnostics, and improved treatment of many of these diseases, it is becoming increasingly essential to complement such approaches with an investigation of the role of the human microbiome on human health. several areas of anticipated important contribution of the human microbiome include zoonotic diseases and other emerging and re-emerging infectious diseases, sexually transmitted diseases, diarrheal diseases, respiratory diseases, eukaryotic diseases, malnutrition, and the integration of probiotics for improving human health. in addition to the translation of findings into practical approaches for improving human health, other opportunities offered by the human microbiome initiative are related to the transfer of technology to developing countries and the associated long-term benefits to training local populations in these developing sciences so that nations can retain the benefits. this will further strengthen capacity in genomics and bioinformatics and all the associated downstream applications that come with these areas of research. it is now appreciated that there is a resident (which constitutes the core microbiome) and a nonresident microbiota. the nonresident microbiota contains known and unknown microbes that cause a wide range of human diseases, most of which remain to be effectively controlled in both the developed and the developing world. human losses in the developing world in terms of mortality and contributions to economic development appear to be greater, however. currently, for example, communicable diseases caused by eukaryotic parasites such as plasmodium spp., leishmania spp., trypanosoma spp., and various viruses, among others, remain serious public health concerns in the developing world and affect more than . billion people (mahmoud and zerhouni, ) . in this context, scientific challenges that include genomics, metagenomics, proteomics, and metabolomics-related activities need to be expanded to ultimately encompass system and ecological understanding of communities of microbes and their interactions with humans. it has in fact been anticipated that the control of these diseases may be accelerated by the complete understanding of the genomes of these species, coupled with an understanding of the changes of the human microbiome that favor or reduce/eliminate their virulence and/or transmissibility. the adaptation processes, for example, by which zoonotic microorganisms that enter the human population adapt to become pathogens overtime can also be accelerated by longitudinal studies that focus on the populations on the bodies of both healthy and diseased individuals. as with most advanced technological and scientific approaches, and as is evident from the developing countries reports presented above, the development and applications of technological advances probably will take a significant amount of time to trickle to the developing world. in the realm of genomics and metagenomics as applied to human health, there is limited evidence that this will happen soon enough to allow developing countries to actively participate and shape research in these new fields. however, a recent award from the bill & melinda gates foundation (bmgf) to dr. jeffrey gordon at the washington state university in st. louis to study childhood malnutrition in developing countries (http://www.gatesfoundation.org/pressreleases/pages/child-malnutrition-microbial-cells-study- .aspx) suggests that there will be more movement in the direction of applying these technologies to problems in the developing world. for the above-mentioned study, gordon's group will investigate the microbes in severe malnutrition with a major focus on severely malnourished infants living in malawi and bangladesh, and whether their microbial flora varies from that found in healthy infants who live in the same environment. it is anticipated that as a result of these studies, we will be better positioned to develop effective treatment regimes for these disease conditions. this award is part of an initiative by the bmgf to fund research on malnutrition (http://mednews.wustl.edu/news/page/normal/ .html?emailid= ). in addition to that award and the anticipated outcome, there have been a significant number of plant and microbial genome projects initiated and conducted in the developing world. the range of microbial species that have been sequenced includes human, plant, and animal pathogens, as well as organisms that have potential benefit to the environment. some of these species include actinobacillus pleuropneumoniae serovar str. jl that causes fibrinous and necrotizing pleuropneumonia in swine, and that was sequenced by the huazhong agricultural university in china and haemophilus parasuis sh also sequenced by the huazhong agricultural university/institute of pathogen biology/chinese academy of medical sciences/peking union medical college. chromobacterium violaceum atcc was sequenced by the lncc (national laboratory of scientific computing in rio de janiero, brazil); this bacterium carries the bacteriocidal pigment violacein and can also cause diarrhea and septicemia in humans. ehrlichia ruminantium str. welgevonden was sequenced at the university of pretoria, south africa. leifsonia xyli subsp. xyli str. ctcb , the causative agent of ratoon stunting disease in sugar cane, was sequenced by the sao paulo state (brazil) consortium and leptospira interrogans serovar copenhageni str. fiocruz l - and xylella fastidiosa were also sequenced by the same group. leptospira interrogans serovar lai str. sequenced by the chinese national hgc, shanghai, and lysinibacillus sphaericus c - sequenced by the chinese academy of sciences/beijing genomics institute, chinese academy of sciences. the developing world has also been involved in the sequencing and analysis of some of the major eukaryotic parasites such as trypanosoma brucei, trypanosoma cruzi, leishmania major, and theileria parva (nene et al., ; berriman et al., ; bishop et al., ; el-sayed et al., ; gardner et al., ) . there have also been several initiatives that have looked at host genotyping in many developing countries. according to coloma and harris ( ) , thailand, south africa, indonesia, brazil, mexico, and india have all devoted resources to studies on human genetics and variation in human populations. as a result of many of these initiatives in developing countries, a limited capacity of tool development for genomics and bioinformatics approaches has occurred. however, much more remains to be achieved in technology and knowledge transfer, particularly in sub-saharan africa and latin america. the main focus should be on developing genomics platforms leveraging on the next-generation sequencing approaches that remain to be established in much of the developing world. events of emerging and reemerging infectious diseases in the human population remain constant occurrences in sub-saharan africa, southeast asia, and south america. emerging infectious disease events such as sars (field, ) and the most recent pandemic of h n illustrate and confirm the constant flow of pathogens from wild and domesticated animals, and other reservoirs into the human population. chikungunya fever, which is an arboviral infection, reemerged in asia in - after a long period of quiescence (bhatia and narain, ) . it is thought that factors including microbial, climatic, social, and economic aspects influenced the reemergence of the disease and the pace at which it spread, eventually resulting in high death rates (bhatia and narain, ) . indeed, there are many microorganisms (viral, bacterial, and eukaryotes) that have moved into the human population and remain part of the human microbiota, which, when able to effectively survive, can cause either new diseases or disease with a much higher severity. such cases of unknown and potentially pathogenic microorganisms in circulation in the human population are usually favored by factors related to ( ) the ability of microorganisms to adapt in new hosts, ( ) human actions (interactions with wild animals, hunting and effects on the environment leading to ecological disturbances), and ( ) human movements as a result of global world travel (field, ) . consequently, at any particular time, there could be a set of known and unknown microorganisms present in a given individual or a population as a result of their presence in and interaction with a specific environment or organisms therein such as animal reservoirs (i.e., bats, mice, and rats) of known and unknown microorganisms. the main challenge in the context of forecasting, and better yet preventing emerging and reemerging infectious diseases has been early detection and genetic identification of such known and unknown microorganisms. global human microbiome studies using metagenomics analysis of known and unknown microorganisms provide unique but powerful opportunities to uncover the near-complete composition of the microbial content of an individual or a population at any given time, thus setting the stage for a comprehensive inventory of the genetic characteristics of potential human pathogens. studies of the human microbiome in the developing world will likely contribute significantly to the discovery of emerging pathogens (viruses, bacteria, and others) in circulation in humans. in fact, in both developed and developing countries the issues of early identification of emerging pathogens have been an impediment for the prevention of emerging and reemerging infections. based on recent studies, human metagenomics coupled with the next-generation dna sequencing provides an opportunity for early detection of microbial organisms even when there is significantly low abundance (relman, ) . because of the extreme importance of monitoring zoonotic infections, metagenomics studies should in principle be extended from humans to domesticated and nondomesticated animals. in fact, based on the technologies already available for human metagenomics studies, there has been increasing interest in launching animal metagenomics initiatives. such initiatives will not only provide insights into the resident and transient microbial populations but also, in the case of natural reservoirs of given microorganisms, provide an opportunity to pinpoint the genetic changes that must occur for their adaptation to a new host -the human body. this is applicable in particular to invertebrate vectors and bats that are known to be host to a number of highly pathogenic viruses that pose significant public health problems to humans. developing countries are particularly affected by the impact of mycobacterium tuberculosis virulence and tb drug resistance. this has been primarily because of genome plasticity in the causative agent. unfortunately, available microarray-based platforms to identify strain diversity have not been fully implemented with the greatest tb incidence largely due the hiv/aids epidemic. the renewed interest and funding for top infectious diseases has recently revamped efforts to accelerate tb research, with a particular focus on the use of integrated approaches to find better control measures. in this context, it is proposed and highly anticipated that key aspects such as the integration of large-scale "omics," datasets focusing on parasite genetic determinants, host genetics, and host-parasite interactions will be crucial for this quest for better control measures. in addition, and given recent reports, the human microbiome would be a great addition to this integration of data in the context of systems biology. to this end, the evaluation of the human microbiome in cases of latent, nonlatent tb, and drug-resistant tb infections will provide insights into the role of the human (resident and nonresident) flora in various aspects of tb infections. such information would most likely contribute to improving diagnosis, control, and spread of tb infection. another example of the potential to come from using human metagenomic research and approaches in the developing world relates to another emerging infectious pathogen that causes leptospirosis. the leptospires cause an infection that is associated with very high levels of mortality annually, but have received relatively little attention, probably because the infection is concentrated in the tropical regions and in the developing world. more than half a million cases are reported annually, and majority of these cases are associated with human exposure to pathogenic leptospira species in the environment. mortality rates as high as % have been recorded. the genus leptospira is serologically divided into two species: l. interrogans, which is pathogenic to humans and animals, and l. biflexa, a free-living nonpathogenic species found in water and wet soil. more than pathogenic and saprophytic species have been recognized. many animals including rodents and dogs are known to be reservoirs of leptospira, and humans are considered to be the accidental hosts of this pathogen. transmission of the pathogen is primarily from soil and water to mammalian tissues (often noticed following on large-scale flooding), with the infection occurring via penetrating leptospires through mucosa or open skin. symptoms of leptospirosis include meningitis, pneumonitis, hepatitis, nephritis, pancreatitis, erythema nodosum, and death. no human vaccine against leptospirosis is available, and mild leptospirosis is treated with doxycycline, ampicillin, or amoxicillin. for severe leptospirosis, the primary therapy is penicillin g. the molecular diagnosis of leptospirosis has been with traditional approaches such as restriction enzyme analysis, nucleic acid probes and hybridization, pulse field gel electrophoresis (pfge), and varying ribotyping approaches. genome sequences from at least six leptospiras have become available in the past few years, and these genomes are providing insight on the diversity of these species. in addition, the availability of these genomes is allowing for the identification of novel virulence factors, and ultimately will facilitate vaccine development. recently, the genome sequence of the free-living l. biflexa was completed (picardeau et al., ) and shown to contain , protein-coding genes distributed across three circular replicons. in the current study, it has been estimated that , genes ( %) represent a progenitor genome that existed before divergence of pathogenic and saprophytic leptospira species. basically, nearly one-third of the l. biflexa genes are absent in pathogenic leptospira. in addition, , pathogen specific genes that are found in the pathogenic leptospires are not present in l. biflexa. of these, genes have no known function suggesting that there are mechanisms that are unique to leptospira and that the pathogenic specific genes need further study. the resulting genome studies suggest that there is still a significant amount of information that is not understood about the leptospiras, particularly as it relates to how the species adapts to new environments and how the genomes mutate. metagenomic studies of samples derived from infected populations will present an opportunity to study the pathogen without repeated passage where it has been shown to have genome rearrangements. in parallel, the pathogen can be studied directly in the environment when it is in transition from its natural host to humans (the accidental host). interestingly, there is a large niaid-funded project underway at the jcvi to sequence the genomes of an additional leptospira isolates (joe vinetz, personal communication; http://gsc.jcvi.org/). leptospirosis is another example of an emerging infectious disease that is prevalent in tropical environments and has not received as much attention as the major diseases in the developed world although the causative organisms result in a high mortality rate. genomics and metagenomics approaches have the potential to increase the understanding of these species and their impact on human health. diarrheal diseases remain one of the leading causes of deaths worldwide (culligan et al., ) . specifically, diarrheal diseases are the second most common cause of child deaths worldwide, and more than % of child deaths due to diarrhea occur in africa and south asia. worldwide, % of deaths from diarrhea are due to unsafe water and poor sanitation or hygiene. three-quarters of all deaths from diarrhea in children younger than years occur in countries. there are about . billion cases of diarrhea among children each year, in addition to those who die from the disease. the un reports that vaccines and better hygiene could decrease the number of deaths from diarrhea among children. since the s, oral rehydration therapy has been the cornerstone of treatment programs. this therapy prevents dehydration that is associated with diarrhea. giving zinc supplements with oral rehydration salts has also been shown to reduce the length of the illness and also the risk of more diarrhea episodes. sixty percent ( %) of children in developing countries do not get the recommended treatment for diarrhea, which is vaccination against rotavirus, the leading cause of the disease. in fact, rotavirus causes about % of hospital admissions of children below years suffering from diarrhea. current therapies are focused on rehydration therapies but the studies from a human microbiome approach, coupled with the development of novel antibiotics and/or probiotics holds significant potential (culligan et al., ) . many diarrhoeal diseases have been associated with viruses (ramani and kang, ) . recent results suggest that viruses are present in as much as % of diarrheal samples in the developing world (ramani and kang, ). there are however a significant number of cases of diarrhea without obvious causes, thus making it difficult to control them. in addition and specifically in the case of rotaviruses, because of their high genetic diversity, the emergence of new genotypes, and the reassortment between different genotypes (matthijnssens et al., ) , there is constant need for surveillance of circulating strains. human metagenomics studies hold the promise for increasing our understanding of the diversity of rotavirus and other etiological agents of diarrheal diseases. based on previous studies, gastrointestinal tract metagenomics studies in both healthy and diarrheal patients in developing countries may lead to the identification and association of additional microorganisms (bacteria, viruses, and eukaryotes) with various cases of diarrheal diseases . as an example, recent human microbiome studies have led to the discovery of a novel virus of the cosavirus genus and its association with acute diarrhea in a child in australia (holtz et al., ) . regular and comprehensive metagenomics analyses focusing on acute and difficult-to-cure cases of diarrhea and diarrhea cases with known and unknown causes primarily in developing countries may provide opportunities for ( ) a constant assessment of the diversity of known causative agents of diarrhea and ( ) identification of new microorganisms as they relate to cases of diarrheal diseases. sexually transmitted diseases (stds) are common infections throughout the developed and the developing world. stds can result in premature birth, stillbirth, and neonatal infections (de schryver and meheus, ) . many ongoing studies on bv aim to understanding the microbial populations that are present in the vaginal ecosystem and how they vary under health and disease conditions. recent studies that are focused on s rrna gene analysis have suggested that the extent of microbial diversity in the vaginal tract is not fully understood, which in turn has implications for current treatment regimes. this has potentially significant implications for asymptomatic disease conditions for example. additional results show a lack of homogeneity within the vaginal tract, highlighting a complex ecosystem (kim et al., ) . metagenomic approaches to studying this environment promise to give additional insights into the extent of diversity within this niche. ongoing studies in several parts in sub-saharan africa reveal that there is some relationship between the population of microbes that exists in the vaginal tract and stds. recently, van de wijgert et al. ( ) described a study in which they investigated the relationships among bv, vaginal yeast, and vaginal practices, mucosal inflammation, and hiv acquisition. from a cohort of , hiv-negative women, they observed that women who were positive for bv or vaginal yeast had a higher likelihood to acquire hiv, and they concluded that bv and yeast may contribute more to the hiv epidemic than previously appreciated (van de wijgert et al., ) . similar observations have been made in a review of all available literature on the extent to which bv may increase the risk of hiv acquisition (atashili et al., ) . earlier, in , van de wijgert et al. ( studied zimbabwean women to determine if intravaginal practices could be associated with changes in the vaginal flora and acquisition of stds. in this study, they found that some disturbances of the flora could be associated with increased likelihood of stds and hiv; the absence of lactobacilli from the vaginal flora was associated with being positive for hiv (van de wijgert et al., ) . martin et al. ( ) had similarly looked at a cohort of sex workers in kenya and demonstrated that although only % of these women were colonized with lactobacillus species at baseline, follow-up studies showed that the absence of culturable vaginal lactobacilli could be associated with the increased likelihood of acquiring hiv- . abnormal vaginal flora on grams-stain was associated with increased risk of both hiv- acquisitions. this group proposed that the treatment of bv and the use of lactobacilli to colonize the vaginal cavity should be evaluated for reduce risk of acquiring hiv- , gonorrhea, and trichomoniasis (martin et al., ) . how the microbial populations in the vaginal cavity can contribute to reduce chances of hiv infection is one of those major areas that need attention, and that will undoubtedly benefit from human microbiome research. according to the world health organisation (who, http://www.who.int/ mediacentre/factsheets/fs /en/), every seconds a child dies of malaria, a disease that can be prevented and cured. in there were million cases of malaria, and these resulted in nearly million deaths mostly among african children. in fact, % of all malaria deaths occur in sub-saharan africa. people who live in lower-income communities, i.e., approximately half of the world's population, are at risk of the disease. the who reports that in malaria was present in countries and territories. the disease, however, can be eradicated, says bill gates. in an interview with the bbc world services world today program in january , gates said "we have a vaccine that's in the last trial phase -called phase three." he added that "a partially effective vaccine could be available within years." a vaccine that is fully effective against malaria would take - years to develop. although most cases of malaria are found in sub-saharan africa, there are other countries, including in asia, latin america, the middle east, and parts of europe, that are also affected. key interventions include prompt and effective treatment with artemisin-based combination therapies; people at risk using insecticide nets; and indoor residual spraying with insecticide to control the vector mosquitoes. genomics approaches have already been used to elucidate the genomes of several of the plasmodium species (gardner et al., ; carlton et al., ; pain et al., ; mitsui et al., ), but new metagenomics approaches present opportunities to monitor the impact of the parasite of the microbial communities that reside on and in the human body, with a longer-term potential to develop novel probiotic approaches to supplement nutrition of infected individuals while the parasite runs its course. in countries that have a high rate of malaria, economic growth rates may be cut by as much as . %. in addition, genomic studies on the environments, in which the mosquitoes reside and breed, are being and will continue to allow for an increased understanding of the communities that they require for their survival (ponnusamy et al., a (ponnusamy et al., , b, ). this is particularly relevant since mosquitoes breed in areas where there are wet conditions, and the transmission of the disease can differ according to local factors such as rainfall, proximity of mosquito breeding sites to people, and the mosquito species in the area. a november report from susan anyangu in nairobi, kenya, carried by inter press service (ips) states that the rts.s vaccine being developed is to be used specifically in africa. it will be for infants and children aged less than years (the most vulnerable to malaria). the vaccine could be ready for use in years time. supplementing nutrition of people with malaria with probiotic solutions that have been derived from a metagenomic approach to understand the human microbiome holds significant promise. the fao/who defines probiotics as "live microorganisms which, when administered in adequate amounts confer a health benefit on the host." probiotics have become more and more valuable over the past few years and are available in a number of food sources, including yogurts and other milk products, fermented and unfermented milk, and some juices. these live microorganisms are in most cases bacteria that are similar to beneficial microorganisms found in the gastrointestinal tract. each species that is present in the gut environment would seem to hold some potential for use as a probiotic and therefore in human health. probiotics have been shown to be effective in treating irritable bowel syndrome (ibs), childhood and traveler's diarrhea, prevention and treatment of vaginal yeast infection and urinary tract infection, preventing and treating inflammation of the colon after surgery, reduction of the recurrence of bladder cancer, shortening the time of intestinal infections, and preventing eczema in children. although the benefits of probiotics are evident, they have yet to be adapted extensively in the developing world (reid and devillard, ) . other ideas on the use of probiotics for reducing the morbidity and mortality associated with hiv/aids have been explored and proposed (reid et al., ) where it has been proposed that lactic acid bacteria could play a role in maintaining the health of the human gut. we can only hope that as a result of the initiatives of the human microbiome project, new probiotics for a range of human health conditions may be developed based on baselines for people in different geographic locales. the efficient implementation of human microbiome research relies on the advanced instrumentation necessary for the processing of collected clinical samples, preparation and amplification of nucleic acid, and dna sequencing. in addition, dna sequence analysis also requires advanced bioinformatics resources. all genomicsrelated technologies developed over the past years remain very expensive to be acquired by developing countries. this is usually justified by low-use volume and high costs of equipment and maintenance (coloma and harris, ) . therefore, as suggested by these authors, involvement of laboratories and institutions in developing countries should take advantage of "north-south" and "south-south" collaborations. previous examples of successful "north-south" collaborations could be leveraged to initiate new ones in the context of human microbiome studies. for the past several years, there have been numerous initiatives in developing countries to reduce the technological divide and hence begin to actively contribute to genomics research. in this context, activities have included training and capacity building in genomics and bioinformatics. in addition, there has also been an emphasis on the development of "centers for excellence" to provide resources and a critical scientific mass at regional levels. four such regional "centers of excellence" are currently being established in eastern and central africa, southern africa, west africa, and north africa. one of the most advanced "centers for excellence," biosciences for eastern and central africa (beca), located at the international livestock research institute (ilri) in nairobi, kenya, has established facilities (with advanced genomics and bioinformatics resources) to support and accelerate research in a wide range of disciplines, including plant/crop sciences and animal sciences. such infrastructure would ideally be poised for use as a focal point for the implementation of a regional initiative on the human microbiome. the existence of such facilities would normally be used to engage various african institutions in south-south collaborations. the "south-south" collaborations indeed provide opportunities to strengthen the scientific capacity of institutions in developing countries, which would be translated into their effective participation in north-south initiatives. genomics and metagenomics initiatives are usually quite expensive, and obviously, most institutions in the developing world would not be able to fund such activities independently. however, given the existence of several human microbiome projects in the united states, canada, europe, china, japan, singapore, and australia, components in developing countries could easily be justified. for example, an african component of the human microbiome would provide elements to answering important outstanding microbiome questions, among which are included: ( ) is there a core human microbiome? ( ) does the composition of the human microbiome vary from one geographical region to another? given the anticipation of such interesting outcomes, existing initiatives could further provide seeds to launch other initiatives in the developing world. furthermore, in the context of the use of biosciences for africa's development, a strong case should be made to various stakeholders such as the african union and other regional organizations to fund the african component of the human microbiome. this next wave of genomics research will not be without its own set of challenges. recent studies, for example, show that many diseases present with similar observations, and as such initial surveys into the human microbiome under health and disease may give unexpected outcomes (yazdanbakhsh and kremsner, ) . bacterial vaginosis and hiv acquisition: a meta-analysis of published studies sequencing the species pan-genome the genome of the african trypanosome trypanosoma brucei re-emerging chikungunya fever: some lessons from asia molecular analysis of the bacterial microbiota in the human stomach analysis of the transcriptome of the protozoan theileria parva using mpss reveals that the majority of genes are transcriptionally active in the schizont stage comparative bacterial proteomics: analysis of the core genome concept comparative genomics of the neglected human malaria parasite plasmodium vivax molecular genomic approaches to infectious diseases in resourcelimited settings bacterial community variation in human body habitats across space and time probiotics and gastrointestinal disease: successes, problems and future prospects epidemiology of sexually transmitted diseases: the global picture helicobacter pylori's unconventional role in health and disease diversity of the human intestinal microbial flora comparative genomics of trypanosomatid parasitic protozoa bats and emerging zoonoses: henipaviruses and sars metagenomic analysis of human diarrhea: viral detection and discovery application of ecological network theory to the human microbiome molecular analysis of human forearm superficial skin bacterial biota substantial alterations of the cutaneous bacterial biota in psoriatic lesions genome sequence of theileria parva genome sequence of the human malaria parasite plasmodium falciparum from where did the 'swine-origin' influenza a virus (h n ) emerge? metagenomic analysis of the human distal gut microbiome topographical and temporal diversity of the human skin microbiome identification of a novel picornavirus related to cosaviruses in a child with acute diarrhea heterogeneity of vaginal microbial communities within individuals strains of escherichia coli o :h differ primarily by insertions or deletions, not singlenucleotide polymorphisms genomic dna amplification by the multiple displacement amplification (mda) method neglected tropical diseases: moving beyond mass drug treatment to understanding the science reduced diversity of faecal microbiota in crohn's disease revealed by a metagenomic approach vaginal lactobacilli, microbial flora, and risk of human immunodeficiency virus type and sexually transmitted disease acquisition rotavirus disease and vaccination: impact on genotype diversity phylogeny of asian primate malaria parasites inferred from apicoplast genome-encoded genes with special emphasis on the positions of plasmodium vivax and p. fragile microbiology: the inside story metagenomics and the global ocean survey: what's in it for us, and why should we care? theileria parva genomics reveals an atypical apicomplexan genome the genome of the simian and human malaria parasite plasmodium knowlesi genome sequence of enterohaemorrhagic escherichia coli o :h the nih human microbiome project genome sequence of the saprophyte leptospira biflexa provides insights into the evolution of leptospira and the pathogenesis of leptospirosis species composition of bacterial communities influences attraction of mosquitoes to experimental plant infusions identification of bacteria and bacteria-associated chemical cues that mediate oviposition site preferences by aedes aegypti diversity of bacterial communities in container habitats of mosquitoes viruses causing childhood diarrhoea in the developing world probiotics for mother and child probiotics for the developing world new technologies, human-microbe interactions, and the search for previously unrecognized pathogens the sorcerer ii global ocean sampling expedition: northwest atlantic through eastern tropical pacific the role of bacteria in onset and perpetuation of inflammatory bowel disease incidence of benign upper respiratory tract infections, hsv and hpv cutaneous infections in inflammatory bowel disease patients treated with azathioprine temperature gradient gel electrophoresis of fecal s rrna reveals active escherichia coli in the microbiota of patients with ulcerative colitis molecular comparison of dominant microbiota associated with injured versus healthy mucosa in ulcerative colitis faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of crohn disease patients diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome a core gut microbiome in obese and lean twins intravaginal practices, vaginal flora disturbances, and acquisition of sexually transmitted diseases in zimbabwean women bacterial vaginosis and vaginal yeast, but not vaginal cleansing, increase hiv- acquisition in african women influenza in africa the sorcerer ii global ocean sampling expedition: expanding the universe of protein families assessing diversity and biogeography of aerobic anoxygenic phototrophic bacteria in surface waters of the atlantic and pacific oceans using the global ocean sampling expedition metagenomes the authors wish to acknowledge the invaluable information found on the world health organisation (who) website and on the mayo clinic website. key: cord- -rm c vu authors: odusanya, kayode; adetutu, morakinyo title: exploring the determinants of internet usage in nigeria: a micro-spatial approach date: - - journal: responsible design, implementation and use of information and communication technology doi: . / - - - - _ sha: doc_id: cord_uid: rm c vu the dearth of information communication technology (ict) infrastructure in the sub-saharan africa region underscores the argument that the spread of broadband infrastructure can foster internet adoption in the region. consequently, the aim of this paper is to present results on the determinants of internet adoption in a sub-saharan african country. drawing on a dataset of households in nigeria, this study presents findings on the demographic, socio-economic and infrastructure factors that predict internet usage in nigeria. the novelty of our analysis stems from a unique dataset constructed by matching geo-referenced information from an inventory of network equipment to a nationally representative street-level survey of over , nigerians, by far one of the largest technology adoption surveys in sub-saharan africa to date within the information systems literature. the results are discussed and concluding remarks highlighting next steps are made. internet access is perhaps one of the most significant indicators of human and socioeconomic development. it fosters productivity and innovation (avgerou ; paunov and rollo ) , social interactions (liang and guo ) and reduces communication and search costs (beard et al. ). yet, there is a digital divide in the level of internet access among developing countries, especially those in sub-saharan africa (ssa) compared to the rest of the world. within ssa, the lack of internet access is a recognized barrier to the adoption of information communication technologies (icts) (afolayan et al. ) . this argument seems to be supported by regional broadband statistics, as shown in fig. where ssa is portrayed to have the lowest levels of internet penetration and wireless broadband infrastructure per capita, relative to other regions of the world. while previous studies have shed light on the regional variation in internet adoption by focusing on the determinants of internet penetration in the context of the "digital divide" (e.g. oyelaran-oyeyinka and lal ; chinn and fairlie ) , these studies often employ infrastructure measures/proxies (such as fixed telephone lines per sq. km, main telephone lines per capita, etc.,) thereby overlooking the peculiar nature of broadband infrastructure in the ssa region. more specifically, we note that internet use across the ssa region is undertaken mainly via wireless broadband access, rather than fixed-line broadband. thus, in this paper, we draw on a unique dataset that combines geo-referenced (longitude and latitude) information on g and g wireless network equipment to examine factors that predict of internet usage in nigeriaa sub-saharan country. consequently, this study offers two potential contributions to the literature. first, unlike previous studies, we demonstrate a measure of broadband infrastructure is micro-spatial in nature, i.e., it is based on the density or concentration of g and g equipment around each household's dwelling over specified spatial domains. to achieve this, we match street-level information from the technology survey to the global positioning system (gps) coordinates of g and g cell towers. this microspatial approach renders more nuanced and invaluable insights on whether/how spatial proximity or access to wireless internet connection shapes adoption decisions at the local level. afterall, without connectivity, it is practically impossible to adopt/use broadband services. furthermore, this spatial approach also embodies the reality that signal quality, a key determinant of actual usage behaviour, is shaped by the physical proximity of users to broadband connections (neto et al. ; destefano et al. ) . hence, in addition to treating the spatial diffusion of wireless network infrastructure as an appropriate measure of broadband infrastructure, it is also a quality-weighted indicator that enriches our analysis. second, our focus on nigeria provides a plausible and timely case study of the effect of broadband infrastructure diffusion on internet usage in ssa and the broader developing country context. given that it accounts for the largest proportion ( %) of the entire ssa region's . billion population (world development indicators, ), we would argue that nigeria is the most representative country of the ssa region. furthermore, itu estimates indicate that more than % of the youth population in developed countries use the internet compared to % in less developed regions of the world. considering that the proportion of nigeria's population below years is projected to reach % by , broadband penetration is likely to have a significant role in shaping nigeria's participation in an increasingly digitalized future economy. finally, despite growing to become africa's largest economy and one of the major emerging economies in the world, nigeria epitomizes the co-existing low levels of internet penetration and ict infrastructure deficit (the economist ). the remainder of this paper is organized as follows. in sect. , we undertake a critical review of related literature on internet adoption and ict infrastructure. this is followed by the model specification and the methods section. in sect. , we discuss the results and conclude in sect. highlighting next steps and expected contributions of our study to the information systems literature and policy. the literature on internet adoption and penetration is large. consequently, due to space constraints, the goal of this review is not to present an extensive discussion of existing literature. rather, we highlight a gap in the use of proxy measures in accounting for technology adoption. a more comprehensive review can be found in cardona et al. ( ) . a dominant strand in the literature pertains to cross-country studies aimed at evaluating the determinants of internet usage and penetration in the context of the digital divide in developing countries. one of such studies is dasgupta et al. ( ) who investigated the determinants of internet intensity (internet subscriptions per telephone mainline) for a cross country sample of oecd and developed countries. similarly, chinn and fairlie ( ) provide an analysis of internet penetration using a larger sample of based on panel data for countries over the - period. they control for a range of macro-level determinants on telecoms prices, per capita income, education, age structure, urbanization, regulatory environment, etc. although this study also controls for ict infrastructure, their reliance on telephone density may not be applicable to the african context. other internet diffusion/penetration studies use large cross-country samples from developing regions of the world (e.g. chinn and fairlie ) . a few studies however focus on internet penetration for more specific sub-groups/regions of the world such as oecd (lin and wu ) , the americas (galperin and ruzzier ), apec (liu and san ) , africa (oyelaran-oyeyinka and lal ) and asia (feng ) . greenstein and spiller ( ) investigate the impact of telecommunication infrastructure (measured by the amount of fiber-optic cables employed by local exchange telephone companies) on economic growth in the u.s. roller and waverman ( ) investigate the linkages between broadband investment and economic growth across oecd countries and developing countries during to . more recent studies have focused specifically on the impact of broadband infrastructure. for instance, czernich et al. ( ) investigated the effect of broadband infrastructure on the economic growth for a panel of oecd countries over the period [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . however, they model this relationship by analyzing how broadband infrastructure (proxied by broadband penetration) shifts the growth parameter of technological progress within a macroeconomic production function setting. tranos ( ) explored the causal effect of broadband infrastructure (internet backbone capacity) on the economic development across european city regions over the period - with ict infrastructure found to stimulate economic development. three important observation can be gleaned from the above literature review. first, the cross-country studies tend to focus on the digital divide, attempting to explain internet adoption and penetration based on changes in economic, social, demographic and regulatory/institutional factors. even when these studies attempt to account for the role of telecoms infrastructure, they do so by using variables such as personal computers per people, main telephone lines per people, customers' equipment (e.g. telephone set, facsimile machine), etc. second, studies based on microdata tend to focus on developed country contexts, while also relying on infrastructure proxies that are analogous to the cross-country studies. moreover, the developing country studies are not free from this problem too. third, even studies that focus mainly on the effect of ict infrastructure on economic measures and internet adoption also employ similar ict infrastructure measures such as investments in telephone/broadband cables. in comparison to the cited studies, we take a different approach by employing a true measure of internet infrastructure that is based on the prevalence of wireless network equipment (i.e. towers and radios). we then explore the effect of wireless network access on internet adoption at the individual level, based on physical proximity to broadband connection. research has shown that variations in technology adoption are shaped by heterogeneity in geographical network access, such that the physical proximity to broadband connection or infrastructure can be expected to shape adoption decisions at the local level. for instance, it is well established that urban areas benefit from higher concentration of ict infrastructure, which may enable social learning and adoption of ict technologies (liu and san ) . hence, unless this type of analysis is undertaken, these disparities in network access may be inadvertently explained away as differences across individual income or demographic characteristics. this paper is also related to a small and evolving body of studies that exploit spatial data towards analyzing the diffusion of telecommunications technologies. our review shows that research conducted by buys et al. ( ) and hodler and raschky ( ) come close to the line of inquiry pursued in this study. however, they differ significantly from this study in two crucial ways. firstly, both studies conduct country-level spatial analysis while we adopt a micro-level spatial approach. secondly, while the former investigates the determinants of mobile operators' spatial location of network sites across sub-saharan africa, the latter explores the role of ethnic politics in shaping the spatial diffusion of mobile phone infrastructure in africa. as far as we know, the closest relative to this study is destefano et al. ( ) where the authors investigated how the arrival of adsl broadband technology influenced the it-productivity gap among uk firms. comparatively, this study is therefore the first to explore the individual-level influence of broadband infrastructure on internet adoption using a micro-spatial approach, especially in a developing country context. this study uses a probit model to examine the determinants of internet usage in nigeria. probit models are used when the dependent variable is dichotomous. we employ a set of explanatory variables in our model, namely: demographic factors include age, gender, marital status and religious affiliation; socio-economic factors such as expenditure, education, whether they are employed or not and a location variable indicating whether respondents live in rural or urban areas. finally, we also include a micro-spatial infrastructure representing the number of internet infrastructure within a radius of where they live (i.e. towers) and the average tariff per megabyte of data used (tariff). both towers and tariffs represent our infrastructure variables included in our model. thus, our model is represented by the equation: internet use = f (age, gender, income and education, marital status, religious affiliation, towers, tariffs, urban). we expect monthly expenditures (our proxy for income) to affect broadband adoption/usage positively. the probability of this adoption decision is also likely to rise for more educated individuals. however, the need for possessing an internet subscription, however, may fall for older and unemployed respondents. in terms of age, one could argue that, whereas younger individuals may have lower income, they tend to demonstrate a greater degree of technological affinity (hübler and hartje ) . we add a gender variable as an additional characteristic, given that the preferences and decisions of men are more dominant than the preferences of their spouse(s) in patriarchal societies (bulte et al. ) . similar considerations can be extended to the marital status of an individual on the adoption of internet technologies. finally, technology adoption decisions are often shaped by religious reasons, as some religious beliefs may restrict the adoption of conventional technological products (fungáčová, et al. ). hence, we control for the religious beliefs of each sampled individual. to examine the effect of broadband infrastructure on internet adoption, used a measure that captures individual-level access to wireless broadband network. hence, we employ a microspatial variable that captures the prevalence of wireless network infrastructure at the individual level. we calculate this variable using information from our two data sources in four steps. first, inspired by hodler and raschky ( ), we extract and map the g and g cell tower locations from opencellid (see fig. b in the appendix section). secondly, we extract and map the street-level dwelling locations from the survey data. thirdly, to use both data for our purpose, we link them by overlaying the towers map with the dwelling location map. finally, we compute a micro-spatial infrastructure variable as the total number of cell towers within -km radius of everyone. this -km specification is premised on the fact that network coverage in ssa is mainly based on base stations that can provide service up to a - km radius (aker and mbiti , p. ) . we achieve this using the stata 'spmap' command. to investigate the effect of wireless connectivity on internet usage, we rely on a unique nationally representative market survey of nigeria carried out by africa's largest mobile operator, mtn during april-july . the mtn survey, which covers localities (i.e., villages or towns), is by far and away one of the largest and most comprehensive technology surveys in sub-saharan africa to date. the data was collected via the use of paper questionnaire distributed to respondents in all states of the country. figure a in the appendix section plots the centroid gps coordinates of surveyed areas at the municipality level. the wide geographical spread of the survey areas confirms the nationally representative nature of the survey. a total number of , observations were obtained for the final analysis. our second data resource is the opencellid database which contains information on the micro-spatial independent variable (towers). the database contains raw information on the geo-location (longitude and latitude) of around seven million unique cell sites across the world (hodler and raschky ) . one key benefit of the opencellid database is the possibility to identify the technology (radio) type for each telecommunications tower (i.e. gsm, umts, lte, etc.). this allowed us to identify the two wireless network classes: "umts" (third-generation technology, g) and the more advanced "lte" (fourthgeneration technology, g) types. specifically, we identified a total of unique tower locations from the opencellid data consisting of g and g sites. these sites are geo-coded at the gps (longitude and latitude) -level (see fig. b in the appendix). our main dependent variable is represented by a broadband usage variable for the use of broadband services. to construct this indicator variable, we convert survey responses on broadband subscription using the question: "which of the following telecommunication services do you use nowadays?". we then calculate the dependent indicator variable as a dummy that takes the value " " if "data service (accessing internet)" was selected in response to the question. otherwise, a dummy value of " " was assigned to the observation. table provides the summary statistics of the variables employed in this study. the internet adoption rate within our dataset is %, falling firmly within the same ballpark as the . % and . % broadband penetration rates reported by business monitor international (bmi ) and the itu, respectively. the summary statistics in table also indicate that there are on average wireless network towers within km of each respondent's street. however, the standard deviation of towers within the km radius suggests a reasonable spread or dispersion of the cell tower variable. table presents the marginal effects from baseline probit estimations. in column , we start by measuring the network infrastructure effects on broadband adoption: probability of adopting internet services, without any control variables or locality effects. due to the cross-sectional nature of our data, we interpret these results as associations. it is clear from the results in columns ( ) that a strong positive correlation exists between the concentration of broadband infrastructure around each individual and internet adoption. this coefficient is significant at the % level. from column to , we add the control variables one by one, but the infrastructure coefficient remains statistically significant at the % level, albeit the magnitude of the coefficient drops. in column , we include locality effects to draw inference only from the variation in individual adoption decisions. besides employing controls and locality effects, we use heteroskedasticity-robust standard errors clustered at the locality level that allow the data to be independent across localities by restricting the error terms to be correlated for individuals within the same areas on account of omitted regional characteristics. ÃÃÃ, ÃÃ, and à denote significance at the %, %, and % level, respectively. as seen in column , the infrastructure coefficient retains its statistical significance but drops further. specifically, infrastructure coefficient of . suggests that a unit increase in the number of cell towers within km of a respondent increases the probability of internet adoption by . %, which corresponds to an increase in the likelihood of adoption from around % to around . % in an average respondent. also, in the full specification in column , the coefficients on the control variables are consistent with intuition and they are all statistically significant at the %-level. for instance, older and unemployed respondents are less likely to adopt broadband services, whereas higher income earners, more educated individuals and urban dwellers are more likely to adopt the internet. for religion, being a christian increases the probability of adoption. the positive coefficient on the male gender variable is consistent with the patriarchal nature of the nigerian society, which indicates that the men are more likely to adopt internet services, perhaps reflecting the stronger socioeconomic power of the male gender. interestingly, in terms of the magnitude of the coefficients, we find age and gender to have the greatest effect on broadband adoption, with both coefficients indicating % and % positive impact on the probability of adoption, respectively. the age coefficient lends weight to our opening arguments on the implications of broadband adoption for the participation of the large projected youth population of nigeria in an increasingly digitalized global economy in the future. for all the specifications in table , the results also show that individuals in areas with a higher concentration of network infrastructure are more likely to adopt and use broadband services. this paper presents first-stage results showing factors that influence internet adoption in nigeria. using geo-referenced information of an inventory of broadband network infrastructure, we employ a more appropriate micro-spatial measure of internet infrastructure based on g/ g network equipment at the local level alongside a range of explanatory variables to explain internet adoption in nigeria. in general, the results obtained are economically important, and they can help explain the adoption patterns of broadband services particularly when network infrastructure effects are likely to play an important role in driving internet penetration. for instance, in many regions across developing countries, network coverage is usually the first modern technology of any kind (aker and mbiti ) . hence, we would argue that the failure to control for this network infrastructure effect in the study of broadband adoption across developing countries could well result in significant omitted variable bias. furthermore, the network infrastructure effect may also explain the nuances embodied in the varied adoption of broadband services across different regions, given that the quality of service (qos) and user experience may well depend on the diffusion and reliability of the underlying network infrastructure. although the first-stage results presented in this paper revealed preliminary drivers of internet adoption, they also provide interesting avenues for further study which we aim to explore in subsequent analysis of the dataset. in the first place, the significant urban variable shows that there are likely to be regional differences with regards to the factors that influence internet adoption in nigeria. given that nigeria has one of the largest rural population in africa (world bank ), we expect that further analysis testing the relationships in this study across rural and urban dwellers, will contribute significantly to the policy debate on bridging the urban-rural internet divide in nigeria. further, having microeconomic information that is representative of the national population of the type used in this research, permits clear visualization of the digital divide as an additional form of inequality that can hinder access to other internet-reliant technologies. for instance, the telecommunications sector in nigeria is currently undergoing several policy changes, one of which is the granting of mobile money licenses to mobile network operators. therefore, it is earmarked that further analysis with our data will explore diffusion constraints for other technologies covered in the survey data and how usage patterns might vary in different parts of the country. we hope that the results of these avenues of research will provide new insights that contribute to both policy and research. − . *** − . *** − . *** − . *** − . *** − . *** − . *** − . *** *** − . *** − . *** − . *** − . *** − . *** information technology usage in smes in a developing economy mobile phones and economic development in africa information systems in developing countries: a critical research review internet use and job search business monitor international (bmi): nigeria telecommunications report gender training and female empowerment: experimental evidence from vietnam determinants of a digital divide in sub-saharan africa: a spatial econometric analysis of cell phone coverage ict and productivity: conclusions from the empirical literature the determinants of the global digital divide: a cross-country analysis of computer and internet penetration ict use in the developing world: an analysis of differences in computer and internet penetration broadband infrastructure and economic growth policy reform, economic growth and the digital divide broadband infrastructure, ict use and firm performance: evidence for uk firms determinants of internet diffusion: a focus on china trust in banks price elasticity of demand for broadband: evidence from latin america and the caribbean modern telecommunications infrastructure and economic activity: an empirical investigation ethnic politics and the diffusion of mobile technology in africa are smartphones smart for economic development? social interaction, internet access and stock market participation-an empirical study in china identifying the determinants of broadband adoption by diffusion stage in oecd countries social learning and digital divides: a case study of internet technology diffusion fostering pro-competitive regional connectivity in sub-saharan africa. global ict department internet diffusion in sub-saharan africa: a cross-country analysis has the internet fostered inclusive innovation in the developing world? world dev telecommunications infrastructure and economic development: a simultaneous approach the causal effect of the internet infrastructure on the economic development of european city regions rural population -nigeria acknowledgements. the authors also gratefully acknowledge the support of africa's leading mobile operator mtn, for providing the market survey and operator data employed in this study. special thanks to the staff of the business intelligence and research departments. we also like to thank participants at various seminars and workshops for their helpful comments. the usual disclaimer applies. opencellid data) key: cord- -quns b authors: cui, shunji title: china in the fight against the ebola crisis: human security perspectives date: - - journal: human security and cross-border cooperation in east asia doi: . / - - - - _ sha: doc_id: cord_uid: quns b the outbreak of the ebola virus disease (evd) in west africa became one of the worst disease-driven humanitarian crises in modern history. the crisis turned the global securitization of health issues into unprecedented levels, at the same time, aligned closely with human security frameworks and thus has significant impacts on national foreign and aid policies. china has played a significant role in the global fight against ebola, indicating important changes in its foreign policy orientations. based on the lessons drawn from china’s operation in africa, it is argued that states must transcend their narrow national interest and seriously consider the dignity and well-being of vulnerable people. in september , when the crisis was at its peak, the number of weekly cases reached almost , . by january , , when the world health organization (who) officially declared the epidemic to be over, the crisis had lasted nearly two years, during which time more than , people were infected with the virus and more than , lives were lost, mostly in guinea, liberia and sierra leone (who b; cbs ) . faced with such a devastating humanitarian crisis, the entire international community has shown great courage in fighting the disease. after the august/september announcement by the who that ebola was a 'public health emergency of international concern' and the united nations security council (unsc) declaration that ebola was a 'threat to international peace and security,' many countries as well as international organizations, non-governmental organizations, companies and individuals participated in the fight against this unprecedented challenge to humanity. china played a significant role in the international efforts to halt the spread of the ebola disease. through four rounds of emergency aid supplied in april, august, september and october , a total of million yuan (about usd million) was contributed to west african countries by china. in addition to financial and material assistance, china also sent more than , medical personnel to the region to help with local epidemic prevention and control work (nhfpc a; undp a) . this was unprecedented in the history of chinese foreign assistance. in fact, china has often been considered as lacking a philanthropic culture, and its international aid and financing models are frequently criticized as resource-backed and tied to aid in a way that simply serves the business interests of the country. thus, the chinese case raises intriguing questions, especially in terms of human security: what are the main motives and driving forces behind these efforts, and how effective are they? this chapter aims to answer these questions through the lens of human security rather than from a general foreign policy perspective. for this purpose, it begins by laying out the criteria and framework for the analysis. this is followed by an examination of china's efforts to fight the crisis. the chapter then goes on to evaluate these policies with a focus on effectiveness, empowerment and motives. based on china's experiences in africa, the concluding section draws some lessons for future human security-oriented foreign policies. when the un security council adopted resolution on september , , declaring the outbreak of ebola in africa to be 'a threat to international peace and security,' the ebola crisis was no longer a mere health issue but an international security crisis (unsc ) . of course, it was not the first time that the security council had acknowledged the link between health and security. in , the council had recognized the hiv/aids pandemic in resolution (unsc , ) , and declared it to be 'a risk to security and stability,' although its main concern was on the 'regional effects' in africa (deloffre a) . resolution is important in terms of human security because the council clearly focused not only on issues such as preventing wars and control of the proliferation of weapons of mass destruction but also dealt with matters concerning human security such as disease (poku , ) . therefore, resolution constitutes a clear securitization of public health issues within the un system. following the ebola crisis, resolution and the creation of the united nations mission for ebola emergency response (unmeer) in pushed the scale and depth of securitization to an unprecedented level, while at the same time brought the securitization processes into close alignment with human security frameworks (snyder ) . the question to be asked in this context is, therefore: what is meant by human security, and what counts as appropriate foreign and aid policies toward human security threats? since its introduction in (undp ) , the concept of human security has increasingly been reflected in global governance and in the foreign and aid policies of many countries. yet the kind of definition one adopts, narrow or broad, will have very different operational and policy implications. in keeping with the approach to human security taken by jica and many east asian countries (see chapter in this book ; tanaka ; jica ) , this chapter takes a broader concept as its working definition and uses this to identify the three features of human security. first, the causes and effects of human security can be far-reaching and multifaceted, and if we underestimate the complexity of such threats, we can never have adequate policies toward human security practices. secondly, human security and human development are so closely related that, even though we can conceptually separate them, we must be aware of the interconnectedness between the two at the operational level (cui ) . amartya sen made the point comprehensively. he argued that on the one hand, human security demands both 'protection' of people from a variety of dangers, and 'empowerment' of people so that they can cope with, and when possible overcome, these hazards. on the other hand, human development is concerned with 'removing the various hindrances that restrain and restrict human lives and prevent its blossoming,' and hence goes beyond 'overarching concentration on the growth of inanimate objects of convenience' (chs , - ) . such a comprehensive understanding is at the heart of his conceptualization of 'development as freedom,' in which poverty, one of the central concerns of human security, is no longer premised solely on income, but seen as a non-fulfillment of basic human rights (sen ) . thirdly, when human security is threatened by conflict situations, natural disasters or pandemics, it is often the case that the most vulnerable people in society are the ones who are most threatened. given these features of human security, what kinds of policy tools are to be considered as most appropriate and effective? tanaka ( , - ) distinguishes between two types of human security instruments: 'fundamental measures' that affect the underlying causes of human security, and 'defensive measures' that affect consequences. this is very similar to johan galtung's ( ) distinction between 'positive peace' and 'negative peace,' because fundamental measures may bring positive peace, while defensive measures are more likely to bring negative peace. for galtung, peace can be defined in a negative way, meaning the absence of violence (both direct and structural). yet more importantly, peace can also be defined positively, that is, the construction of an appropriate environment for lasting peace. in other words, the conditions for positive peace may be built through a process analogous to the 'building of a healthy body capable of resisting diseases, relying on its own health forces or health sources' (galtung , - ) . drawing on these ideas, this chapter is framed around three measures by which human security policies can be assessed. the first measure is effectiveness. once human security threats have occurred, how should we respond to the problem more effectively? the issue here is how swiftly and decisively can a country reduce the negative impacts of disease and human suffering. this is in line with tanaka's defensive measure or galtung's negative peace. effectiveness means more than speed, scale and comprehensiveness; it also refers to the ability to cooperate with a variety of actors to tackle human security threats. speed and scale are extremely important; however, if they are pursued singlehandedly, their impact remains limited. cooperation is imperative when trying to effectively handle deadlier challenges. the ebola crisis is a good demonstration of how a problem goes beyond the capacity of a single state. unmeer was created specially to coordinate a variety of actors to fight the crisis more effectively. thus, both comprehensiveness and cooperation are required if human security policies are to be effective. the second measure is empowerment. if human security practices are only prepared to tackle problems once they emerge, only negative peace can be achieved. taking individual health as an example, although a person may be cured of a disease, if they do not build up their bodily conditions, illness will reoccur. empowerment is more closely related to dealing with structural violence as the underlying cause, building capacities, and creating a more secure environment, so that the occurrence of human security threats can be prevented or the likelihood of them occurring be reduced (cui ) . in this way, even if threats occur, people have the ability, or at least an increase in the ability, to address those threats on their own. thus, if the first evaluate of effectiveness is used to assess more short-term defensive approaches, empowerment is used to evaluate longer-term fundamental approaches to human security. thirdly, in addition to the above measures, motives or moral imperatives are important in assessing human security policies. traditionally, theorists, particularly realists, emphasized national interests when measuring national foreign policies. hans morgenthau ( morgenthau ( , argued explicitly that a 'foreign policy derived from the national interest is in fact morally superior to a foreign policy inspired by universal moral principles.' of course, morgenthau did not deny political morality and prudence, or the need for a logic of consequences to save policy makers from both moral excess and political folly. however, because most human security-related governance activities do not directly relate to national interests in the narrow realist sense, the notion of raison d'état provides poor guidance and does not fully explain the current global efforts to achieve human security. thus, the practice of human security requires a certain degree of consideration of those people who are socially vulnerable, and concern should be given to the possibility of their dignity being exposed to existential threats. the ebola virus disease (evd) in west africa broke out in december and the who put out its first alert in march . what followed was the largest, longest, and most severe and complex outbreak of the virus since it was discovered in (who a). although at the initial stage the impact of the outbreak was underestimated, following the declaration of emergency and threat by the who and the unsc in august and september , the international community has made great efforts and shown solidarity in the fight against the deadly disease. among the countries fighting evd, traditional donors, such as the usa and the uk, played a leading role. by october , the us government was ranked as the largest donor having contributed around usd million in aid, with the uk coming in second with about usd million (who a). yet, the crisis also saw intense media attention given to some non-traditional donors, like china. by october , china had contributed close to usd million in financial aid. although this was much lower than that of the usa, it was still above the contribution of traditional donor countries such as france, japan and canada (undp a; see also fig. . ). accordingly, china's role and its impact on human security merit more detailed examination. china's participation in fighting the ebola epidemic is regarded as being historic, marking the first time it offered such aid to help combat a foreign health crisis (tiezzi ) . the chinese government also admits that it was the largest medical aid program to be implemented by china at the time (nhfpc b). china's role in fighting ebola was particularly important in the early stages and was in stark contrast to the delayed response of the rest of the international community. for instance, even though the who was first alerted to the outbreak on march , , it was not until april that médecins sans frontières (msf) first warned that ebola was getting out of control. by june, the spread and scale of the epidemic was obvious to many experts, yet it was not until august that the who declared that it was a public health emergency. as a result, the international response generated criticism as being both too small and too slow (dearden ; grépin ) . in comparison, china's response was swift. there are two reasons for this swift response: first, given china's long-term medical cooperation with african countries, many doctors and medical staff were already present in african countries when the outbreak began. for example, when the epidemic first emerged in guinea, a chinese medical team of nineteen people from beijing's anzhen hospital was working at the china-guinea friendship hospital in conakry, the capital of guinea. during this time, one infected patient was treated in the hospital without anyone realizing it was ebola and was thus faced with the risk of death. secondly, the chinese experience with sars in and its struggle to stop its spread, coupled with an awareness of the weaknesses in the medical system in west africa, made chinese officials and medical experts particularly alert to pandemics in west africa. in fact, the weak healthcare systems in all three countries were emphasized by many medical experts after ebola broke out. as marie-paule kieny ( ) notes, ebola became epidemic in guinea, liberia and sierra leone in large part due to their weak healthcare systems. indeed, all these countries lack adequate numbers of qualified health workers, particularly in rural areas. other limitations included weak or absent rapid response systems, and a lack of electricity and running water in some health facilities (kieny ; who c) . in march , when the outbreak of ebola in africa began to be reported, the news placed policy makers and medical experts in china on high alert. immediately, high-level meetings were held with the ministry of health calling for discussions on the ebola virus and how to help africa deal with it. among those involved in the meetings was the deputy director of the center for disease control and prevention (cdc) in beijing, he xiong, who was a frontline veteran of china's battle with sars. in april , the chinese government announced its first emergency assistance plan, under which it would send disease prevention and control materials worth million yuan (about usd , ) to guinea, liberia, sierra leone and guinea-bissau; by may , the assistance had arrived (china daily, october , ; nhfpc a) . by june , , the ebola situation had become even more urgent as it had reached the liberian capital, monrovia. six days later, the death toll had risen to and it had officially become the worst ebola outbreak on record (nhfpc ). in august, the epidemic accelerated as the total number of cases reached almost , , with more than , deaths in guinea, liberia and sierra leone alone. cases of infections among american, british and spanish citizens were also reported. on august , , the who declared that the epidemic had gone from being an african problem to an 'emergency of international concern' (who b). this situation alerted the top chinese leaders. on august , , beijing announced its second round of assistance, whereby it would provide emergency anti-epidemic supplies worth million yuan (about usd . million) to the three most affected countries. the supplies were mainly medical protective clothing, sterilization equipment, drugs and other much-needed medical equipment and supplies. due to the urgency of the situation, china even used chartered planes to deliver medical supplies, which arrived on august , just one week after the announcement. the initial aid was followed by another three chinese medical teams dispatched across west africa to help with prevention and treatment. by this stage, more than medical workers had been dispatched (china daily, september , ) . the situation further developed and reached a devastating level. by september , the total number of infected cases had reached , including deaths (medical express, september , ) . two days later, the unsc declared the outbreak of ebola to be a 'threat to international peace and security' (unsc ). on september , the unmeer, the first-ever un emergency health mission, was formed. this mission was led by a full range of un actors, who utilized their expertise under the leadership of a special representative of the secretary general. it was in such crisis atmosphere that many countries pledged more aid and manpower to help. on september , us president barack obama announced 'major increases' in the us response to fighting ebola in africa including up to troops, material to build field hospitals, additional healthcare workers, community care kits and badly needed medical supplies (new york times, september , ) . in a speech to the un high-level meeting on the response to the evd outbreak on september , , japanese prime minister shinzo abe also promised that japan would provide , sets of protective gear for medical personnel working to combat ebola in africa. in october, japan used civilian aircraft to deliver , sets of protective gear to liberia and sierra leone (asahi shimbun, february , ) . in september, as its third phase of assistance, china increased its contribution significantly by opening a biosafety lab and providing protective treatment supplies and food assistance. additionally, to help sierra leone improve lab testing, china sent a laboratory team of (thirty doctors and twenty-nine laboratory technicians) to work at the sierra leone-china friendship hospital (china daily, september , ). on october , china announced its fourth round of emergency aid worth million yuan (usd million), which would mainly be used to finance the construction of a -bed treatment center in liberia, where the epidemic was most serious. as the chinese foreign ministry explained, the treatment center, which was completed on november , would be managed and operated by a medical team from the people's liberation army (pla) (xinhua, november , ). the treatment center was able to accept patients for observation and testing from december , (nhfpc b). the aid package also included sending medical equipment and materials, such as ambulances, motorcycles, , healthcare kits, , pieces of personal protection equipment, and other materials (larson ) . china continued its commitment to fighting ebola after these four phases of contributions, as lin songtian, director of the foreign ministry's african affairs department, stated, 'china's assistance will not stop as long as the ebola epidemic continues in west africa' (xinhua, october , ) . thus, in early november, the nhfpc announced that china planned to send medical workers and experts to west africa over the months that followed (xinhua, november , ) . in february, china handed over a p -level biolab to sierra leone as part of its continued contribution to fighting ebola; it also delivered a consignment of metric tons of food assistance for distribution to ebola patients at various treatment units across the country. evaluating china's role: an emerging human security-oriented foreign policy? from the above discussion, it is not difficult to see how china actively participated in the global efforts to address the ebola outbreak. how then should china's role be assessed through the specific lens of human security? what lessons can be drawn for future human security-oriented foreign policies? the following section will analyze china's role in terms of effectiveness, empowerment and motives. as previously argued, effectiveness comprises both comprehensiveness and the ability to enhance multiple-level cooperation. first, china's assistance is considered as comprehensive and wide-reaching. its contribution of personnel is particularly highlighted compared with many other countries, especially asian countries. at a news conference in seoul on november , , the world bank group president, jim yong kim, lamented the fact that although they may have the capacity, many asian countries were not doing enough to help. he called upon asian leaders to send trained health professionals to west african countries (aljazeera, november , ) . the lack of assistance by asian countries is true to some extent. japan, for example, while making significant financial and material contributions lagged behind many other countries in terms of the provision of personnel. by the end of , japan had sent a total of twenty japanese experts to participate in who missions to liberia and sierra leone, two self-defense force (sdf) personnel to the headquarters of the us africa command (africom) in germany to support liaison activities, and one to unmeer as a senior advisor (government of japan ). there were suggestions from japan's defense ministry that a ground sdf unit would be dispatched to join the fight in sierra leone. the plan was submitted to the prime minister's office on february , , and called for gsdf personnel to begin operations in april, with a possible maritime sdf contingent to serve as the base of operations. however, for many reasons japan did not go ahead with the plan. this decision generated some criticism because although prime minister abe promotes a vision of 'proactive pacifism,' he chose to put japanese lives and his government's own political interests ahead of global well-being (pollmann ; the japan times, february , ) . south korea made a large step in its contribution to international personnel at this time. in addition to the usd . million of assistance it had already provided, between december and april , seoul sent three emergency relief teams (a total number of thirty people), comprising mostly skilled military and civilian healthcare workers, to west african countries to carry out medical activities (the korea times, october , ; china news, april , ) . this represented the first time that the south korean government had sent an emergency relief team to fight the outbreak of an epidemic overseas. in comparison, china's participation was much swifter and of greater weight. the un secretary general ban ki-moon acknowledged 'the speed and breadth' of china's response and emphasized the commitment and dedication made by chinese medical staff to fighting ebola (china daily, february , ) . but, there were also other countries who made significant contributions, including personnel, to this global effort to fight ebola. since mid-september , the usa had shown renewed engagement and significantly enhanced the global scale of the fight against ebola. over the course of the epidemic, the usa deployed more than personnel to the affected region ; as a superpower and as a longstanding traditional donor country, the usa did play a leading role in this humanitarian effort. nevertheless, as a rising great power and as a non-traditional donor country, china's growing role in international aid and global governance is commendable for its willingness and comprehensiveness. secondly, in terms of cooperation, china's role is, however, less straight-forward. the complexity and devastation of the ebola crisis again demonstrated the value and necessity of cooperation among a variety of actors. of course, in the process of engaging in the global effort to fight ebola, china did cooperate with many countries and international and regional organizations by providing financial support to the un, the who and the au, and assisting them in playing leading and coordinating roles. china also made many bilateral and trilateral agreements to combat the unprecedented spread of ebola, including with the usa, france and the uk (focac ). the health ministers of china, japan and south korea also agreed to boost information-sharing on the ebola epidemic and countermeasures against other types of diseases, such as pandemic influenza (the japan times, november , ). however, in comparison with many traditional donor countries, china had less experience of coordinating with non-governmental actors, and the ebola crisis, in a sense, highlighted the shortcomings of china's private sector participation and its philanthropic shortfalls (rajagopalan ) . even though at the government level china contributed over usd million to fight ebola, at the private sector level it donated little to the cause. many firms and business people in china still assume that the chinese government should take the lead on international assistance. in a deeper sense, this philanthropic shortfall is the result of china's international aid tradition, which has been predominantly bilateral and government-to-government. this is clearly revealed in china-africa relations. since china began its assistance to africa in the s, it has been the government that has initiated the sending of medical practitioners and the building of roads and railways (chan , - ) . even at present, this tendency has not changed very much; hence, the aid commitment under the multilateral mechanism of the forum on china-africa cooperation (focac) is also realized mainly through a bilateral mechanism (xu ) . with global multilateral cooperation frameworks growing in sophistication, china faces the challenges of how to better integrate itself into the multilateral development framework. to what extent has china's approach to the ebola crisis contributed to empowerment rather than just protection? as argued earlier in this chapter, empowerment refers to a longer-term positive/fundamental approach to human security that looks at the underlying causes of human security threats and should ultimately lead to an improved capacity to overcome threats. strictly speaking, capacity building and empowerment may not be entirely identical, as the former is more related to organizational capabilities, while the latter is more concerned with people. yet, the two are closely related to each other, and building organizational capabilities such as proper health systems can directly and indirectly enhance individual health resilience in the long term. thus, this chapter examines the following two aspects in detail: china's effort in offering help to build public healthcare systems and its active engagement in african economic and social reconstruction. first, in fighting the ebola crisis, china has not only devoted itself to tackling the deadly disease but has also offered valuable help to african countries to improve their capacity to respond to public health emergencies. if china's four major rounds of assistance between april and october were dedicated mainly to stopping the spread of the ebola epidemic, since then china has focused more on long-term capacity building (embassy of the prc ). in november , china sent its public health training team to sierra leone to study the ways they could carry out training for public health professionals in west africa. the team was to smooth the way for large-scale training programs in the future. by august , chinese public health training teams had trained more than , residents, including medical staff, community healthcare workers, government officials and volunteers. using china's fight against sars as a way of sharing their experiences, the training teams were able to deliver useful prevention and control knowledge and skills to the participants (nhfpc a; embassy of prc ). indeed, empowerment through improving regional health systems has become an important part of the china-africa health cooperation. at the second ministerial forum of china-africa health development in early october , ministers emphasized the importance of african people being able to access quality essential health commodities, medicines, vaccines and medical services (nhfpc c). to that end, china pledged to send medical workers to africa in the next three years, and it encouraged ten of its large pharmaceutical and medical equipment enterprises to cooperate with various african counterparts, through measures such as technology transfers in the production, maintenance and distribution of quality pharmaceutical products (china daily, october , ) . secondly, along with establishing and improving public health systems, poverty reduction and economic and social reconstruction have become china's key goals in its efforts to address the ebola epidemic. the chinese foreign minister wang yi emphasized this point while on a visit to the three countries worst hit by ebola, by saying that 'poverty was the root cause' of the ebola outbreak (xinhua, august , ) . from china's perspective, the fundamental solution to preventing the reoccurrence of ebola and other epidemics of this kind is to find effective paths to eliminate poverty and achieve development as soon as possible. for this purpose, china's cooperation would prioritize areas such as infrastructure building, resumption of trade and export, food security and other areas to enhance their resilience to crises (xinhua, august , ; august , ) . of course, rebuilding the fragile health system and enhancing socio-economic reconstruction in these countries will not be easy and will require a much longer time-period and persistent efforts. in this sense, whether wang yi's visit to the african continent will lead to more substantial engagement from china, or whether it will bear positive fruits, remains to be seen. however, china's commitment to african development and to the recovery of the three countries was demonstrated at the forum on china-africa cooperation (focac). indeed, in the past three focac meetings, china has consistently doubled its financing commitment to africa-from usd billion in to usd billion in and usd billion in (sun ) . additionally, at the forum, china pledged usd billion worth of assistance and loans for african development. it also specified ten areas of cooperation and assistance, including agriculture modernization, public health and poverty reduction that it would engage in. in the declaration, china promised it would transfer agricultural technology to africa; cancel outstanding debt for some of the poorest african countries; help build an african center for disease control; and back cooperation between twenty chinese and african hospitals. china also hoped to explore the possibility of linking china's belt and road initiative and africa's economic integration. if these efforts can be materialized, they would certainly have a positive impact on africa. finally, why did china participate so actively in the global efforts to contain ebola? as discussed, realist notions of raison d'état cannot provide sufficient answers about the international efforts for human security purposes. the question is this: to what extent can china's role transcend this notion of national interests? of course, one cannot deny that china's national interests are growing in africa, including in the three most affected countries. when evd emerged, there were approximately , chinese nationals living in the three afflicted countries (beijing youth daily, august , ) . moreover, when chinese foreign minister wang yi visited the three countries in august to prepare for the post-ebola reconstruction, he promised more funding and joint projects including infrastructure building, and resumption of trade and export (xinhua, august , ) ; this was an indication of china's growing economic interests in these countries. however, national economic interests alone cannot explain china's proactive engagement in the global fight against ebola, given that these countries are the least developed countries in africa. if china was purely seeking economic interests in the area, it should have invested in countries that had a greater chance of return. therefore, we should examine the ways in which human security as a fundamental value has an increasing impact on national foreign policy and strategic choices. china's active participation in and significant contributions to the global fight against ebola indicates its 'growing position within the international community as a global actor in humanitarian aid' (undp a, ) . it also reflects some important changes in its foreign policy orientations, particularly in foreign aid strategy. this is clear in china's second white paper on foreign aid (wp ii) (state council of china ). in , china published its first-ever foreign aid white paper (wp i), which was already indicative of its effort and strategy to become a responsible great power in international society. by moving its focus from its own development to the provision of assistance to other developing countries, china is 'fulfilling its due international obligations' (state council of china , ), and is enhancing its image as a responsible great power (liu and huang ) . in wp i, the underpinning principles for china's foreign aid were clearly put forward: the 'five principles of peaceful coexistence' and the 'eight principles' for economic aid and technical assistance to other countries. china often defended its role as being 'an alternative to western donors who impose more conditions on recipients' (state council of china , - ) . by comparison, there are some noticeable modifications contained in the wp ii, which sets out the following two areas-'helping improve people's livelihood' (改善民生) and 'promoting economic and social development'-as its major foreign aid objectives (state council of china , - ) . of course, this does not mean that china has abandoned the principles of non-conditionality, non-interference, and respect for sovereignty, which continue to underpin the basic principles of china's foreign and aid policies. however, the growing emphasis on poverty reduction (减少贫困) and improvement of people's livelihood (改善民生) means that these are increasingly attuned to those values of human security which have been endorsed and promoted by the un and the international community (state council of china ; undp b). the shift also reflects some important changes in the way china assesses global security threats and identifies its national interests; this is increasingly in line with the broader definition of human security. as china's foreign aid specialist wang xiaolin argues, the trend of china's foreign assistance has changed significantly from being driven by ideology and only aiding socialist countries to being based on its assessment of global security challenges. china sees the global security agenda, such as poverty reduction and tackling climate change, as being part of its foreign aid agenda, and hence its foreign assistance is more consistent with the millennium development goals (now the sustainable development goals) (wang ) . importantly, as the global security agenda expands, human security norms such as poverty reduction and environmental responsibility have emerged and been institutionalized as important norms and institutions in international society (kozyrev ; kopra ) . the global adoption of mdgs ( ) and sdgs ( ) has hugely contributed to the institutionalization of a human security norm in international society. building on the success of the mdgs, the sdgs with goals and targets are particularly determined to eradicate poverty and hunger in all their forms, which are the core elements of human security. moreover, the sdgs are also truly global in nature and universally applicable, and all countries have a shared responsibility to achieve them (unga ) . in this way, human security norms have become an important and legitimate basis for moral claims within international society and even have an impact on 'the criteria for rightful membership' of international society (falkner and buzan , ) . given that china is so eager to build its global image as a responsible 'great power,' it cannot ignore these changes. thus, the argument can be made that china may not entirely abandon its national interests and would not promote its foreign aid purely out of altruistic aspirations; however, it does indicate the ways in which china assumes and identifies its national interests in the changing international environment of the twenty-first century. in other words, china is increasingly seeing its national interests and security in terms of the interests and security of international society as a whole; in so doing, china is showing a growing sense of raison de système in global international society, in which human security considerations are becoming an important part of its foreign policy projection. china's participation in the global effort to address the ebola outbreak provides us with several important lessons as to how human security-oriented foreign and aid policies should be conducted, especially in an environment of emerging and complex human security challenges. the destructive nature of the ebola crisis and the devastation it brought with it again demonstrated the changing nature of global security threats. as ginsburg vividly illustrates: 'it is shocking to realize that a tiny virus with just a handful of genes can fracture families, shred communities, destroy national economies and destabilize whole regions in just a matter of months. but this is what we are witnessing with ebola.' (guardian, october , ). diseases like ebola can become as serious and deadly as the threats caused by conflicts and even wars. moreover, as viruses know no borders, once a breakout occurs, it can easily affect people across countries, regions and worldwide. as is often the case, it is always the most vulnerable individuals and groups who are the most affected. given the complexity and potential destructiveness of infectious diseases, future health security governance should be prepared with greater care. first, it is imperative that early warning systems for future health crises should be developed at the national, regional and global levels, especially in low-and middle-income countries. one of the important lessons that was drawn from the ebola crisis was the weak (or even lack of) healthcare systems in the three most affected countries. according to anthony fauci, a health expert based in bethesda, usa: 'if there was a system to have recognized and stopped the outbreak that began with the child in guinea in december , we might have avoided the explosive outbreaks in sierra leone and liberia' (kupferschmidt ) . it is in this sense that the un secretary general ban ki-moon stressed 'the need to strengthen early identification systems and early action' (snyder ) . the east asian region has also been faced with many health and security challenges, for instance, the outbreaks of sars in and h n bird flu in - , both of which had the potential to turn into pandemics (fidler ) . the sars outbreak did indeed spark regional health security initiatives (caballero-anthony and amul , ). yet, to prepare for complex challenges in the future, more enhanced and sophisticated regional public health systems are required. secondly, the ebola crisis strongly demonstrated the value of cooperation between actors at various levels, including both state and nonstate actors (nsas). particularly, cooperation between external militaries and ngos is a notable development. both china and the usa deployed many troops to help control the epidemic. importantly, some ngos, such as msf, which had previously refused to work with national militaries, are now calling for military intervention as part of outbreak responses. in fact, it has been proven that with their adaptability, discipline, ability to operate in challenging environments and logistical capabilities, the military can be a particularly valuable resource during large-scale public health crises (edelstein et al. ) . however, it should be emphasized that in this situation the operationalization of the role of states and their militaries cannot be properly understood in the traditional sense of state centrism. importantly, as the most powerful state in the world, the usa acknowledges that global health security is a 'shared responsibility' that cannot be achieved by a single actor or sector of government (white house, september , ) . thus, in any future health security governance, ngos and other nsas should become important partners, and through state-ngo or public-private partnerships (ppp), they should achieve their common objectives through collaboration. in addition to public-private partnerships, future health security governance should also pay sufficient attention to the idea of 'local ownership,' which values cooperation between international actors and local actors. exploring the concept of 'local ownership' in the field of conflict resolution and peacebuilding, shinoda ( , ) argues that unless it is solidly rooted in local society, conflict resolution and peacebuilding would end up becoming 'superficial' and 'short-sighted.' this is true with international development cooperation, because the ultimate aim of such cooperation should empower stakeholders of a local society to enable them to take responsibility for dealing with the situation. finally, the close link between health security and poverty is another case in point. indeed, the fact that 'poverty and infectious diseases interact in subtle and complex ways' has long been recognized by scholars through various case studies (alsan et al. ). the ebola case further supported the argument that human security and human development cannot be treated in isolation. poverty can and has often been the root cause of many human security threats. in this sense, future human security governance must combine proper defensive measures with more fundamental measures so that human security can be achieved and sustained not only through protection, but more importantly, through empowerment. in all these cases, should future human security-oriented foreign policies be truly realized, states must transcend their narrow national interest and seriously consider the dignity and well-being of the most vulnerable people in society. china's foreign policy. the 'eight principles' were announced by premier zhou enlai in during a visit to africa. the principles 'established the notion of non-conditionality of chinese foreign aid the militarization of aid in a variety of global contexts has long been a concern for humanitarian actors, who worry that such actions violate important principles of ethical humanitarian aid, namely: 'neutrality' (not taking sides in a conflict); 'impartiality' (not discriminating in aid provision); and 'independence accordingly, several ngos have renounced working with military forces in the provision of humanitarian relief poverty, global health and infectious disease: lessons from haiti and rwanda asia 'not doing enough' to fight ebola japan weighs sdf mission to sierra leone to help in fight against ebola jin wan zhongguo gongmin zai xifei aibola yiqu shenghuo [approximately , chinese nationals living in the west africa ebola epidemic areas health and human security: pathways to advancing a human-centered approach to health security in east asia.' in routledge handbook of global health security who declares official end to ebola outbreak in west africa china engages global health 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international peace-keeping operations, sc/ with spread of ebola outpacing response, security council adopts resolution ( ) urging immediate action, end to isolation of affected states, sc/ remarks by the president at global health security agenda summit who (world health organization). a. ebola situation summary. geneva: world health organization b. statement on the st meeting of the ihr emergency committee on the ebola outbreak in west africa c. high level meeting on building resilient systems for health in ebola-affected countries, meeting report. december - ebola virus disease latest ebola outbreak over in liberia; west africa is at zero, but new flare-ups are likely to occur china pledges continuous aid to africa in anti-ebola efforts china uses anti-sars experience to fight ebola in w china plans , more staff to fight ebola in africa china's anti-ebola efforts further enhance china-africa community of common destiny wang yi: xifei sanguo zhansheng aibola zui genben de shi yao fazhan qilai wang yi tan xifei sanguo xing forum on china-africa cooperation: creating a more mature and efficient platform key: cord- -s iavz u authors: ali, harris; dumbuya, barlu; hynie, michaela; idahosa, pablo; keil, roger; perkins, patricia title: the social and political dimensions of the ebola response: global inequality, climate change, and infectious disease date: - - journal: climate change and health doi: . / - - - - _ sha: doc_id: cord_uid: s iavz u the ebola crisis has highlighted public-health vulnerabilities in liberia, sierra leone, and guinea—countries ravaged by extreme poverty, deforestation and mining-related disruption of livelihoods and ecosystems, and bloody civil wars in the cases of liberia and sierra leone. ebola’s emergence and impact are grounded in the legacy of colonialism and its creation of enduring inequalities within african nations and globally, via neoliberalism and the washington consensus. recent experiences with new and emerging diseases such as sars and various strains of hn influenzas have demonstrated the effectiveness of a coordinated local and global public health and education-oriented response to contain epidemics. to what extent is international assistance to fight ebola strengthening local public health and medical capacity in a sustainable way, so that other emerging disease threats, which are accelerating with climate change, may be met successfully? this chapter considers the wide-ranging socio-political, medical, legal and environmental factors that have contributed to the rapid spread of ebola, with particular emphasis on the politics of the global and public health response and the role of gender, social inequality, colonialism and racism as they relate to the mobilization and establishment of the public health infrastructure required to combat ebola and other emerging diseases in times of climate change. poor nutrition, eroding infrastructure, and ebola transmission rates. section "stigmatization and the local and global response to ebola", discusses the role of stigmatization in the political and global aid response to ebola. section "community engagement and the ebola response", examines the long-term impact of global health assistance on sustainable community-based health services. the conclusion builds on this background to consider ebola's lessons in relation to future and emergent health risks in times of climate change. ebola's emergence is grounded in the legacy of colonialism and its contribution to enduring inequalities within african nations and globally. the contemporary expression of this history is seen in the "washington consensus," the international aid industry and the underfunding and decentralization of service delivery, through privatization, reduced public expenditures, and lack of access to health care for the most vulnerable. developmentalism still informs and has implications for the effectiveness of current public health responses. the racist discourse of the diseased, incapable african, requiring outsiders to swoop in to save the day, can only be superseded through sincere and authentic participatory approaches-real collaboration between global institutions such as the world health organization (who) and local public health and government officials. the whole world bears the responsibility for the ebola crisis. as noted by the people's health movement, "the epidemic, in all probability, will run its course and die down after leaving a trail of death and destruction (not) because we as a global community would have done very much right, but because of the nature of the virus itself. the moot question is, will we have learnt anything? or will it be back to business as usual?" (phm : ) . market demand from consumers in the global north fuels the resource exploitation that produces the conditions in which the ebola epidemic emerged, and other diseases are sure to follow. ebola has its origin in "the unchecked exploitation of natural resources by international timber and mining companies," as the observer ( ) noted in early october based on a who report on the disease. as long as ebola erupted sporadically in small villages along the global resource economies' path, as it did beginning in the s, the outbreaks flared up and went away as quickly as the global corporations leave their tailings ponds behind. the situation is different now. the virus found its way along the human food chain towards the exploding centres of a rapidly urbanizing africa. it reached large cities with their huge inequities, overcrowding, and underdeveloped sanitation and public health systems, and only extreme measures fuelled by moral panic have thus far (and perhaps temporarily) prevented its global spread in the same way sars expanded across the globe in . the unspoken divisions in how these measures play out reveal deep injustices at the global level. for example, in the early days of the ebola crisis, some criticized the unavailability of vaccines to help the sick, despite the fact that several vaccines had been in development for many years in the global north (stanford ) . it was also pointed out that a large pool of exposed but disease-resistant people, such as those now living in ebola-ravaged areas of west africa, would facilitate the development of a serum-based vaccine. even if a vaccine is developed and tested, will it ever be widely available and accessible to all those who need it, in africa and globally? will this become yet another source of profits for big pharma? as has often been noted, there are "tensions inherent in the socioeconomic construct that is today's pharmaceutical industry [which on one hand seeks to protect] the health of the public, but on the other it seeks to maximize profit" (cohen et al. : ) . there may, then, be an understandable concern that seeking a cure or antidote for ebola might become either an opportunity for the pharmaceutical industry to use africa as a laboratory (see chippaux ) , or as another source of profits for the pharmaceutical industry, rather than promoting the enhancement of well-being. or, as david healy has said more dramatically, "an incentive to chase blockbuster profits-doing so regardless of patient welfare" (healy : ) . the who, hit hard by un retrenchment related to the global financial downturn, cut its budget and downscaled its activities rather than insisting on adequate support and new funding approaches, which left the who woefully unprepared to help guinea, liberia and sierra leone mount a speedy and effective ebola response in early (phm ; lee ; harman ; kay and williams ). this put organizations like medecins san frontières (msf), missionaries, and cuban doctors in the position of heroic first responders in very difficult circumstances. points out ibrahim abdullah, who teaches at the university of sierra leone (the oldest university in west africa) in freetown, the epicenter of the epidemic, "this is the neo-liberal scourge: if you privatize health care in the context of mass poverty, you get the ebola epidemic. if, however, you put people at the centre of development by modernizing health and education, you can prevent ebola. ebola is about governance and modernity" (personal communication ). this crisis is neoliberal precisely because each of the three hardest-hit countries (liberia, sierra leone and guinea), in addition to suffering civil wars and large-scale human displacement over the past decade, were also encouraged to privatize health care and introduce-fee-for-service systems that crumbled amidst poverty-a recipe for the ebola disaster (phm ) . this impoverishment has also opened up the same countries for land-grabs, mining exploitation, rapacious foreign direct investment, agro-forestry, habitat destruction, and human displacement which destroys social resilience, endangers public health, and makes quarantine and disease-control systems nearly impossible to manage. the only way to combat these trends is for african states to be encouraged and supported in the harder part of development: building health care and education systems that are public and sustainable. the ebola crisis reveals, thus, both shorter term and longer term issues of development, which represent the deeper crisis affecting not only the three main ebola-affected countries but global distribution in general. the west africa of the ebola epidemic is one of the fastest urbanizing regions on the planet (diallo and dilorenzo ; salaam-blyther ). perhaps the most dynamic social process in africa is its rapid urbanization (including peri-and suburbanization). the ravaging of the countryside by resource companies and the expansion of the urban fabric into regional hinterlands demonstrate the interface between humans and infectious disease. this is, of course, not just an african story. a planetary process of urbanization is underway across vast networks of infrastructure lines, resource supply chains and human travel (brenner ) . as much of this urbanization leads to massive peripheral settlement in existing and new urban centres, often in contiguity with previously mostly undisturbed natural landscapes, we can speak of "suburban constellations" at the heart of the process (keil ; bloch ; mabin ; leahy ) . a new landscape of risk emerges (bloch et al. ) . in mining towns, sometimes physically remote and isolated but connected through global metabolisms and labour markets, we can speak of a "feral" form of suburbanization that confronts human and non-human nature in direct encounter (shields ) . by , it is expected that urbanized land on the planet will cover . million square kilometres which is twice as much as in . this massive urbanization is unequally distributed across the globe, with china and africa absorbing the lion's share of global urbanization during the next generation. we can expect significant consequences for climate change, biodiversity, etc. (seto et al. ; oxfam ) . in this context, ebola, once thought of as being an isolated problem in remote rural areas, has become an urban disease affecting cities and their peripheries, where its spread tends to be rapid and seemingly random due to massive human interaction and often dense and unhygienic living conditions. in the past, disease outbreaks were associated with squalid and unhygienic urban conditions and the immobility of affected communities (keil ) . the new bundled problematique of urbanization, density, and migration has often been the source of huge moral panic (wald : - ) . emerging forms of urbanization lack the infrastructure necessary to support communities in a health emergency. places like kroo bay in freetown, described by a journalist as "a labyrinth of shacks and muddy pathways perched at the edge of a large rubbish dump stretching out into the atlantic ocean", caused concern amongst health care professionals. one was quoted as saying that "these places are always prone to outbreaks" (trenchard : n.p.) . but now the attention is on the (transnational) network of extended urbanization as "the virus is travelling effortlessly across borders by plane, car and foot, shifting from forests to cities and springing up in clusters far from any previously known infections. border closures, flight bans and mass quarantines have been ineffective" (diallo and dilorenzo : n.p.; see also salaam-blyther ; keil ) . standard textbooks on globalization and health tend to overlook the urban dimension and lean towards seeing urban political pathologies in the framework of the nation state system (cockerham and cockerham ; price-smith ). with the sars crisis of , the world was made aware of the importance of cities in the governance of global health crises (ali and keil ) . but this also meant moving from public health governance in and by cities to global public health governance in urban society-a different challenge altogether. the ebola crisis points further in this direction: public health institutions and procedures in cities are absolutely critical (and they often failed in the cases of sars as well as ebola). the time has come for a systemic and networked view of governance (and not just health governance) across the global urban expanse, the entire field of extended urbanization. global institutions, in their imperfection, have begun to act. urban public health systems could be a prime target of international aid to stave off the ebola threat while creating the conditions for future epidemic prevention. the who made a courageous step in to strengthen the roles of cities in improving public health and in the fight against emerging infectious diseases (who ). while ebola proved to be resistant to many conventional containment measures, the strengthening of urban public health institutions in the overall architecture of global health governance and responses is certainly a path that must be pursued in future outbreaks of this and other infectious diseases as cities grow faster and in different patterns than in the past. the impoverished public health sector and desperate state of critical infrastructure in guinea, liberia, mali and sierra leone-barely functioning hospitals, inaccessible and inadequate care with few medical staff, intermittent electricity, underdeveloped transportation networks and non-existent communication networks-are markers of the extent to which the ebola outbreak was able to spread and impact the region (who ; oladele et al. ) . lack of surveillance, monitoring, andlaboratory facilities delayed early ebola diagnoses until march . the region's history, beset by political and social unrest and internal strife, adds to the complexity. both liberia and sierra leone experienced over a decade long civil conflict that decimated their already weak public health infrastructure. health care expenditures in these countries are heavily dependent on foreign aid, tied to commitments that often prohibit investments in public infrastructure (undp ) (table . ). furthermore, countries with a health care workforce below who's recommended critical threshold of professionals (physicians, nurses and midwives) per , people have a lower resilience for diseases and epidemics (afri-dev.info ; who a) (table . ). it is no surprise that the ebola response was weak and characterized by what msf ( ) cites as huge gaps "in medical care, training of health staff, infection control, contact tracing, epidemiological surveillance, alert and referral systems, community mobilization and education"-important components of a comprehensive ebola preparedness and response plan as outlined by the who. mistrust, miscommunication, and rumours fuelled community resistance and avoidance that interfered with public health measures in the region (fofana ) . unlike nigeria and mali, sierra leone, liberia and guinea's outbreak started in rural areas with porous geopolitical borders, plus woefully inadequate and inaccessible public health care, forcing people to seek alternative affordable and accessible traditional medicine (who ). nigeria and mali had successful outcomes for several reasons. first, as the epidemic was in its fourth month, they had enough time to draw up ebola preparedness and response plans. second, both countries repurposed existing infrastructure for ebola: nigeria used its polio facility as an ebola response centre and mali equipped an existing laboratory for ebola testing (who b (who , c (who , . third, the index case arrived in urban cities, where medical care was available (nigeria's by air to lagos city and mali's via road to bamako), allowing for quick diagnosis and activation of monitoring and contact tracing. the region's colonial history depicts an exploitative and extractive relationship with the global north since the s, plus a history of disease importation to the region, and is the backdrop that sheds light on the level of mistrust of national and international agencies that partly shaped public response to the ebola outbreak. for example, in august , the spanish influenza arrived on the shores of sierra leone aboard a british naval vessel (rashid ; olaniyan ) . rural areasthe disease epicenter-are underserved. post independence, national governments perpetuate this exploitative legacy. in sierra leone, rural agriculture and minerals account for a high percentage of national gdp, yet rural areas have not had proportional investment in basic infrastructure like health, water and sanitation and transportation networks (bti ) . it is increasingly evident that climate change is adversely affecting human health. the health burden of climate change also includes the emergence and source: afri-dev.info ( ), dumont and zurn ( ) increased incidence of infectious and water borne diseases. the current ebola outbreak was a chance encounter between a -year old child and a fruit bat, the reservoir for the virus (baize et al. ; saéz et al. ; who ) . some studies cite climate variability as the cause for fruit bats to migrate long distances and reside near cities and towns (frumkin et al. ; pinzon et al. ). an action aid ( ) study on the increasing flood frequency in six african cities reports that "climate change is altering rainfall patterns and tending to increase storm frequency and intensity". in sierra leone, recent extreme weather observed includes heavy rains that cause flash floods, mass land movement, injuries and fatalities, and infrastructure damage ( women accounted for roughly - % of deaths in the ebola epidemic (wolfe ). ebola's gendered impacts-including greater fatality rates for pregnant women, higher risks for caregivers who are often women, and dangers from sexual violence due to ebola-related economic collapse (thomas )-have implications for social resilience, survival of caregivers and mothers, economic in sierra leone, june to august is called "the hungry season," when heavy rains make it hard to harvest and obtain food decline and subsequent recovery in disease-affected areas, and the strength of public health systems (perkins ) . when economic and ecological pressures, exacerbated by climate change, bring people and animals into closer contact while uprooting communities, depleting health care systems, undermining social resilience, and degrading infrastructure, this becomes a "perfect storm" for the emergence and spread of infectious disease. disease ecology reminds us that the transmission dynamics of infectious disease spread involves a complex interplay between natural ecosystems, human economic activity and cultural belief systems (mayer ). an oft-neglected consideration of the disease ecology is the role that stigmatization may play in disease transmission dynamics. stigma is a common aspect of all cultural systems and quite often used in the service of social control (goffman ) . as such, despite the reality of the lethality of ebola, the challenges that stigmatization poses for the effectiveness of outbreak response should not be trivialized. patients may conceal the fact that they are infected, for various reasons related to stigmatization. for instance, one liberian physician observed that "some patients don't tell the truth. they come to you with a different story, like 'abdominal pain'. it's because of the stigma of ebola. they think they won't be treated and they'll be sent away" (york c ). stigmatization in the ebola outbreak situation is not limited to patients. health care workers, for example, were evicted from their homes by landlords out of fear (york b) . furthermore, mobs in rural villages attacked journalists and health care workers (including those engaged in educational efforts but especially those responsible for removing the deceased). similar to the situation with hiv/aids (lewis ) , orphans whose parents had succumbed to ebola also became stigmatized during the earlier stages of the outbreaks. given that unicef found that as of february , there existed , orphans in the ebola-affected west african countries (un newscentre ), the potential for a tragic problem has loomed. however, a unicef official remarked on a positive note that: there were fears that stigma around ebola would isolate the orphaned children, which would mean there would be thousands of abandoned children, but that has, luckily, not materialized. (un newscentre : n.p.). unicef programs provided cash support, material assistance, psycho-social support, and implemented programs to refer families for food assistance. this collectively helped to mitigate the effects of stigmatization and led to % of the orphaned children being reunified with their extended families (ibid.). combatting stigma in populations where half the population is illiterate poses challenging problems. programs that have successfully addressed such challenges may however be found. in monrovia, billboards and posters visible on every major street helped to raise awareness, while thousands of "social mobilizers", consisting of health workers, teachers, religious leaders and youth activists, were recruited in ebola-affected areas to spread the message about the disease (york b) . unicef produced videos and catchy songs with the same intent (ibid.). public health responders from outside west africa were themselves hampered by stigmatization. this is an especially important issue in light of the observation by the who director-general that the ebola outbreak response urgently required outside assistance (weintraub ) . western hospitals were reluctant to allow medical staff to go to west africa, or take in ebola-infected patients, due to worries of being labelled as the "ebola hospital" in their community, or because of concerns that taking such actions would cause anxiety amongst in-house hospital staff (york a) . at another level, stigmatization may be understood as coming from the conflation of race with disease. this association may be bolstered by the term "ebola" itself. according to one linguist, "ebola" connotes to american listeners the very idea of africa because of its sound similarities to 'ebonics' or 'ebony' in the american vernacular (troutman ) . these types of stigmatization have deep structural origins that can be traced to the legacies of imperialism and colonialism in which "tropicality" is associated with disease (bankoff ) . in this type of colonialist discourse, "other" parts of the world are depicted as dangerous, particularly those with "warm climates" from where "new and emerging diseases" are seen to emanate in the twenty-first century (ibid). the effects of such neocolonial influences are seen, for example, in the way in which medical research in the global north has benefited from blood, parasites, and viruses collected from the people of the global south. the patented vaccines developed from such materials benefit those in the global north (and especially the private pharmaceutical companies). as noted by fearnley ( ) , such biomedical gains did little to help build public health capacity and infrastructure within west africa. dealing with such enduring forms of stigmatization is vexing because of the structural dimensions involved in the geopolitics of dependency and global north-south relations. one way forward, however, may be seen in the recent efforts of the african union to establish an ebola solidarity fund and an african centre for disease control by mid- (anders ) . this initiative may have the potential to serve as an impetus to organize and institutionalize efforts against the types of stigmatization that ensue from structural dependency and power differentials embedded in neocolonialism. while ebola may be lethal for those contracting the disease, many, especially the medical practitioners involved in fighting ebola (see gbakima et al. ) , as well as a number of mainstream journalists, have pointed to the media sensationalism surrounding the disease. as such it has been noted that there is a "tendency (in) the international media to attract viewers (which) has led some careless journalists to focus almost exclusively on the fear-invoking mode of death from the disease" such as the garish images of victims "coughing up blood" (wallace ) . such foci are often fed by stereotypes about africa, which are also linked to the oft-depicted image of africa as a site of primitivism and catastrophe, the sources of which lie in colonial discourses of backwardness, exoticism and savagery. thus, while it may be that having a fear of ebola is a somewhat understandable response and not in itself a colonial attitude, the colonial legacy nevertheless exerts a tacit and often unrecognized influence on the fear. specifically, it may "fan the flames of fear" or to put it in more technical terms, the colonial legacy may contribute to the phenomenon known as the "social amplification of risk", whereby peoples' perceptions of risk are unreasonably intensified (kasperson et al. ). one criticism of the international ebola response has been the failure of some international agencies to partner effectively with local government agencies, ngos, and community organizations to respond appropriately and effectively to the epidemic, and to build capacity for the future (gundan ; kaba jones and norman ). the need to engage communities in successful health initiatives is well-established (israel et al. ) and yet this seems to have been lost in the urgency of the international response. international initiatives responding to the ebola epidemic focused on immediate treatment responses, the development and delivery of vaccines, security and containment, and large initiatives like building hospitals. for example, canada's contribution to the ebola campaign was the provision of protective gear, setting up mobile labs, and the delivery of an experimental vaccine (public health agency of canada ). at best, these responses have been slow, expensive, difficult to coordinate, and unsustainable (gundan ). at their worst, the responses met resistance by local populations, and were slow to adapt to the local contexts, thus rendering such responses ineffective and inefficient, and in the end, leaving the communities vulnerable to the next health crises. the importance of acknowledging and respecting concerns and practices of local communities and their socio-political context has been identified as a major issue in implementing health policies and practices (nichter ) . in reviewing the trajectory of the response to the ebola outbreak, petherick ( ) noted the general lack of trust between medical teams and local communities. this lack of trust contributed to community responses ranging from hiding ebola cases from health workers, to attacking health workers and health facilities, driven by the belief that medical staff were spreading the infection, rather than trying to contain it. mitman ( ) argues that the colonial history between africa and europe is one underlying source of this mistrust, a history that began with slave traders and missionaries and continues with the current european exploitation of resources and labour and western military involvement in a range of conflicts. in the early to mid s, american medical researchers followed this path of exploitation, extracting blood, tissue and, ultimately, knowledge, on expeditions to africa, with some amount of coercion and without benefit or explanation to local populations (karamouzian and hategekimana ) . this history of violence, invasion and exploitation has not been forgotten and could only have been reinforced by the presence of western military personnel supporting biohazard-suited health workers (bayntun et al. ) . community based health initiatives are rapid and culturally appropriate responses from agencies trusted by the communities, and as such are more likely to be successful (teutsch and fielding ) . effective and innovative grassroots community led responses began immediately in ebola-affected areas across west africa and have been successful (kaba jones and norman ) . moreover, strengthening these local community organizations can also be part of a strategy to build primary health care in general (anders ) . however, obtaining international support for grassroots initiatives is challenging. most international funding is directed to eu or us organizations, which may have local initiatives and a history of working successfully in the area, but little funding is generally directed to local grassroots organizations or to the development of sustainable health infrastructure (gundan ). the ebola epidemic rose rapidly in countries experiencing severe poverty, with a recent history of political unrest and conflict, and with very poor health care systems and infrastructure. prevention of future epidemics requires development of strong social, political and health infrastructure (kaba jones and norman ). the challenge is that international responses often do little to produce sustainable development. in an interview with journalist flavie halais, development expert ian smillie noted that canada's interventions in sierra leone would have no lasting impact on the health care system (halais ) , and thus make no contribution towards the prevention of future epidemics. representatives of the uk department for international development (dfid) now claim that they should have focused on prevention and social mobilization earlier, and funneled more funding to local grassroots organizations to do so effectively (j oźwiak ). in the same article, however, the author noted that dfid's funding policies made it difficult to fund local agencies, and that they report no plans to shift funding policies, reflecting the disconnect between evidence based practices in population health, and the politics of international aid funding. ebola is a well-studied disease, not an unknown one like sars was when it first appeared in , with a fatality rate of %. ebola's genomes have been sequenced and patented, and supportive health care can reduce its fatality rate to about %, according to health researcher laurie garrett (cbc ) . but as former who staffer akong charles ndika notes, the desperate state of most african health-care systems enables the threat posed by ebola outbreaks to be maintained, and these inequities "will continue in [the] future to manufacture new and re-emerging epidemics like ebola . . . with frightening impact on a global scale" (ndika : n.p.) . moral panic is not helpful. health-care workers need the training and equipment to protect themselves, and basic health education for the general public is crucial to counter stigma, fear, ignorance, and superstition. participatory education and logistics are the main challenges, not just to build hospitals and public health interventions, but also to support food security, infrastructure and governance systems, especially at local levels across the global south. this is a huge and pressing endeavour which only the who can coordinate, working closely with local institutions. so the who must be supported-not just in words but with significant financial and material resources-in order to meet the immediate challenges of new disease outbreaks and also to build the longer-term capacity of local public health agencies so that local units can function effectively and sustainably, since future outbreaks are inevitable in today's globalized world. this applies not only to the need to increase the supply of material resources needed for the emergency response, but also the training of local staff so that they can thwart the threat themselves. broad public participation in governance of the entire health care system is also necessary, both locally and globally, so that education and democracy go hand in hand with the development of strong health care systems. urban public health systems should become a prime focus of who and international support. analysis of the social and economic roots of the ebola epidemic demonstrates that the crisis was grounded in global income inequality and the same impoverishment that had opened up countries for land grabbing, rapacious foreign direct investment and agro-forestry, the displacement of more and more people, the destruction of natural habitats and the erosion of the capacity for social resilience. these conditions will continue to produce outbreaks of emergent diseases in times of climate change, and unless they are addressed, these outbreaks will continue to facilitate ongoing global health threats. political and physical environments. this includes work on culture, migration and health inequities; climate change adaptation; and social integration of refugees. pablo idahosa (ph.d. political economy, university of toronto) is a professor in the department of social science at york university, where he directs the african studies program, and teaches development studies. he has written on development ethics, the politics of ethnicity, and national development. he is author of the populist dimension of african political thought, co-editor of the somali diaspora, and co-editor of development's displacements. among his ongoing research interests are the relationships between development and cultural production in africa, and the politics of disease in africa. he has served on the executive of the international development ethics association. he is completing a book on social welfare in africa. roger keil (dr. phil political science, goethe university, frankfurt) is york research chair in global sub/urban studies in the faculty of environmental studies at york university in toronto. a former director of york university's city institute, he researches global suburbanization, urban political ecology, cities and infectious disease, and regional governance and is principal investigator of a major collaborative research initiative on "global suburbanisms: governance, land and infrastructure in the st century" ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) . he is the editor of suburban constellations (jovis ) and co-editor (with pierre hamel) of suburban governance: a global view (utp ) . patricia e. perkins (ph.d. economics, university of toronto) is a professor in the faculty of environmental studies, york university, toronto, where she teaches and advises students in the areas of ecological economics, community economic development, and critical interdisciplinary research design. her research focuses on feminist ecological economics, climate justice, and participatory governance. she has directed international research projects on community-based environmental and watershed education in brazil and canada and on climate justice and equity in watershed management with partners in mozambique, south africa and kenya, and is the editor of water and climate change in africa: challenges and community initiatives in durban, maputo and nairobi. unjust waters: climate change, flooding and the protection of poor urban communities: experiences from six african cities african factsheet on ebola challenges, health workforce and human resources for health shortages emerging diseases in the global city. blackwell, oxford anders m ( ) ebola responders tap past survivors. youth in community-based strategy emergence of zaire ebola virus disease in guinea rendering the world unsafe: 'vulnerability' as western discourse ebola crisis: beliefs and behaviours warrant urgent attention suburban governance: a global view suburbs at risk. in: keil r (ed) suburban constellations: governance, land and infrastructure in the st century sierra leone country report. bertelsmann stiftung's transformation index (bti) csi ebola: tracking the outbreak's origins. quirks and quarks ebola making a comeback in places it was contained. the toronto star immigrant health workers in oecd countries in the broader context of highly skilled migration. international migration outlook the disease that emerged. limn issue number , ebola's ecologies sierra leone ebola patient, recovered from family, dies in ambulance. reuters climate change: the public health response the truth about ebola: the real way to control ebola is to stop the fear and misunderstanding englewood cliffs gundan f ( ) liberia: how africa and africans are responding to the ebola crisis money (not) well spent? concerns raised over canada's response to ebola. devex global health governance: crisis, institutions and political economy review of community-based research: assessing partnership approaches to improve public health dfid has learned 'a lot' in ebola response. devex fighting ebola from the grassroots ebola treatment and prevention are not the only battles: understanding ebola-related fear and stigma the social amplification of risk: a conceptual framework introduction: the international political economy of global health governance transnational urban political ecology: health, environment and infrastructure in the unbounded city suburban constellations: governance, land and infrastructure in the st century the handbook of mobilities. routledge climate change and transdisciplinary science: problematizing the integration imperative corrupt global food system, farmland is the new gold. inter press service the world health organization (who) race against time: searching for hope in aids-ravaged africa suburbanisms in africa? in: keil r (ed) suburban constellations: governance, land and infrastructure in the st century geography, ecology and emerging infectious diseases ebola in a stew of fear triangulation and integration: processes, claims and implications ebola crisis update-sept th ebola: recovery of americans sharpens divisions in global health global health: why cultural perceptions, social representations and biopolitics matter an assessment of the emergency response among health workers involved in the cholera outbreak in northern nigeria africa: varied colonial legacies another inconvenient truth: how biofuel policies are deepening poverty and accelerating climate change climate justice and gender justice: building women's political agency in times of climate change. paper presented at the international association for feminist economics (iaffe) conference, accra ebola in west africa: learning the lessons ebola epidemic exposes the pathology of the global economic and political system trigger events: enviroclimatic coupling of ebola hemorrhagic fever outbreaks contagion and chaos: disease, ecology and national security in the era of globalization. mit, cambridge public health agency of canada ( ) speaking notes for the honorable rona ambrose, minister of health: the government's response to the ebola outbreak epidemics and resistance in colonial sierra leone during the first world war taking complexity seriously: policy analysis, triangulation and sustainable development the ebola outbreak: international and u.s. responses. congressional research service global forecasts of urban expansion to and direct impacts on biodiversity and carbon pools feral suburbs: cultural topologies of social reproduction, fort mcmurray, canada ebola vaccine story shows folly of free-market drugs rediscovering the core of public health ebola's gender bias sierra leone capital now in grip of ebola. aljazeera race and disease: should we change the name of ebola? aid sustainability and equity: a better future for all west african communities receiving ebola's orphans with open arms contagious: cultures, carriers, and the outbreak narrative ebola's exaggerated fear being fed by stigma and stereotypes as ebola's spread continues, warnings of an inadequate global response cities and public health crisis cholera in sierra leone: the case study of an outbreak: world health organization atlas of african health statistics : health situation analysis of african region ebola virus disease outbreak response plan in west africa nigeria is now free of ebola virus transmission. world health organization updates one year into the ebola epidemic: a deadly, tenacious and unforgiving virus. world health organization updates why are so many women dying from ebola? foreign policy only a few aid agencies willing to help fight ebola in africa. the globe and mail fear and education play crucial role in ebola crisis. the globe and mail u.s. troops arrive in west africa to help fight ebola outbreak. the globe and mail his research focuses on the analyses of 'disaster incubation': how normally unnoticed social and ecological processes converge to create a disaster, including disease outbreaks. he is currently studying the social and political implications of oil sands extraction, with a special focus on the state surveillance and monitoring of environmental activists in canada barlu dumbuya is a graduate student in the disaster and emergency management program with a concentration in environmental issues, technology and disaster management at york university. she is interested in social vulnerability, community resilience and capacity building in developing countries she conducts collaborative research with students, communities and organizations, both locally and internationally, on the relationship between different kinds of social connections (interpersonal relationships, social networks) and resilience in situations of social conflict and displacement key: cord- -dtqjuemu authors: calitz, andre p.; cullen, margaret; fani, dudu title: the influence of culture on women’s it career choices date: - - journal: responsible design, implementation and use of information and communication technology doi: . / - - - - _ sha: doc_id: cord_uid: dtqjuemu skilled information technology (it) professionals are essential to support businesses and the economy. businesses increasingly require more qualified it professionals, be they male or female. in south africa, the number of women professionals participating in the it industry is less than %. a number of factors influence women’s it career choices, such as previous programming exposure, parents, teachers and role models. research suggests that there are gender differences in preferences and beliefs that may affect career choices, including cultural influences. the role of culture in women’s it career decisions has not been extensively explored in south africa. the aim of this exploratory study was to determine if the factor, culture influences women’s it career choices in south africa. an on-line survey was conducted amongst women it professionals in south africa to determine the factors that influenced their it career choices. the data from the survey were analysed using exploratory factor analysis. the results, specifically relating to the factor culture, are reported in this paper. the findings indicate that the factor culture plays an important role when women make it career choices as well as when females decide to remain in an it career. the study found that culture does play a significant role in it career decisions for different ethnic groups in south africa. the findings suggest that efforts must be made to educate young women in computational thinking and expose them to the many career opportunities available for women in the it industry. the it industry has been a vital component in modern business evolution and has enabled sustained business operational success. skilled it professionals are an essential component for business success, however businesses are experiencing an it skills shortage. the european commission estimated that there will be approximately , vacant positions in all sectors of the economy for it specialists by [ ] . worldwide, females are a large pool of participants in the workforce, with over half the global workforce being female [ ] . however, in the it industry there is a notable gender imbalance with fewer females participating in the workforce with a lesser number involved in technical leadership positions [ , , ] . the oecd [ ] report indicates that men are four times more likely than women to become it specialists. in south africa, the number of women professionals participating in the it industry is less than % [ ] . a number of factors influence young persons' career decisions. sources of information and the impact of relatives, teachers and it role-models have been highlighted as important career choice influencers [ ] . a young person's intrinsic and extrinsic motivation, previous exposure to technology and specific programming, all strongly correlated with the decision to pursue a career in it [ , ] . culture can also influence peoples' career decisions [ ] . culture is defined as the arts, customs and habits that characterise a certain society or nation. culture includes the way the people in a society dress, the customs they practice in their marriages, the languages they speak, as well as their family lives, their work patterns, religious ceremonies and leisure pursuits [ ] . zimmermann [ ] further describes culture as the beliefs, values and material objects that constitute a people's way of life. culture is the characteristics and knowledge of a particular group of people encompassing language, religion, cuisine, social habits, music and arts [ ] . cultural factors that influence career choice include but are not limited to religion, personal relations, family responsibilities and attitudes towards networking [ ] . the aim of this exploratory study is to determine the influence of culture on career decisions made by women working in the it sector. this paper provides preliminary insights into the role of culture in career decisions by women working in the it industry. the results highlight the importance of culture and the traditional roles bestowed on women. the layout of the paper is as follows: the research problem, research question and the women in it survey are discussed in sect. . literature on culture and the influence of culture on career decisions for women are discussed in sect. . the women in it survey results are presented in sect. . conclusions and recommendations, relevant to young women wanting to choose a career in it and future work are presented in sect. . the field of it is one of the most evolving fields requiring expert skills. according to careerjunction [ ] , it is one of south africa's top five employment sectors. software development is named as the most sought-after skill in the job market having grown by % from month to month during . in addition, informationweek states that fastgrowing jobs are emerging in the tech space with many relating to artificial intelligence and machine learning [ ] . careerjunction [ ] advertised it jobs in south africa and the it jobs most in demand are software development and programming. south africa is a developing country where it skills are in high demand. these it skills are not met by higher education institutions' it graduate numbers [ , ] . in examining the contrasts of the genders participating in it leadership positions, rogers [ ] noted that the number of women professionals involved in high ranking professional it jobs was significantly lower compared to their male counterparts. less than % of females are in leadership positions in the it industry [ ] . during the year , technology companies that are it industry drivers disclosed their staff demographics. companies such as google, revealed that only % of their it staff were female, while apple and facebook had % and % respectively [ ] . careers in the field of science, technology, engineering and mathematics (stem) have historically experienced low levels of representation from females [ , ] . study fields such as medicine [ , ] have achieved successes in recruiting more females to the profession than in the past, due to their early career education, focused training methods and research strategies that are designed to attract female participants to the profession. it on the other hand, continues to lag behind and is experiencing the opposite, with decreasing numbers of women participants compared to earlier decades [ ] . career choices are made by young people during their early secondary school career [ ] . this is a similar assertion made by armstrong and riemenschneider [ ] who examined an earlier model by scholar ahuja [ ] , which noted that the choice of a career in it is made years before the individual starts working. the high school era is a critical time where young people are guided by their family, teachers, career counsellors and role models most influential to them, to choose school subjects that later direct them to future fields of study and careers. teachers who act as career counsellors have been noted to have a strong influence on the career choices of their scholars, however this advice has resulted in furthering the gender imbalance in it. adya and kaiser [ ] discovered that teachers were more likely to encourage girls towards traditionally female careers such as pre-primary teaching, nursing and secretarial work and males towards technical careers [ ] . this is due to their own limited perspectives, societal biases with partial information of the profession of it and other career options. cultural factors also influence career choice and include but are not limited to religion, personal relations, frame of reference and attitudes towards networking among others [ ] . although women outnumber men in terms of enrolment in higher learning institutions, when it comes to technology-based degrees, men dominate. the number of women obtaining degrees in computer and information systems continues to decrease while the number of women in law school, medical school and other stem fields gradually increases [ ] . the major influences that jung et al. [ ] identified were the influence of marketing, media portrayal of women in technology, role models, social encouragement and education impact. factors influencing the career choices of scholars according to snyman [ ] are self-efficacy, outcome expectations, goal representations, interest and sources of advice, financial expectations and the gender gap. the gender gap particularly identifies factors that influence women. seeing women working in the technical field and female it role models also influences girls when deciding on their careers [ ] . it is important for children to have access to and use computers at home and in schools [ ] . parental support is another influential factor on whether women choose a technology related major. researchers have highlighted the important role of parents, specifically the role the father plays in the children's career choices [ , ] . high performance in school in problem solving subjects like mathematics is linked to increased self-confidence. women who opt for a successful career in it have been noted to be those who experimented with technology and viewed themselves early in life as capable. by choosing this career path, women often want to engage with their skills, grow through promotional opportunities and have the ability to reach top management levels. women who have opted for it find the salaries, future status and lifestyle attractive features of a career in it [ ] . women with stem degrees were noted to earn more than their peers who opted for other degrees and had projected job growth of % compared to . % of those in non-stem degrees [ ] . great lengths have been taken by society and families to attract and encourage young high school scholars of all genders to enter professional careers due to increased status for the family [ , ] . the careers include doctors, accountants and lawyers. however it, whilst misunderstood as a profession by society and families at large, is seen and respected as a smart profession often reserved for technical males [ , ] . the lack of prominent female it role models influences societal views on the profession. culturally, females have not been socialised to view the field of it as an important field of study. pretorius and de villiers [ ] revealed that % of females in south africa view the field of it as cold with great emphasis on functional, abstract, procedural and task-oriented characteristics. they associate it as mainly concerned with programming and building hardware. male dominance and the results of one-sided involvement in the it field can be seen in the entertainment industry of gaming where technology has been used to develop recreational games. these games largely cater for the male population thus possibly reducing the potential profits that could be earned from involving female participants. games are not being used as a tool to raise interest in technology in females [ ] . the use of video games was noted by main and schimpf [ ] as a contributing factor to computer biases. access to games arouses technical interest, improves skills, such as design and rotational abilities and thus serves as an entry to the it field and is a promoter of interest as it develops skills such as graphic design in participants. females are often noted to have strong societal ties to family units, religion and cultural activities and thus participation in a career often hinges on the support from these communities and the ability to continue with the associated activities with these groups [ , ] . du bow [ ] outlined that even though high achieving females outnumber males in the mathematics field, the under-representation of women in it reflects social, cultural and family thinking [ ] . while women live in modern times, the traditional family structure has not changed. women continue to be the primary care givers of families. pretorius and de villiers [ ] observed that women battle to balance a demanding it job while still being heavily involved at home. family influence is the reason for the high volume of females participating in the it field in mauritius, as the family and national culture encourage females to view it as a potentially viable career [ ] . over % of computer science enrolments in mauritius in were women. this is a similar situation in the indian society, where the family structure supports the idea of women actively choosing the it field as a career of choice. in societies such as india and the soviet union, women participate in it careers in higher numbers when compared to men [ ] . in south africa, this reality is different as women view themselves according to traditional society's expectations, which emphasise women as homemakers before being viewed as career women. adya and kaiser [ ] concurred that females who opt for it have been noted to come from families where the parents are highly educated. the influence of parents with degrees allows the family structure to choose nontraditional careers where success is highly valued. women are under-represented in the south african it industry with only % of women pursuing careers in the it sector [ ] . a higher percentage of males graduate with it qualifications from universities and colleges than women [ ] . scholars making career choices are influenced by parents, role models, society and the educational system. it has been shown that culture does play a role in the career choices women make worldwide [ ] . the research problem addressed in this study is that many young south african women (female scholars) do not consider a career in it, possibly as a result of cultural influences. the research question addressed in this study is: does the factor culture influence women it professionals' it career choices? a questionnaire was compiled from a combination of similar questionnaires used in previous gender based studies and from literature [ , ] . an anonymous survey was conducted and the questionnaire included both closed and open-ended questions. the questionnaire was divided into two sections consisting of demographic information and items relating to the independent factors. a five-point likert rating scale ( = strongly disagree to = strongly agree) was used to gather information from respondents regarding the factors that led them to choose a career in it and to stay in the it profession. the institute of information technology professionals south africa (iitpsa) represents it professionals in south africa. iitpsa has over members including over female members. the request to participate in the study was sent to the female members. in addition, the questionnaire was sent to the computer science and information systems alumni of three s.a. universities. the questionnaire was captured using the nelson mandela university on-line survey tool, questionpro. the data were statistically analysed using statistica. the following hypotheses relating to culture were tested in this study: • h : culture and societal attitudes regarding an it career exert no influence on females opting for a career in it. • ha : culture and societal attitudes regarding an it career positively influence females on opting for a career in it. • h : culture and societal attitudes regarding it career exert no influence on females remaining in the field of it. • ha : culture and societal attitudes regarding it career positively influence females remaining in the field of it. a conceptual model was designed to test the various factors that contribute to participation levels. the independent variable was culture and the two dependant variables were females opting for an it career and females remaining in an it career. the model to test the factor culture is demonstrated in fig. . the items for the factor culture were obtained from a literature study [ , , ] . the items relating to the independent factor culture were as follows: • an it career is respected in my community; the two dependent factors with items were: ( ) females opting for an it career; and ( ) females remaining in an it career. decisions to choose and persist in a career or to change careers, are made from adolescence to middle age and are influenced by a number of factors. these factors may be internal to the individual, such as interests or skills, or external, such as influences by families, the economy, or even certain policies [ ] . an important theory that relates to career choices is the theory of reasoned action (tra) by azjen and fishbein [ ] , which states that an individual's behavioural intention is influenced by his/her own attitude and the social subjective norms prevalent in their environment. this theory is derived from the expectancy theory, which indicates that motivation for career decision is the result of the individual's belief in future possible outcomes. the theory of reasoned action stresses that an individual's behaviour can be examined and predicted through the examination of their underlying basic motivation. thus, voluntary the survey was completed by respondents after three calls for participation. the marital status of the female respondents (fig. ) indicated that out of responses, % (n = ) were divorced, % (n = ) living together, % (n = ) were married, % (n = ) were single and one widowed. the respondents indicated that % (n = ) did not have any children, % (n = ) had one to two children, while % (n = ) had three or more. the age responses (fig. ) showed that % (n = ) were twenty one to twenty nine years old, % (n = ) were thirty to thirty nine years old, % (n = ) were forty to forty nine years old, % (n = ) were fifty to fifty-nine years old. there was no one older than sixty. the majority of the women were white % (n = ), followed by africans % (n = ), and the rest are % (n = ) coloured, % (n = ) indian and % (n = ) did not discloses their ethnicity (fig. ) . the highest it qualification indicated (fig. ) by respondents were that % (n = ) had certificates, % (n = ) had diplomas, % (n = ) had degrees, % (n = ) had honours degrees and % (n = ) had a masters degree or above. twenty percent (n = ) had zero to two years of it work experience, % (n = ) had three to four years experience, % (n = ) had five to nine years experience, % (n = ) had ten to nineteen years experience, % (n = ) had more that years experience. twenty nine percent (n = ) indicated that they had role models when they started their career. the five point likert scale responses to the items below are reported by combining the results for strongly disagree/disagree, as well as for agree/strongly agree. mixed responses were received pertaining to culture and societal attitudes about it (fig. ). eighty eight percent (n = ) of the respondents agreed that a career in it was respected in the community. in contrast, sixty-nine percent (n = ) did not agree with the statement that culturally it was not seen as a career for women, thus implying that culturally it was seen as a career for women. a mixed response to the statement that people in their respective cultures had a clear understanding of it was made with % (n = ) disagreeing, % agreeing while % were neutral regarding the statement. fifty one percent (n = ) disagreed that people in their cultures had a clear understanding of it careers, % (n = ) agreed that their community was familiar with careers in it. when it came to societal and cultural perception of females, % (n = ) disagreed that in their cultures having a large family was important and % (n = ) agreed that in their culture a woman is expected to have a family and children. these findings are supported by the efa results presented below. the cronbach alpha for the items for the factor culture was . (n = ) indicating 'excellent reliability'. the correlations were statistically significant at . level for n ranging from to if |r| ! rcrit ranging from . to . and practically significant if |r| ! . . in table , the null hypothesis was accepted (ho ) indicating that culture and societal attitudes regarding an it career exert no influence on females opting for a career in it. the alternative hypothesis was accepted indicating that culture and societal attitudes regarding it career positively influence females remaining in the field of it. the exploratory factor analysis (efa) for the factor culture indicated that one item had to be deleted and three items reversed ( table ). the six remaining items explained % of the total variance for this factor. the t-test conducted with two categories and one-way anova for the demographic variables with three or more categories indicated no statistical difference between culture and the demographic variables marital status, age and number of children for different groups. the demographic variable ethnicity, however indicated a statistical difference (p = . ) between the groups african/coloured/indian and white, with a medium practical statistical difference (cohen's d = . ) for the factor culture (table ) . the demographic variable highest qualification, further indicated a statistical difference (p = . ) between the highest qualifications diploma/degree and honours/masters and above with a medium practical statistical difference (cohen's d = . ) for the factor culture (table ). no statistical differences were recorded for the demographical variables it work experience and role models. the theory of reasoned action indicates that voluntary decisions of women such as career choices can be predicted based on their respective attitude and the influence of those in their social circle and in this case, culture [ ] . in formative years, the influence of others is important, specifically the father [ , ] . a young person's preferences may be influenced by the perceptions of those in their culture. this study contributes to the tra theory as the subjective norms, included in the tra model, which reflect the perception of how others think an individual should behave [ ] are evident in this study's findings. societal gender stereotypes and social norms regarding careers and specifically it, limit the number of females attracted to and staying in the it profession [ ] . women, in general are less informed about the content of the work in it, however they are informed about the inequalities in the field [ , ] . the findings of this study indicate that although it is noted as not being understood in the community ( %, n = ), it is seen as a respectable profession in society ( %, n = ). the pearson correlation analysis confirmed that culture and societal attitudes regarding an it career exert no influence on females opting for a career in it and that culture and societal attitudes regarding it career positively influence females remaining in the field of it. an important finding in this study (table ) indicates that for the two ethnic groupings, african/coloured/indian and white, the respondents perceived the influence of culture on an it career choice statistically differently. thus, the ethnic groups of african, coloured and indian women working in the it industry perceive that culture does play a statistical significant role in women's it career choices. these findings table . ethnicity t-test table . highest it qualification t-test support gathungu and mwangi [ ] that culture does influence women's career choice. additionally, a statistical difference (table ) was also observed between the undergraduate vs the post-graduate degree groups regarding their perceptions on the role of culture in women's it career choices. this exploratory study has provided the foundation for evaluating woman in it career choices in south africa and the influence of the factor culture on the career choices and remaining in the it industry. future research will investigate the role of culture in women's it career choices in more detail, by obtaining a larger sample size and evaluating the views of men as well. the study will be extended internationally and compare the south african results with other countries. early determinants of women in the it work-force: a model of girl's career choices women in the information technology profession: a literature review, synthesis and research agenda early programming education and career orientation: the effects of gender, self-efficacy, motivation and stereotypes the barriers facing women in the information technology profession: an exploratory investigation of ahuja's model gender differences in college students' perceptions of technology-related jobs in computer science understanding attitudes and predicting social behaviour women in stem: the impact of stem pbl implementation on performance, attrition and course choice of women careerjunction: south africa's most in-demand skills (executive summary you don't have to be a white male that was learning how to program since he was five:" computer use and interest from childhood to a computing degree top emerging technology jobs for seeking congruity between goals and roles: a new look at why women opt out of science, technology engineering and mathematics careers women technology leaders: gender issues in higher education information technology attracting and retaining women in computing post-graduate cs and is students' career awareness digital skills & jobs entrepreneurial intention, culture, gender and new venture creation: critical review gender gap in computer science does not exist in one former soviet republic: results of a study reasoned action analysis theory as a vehicle to explore female students intention to major in information systems the underrepresentation of women in the software industry: thoughts from career-changing women sociological concepts of culture and identity closing the gender gap in the technology major unfulfilled need: reasons for insufficient ict skills in south africa the underrepresentation of women in computing fields: a synthetic of literature using a life course perspective does automation influence career decisions among south african students? in: saicsit conference women and men in the it profession women engagement in ict professions in tanzania: exploring challenges and opportunities ict definition implication on ict career choice and exclusion among women south african perspective of the international discourse about women in information technology women in it: the endangered gender factors influencing career choices unpublished honours study. department of computing sciences the trouble with 'women in computing': a critical examination of the deployment of research on the gender gap in computer science what is culture? live science key: cord- - g ov t authors: kurpiers, laura a.; schulte-herbrüggen, björn; ejotre, imran; reeder, deeann m. title: bushmeat and emerging infectious diseases: lessons from africa date: - - journal: problematic wildlife doi: . / - - - - _ sha: doc_id: cord_uid: g ov t zoonotic diseases are the main contributor to emerging infectious diseases (eids) and present a major threat to global public health. bushmeat is an important source of protein and income for many african people, but bushmeat-related activities have been linked to numerous eid outbreaks, such as ebola, hiv, and sars. importantly, increasing demand and commercialization of bushmeat is exposing more people to pathogens and facilitating the geographic spread of diseases. to date, these linkages have not been systematically assessed. here we review the literature on bushmeat and eids for sub-saharan africa, summarizing pathogens (viruses, fungi, bacteria, helminths, protozoan, and prions) by bushmeat taxonomic group to provide for the first time a comprehensive overview of the current state of knowledge concerning zoonotic disease transmission from bushmeat into humans. we conclude by drawing lessons that we believe are applicable to other developing and developed regions and highlight areas requiring further research to mitigate disease risk. amplifi er hosts from which spillovers to humans have been documented (childs et al. ; daszak et al. ) . not surprisingly, the most devastating pandemics in human history, the black death, spanish infl uenza, and hiv/aids, were all caused by zoonoses from wildlife (morens et al. ) . zoonotic diseases can spill between animal hosts and humans in a variety of ways, including through (a) shared vectors, such as mosquitoes for malaria, (b) indirect contact, such as exposure to rodent feces in a peridomestic setting, or (c) direct contact with an animal through consumption, animal bites, scratches, body fl uids, tissues, and excrement (wolfe et al. a ) . most pathogens infecting animals fail to make the jump into humans, but % of zoonotic pathogens (~ out of zoonotic pathogen species studied) that have spilled over are known to be transmissible between humans (taylor et al. ) . of all eids, zoonotic spillovers from wildlife have been identifi ed as the most signifi cant, growing threat to global health (cleaveland et al. ; jones et al. ) . recent evidence highlights the link between infectious diseases and biodiversity loss, land use changes, and habitat fragmentation (cleaveland et al. ; maganga et al. ; gottdenker et al. ) . although additional research on the relationship between habitat degradation and eids is needed, gottdenker et al. ( ) reviewed studies incorporating a broad variety of diseases and found that the most common land use change types related to zoonotic disease transmission were deforestation, habitat fragmentation, agricultural development, irrigation, and urbanization. functionally, the mechanisms infl uencing disease spillover include disruption of food web structures, changes in host-pathogen interactions, and mixing of pathogen gene pools resulting in increased pathogen genetic diversity (jones et al. ) . many studies have shown that habitat fragmentation and biodiversity loss correspond to an increase in disease and pathogen abundance and diversity within a host species (allan et al. ; gillespie et al. ; keesing et al. ; salzer et al. ; cottontail et al. ; young et al. ) . specifi cally, the emergence or re-emergence of many zoonotic diseases including yellow fever, lyme disease, hantavirus pulmonary syndrome, nipah virus encephalitis, infl uenza, rabies, malaria, and human african trypanosomiasis have been linked to anthropogenic habitat changes (jones et al. ) . many of these human environmental changes are occurring in sub-saharan africa where human bushmeat activities have been linked to numerous virulent disease outbreaks, including ebola (leroy et al. a ) , hiv (van heuverswyn and peeters ) , and monkeypox . pathogen spillover from bushmeat can occur through consumption; however, the main risks are associated with exposure to body fl uids and feces during handling and butchering (kilonzo et al. ; paige et al. ) . historically, when a spillover occurred, the likelihood of an epidemic was limited because hunter-gatherer tribes were generally small and widely dispersed, hampering disease transmission between groups of people. once agricultural expansion occurred, human population densities increased, and people became better connected, diseases could spread more easily. as a result, transmissions of infectious diseases from animals to humans have led to devastating outcomes across the globe (lebreton et al. ) . eids cause hundreds of thousands of deaths annually (bogich et al. ) . some outbreaks have spread across large regions and became pandemics, costing the global economy tens of billions of dollars (e.g., sars, h n , the - west african ebola outbreak) and bringing entire nations to the brink of economic collapse. in this review, we explore the links between bushmeat-related activities and eids in sub-saharan africa, where the vast majority of african emerging infectious zoonotic diseases occur (jones et al. ) . the recent ebola outbreaks have highlighted the potential role of bushmeat as a source of pathogens, but a comprehensive review of the different pathogens that may emerge from wildlife through bushmeatrelated activities is lacking. although we are in no way suggesting that this issue is more important than other pressing health crises in sub-saharan africa (such as malaria prevention/treatment and improving healthcare infrastructure), we argue that a better assessment of the public health threats associated with this humanwildlife interaction is warranted and necessary to improve management of future disease outbreaks. the term "bushmeat" refers to the meat derived from wild animals for human consumption (milner-gulland and bennett ) ( fig. . ). it includes a wide range of animals, such as invertebrates, amphibians, insects, fi sh, reptiles, birds, and mammals, including as many as species in sub-saharan africa (ape alliance ). although research has focused largely on mammals and, to a lesser extent, birds, theoretically any wildlife species harvested for bushmeat could be a potential source of zoonotic disease that can spillover during the hunting, butchering, and preparation process (wolfe et al. ; karesh and noble ) . hunters face risk of injury from live animals, which might allow animal blood to enter the hunter's bloodstream through open wounds. while small animals can be carried in bags, large animals are commonly carried on the shoulder or back, bringing the hunter in close contact with the animal and facilitating transfer of body fl uids (lebreton et al. ) . the highest risk of disease transmission occurs during the butchering of animals, e.g. skinning, opening of the body cavity, removal of organs, and cutting of meat. more people butcher than hunt animals ( % and %, respectively, lebreton et al. ) and butchering involves the use of sharp tools, which may lead to cuts during the process. subramanian ( ) found that % of respondents cut themselves on a regular basis during butchering. women are especially at risk of disease transmission as they engage more often in butchering and in food preparation than men. in discussing the links between bushmeat and disease, we refer to this all-encompassing suite of risky behaviors as "bushmeat-related activities." nonhuman primates, rodents, and bats have all been linked to the spillover of zoonotic diseases into humans (cleaveland et al. ; jones et al. ; kilonzo et al. ) . a review of the west and central african bushmeat literature including market, offtake, and consumption surveys documented a total of species from orders that were harvested for bushmeat, including ( %) mammal species, ( %) bird species, ( %) reptile species, and (< %) amphibian species (taylor et al. ) . among mammals, the largest group was primates ( species) including western gorillas ( gorilla gorilla ), bonobos ( pan paniscus ), and common chimpanzees ( pan troglodytes ), followed by ungulates ( species), carnivores ( species), and rodents ( species). in terms of biomass offtake, however, ungulates are generally the most prominent group. although the taylor et al. ( ) study is very comprehensive, it only included studies that: ( ) provided a quantitative measure of bushmeat offtake, consumption, and/or market availability/sales; ( ) used non-biased data collection methods and systematically sampled settlements/hunters to prevent selection bias; ( ) identifi ed carcasses to the species level; and ( ) recorded either the number of carcasses or the total biomass (kg). for a more inclusive and general review of existing central african bushmeat studies, see wilkie and carpenter ( ) , and for west african studies, see schulte-herbrüggen ( ). fa et al. ( ) found that of the approximately one million carcasses traded in the cross-sanaga region of nigeria and cameroon, % were mammals; of which around % were ungulates, % rodents, and nearly % primates. however, as wildlife populations become depleted, such as near urban areas and intensively used agricultural landscapes, smaller bodied mammals comprise a larger share of hunters' offtake (bowen-jones et al. ; schulte-herbrüggen et al. a ). humans have hunted wild animals for consumption and to protect their crops for millennia (shipman et al. ; grubb et al. ; davies et al. ) , and it remains an important source of food and income security among rural communities today (de merode et al. ; brashares et al. ) . bushmeat is an important source of animal protein in many west and central african countries, with up to % of total animal protein consumption coming from wild animals (fa et al. ) . overall, the contribution of bushmeat to protein and food security is generally lower in urban than rural areas and is highest among remote rural communities . for example, the relative importance of bushmeat in the diet of rural gabonese households ranged from % of total household consumption value in a village near a town to % in a remote community (starkey ) . similarly, for rural equatorial guinea, allebone-webb ( ) showed that bushmeat consumption contributed % to total protein consumption in a village with poor transport links, but only % in a village with good connections. in remote cameroonian communities with very few opportunities for purchasing alternative protein sources, bushmeat comprised - % of animal protein consumption (muchaal and ngandjui ) . in rural communities with relatively good market access and low levels of bushmeat consumption, the importance of bushmeat for food has been shown to increase seasonally during the agricultural lean season (e.g. the planting season between harvests) when farming households receive little income (dei , de merode et al. , schulte-herbrüggen et al. b ) and during the dry season when fi sh is not available (poulsen et al. ). bushmeat is also an important source of nutrients, especially among children. evidence from rural madagascar shows that removing bushmeat consumption would result in a % increase in the number of children suffering from anemia and triple the cases of anemia among children in the poorest households most hunters sell at least part of their harvest making it an important source of income, especially where alternative income-generating activities are lacking. the importance of bushmeat in household economies varies across sites and individual hunting households, ranging from % to more than % of the total cash income earned (reviewed in schulte-herbrüggen ). in rural gabon, hunting accounts for up to % of household incomes, with the proportion rising in poorer, more remote communities (starkey ) . hunters are also more likely to sell large animals and keep small animals for their own consumption, because the latter fetch a lower price per animal and may be less marketable (van vliet and nasi ) . finally, households facing income shortages during the agricultural lean season and requiring cash income to pay for urgent expenditures, such as hospital bills, are more likely to sell bushmeat than keep it for own consumption (de merode et al. ) . overall, income from bushmeat sales can be lucrative and compare favorably with alternative work in many rural places. vega et al. ( ) found that commercial hunters in equatorial guinea generated a mean of us$ per year from bushmeat sales. hunters supplying markets in central african logging concessions earned twice the income of junior technicians working at a logging company (tieguhong and zwolinski ) . rural kenya hunters can earn . times the average salary in the area (fitzgibbon et al. ) , and ghanaian hunters can earn income similar to that of a graduate entering wildlife service, and up to . times the government minimum wage (ntiamoa-baidu ) . very successful zambian hunters have been reported earning just below the mean annual income in a single hunting trip (brown ) . the sale of bushmeat historically occurred at a local level, but with increased transportation routes and globalization , the bushmeat trade is expanding to supply urban and international demand. in the past, novel pathogens entering the rural communities may not have spread beyond the community, but this is no longer the case as remote rural areas are connected to urban areas, and increased global trade networks and air travel increases the risk of disease transmission worldwide . this expanding trade network links hunters to consumers, and with many people along this commodity chain coming into contact with bushmeat, the opportunity for disease spillover can occur at many points. for example, the commodity chain supplying bushmeat to an urban market in ghana includes hunters, wholesalers, market traders, restaurant owners, and consumers (mendelson et al. ) . the bushmeat commodity chain supplying an urban market in democratic republic of the congo is comprised of hunters, porters who carry the meat to the road, the bicycle traders who transport the meat into town, and the market-stall owners who sell the bushmeat to consumers (de merode and cowlishaw ) . a recent study from ghana estimates that a minimum of , bats are sold each year through a commodity chain that stretches up to km and involves multiple vendors (kamins et al. a ) . in zambia, mozambique, and malawi, well-developed and complex rural-urban trade supply networks link rural hunters to urban consumers who are willing to pay high prices for bushmeat (barnett ) . understanding commodity chains is important, as pathogens likely remain viable for some period after an animal is killed. for example, prescott et al. ( ) demonstrated that ebola virus remains viable on monkey carcasses for at least seven days, with viral rna detectable for weeks. bushmeat has become a multi-million dollar business due to a growing human population and is now serving both subsistence and trade objectives. harvest volumes have been estimated at , tones per year in the cross-sanaga rivers region of nigeria and cameroon (fa et al. ) , , tones per year in côte d'ivoire (caspary ) , , tons per year in ghana (ntiamoa-baidu ) , and at total of - . million tons per year in central african forests (wilkie and carpenter ; fa et al. ) . however, it is important to recognize that our understanding of the scale of bushmeat harvest is limited by the availability of information and hence current regional harvest estimates might underestimate actual harvest volumes. despite substantial effort in recent years, our knowledge is still site-specifi c and data are lacking from many regions. most surveys have been restricted to relatively small areas or market catchments from which national estimates were extrapolated. research efforts have focused on central africa with some data available for % of countries compared to % of west african countries (taylor et al. ) . a large number of sites with detailed bushmeat data are concentrated in the cross-sanaga region of nigeria and cameroon, where fa et al. ( ) collected market data at sites, hence presenting a geographical bias in our understanding of bushmeat harvest . furthermore, the majority of available data samples ( . % and . %, in west and central africa, respectively) identifi ed by taylor et al. ( ) come from market surveys with poorly defi ned catchment areas, compared to offtake and consumption surveys. strong variation between individual estimates highlights the problems with extrapolation of survey data to national or regional levels and the effects of sampling strategies (hunter versus market surveys), timing of survey (open season versus lean season), survey location, and extrapolation methods. individual fi gures should therefore be treated with caution, but the overall message remains: bushmeat is harvested at an enormous scale exposing those involved in the bushmeat commodity chain to zoonotic diseases. the current scale of bushmeat hunting is primarily the result of socio-demographic changes (wilkie and carpenter ) . africa's human population has risen from . billion in to . billion in and is expected to rise to . billion by (united nations ). where alternative sources of animal protein and income are scarce, human population growth has been linked to increasing hunting intensity (brashares et al. ) . bushmeat has been and remains a staple source of animal protein among the rural poor, yet recent attention has focused on urban consumers of bushmeat as a driver of increased hunting. urban consumers generally have a range of meat sources from which to choose, but value bushmeat for its taste, cultural connotations, and as a luxury food item (fa et al. ). while urban consumers generally consume less bushmeat than rural consumers , urban populations in africa have increased dramatically from about % of the total population in to % in (united nations ) and have created a strong demand for bushmeat and hence market for rural hunters. the increasing demand for bushmeat has been accompanied by changes in hunting technology and improvements in hunting effi ciency. traditional hunting tools , such as nets and bow and arrow, have been replaced with more modern tools of guns and snares. modern guns have an up to -times higher rate of return compared to traditional weapons (wilkie and curran ) , substantially increasing the ease and cost-effectiveness of hunting (alvard ) . this enables hunters to catch more animals and sell a larger part of their catch (bowen- jones and pendry ; bowen-jones et al. ; nasi et al. ) . hunting effi ciency has also improved as remote forests have become more accessible through the construction of logging roads and improved transportation (wilkie et al. ; auzel and wilkie ) . for example, after the construction of km of logging roads in northern congo, the average time for a hunting trip was reduced from to hours (wilkie et al. ) . development of rural businesses , such as timber companies, attracts workers and their families to remote locations, increasing bushmeat demand, especially when no hunting regulations are in place and alternative protein sources are not provided bennett and gumal ; poulsen et al. ). the effect of logging company presence on hunting pressure was documented in gabon where ape populations decreased % between and as a result of hunting (walsh et al. ). in addition, agricultural expansion and mining have exerted a strong force in changing the african landscape and infl uencing human migration patterns (norris et al. ). due to increased access, people are brought into closer contact with wildlife, which facilitates accessibility to bushmeat hunting and makes transportation of bushmeat from rural to urban areas easier and more cost-effective (wolfe et al. a ) . along with increased ease of transportation comes the opportunity for bushmeat to be traded on the international market. the international trade in bushmeat has recently gained attention as both a driver of bushmeat hunting and the cross-border spread of zoonotic diseases. illegal wildlife trade is the second-largest black market worldwide, involving millions of animals and estimated to be worth us$ - billion per year (united nations environment programme ). case studies at airports screening passenger luggage for bushmeat estimated that approximately tons of bushmeat per week arrive at paris roissy-charles de gaulle airport (chaber et al. ) and . tons per year at zurich and geneva airports (falk et al. ) . as bushmeat hunting, globalization, and human interconnectedness increase, the potential for zoonoses leading to eids also increases. this risk was highlighted when retroviruses (e.g., simian foamy virus) and herpesviruses (cytomegalovirus and lymphocryptovirus) were found in confi scated primates at us airports (smith et al. ). indisputable evidence of the transmission of pathogens from wildlife to humans exists only for relatively few cases because the standard of proof is very high. nevertheless, the evidence for spillovers is very strong and many pathogens can be classifi ed as very likely to spillover (jones et al. ; kilonzo et al. ) . furthermore, countless pathogen species of zoonotic potential will likely be discovered as surveillance increases (taylor et al. ; jones et al. ). our close phylogenetic relationship with nonhuman primates increases the likelihood that pathogen spillover from these animals to humans will cause infection (childs et al. ). moreover, it is not surprising that many studies have focused on spillover events from nonhuman primates to humans given the high prevalence of these largely diurnal mammals in the bushmeat trade (taylor et al. ) . for instance, nonhuman primates of the family hominidae include the gorillinae and paninae, which show a genetic difference of only % or less with humans (gonzalez et al. ) , and members of these subfamilies share many morphological, physiological, and ecological features that may have a direct role in the transmission of infectious diseases (davies and pedersen ) . cleaveland et al. ( ) , in their assessment of the risk of disease emergence by taxa, found that the relative risk of disease emergence was highest for bats, followed closely by primates, then ungulates and rodents. there have been surprisingly few studies of the connection between hunting of birds or other vertebrates and eids, especially in africa, but surveillance for zoonotic pathogens in african birds is strongly needed (e.g., for avian infl uenza tracking see simulundu et al. simulundu et al. , . the characteristics of different species may render them more or less susceptible to hunting. behavioral traits such as communal nesting, large-group living, loud acoustic performances, and a diurnal lifestyle-which are found in many primate species-may facilitate the detection and harvesting of several individuals at one time (bodmer ) . taste preferences for certain species infl uence hunters' decisions as do attempts to maximize returns by preferring large-bodied animals that provide more food or fetch a higher price when sold than small-bodied species (bodmer ) . bats, especially the larger fruit bats popular in the bushmeat trade, are susceptible to hunting because they are often found in large, sometimes vocal groups that are visible during the day or in high concentrations in caves (mickleburgh et al. ). increased human encroachment in recent decades (kamins et al. b ) has driven some bat species to become peridomestic (o'shea et al. ; plowright et al. ) , which renders them easy targets for hunting. finally, sick animals may be less successful in evading hunters and hence more easily hunted, thereby increasing the risk of disease transmission to hunters. in addition to the behavioral traits that may infl uence which species are hunted, physiological traits of these species may make them more likely to harbor and transmit diseases. for example, bats, which are present in the bushmeat trade and comprise the highest risk among all wildlife for harboring emerging diseases (cleaveland et al. ) , present unique traits that suit them to hosting pathogens. these traits include: ( ) relatively long lifespans for their body size (munshi-south and wilkinson ), which may facilitate pathogen persistence for chronic infections; ( ) fl ight, which allows movement and dispersal over long distances and which creates high body temperatures that may select for co-evolution with viruses that can live at febrile temperatures and are therefore highly virulent in humans (o'shea et al. ); ( ) physiological similarity across sympatric species that roost together in high densities enabling pathogens adapted to any of the sympatric species to spillover to others (streicker et al. ) ; and ( ) regulation of their immune systems in such a way as to make them more likely to host, but remain unaffected by viral pathogens, serving as the reservoir host for emerging and highly virulent viruses . despite the fact that pathogens are common and often occur in high numbers in basically all animals, only a relatively small proportion of these pathogens will spillover to humans (cleaveland et al. ) . that said, when spillover events do occur, they can be not only deadly but costly. for example, the united nations development program ( ) has estimated that west africa as a whole may lose us$ . billion per year between and due to the - ebola outbreak. this loss stems from the cumulative effects of closed borders, decreased trade, decreased foreign direct investment, and decreased tourism, resulting in increased poverty levels and food insecurity. to understand the dynamics of spillover events and risks in relation to the pathogen, a number of factors must be considered, including: ( ) the evolutionary history of the pathogen, ( ) how the pathogen is maintained among its wildlife host(s), ( ) how the pathogen is transmitted across a species barrier, ( ) whether a productive infection is produced in the new host, ( ) whether that infection produces signifi cant disease in that host, and ( ) whether morbidity and/or mortality levels in the secondary host are suffi cient to be considered signifi cant (childs et al. ) . from this, it follows that emerging pathogens are not an arbitrary selection of all pathogens. becoming established in a human host typically requires adaptations, often for increased virulence, as has been documented in hiv (wain et al. ; etienne et al. ) . generalist pathogens have the ability to infect more than one host species and have higher relative emergence risk than pathogens that are very hostspecifi c (cleaveland et al. ); this is especially true for pathogens that can infect species in more than one taxonomic order. one example of this generalist "broad" host range is found in the newly described african henipavirus, which can enter and infect cells of nonhuman primates, bats, and humans (lawrence et al. ) . of particular importance for understanding bushmeat-related spillover events is whether a wildlife species is a natural or incidental pathogen host. natural or reservoir hosts are a natural part of the pathogen life cycle and may maintain the infectious pathogen for prolonged periods of time, often without showing symptoms. in contrast, an incidental or dead-end host may be infected by the pathogen and may even transmit it, but it is not a part of the normal maintenance cycle of the pathogen and is more likely to be affected by it than natural hosts. for example, contact with sick common chimpanzees and western gorillas has been tightly linked to ebola virus spillover in several outbreaks (leroy et al. b ) . like their human cousins, these great apes are largely considered incidental or dead-end hosts for this virus and do not maintain it long-term in nature. in the case of this deadly fi lovirus, understanding what species are true reservoirs (likely fruit bats in the family pteropodidae; pourrut et al. pourrut et al. , hayman et al. hayman et al. , and the spillover events between these reservoirs and other mammals (including apes, carnivores, and ungulates; leroy et al. a ) will prove critical to mitigating the components of disease transmission that are due to bushmeat-related activities. unfortunately, it is often diffi cult to defi nitively determine the natural host(s) of a particular pathogen as it requires, in descending order of importance, isolation of the agent from individuals of the target species, detection of pathogen-specifi c nucleic acid sequences from individuals, and serological evidence that an individual has been exposed previously. indeed, the study of reservoir systems and how infectious agents move between and within them can be complex, requiring rigorous and sophisticated analyses of multiple interrelated variables (gray and salemi ; viana et al. ) . descriptions of the types of pathogens potentially encountered through bushmeatrelated activities can be found below, with several important and well-studied examples described in more detail. in their review of global trends in eids, in which they separately listed each antimicrobial pathogen strain that has recently emerged, jones et al. ( ) report that the vast majority of pathogens involved in eids are bacterial or rickettsial, followed by viral or prion, then protozoa, fungi, and helminths. other studies have ranked viruses as more prevalent (taylor et al. ; woolhouse et al. ; cleaveland et al. ). in jones et al.'s ( ) analysis of eid events between and , only four eids list bushmeat as the driver; other signifi cant drivers were socioeconomic factors such as human population density. these four bushmeat-related eid events were all signifi cant events; all due to viruses (ebolavirus, human immunodefi ciency virus- , monkeypox virus, and sars), suggesting that viruses are the most important pathogens in regard to spillover due to bushmeat-related activities (see also kilonzo et al. ) . we review the literature from sub-saharan africa in relation to bushmeat species by pathogen type (viruses, bacteria, helminths, protozoa, fungi, and prions), noting the signifi cant potential for pathogens not yet associated with bushmeat-related activities to also be involved. very few studies have considered all of the potential zoonotics in a region or in a taxonomic group. magwedere et al.'s ( ) comprehensive study of zoonotics in namibia is an exception. table . summarizes these pathogens by bushmeat host taxonomic group, conservatively listing only those species/pathogen combinations that have been tied strongly to spillovers from wildlife to humans via bushmeat-related activities and recognizing that this link is often putative and diffi cult to establish. thus, table . does not include some of the potential but not demonstrated spillover risks of poorly studied groups such as helminths and protozoans. furthermore, due to their close genetic relationship with humans, common chimpanzees and western gorillas may share many pathogens of all varieties with humans, but the direction of spillover is not always clear (e.g. tourist interactions may spread disease from humans to apes) and much of these data are not discussed herein. also not included in the table are studies where pathogens are not determined to species and, consequently, the bushmeat host-human link is unclear, or where exposure would be via an insect vector, which could be encountered when handling bushmeat. while we have attempted a very thorough treatment of pathogens that meet our criteria for inclusion in the table, it is possible that some relevant studies have been missed. viruses are obligatory intracellular parasites characterized primarily by the nature of their nucleic acids (dna or rna; single or double stranded, etc.). they are the most abundant form of life on earth; many viruses are recognized as important disease-causing agents, and they are subject to frequent mutation and thus evolution. the advent of modern molecular techniques has advanced our understanding of viral diversity and pathogenesis in both animal and human hosts. for example, in relation to bushmeat, it is now clear that many virus variants are present in hunted nonhuman primate species, which have received most of the research attention, and that these variants have crossed between nonhuman primates and humans on multiple occasions (peeters and delaporte ; table . ). bats and rodents are also major zoonotic virus carriers (meerburg et al. ; baker et al. ); other taxonomic groups are less studied, at least in sub-saharan africa. several sub-saharan african viruses of importance are vector-borne, including rift valley fever and crimean-congo hemorrhagic fever. while one presumes that this would make them unlikely to spread via bushmeat-related activities, the possibility remains that animal handling could present a risk (magwedere et al. ). however, no signifi cant links between vector-borne viruses and bushmeat hunting have been made, and we will not include a discussion of these viruses here. . evidence suggests that siv crossed over to humans by blood contact when hunters had an exposed open wound or injured themselves during the butchering of nonhuman primates (hahn et al. ; wolfe et al. a , b ; karesh and noble ) . the closest relatives of hiv- found among nonhuman primates are sivcpz and sivgor, from common chimpanzees and western gorillas in west central africa (gao et al. ; sharp et al. ; keele et al. ; van heuverswyn et al. , takehisa et al. ) and at least four separate spillovers have occurred (peeters et al. the potential for future and continued spillovers from sivs is high, and multiple species-specifi c variants exist. for example, peeters et al. ( ) and peeters ( ) estimated that more than % of nonhuman primates hunted for food are infected with a variant of siv; locatelli and peeters ( ) and peeters et al. ( ) noted that at least species-specifi c variants of siv from at least primate species are currently recognized. aghokeng et al. ( ) sampled nonhuman primate carcasses from species found in bushmeat markets in cameroon. they documented low overall prevalence of siv (only . % of carcasses), with the lowest prevalence found among the most common species in the market. however, they did fi nd siv variants in about % of the tested primate species. in total, serological evidence of siv infection has been documented for at least different primate species (aghokeng et al. ; liégeois et al. liégeois et al. , . cross-species transmission of strains and co-infection with more than one strain have been documented, sometimes followed by genetic recombination (hahn et al. ; bibollet-ruche et al. ; aghokeng et al. ; gogarten et al. ), a recipe for future spillovers into humans (locatelli and peeters ) . human t-cell lymphotropic virus (htlv) : similar to hiv, human t-lymphotropic viruses (htlv) are related to simian viral lineages in which signifi cant diversity has been found (ahuka-mundeke et al. ; peeters and delaporte ) . all three sub-saharan great apes and additional nonhuman primates have been documented to have stlv/htlv variants and a variety of htlv viruses have been documented in wildlife and in central african hunters (calattini et al. (calattini et al. , courgnaud et al. ; sintasath et al. a , b ; wolfe et al. b ; zheng et al. ; locatelli and peeters ) . similar to hiv/siv, dual infections with more than one variant have been documented in nonhuman primates (agile mangabeys, cercocebus agilis ; courgnaud et al. ) and in humans (calattini et al. ; wolfe et al. b ) . simian foamy virus : simian foamy retroviruses ( sfv ) are endemic in most african primates (hussain et al. ; switzer et al. ; peeters and delaporte ) and are known to transmit to humans (sandstrom et al. ; switzer et al. ; calattini et al. ; mouinga-ondémé et al. , . like the other retroviruses discussed above (hiv and htlv), sfv is genetically diverse and relatively host species-specifi c. in cameroon, wolfe et al. ( b ) documented three geographically independent sfv infections, which could be traced to de brazza's monkey ( cercopithecus neglectus ), mandrill ( mandrillus sphinx ), and western gorilla. likewise, in gabon, mouinga-ondémé et al. ( , documented human spillover events involving multiple strains of sfv, with infected humans having been bitten by common chimpanzees, western gorillas, or mandrills infected with their respective variant of sfv. ebola and marburg viruses : there are seven species of fi loviruses currently identifi ed, fi ve of which occur in sub-saharan africa-genus ebolavirus : tai forest ebolavirus (tafv), sudan ebolavirus (sudv), zaire ebolavirus (ebov), bundibugyo virus (bdbv); genus marburgvirus: marburg virus ( marv ) . these pathogens are periodically emerging viruses, typically from single spillover events, which cause hemorrhagic fevers (reviewed by olival and hayman ; rougeron et al. (but note that rougeron's listing for a single case of sudv in sudan in is erroneous)). the - west africa outbreak of ebov is still ongoing at the time of this writing (labouba and leroy ) . while the zoonotic source of this outbreak is unknown, three initial outbreaks of the ebola virus in the democratic republic of the congo from to involved victims who were reported to have handled western gorilla or common chimpanzee carcasses or to have had physical contact with people who touched the animals (leroy et al. a , b ) . similarly, marburgvirus was fi rst identifi ed in laboratory workers who had dissected imported grivet ( chlorocebus aethiops ) (martini et al. ; siegert et al. ). both western gorillas and common chimpanzees have suffered signifi cant mortality from fi lovirus outbreaks (walsh et al. ; leroy et al. a , b ; bermejo et al. ; rizkalla et al. ) and antibodies to ebov were documented in several other primate species by leroy et al. ( b ) . the single case of tafv occurred in an ethnologist likely infected while performing a necropsy of a dead common chimpanzee following a rash of common chimpanzee deaths in the tai national park in côte d'ivoire (le guenno et al. ; wyers et al. ) . beyond primates, other incidental hosts in the wild are possible, as was demonstrated for duikers ( cephalophus spp.) (leroy et al. a ; rouquet et al. ) . as reviewed by weingartl et al. ( ) , both dogs (naturally) and pigs (at least experimentally) can also be infected. during the - ebov outbreak in gabon, allela et al. ( ) found over % seroprevalence in dogs living in villages with ebov human and animal cases. those dogs appeared to be asymptomatic and were presumed to be exposed by scavenging wild animals. although incidental hosts likely play important roles in the ecology of these viruses, especially when moribund or dead animals are consumed, strong evidence suggests that bats are the natural reservoir hosts for at least marburgvirus and ebov. for marburgvirus, the cave dwelling and densely packed egyptian rousette fruit bat ( rousettus aegyptiacus ) is now well-documented as a reservoir host amman et al. ), but antibodies against the virus and/or the presence of viral rna have been found in several other species (see table . ). the strong association of marburgvirus with the egyptian rousette makes sense in light of the outbreaks of this virus in people visiting tourist caves or working in mines (adjemian et al. ; timen et al. ; towner et al. ; amman et al. ). the picture for ebov is less clear, but evidence of infection has been found in at least eight sub-saharan bat species (pourrut et al. , hayman et al. hayman et al. , table . ). of the ten bat species listed in table . for marburgvirus and ebov, seven are fruit bats, which are relatively larger and more visible, and thus targets of bushmeat hunters. that said, bushmeat hunting of these bats is not ubiquitous throughout their range and cannot solely explain fi lovirus spillovers. mari saéz et al. ( ) unconvincingly suggested the non-fruit bat, mops condylurus, might have been the source of the - west african ebola outbreak. pourrut et al. ( ) found evidence of antibodies against zebov in this species, but there is no real evidence that this free-tailed bat played a role in the - outbreak. to date, no bat host has been identifi ed for bdbv, sudv, or tafv and broader surveillance for indications of these viruses in bats and other hosts should be conducted. henipaviruses and other paramyxoviruses : hendra virus and nipah virus (hnvs) are paramyxoviruses in the genus henipavirus that emerged in australia and southeast asia, respectively, with fruit bats in the genus pteropus (family pteropodidae) as reservoir hosts (reviewed by croser and marsh ) . however, recent studies have identifi ed henipavirus and henipa-like viruses in sub-saharan african fruit bats, which are a phylogenetically distinct clade of pteropodid bats that do not overlap distributionally with any pteropus species. documentation of henipavirus and related rna (drexler et al. ; muleya et al. ; baker et al. ) and anti-henipavirus antibodies (hayman et al. ; pernet et al. ) in the african straw-colored fruit bat ( eidolon helvum ) clearly show that this deadly and diverse viral group is present in sub-saharan africa. this bat species is a frequent target of hunters and a signifi cant protein source where it is found (kamins et al. b ). weiss et al. ( ) documented the presence of this group of viruses in these bats found live in bushmeat markets. strong evidence of spillover to humans was documented by pernet et al. ( ) who found antibodies against hnvs in human samples from cameroon. these seropositive human samples were found almost exclusively in individuals who reported butchering these bats. this bat is also a long-distance migrator with signifi cant panmixia across the continent, which could facilitate viral transmission between bats (peel et al. ) . the paramyxovirus story in sub-saharan africa is still unfolding. both drexler et al. ( ) and baker et al. ( ) describe great diversity in paramyxoviruses from sub-saharan bats. in their comprehensive study of the evolutionary history of this virus family, drexler et al. ( ) found that the henipavirus lineage originated in africa and identifi ed bats as the likely origin of this large family of viruses. a precautionary tale from sub-saharan africa comes from the recent discovery and naming of the sosuga virus from a wildlife researcher who became very ill after handling and dissecting hundreds of bats and rodents in uganda and south sudan (albariño et al. ). this virus is most closely related to tuhoko virus , a rubulalike virus recently isolated from the leschenault's rousette fruit bat ( rousettus leschenaultii ) in southern china. amman et al. ( ) subsequently found sosuga virus in r. aegyptiacus captured from multiple locations in uganda; the researcher infected by this virus handled this species extensively in her studies. lyssaviruses : rabies is the oldest known zoonotic eid, recorded as early as the twenty-third century bc (steele and fernandez ) . an estimated , people die in africa each year from rabies (dodet et al. ) , some portion of which may be from exposure that occurs in bushmeat-related activities, although most human cases can be attributed to domestic dogs. rabies virus (rabv) is in the lyssavirus genus. it is joined in africa by at least fi ve additional species: lagos bat virus (lbv), mokola virus (mokv), duvenhage virus (duvv), shimoni bat virus (shibv), and the newly proposed ikoma lyssavirus (ikov). these viruses have bat(s) as their reservoir host ) with two exceptions. the mokola virus is found in shrews ( crocidura spp.), rusty-bellied brush-furred rat ( lophuromys sikapusi ; saluzzo et al. ) , and companion animals (delmas et al. ; kgaladi et al. ). the ikoma virus has thus far only been documented in african civets ( civettictis civetta ; table . , marston et al. ) . a variety of wildlife species can be secondary hosts of rabies (e.g., in botswana, see moagabo et al. ) and rabies has been documented to occur in a number of nonhuman primate species, including those encountered in the bushmeat trade (gautret et al. ) . lyssaviruses are found worldwide, but the greatest genetic diversity is in africa and lagos bat virus may be more than one species (delmas et al. ; markotter et al. ; kuzmin et al. a ) . while most human cases are due to rabies virus, duvenhage virus has been documented in human fatalities associated with bat scratches that likely transmitted the virus (van thiel et al. ; paweska et al. ) . mokolo virus has been detected in two human cases without mortality (kgaladi et al. ) . the lyssavirus story in africa will continue to emerge due to increased surveillance and improved molecular techniques. the discovery of ikoma virus in an african civet in serengeti national park in tanzania, where domestic dogs are largely absent and detection in bat hosts is nonexistent (marston et al. ; horton et al. ) , highlights the likelihood that many more lyssaviruses exist in a variety of host species. the true diversity of lyssaviruses in africa, and the potential for human spillover via bushmeat-related activities, remains to be discovered. lassa and other arenaviruses : arenaviruses include a number of zoonotic species, typically transmitted from rodents to humans. lassa virus is the best known of the viral hemorrhagic arenaviruses in africa and is well-documented in west africa, especially guinea, sierra leone, nigeria, and liberia. as with some of the bacterial pathogens described below, the primary risk comes from peridomestic exposure to the rodent host, the natal mastomys ( mastomys natalensis ), via exposure to urine or fecal materials. however, ter meulen et al. ( ) found a strong association between hunting of peridomestic rodents and antibodies to and symptoms of lassa virus, tying bushmeat-related activities to the spillover of this virus to humans. human monkeypox virus : contrary to its moniker, the reservoir hosts of human monkeypox virus (mpx) are neither monkeys nor humans, but rather rodents. the fi rst case of human monkeypox was identifi ed in in the democratic republic of the congo, with subsequent outbreaks in liberia, sierra leone, côte d'ivoire, nigeria, and democratic republic of the congo (reviewed by reynolds et al. ; rimoin et al. ) . recent mpx increases in the democratic republic of the congo and elsewhere have been attributed to cessation of the human smallpox vaccine, which conferred some immunity to other pox viruses . human and nonhuman primate infections are suspected to result from wildlife exposure such as would occur in bushmeat-related activities; infected species include squirrels (e.g., thomas's rope squirrel, funisciurus anerythrus ; khodakevich et al. ; african ground squirrels; xerus sp.; reynolds et al. ) , dormice ( graphiurus sp.; reynolds et al. ) , and giant pouched rats ( cricetomys sp.; reynolds et al. ) . the outbreak that occurred in the usa in after exposure to rodents in the illegal pet trade also linked human monkeypox to rope squirrels, dormice, and pouched rats (hutson et al. ). while dormice are small and not likely to be the target of hunting, the diurnal and highly visible squirrels and the giant pouched rats are routinely hunted (taylor et al. ) , making the spillover to humans highly plausible. jones et al. ( ) list . % of eid events as being caused by bacteria and there is good evidence to suggest that bacterial pathogens have the potential to be just as important as viruses when it comes to those that may spillover due to bushmeat-related activities, but in this capacity they have received far less attention (cantas and suer ) . transmission pathways for bacterial pathogens can occur through direct exposure to body fl uids or feces, but they can also possibly be transferred indirectly through exposure to disease vectors such as fl eas and ticks when handling animals. in a rare survey of bacterial pathogens that might spillover via bushmeat-related activities, bachand et al. ( ) sampled muscle from bushmeat carcasses from multiple species at markets in gabon for the presence of campylobacter , salmonella , and shigella . while they only recorded the presence of salmonella , the potential for contamination and thus spillover of enteric pathogens from carcass handling remains high, especially in the days after purchase when pathogens continue to replicate. bacteria in the genus leptospira are endemic sub-saharan african pathogens that have a high risk of spillover during bushmeatrelated activities as they are shed in urine. jobbins and alexander ( ) documented their widespread presence in wild mammals, birds, and reptiles, highlighting the role that wildlife may play in leptospirosis. the bushmeat interface may also play a role in human cases of anthrax, caused by bacillis anthracis , which is largely a disease of grazing herbivorous mammals, but to which common chimpanzees are also susceptible (leendertz et al. ). if bushmeat includes not only the hunting of apparently healthy animals but also sick animals or salvage of contaminated carcasses, the risk of human outbreaks increases (hang'ombe et al. ) . a number of bacterial pathogens are vector-borne, which at face value would make them unlikely to spread via bushmeat-related activities. however, especially for bacteria with fl ea or tick as vectors, as opposed to mosquitoes for example, one can envision that animal handling could present a risk. the most frightening among the vector-borne bacterial pathogens is plague, caused by the bacteria yersinia pestis and transmitted through the infected fl eas of rodents. africa remains an endemic region of importance for this pathogen (world health organization ; davis et al. ) . fleas and ticks are also responsible for transmitting rickettsial pathogens, such as rickettsia africae , which causes african tick-bite fever ( atbf ) . mediannikov et al. ( ) collected ticks from duikers and a pangolin that were living in close proximity to humans in guinea and found r. africae in % of ticks collected from the tree pangolin ( manis tricuspis ), suggesting the potential for spillover with the close handling of these animals. further research is clearly and urgently needed to fully assess the potential for bacterial disease spillovers via bushmeat-related activities. the helminths or "worm-like" animals include many parasites of zoonotic potential, although taylor et al. ( ) found helminthes less likely to cause eids. humans engaging in bushmeat-related activities are likely exposed to these pathogens via exposure to fecal material in which eggs are shed, from transcutaneous exposure to infectious larvae, or from consumption of uncooked meat (mccarthy and moore ) . several studies have examined the prevalence of helminths in animals from bushmeat markets and found high rates of multiple species. for example, adejinmi and emikpe ( ) collected fecal samples from greater cane rats ( thryonomys swinderianus ) and bush duikers ( sylvicapra grimmia ) in bushmeat markets in nigeria and documented high prevalence rates ( . % and . %, respectively) of helminth ova in feces as well as larvae from fecal cultures. likewise, magwedere et al. ( ) and mukaratirwa et al. ( ) reviewed the evidence for trichinella infection in humans, livestock, and wildlife in sub-saharan africa and noted that bush-pigs ( potamochoerus spp.) and desert warthogs ( phacochoerus aethiopicus ) are a source for human infection. as is the case with many other pathogens, humans and nonhuman primates share susceptibility to many parasitic helminth species (pedersen et al. ; pourrut et al. ). pourrut et al. ( sampled gastrointestinal parasites from wild monkeys of species collected from bushmeat markets in cameroon and documented high helminth loads, including species known to infect humans. gillespie et al. ( ) had similar fi ndings from common chimpanzee fecal samples. overall, the available evidence suggests that spillover of many of these pathogens during bushmeat-related activities is likely. protozoans are a paraphyletic group of eukaryotic organisms that are neither animals, plants, nor fungi and include amoebas and giardia. the risk of protozoan spillover from bushmeat-related activities is similar to that for helminths and bacteria in that exposure to feces, bodily fl uids, and even potentially to meat could transmit disease to a permissive human host (pourrut et al. ) . a number of protozoans are important pathogens with zoonotic potential (taylor et al. ). perhaps the best example are the amoebozoa, which cause diarrheal disease and which are documented in a variety of animals, including bushmeat species such as nonhuman primates (gillespie et al. ; pourrut et al. ) . gillespie et al. ( ) documented the amoeba entamoeba histolytica and the ciliated protozoan balantidium coli in common chimpanzees; both are human pathogens (although the direction of spillover is uncertain, as common chimpanzees and other primates may have obtained this parasite from humans). indeed, lilly et al. ( ) documented both protozoans in common chimpanzees, western gorillas, agile mangabeys, and humans living in the same region in central african republic. a number of other nonhuman primates have had documented e. histolytica infections as well (see table . ). other protozoan examples include toxoplasma gondii , which causes the disease toxoplasmosis, but could not be detected during a recent, albeit small scale, survey of bushmeat (prangé et al. ) and water/foodborne parasites such as giardia. recent studies have documented giardia in a variety of species that exist in the bushmeat trade, including western gorilla and african buffalo ( syncerus caffer ) (hogan et al. ). fungi are increasingly being recognized as important pathogens that may emerge, even in humans (jones et al. ; fisher et al. ) , and a number of fungi are considered medically important. in particular, fungal infections are problematic for people who are immunosuppressed (e.g., from hiv infection), in which case their immune systems are unable to adequately fi ght the infection. nonetheless, we have uncovered no examples of eids in africa caused by fungal pathogens not related to human immunosuppression, as even the s outbreak of cryptococcal meningitis in the democratic republic of the congo has been likely linked to co-infection by hiv (molez ; jones et al. ). only % of prion diseases are acquired (as opposed to inherited), but these include the well-publicized outbreaks of scrapie, bovine spongiform encephalopathy (bse, or "mad cow disease"), and chronic wasting disease (cwd) in ungulates from europe and north america. of these, only bse has been detected in humans and in captive-held primates (imran and mahmood a , b ; bons et al. ; lee et al. ) , likely due to consumption of contaminated meat products. the authors have found no descriptions of infectious prion diseases in africa, but this poorly studied pathogen type may well be present in the world's second largest continent. as it relates to bushmeat-related practices, prions can be found in nearly all tissues and are resistant to degradation, even by cooking, rendering them a potential pathogen worth watching. the risk of disease spillover from bushmeat to hunters is highest during butchering and especially if no precautions are taken. whether hunters take precautions may depend on their knowledge and perception of disease risk. there is increasing evidence that the perception of and knowledge about zoonotic diseases is generally low but varies strongly between sites. a survey among rural bushmeat hunters and traders in sierra leone showed that % reported knowledge of disease transmission from animals to humans (subramanian ) . similarly, % of rural-urban hunters and traders in ghana perceived a disease risk from a bat-bushmeat activity, with signifi cantly more respondents associating risk with bat consumption than bat preparation or hunting (kamins et al. ) . individuals who participate in butchering wild animals typically associate less risk to meat preparation and consumption than those who do not participate in butchering (kamins et al. ) (fig. . ) . lebreton et al. ( ) found that hunters and butchers who perceived personal risks were signifi cantly less likely to butcher wild animals, but that risk perception was not associated with hunting and eating bushmeat. thirty-three percent of bushmeat consumers in a ghanaian market were not aware that zoonotic diseases could be transmitted from bushmeat to humans. those who were aware gave ebola ( %) and anthrax ( %) as examples of zoonotic diseases (kuukyi et al. ). in contrast, a large-scale survey among rural central african population showed that the majority ( %) of respondents perceived contact with bushmeat blood or body fl uids as dangerous (lebreton et al. ) . unfortunately, studies in this fi eld can be challenging, as reported perceptions may differ from actual or 'revealed' behaviors and beliefs (wilkie ) . although there seems to be some level of risk awareness in certain human populations, several studies report a distinct lack of precautionary behavior, resulting in hunters, butchers, and consumers exposing themselves to zoonotic diseases. lebreton et al. ( ) found that only % of hunters and % of people reporting butchering indicated that they took precautions against contact with animal blood and fl uids while hunting and butchering. furthermore, the few that took precautions may not have protected themselves adequately, as the most common response was "generally being careful." this was followed by "washing hands," and the least number of participants reporting "avoiding contact with blood, draining blood from carcasses and wearing suitable clothing." paige et al. ( ) examined human-animal interactions in western uganda and found that nearly % of participants reported either being injured by an animal or having contact with a primate. the most commonly reported animal injuries were bites ( . %) and scratches ( . %). in a separate study, it was also shown that although ghanaian hunters generally handle live bats, they do not typically use protective measures such as gloves, and thereby come into contact with blood through scratches and bites (kamins et al. ) . given the lack of awareness and precautionary measures taken among people who come into contact with bushmeat, the opportunity for new zoonotic pathogens to spillover into humans remains high (lebreton et al. ) . this is especially true, since the current rate of hunting wild animals will likely continue-at least until domestic animal production increases and can support the protein needs of the local people. current global disease control efforts focus almost exclusively on responding long after a spillover event has occurred, which increases the risk of a single spillover event causing an epidemic or pandemic. this retroactive response to emerging disease outbreaks is often costly economically and in terms of human well-being (childs and gordon ; united nations development program ) . increased pre-spillover surveillance measures along with quantifi cation of spillover risk is critically needed. for example, wolfe et al. ( b wolfe et al. ( , b found that % of rural cameroonians are infected with wild primate variants of t-lymphotropic viruses and another % are infected with wild primate variants of simian foamy virus. these sorts of data are simply lacking for most emergent disease systems. here we will discuss the regulatory and educational measures that could be taken to mitigate the risk of a zoonotic spillover event and spread. such efforts should be undertaken as a part of a comprehensive response to other sub-saharan public health crises so as to not divert scarce resources. for example, increases in eid surveillance efforts and in post-emergence management go hand in hand with the improved healthcare infrastructure that must become a priority for sub-saharan africa. at face value, the risk of disease transmission would be reduced if people stopped harvesting bushmeat; however, this scenario is not realistic given the importance of bushmeat in many communities in africa for which there is limited affordable access to alternate protein sources (pike et al. ; gebreyes et al. ) . a more practical option may be to restrict hunting of nonhuman primates, as many zoonotic eids have come from them, and instead allow communities to hunt smaller-bodied mammals with higher reproductive rates. any intervention aiming to restrict access to wildlife should involve community leaders and stakeholders during public outreach to reduce the risk of alienating communities (monroe and willcox ) . the education and enforcement necessary to implement such a restriction must consider the cultural and economic contexts surrounding individual communities. consider, for example, the problems with enforcement of access restrictions and the history of antagonistic relationships due to exclusion from protected areas between conservationists and local communities. without proper educational outreach, this could result in backlash from local communities. furthermore, using zoonotic diseases to enforce hunting restrictions runs the risk of demonizing species considered to be the main disease carriers. nonhuman primates could then become targets and their populations could be decimated (pooley et al. ) . a more realistic strategy may be to concentrate on preventing future zoonotic spillover events through culturally appropriate education and preventing the spread of diseases through better disease surveillance. in that effort, it would also be important to incorporate collaborative and interdisciplinary approaches between veterinary researchers, ecologists, microbiologists, public health researchers, and anthropologists to develop surveillance and research approaches that will be both culturally appropriate and improve detection of zoonotic diseases tied to bushmeat hunting (kilonzo et al. ). the risk of disease transmission could be reduced through community education that focuses on people with high levels of exposure to wild animals (wolfe et al. ). communicating with hunters and butchers about the risks associated with bushmeat and promoting awareness of safer techniques may reduce current levels of pathogen exposure and transmission. to enhance the effectiveness of prevention campaigns, it is particularly important to reinforce the potential for infections during hunting and butchering as this may be overlooked by some hunters (lebreton et al. ) . because the risk perception of hunters and those engaging in butchering wild animals has a negative association with the level of participation in meat preparation and consumption (kamins et al. ) , this may reduce current levels of pathogen exposure and transmission, if not by discouraging individuals to participate in preparation and consumption, then by encouraging those individuals to more proactively consider safety and preventative measures. global viral forecasting (gvf; now "global viral" and "metabiota") has been pivotal in educating vulnerable populations in rural central africa by providing information on the risk of zoonotic disease transmission from hunting wild animals (lebreton et al. ) . hunters are informed about disease risks associated with different species, what steps can be taken to avoid infections, and how they can reduce their contact with blood and body fl uids of wild animals. hunters are urged to redirect hunting efforts away from apes and monkeys and towards less risky species such as antelope and rodents, while also being discouraged from butchering animals when there are cuts or injuries on their hands and limbs. of course, a common aspect of such attempts at social outreach and education is that even when it is possible to promote awareness, individuals may not believe the hazard is important or that it could affect them. some authors have even found that when people do believe the risk is real and relevant, there is often little evidence that this knowledge promotes a change in behavior (mccaffrey ) . for example, a pilot education program among ghanaian hunters resulted in substantially improved understanding of disease risk, yet largely failed to change peoples' behavior (kamins et al. ) . when asked about what would change their behavior, participants responded; becoming ill from zoonotic disease followed by alternative livelihoods and stricter laws. because awareness is not directly related to behavior, monroe and willcox ( ) suggest that campaigns should not rely on the threat of infection to change behavior, but should rather use community leaders to change cultural norms associated with hunting and educate people involved in butchering about best practices of how to protect themselves. with the increasing prevalence of zoonotic disease emergence and the associated risk for public health, we have to improve our understanding of the dynamics of spillover events of pathogens from animal to human hosts (rostal et al. ) and improve systematic global monitoring efforts. this could help detect, defi ne, and control local human emergence while it is still locally confi ned and before it has a chance to spread globally. improved detection and surveillance will lead to a better prioritization of public health efforts. one of the most effective strategies in terms of early detection of an emergent pathogenic threat would be to focus surveillance efforts among people who are highly exposed to at-risk animals and on the animal populations to which they are exposed (lebreton et al. ) . bushmeat hunters would be an important target group, as they are in contact with bodily fl uids from animals and are at risk for transmission and infection from novel pathogens. as an example, gvf has established monitoring programs at multiple sites throughout central africa to detect the moment of a pathogen spillover, which can then be used to predict and ultimately prevent zoonotic disease emergences (evans and wolfe ) . in order to track and provide data for eids, this effort coordinates the collection of fi lter-paper blood samples from both hunted animals and people who hunt and butcher wild animals. early results have shown that this type of surveillance can assist in early detection of new diseases by offering insight into pathogen origin. it would also help describe the spillover dynamics of new or existing diseases. such data are valuable for developing a detailed, mechanistic understanding of the processes that drive disease emergence and prevent spillovers from spreading in early stages of an outbreak. contextualizing the relative or actual risks of spillovers would be vital for the preferential allocation of resources to high-risk regions or humans who perform high-risk activities (daszak et al. ). as part of these efforts, improved knowledge of how anthropogenic environmental changes and sociological or demographic factors affect the risk of disease emergence will likely be a cost-effective and sustainable mechanism to reduce or control disease spillover risks (daszak et al. ). the social and environmental issues surrounding bushmeat represent a complex problem for conservation, global public health, and sustainable development, as it is often the poorest and most vulnerable populations who depend on bushmeat for income or food security. accordingly, the challenge should be addressed in a holistic manner, by integrating multiple efforts to achieve common objectives. although much progress has been made not only in addressing the problems concerning bushmeat harvest and zoonotic disease spillover, there is much work to be done. research that would pave the way for future efforts would include the quantifi cation of social response to environmental policy change (e.g., in the context of harvest restriction), development of a more representative picture of bushmeat consumption in africa, a broader exploration of the many classes of pathogens within wildlife, and more thorough understanding and quantifi cation of the dynamics behind spillover events and the risks to humans. such efforts could facilitate the development of policy and infrastructure that would help curb the dependency on bushmeat, reduce risks associated with bushmeat harvest, and help understand in what circumstances zoonotic disease spillover events occur. there is still uncertainty as to how education should be implemented in different regions and what features of such education would be most valuable for local people. such an effort might consist of surveying rural bushmeat-harvesting populations across africa and using the resulting data to contextualize priorities and goals in a way that could help standardize education approaches. while some locations in africa have had extensive research in the scope and impact of bushmeat harvest, much of africa has been neglected in those efforts. a more developed understanding of the location, scale, and structure of bushmeat harvest throughout the continent would help researchers and policy-makers prioritize efforts related to disease surveillance, education, or 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cross-species emergence and establishment of rabies virus in bats zoonotic disease risk and the bushmeat trade: assessing awareness among hunters and traders in sierra leone antigenic characterization of the bangui strain (ancb- d) of lagos bat virus studies of reservoir hosts for marburg virus frequent simian foamy virus infection in persons occupationally exposed to nonhuman primates ancient co-speciation of simian foamy viruses and primates origin and biology of simian immunodefi ciency virus in wild-living western gorillas high prevalence of simian t-lymphotropic virus type l in wild ethiopian baboons bovine tuberculosis and brucellosis in cattle and african buffalo in the limpopo national park risk factors for human disease emergence synthesising bushmeat research effort in west and central africa: a new regional database hunting of peridomestic rodents and consumption of their meat as possible risk factors for rodent-to-human transmission of lassa virus in the republic of guinea supplies of bushmeat for livelihoods in logging towns in the congo basin response to imported case of marburg hemorrhagic fever, the netherlands marburg virus infection detected in a common african bat isolation of genetically diverse marburg viruses from egyptian fruit bats molecular epidemiology of simian t-cell lymphotropic virus type in wild and captive sooty mangabeys united nations, department of economic and social affairs, population division united nations, department of economic and social affairs, population division socio-economic impact of ebola virus disease in west african countries the simian t-lymphotropic virus stlv-pp from pan paniscus is distinctly related to htlv- but differs in genomic organization identifi cation in gelada baboons ( theropithecus gelada ) of a distinct simian t-cell lymphotropic virus type with a broad range of western blot reactivity the origins of hiv and implications for the global epidemic human immunodefi ciency viruses: siv infection in wild gorillas genetic diversity and phylogeographic clustering of sivcpzptt in wild chimpanzees in cameroon fatal human rabies due to duvenhage virus from a bat in kenya: failure of treatment with coma-induction, ketamine, and antiviral drugs hunting for livelihood in northeast gabon: patterns, evolution, and sustainability contrasts in livelihoods and protein intake between commercial and subsistence bushmeat hunters in two villages on bioko island, equatorial guinea assembling evidence for identifying reservoirs of infection simian t-lymphotropic virus type (stlv- ) infection in wild yellow baboons ( papio hamadryas cynocephalus ) from mikumi national park adaptation of hiv- to its human host catastrophic ape decline in western equatorial africa review of ebola virus infections in domestic animals henipavirusrelated sequences in fruit bat bushmeat bushmeat: a disease risk worth taking to put food on the table? bushmeat hunting in the congo basin: an assessment of impacts and options for mitigation why do mbuti hunters use nets? ungulate hunting effi ciency of archers and net-hunters in the ituri rain forest mechanized logging, market hunting, and a bank loan in congo defaunation or deforestation: commercial logging and market hunting in northern congo exposure to nonhuman primates in rural cameroon naturally acquired simian retrovirus infections in central african hunters bushmeat hunting, deforestation, and prediction of zoonotic disease emergence of unique primate t-lymphotropic viruses among central african bushmeat hunters origins of major human infectious diseases emerging pathogens: the epidemiology and evolution of species jumps world health organization ( ) ebola haemorrhagic fever in sudan origin of aids: contaminated polio vaccine theory refuted histopathological and immunohistochemical studies of lesions associated with ebola virus in a naturally infected chimpanzee declines in large wildlife increase landscape-level prevalence of rodent-borne disease in africa emergence of a novel and highly divergent htlv- in a primate hunter in cameroon key: cord- -yxttl gh authors: siegel, frederic r. title: progressive adaptation: the key to sustaining a growing global population date: - - journal: countering st century social-environmental threats to growing global populations doi: . / - - - - _ sha: doc_id: cord_uid: yxttl gh adaptation is an evolving long-term process during which a population of life forms adjusts to changes in its habitat and surrounding environments. adaptation by the global community as a unit is vital to cope with the effects of increasing populations, global warming/climate change, the chemical, biological, and physical impacts on life-sustaining ecosystems, and competition for life sustaining and economically important natural resources. the latter include water, food, energy, metal ores, industrial minerals, and wood. within this framework, it is necessary to adapt as well to changes in local and regional physical conditions brought on by natural and anthropogenic hazards, by health threats of epidemic or pandemic reach, by social conditions such as conflicts driven by religious and ethnic fanaticism, and by tribalism and clan ties. the principal problems with growing populations do not involve space although population density is a problem unto itself for reasons discussed in previous chapters. the main problems are how to nourish people with food and water. the chronic malnutrition that about billion people suffered from in is likely to grow in number in some regions due to global warming/climate change because humans cannot adapt to less food if they are already at subsistence rations. for example, the population in sub-saharan africa is million people. the population is projected to increase to about . billion in , an increase of about %. within the same time frame, the united nations estimates that acreage under maize cultivation in the region will decline by % because of heat and drought brought on by climate change. the loss of arable land for food production can be countered in sub-saharan africa if marker assisted hybridization of maize or maize genetically modified to withstand heat and drought come onto the seed market together with modified seeds for other food staples and if african nations that do not now accept gmo seeds do so in the future. if not, nations favored for food production by climate change will have a moral obligation to provide food staples to people in nations with declining food production at accessible costs based on their economies. it is clear that what happens in sub-saharan africa and other regions with declining cultivation acreage or that will bear other effects of climate change (e.g., drought, shifting rain patterns) will affect the rest of the worldwide community politically, economically, and socially. the earth's problems that associate with global warming/climate change will be further discussed in the last section of this chapter. water is the staff of life. it keeps the body hydrated and is necessary to grow food crops, hydrate food animals, and grow feed grains. chemically or biologically polluted water does not serve these ends. if ingested, contaminated water can result in sickness as discussed in chap. . water stokes industry and manufacturing as well, thus keeping economies in many countries contributing to a population's wellbeing by providing employment, goods, and services. ideally, these businesses contribute their fair share to a tax base that supports social needs (e.g., education, healthcare, maintenance of infrastructure). factory owners adapt and plan against water shortages by having a water recycling system in place but may also slow or stop production until operational water conditions return. citizens with a reliable water supply can adapt to periods of water shortage by limiting use according to mandates by government officials but still have water for basic daily needs. however, persons in nations with a chronic per capita water shortage may not have this option to serve their daily needs unless water is imported or new water sources are found (see chap. ). if imported water is not an option to meet immediate essential needs, an alternative adaptation for people (and animals) is to try to reach a location where water would be available to them. with growing populations, per capita water availability is greatly diminished (table . ), water shortages become endemic, and people are at risk of existing at subsistence levels or dying. most at risk from the lack of a basic water ration are pregnant women, infants, young children, and old people. water wars are a future possibility as nations battle for their peoples' survival unless political differences are set aside and projects are supported to develop and share water sources. in a welcome effort, jordan, israel, and the palestinian authority signed a memorandum of understanding in the world bank, december , with specific aims: ( ) produce millions of cubic meters of drinking water for a water-deficient region; ( ) pipe million cubic meters of water annually * km ( mi) from the red sea to the dead sea; ( ) build a desalination plant at aqaba that would supply water to aqaba and eilat; ( ) the israeli water utility would supply - million cubic meters of drinking water to the palestinian authority for the west bank population at a reduced cost; and ( ) there would be an inflow of water to slow and in the future perhaps abate and reverse the shrinking of the dead sea. funding for the estimated $ million, year project will come from the world bank, donor nations, and philanthropic groups. as the global population increases and more people in developing and less developed nations have more disposable income, there will be a growing draw on natural resources other than water and food to service their industrial, agricultural, and manufacturing needs and wants. competition can force economic wars among national and multinational corporations for the resources necessary to provide goods and services and thus drive up prices for resources. industries and manufacturing units that cannot compete economically for natural resources will shut down, thus contributing to unemployment and downturns in economies because of falling domestic demand. to keep order in the increasingly interdependent world economy, accommodation for shared natural resources (or substitutes for them) at affordable prices is the adaptationnecessary. this can be mandated by the world trade organization backed by other practical-minded international groups. another adverse effect of growing populations that is a national resource that can be lost at the expense of some countries to the benefit of others is brain power. this brain power has been cultivated at excellent universities in developing countries, often times at little or no cost to students (e.g., in medicine, science, engineering, economics, the arts) who attend and graduate in increasing numbers. where there are too many well-educated professionals but lack of employment opportunities for them in their fields of expertise, educated people have the option of relocating to another country that can nurture and use the expertise. many adapt to the employment problem by taking up this option. this may mean moving from a developing country to a developed country or from a less developed country to a developing or developed country. ultimately, this loss of citizens with special skills can hurt a country. to counter this brain drain or reverse it, a country can adapt by investing in its future to create programs and conditions that keep talented professionals home, or if they have emigrated, entice them to return. china and india are examples of countries that have successfully taken this tact. when there are increases in a population because of immigration, problems can ensue between immigrants and a general population. adaptation to diversity and the multicultural experiences it brings to a community is often not a comfortable change. the antipathy of some in a host country is based on slowness of the immigrants to learn the language and inability of host country citizens to understand what immigrants are saying among themselves. this makes citizens feel uneasy. some view immigrants as a threat to their own or a family member's employment or advancement. race difference is a factor that some cannot readily adapt to as is ethnicity with its traditions and customs unfamiliar to the general public. religion can be divisive if adherents to its beliefs engage in acts of hatred detrimental to the host country fueled by fundamentalists and zealots who interpret religious writings as giving them license to commit crimes or absolving them of the crimes. sadly, many citizens paint an entire religious community with the taint of the relatively few evildoers. adaptation to diversity is essential for our earth's citizenry with joint efforts by all to resolve worldwide issues (e.g., global warming/climate change) so as to become the keys to providing a sound future for coming generations. there has to be a shared attack on global threats, no matter what the language, race, ethnicity, or religious beliefs are, no matter social or economic status, no matter whether a threat affects less developed, developing, or developed countries. adaptation is a progressive process when dealing with natural hazards because as each type of natural hazard impacts global communities over time, lessons are learned from each one that give direction to the methods of adjustment. adaptation to living where hazards can be expected to strike and where populations continue to increase is dependent on what we learn from the study of past hazards. we can use this evaluation of measured and observed data to minimize the immediate effects and aftermaths of hazards and protect citizens from injury, death, and from damage or destruction of property or infrastructure when hazards strike in the future. in areas prone to earthquakes, we know that earthquakes do not kill and injure people but that collapsing buildings and infrastructure do. earthquakes are not predictable so that there is no adaptation by a timely evacuation to minimize deaths and injury. however, building structures to make them more earthquake resistant can save lives, reduce injuries, and protect property. thus, after a high-magnitude earthquake, forensic engineering teams come to assess the damage and determine where and why damage and destruction took place within the context of the magnitude of an earthquake, the type of motion it originated (shaking, jarring, rolling), its duration, the area it affected, and the geologic properties of rocks underlying structures' foundations. hazard assessment teams also evaluate other factors that contributed to additional damage such as ruptured gas lines that feed fires and ruptured water lines that inhibit fire control. the engineers establish how construction can be improved in the future in terms of construction techniques and materials to prevent the types of collapses and utility failures they investigated. municipalities revise building codes accordingly to direct reconstruction and future building projects. where possible, structures that withstood an earthquake with minor or no visible damage should be retrofitted to improve their resistance to the next "big one." with each event, we gain more data on how to better construct earthquake-resistant structures and alter building codes to more stringent specifications. in theory, this adaptationto an irregularly recurring global event is good, but in practice it is most applicable to nations with the economic resources for reconstruction according to revised building codes and where there is no corruption to allow a bypass of the code. the same can be stated for retrofitting to give more resistance to earthquakes to existing structures. many developed nations and nations rich in commodity exports (e.g., oil) have a moral obligation to donate funds, material, and expertise to help citizens in economically disadvantaged nations recover from a destructive earthquake. some commodity-rich and economically sound nations do not do so directly, whereas others, big and small, rally to help disaster victims. for example, immediately after megatyphoon haiyan devastated many regions in the central philippines in , israel sent medical doctors and nurses and field hospitals to help philippine citizens recover from the impacts of the typhoon. as discussed in an earlier chapter, volcanoes are predictable in terms of becoming active by emitting wisps of smoke, bulging on a slope, warming of the soil or nearby pond or lake waters, emitting increasing concentrations of gases, and showing increased low-frequency seismicity. however, this activity does not always result in an eruption. a marked increase in measurements and observations, especially the low-frequency seismic activity, suggests that an eruption is imminent. adaptation to living and working on or near a volcano means investing in equipment to monitor volcanic activity and listening to alerts from scientists monitoring its activity and being ready to evacuate by gathering important papers and precious mementos and prepared to load into transportation for evacuation to safe locations. governments adapt by charging geologists to map out areas considered as high-, moderate-, and low-hazard zones in the volcano environs. geologists do this by studying rocks deposited from past eruptions and assessments of the topography. municipalities then pass zoning regulations applicable to the hazard level. governments have adapted to repeated periodic flooding in areas by creating flood control systems described in chap. . dams hold water during times of heavy and/ or extended rainfall and release any overflow into channels that move water away from urban or rural population centers. levees increase the volume of water that can move through a channel, thereby keeping it from spreading into populated areas and cultivated farmland. for smaller waterways that flow through cities, municipalities may invest in deepening, widening, and straightening channels as well as erecting walls so that more water can flow through the area more rapidly without coming out of a channel. governments define zones on flood plains according to a recurrence interval of damaging floods (e.g., years) as being off limits for residential and factory/plant construction. as much as we plan to adjust to living in an area prone to flooding, there is always the possibility of a megaevent that can overcome in situ control systems. therefore, as described chap. , governments adapt to this possibility by installing flood prediction equipment in drainage basins to provide warning to those at risk from rising and sometimes raging waters. the warning gives people time to gather important documents and personal treasures and evacuate to safe areas. the apparent increase in the frequency and magnitude of storms and resulting flooding in recent years is thought by many weather scientists to be related to global warming and the increased amount of moisture in the atmosphere from warmer oceans that gathers in clouds and precipitates during storms. this will be discussed further in this chapter. adaptation to extreme weather events such as an extended period of drought, heat waves, and frigid weather means preparation to wait them out. some municipalities adapt to repeated, sometimes seasonal, times of short-term drought by storing a - month water supply in surface or underground reservoirs during periods of normal precipitation that can be tapped (conservatively) as needed. others may plan to move water via pipes or water tankers from where it is plentiful to where drought conditions exist. otherwise, to survive, people move as best they can to where they have access to water. in instances of years long drought, crops and livestock and other life forms may be lost. heat waves can kill. adaptation to heat wave conditions means that water has to be available to people to avoid dehydration. where possible, homes should have air-conditioning or fans to keep people comfortable and municipalities should have cooling centers to which people can go. personnel should check on senior citizens and escort them to cooling centers if necessary. clearly, economically advantaged nations have the resources to give support to citizens during natural hazards such as these. these nations, international organizations, and ngos have a moral obligation to help economically disadvantaged nations as is possible when hazard conditions such as these threaten populations. the most extreme of weather conditions that can injure and kill people and destroy housing and infrastructure are tropical storms that evolve into violent hurricanes (typhoons, monsoons) by increasing wind speeds and sucking up moisture (water) as they track across oceans toward land. when these storms make landfall, they drive storm surges that can wreak havoc onshore communities, and as they move inland precipitate heavy rains that cause life-threatening and destructive flooding. these violent storms are destructive to coastal populations and island nations and have regional reach inland as they move along paths until they finally spend their energy or move out to sea. on november , , the typhoon named haiyan, the strongest recorded typhoon ever to make landfall smashed into the central philippines killing more than , people, injuring about , , and displacing almost , people. there was a -m (* ft) storm surge driven by winds measured at over km/h ( mi/h) with gusts reaching km/h ( mi/h). the typhoon flattened the city of tacloban that was home to , residents, and there was major flooding inland. the weather alerts led to a government call for evacuation away from the predicted path of the storm, and about million people followed the evacuation warning, surely saving many lives. access to aid typhoon-ravaged areas was difficult, and there were shortages of water, food, and medical care for many evacuees for several days. the philippine central government and local officials were not prepared to deal with a storm of this magnitude but help started arriving from many nations worldwide. there was a post-event concern of attending to sanitation needs of survivors to prevent outbreaks of diseases such as cholera, typhoid fever, hepatitis, and dysentery. if the philippine government had adapted by adopting better policies with respect to response to high-category typhoons in addition to the call for evacuation, the impact of haiyan would have been ameliorated. one would hope that this deficiency would be dealt with to limit the effects of future like disasters. evacuation to prevent injury and death in coastal zones that could be struck by high winds, heavy sustained rains, and storm surges is dependent on weather bureau forecasts and warnings from police, firefighters, or other government-authorized personnel. homeowners adapt to hurricanes by securing roofing with additional nails or special fasteners as a retrofit precaution and by boarding up windows on structures before an incoming storm hits. governments have adapted to the onslaught of violent high-energy storms by constructing seawalls of varying designs and heights to protect population centers by damping the force of storm surges. in china, for example, a seawall . m (* ft) in height and that has been heightened in the past protects shanghai from the full damaging effects of high-category typhoons. as a result of rising sea level, the shanghai seawall and other that protect coastal cities from being flooded by surges from high-energy tropical storms will have to be heightened to afford a greater degree of protection to people and property. wildfires can be a natural hazard when ignited by a lightening strike. however, most wildfires are started by human carelessness such as tossing a lit cigarette on a forest floor or failing to completely extinguish a campfire, or by arsonists. one may adapt to living in an area with a history of wildfires in two ways, neither of which is practical or promises % protection. first would be to clear an area of vegetation in a -m ( ft) swath around a dwelling or site for building. second would be to build with nonflammable materials so that embers propelled during a wildfire could not ignite a structure. adaptation to the advance of a wildfire would be to heed warnings to evacuate carrying a prepared case with important documents and other items of personal value. to delay evacuation by going back to retrieve something from then home can be fatal as it was for two people in a recent (june, ) wildfire that destroyed almost homes in colorado springs, colorado, usa. when there is a hazard event coming that calls for evacuation, responsible and often economically advantaged governments have adapted to the threat by designating evacuation routes, by providing transportation for people who need it, by having evacuation centers stocked with water and food, cots and blankets, basic medical supplies and medical personnel, and by having phone service available for people that need it. in the case of a primary or triggered hazard that happens with little or no warning (e.g., an earthquake, a tsunami, a volcanic mud flow), search and rescue teams should be ready to move in soon after dangerous conditions ease and they can move with safety. there should be medical attention to treat injured survivors, and stations set up as soon as possible to provide water, food, and other essentials available to those that survived with little or no physical hurt. these first steps at adaptation are the keys to survival. recovery after a shock phase can be long and drawn out, depending in grand part on a nation's social and economic resources and physical and economic assistance from other nations, international institutions, and ngos. change on our earth's inhabitants global warming is a fact attested to by an overwhelming majority of the scientific community and unwaveringly supported by a february joint publication of the us national academy of sciences and the royal academy in the uk on the causes and evidence for global warming [ ] . as noted in earlier chapters, during the past century, measurements show that the earth has warmed by * . °c (* . °f). global warming is an ongoing process that is attributed in grand part to a slow but continuous and increasing buildup of greenhouse gases in the atmosphere. the greenhouse gas most associated with global warming is carbon dioxide (co ). a plot of the increase of co content in the atmosphere with time against the increase in global temperature shows an excellent correlation of one with the other. additional lesser contributors include methane (ch ), nitrous oxide (no ), and chlorofluorocarbons (cfcs). with the beginning of the industrial revolution and the increased use of coal as the principal energy source, the content of co in the atmosphere was parts per million ( . %). the combustion of coal and later oil (petroleum) and natural gas emits co to the atmosphere. initially, and for many years thereafter, the added greenhouse gases were taken up by vegetation for photosynthesis and was also absorbed by the oceans and other water bodies. this kept the atmosphere co close to the ppm pre-industrial level. however, with increased industrialization, the need for electrical power, and the use of internal combustion engines, the amount of co generated was greater than what could be absorbed by nature and the content of co in the atmosphere increased. during june , its concentration reached more than ppm, an increase of over % over the pre-industrial concentration (scripps institute of oceanography mauna loa measurement). the increasing co content, other greenhouse gases, aerosols, and particles acted as a media that admitted sunlight (heat energy) to the earth's surface but did not let all of the heat escape back into the atmosphere. this abets global warming. in the past two to three decades, the rush to industrialization in developing countries (e.g., china, india, and brazil) and their growing power needs and vehicular use has thwarted the implementation of international agreements to reduce emissions from coal-fired power plants, other industrial and manufacturing operations, and the transportation sector. a direct consequence of global warming is sea level rise (slr) caused by the progressive melting of icecaps and ice sheets in greenland, the arctic, and antarctica, and of mountain glaciers in the himalayas, the alps, the rocky mountains, and the andes. the * -cm (* in) sea level rise during the past century may see a rise of another * cm (* in)- m (* in) during this twenty-first century. one-third of the rise would be from the expansion of warmer sea water, one-third from icecap and ice sheet melt, and one-third from mountain glacier melt [ ] . in , other researchers used computer models on existing data and proposed that % of sea level rise between and was from glacial melt [ ] . following the same line of investigation, other scientists studied satellite data and ground measurements from alaska, the canadian arctic, greenland, the southern andes, the himalayas, and other high mountains of asia and estimated that glacier contributions to sea level rise from to was % and together with ice sheet melt explained % of slr [ ] . a publication in estimated that ocean thermal expansion - m deep and - m deep contributed up to % to sea level rise [ ] . these latter two estimations are in line with the ipcc prediction for melting ice and ocean thermal expansion contribution to the estimated rise of sea level by the end of the century [ ] . with a rise in sea level, marine waters encroach on land. as the rise continues, possibly at an increasing rate, it threatens habitation in lowlying islands, coastal villages and farmland in lowlying zones, and heavily populated cities worldwide settled on inshore terrain close to sea level (e.g., bangkok, ho chi minh city, jakarta, manila, miami, new york, boston, buenos aires, london, rotterdam). rising sea level and warming of ocean waters have other ramifications that affect coastal communities as well as inland areas. as explained in chap. , the warmer surface water releases more water vapor with heat energy into the atmosphere. when the water vapor molecules condense in clouds, heat energy is released. this energy gives more force to tropical storms as they form, track to shore, and move inland, or storms that move close to and along a coast. these storms may transition to hurricanes (typhoons, monsoons) with the violent winds that cause destruction, and heavy rainfall that triggers flooding if they move onto land. we recognize that rising sea level means that tropical storms that impact a coast with storm surges have a farther reach inland with their destructive energy that is more pronounced when the surge occurs at high tide. the surges also saturate farmland they reach with salt water that harms crops. they also carry salt water into fresh water marshes and ponds, thus disrupting ecosystems there. the increase in the number of these extreme weather events and the increase in violence and destruction they wreak on land compared with like weather events in the recent past (e.g., during the past years) strongly suggest that they are fueled to a significant degree by global warming. there are two possibilities for adapting to the effects of rising sea level on coastal urban centers, one impractical, the other very costly but doable. the impractical adaptation possibility is to move at-risk population centers inland, out of the reach of the destructive tropical storms. this does not lessen the threat of flooding. the move is possible in some cases where land is available, but such a move is not economically feasible. one practical but costly adaptation to mitigate encroachment from sea level rise and the effects of tropical storm surges is to surround cities at risk within place seawalls - m higher than recorded high tides or higher depending on historical records and contemporary published data. the walls can have a concave configuration so that surging waves lose energy when their lower parts hit and are curled back on themselves damping some wave energy or there can be a different configuration best for the site(s) to be protected. similarly, gates buried at strategic locations where there is ship access to consider can be built to be hydraulically driven so that they can rise from a near shore seabed site to mitigate the effects of storm surges. both techniques have been used at different global locations. we have read that climate change affects land-based agricultural production, both for crops and animal husbandry. the warming climate at higher mid-hemispheric latitudes and at higher altitudes does not favor the growth and normal yield and/or quality of many crops. depending upon the degree of climate change and the linked change(s) that may follow it, farmers can adapt in several ways to maintain or increase crop yield and nutrition value. for example, when warming starts diminishing the productivity of a traditional crop, farmers can sow crops that are known to grow well in warmer temperature and give a satisfactory economic benefit. however, new groups of weeds, pests, and diseases will migrate to the warmer growth environment and will have to be dealt with in order to protect the new crops. where the effect of global warming reduces water supply for rain-fed agriculture, for crops irrigated with surface waters, and for groundwater-irrigated crops when aquifer recharge does not balances discharge, agriculturalists can adapt in two ways. first is the use of a more efficient irrigation method that delivers water directly to a growing plant (e.g., drip or focused irrigation). this minimizes runoff and loss to evaporation. second and similar to what was mentioned earlier is to sow a crop that needs less water to thrive and that delivers a good yield, good-quality product. another result of global warming for some farmlands is a longer growing season. in this situation, growers can adapt by planting earlier and have the possibility of double cropping. they can also grow a cultivar that is later maturing and that gives a product that brings a good market price. however, switching to new crops in a warmer growth environment means that there will be an invasion of a new set of weeds, pests, and diseases to ward off. in any efficient operation, and as emphasized in earlier chapters, farmers adjust to a changing growth environment for a given cultivar by applying the optimum amounts of fertilizer and other agricultural chemicals as might be needed that nurture and protect it most effectively. this reduces agricultural costs and lessens runoff of these chemicals to ecosystems where they can be harmful. global warming can bring on abnormal weather extremes that affect agricultural productivity. in these cases, farmers have to plan ahead based on recent history of these conditions in their regions. drought, heat waves, and long-term rain or heavy rain in a short time present problems for both cultivars and food animals. periods of less than average precipitation may last months or years. depending on the amount of the deficit precipitation, adaptation can include storing water in reservoirs and cisterns during times of rainfall to be tapped during a drought to sustain food animals and crops during a short-term, not too severe drought. there is also the option of trucking in water to sustain livestock. long-term droughts when precipitation deficits are high take their toll on plants and animals to the detriment of agriculture in a region especially when accompanied by heat waves. they have caused recent disasters for crops and food animals on all continents less antarctica. farmers either wait out the "bad times," change the type of cropping they do, the livestock they tend to, or change careers. the adaptation from crops that have been grown successfully before the effects of global warming reduced yields and quality of a harvest, to those "same" crops that can grow successfully under the advancing warming changes just described generally means that hybridized species have to be developed and used as warming increases at a location and slowly tracks to higher latitudes and higher altitudes. thus, growers turn to plants that are created by hybridization as described in chap. : traditional methods and marker-assisted selection methods within the same species, and genetically engineered (-modified, -manipulated) methods using different species. hybridization is a slow process, sped up markedly by genetic engineering, a method that yields foodstuff not accepted by the european union and many nations outside the union, especially in africa. bred species are developed to carry one or more characteristics that favor crop resilience against the effects of climate change. these include resistance to disease, weeds, and pests, and tolerant of drought (water stress), heat, short-term inundation, and short-term saline exposure (see chap. ). hybrids have also been developed to give higher yields and more nutritious crops. thus far, research has been focused mainly on improving seed for world staples such as rice, maize (corn), wheat, sorghum, and soybean. there have been great successes where hybrid crops were agriculturalists' adaptation so that the possibility exists that we can feed the earth's growing populations and reduce chronic malnutrition. when this is coupled with the opening of additional arable acreage and the use of improved farming methods for seeding, watering, and harvesting, global food security can be strengthened for the existing world population and the future generations on earth. however, this will require economic and technical input by developed nations and international groups. without basic sustenance, people will have less resistance to diseases and there may be local or regional population crashes if diseases evolve into epidemics or pandemics that invade susceptible populations. warming of the open ocean water, enclosed aquaculture operations in ocean waters and on land water bodies has affected marine fisheries and marine and estuarine aquaculture that grow food fish and shellfish, and lakes that sustain fisheries. in marine fisheries worldwide (e.g., in the north atlantic, off the coast of peru, off the coast of the philippines), some food fish or fish captured for other purposes (e.g., to use in pet food, to use to make fertilizer) have migrated to cooler water in ecosystems with conditions conducive to their spawning and growth. in some cases, predators follow fish they prey upon that have migrated to cooler waters, but in other cases they find new prey to sustain them. in other situations, they may become prey for larger fish in an ecosystem. fishing fleets adapt by following the fish they hunt into cooler waters where ideally they capture the hunted species in quantities allotted them by national and international fishery governing body regulations. if the quota system is followed, this will allow recovery of fish populations and sustainable harvesting. aquaculture operations that provide important supplies of food fish worldwide can adapt to warming waters by raising food fish or shellfish that will grow and multiply under the changed range of day/night temperature conditions if the fish they are farming cannot survive in the warmer waters. aquaculturalists also have the option to move their facilities to cooler-temperature waters, but the economic feasibility of doing this has to be evaluated by a benefit to cost analysis. this analysis has to be for the time frame during which the cooler-ecosystem waters are estimated to remain stable within the framework of a time range against global warming/climate change. another adaptation is that food fish currently being raised can be genetically engineered to be resistant to a warmer growth environment without changing their nutrition yield, growth rate, and ability to reproduce. there are diseases that are global threats, others that put regions at risk, and yet others that menace smaller political divisions. humans adapt to the threat of sickness in a population or a sickness itself in several ways. scientists develop methods to eradicate a virus or bacterium health threat, or a chemical/radioactivity threat. failing this, health professionals act to control a disease, to slow or minimize its transmission, and to apply approved therapies and support research to find therapies to treat an illness if one is transmitted. the following discussion draws strongly on the disease fact sheets put out by the world health organization. vaccines provide a main line of defense against many diseases. smallpox has been eradicated on earth by vaccination. polio has all but been eradicated globally except for a few pockets of the disease in pakistan, afghanistan, and nigeria where, in some cases, religious fundamentalists have beaten and killed health workers tasked with giving the vaccine to children, and in other cases where parents have been warned by the zealots against allowing their children to be vaccinated. recently, polio cases were diagnosed mainly in somalia but also in kenya. this is attributed to the fact that by , , children in somalia have not received the vaccine and are at risk from this highly contagious disease. it is also attributed to crossborder migration of infected persons into kenya. both governments are stepping up their vaccination programs. there were cases of polio diagnosed in the rest of the world in . measles is a global disease that can be prevented by a vaccine that is safe and cost-effective. measles may soon reach the near-eradication stage. in and subsequent years, . million people, mainly children under years of age, died from measles. since , billion children were vaccinated, million in . by , % of the world's children received the measles vaccine, up from % in . from to , deaths from measles dropped to %, from , to , . when the vaccination rate reaches %, mainly in low-income countries, the world will have brought another disease close to elimination [ ] . seasonal influenza is a global viral illness that afflicts - million people. the sickness kills , - , people with severe symptoms annually. transmission of the virus takes place when an infected individual coughs or sneezes without covering his/her mouth and releases droplets that can be inhaled by someone up to a meter away. transmission can also be from hands carrying the virus. seasonal influenza affects all age groups, but children less than years old, people over , and those with complicating medical problems are most at risk. influenza is a disease to be controlled. the principal control is by safe and effective vaccines that can prevent - % of influenza cases in healthy adults. secondary controls are obvious for infected persons: cover the mouth when sneezing or coughing, and wash the hands frequently. the influenza vaccine is taken once annually. because strains of the influenza virus change from year to year, adaptation is needed. the adaptation is via a vaccine that is prepared with or strains that scientists determine will be most common during a coming season [ ] . other types of influenza and respiratory illnesses have the potential to cause an epidemic or pandemic. they include avian flu and its strains and swine flu if the strains develop the ability for person-to-person transmission after infection, and sars (severe acute respiratory syndrome) and middle east respiratory syndrome (mers) because there is human-to-human transmission of the sicknesses. to the present, the outbreaks of the animal influenza diseases have been contained by quarantining infected people during treatment and by culling flocks and herds, or if available, vaccination of healthy animals. the latter two respiratory illnesses are caused by the coronavirus, and infected people have been in isolation wards. for sars, an illness that broke out in and spread to countries, isolation of victims and treatment with antiviral drugs and steroids stopped the disease during . mers is a recent ( / ) illness that has been confined to jordan, saudi arabia, qatar, and the united arab emirates. the mers virus has been found in camels. infected persons are quarantined in hospitals, but an effective drug treatment is still being sought to complement the normal hospital care-afforded patients. hiv/aids is a global epidemic that killed million people in three decades since . worldwide, in , there were million people with hiv, mainly ( million or %) in sub-saharan africa and south/southeast asia. the illness is caused by the exchange of body fluids (semen, vaginal excretions, blood, breast milk) from an infected individual with an uninfected person. more than % of the cases of hiv are from heterosexual activity. there is no vaccine against hiv/aids, no cure for it, but there is a cocktail of medicines (antiretroviral treatment) that control viral replication and allow an infected person's immune system to strengthen. this keeps the illness at bay and afflicted people in general good health and productive in their communities. in , only . million (less than %) of those with hiv in low and middle economies received the antiretroviral treatment. this is changing as more hiv carriers have access to antiretroviral therapy and there are more donations from economically advantaged countries to support hiv stabilization and reduction programs. the number of new cases of hiv is not exploding because more than % of those infected are following protocols that reduce the transmission of the disease. the prevention of transmission methods include access to male and female condoms, blood screening before transfusions, and needle and syringe exchange programs for sterile injections by drug users. hiv testing and education programs and hiv treatment help prevent transmission because individuals in continuous treatment have a very low probability of passing on the disease. male circumcision reduces the infection in men by about %. there is still much progress to be made because there were . million new cases of hiv in , with . million of that total in sub-saharan africa. the hiv/aids is a global sickness that is slowly coming under control because of generous donations from governments and foundations in developed countries added to what low-and middle-income countries themselves provide to lower the prevalence and incidence of hiv in their populations [ ] . tuberculosis (tb) infected . million people globally in , killing . million persons. it is a bacterial disease that spreads among people when infected individuals cough, sneeze, or spit, releasing bacteria into the air where they can be inhaled by others a meter away. although tb occurs worldwide, developing countries carry the largest burden of cases and deaths ( %). the bulk of new cases are regional in asia ( %) with sub-saharan africa reporting a large share as well with , new cases per million inhabitants. there is no vaccination for tb, but the disease can be treated and cured. the treatment is a half-year course of four antimicrobial drugs that must be taken without fail and thus requires continual supervision by healthcare personnel. more than million people have been treated and cured of tb since and perhaps million lives saved by following the who stop tb strategy protocols including securing adequate, sustained financing, ensuring early reliable detection and diagnosis, and providing approved treatment with a secure effective drug supply. the number of people infected with tb is declining, and from to , the tb death rate dropped more than %. the success in dealing with tb is muted somewhat because a strain of the bacterium that causes tb has evolved to be multidrug resistant (mdr-tb). in , , cases of this variant were reported (of the . million cases worldwide), mainly from india, china, and the russian federation. these are treated with, but do not always respond to, the most effective anti-tb drugs. research into new drugs to deal with this problem is ongoing [ ] . there is the question of whether people visiting or immigrating from these countries should be screened before a host country issues them entry visas. regional illnesses threaten the health of s of millions of people mainly in tropical and subtropical areas and often affecting children. one of these, the guinea worm disease, is trending toward elimination, if not eradication. this is a parasitic disease caused when people swallow water contaminated with infected water fleas (microscopic copepods) carrying worm larva. the worms release, penetrate the intestines, and move through the body migrating under the skin until they emerge causing swelling and blistering. people infected with guinea worm disease cannot contribute to their communities for months. during the mid- s, there were . million cases mainly in african nations. but attention to where the sources were so that they could be avoided and treated, and assistance in generating clean water, were adaptations that brought the number of cases down to less than , in . the number of cases continued to decline and was reduced to in in four african countries: south sudan, chad, ethiopia, and mali. there is no vaccine against guinea worm disease. health officials adapt to counter this sickness in several ways. as noted above, access to clean drinking water is the best way to prevent infection. the prevention or transmission of the worms from infected individuals to healthy persons by proper treatment and hygiene and the use of the larvacide temephos to eliminate the parasite-infected water flea vector and other prevention protocols are important in the control and effort to eliminate/eradicate the disease [ ]. the (jimmy) carter institute, atlanta, georgia, usa, has been a principle force since in the fight to rid the world of guinea worm disease. in tropical and subtropical regions, there are three mosquito-vectored diseases that put millions of people at risk: yellow fever, malaria, and dengue fever. yellow fever is an endemic viral disease in tropical regions of africa and latin america with , cases reported annually that cause , deaths. there is no set treatment for afflicted people, but there is an adaptive preventive measure. a vaccine against yellow fever is available that is safe, affordable, and that gives lifelong immunity to the disease with one dose after - days for % of the people vaccinated. when there is the onset of a yellow fever outbreak where the population lacks vaccination protection, mosquito control is an essential first step in adaptation to prevent or slowdown transmission of the yellow fever virus. spraying insecticides to eliminate breeding sites and kill adult mosquitos is the control used during epidemics to make time for vaccination campaigns in a population and for immunity to take hold. there are limitations to the application of the yellow fever vaccine. first is that babies less than months of age should not be vaccinated or, during an epidemic babies less than - months of age should not receive the vaccine. second, pregnant women should not be vaccinated except when there is an outbreak of the disease. third, people with a strong allergy to egg protein or those with a marked immunodeficiency or with a thymus problem should not receive the vaccine [ ] . malaria is a parasitic disease caused by the bite of an infected mosquito. there is no vaccine against malaria, but one is undergoing a clinical trial in seven african nations with results expected in . a use or no use decision as a control method for malaria will be made in . promising results from an early-stage clinical trial of an unconventional vaccine prepared with live, weakened sporozoites of the malaria parasite were published in . plasmodium falciparum was given to healthy - year-old volunteers intravenously. the volunteers were grouped to receive - doses and subsequently exposed to bite by five mosquitoes carrying the parasite. none of the six that received five doses were infected with malaria. three of the that received four doses became infected, whereas of the that received lower doses became infected. of that received no vaccine, became infected. those that became infected were treated with malarial drugs and cured. clearly, higher dosages give protection against infection by malaria [ ] . more research and extensive clinical trials are necessary to determine how children respond to the vaccine with adjusted dosages and whether the results from earlystage trial are reproducible in larger volunteer populations. if the results of additional clinical trials go well, the hurdle of producing enough vaccine and adapting it to injection has to be faced. forty percent of the deaths from malaria are of african children in the democratic republic of congo and nigeria. in addition to sub-saharan africa, populations in asia (especially india and the greater mekong region) and latin america suffer from the disease. the effort to deal with the disease that is preventable and curable now centers on control and treatment to reduce the number of cases. in , the who reported that there were million cases and , deaths (with an uncertainty range of , - , ). in a report, researchers suggested that the number of deaths was understated and that their computer model gave a figure for almost double, , , deaths ( % uncertainty interval of , - , , ) [ ] . the who stood by its figure stating that much of the data in the cited study were based on verbal testimony of how people had died, not on laboratory diagnosis of samples. either figure represents too many deaths from the disease and have to be reduced. mosquito control is the adaptation that can reduce the transmission of the disease greatly. this includes personal protection by use of proper clothing and/or the application of mosquito repellent, the use of longlasting insecticidal (pyrethroids treated) nets to kill mosquitos and prevent nighttime bites, and indoor residual spraying (remains effective for months). those people infected can be treated with oral artemisinin monotherapy followed by a second drug. failure to complete the treatment as prescribed leaves parasites in a person's blood. no other antimalarial treatment is available so that parasite resistance could become a serious problem. for visitors to a malaria region, antimalarial drugs taken before, during, and after a trip can protect them from the disease. many countries in tropical and subtropical areas have used the above-cited strategies and others to work toward the elimination of malaria. malaria eradication is the goal of the who [ ] . dengue fever is a female mosquito-borne virus that infects people with an influenza-like disease in tropical and subtropical regions worldwide. the disease can kill if it evolves to severe dengue. it is endemic in latin america and asia where most cases now occur. since the s, the sickness has spread to more than countries putting about % of the world's population ( . billion people) at risk. dengue fever is especially endemic to urban/semi-urban environments. humans are the main carrier of the virus. after a mosquito bites an infected person, each subsequent bite by the infected mosquito creates another carrier. a mosquito can bite many people each time it feeds. in the americas alone, there were . billion cases of dengue fever reported in with , being severe dengue. there is no vaccination against dengue fever, but research continues to develop one. the main treatment for afflicted persons is to keep them hydrated. adaptation to deal with slowing or stopping the spread of dengue fever involves three main tracks in addition to spraying insecticide to kill mosquitos. the best control method to prevent the transmission of the virus is to deprive mosquitos of sites with shallow, standing water where they can lay eggs and multiply. control can be improved if communities cover and clean water storage containers regularly, and use proven insecticides on them as necessary. finally, individual protection such as the use of mosquito repellants and insecticide-impregnated bed nets can help reduce the incidence of dengue fever as it has with malaria [ ] . although controls are known, they are not always applied because of economics and other factors that prevent access to protection methods. the result is that the number of cases of dengue fever reported continues to grow globally. as populations increase in urban locations, the incidence of dengue fever can be expected to increase as well unless strict controls are enforced until a safe and cost-effective vaccine is developed. a positive aspect of the dengue fever problem is that recovery from one serotype of the virus gives immunity for life. however, there are four serotypes of the infectious virus so that recovery from one leaves a person susceptible to the others [ ] . chagas is another regional disease. it infects - million people annually, mostly in latin american countries. it is a parasitic illness that evolves after the bite of a blood-feeding triatomine bug, often on the face, where it defecates close by leaving parasite-bearing feces. parasites access the body when the feces are inadvertently smeared into the bite, the eyes, the mouth, or any skin lesion. the parasites circulate in the blood expressing their presence as a purplish swelling of one eyelid or as a skin lesion. there are several other symptoms as well in this acute stage of the illness, but these may be absent or mild. if diagnosed early during this stage, chagas disease is treatable. the parasite is killed with the medicines benznodazole and nifurtimox taken for months. there are limitations as to who can take these medicines (e.g., not by pregnant women or people with kidney or liver problems). the untreated sickness can cause cardiac alterations and digestive problems that show up - years after an untreated infection. chagas disease can be spread by blood transfusion and by organ transplant, making blood screening for the parasite essential before a procedure. it can also pass to a fetus from an infected woman. there is no vaccination against the illness so that control of the vector (triatomine sp.) is necessary. the controls adapted by many municipalities include insecticide spraying inside a home, the use of treated bed nets, and hygiene practices that protect food, its preparation, and its storage before eating it [ ] . the sickness may recur if control practices become lax. chagas disease is spreading as populations emigrate from latin america to northern countries. blood screening of visitors or immigrants from the countries where chagas is endemic may be necessary, and treatment followed by an infected individual before a host country issues an entrance visa. this would prevent the ingress and possible spread of chagas. outbreaks of diseases in town and cities is most often caused by bacterium-contaminated water or food and poor sanitation. sicknesses such as cholera, typhoid, and various other diarrhea types are examples of such diseases. they are all highly infectious if good hygiene practices are not followed. these diseases are endemic in many countries where populations do not have access to safe water and adequate sanitation. there are vaccinations for some of these sicknesses that may require more than one dose, but they may not be completely effective or long lasting and require revaccination at times specified by medical personnel (e.g., after - years). otherwise, infected persons can be treated with medicines such as oral rehydration pills or antibiotics. adaptation for prevention is easier called for than realistically available: washing hands with soap and clean water after visiting the toilet, and as noted above, access to safe water and good sanitation. given the millions of people infected by these bacterial diseases and the hundreds of thousand that die from them annually, generally in economically disadvantages countries, there should be an expanding global priority to eliminate the disease-causing conditions, and preparedness to combat an outbreak when it is reported. there are important factors to consider when adopting plans to halt or meliorate the effects of health threats to people in the near and extended future. one is the climate change-driven spread of tropical and subtropical diseases discussed earlier to newly warmer and moister higher-latitude and higher-altitude zones. another is the growth of populations mainly in tropical and subtropical regions in africa, asia, and latin america. together with this latter factor are the increasing populations and population densities in urban centers especially in the regions just cited. an additional factor to consider is whether there is accessibility to populations by healthcare workers or by people to healthcare clinics or hospitals, well-staffed and well-stocked with necessary pharmaceuticals. certainly, future planning has to include funding to support research to develop vaccines for diseases that do not have vaccination as an option against an illness (e. g., malaria, dengue fever) . in addition, improvement of vaccines that are available but that are not completely effective in terms of protection or the length of time they are effective should be a priority in pharmaceutical and biotechnology laboratories. scientists presented a fine review of the status of vaccine research from the design and development of vaccines to discussion of vaccines and infectious diseases (e.g., hiv, malaria, tuberculosis, pneumococcal disease, and influenza) [ ] . they also discuss vaccines against enteric infections and viral diseases of livestock as well as vaccines against non-infectious diseases (e.g., cancer) and against chronic noninfectious diseases. continued and repeated education classes on how to prevent the transmission of diseases and free supplies of materials that work to this end (e.g., insecticide-treated bed netting, male and female condoms) are essential to reducing the prevalence and incidence of diseases as are safe water and uncontaminated food. as new medicines or combinations of medicines are developed, tested, and found to be effective in controlling diseases, they become part of the protocol for either curing disease or controlling disease to reduce transmission while allowing persons to carry on with their lives. in these times of easy and rapid migration, one wonders whether screening of visitors or immigrants for diseases known to be endemic or active in the countries or regions from which they come should be required so as to prevent a carrier from infecting others and spreading a disease (e.g., chagas disease, cholera, tuberculosis). this was done at airports during the sars scare for people leaving or entering a country (e.g., china) and likely limited the transmission of the sars virus and spread of the disease. preparedness for a disease outbreak, response to an outbreak, and management of resources during and post-outbreak are the keys to adapting to health threats that could affect future generations. this means developing the capability to extend the reach of health services to regions where climate change brings warmer, moister conditions to higher-latitude and higher-altitude ecosystems that are now reached by disease vectors that have expanded into these formerly cooler and drier environments as a result of global warming. adapting to this reality and planning ahead makes it possible to deal with and stem an incipient outbreak of disease before it is transmitted and spread to the general population. this becomes essential when there is a future disease outbreak in large, dense populations in tropical and subtropical urban centers as well as those in regions warmed and humidified by climate change to subtropical and tropical settings. remember that urban populations worldwide, especially in africa, asia, and latin america, are where much of the global population growth will take place during the next few generations. under these conditions, diseases can spread rapidly in many ways. these include from bites of vectors, by respired droplets after an infected person coughs or sneezes, and by touching surfaces bearing viruses, bacteria, or parasites. diseases are also spread by ingestion of contaminated water and/or tainted food, and by other methods of infection transmission. disease transmission can be checked by rapid response teams with appropriate and sufficient supplies to treat (and perhaps places to quarantine) those in the infected population. lastly, it must be noted that there are many other diseases in addition to those cited previously for which prevention, treatment, and cures are research priorities in laboratories worldwide. in addition, there are addiction diseases that can trigger health problems in important segments of society. these include smoking (e.g., emphysema, lung cancer), alcoholism (e.g., cirrhosis of the liver), drugs (e.g., various psychological and physical ills), and overeating (obesity, diabetes, high blood pressure). adaptation to these health threats involves public education forums through various media outlets, counseling, and sponsored groups with their individual group meeting, and programs are assisting many in breaking from an addiction to the benefit of a healthier life. adaptation to meet the health challenges in the past, and in contemporary times has been a slow, progressive adventure with many successes but with much yet to be done. this is the planned path for the future: meet the challenges of societal health threats, resolve many, and keep researching to resolve others. a special ipcc report in examines in a general way adaptation to a changing climate as a risk management approach [ ] . it uses pre-planning to reduce exposure and vulnerability to extreme hazard events by preparing for them beforehand, responding to their impacts on people, structures, and infrastructure, and having in place recovery systems that can act when a danger condition eases. in this way, there will be an ability of populations to cope with future risks brought on by a changing force with which a hazard impacts a community, changes in the frequency of an occurrence, and extension of the spatial reach of its destructive power. much of this has been discussed in the chapters of the book you are reading. an understanding of what is being done now to adapt to the various problems society faces during the second decade of the twenty-first stimulates proposals of how to adapt to them as global conditions change in the future. to this end, the world bank commissioned a study on the effects global warming as it increased from . °c that exists on our planet now to what can be expected if the warming reached °c, a change that many scientists believe we can adapt to, and then reached °c as warming continues [ ] . the study centered on regions with high population growth and great susceptibility to be negatively impacted by climate changes: ( ) sub-saharan africa where food production is at risk: ( ) southeast asia where coastal zones and productivity are at risk; and ( ) south asia where there could be extremes of water scarcity and excess. the effects of higher temperatures from global warming and climate change included what has been discussed in previous chapters of this book: heat, drought, sea level rise, coastal zones, typhoons, flooding, river runoff, water availability, ecosystem shifts, crop yields, fishing, aquaculture, livestock, health and poverty, and tourism. projections such as those published in the world bank study give impetus to governments, international institutions, multinational companies, private foundations, and ngos to think now, to invest now, and to research now for adaptations that can be realized in good time and that will provide global citizenry with a good quality of life where needed. in this book, we have examined existing human populations and the problems they are experiencing in the second decade of the twenty-first century and have also considered growing populations globally and additional problems future generations will experience. we have discussed strategies on how to cope with manyfaceted threats to citizens. these include how to nourish those who need food and water, how to shelter people safely from natural and anthropogenic hazards, how to provide them with healthcare, education, and employment, and how to prepare them for the evolving global warming and the physical and biological dangers that ensue from climate change. given the present global conditions with about % of our earth's population suffering from malnutrition and more than % not having access to safe water, our capability of nourishing a billion and a half more people by is in question. also problematical is our capability to provide for an additional billion people years later, or a total of at least . billion people by the turn of the century, that is, if we reach those population figures or have population crashes such as from pandemics that can kill scores of millions if a disease is not immediately treatable, or an unlikely but possible nuclear conflagration that could do the same. less likely yet is an explosion of a small asteroid or comet in the atmosphere such as happened in a poorly inhabited area of siberia in . here, an exploding mass more than m in size knocked down millions of trees in an area greater than , km (close to mi ) with energy thought to be , times greater than the hiroshima atomic bomb. clearly, such an event could kill the population of a megacity if it were to occur. another question is whether national governments are economically strong enough and have the will to set priorities that adopt strategies to protect citizens from natural (e.g., earthquakes) and anthropogenic (e.g., pollution) hazards as well as from extreme weather conditions that are supported by global warming (pollution of the atmosphere) but are naturally occurring. countries can also improve social and economic conditions by investing in health care and education for their citizens in order to form a sound and knowledgeable cadre that would be attractive to investors interested in locating a development project that would provide employment. again, this is in question given limited national economic capabilities and the increasing numbers of people to be accommodated, especially in several developing and less developed countries in africa, asia, latin america, and the middle east. at this point, we must ask, "what is the carrying capacity of the earth?" have we reached it at billion given the billions who are today under served in developing and less developed countries? some scientists will answer yes, whereas others believe that advances in agriculture and technology can allow population expansion although to what point is not defined. can countries that are poisoning their environments do a turn around to save their citizens from grief? can they exert controls on operations that create unhealthy conditions that sicken people, lessen agricultural production, and otherwise disrupt local, regional, and global climate change: evidence and causes ( p) intergovernmental panel on climate change ( ) climate change (as four part report). part . the physical science basis mitigation of climate change past and future sea level change from the surface mass balance of glaciers a reconciled estimate of glacier contributions to sea level rise ocean thermal expansion and its contribution to sea level rise tuberculosis. fact sheet no. p . world health organization ( ) dracuncukiasis (guinea-worm disease) protection against malaria by intravenous immunization with a non-replicating sporozoite vaccine global mortality between and : a systematic analysis world health organization ( ) malaria. fact sheet no. p . world health organization ( ) dengue and severe dengue chagas disease (american trypanosomiasis). fact sheet no vaccines and global health ) ipcc special report summary for policy makers. managing the risks of extreme events and disasters to advance climate change adaptation turn down the heat: climate extremes regional impacts and the case for resilience. a report for the world bank prepared by potsdam institute for climate impact research and climate analytics key: cord- -oatjcmy authors: arata, andrew a. title: old and new pestilences date: journal: understanding the global dimensions of health doi: . / - - - _ sha: doc_id: cord_uid: oatjcmy a. “any fatal epidemic disease, affecting man or beast, and destroying many victims.” the oxford universal dictionary, (rd) edition, , oxford press, pp. b. “a contagious or infectious epidemic disease that is virulent and devastating.” webster’s seventh new collegiate dictionary, . g. & c. merriam co., springfield, mass., pp. accordingly, a pestilence should be an infectious disease, devastating (killing) a large number of people (or animals). there has been much popular interest in, as well as technical concern over, newly emerging diseases, and there is a fear that heretofore unknown virulent pathogens will create new, global epidemics. at the time of this writing, two such pathogens are active, warranting such concern: a) cases of sars (severe acute respiratory syndrome, caused by a coronavirus) appeared in china in november, , and has spread to western and central europe and north america; b) a strain of avian influenza virus (n h ), first identified in hong kong in , reemerged in in southeast asia. other avian flu strains found simultaneously in poultry in north america have underscored the concern of local and international health authorities. both sars and avian flu demonstrate high mortality rates, but, to date, the number of cases has been only in the hundreds. so, are these pestilences? what constitutes a pestilence? is the term synonymous with newly emerging diseases? two definitions of pestilence have near unanimity, but are not very specific: a) "any fatal epidemic disease, affecting man or beast, and destroying many victims." the oxford universal dictionary, rd edition, , oxford press, pp. b) "a contagious or infectious epidemic disease that is virulent and devastating." webster' s seventh new collegiate dictionary, . g. & c. merriam co., springfield, mass., pp. accordingly, a pestilence should be an infectious disease, devastating (killing) a large number of people (or animals). the truly epidemic diseases are usually of viral or bacterial origin (although we will make a case for some other types of pestilences). the classification of that may have been bubonic plague continuing until a.d. ). the "black death" of the fourteenth century, which continued to appear in chronic pockets of europe and the middle and near east for centuries thereafter, is by far the best-known plague, and the one that produced the greatest mortality and social impact on the affected populations. consider that as a conservative estimate, − % of the european population died, and maybe more. this death rate reduced the available work force so that, for the first time, peasants and landless people could sell their labor, which introduced freedom of movement and resulted in economic changes that eventually contributed to the decline of the feudal system. the rd pandemic of plague began in the s and continues to this date, although reduced in more recent years. a major characteristic of this epidemic has been the dissemination of plague from its traditional homes in africa and asia into areas previously plague free, especially north and south america, by the inadvertent transport of rats and their fleas by boat. the infection is now well established in africa (gerbils); central asia (gerbils, ground squirrels or "susliks," and marmots); southeast asia (various rattus species); north america (ground squirrels and some native field mice); and south america (introduced rattus). the last major urban outbreak was in surat, india in : more than , cases and deaths were reported. however, the impact of this outbreak was also seen in the number of people who fled the plague zone, and the over two billion dollar loss that ensued. only a few outbreaks are reported to who each year. indochina and burma frequently report, as well as sites in africa (ovamboland on the frontier between namibia and angola); the united states has a vast infected area in the west of the country, but only - cases per year are reported, with - deaths on average every years. many other sites of infection are known and should be monitored, as some rodent species are highly susceptible to serving as effective amplifying reservoirs, whereas others maintain low-level infections for long periods of time, allowing much time to pass between outbreaks. environmental measures (rat-proofing, rodent and flea control, etc.,) are the first measures of control. surveillance, prompt diagnosis, and treatment with antibiotics (e.g., streptomycin and tetracycline) are recommended. yellow fever is the best known of the arboviral (arthropod-borne virus) diseases. there are some known arboviruses, of which about , produce disease in man. both the yellow fever virus and the primary mosquito vector, aedes aegypt, are of african origin -the species name, 'aegypti,' refers to classical africa in general, not, specifically, modern egypt. most cases in africa occur east to west along the transition zone (ecotone) between the savannas and the rain forests inhabited by numerous aedine vectors as well as a. aegypti. the disease has two cycles: a 'jungle' cycle involving various tree dwelling mosquitoes and nonhuman primates as reservoirs, and an 'urban' cycle, with a. aegypti as the vector and humans as reservoirs. the last reported major african outbreak vectored by a. aegypti occurred in nigeria and involved some , cases and over , deaths between and . yellow fever was introduced into the americas one or more times most likely during the age of sail: the virus can be transmitted vertically (transovarian passage) in a. aegypti. the mosquito' s eggs can easily be laid in water barrels and withstand desiccation for months, only to hatch and develop when submersed at a later date. epidemics of yf raged throughout the caribbean and tropical america until the end of the s, when the transmission cycle was elucidated by the team led by walter reed, confirming the role of a. aegypti which had been proposed by, but not confirmed by, carlos finlay. epidemics occurred as far north as philadelphia in the united states and the last epidemic in north america occurred in new orleans as late as , with over , deaths. cases (with - %) mortality continue to occur sporadically in brazil and in the foothills of several andean countries (bolivia, peru, ecuador, and colombia) . often the victims are young, indigenous males from the highlands who were temporarily working in the coca processing plants in the forests. these infected areas are only kilometers from large cities (with populations of more than million people) such as santa cruz, bolivia, which are accessible by public transportation and are heavily infested with a. aegypti. although the yf vaccine is one of the oldest, safest, and most effective available, and immunological protection is rated for at least years, vaccination coverage in many of the affected areas of africa and south america is low. the cholera pathogen, vibrio cholera, originally described by robert koch, was one of the first human pathogens (along with anthrax and tuberculosis) to be identified, in the late s, shortly after pasteur' s publication of the "germ theory." koch and his students studied material they collected in alexandria, egypt, during an outbreak. it was difficult to determine the origin of cholera and/or to distinguish it historically from other diarrhetic diseases except by the severity and rapidity of onset. health historians such as mcneill suggest an origin on the indian sub-continent, associated with dense populations, poor hygiene, and certain religious practices such as communal bathing; thus the term "asiatic cholera," by which the disease became known in europe in the s. the disease' s appearance in europe and the americas (london and new york in , and again in ) were clearly associated with intercontinental traffic. it was during the epidemic in london that a physician, john snow, noted the clustering of cases and deaths in people using the same water source, and proposed what turned out to be the correct action to stop the epidemic ("take the handle off the broad street pump!!"), although he had no idea of the actual cause of the disease. however, it was such observations, along with structural, hygienic, and administrative changes in major cities, particularly in europe and north america, that established the public health measures that we tend to take for granted in this early part of the st century. cholera is still with us: various serotypes of the vibrio have spread since the early s, affecting over countries in asia, in the americas, and into the west pacific. in , approximately , cases and , deaths from cholera were reported. in , the el tor strain of cholera was reported in lima, peru; by , almost a million cases had been reported in the western hemisphere. measles is one of the oldest known and most widespread infections of man: epidemics ascribed to measles appear in the oldest literature, although they are often confused with smallpox. however, in a.d., ad ahrun, a christian priest living in alexandria, egypt, described the pox lesion, and in a.d. the arab physician al-razi distinguished between the two diseases. prior to widespread immunization, measles was common in childhood-more than % of people were infected by age . although endemic in large communities, measles became epidemic every several years, with the severity of infection decreasing with the frequency of the epidemics. in his study of the history of plagues, mcneill makes mention of the importance of animal husbandry and zoonotic diseases in the area. measles, he claims is probably related to both rinderpest (in hoofed-mammals) and canine distemper. because dogs, sheep, and goats have been domesticated for at least , years, measles may have been among the first viral diseases to have "jumped the species barrier." as we will see, most, if not all, of the new pestilences are, or may be, derived from animal wild or domesticated reservoirs. measles was responsible for (or contributed to, along with smallpox) the decimation of the indigenous amerindian populations, first in central and south america at the time of the spanish conquest ( s), and later ( s and s), in north america. amerindian populations lacked immunological protection from these and other imported infectious diseases. some attribute this immunological naïveté to the comparatively small number of domesticated animal species-dogs, ducks and turkeys, guinea pigs, and cameloids (llamas and relatives) in the andes, and few, if any, in large number prior to the european invasion. in any case, the attack and mortality rates were staggering. by one estimate, a pre-conquest amerindian population of perhaps thirty million by was reduced by %, down to only million. this catastrophe occurred in less than years after the spanish entered the american mainland. influenza is another viral disease that has many unstable varieties infecting a host of mammalian and avian species, both wild (sylvatic) and domestic. epidemics with symptoms similar to modern influenza were noted by hippocrates as early as b.c., and later, in rome, by livy. various medieval and renaissance writings describe influenza-like illnesses. robert johnson of philadelphia is credited with the first "modern" description of an influenza epidemic, which occurred in that city in . his description was applied to subsequent epidemics in , , , - , and . antigenic shifts in the structure of the influenza virus may change the virulence of the strains, increasing the likelihood of epidemics. the most severe flu epidemic ever recorded ( ) ( ) -also known as the spanish flu (although it did not originate there)-first struck world war i troops of all combatant nations while in northern france, and it continued on to become a global pandemic. conservative estimates of mortality range between twenty and forty million persons, and other estimates more than double these figures. the ease with which the various influenza strains infect domestic mammals, pigs, and poultry (chickens and ducks) producing huge reservoirs of potentially infectious material, often proximate to human habitations, is a major public health concern. especially worrisome are the conditions under which millions of such animals are raised and brought to market. the 'old' diseases examined above are only a few of those which might be used as examples of the old pestilences: others might prefer to include schistosomiasis, typhus (murine and/or louse-borne), and several of the classic childhood diseases (diptheria, pertussis, tetanus, rubella), as well as leprosy, yaws, the leishmaniases, and, certainly, smallpox. fortunately many of those mentioned here (schisto and others) are being controlled rather well in some areas by vaccines, specific drugs, and/or antibiotics when applicable, at least in the more developed countries. even polio, which had been a major epidemic threat for centuries, has been virtually eliminated as a threat in areas where the politics and health infrastructure allow the efficient application of this very effective vaccine. much of the fear engendered by specific diseases depends on the time, place, and severity of the local outbreaks, as well as the knowledge and perception of the community. for example, i was raised in new orleans, in the southeast of the united states, during the s. although i and my brothers were normal, well nourished children, our parents were fearful of dogs (rabies), cuts on unshod feet (tetanus), and any summer colds or stiffness/weakness of the extremities (polio), and they preached cleanliness as a means to prevent anything bad happening. these diseases are old, but at present each has developed certain new characteristics that make their modern expression different from their historic ones, and decreases our ability to control them. in the last years, malaria parasites have developed resistance to chloroquine, the most common, globally used anti-malarial drug; at the same time, the anopheline mosquito vectors of malaria have progressively developed a parallel resistance to the insecticides used to control them. dengue, and dengue hemorrhagic fever (dhf), have spread globally, infecting vast new areas, especially urban areas where the human living conditions are substandard, but readily suited for vector breeding. finally, tuberculosis, whose incidence was slowly reduced in the late s and early s by improved public health, housing conditions, and nutrition, has again surfaced as a secondary infection to immuno-compromised persons, especially those suffering from hiv infections. at the same time, the causative agent, mycobacterium tuberculosis, continues to develop resistance to the most economic and readily available antibiotics. malaria is caused by blood parasites of the genus plasmodium and vectored by anopheline mosquitoes. there are four species of human malaria parasites: p. falciparum, p. malariae, p. vivax, and p. ovale, as well as a number of related species infecting other mammals (non-human primates, rodents, etc.). historians note that malaria-like symptoms were discussed in the chinese canon of medicine ( b.c.) and malaria-like illnesses were described in th -century b.c. cuneiform literature from nineveh (now part of iraq). hippocrates made a connection between stagnant water and fevers in the local population. it is estimated that there are still several hundred million unreported cases each year resulting in - million deaths per annum, mostly children. although malaria is still endemic in asia, latin america, and africa, % of the cases are found in africa, where p. falciparum is the most common malaria parasite. such huge figures mask the focal, and sometimes epidemic, nature of malaria, which may be brought about by natural or man-made environmental conditions. some of the human activities that may enhance malaria transmission may be development projects for agriculture (e.g., irrigation schemes), other water and land use projects (as in the amazon basin, converting forest areas through resource extraction such as mining and logging) into marginal livestock and farming areas. often such environmental changes bring about changes in malaria transmission from 'stable' (endemic) to 'unstable' (epidemic). in highly endemic areas, severe malaria and death is concentrated in the younger age groups, whereas in the areas of unstable (epidemic) transmission, severe malaria and death is more evenly distributed throughout all age groups. needless to say, prevention and /or case control strategies must be different for each transmission type. in many parts of the world the anopheline vectors of malaria have developed resistance to the insecticides used for their control. frequently, this is due to the use, often excessive, of the same or similar insecticides for control of agricultural pests in the same geographic areas. such resistance not only hinders control operations directly, but also indirectly, by increasing the need for greater quantities and/or more costly insecticides. broadscale usage of insecticides has also become limited on environmental grounds, because some donors have reduced funding insecticide purchases. by far the most serious setback to malaria control in recent decades has been the emergence and spread of chloroquine-resistant strains of p. falciparum, the causative agent of the most severe form of malaria, and the most common in africa. emerging in the s in southeast asia and south america, resistance spread rapidly from these focal points. it was not noted in africa until - but spread rapidly in the ensuing ten-fifteen years. chloroquine-resistant strains of p. vivax have been identified in some areas of southeast asia, new guinea, and indonesia. efforts to produce a malaria vaccine(s) have been under way for over years. a number of candidate vaccines have been produced, but none are operational in humans as yet. like yellow fever, described earlier, dengue and dengue hemorrhagic fever are vector-borne diseases transmitted (primarily but not exclusively) by the mosquito aedes aegypti. "classical" dengue is caused by infection with one of the four serotypes of the dengue virus. dhf may occur following a subsequent infection with a different serotype. the following quotation is from an article written by the author in (r. lennox and a. arata, dengue fever: an environmental plague for the new millennium. capsule report, environmental health project/usaid. pp.): with . billion people at risk and estimated cases in the tens of milllions, dengue is considered by many to be the second most important vector-borne disease in the world (surpassed only by malaria). classical dengue and its more lethal form, dengue hemorrhagic fever (dhf), now circle the world with endemic illness and continuing threats of epidemics. dengue is very much an environmental disease, affecting urban and periurban settlements in more than countries. it is characterized by seasonal outbreaks of illness carried by mosquitoes that thrive in household containers which collect water (such as flowerpots and washtubs) and in the detritus of human consumption, such as bottles, tin cans, and old bottles. children, specially in asia, are most frequently and seriously affected by the severe form of the infection, dhf. mosquito control is the only effective approach to prevention, although effective case management will reduce mortality. insecticides targeted at larval mosquitoes are effective, but resistance of mosquitoes to affordable and environmentally safe chemicals as well as declining will and infrastructure have all but eliminated this approach in most countries. vaccines are in the pipeline, but a system which could deliver them to half the world' s population is probably at least a decade away. community action-to protect containers from becoming havens for mosquito breeding and to dispose of empty containers and trash, along with surveillance and personal protection-is the best hope for transmission risk reduction. tuberculosis is another ancient disease that has bridged the old to new definition: the tb bacillus, mycobacterium tuberculosis, was among the first to be scientifically identified and described (by robert koch, in ). the disease is transmitted by airborne droplets from people with pulmonary or laryngeal tuberculosis. this mode of transmission is most effective in dense populations, and hence tb became widespread with the development of urban centers in the middle ages (europe), and was very common from the th century until recently in europe. with improvements in housing and nutrition tb rates continued to decline (except for periods of war) until the first half of the th century. at that time, two conditions emerged: the development of multiple drug resistant tb (mdrtb) and the emergence and spread of acquired immune deficiency syndrome (aids) upon which tb is an opportunistic infection. prior to , about % of tb bacilli isolated from patients in the u.s. were resistant to even one antibacterial drug: in , % were resistant to at least one drug, and % were resistant to more than one drug. in the u.s. the cost of treatment of ten cases of mdrtb in texas in was us$ , . who lists tb as one of the major causes of mortality in the world. a new major funding effort (who and world bank and various bilateral donor groups) is focusing on hiv/aids, tb, and malaria as the most serious, and intractable, causes of death. other forms of tb, including non-pulmonary cases and those associated with other species of mycobacterium sp. (e.g. m. bovis), are sporadic, but suggest the possible very early animal origin of the pathogen group. diseases such as chagas disease and schistosomiasis are examples of diseases that do not easily fit the epidemic definitions of a pestilence mentioned earlier in this chapter, but they do heavily impact the affected populations, not only through mortality rates, but especially through morbidity/disability. there are several forms of schistosomiasis caused by different species of schistosoma, a blood fluke (trematode)-this is an ancient illness, known from egyptian antiquity. infections occur in fresh water where people work and/or wash and children play. larval worms, known as cercaria, developed in a snail intermediate host, pass through the skin and penetrate diverse organs according to species. the most important effects are those that arise from chronic, and cumulative, infection. chagas disease has a very different etiology, mode of transmission, and pathology than does schistosomiasis. by definition it could be new because it was first described in by the brazilian carlos chagas, who subsequently described the pathogen, a flagellate protozoan, trypanosoma cruzi, and the vectors, bloodfeeding triatomine bugs. the disease is also know as american trypanosomiasis, and occurs only in the western hemisphere, from mexico to argentina-a few cases have been reported in north america. this form is very different from african trypanosomiasis (sleeping sickness). the initial (acute) phase of the disease usually occurs in children; there is then a long latent phase (∼ years or more), culminating later in life in a chronic phase which may include irreversible cardiac and/or intestinal manifestations and shortened life spans in the victims. paho and who consider chagas disease to be the most serious parasitic disease in latin america and the main cause of heart disease in the region. there is no adequate medical intervention. the infection can be transmitted by vectors, congenitally, or by transfusion of blood or blood products. an estimated million persons in the region are at risk, and in some countries (e.g., bolivia) % of the million inhabitants have been shown to be seropositive. in addition, in bolivia, one study demonstrated that the burden of chagas disease, in terms of disability adjusted life years (dalys), was million dalys, or estimated loss of million bolivianos: equal to more than million us dollars at the time of the report ( ). the purpose of this brief segment is to emphasize that pestilences need not carry with them only high mortality. very high morbidity and sustained disability with all the concurrent social and economic implications can be a tremendous burden on a population-or a nation. puerperal fever, a forgotten pestilence, is caused by a streptococcal infection and is an iatrogenic disease (induced by a physician) that was once the scourge of pregnant women, before physicians learned to wash their hands before examining pregnant women and/or assisting at childbirth. improved hygiene in hospitals was concurrent with the development of the germ theory and mortality rates dropped quickly. this disease, also called childbirth fever, was never reported as one of the great pestilences, however a few figures reveal the state of scientific knowledge regarding any infectious diseases, both endemic and epidemic. it is frightening that not only was the incidence of puerperal fever higher in the hospitals, but so was the associated mortality: % of the patients died if the disease occurred after a home delivery, but - % died if the disease was contracted in a hospital. although we have no crystal ball to predict what, if any, new pestilences are in store for mankind in the future, several groups of zoonotic viruses include likely candidates (table ) . also included is hiv/aids, truly a new pestilence that already, in a relatively brief period, has taken its place among the worst pestilences ever known to man. as mentioned above, there are over arboviruses isolated and characterized-about are capable of infecting humans, from nonapparent infections to very severe ones. two of these have already been mentioned above (dengue and dhf and yellow fever), but the arboviruses as a group represent the source of many potentially new diseases-or, put more correctly, existing zoonotic diseases that emerge when humans accidentally become involved in their cycles. a good example is the recent outbreak of west nile encephilitis in the u.s. in and , the virus was isolated from/around new york city from large numbers of dead birds (especially crows and jays): human cases and two deaths were confirmed. by , the disease moved west toward the mississippi river, infecting people and killing nine. in , there were over , cases ( fatal); by , the virus, and human cases, were found in all contiguous states (excepting alaska and hawaii). the virus has been found in mammals, birds, and mosquitoes throughout the u.s. but is this a new disease, or just a disease new to us? west nile virus has been found in over countries since its discovery in in uganda, and has been most of the above are mosquito-borne, and the major mosquito vector genera, culex, aedes, and anopheles, have global representatives from which a competent vector might be found. the same is true of ticks, sandflies, and other potential vectors. rodents, or other local vertebrates, may serve as reservoir hosts while infected migratory birds may provide distribution of the infection. although many arboviral infections have broadly similar transmission cycles, the ecology and dynamics of each may differ widely. arboviruses do not belong to a single viral family, but rather, to several,which increases their diversification. although the potential for increased arboviral epizootics or epidemics is high, the most recent episodes have not been high on the pestilence scale; rather, the most severe arboviral epidemics have been yf and dengue/dhf, the oldest of the group. the arenaviruses were thought for years to be monotypic, a single species, lymphocytic choriomeningitis (lcm), occurring primarily in the house mouse/ laboratory mouse, mus musculus. the virus (first described in ) has been isolated in numerous locations, but human disease is known only from europe and the americas. a second arenavirus was isolated from a phyllostomatid (fruit-eating) bat from trinidad, but there was no associated human disease. severe hemorrhagic cases in argentina and later in bolivia in the s and s resulted in the discovery of new viruses and diseases in these countries-junin virus/argentine hemorrhagic fever (ahf) and machupo virus/bolivian hemorrhagic fever (bhf). more recently, additional arenaviruses found in brazil (sabia virus) and venezuela (guanarito virus) produce similar hemorrhagic symptoms. ahf is the most common, - , recorded annually between and -the others are only sporadic, but mortality rates are high in all these diseases. in each of these, transmission is by contact with infected rodent excreta, dust, and other substances associated with grain harvesting and storage. there are another five arenaviruses in the americas that are not known to cause any illness in humans or their rodent hosts. all of the rodents associated with these viruses belong to only one of the rodent families currently inhabiting south america. these rodent genera (calomys, sigmodon, oryzomys, et al) , are very closely related, and share a common ancestry. paleontological evidence indicates that the isthmus of panama was a bridge connecting north and south america more than - million years ago, allowing a faunal interchange. the sigmodont rodent progenitors entered south america at that time, and rapidly evolved into the modern genera and species. presumably the "ancestor virus" tagged along, co-evolving into the situation that now exists. by far the most important arenaviral disease is lassa fever: discovered in nigeria in , it is known from african countries, mostly in west and central africa, but also zimbabwe and mozambique. the natural host of lassa virus is the multi-mammate rat, mastomys natalensis, one of the most common and widely distributed african field rats. like their south american counterparts, the ahf and bhf hosts, mastomys, is basically a grassland species, easily adapting to the man-made grasslands of maize, sorghum, millet, sugarcane, and other cultivated grasses. cases of lassa are generally associated with agricultural activities and food storage: transmission is by contact with excreta of infected rodents. without laboratory facilities for confirmation, it is difficult to distinguish lassa fever from ebola, yf, or even severe cases of malaria. there are an estimated , cases a year, with more than % mortality rate in hospitalized cases. the disease is more severe in pregnancy, with fetal mortality reported at more than %. in the early s (and before ebola outbreaks occurred), lassa caused great consternation in europe and the americas over the possibility of introduction of this disease. these concerns still exist and have been heightened after the appearance of these other groups of viral hemorrhagic diseases. the hantaviruses are comprised of two large groups of viruses, all transmitted by rodents and producing a range of hemorrhagic, renal, and/or pulmonary complications. the old world hantaviruses are comprised of over different viruses, several known for some time under a different classification (e.g., hanta virus is the cause of korean hemorrhagic fever with renal syndrome, an important military disease in the s). most cases still occur in agrarian and military populations and occur in over countries in asia, africa, and europe: each year approximately , cases occcur in eurasia, with more than % of these reported in china. case fatalities range from . % to . % depending on the virus. the or so new world hantaviruses produce a pulmonary, rather than a renal, syndrome. since being described as a group in , approximately , cases have been reported in the americas, with a high case fatality rate ( - %). the natural hosts/reservoirs for the hantavirus groups are mostly muroid rodents (old world group), and cricetid rodents (new world group). this is not surprising, as these two are amongst the largest and most widely distributed mammalian families. however, the manner and zones of transmission are similarrodent contamination of grain crops in the field and storage where people come in contact with rodent excreta. the two closely related filoviruses (marburg and ebola) are among the most virulent viruses yet described with an overall fatality rate of more than %, and higher in several outbreaks (possibly augmented by use of dirty syringes and needles to give injectable chloroquine (an anti-malarial drug) to the patient' s friends who carried him/her to the hospital. marburg virus was first described ( ) among monkeys sent from east africa to european laboratories, there killing laboratory technicians. subsequent outbreaks have occurred in africa. ebola virus appeared in in simultaneous outbreaks in zaire (democratic republic of congo). (barry, ) one ebola strain was implicated in an outbreak in an animal holding facility in reston, virginia, u.s.a. several humans seroconverted but showed no disease symptoms. the repeated outbreaks of ebola and marburg virus, mostly in central africa, have been described as commencing with "rapidity and devastation." during an epidemic, transmission is generally by contact with contaminated blood or other tissues from infected persons. most outbreaks have been in rather remote areas with poor health care facilities, so that patients are seen only with advanced symptoms. we have not been able to find reservoir organisms (there have been subsequent, better equipped expeditions than the one described in the footnote, but none have been successful), nor do we know the mechanism(s) of transmission in the wild. one distinct ebola virus strain from ivory coast was isolated from a chimpanzee: primates are hunted and eaten by humans in parts of africa and this may serve as the 'link' at which the virus(es) are able to "cross the species barrier" and enter the human population. (barry, ) the government of sudan requested who assistance, and the government of zaire requested the same from the u.s. government (cdc). representatives of who and cdc met in the next few days at the london school of hygiene and tropical medicine to work out details and coordination (who was represented by dr. paul bres and the author, and cdc by dr. karl johnson). we had all thought of lassa and marburg viral fevers, and were surprised when dr. johnson said it was neither: he then showed us electron photomicrographs of tissue taken from an early case-the stringlike " and " figures were just like marburg. but, he explained, this one was serologically distinct from marburg, and they proposed to name it after a river in the area, the 'ebola'. we agreed that i (aaa) and a virologist (dr. bruce johnson) from the lshtm would go to the site in sudan to sample potential reservoirs and/or vectors. bruce would bring the supplies needed for taking tissue samples and the liquid nitrogen containers needed to return the samples to the uk. i was to gather the animal collecting materials. who had no such equipment in geneva, of course, so i borrowed 'mist' nets for collecting bats from the british musum (natural history) and the museé d' histoire naturelle in geneva and borrowed sample rodent traps from the swiss agricultural research station in nyon, near geneva. we had the traps made in nzara, one of the sites of the outbreak in sudan. to autoclave the dissecting instruments we purchased two household 'pressure cookers' at the local super market (migros) in geneva. placed on stones over an open fire, they served well. an experimental ebola vaccine has been reported to be successful in trials with non-human primates. human trials will be conducted soon. two previously unknown and unrelated human viral infections, severe acute respiratory syndrome (sars) and an asian avian influenza (strain h n ), originating in southeast asia, have received a great deal of popular attention and public health concern. in november , cases of a respiratory illness, subsequently labeled sars, appeared in china. a delay in timely reporting of the initial cases allowed it to spread to other southeast asian countries, australia, the americas, and at least european countries. reports of the actual number of persons infected varied, but cases numbered in the thousands, and mortality rates of up to % were indicated. surveys of wild animals captured for human consumption quickly showed that ferrets, civets (related to mongooses), and raccoon dogs (shaggy fox-like carnivores) were positive for harboring the virus, but it is not known if any of these are the true reservoir in nature. the who has reported that the chain of transmission may have been broken (no new cases reported in a period of time equal to two consecutive day incubation periods). this is clearly a case of a virus "species jumping". in the world' s largest, most densely populated country this could spell disaster, especially if the reporting network is compromised. the asian avian influenza strain initially appeared in poultry in hong kong in , when it jumped the species barrier and killed out of infected persons. this recent outbreak spread to korea (december, ) , then japan and vietnam (january ). hong kong reportedly slaughtered . million chickens and ducks, and as many as three million slaughtered through the southeast asia region, but other reports indicate that there are nonspecific wild variants of this strain in wild birds that serve as natural reservoirs. of major concern is that outbreaks of highly pathogenic avian influenza are increasing in frequency and severity. reportedly, in the years from to , there were only outbreaks, but in the past six years, from to , there have been six, not including the most recent incidents. if bubonic plague was the quintessential pestilence of the ancient and medieval worlds, acquired immunodeficiency syndrome, caused by the human immunodeficiency virus (aids/hiv) is the chief pestilence of the modern world; and it is still growing, not receding. there is also a vast literature that will not be reviewed here, but the following data points describe the severity of the pandemic pestilence: r aids is gaining a firmer foothold in the large populations of india and china; r world wide, million people are infected with hiv; r - million of these infected people live in sub-saharan africa; r million persons became infected this year, , are children; r million persons died of aids this year, , of them less than years old; r existence of simian immunodeficiency virus (siv) suggests animal origin. the social damage accompanying this pandemic is not reflected in the bare figures given above; especially the orphaned children, destroyed family structures, and so forth. it has been estimated that billion dollars us, per annum, is required to provide the prevention and treatment facilities and services needed: to date, less than one-half ($ . billion per annum) has been made available. some of the old category diseases are still strongly with us (e.g., malaria, tb, influenza), and, by adapting traits such as drug-resistance and crossing or jumping species, they expand their reservoir-host base. as such, they could be considered new. some other old diseases are rather well controlled in the developed countries where the surveillance systems are efficient and vaccination and other preventive services are readily available and properly used. these would include smallpox (eradicated), polio (eradicated in some areas), and childhood illnesses such as pertussis, diptheria, tetanus, measles, and so on. even bubonic plague could be characterized as being under control-it is widespread, but also well understood, and with vector control and appropriate antibiotics, outbreaks are not severe and mortality is low. on the other hand, some of the new (most recently discovered) diseases like ebola and hiv/aids are hard to handle. we know little about the natural history of ebola, lassa, or the south american hemorrhagic fevers, and our knowledge of hiv/aids in the laboratory probably exceeds our understanding of the socioeconomic impacts it is having on whole cultures. when lassa virus "jumped" from the field rat, mastomys, to humans it was dreadfully virulent, and it seemed to come from nowhere. but, after a few years, we know that (with one exception from a bat) all arenaviruses are well adapted to particular rodent groups; most rodents are grass eaters, and lots of crops are grasses (wheat, maize, sugarcane, rice, etc.); therefore, the arenaviral fevers are seen primarily in agricultural settings and with stored grain. yet, for the more recently known hantavirus group, or even less with the multiferous arboviruses, we do not have good data on ecological determinents, or even host-reservoir relationships. at the same time, people are modifying environmental conditions rapidly and extensively, and we have little information indicating whether such changes will eliminate potential disease cycles or exacerbate them. this may be even more important for diseases like influenza. if they have obligate or opportunistic vertebrate hosts and these are coincidentily reduced in number or eliminated, what selection pressures are set in action on the virus population to select new hosts? and when it comes to modifying environments, man has no equal. yet we know that this microbial evolution is going on at a rapid pace-just look at how fast drug-resistance develops and spreads! in reading articles and researching references for this document, i was amazed to discover again how many human illnesses have their direct animal (zoonotic) counterparts, or were vectored/hosted by arthropods, rodents, or snails, and how an avian influenza can become a mammalian influenza very quickly, and how a bat or an oppossum can do the same for the chagas disease trypanosome. it is in this context that i feel that we know very little of the natural history or the ecological dynamics of the disease transmission cycles we teach. especially disturbing is to read of a new strain of asian avian influenza and the necessity, around the world, to kill millions of birds. if one was to dream up a model pathogen incubator and dissemination engine, the perfect model would be a modern chicken farm of , birds, defecating as birds do, and that at a constant temperature and with residues of organic chicken feed all about. and we wonder why new diseases emerge? any farmer worth his/her salt knows that monoculture breeds pests. this is a good place to bring up one other difficult subject-bioterrorism. it is difficult for one dedicated to public health principles to imagine why anyone would even consider using infectious diseases as a weapon, but it is being done, and we need to be able to distinguish between a natural epidemic and one orchestrated by man. again, knowledge of the natural history of the organisms, their natural hosts and reservoirs, will help. already the u.s.a. is stockpiling smallpox and anthrax vaccines in large quantities. one final point; most people concerned with new versus old pestilences work as epidemiologists, infectious disease specialists, hospital officials, and so forth. but public health work is broader than the study and treatment of infectious diseases, and the study the global burden of disease, sponsored by the who, world bank, and harvard university, based on measuring dalys, predicts that fewer infectious disease will be as important in the future as they are at present. for example, "the next two decades will see dramatic changes in the health needs of the world' s populations, and non-communicable diseases such as depression and heart disease . . . are replacing the traditional enemies, such as infectious diseases and malnutrition." maybe toxic smog and non-communicable diseases will replace pestilences, both old and new! the great influenza control of communicable diseases manual exotic viral diseases death by migration plague: an ancient disease in the twentieth century (rev emerging infections plagues and people the global burden of disease the doctor's plague viruses, plagues, and history emerging infectious diseases (vol. - ). www.cdc.gov/eid or hard copy from cdc key: cord- -jf xl vl authors: le duc, james w.; nathanson, neal title: emerging viral diseases: why we need to worry about bats, camels, and airplanes date: - - journal: viral pathogenesis doi: . /b - - - - . - sha: doc_id: cord_uid: jf xl vl the emergence of a new viral disease is one of the most dramatic aspects of virology, which often receives widespread attention from the scientific community and the lay public. considering that the discipline of animal virology was established over years ago, it may seem surprising that new virus diseases are still being discovered. how this happens is the subject of this chapter. one of the most dramatic aspects of virology is the emergence of new virus diseases, which often receives widespread attention from the scientific community and the lay public. considering that the discipline of animal virology was established over years ago, it may seem surprising that new virus diseases are still being discovered. how this happens is the subject of this chapter. there are many recent books and reviews (see further reading) that list the plethora of determinants that can lead to the emergence of infectious diseases (table ) . in this chapter, we concentrate on those determinants that relate to viral pathogenesis and deal only briefly with the many societal and environmental factors that can be instrumental in disease emergence. in some instances, the "emergence" of a viral disease represents the first identification of the cause of a well-recognized disease. an example is la crosse virus, a mosquitotransmitted bunyavirus that was first isolated from a fatal case of encephalitis in . the isolation of the causal agent and the development of serological tests made it possible to distinguish la crosse encephalitis from the rubric of "arbovirus encephalitis, etiology unknown." since that time, about cases have been reported annually, without any significant increase since the s. it appears that the emergence of this "new" disease reflected only the newfound ability to identify this etiologic entity, rather than any true change in its occurrence. hantavirus pulmonary syndrome is another example of the "emergence" of an existing but previously unrecognized disease. in , in the four corners area of the southwestern united states, there occurred a small outbreak of cases of acute pulmonary illness with a high mortality. epidemiologic and laboratory investigation rapidly identified the causal agent, a previously unknown hantavirus, now named sin nombre virus (snv). snv is an indigenous virus of deer mice (peromyscus maniculatus) that are persistently infected and excrete the virus. apparently deer mice produce virus-infected excreta and, when they infest human dwellings, aerosolized fomites can result in occasional human infections. the outbreak is thought to reflect a transient rise in deer mouse populations associated with an unusual crop of pine nuts, a major food source for these rodents. the recognition of snv soon led to the discovery of other heretofore unrecognized hantaviruses in north, central and south america, many of which also cause serious human disease. on occasion, a virus that is already widespread in a population can emerge as a cause of epidemic or endemic disease, due to an increase in the ratio of cases to infections. such an increase can be caused by either an increase in host susceptibility or enhancement of the virulence of the virus. although counterintuitive, there are some dramatic instances of such phenomena. increase in host susceptibility. poliomyelitis first appeared as a cause of summer outbreaks of acute infantile paralysis in sweden and the united states late in the nineteenth century (figure ). isolated cases of infantile paralysis had been recorded in prior centuries, and an eygptian tomb painting indicates that poliomyelitis probably occurred in early recorded history. why then did poliomyelitis emerge abruptly as an epidemic disease? when personal hygiene and public health were primitive, poliovirus circulated as a readily transmitted enterovirus, and most infants were infected while they still carried maternal antibodies (up to - months of age). under these circumstances, the virus produced immunizing infections of the enteric tract, but passively acquired circulating antibodies prevented invasion of the spinal cord. with the improvement of personal hygiene in the late-nineteenth century, infections were delayed until - years of age, after the waning of maternal antibodies. infections now occurred in susceptible children, resulting in outbreaks of infantile paralysis. this reconstruction is supported by seroepidemiological studies conducted in north africa in the s, when epidemic poliomyelitis first emerged in this region. increase in viral virulence. viruses may undergo sudden increases in virulence resulting in emergence of dramatic outbreaks. an outbreak of lethal avian influenza in pennsylvania in is one documented example. in eastern pennsylvania, avian influenza appeared in chicken farms early in , but the virus was relatively innocuous and most infections were mild. however, in the fall of that year a fatal influenza pandemic spread rapidly through the same farms. when viruses from the spring and fall were compared, it appeared that both isolates had almost identical genomes. the fall virus had acquired a single point mutation in the viral hemagglutinin that facilitated the cleavage of the hemagglutinin. the virus could now replicate outside the respiratory tract, markedly increasing its virulence (discussed in chapter , patterns of infection). this point mutation led to the emergence of an overwhelming epizootic, which was only controlled by a widespread slaughter program involving millions of birds. similar outbreaks of avian influenza have occurred subsequently in other countries. a virus that is endemic in a population may "fade out" and disappear, because the number of susceptibles has fallen below the critical level required for perpetuation in that population. if the population is somewhat isolated, the virus may remain absent for many years. during this interval, there will be an accumulation of birth cohorts of children who are susceptible. if the virus is then reintroduced, it can "reemerge" as an acute outbreak. in the years - , iceland had a population of about , , which was too small to maintain measles virus, and measles periodically disappeared. when travelers to iceland reintroduced the virus, measles reemerged in epidemic proportions. on occasion, a virus can enter and spread in a region where it had never previously circulated, leading to the emergence of a disease new to that locale. a dramatic example is afforded by the emergence of west nile virus (wnv) in the united states, beginning in ( figure ). wnv, like most arboviruses, is usually confined to a finite geographic area, based on the range of its vertebrate reservoir hosts and permissive vectors. in an unusual event, wnv was imported into new york city, probably by the introduction of infected vector mosquitoes that were inadvertent passengers on a flight from the middle east, where the virus is enzootic. this hypothesis was supported by the finding that the genomic sequence of the new york isolates was closely related to the sequence of contemporary isolates from israel. some american mosquito species were competent vectors for wnv, and certain avian species such as american crows were highly susceptible. as a result, west nile encephalitis emerged as a significant disease new to the united states. over a period of several years wnv spread across the continent, finally reaching the west coast and many areas in latin america. chikungunya virus (chikv), another mosquito-borne arbovirus, has been endemic for many years in regions of africa and asia where it periodically caused outbreaks of a febrile illness associated with severe arthritis and arthralgia. in - , chikv caused a large epidemic on the island of reunion in the indian ocean, apparently associated with a mutation that allowed the virus to be more efficiently transmitted by vector mosquitoes. chikungunya subsequently spread to india and elsewhere in asia, followed by the americas. as of november , transmission of chikv had been documented in countries or territories in the caribbean, central, south and north america, resulting in nearly one million suspected cases each year. it appears that chikv may become established in the new world, where virtually the entire human population currently lacks immunity. zoonotic infections of animals that can be transmitted to humans are a major cause of emerging virus diseases of humans. these viruses are transmitted by direct contact, by virus-laden droplets or aerosols, or by insect vectors. all zoonotic viruses have one or more animal reservoir hosts, which play an important role in the epidemiological dynamics of human infections. although many zoonotic viruses can be transmitted to humans on occasion, their relative ability to spread from human to human determines whether or not they emerge as significant new virus diseases of mankind (table ). most zoonotic viruses that are transmitted to humans cannot be spread directly from person to person, so humans are considered to be "dead-end hosts." one familiar example is rabies, which is enzootic in several animal hosts, such as dogs, skunks, foxes, raccoons, and bats. humans are infected by bite of a rabid animal or by aerosol exposure (in caves with roosting bats). several zoonotic arenaviruses, such as lassa, machupo (bolivian hemorrhagic fever), and junin (argentine hemorrhagic fever) viruses, are likely transmitted from the reservoir host (wild rodents) by inhalation of contaminated aerosols. there are more than viruses-belonging to several virus families-that are also classified as arboviruses (arthropod-borne viruses), based on a vertebrate-arthropod maintenance cycle in nature. arboviruses replicate in both the vertebrate host and the arthropod vector (mosquitoes, ticks, sandflies, and others), and transmission occurs when the vector takes a blood meal. typically, arboviruses have only a few vertebrate hosts and are transmitted by a narrow range of arthropods. humans are not the reservoir vertebrate hosts of most arboviruses, but can be infected by many of these viruses, if they happen to be bitten by an infected vector. in most instances, arbovirus-infected humans are dead-end hosts for several reasons. many arthropod vectors competent to transmit a zoonotic arbovirus prefer nonhuman hosts as a blood source, reducing the likelihood of transmission from human to vector. also, infected humans are usually not sufficiently permissive to experience a high titer viremia, so they cannot serve as effective links in the transmission cycle. there are only a few exceptions: in urban settings, dengue, urban yellow fever, oropouche, and chikungunya viruses can be maintained by an arthropod vector-human cycle. as table shows, a few zoonotic viruses can be transmitted directly from human to human, at least for a few passages, and can emerge as the cause of outbreaks involving a few to several hundred cases. since many viruses in this group cause a high mortality in humans, even a small outbreak constitutes a public health emergency. these viruses belong to many different virus families, and there is no obvious biological clue why they should be able to spread from human to human, in contrast to other closely related viruses. typically, infections are mainly limited to caregivers or family members who have intimate contact with patients, often in a hospital setting. however, transmission is marginal, so that most outbreaks end after fewer than - serial transmissions, either spontaneously or due to infection-control practices. in the history of modern virology (the last years) there are very few documented instances where zoonotic viruses have established themselves in the human population and emerged as new viral diseases of mankind (table ). most viruses have evolved to optimize their ability to be perpetuated within one or a few host species, and this creates what is sometimes called the "species barrier." in most instances, a virus must undergo some adaptive mutations to become established in a new species. sars coronavirus. in november, , an outbreak of severe acute respiratory disease (sars) began in guangdong province, in southeast china near the hong kong border. in retrospect, the first cases were concentrated in food handlers, who then spread the virus to the general population in that region. although not recognized immediately as a new disease, the outbreak continued to spread both locally and in other parts of china. in february, , a physician who had been treating likely sars patients, traveled to hong kong, where he transmitted sars to a large number of contacts in a hotel. these persons, in turn, spread the infection to singapore, taiwan, vietnam, and canada, initiating a global pandemic that eventually involved almost countries. from patient samples, several research groups isolated a novel coronavirus, which has been named the sars coronavirus (sars cov). clearly, this virus is new to the human population, and there is circumstantial evidence that it was contracted from exotic food animals that are raised for sale in restaurants in guangdong province. recent studies suggest that horseshoe bats (genus rhinolophus) may be the reservoir hosts and palm civets, consumed as food in china, may be the intermediary hosts for sars cov. sars cov went through a large number of human passages (perhaps ) before being contained by primary control measures, such as respiratory precautions, isolation, and quarantine. the virus has been eliminated from the human population, but the outbreak showed that it could be maintained by human-to-human transmission. from that perspective, it is potentially capable of becoming an indigenous virus of humans. since many coronaviruses infect the respiratory system and are transmitted by the respiratory route, the sars virus did not have to undergo any change in its pathogenesis. however, the virus did have to replicate efficiently in cells of the human respiratory tract and it is unknown whether this required some adaptive mutations from the virus that is enzootic in its reservoir hosts. middle eastern respiratory syndrome. mers is an acute respiratory disease of humans that was first recognized in , when a novel coronavirus (mers-cov) was isolated from two fatal human cases in saudi arabia and qatar. since that time, more than clinical cases of mers have been recognized, the great majority in saudi arabia but also in most of the other countries in the arabian peninsula and beyond ( figure ). hospitalized cases of mers are characterized by an acute respiratory disease syndrome (ards) with a fatality rate over %. however, evolving evidence suggests that there may be many additional human infections with little or no associated illness. what is the origin of this new disease? based on fragmentary data now available, it appears that mers-cov is likely to be an enzootic virus of one or more species of bats. camels are probably an intermediary host, and humans in close contact with camels can acquire infection. also, mers-cov can spread from human to human, particularly to caretakers or others in close contact with acutely ill patients. however, there are many unknowns in this speculative reconstruction: how do camels become infected? are camels the main source of human infections? what has caused this disease to emerge in , or had it preexisted but was just recognized at that time? is this an evolving outbreak, and if so, what is driving it? several relevant facts have been ascertained from basic studies. mers-cov replicates well in cell cultures obtained from many species, including bats and humans. the pantropic nature of this virus is explained in part by its cellular receptor, dipeptidyl peptidase (dppt ), a widely distributed cell surface molecule. this would facilitate the transmission of this zoonotic infection from bats to camels to humans. of interest, mers-cov infects type ii alveolar pneumocytes while sars cov uses a different cell receptor (angiotensin-converting enzyme , ace ) and infects type i alveolar pneumocytes. however, both viruses appear to cause a similar ards. type a influenza virus. genetic evidence strongly implicates avian and porcine type a influenza viruses as the source of some past pandemics of human influenza. it appears that new epidemic strains are often derived as reassortants between the hemagglutinin (and the neuraminidase in some cases) of avian influenza viruses with other genes of existing human influenza viruses. the new surface proteins provide a novel antigenic signature to which many humans are immunologically naïve. the human influenza virus genes contribute to the ability of the reassortant virus to replicate efficiently in human cells. it is thought that reassortment may take place in pigs that are dually infected with avian and human viruses. currently, there is concern that a new pandemic strain of type a influenza could emerge as a derivative of highly virulent avian h n or h n influenza viruses now causing epidemics in domestic chickens in southeast asia. there have been several hundred documented human infections with each of these avian viruses in recent years-mainly among poultry workers-with significant mortality. however, few if any of these infections have spread from human to human, perhaps because the infecting avian virus has not undergone reassortment with a human influenza virus. a critical determinant is that avian influenza viruses preferentially attach to α - sialic acid receptors while human viruses attach to α - sialic acid receptors. the pandemic of influenza is presumed to be an example of a zoonotic influenza virus that crossed the species barrier and became established in humans where it caused an excess mortality estimated at - million persons. recent viral molecular archaeology has recovered the sequences of the h n influenza virus from the tissues of patients who died during the epidemic. all of the genes of the reconstructed virus are avian in origin, but it is unknown whether the virus underwent mutations that enhanced its ability to be transmitted within the human population. the reconstructed hemagglutinin of the virus has been inserted into recombinant influenza viruses, and-in mice-markedly increases the virulence of primary human isolates of influenza virus (table ) , but the full virulence phenotype appears to require many of the avian influenza genes. several physiological factors play a role in disease enhancement, including increased replication in pulmonary tissues and an enhanced ability to stimulate macrophages to secrete pro-inflammatory cytokines which, in turn, cause severe pneumonitis. human immunodeficiency virus. hiv has emerged as the greatest pandemic in the recent history of medical science. modern methods have made it possible to reconstruct its history in great detail (see chapter , hiv/aids). a provisional reconstruction of the sequence of events is summarized in figure . the emergence of hiv may be divided into two phases: what was the zoonotic source of hiv and when did it cross into humans? and when did hiv spread from the first human cases to become a global plague? there have been several transmissions of simian immunodeficiency virus (siv) to humans (sharp and hahn, ) , and this account will focus on hiv- which appears to have been transmitted to humans in at least four separate instances, identified by individual hiv- lineages called groups (m, n, o, p). of these, the most important was the m group of hiv- , which has been responsible for the vast majority of human infections. furthermore, hiv- is most closely related to sivcpz, the siv strain infecting two subpopulations of chimpanzees. different segments of the sivcpz genome, in turn, are closely related to genome segments of two sivs of african monkeys, red-capped monkeys and cercopithecus monkeys. it is hypothesized that chimpanzees, which regularly kill and eat monkeys, were infected during consumption of their prey; and that a recombination event produced sivcpz, which was derived from parts of the genomes of the two acquired monkey viruses. it is speculated that a further transmission from chimpanzees may have occurred during the butchering of nonhuman primates, which occurs in rural africa ( figure ) . amazingly, genomic similarities tentatively map the substrain of sivcpz that is the ancestor of the m group of hiv- , to chimpanzees in the southeastern corner of cameroon, a small country in west africa. using a sequence analysis to compare diversity within current isolates, the common parent of the m group can be reconstructed. a molecular clock, derived from dated isolates, indicates that this virus was transmitted to humans during the period - . the period from to is a mystery (pepin, ) , but there are fragmentary data suggesting that the virus persisted as a rare and unrecognized infection in residents of jungle villages in west africa during this time. it has also been proposed that the reuse of unsterilized needles-a frequent practice during the period of colonial rule-could have inadvertently helped to spread the virus. starting about , the virus began to spread more rapidly. it appears that accelerated spread began in the region centered on kinshasa (previously leopoldville) in the democratic republic of the congo (previously the belgian congo, then zaire) and brazzaville, just across the congo river in congo. transmission was exacerbated by the chaos in postcolonial zaire. during the period - , hiv infection spread widely in africa as shown in figure . in the countries worst affected, the prevalence of infection among adults aged - years reached levels higher than %. the rapid spread was driven by many factors among which were: ( ) a high frequency of concurrent sexual contacts in some segments of the population and the hidden nature of sexual networks; ( ) the long asymptomatic incubation period during which infected individuals able to transmit the virus were sexually active; ( ) the spread along commercial routes of travel within africa; ( ) the failure of health systems to concomitantly with the spread of hiv in africa, the m group of hiv- evolved into nine different subtypes (a-d, f-h, j, k), based on sequence diversity. during the spread within africa, there were population bottlenecks that resulted in the predominance of different m group subtypes in different regions. subtype c is most frequent in southern africa, and subtypes a and d are most frequent in eastern africa. during the s, hiv also spread globally, although prevalence rates did not reach the levels seen in some african countries. subtype b is dominant in the western hemisphere and europe, while subtype c is most frequent in india and some other asian countries. this implies that each of these regional epidemics was initiated speculative reconstruction of events following the transmission of sivcpz to humans. this reconstruction is based on data in hahn ( ), pepin ( ) . bushmeat is part of the diet in rural africa. photograph courtesy of billy karesh ( ). by a small number of founder strains of hiv- , improbable though that may seem. thirty years after its appearance as a global disease, almost million persons have died, and there are more than million people living with hiv/aids. although the global incidence of hiv has fallen slightly since , there are still more than two million new infections each year ( ). ebola hemorrhagic fever. the ebola pandemic of - is the most recent emerging virus disease that has riveted the attention of the world. where did it come from? why did it cause a pandemic? why did the international health community fail to control it? where will it end? these questions are discussed below. ebola is a filovirus indigenous to africa that is maintained in one or more reservoir species of wild animals, among which bats are a likely host. the transmission cycle is not well documented but it is thought that humans get infected, either by direct contact with bats, or while slaughtering infected wild animals who may act as intermediate hosts. human-to-human spread can then occur. the pathogenesis of ebola virus infection may be briefly summarized. presumably ebola enters the human host via the mucous membranes or cuts in the skin. the virus infects mononuclear cells including macrophages and dendritic cells and traffics to lymph nodes, whence it spreads to target organs including the liver, spleen, and adrenal glands. it causes a high titer viremia and a dysregulation of the innate immune system. clinically, ebola patients undergo severe vomiting and diarrhea with massive fluid losses and become very dehydrated, with a mortality that varies from % to %. in fatal cases, the infection of the liver leads to disseminated intravascular coagulopathy, a shock syndrome, and multiorgan failure, although the sequential details are not well understood. infection is transmitted between humans by contact with bodily fluids of patients, but not by aerosols. therefore, the virus is spread most frequently to caregivers or others who are in intimate contact with patients and their fomites. rituals associated with funerals and burial practices often serve to transmit the virus. ebola virus was first isolated in in an outbreak near the ebola river in the democratic republic of the congo (then called zaire) and almost concurrently in a second outbreak in southern sudan. viruses recovered from these two outbreaks were subsequently shown to be different and are now known as ebola-zaire and ebola-sudan. since that time there have been more than individual outbreaks of ebola disease, mainly in central africa. past outbreaks have been controlled by use of protective garments by caregivers and quarantine of infected or potentially infected contacts. these controlled outbreaks have been limited to no more than ∼ serial human-to-human transmissions, and mainly ranged from about to cases. in december, , an ebola-zaire outbreak began in guinea, west africa. it appears that the initial case was in an infant who may have been infected by contact with bats. the outbreak then spread to two contiguous countries, liberia and sierra leone. by the fall, , the epidemic had become a catastrophe, and was raging out of control in several parts of these three countries. although the data are incomplete, it is estimated that there have been at least , cases (with at least % mortality) through february, (figure ) . the infection has spread to nigeria, senegal, mali, the united states, and a few european countries, but these invasions have so far been controlled, with limited secondary cases. a global effort to control this pandemic was initiated, with participation from doctors without borders, the red cross, other nongovernment organizations, the world health organization, and the u.s. centers for disease control and prevention. as of march, , it appeared that the epidemic was coming under control. aggressive border screening, both on exit from the affected countries and on arrival at destinations, has limited spread by air travelers, but the porous land borders remain areas of concern. from an epidemiological viewpoint, why did this outbreak of ebola explode into a massive pandemic, in contrast to the many prior outbreaks that were limited to no more than a few hundred cases at most? the outbreak began in guinea and was mainly confined to that country for about months before it spread to neighboring liberia and sierra leone (figure ). during this first months, incidence in guinea varied from a few to about cases a week, and cases were concentrated in rural areas. from a public health viewpoint, this represented a missed opportunity to contain the outbreak. contributing to this omission were a combination of factors: a weak health system fragmented by social disruption, a failure of local health authorities to recognize or respond to the outbreak, the failure of international health organizations such as who to take aggressive action, and local societal norms that brought family and friends into close contact with ebola victims, during their illness and at their funerals (washington post, october , ; cohen, ) . once ebola infections spread from rural villages to urban centers, the outbreak exploded. beginning in the fall of , it was recognized that the pandemic was a global threat. in response, a number of countries and international organizations provided resources to africa, including building facilities, sending equipment, and recruiting personnel to work in the pandemic areas. a major effort was made to get the local population to temporarily change some of their normal social responses to illness and death, to reduce the spread within the population. combined with the efforts of the affected countries, these initiatives started to take hold about january, . however, as of march, , the epidemic was not yet terminated. in retrospect, the international community has acknowledged that it lacks a contingency plan to respond to global outbreaks wherever they may occur. futhermore, because ebola was a "neglected" disease, the tools to combat it had not been developed. the ebola pandemic has spurred crash programs to develop a rapid diagnostic test, drugs and antibodies for treatment, and a vaccine for prevention (product, ; mire et al., ) . canine parvovirus. cpv is another example of a disease that emerged due to the appearance of a virus new to its host species. in the late s, a highly lethal pandemic disease appeared in the dog populations of the world. the etiologic agent was a parvovirus previously unknown in canines. the sequence of cpv is almost identical to that of feline panleukopenia virus (fpv), an established parvovirus of cats, which causes acutely fatal disease in kittens. cpv has a few point mutations that distinguish it from fpv, and these mutations permit cpv to bind to and infect canine cells, a property not possessed by fpv. it is presumed that these mutations permitted the emergence of a new virus disease of dogs. many mammalian viruses have evolved with their hosts so that different members of a virus family are associated with each host species. furthermore, under natural circumstances, each member of the virus family usually "respects" the species barrier and does not cross into other species, although it spreads readily between individual animals within its host species. diverse mechanisms contribute to the species barrier, including host defenses and viral genes. for a zoonotic virus to establish itself in humans or another new species, it is probable that mutations are needed for full adaptation. this requirement is likely part of the explanation for the rarity of such events. one of the best-studied examples is the transmission of sivcpz, a virus of chimpanzees, to hiv, a human virus. several recent studies have shown that apobec and tetherin are two very important gate keepers for transmission of lentiviruses between different primate species (reviewed in sharp and hahn, ) . apobec proteins represent a powerful first line of defense, believed to be responsible for preventing the transmission of sivs from monkeys to chimpanzees and from monkeys to humans (etienne et al., ) . however, apobec proteins can be counteracted by the hiv/siv viral infectivity factor (vif), albeit generally in a species-specific fashion. thus, mutations in vif were required for monkey sivs to be able to infect chimpanzees and then humans (letko et al., ) . tetherin is a second line of defense, and only hivs that have evolved an effective tetherin antagonism have spread widely in humans (kluge et al., ) . different lentiviruses use different viral proteins to antagonize tetherin: hiv- group m uses the viral protein u (vpu); hiv- group a uses the envelope glycoprotein (env), and hiv- group o uses the negative regulatory factor (nef). in contrast, hiv- groups n and p, whose spread in the human population has remained very limited, are unable to counteract tetherin efficiently. turning to another virus, recent studies using a mouseadapted strain of ebola virus to infect a panel of inbred mice provided by the collaborative cross (see chapter , animal models) found striking variation in the response to ebola virus infection, from complete resistance to severe hemorrhagic fever with % mortality. this underlines the role of host genetic background as a determinant of susceptibility. consistent with this are comments of clinicians that there are unpredictable differences in the outcome of individual ebola cases. these studies suggest a dynamic relationship between host and pathogen that may determine when a virus can cross the species barrier and create a new virus disease of humankind. although difficult to document in a rigorous manner, it does appear that new virus diseases of humans (and perhaps of other species) are emerging at an increased tempo. there are a number of reasons for this trend (table ) . the human population is growing inexorably, and is becoming urbanized even faster. as a result, there are an increasing number of large-crowded cities, which provide an optimal setting for the rapid spread of any newly emergent infectious agent. in the nineteenth century, it was noteworthy that someone could circumnavigate the globe in days, but now it can be done in less than h. however, the incubation period of viral infections (several days to several months) has stayed constant. someone can be infected in one location and-within a single incubation period-arrive at any other site on earth. this enhances the opportunity for a new human virus to spread as a global infection before it has even been recognized, markedly increasing the opportunity for the emergence of a new disease. the same dynamics also apply to viral diseases of animals and plants, which has important economic and social consequences for humankind. the sars pandemic of - , described above, is an example of how rapidly and widely a new virus disease can emerge and spread globally. in this instance, it is extraordinary that the disease was brought under control-and eradicated from the human population-by the simple methods of isolation, quarantine, and respiratory precautions. although conceptually simple, a heroic effort was required for success. another example is the emergence of a novel h n strain of influenza a virus that spread rapidly around the world before a vaccine could be produced. remote areas of the world are now being colonized at a high frequency, driven by population pressures and economic motives, such as the reclamation of land for agriculture or other uses, and the harvest of valuable trees and exotic animals. the construction of new dams, roads, and other alterations of the natural environment create new ecological niches. it is possible that this is the origin of urban yellow fever. yellow fever virus is an arbovirus maintained in a monkey-mosquito cycle in the jungles of south america and africa. humans who entered jungle areas became infected. when they returned to villages or urban centers, an urban cycle was initiated, where aedes aegypti mosquitoes-that are well adapted to the urban environment and preferentially feed on humansmaintained the virus. in the last years, agriculture has undergone a dramatic evolution with the development of "agribusiness." food and food animals are now raised on an unprecedented scale and under very artificial conditions, where the proximity of many members of a single plant or animal species permits an infection to spread like wildfire. furthermore, increasing numbers of plants, animals, and food products are rapidly transported over large distances; we enjoy fresh fruits and vegetables at any time, regardless of the season. international shipment of plants and animals can import viruses into new settings where they may lead to the emergence of unforeseen diseases. one example is the outbreak of monkeypox that caused about human cases in the united states. this was traced to the importation from africa of gambian giant rats as exotic pets; several rodent species in west africa appear to be reservoir hosts of this poxvirus. monkeypox spread from these animals to pet prairie dogs and from prairie dogs to their owners. because monkeypox causes infections in humans that resemble mild cases of smallpox, this outbreak was a major cause of public health concern. on occasion, a virus has been deliberately introduced into a susceptible population where it caused the emergence of a disease epidemic. for sport, rabbits were imported from europe into australia in the mid-nineteenth century. because of the absence of any natural predator the rabbits multiplied to biblical numbers, and threatened natural grasslands and agricultural crops over extensive areas of southern australia. to control this problem, myxomatosis virus was deliberately introduced in (fenner, ) . this poxvirus is transmitted mechanically by the bite of insects and is indigenous to wild rabbits in south america, in which it causes nonlethal skin tumors. however, myxomatosis virus causes an acutely lethal infection in european rabbits, and its introduction in australia resulted in a pandemic in the rabbit population. following the introduction of myxomatosis virus in , co-evolution of both virus and host were observed. the introduced strain was highly virulent and caused epizootics with very high mortality. however, with the passage of time field isolates exhibited reduced virulence, and there was a selection for rabbits that were genetically somewhat resistant to the virus. strains of moderate virulence probably became dominant because strains of lowest virulence were less transmissible and strains of maximum virulence killed rabbits very quickly. concern has also been raised about disease emergence due to the deliberate introduction of viruses into either human or animal populations, as acts of bioterrorism. because of the shortage of human organs for transplantation recipients, there is considerable research on the use of other species-particularly pigs-as organ donors. this has raised the question whether known or unknown latent or persistent viruses in donor organs might be transmitted to transplant recipients. since transplant recipients are immunosuppressed to reduce graft rejection, they could be particularly susceptible to infection with viruses from the donor species. in the worst scenario, this could enable a foreign virus to cross the species barrier and become established as a new human virus that might spread from the graft recipient to other persons. the impetus to identify a new pathogenic virus usually arises under one of two circumstances. first, a disease outbreak that cannot be attributed to a known pathogen may set off a race to identify a potentially new infectious agent. identification of the causal agent will aid in the control of the disease and in prevention or preparedness for potential future epidemics. sars coronavirus, west nile virus, and sin nombre virus are examples of emergent viruses that were identified in the wake of outbreaks, using both classical and modern methods. alternatively, an important new virus may be discovered as a serendipitous by-product of research directed to a different goal, as was the case with hepatitis b virus (hbv). in this instance, a search for alloantigens uncovered a new serum protein that turned out to be the surface antigen (hbsag) of hbv, leading to the discovery of the virus. when a disease outbreak cannot be attributed to a known pathogen, and where classical virus isolation, propagation, and identification fail, molecular virology is required. hepatitis c virus (hcv), sin nombre and other hantaviruses, certain rotaviruses, and kaposi's sarcoma herpesvirus (hhv ) , are examples of emergent viruses that were first discovered as a result of molecular technologies. below, we briefly describe some methods of viral detection and identification. more detailed information and technical specifics can be found in several current texts. the first question that confronts the investigator faced with a disease of unknown etiology is whether or not it has an infectious etiology? evidence that suggests an infectious etiology is an acute onset and short duration, clinical similarity to known infectious diseases, a grouping of similar illnesses in time and place, and a history of transmission between individuals presenting with the same clinical picture. for chronic illnesses, the infectious etiology may be much less apparent and a subject for debate. faced with a disease that appears to be infectious, the next question is whether it is caused by a virus. a classical example that predates modern virology is the etiology of yellow fever. in a set of experiments that would now be prohibited as unethical, the yellow fever commission, working with the us soldiers and other volunteers in cuba in , found that the blood of a patient with acute disease could transmit the infection to another person by intravenous injection. furthermore, it was shown that the infectious agent could pass through a bacteria-retaining filter and therefore could be considered a "filterable virus." virus isolation in cell culture and animals. the first step in identification of a putative virus is to establish a system in which the agent can be propagated. before the days of cell culture, experimental animals were used for this purpose. many viruses could be isolated by intracerebral injection of suckling mice, and some viruses that did not infect mice could be transmitted to other experimental animals. human polioviruses-because of their cellular receptor requirements-were restricted to old world monkeys and great apes; the virus was first isolated in by intracerebral injection of monkeys and was maintained by monkey-to-monkey passage until when it was shown to replicate in primary cultures of human fibroblasts. the modern era of virology (beginning about ) can be dated to the introduction of cultured cells as the standard method for the isolation, propagation, and quantification of viruses. there are now a vast range of cell culture lines that can be used for the isolation of viruses, and currently this is the first recourse in attempting to isolate a suspected novel virus. some viruses will replicate in a wide variety of cells but others are more fastidious and it can be hard to predict which cells will support their replication. it is also important to recognize that some viruses will replicate in cell culture without exhibiting a cytopathic effect. an important example is the identification of simian virus (sv ). poliovirus was usually grown in primary cell cultures obtained from the kidneys of rhesus monkeys, but sv had escaped detection because it replicated without causing a cytopathic effect. when poliovirus harvests were tested in similar cultures prepared from african green monkeys, a cytopathic effect (vacuolation) was observed, leading to the discovery of sv virus in . because inactivated poliovirus vaccine produced from to had been prepared from virus grown in rhesus monkey cultures, many lots were contaminated with this previously unknown virus, which inadvertently had been administered to humans. since that time, viral stocks and cell cultures have been screened to exclude sv and other potential virus contaminants. a number of methods are available to detect a noncytopathic virus that is growing in cell culture. these include visualization of the virus by electron microscopy, detection of viral antigens by immunological methods such as immunofluorescence or immunocytochemistry, the agglutination of erythrocytes of various animal species by virus bound on the cell surface (hemagglutination), the production of interferon or viral interference, and the detection of viral nucleic acids. detection of nonreplicating viruses. during the period from to , there was a concerted effort to identify the causes of acute infections of infants and children. in seeking the etiology of diarrheal diseases of infants, it was hypothesized that-in addition to bacteria, which accounted for less than half of the cases-one or more viruses might be responsible for some cases of infantile diarrhea. numerous unsuccessful attempts were made to grow viruses from stools of patients with acute diarrhea. it was conjectured that it might be possible to visualize a putative fastidious virus by electron microscopy of concentrated fecal specimens. when patients' convalescent serum was added to filtered and concentrated stool specimens, aggregates of nm virions were observed in stools from some infants with acute gastroenteritis. the ability of convalescent but not acute illness serum to mediate virion aggregation provided a temporal association of the immune response with an acute diarrheal illness. within years, rotavirus was recognized as the most common cause of diarrhea in infants and young children worldwide, accounting for approximately onethird of cases of severe diarrhea requiring hospitalization. once an emergent virus has been identified, it is necessary to classify it, in order to determine whether it is a known virus, a new member of a recognized virus group, or represents a novel virus taxon. this information provides clues relevant to diagnosis, prognosis, therapy, and prevention. in , an outbreak of acute hemorrhagic fever occurred in laboratory workers in marburg, germany, who were harvesting kidneys from african green monkeys (chlorocebus aethiops, formerly cercopithecus aethiops). in addition, the disease spread to hospital contacts of the index cases, with a total of over cases and % mortality. clinical and epidemiological observations immediately suggested a transmissible agent, but attempts to culture bacteria were unsuccessful. however, the agent was readily passed to guinea pigs which died with an acute illness that resembled hemorrhagic fever. after considerable effort, the agent was adapted to tissue culture and shown to be an rna virus. when concentrated tissue culture harvests were examined by electron microscopy, it was immediately recognized that this agent differed from known families of rna viruses, since the virions consisted of very long cylindrical filaments about nm in diameter. this was the discovery of marburg virus, the first recognized member of the filoviruses, which now include marburg and ebola viruses. isolation of a virus from patients suffering from an emergent disease provides an association, but not proof of a causal relationship. formal demonstration that an isolated virus is the causal agent involves several criteria formulated over the past years. these are often called the henle-koch postulates, after two nineteenth-century scientists who first attempted to enunciate the rules of evidence. sidebar summarizes these postulates, which have been modernized in view of current knowledge and experimental methods. the classic version of the henle-koch postulates required that the causal agent be grown in culture. however, as discussed below, a number of viruses that cannot be grown in culture have been convincingly associated with a specific disease. usually, this requires that many of the following criteria can be met: ( ) viral sequences can be found in the diseased tissue in many patients, and are absent in appropriate control subjects; ( ) comparison of acute and convalescent sera document induction of an immune response specific for the putative causal virus; ( ) the disease occurs in persons who lack a preexisting immune response to the putative virus, but not in those who are immune; ( ) the implicated virus or a homologous virus causes a similar disease in experimental animals; and ( ) epidemiological patterns of disease and infection are consistent with a causal relationship. some very important human diseases-such as hepatitis b and hepatitis c-are caused by viruses that cannot readily be grown in cell culture. experiences with these viruses have given credibility to the view that an infectious etiology can be inferred by clinical and epidemiological observations in the absence of a method for growing the causal agent. also, they have stimulated researchers to devise novel techniques that bypass the requirement for replication in cell culture. furthermore, the application of molecular biology, beginning about , has led to an array of new methods-such as the polymerase chain reaction (pcr), deep sequencing, and genomic databases-that can be applied to the search for unknown viruses. several case histories illustrate the inferences that lead to the hypothesis of a viral etiology, the strategy used to identify the putative causal agent, and the methods exploited by ingenious and tenacious researchers. sin nombre virus. hantavirus pulmonary syndrome was described above, as an example of an emerging virus disease. the disease was first reported in mid-may, , the henle-koch postulates were formulated in by henle, revised by koch in , and have undergone periodic updates to incorporate technical advances and the identification of fastidious agents with insidious disease pathogenesis. many of the following criteria should be met to establish a causal relationship between an infectious agent and a disease syndrome. . the putative causal agent should be isolated from patients with the disease; or the genome or other evidence of the causal agent should be found in patients' tissues or excreta; and less frequently from appropriate comparison subjects. temporally, the disease should follow exposure to the putative agent; if incubation periods can be documented they may exhibit a log-normal distribution. if an immune response to the putative agent can be measured, this response should correlate in time with the occurrence of the disease. subjects with evidence of immunity may be less susceptible than naïve individuals. . experimental reproduction of the disease should occur in higher incidence in animals or humans appropriately exposed to the putative cause than in those not so exposed. alternatively, a similar infectious agent may cause an analogous disease in experimental animals. . elimination or modification of the putative cause should decrease the incidence of the disease. if immunization or therapy is available, they should decrease or eliminate the disease. . the data should fit an internally consistent pattern that supports a causal association. and tissues and blood samples from these cases were tested extensively, but no virus was initially isolated in cell culture. however, when sera from recovered cases were tested, they were found to cross-react with a battery of antigens from known hantaviruses, providing the first lead (in june, ) . dna primers were then designed, based on conserved hantavirus sequences, and these were used in a pcr applied to dna transcribed from rna isolated from tissues of fatal cases. sequence of the resulting amplicon suggested that it was a fragment of a putative new hantavirus (july, ) , yielding a presumptive identification of the emerging virus within months after the report of the outbreak. an intense effort by three research teams led to the successful isolation of several strains of snv by november, . snv is a fastidious virus that replicates in vero e cells but not in many other cell lines. kaposi's sarcoma herpesvirus (hhv ). ks was described over years ago as a relatively uncommon sarcoma of the skin in older men in eastern europe and the mediterranean region. in the s, ks emerged at much higher frequency, as one of the diseases associated with aids. furthermore, ks exhibited an enigmatic epidemiological pattern, since its incidence in gay men was more than -fold greater than in other aids patients, such as injecting drug users and blood recipients. these observations led to the hypothesis that ks was caused by a previously undetected infectious agent that was more prevalent among gay men than among other hiv risk groups. however, researchers were unable to isolate a virus from ks tissues. searching for footprints of such a putative agent, chang and colleagues used the method of representational difference analysis to identify dna sequences specific for ks tumor tissue. several dna fragments were identified, and found to be homologous with sequences in known human and primate herpesviruses. in turn, these sequences were used to design primers to obtain the complete genome of a previously undescribed herpesvirus, since named hhv , human herpesvirus . to this date, hhv defies cultivation in tissue culture. is computer modeling a useful adjunct to the analysis or control of emerging viral diseases? the - ebola pandemic in west africa offers an interesting case study. as the epidemic unfolded, several groups attempted to project how it would evolve (meltzer et al., ; butler, ) . these projections had very wide confidence limits, and several of them had upper limits in the range of , or more cases. what the modelers could not foretell was that the infection did not spread across sub-saharan africa, and that several introductions (into countries such as nigeria and mali) were controlled by case isolation, contact tracing, and quarantine. however, modeling did contribute useful insights. dobson ( ) suggested that rapid quarantine (within - days) of contacts of ebola patients could be critical in epidemic control. one of the most exciting current issues in virology is the emergence of new viral diseases of humans, animals, and plants. even though the era of modern virology has been well established for more than years, virus diseases continue to appear or reemerge. the ebola pandemic of - highlights the associated dangers and obstacles to control. there are several explanations for emergence: ( ) discovery of the cause of a recognized disease; ( ) increase in disease due to changes in host susceptibility or in virus virulence; ( ) reintroduction of a virus that has disappeared from a specific population; ( ) crossing the barrier into a new species previously uninfected. many zoonotic viruses that are maintained in a nonhuman species can infect humans, but most cause dead-end infections that are not transmitted between humans. a few zoonotic viruses can be transmitted between humans but most fade out after a few person-to-person transmissions. rarely, as in the case of hiv, sars coronavirus, and ebola filovirus, a zoonotic virus becomes established in humans, causing a disease that is truly new to the human species. there are many reasons for the apparent increase in the frequency of emergence of new virus diseases, most of which can be traced to human intervention in global ecosystems. emergent viruses are identified using both classical methods of virology and newer genome-based technologies. once a candidate virus has been identified, a causal relationship to a disease requires several lines of evidence that have been encoded in the henle-koch postulates, guidelines that are periodically updated as the science of virology evolves. identifying, analyzing, and controlling emerging viruses involve many aspects of virological science. virus-host interactions play a key role, to explain persistence in zoonotic reservoirs, transmission across the species barrier, and establishment in human hosts. thus, the issues discussed in many other chapters contribute to our understanding of emerging viral diseases. hendra and nipah viruses: different and dangerous biological control as exemplified by smallpox eradication and myxomatosis sequence-based identification of microbial pathogens: a reconsideration of koch's postulates emerging virus diseases: can we ever expect the unexpected? emerging microbes and infection epidemiology and transmission dynamics of west nile virus disease emerging infections the emergence and evolution of canine parvovirus -an example of recent host range mutation social and environmental risk factors in the emergence of infectious diseases diseases of the central nervous system caused by lymphocytic choriomeningitis virus and other arenaviruses middle east respiratory syndrome coronavirus (mers-cov) evidence and speculation human monkeypox: an emerging zoonosis isolation of the causative agent of hantavirus pulmonary syndrome cultivation of the lansing strain of poliomyelitis virus in cultures of various human embryonic tissue. science mission to mers origin of hiv- in the chimpanzee pan troglodytes genomic surveillance elucidates ebola virus origin and transmission during the outbreak a decade after sars: strategies for controlling emerging coronaviruses chikungunya disease outbreak, reunion island enhanced virulence of influenza a viruses with the haemagglutinin of the pandemic virus mers surges again, but pandemic jitters ease origin of the west nile virus responsible for an outbreak of encephalitis in the northeastern united states genesis of a highly pathogenic and potentially pandemic h n influenza virus in eastern asia bats are natural reservoirs of sars-like coronavirus the many projected futures of dengue ks-associated herpesvirus, and the criteria for causality in the age of molecular biology genetic identification of a hantavirus associated with an outbreak of acute respiratory illness host genetic diversity enables ebola hemorrhagic fever pathogenesis and resistance recent researches concerning etiology, propagation and prevention of yellow fever, by the united states army commission recognition determinants of broadly neutralizing human antibodies against dengue viruses a single mutation in chikungunya virus affects vector specificity and epidemic potential characterization of the reconstructed spanish influenza pandemic virus molecular changes in a/chicken/ pennsylvania/ (h n ) influenza virus associated with acquisition of virulence ebola references models overestimate ebola cases breakdown of the year: ebola mathematical models for emerging disease mobilizing ebola survivors to curb the epidemic ebola hemorrhagic fever genomic surveillance elucidates ebola virus origin and transmission during the outbreak basic clinical and laboratory features of filoviral hemorrhagic fever ebola virus vaccines: an overview of current approaches. expert review of vaccines estimating the future number of cases in the ebola epidemic -liberia and sierra leone single-dose attenuated vesiculovax vaccines protect primates against ebola makona virus pathogenesis of the viral hemorrhagic fevers product: reebov™ antigen rapid test kit host genetic diversity enables ebola hemorrhagic fever pathogenesis and resistance who ebola response team. ebola virus disease in west africa-the first months of the epidemic and forward projections gene loss and adaptation to hominids underlie the ancient origin of hiv- sharp pm aids as a zoonosis: scientific and public health implications nef proteins of epidemic hiv- group o strains antagonize human tetherin vif proteins from diverse primate lentiviral lineages use the same binding site in apobec g the origins of aids origins of hiv and the aids pandemic key: cord- -giijfhbz authors: khubone, thokozani; tlou, boikhutso; mashamba-thompson, tivani phosa title: electronic health information systems to improve disease diagnosis and management at point-of-care in low and middle income countries: a narrative review date: - - journal: diagnostics (basel) doi: . /diagnostics sha: doc_id: cord_uid: giijfhbz the purpose of an electronic health information system (ehis) is to support health care workers in providing health care services to an individual client and to enable data exchange among service providers. the demand to explore the use of ehis for diagnosis and management of communicable and non-communicable diseases has increased dramatically due to the volume of patient data and the need to retain patients in care. in addition, the advent of coronavirus disease (covid- ) pandemic in high disease burdened low and middle income countries (lmics) has increased the need for robust ehis to enable efficient surveillance of the pandemic. ehis has potential to enable efficient delivery of disease diagnostics services at point-of-care (poc) and reduce medical errors. this review provides an overview of literature on ehis’s with a focus on describing the key components of ehis and presenting evidence on enablers and barriers to implementation of ehiss in lmics. with guidance from the presented evidence, we proposed ehis key stakeholders’ roles and responsibilities to ensure efficient utility of ehis for disease diagnosis and management at poc in lmics. the health sector is lagging behind in the era of information and technology (it). the main purpose for use of it in the health sector include the following: extending geographic access to health care; enhancing client communication with the health provider; improving disease diagnosis and treatment; improved data quality management; and to avoid fraud and abuse of client's confidentiality [ ] [ ] [ ] . the introduction of digitization has revealed the possibilities and costs benefits to health care management. it systems such as electronic health information systems (ehis) have been shown to be a useful tool for improving disease diagnosis and treatment at point of care (poc), globally [ ] [ ] [ ] . ehis is the digital version of a patients' paper chart, which has capacity to store health data such as test results and treatments. it is also designed to enable real-time, patient-centered records that make information available instantly and securely to the authorized users [ ] . the term ehis is used interchangeably with electronic health records (ehrs), ehealth and electronic medical records (emrs). ehis are a vital part of health it built to go beyond standard clinical data collected in a providers' office and can be inclusive of a broader view of a patient care [ ] . an efficient functioning ehis requires the use of digital health systems such as three interlinked electronic register (tier.net), which has an ability to facilitate information exchange between software [ ] . tier.net is used by healthcare facilities to enable electronic collection, storage, management and sharing records (emrs). ehis are a vital part of health it built to go beyond standard clinical data collected in a providers' office and can be inclusive of a broader view of a patient care [ ] . an efficient functioning ehis requires the use of digital health systems such as three interlinked electronic register (tier.net), which has an ability to facilitate information exchange between software [ ] . tier.net is used by healthcare facilities to enable electronic collection, storage, management and sharing of patient's electronic health or medical records for the purpose of patient care, research and quality management [ ] . countries are currently battling with a global pandemic caused by the outbreak of sars cov- , a virus that causes coronavirus disease . the advent of covid- in high disease burdened low and middle income countries (lmics) such as south africa has increased the need for robust ehis to enable efficient surveillance of the pandemic [ ] . the main objective of this review is to presents an overview of literature on the characteristics of ehis and implementation of ehiss for improving disease diagnosis and treatment at point-of-care in the lmics. we search for literature from the following databases: pubmed and google scholar and included relevant literature from lmics. an efficiently functioning ehis is key to health service delivery as it promises a number of substantial benefits, including improving the quality of healthcare service delivery, decreased healthcare costs as well as reduce serious unintended consequences [ ] . a poorly implemented ehr system can lead to ehr-related errors that jeopardize the integrity of the information in the ehr, leading to errors that endanger patient safety as well as compromise the quality healthcare services [ ] . the following key components are required for an efficient functioning ehis: patient management component; activity component; clinical component; pharmacy component; laboratory component; radiology information system; and billing system ( figure ) [ ] . table provides a description on the functions of ehr components within the electronic health system and patient care. patient registration includes key patient information such as demographics, insurance information and contact information [ ] populations and their needs are analyzed at a point of care to determine the services to be rendered to them [ ] activity ehis flow processed from when a client is entering the point of service till data is digitized on the system [ , ] traceability of health data habitation of multiple sub-components, e.g., computerized provide order entry (cpoe), electronic documentation, nursing component [ ] electronic clinical documentation systems enhance the value of ehrs by providing electronic capture of clinical notes; patient assessments; and clinical reports, such as medication administration records (mar) [ ] pharmacy ehis islands of automation, such as pharmacy robots for filling prescriptions or payer formularies, that typically are not integrated with ehrs [ ] improve efficiency of pharmacy services consists of two subcomponents: capturing results from lab machines; and integration with orders, billing and lab machines. the lab component may either be integrated with the ehr or exist as a standalone product [ , ] improve efficiency of pathology laboratory services manages patient workflow, ordering process and results [ ] enables improved service delivery the billing system (hospital and professional billing) captures all charges generated in the process of taking care of patients. these charges generate claims, which are subsequently submitted to insurance companies, tracked and completed [ ] tracking of patient data and quality assurance evidence on ehis in developing countries revealed the following ehealth attributes: tracking of patients who were initiated on treatment; monitoring of adherence to care and early detection of potential loss to follow up; minimize the time it takes to communicate data between different levels; reduction of errors especially the laboratory data; linkage to bar code for unique identification and laboratory samples and the prescription of medication [ ] . in mozambique, a robust electronic patient management system facilitated a facility-level reporting of required indicators, improved ability to identify patients lost to follow-up; and support facility and patient management for hiv care [ ] . an implementation study aimed at implementing an integrated pharmaceutical management information system for antiretroviral treatment (art) and other medicines in namibia showed the system's reliability in managing art patients, monitoring art adherence and hiv drug resistance early warning indicators [ ] . enables of ehis implementation in the lmics are aligned with leadership abilities, sound policy decision and financial support with the goals of purchasing it, connectivity and capacity building [ ] . enablers for ehis in lmics includes: legislation, financial investment; staff training, political leadership; acceptability of technology; performance expectancy; and social influence among professionals [ ] [ ] [ ] . many lmics are supporting financial investment to help scaling up of ehis. a study from china recommended that in order to achieve the national childhood immunization information management system objectives for , the funding for system-building should be increased [ ] . a three-country qualitative study was conducted in southern africa on the sustainability of health information systems which revealed; more government commitment in funding ehis such as printer ink, it infrastructure, recruitment of personnel and running costs [ ] . in ghana, cooperation between the vendors and management was demonstrated [ ] . this successful cooperation translated into regularly provision of feedback and sucessful system maintenance [ ] . this has helped the facility in alleviating the common challenge faced by most information communication and technology (ict) implementers in limcs [ ] . south africa national health act of is a good example of a legislation, policy, norms and standards defining the role of national, provincial and local governments in terms of ehis implementation in lmics [ ] . south africa has advocated the scale up of digital health technologies to improve access to health care and for health systems strengtherning through systems such as tier.net and district health information software (dhis and patient registration systems [ ] . the delivery of ehis or ehealth in south africa's public sector facilities is the responsibility of the provincial departments of health, while policy development resides with the national department of health (ndoh). in terms of section of the national health act, the ndoh is also responsible for facilitation and coordination of health information. there is growing evidence on the value of well-trained health informatics workforce in lmics [ ] . studies conducted in botswana and uganda showed the on-the-job training and mentorship as a major enabler for ehis in lmics [ , ] . this were shown to be an effective approach for strengthening monitoring and evaluation capacity and ensuring data quality within a national health system [ ] . it was demonstrated that on-the-job training can also improves performance through timely and increased reporting of key health indicators [ ] . effective leadership can positively contribute to the successful adoption of new ehis in any organization [ ] . in ethiopia, the role of ict towards universal health coverage prompted academic and political spheres to make ict on the agenda especially for disease diagnosis and treatment in the lmics [ ] . the rwandan government has also shown commitment to telemedicine, through their strategic choice of using low-cost and less complex technologies, and strategic partnerships with educational and technology companies to help in the implementation of telemedicine [ ] . research has shown that factors such as english language proficiency level, computer literacy and emr literacy level and education level can influence the level of use of ehis [ ] . liu and others revealed that the usage of ehis by health workers in lmics can be influenced by the level of system simplicity and user friendliness [ ] . an economical mobile health application to improve communication between healthcare workers was introduced in kwazulu-natal, south africa using an iterative design process [ ] . this application was received positive feedback from healthcare workers due to its ability to improve team spirit between community and clinic based staff [ ] . there are various factors impeding the successful implementation and scale up of ehis in lmics. these include the following: complexity of the intervention and lack of technical consensus; limited human resource, poor leadership, insufficient finances, staff resistance, lack of management, low organizational capability; misapplication of proven diffusion techniques; non engagement of both local users and inadequate use of research findings when implementing [ ] . the complexity of the ehis which and lack of consultation as key barriers on the implementation in lmics [ ] . designing an organizational ehis with a complex design is a serious threat of the implementation in lmics [ ] . in rwanda, the interfaces between the existing and new ehis are the inhibitors to the implementation [ ] . there are instances of patient information that are captured into the computer; but challenged with bandwidth requirements in health facilities [ ] . the main barriers in implementing ehis on the lmics relate to lack of capacity: human, leadership and management [ ] . human resource capacity is the main barrier not only in terms of the supply but also in terms of the ability to perform the task. the exodus of skilled cadres to the well-paying non-government organizations are the contributing factors to human resource capacity [ ] . ineffective coordination, poor management and lack of supervision for ehis are the main challenges in the lmics [ , ] . management capacity and the ability to use data were reported as the root causes in facilities with inadequate human resource, computers and data capturing skills [ ] . late submission of health data and absence of feedback from the supervisors are the key barriers to ehis implementation in lmics [ ] . ehis implementation is costly as there is hardware, software, maintenance, training and human resource investment making implementation unaffordable to many lmics [ ] . cost is the main constraint to adoption and implementation of ehis in lmics [ ] . running costs and political will are the prerequisite for sustaining ehis [ ] . unreliable electricity supply, shortage of it equipment, poor connectivity and safe accommodation for the equipment are the restraining elements to the successful implementation of ehis [ ] . poor public healthcare system with ever changing policies are a hindrances to the successful implementation of the ehis in lmics [ ] . leon and others used a framework for assessing the health system challenges to scaling up m-health in south africa and revealed a weak ict environment and limited implementation capacity within the health system [ ] . katuu explored the barriers in improving south african public health sector through ehealth strategy particularly by integrating electronic document and records management system. inequality, historical red tape and curative structure are the main barriers [ ] . in asia, incapacitated human resources and shortage of it skills were identified as inhibiting factors to ehis implementation [ ] . in iran, lack of users' knowledge about system and working with it were the barriers identified [ ] . in most of the lmics; the need for a trained workforce in health informatics is great [ ] . there are instances where computer illiterate and low morale to use the system are affecting the implementation [ , ] . some of the challenges include related to ehis software, cost drivers, interoperability, connectivity in rural set up and data quality [ ] . a study conducted in south africa, demonstrated difficulties with implementing a dual ehis as a result of clinicians' resistance to using the ehis and feel more comfortable using paper based system [ ] . in iran, the negative staff attitudes of system developers and lack of acceptability are the main barriers to successful implementation of hospital-based ehis [ ] . although south africa ehis catered for all required information, the hospital officials show poor due to the attitude and resistance to using ehis for patient treatment and prescriptions [ ] . an assessment was conducted by khasi ehis state of readiness for rural south african areas, which revealed that the resistance to change and negative perceptions were two key causes for not accepting the intervention. any new ehis intervention must address them in order to succeed [ ]. studies revealed incompleteness of tb data across multiple information systems in south africa. variances between % and % of the missed cases due to poor recording from the source documents (either patient records or laboratory records) were demonstrated [ , ] . data collected and reported in the public health system across three large, high hiv-prevalence districts was neither complete nor accurate enough to guide patient tracking as part of prevention of mother to child transmission (pmtct) care [ ] . this review has provided us with a great platform to depict opportunities of ehis implementation in lmics. it has also enabled us to identify and classify barriers and challenges implementation of ehis that must be addressed pre-implementation to ensure the success. key to the success of ehis is the leader's willingness to play a leading role in adopting data demand and supply principles for decision making. the presented literature reveals the need for well-defined roles of ehis stakeholders to ensure successful implementation and utility. here, we proposed key stakeholders roles and responsibilities in the implementation of ehis for disease diagnosis and management at point-of-care (poc) in lmics ( figure ). in the proposed key stakeholders' roles and responsibilities we emphesise on that the information culture should be cascaded through different hierarchy levels of an organization. in the absence of the such culture there is likely to be poor adoption, poor data quality and utilization [ ] . the advent of ehis has revolutionize patient care through improving both disease diagnosis and treatment at poc. however, its use in lmics is still limited, despite the high disease burden in these settings. ehis implementation need to be one of the global health priorities to help respond to community's health needs, particularly during the current covid- pandemic. successful implementation of ehis requires commitment from health leaders to play a strategic role in terms of the advent of ehis has revolutionize patient care through improving both disease diagnosis and treatment at poc. however, its use in lmics is still limited, despite the high disease burden in these settings. ehis implementation need to be one of the global health priorities to help respond to community's health needs, particularly during the current covid- pandemic. successful implementation of ehis requires commitment from health leaders to play a strategic role in terms of the policy directive, resource mobilization and evidence-based decision-making. to help optimize the implementation and use of ehis in lmics, we have proposed roles and responsibilities of stakeholders to ensure efficient and sustainable implementation of ehis. a systematic approach for stakeholder engagement would be crucial to ensuring successful operationalization of the proposed roles and responsibilities. a scoping review of geographic 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on the dual-factor model: a validation in taiwan a pilot study of an mhealth application for healthcare workers: poor uptake despite high reported acceptability at a rural south african community-based mdr-tb treatment program what are the barriers to scaling up health interventions in low and middle income countries? a qualitative study of academic leaders in implementation science architectural frameworks for developing national health information systems in low and middle income countries an architecture and reference implementation of an open health information mediator: enabling interoperability in the rwandan health information exchange role of health management information system in disease reporting at a rural district of sindh the benefits and challenges of e-health applications: a content analysis of the south african context ekinya, i. improving the routine hmis in nigeria through mobile technology for community data collection pakistan's health management information system: health managers' perspectives determinants of health management information systems performance: lessons from a district level assessment understanding health information needs and gaps in the health care system in uttar pradesh evaluation of health it in low-income countries benefits of telemedicine and barriers to its effective implementation in rural india: a multicentric e-survey applying a framework for assessing the health system challenges to scaling up mhealth in south africa transforming south africa's health sector: the ehealth strategy, the implementation of electronic document and records management systems (edrms) and the utility of maturity models utilisation of electronic health records for public health in asia: a review of success factors and potential challenges prioritizing barriers to successful implementation of hospital information systems health informatics in developing countries: going beyond pilot practices to sustainable implementations: a review of the current challenges electronic medical records in low to middle income countries: the case of khayelitsha hospital electronic records management in the public health sector of the limpopo province in south africa we would like to thank the kwazulu-natal department of health for granting us access to library databases and referencing software. the authors declare no conflicts of interest. diagnostics , key: cord- -hprwqi n authors: löscher, thomas; prüfer-krämer, luise title: emerging and re-emerging infectious diseases date: - - journal: modern infectious disease epidemiology doi: . / - - - - _ sha: doc_id: cord_uid: hprwqi n emerging infectious diseases (eids) are characterized by a new or an increased occurrence within the last few decades. they include the following categories emerging diagnosis of infectious diseases: old diseases that are newly classified as infectious diseases because of the discovery of a responsible infectious agent. europe including great britain as well as in india, china, and japan. emerging vector-borne disease events concentrated in densely populated subtropical and tropical regions mostly in india, indonesia, china, sub-saharan africa, and central america (see figs. . , . , and . ). the identification of new infectious agents in old diseases with unknown etiology is still the basis in many epidemiological studies. such newly detected bacteria and viruses in the last few decades are listed in table . . since the detection of helicobacter pylori in , this infection has been identified as the causative agent in % of b-gastritis cases. the risk of duodenal ulcer is increased by - -fold in patients with helicobacter-associated gastritis. who declared h. pylori as a carcinogen of first order because of its potential to enhance the risk of stomach carcinoma and malt lymphoma in long-term infection. in highprevalence regions for h. pylori, the frequency of stomach carcinoma is significantly higher compared to low-endemic areas (correa et al. ). the identification of h. pylori facilitates curative treatment of most associated diseases in individuals. but the most important epidemiological effect on associated diseases is attributed to increased hygienic standards in industrialized countries with a substantial reduction of h. pylori prevalences in younger age cohorts. transmission of h. pylori occurs mainly in childhood. in western developed countries the overall prevalence is around %, higher in older age groups due to a cohort effect, and this increases with low socioeconomic status (rothenbacher et al. ). in countries with low hygienic standards the prevalences are still high in younger age groups and reach % in developing countries. in developed countries, migrant subpopulations from less-developed regions show significantly higher prevalences in comparison to the nonmigrant population (mégraud ). since the early th century, a characteristic expanding skin lesion, erythema migrans (em), and an arthritis associated with previous tick bites were known. borrelia for many decades. increased outdoor activities facilitated contacts between humans and ticks in the s and the s and increased transmission of borrelia to humans at the northeastern coast of north america, leading to the discovery of borrelia burgdorferi in by willy burgdorfer. three different stages of the disease that describe the stage of infection and the involvement of different organ systems are known: stage , early localized infection; stage , early but disseminated infection; and stage , late stage with persistent infection. lyme disease is endemic at the east coast and in minnesota in the united states, in eastern and central europe, and russia. seroprevalence rates that reflect about % of nonclinical infections vary between and % in the general population in germany (hassler et al. ; weiland et al. ) . in high-risk groups like forest workers in germany the prevalences reach - % (robert koch institute a). in ticks (ixodes) the prevalences are between and % depending on the geographical area and the testing method used [immunofluorescence test, ift and polymerase chain reaction (pcr)]. in most studies the main risk factors of infection are age (children: - years, adults - years), outdoor activities, skin contacts with bushes and grass, and the presence of ticks in domestic animals (robert koch institute b) . the probability of infection (seroconversion) after a tick bite in germany is - % and the probability of a clinical disease is . - . %. the probability that the bite of an infectious tick leads to infection in the host is - %. this depends on the time duration that the tick is feeding on the human body. since the detection of the etiologic infectious agent and the subsequent development of laboratory diagnostic tests in the s, the number of reported cases of lyme disease has increased from to , per year, indicating that it is an "emerging diagnosis." the reported numbers vary depending on the reproduction of the hosting rodents for ticks as well as the contacts between humans and nature (spach et al. ) . ticks may live for several years and their survival, reproduction rate, and activity are directly affected by changes in seasonal climate through induced changes in vegetation zones and biodiversity, hence causing local alterations of the tick's habitat and in the occurrence of animals that are carriers of different pathogens (like small rodents). several studies in europe have shown that in recent decades the tick ixodes ricinus, transmitting lyme borreliosis and tick-borne encephalitis (tbe), has spread into higher latitudes (e.g., sweden) and altitudes (e.g., czech republic, austria), and has become more abundant in many places. such variations have been shown to be associated with recent variations in climate. as a result, new risk areas of both diseases have recently been reported from the czech republic. climate change in europe seems likely to facilitate the spread of lyme borreliosis and tbe into higher latitudes and altitudes, and to contribute to extended and more intense transmission seasons. currently, the most effective adaptive strategies available are tbe vaccination of risk populations and preventive information to the general public (danielova et al. ; lindgren et al. ; materna et al. ). an effective vaccine was licensed for b. burgdorferi in . in europe, where different variants of borrelia are present (mostly b. afzelii and b. garinii), this vaccine is not protective. trivalent vaccines for europe are in clinical trials. in recent years, norovirus infections are increasingly recognized as the cause of large outbreaks of diarrheal diseases in the general population, school classes, nursing homes, hospitals, and cruise ships in western countries with peaks in colder seasons (winter epidemics) (centers of disease control ; verhoef et al. ; robert koch institute a) . this is a typical example for emerging diagnosis due to increasing availability of routine pcr testing for these viruses in stool samples. noroviruses (family caliciviridae) are a group of related, single-stranded rna viruses first described in an outbreak of gastroenteritis in a school at norwalk, ohio, in . five genogroups are known. immunity seems to be strain specific and lasts only for limited periods, so individuals are likely to get the infection repeatedly throughout their life. it is estimated that noroviruses are the cause of about % of all food-borne outbreaks of gastroenteritis. for several years there has been an ongoing epidemic in several european countries due to drift variants of a new genotype (gg ii. jamboree) previously unknown to this nonimmune population (robert koch institute a). as a result of an analysis of outbreaks in the united states between and , direct contamination of food by a food handler was the most common cause ( %), person-to-person transmission was less prevalent ( %), and even less frequently waterborne transmission could be proved ( %) (centers for disease control ). vomiting is a frequent symptom of norovirus enteritis and may result in infectious droplets or aerosols causing airborne or contact transmission. this may explain the difficulty to stop outbreaks in hospitals, nursing homes, and similar settings despite precautions to prevent fecal-oral transmission. also on cruise ships, person-to-person transmission is most likely in those closed settings, and drinking tap water is a risk factor as well (verhoef et al. ). searching for an agent which causes large outbreaks of enterically transmitted non-a hepatitis in asia and other parts of the world, the hepatitis e virus (hev) was first described in and cloned and sequenced in (reyes et al. ). meanwhile, hev has been shown to be a zoonotic virus circulating in pigs and other animals. it is implicated in about % of sporadic cases of acute hepatitis in developing countries and associated with a high case fatality rate in the third trimester of pregnancy ( - %). hev is a major cause of large epidemics in asia, and to a lesser extent in africa and latin america, typically promoted through postmonsoon flooding with contamination of drinking water by human and animal feces. recent data show hev also to circulate in european countries and to be associated with severe and fatal disease not only during pregnancy but also in the elderly and in patients with chronic liver conditions. in patients with solid organ transplants, hev may even cause chronic hepatitis and liver cirrhosis (kamar et al. ) . a recombinant hev vaccine candidate has demonstrated a high protection rate of approximately % during clinical trials in nepal (shrestha et al. ). for years, specific human papillomaviruses have been linked to certain human cancers and have been identified as causative agents of malignant proliferations. in the s the detection of papillomavirus dna from cervical carcinoma biopsies were published, showing that hpv types and are the most frequent (dürst et al. ; boshart et al. ) . the relation of hpv infections and cancer is further discussed in chapter . definition: only infections that are newly discovered in humans are listed in this chapter: hiv, new variant of creutzfeldt-jakob disease (vcjd), hemorrhagic uremic syndrome (hus) caused by enterohemorrhagic escherichia coli, viral hemorrhagic fevers like hanta, lassa, ebola, and marburg fever, nipah virus encephalitis, monkeypox, human ehrlichiosis, severe acute respiratory syndrome (coronavirus infection, sars), and avian influenza (h n ) (see fig. . and table . ). these infections mostly have their origin in zoonotic wildlife (e.g., avian influenza, monkeypox, hantavirus, nipah virus, and filoviruses) or livestock (e.g., vcjd). factors promoting the spread of these infections in humans are contacts with wildlife, mass food production of animal origin, and globalization (migration, transportation of goods and vectors) (see fig. . ). in addition, new strains or variants of well-known pathogens have emerged showing increased or altered virulence such as clostridium difficile ribotype or staphylococcus aureus strains expressing the panton-valentine leukocidin (see also chapter ). the epidemiology of hiv is treated in chapter and that of avian influenza and new influenza h n in chapter . in the year , years after the peak of the bse epidemic in the united kingdom, with an annual incidence rate in cows of . per million bovines aged over months, the first mortalities in humans with a new variant of creutzfeldt-jakob disease were observed in the united kingdom. until , smaller incidence rates of bse cases had been reported by other european countries in indigenous bovines and up to more than , per million in in ireland. from , bse started to increase in switzerland and portugal, from in spain and in recent years has spread to eastern european countries (organisation mondiale de la santé animale ). the infectious agent is a self-replicating protein, a "prion." the source of infection for cows is infectious animal flour. the transmission to humans occurs through oral intake of cow products, most likely undercooked meat and nerval tissues as well as transplants of cornea, dura mater, contaminated surgical instruments, or the treatment with hypophyseal hormones extracted from animal tissues. after a statuary ban on the feeding of protein derived from ruminants to any ruminant and the export ban of all cow products from england, the epidemic of bse in cows and the occurrence of human infections decreased in the united kingdom since . by june the total number of deaths in definite/probable cases of vcjd in the united kingdom was (the national creutzfeldt-jakob disease surveillance unit ). only a few numbers of vcjd were reported from other european countries and the united states (who ). nipah virus encephalitis was first observed in / in malaysia. the disease was transmitted by pigs to laborers in slaughterhouses and showed a lethality of %. the infectious agent was detected in (chua et al. ; lam and chua ) . since then, several outbreaks of nipah virus infections have been observed in asian countries: singapore in , india , and bangladesh since (who a harit et al. ) . the virus has been isolated repeatedly from various species of fruit bats, which seem to be the natural reservoir (yob et al. ). west nile is a mosquito-borne flavivirus that was first isolated from a woman with a febrile illness in uganda in . from the s, west nile fever endemicity and epidemics started being reported from africa and the middle east. severe neurological symptoms were thought to be rare. more recent epidemics in northern africa, eastern europe, and russia suggested a higher prevalence of meningoencephalitis with case fatality rates of - %. in , west nile virus was identified as the cause of an epidemic of encephalitis at the east coast of the united states (nash et al. ) . a seroepidemiological household-based survey showed that the first outbreak consisted of about , infections of which about , developed fever and less than % experienced neurological disease ). since then, epidemics occur during summer months in north america each year, with an estimated , febrile illnesses and over , encephalitis or meningitis cases in the united states in (centers for disease control ). age above years is the main risk factor for developing severe disease. the virus is transmitted mainly by culex mosquitoes, but also by sandflies, ceratopogonids, and ticks, with birds as reservoir hosts and incidental hosts such as cats, dogs, and horses. efforts are made to reduce the transmitting mosquito population and to prevent mosquito bites through personal protection as well as to prevent transmission through blood donations by screening (centers of disease control ). the first case of sars occurred in guangdong (china) in november of , leading to an outbreak with cases in china and hong kong ( cases worldwide) until july . the case fatality rate was . %. a new coronavirus (sars-cov) was identified as the causative agent (drosten et al. ) , being transmitted first by infected semidomesticated animals such as the palm civet and subsequently from human to human. some cases were exported to other countries, causing smaller outbreaks there, canada being the most affected country outside asia with cases, before control of transmission was effective. eight thousand and ninety-six cases were reported worldwide, until july , then further transmission stopped (besides one more case of laboratory transmission in ), indicating an efficient international cooperation in disease control (who b) . recently, sars-cov has been found in horseshoe bats, which seem to be the natural reservoir of the virus. about , - , cases of hemorrhagic fever with renal syndrome (hfrs) caused by hantaviruses are reported annually worldwide, with more than half in china, many from russia and korea, and numerous cases from japan, finland, sweden, bulgaria, greece, hungary, france, and the balkan with different death rates depending on the responsible virus, ranging from . % in puumala to - % in hantaan infections (schmaljohn and hjelle ) . hantaviruses are transmitted from rodent to rodent through body fluids and excreta. only occasionally do humans get infected. different types of hantaviruses are circulating in europe and the eastern hemisphere, predominantly puumala virus, dobrava virus, and tula virus, adapted to different mouse species. depending on the virus type the case fatality rate is between and %. as an example, the annual rate of reported cases in germany was about cases per year from onward. this started to change in with reported cases and rose dramatically to cases in . that year, hantavirus infections were among the five most reported viral infections in germany. reasons for the rise in human infections were an increase in the hosting rodent population due to a very mild winter / and an early start of warm temperatures in spring which led to favorable nutritional situations for the mice influencing their population dynamics. in addition, favorable climatic conditions enhanced the outdoor behaviors of humans facilitating transmission in rural areas (robert koch institute b; hofmann et al. ) . since , a previously unknown group of hantaviruses (sin nombre, new york, black creek canal, bayou-in the united states and canada; andes, in south america) emerged in the americas as a cause of hantavirus pulmonary syndrome (hps), an acute respiratory disease with high case fatality rates (approx. %), causing a new, significant public health concern. a total of cases had been reported until march in states, most of them in the western part of the united states (centers for disease control ). lassa virus was detected for the first time in during an outbreak affecting nurses in a missionary hospital in lassa, nigeria. however, the disease had previously been described in the s. lassa virus is enzootic in a common peridomestic rodent in west africa, the multimammate rat mastomys natalensis, which is chronically infected and sheds the virus in urine and saliva. human infection through direct or indirect contact with rats or their excretions is rather common in some west african countries and estimates from seroepidemiological and clinical studies suggest that there are several hundred thousand cases annually. however, only a minority of infections seems to progress to severe hemorrhagic disease with a case fatality rate of - % in hospitalized cases. the virus can be transmitted by close person-to-person contact and nosocomial spread has been observed under poor hygienic conditions. marburg and ebola viruses, which were first detected during outbreaks in and , respectively, have so far been observed only during several limited outbreaks and a few isolated cases in certain countries of sub-saharan africa. however, very high case fatality rates ( - %), the occurrence of outbreaks that were difficult to control in resource-poor settings, and the obscure origin of these viruses have attracted considerable public interest worldwide. recently, evidence was found for both marburg and ebola viruses to occur in certain species of bats that probably constitute the natural reservoir of these filoviruses (towner et al. ). although the disease burden of these viral hemorrhagic fevers is low, they gained considerable international attention due to -their high case fatality rates, -the risk of person-to-person transmission, -several imported cases to industrialized countries, and -fears of abuse of these agents for bioterrorism. as a consequence, considerable resources have been invested, even in nonendemic countries, in the setting up of task forces and high containment facilities for both laboratory diagnostic services and treatment of patients using barrier nursing. this highly virulent strain of c. difficile expresses both cytotoxins a and b and, in addition, the binary toxin cdt, an adp-ribosyltransferase. due to a deletion in the regulatory tcdc gene, the synthesis rates of toxin a and b are increased by -and -fold, respectively. this strain was detected in for the first time in pittsburgh, usa. since then it has spread to canada, and in it reached europe causing multiple outbreaks in hospitals and nursing homes (warny et al. ) . c. difficile -associated colitis has shown high case fatality rates ( - %) and an increased relapse rate. containment of outbreaks in hospitals and other institutions necessitates isolation of patients or cohorts and strict hygienic measures. during recent decades, a large variety of well known infectious diseases has shown regional or global re-emergence with considerable public health relevance (table . ). globally, tuberculosis is probably the most important re-emerging infectious disease. in developing countries, tb infection still is extremely common and, in the wake of the hiv pandemic, the percentage of those developing overt disease has increased dramatically. worldwide, tb is the most common opportunistic infection in patients with aids. the significance of tb and hiv/tb coinfection is reviewed in chapters and . the re-emergence of some infectious diseases is closely related to the lack or the breakdown of basic infrastructures as seen in periurban slums and in refugee camps in developing countries, or as a consequence of war, breakdown of the civil society, or natural or man-made disasters. cholera is a formidable example for both re-emergence and epidemic spread under those conditions. another important group of re-emerging infectious diseases is caused by various vector-borne infections, such as malaria, dengue fever, and yellow fever. these major vector-borne diseases are treated in more detail in chapter . in addition, there are a variety of re-emerging infections transmitted by arthropod vectors such as various arboviral diseases and some protozoal diseases other than malaria (i.e., leishmaniasis, human african trypanosomiasis). the reasons for the emergence of several vector-borne diseases are rather variable and may range from climatic factors (e.g., global warming, rainfall), lack or breakdown of control, to changes in agriculture and farming and in human behavior (e.g., outdoor activities). these factors are usually quite specific for each of these diseases and largely depend on the specific ecology of the agent, its vectors, and reservoirs. cholera, an acute diarrheal infection transmitted by fecally contaminated water and food, had been endemic for centuries in the ganges and brahmaputra deltas in the th century before it started to spread to the rest of the world. since , six pandemics caused by the classical biotype of vibrio cholerae were recorded that killed millions of people across europe, africa, and the americas. it has been a major driving force for the improvement of sanitation and safe water supply. the seventh pandemic was caused by the el tor biotype, first isolated from pilgrims at the el tor quarantine station in sinai in . it started in in south asia, reached africa in , and is still ongoing. after more than hundred years, cholera spread to the americas in , and beginning in peru, a large epidemic hit numerous latin american countries with . million cases and more than , fatalities reported within years. out of the serogroups of v. cholerae, only o and o can cause epidemics. the serogroup o , first identified in bangladesh in , possesses the same virulence factors as o and creates a similar clinical picture. currently, the presence of o has been detected only in southeast and east asia, but it is still unclear whether v. cholerae o will extend to other regions. since , the re-emergence of cholera has been noted in parallel with the everincreasing size of vulnerable populations living in unsanitary conditions. cholera remains a global threat to public health and one of the key indicators of social development. while the disease is no longer an issue in countries where minimum hygiene standards are met, it remains a threat in almost every developing country. the number of cholera cases reported to the who during rose dramatically, reaching the level of the late s. a total of , cases were notified from countries, including , deaths, an overall increase of % compared with the number of cases reported in . this increased number of cases is the result of several major outbreaks that occurred in countries where cases had not been reported for several years such as sudan and angola. it is estimated that only a small proportion of cases -less than % -are reported. the true burden of disease is therefore grossly underestimated. the absence or the shortage of safe water and sufficient sanitation combined with a generally poor environmental status are the main causes of spread of the disease. typical at-risk areas include periurban slums where basic infrastructure is not available, as well as camps for internally displaced people or refugees where minimum requirements of clean water and sanitation are not met. however, it is important to stress that the belief that cholera epidemics are caused by dead bodies after disasters, whether natural or manmade, is false. on the other hand, the consequences of a disaster-such as disruption of water and sanitation systems or massive displacement of population to inadequate and overcrowded camps-will increase the risk of transmission. chikungunya virus, an arbovirus belonging to the alphavirus group, is transmitted by various mosquitoes. the virus was first isolated in tanzania in and since then has caused smaller epidemics in sub-saharan africa and parts of asia with low public health impact. in , the largest epidemic ever recorded started in east africa, spread to réunion and some other islands of the indian ocean, and then spread further to asia, with more than . million cases in india alone so far. characteristics of the disease are high fever and a debilitating polyarthritis, mainly of the small joints that can persist for months in some patients. now, for the first time, severe and fatal cases have been observed that may be due to certain mutations of the epidemic strain (parola et al. ) . the asian tiger mosquito aedes albopictus has proved to be an extremely effective vector in recent epidemics causing high transmission rates in big cities and leading to epidemics with high public health impact. this southeast asian mosquito species has been shipped by transport of used tires and plants harboring water contaminated with larvae to other continents and, since , ae. albopictus has successfully spread in italy and other parts of southern europe. in august , an outbreak of chikungunya fever occurred in northern italy with more than confirmed cases. the index case was a visitor from india who fell ill while visiting relatives in one of the villages and further transmission was facilitated by an abundant mosquito population during that time, as a consequence of seasonal synchronicity (rezza et al. ). ross river virus (rrv) is another arbovirus of the alphavirus group that causes an acute disease with or without fever and/or rash. most patients experience arthritis or arthralgia primarily affecting the wrist, knee, ankle, and small joints of the extremities (epidemic polyarthritis). about one-quarter of patients have rheumatic symptoms that persist for up to a year. the disease can cause incapacity and inability to work for months. it is the most common arboviral disease in australia with an average of almost , notified cases per year. rrv is transmitted by various mosquito species and circulates in a primary mosquito-mammal cycle involving kangaroos, wallabies, bats, and rodents. a human-mosquito cycle may be present in explosive outbreaks which occur irregularly during the summer months in australia and parts of oceania. heavy rainfalls as well as increasing travel and outdoor activities are considered as important factors contributing to the emergence of rrv epidemics. this flavivirus is transmitted by certain culex mosquitoes and is a leading cause of viral encephalitis in asia with , - , clinical cases reported annually. it occurs from the islands of the western pacific in the east to the pakistani border in the west, and from korea in the north to papua new guinea in the south. only in - infections will lead to encephalitis, which is, however, often severe with fatality rates of - % and with a high incidence of neurological sequelae. despite the availability of effective vaccines, je causes large epidemics and has spread to new areas during recent decades (e.g., india, sri lanka, pakistan, torres strait islands, and isolated cases in northern australia). je is particularly common in areas where flooded rice fields attract water fowl and other birds as the natural reservoir and provide abundant breeding sites for mosquitoes such as culex tritaeniorhynchus, which transmit the virus to humans. pigs act as important amplifying hosts, and therefore je distribution is very significantly linked to irrigated rice production combined with pig rearing. because of the critical role of pigs, je presence in muslim countries is low. crimean-congo virus is a bunyavirus causing an acute febrile disease often with extensive hepatitis resulting in jaundice in some cases. about one-quarter of patients present hemorrhages that can be severe. fatality rates of . - % have been reported in hospitalized patients. cchf is transmitted by hyalomma ticks to a wide range of domestic and wild animals including birds. human infection is acquired by tick bites or crushing infected ticks, and also by contact with blood or tissue from infected animals that usually do not become ill but do develop viremia. in addition, nosocomial transmission is possible and is usually related to extensive blood exposure or needle sticks. human cases have been reported from more than countries in africa, asia, southeastern europe, and the middle east. in recent years, an increase in the number of cases during tick seasons has been observed in several countries such as russia, south africa, kosovo, and greece. in turkey, where before no human cchf cases had been observed, a total of , confirmed cases, including deaths, were reported between and june . the emergence of cchf has been associated with factors such as climatic features (temperature, humidity, etc.), changes of vector population, geographical conditions, flora, wildlife, and the animal husbandry sector. rvf is a mosquito-borne bunyavirus infection occurring in many parts of sub-saharan africa. it infects primarily sheep, cattle, and goats, and is maintained in nature by transovarial transmission in floodwater aedes mosquitoes. it has been shown that infected eggs remain dormant in the dambos (i.e., depressions) of east africa and hatch after heavy rains and initiate mosquito-livestock-mosquito transmission giving rise to large epizootics. remote sensing via satellite can predict the likelihood of rvf transmission by detecting both the ecological changes associated with heavy rainfall and the depressions from which the floodwater mosquitoes emerge. transmission to humans is also possible from direct and aerosol exposure to blood and amniotic fluids of livestock. most human infections manifest themselves as uncomplicated febrile illness, but severe hemorrhagic disease, encephalitis, or retinal vasculitis is possible. in , rvf has been transported, probably by infected camels to egypt, where it caused major epidemics with several hundred thousand infections of humans. it has been suggested that introduction of rvf may be a risk to other potentially receptive areas such as parts of asia and the americas. floods occurring during the el niño phenomenon of in east africa subsequently gave rise to large epidemics and further spread to the arabian peninsula. most recent epidemics occurred in and following heavy rainfalls in kenya, somalia, and sudan, causing several hundred deaths. besides mosquito control, epidemics are best prevented by vaccination of livestock. leishmaniasis, a protozoal transmitted by sandflies, has shown a sharp increase in the number of recorded cases and spread to new endemic regions over the last decade. presently, countries are affected with an estimated million cases worldwide. there are about . million new cases of cutaneous and mucocutaneous leishmaniasis, a nonfatal but debilitating disease with % of cases occurring in afghanistan, brazil, bolivia, iran, peru, saudi arabia, and syria. the incidence of visceral leishmaniasis (vl), a disease with a high fatality rate when untreated, is estimated at around , per year. the situation is further aggravated by emerging drug resistance (table . ) and the deadly synergy of vl/hiv coinfection. epidemics usually affect the poorest part of the population and have occurred recently in bangladesh, brazil, india, nepal, and sudan. for many years, the public health impact of the leishmaniases has been grossly underestimated. they seriously hamper socioeconomic progress and epidemics have significantly delayed the implementation of numerous development programs. the spread of leishmaniasis is associated with factors favoring the vector such as deforestation, building of dams, new irrigation schemes, and climate changes, but also with urbanization, migration of nonimmune people to endemic areas, poverty, malnutrition, and the breakdown of public health. antimicrobial resistance of epidemiological relevance has emerged as a major problem in the treatment of many infectious diseases (table . ). resistance is no longer a problem that predominantly affects the chemotherapy of bacterial infections. it became increasingly important in parasitic and fungal diseases, and despite the short history of antiviral chemotherapy, it already plays a prominent role in the treatment of hiv infection and other viral diseases. resistance is also a problem in some of the emerging infections and will further complicate their treatment and control. resistance of bacterial pathogens has become a common feature in nosocomial infections, especially in the icu and in surgical wards. currently, the number one problem in most hospitals is s. aureus resistant to methicillin (mrsa, see chapter ). however, common problems of resistance also extend to other major bacterial pathogens such as enterococci, various gram-negative enteric bacilli, and pseudomonas species. resistance has developed not only to standard antibiotics (e.g., penicillins, cephalosporins, aminoglycosides, macrolides, or quinolones) but also to second-line antibiotics including carbapenems, glycopeptides, and newer quinolones. however, there is considerable geographic variation. in , the european antimicrobial resistance surveillance system (earss), a network of national surveillance systems, reported vancomycin-resistant rates among enterococci ranging from none in iceland, norway, romania, bulgaria, denmark, and hungary to % of enterococcus faecium strains in greece (earss ) . a surveillance study conducted in the united states hospitals from to showed that % of nosocomial bloodstream infections were caused by enterococci and that % of e. faecalis isolates and % of e. faecium isolates were vancomycin resistant (wisplinghof et al. ) . rates and spectrum of antibacterial resistance of e. coli and other gram-negative enteric bacilli may differ considerably from one hospital to the other. in some important pathogens of hospital-related infections such as klebsiella, enterobacter, and pseudomonas species, resistance to almost all available antimicrobials has been observed. this may complicate the choice of an effective initial chemotherapy considerably. therefore, each hospital has to monitor the epidemiological situation of resistance regularly, at least for the most important bacteria causing nosocomial infections, such as staphylococci, enterococci, gram-negative enteric bacilli, and pseudomonas. even in community-acquired infections, there has been a considerable increase in resistance problems. at present, approximately % of pneumococcal isolates in the united states are resistant to penicillin, and % exhibit intermediate resistance. the rate of resistance is lower in countries that, by tradition, are conservative in their antibiotic use (e.g., netherlands, germany) and higher in countries where use is more liberal (e.g., france). in hong kong and korea, resistance rates approach %. in addition, about one-quarter of all pneumococcal isolates in the united states are resistant to macrolides. this rate is even higher in strains highly resistant to penicillin, and increasingly there is multiresistance against other antibiotics such as cephalosporins. the prevalence of meningococci with reduced susceptibility to penicillin has been increasing, and high-level resistance has been reported in some countries (e.g., spain, united kingdom). although high-dose penicillin is effective in infections with strains of intermediate resistance, most national and international guidelines recommend broad-spectrum cephalosporins such as ceftriaxone as first-line drugs. however, in most developing countries, penicillin and chloramphenicol are the only affordable drugs. in recent years, certain strains of community-acquired s. aureus with resistance to methicillin (cmrsa) have been observed which produce a toxin (panton-valentine leukocidin) that is cytolytic to pmns, macrophages, and monocytes, and which are an emerging cause of community-acquired cases and outbreaks of necrotic lesions involving the skin or the mucosa, and in some patients also of necrotic hemorrhagic pneumonia with a high case fatality (vandenesch et al. ) . development of resistance is mainly determined by two factors: -the genetic potential of a certain pathogen, i.e., mobile elements such as plasmids, transposons, or bacteriophages, genes coding for resistance, and mutation rate. -the selection pressure caused by the therapeutic or the para-therapeutic application of antimicrobial drugs. in the hospital these factors are supported by -microbial strains that are highly adapted to this environment (e.g., rapid colonization of patients, resistance to disinfectants), -an increasing percentage of patients who are highly susceptible to infections due to old age, multimorbidity, immunosuppression, extended surgery, and invasive procedures, and -the frequent use of broad-spectrum antibiotics or combinations of antimicrobial drugs. another source of resistant bacteria has been identified in mass animal production and the use of antimicrobials as growth promoters (e.g., the glycopeptide avoparcin, the streptogramin virginiamycin) or as mass treatment in the therapy or the prevention of infections. the inadequate use of antimicrobial drugs is also an important factor responsible for the development of resistance in community-acquired infections. this is especially true in developing countries where only a limited spectrum of antibiotics is available, where shortage of drugs often leads to treatment that is underdosed or too short, and where uncontrolled sale and use of antibiotics is commonplace. as a consequence, resistance of gonococci is extremely frequent in southeast asia, and resistance of salmonella typhi, shigella, and campylobacter to standard antibiotics is common. some of the still effective second-line antibiotics have to be given parenterally or are not available because they are too costly. a typical example of the consequences of insufficient chemotherapy due to lack of compliance and/or unavailability of drugs is the alarming increase in multiresistance and extreme resistance in tb (see chapter ). resistance is also a problem in parasitic diseases such as malaria (see chapter ), leishmaniasis, or african trypanosomiasis. plasmodium falciparum developed resistance against all major antimalarial drugs as soon as they were used on a broad scale. resistance had contributed significantly to the increase in malaria-associated morbidity and mortality observed in many endemic areas (wongsichranalai et al. ) . a recent report on failures of the new artemisinin combination treatment for p. falciparum malaria at the thai-cambodian border supports fears of the development of resistance to this most promising class of drug at present (dondrop et al. ). resistance against antiviral drugs has developed almost from the beginning of antiviral chemotherapy (table . ). in the treatment of hiv infection, the risk of development of resistance has been drastically reduced by the combination of several drugs with different mechanisms of action (see chapter ). however, drug resistance remains the achilles' heel of the highly active antiretroviral therapy (haart) and may be at a considerable risk of expanding haart to the developing world. today, we have to realize that as we develop antimicrobial drugs, microbes will develop strategies of counterattack. antimicrobial resistance occurs at an alarming rate among all classes of pathogens. even in rich countries it causes real clinical problems in managing infections that were easily treatable just a few years ago. in life-threatening infections such as sepsis, nosocomial infections, or falciparum malaria, there is a substantial risk that the initial chemotherapy might not be effective. in addition, the delay caused by inadequate treatment might favor transmission to other people and support the spread of resistant pathogens (e.g., multiresistant tb). last but not the least, surveillance and control and the necessity to use expensive second-line drugs or combinations of antimicrobials are enormous cost factors. for developing countries this is a major limitation in the treatment and control of infections caused by resistant agents. so, in many ways, emerging resistance contributes to the emergence of infectious diseases. despite the availability of effective strategies for treatment and prevention, infectious diseases have remained a major cause of morbidity and mortality worldwide. however, the problems associated with infections are due to considerable changes. in industrialized countries the mortality caused by infectious diseases has decreased tremendously during more than years. however, during recent years, both mortality and morbidity associated with infections are increasing again. ironically, this is closely associated with the advances in medicine which have contributed to profound changes in the spectrum of both patients and their infections. advanced age, underlying conditions, and an altered immune response are common features in the seriously infected hospital patient today. immunosuppressive therapy is frequently used to treat neoplastic and inflammatory diseases or to prevent the rejection of transplants. some infections, most notably hiv/aids, cause immunosuppression by itself. in the compromised patient, infections are generally more severe or may be caused by opportunistic pathogens that will not harm the immunocompetent host. antimicrobial treatment is often less effective in these patients and tends to be further complicated by antimicrobial resistance which may manifest itself or develop at a higher frequency in the immunocompromised patient. an increasing percentage of infections are hospital acquired or otherwise health care associated. it is estimated that nosocomial infections affect . million patients and contribute to approximately , deaths in us hospitals annually (klevens et al. ). considering the rising number of elderly and immunocompromised patients, a further increase in severe infections can be predicted. in developing countries, the significance of infectious diseases has remained high for ages and despite the advances in medicine. until now, infections are by far the leading cause of both disability-adjusted life years and life years lost. the reasons are obvious and mostly related to poverty and lack of development causing poor and unhealthy living conditions, inadequate health systems, and lack of resources for prevention and treatment. this is, of course, just an integral part of the general socioeconomic problems of developing countries. however, poor health conditions per se are an important obstacle to development, and infections such as hiv/aids in sub-saharan africa can be a major cause of lack of development, increasing poverty, and political instability. generally, the situation of many developing countries has not improved during the last two decades, and the gap between the first and the third world has increased. however, most of the mortality and morbidity associated with infectious diseases is avoidable. as laid down in the millennium goals, a major task of the world community will be to counteract the imbalance between the industrialized and the developing countries and to find strategies to ensure participation in the progress of modern medicine for all. developing countries also carry the main burden of diseases caused by newly emerging and re-emerging infections (table . and . ) . however, the consequences of economical and political crises on emerging infectious diseases are obvious in industrialized countries also-such as the return of diphtheria or the increase in tb and multiresistant tb after the breakdown of the former soviet union. today, all countries worldwide are affected by emerging infections as well as by emerging antimicrobial resistance. in the age of globalization, travel and transport of people, animals, and goods of all kinds have increased tremendously. as a consequence, infectious agents may travel over long distances and at high speed. this is clearly evident with influenza pandemics or outbreaks such as the sars epidemic or with imported cases of viral hemorrhagic fever transmissible from person to person. the spread of antimicrobial resistance or the re-emergence of tb seems to be less spectacular, but the consequences may be at least as important in the long run. management and control of emerging and re-emerging infectious diseases can be very different from disease to disease and has to allow for all relevant factors of the populations at risk and of the specific disease including the ecology of the agent, its vectors, and reservoirs. however, some basic principles apply to all situations: -surveillance -information and communication -preemptive planning and preparedness -provision and implementation of • adequate treatment • adequate control and prevention -international cooperation active and passive surveillance systems with rapid reporting and analysis of data are essential for the early detection of outbreaks, changes in epidemiology, and other events of public health concern (see chapters and ). however, many resourcepoor countries do not have functional surveillance systems. in addition, reporting of infectious diseases may be neglected or delayed because of fears of stigma, international sanctions including trade and travel restrictions, or interference with tourism. classical examples are plague and cholera, but also recent examples such as the bse/vcjd crisis in the united kingdom or sars originating from china showed undue delays between first occurrence of cases and information to the public. although, in outbreaks of new and unknown diseases it may be difficult, or even impossible, to predict or assess the magnitude of the problem and the potential consequences, timely and adequate information and communication is not only obligatory, according to international regulations, but also the best strategy to avoid rumors, misbeliefs, panic, or disregard. in recent years, many countries have installed national plans of action for important epidemiological scenarios and outbreaks such as pandemic influenza, bioterrorism, import of viral hemorrhagic fevers transmissible from person to person, sars, and comparable diseases or outbreaks. all member states of the world health assembly that have so far not been able to install functional surveillance and/or pre-emptive planning are obliged to do so within a maximum of years after their ratification of the new international health regulations (who ) . preparedness not only means surveillance and planning but also has to include the provision of facilities to adequately treat and, if necessary, to isolate patients with infectious diseases of public health importance and relevant epidemic potential and/or at risk of transmission to other persons including health-care workers. task forces and high containment facilities for both laboratory diagnostic services and treatment of patients using barrier nursing have been set up in several countries. however, all health facilities of a certain level such as general hospitals should be prepared by their organization and structure to treat patients with infections of public health relevance such as multiresistant tb under appropriate isolation and barrier nursing conditions. this also applies to hospitals in resource-poor countries. adequate training of health-care workers and strict management have been effective to control outbreaks of highly contagious infections within rural african hospitals lacking sophisticated technical equipments (cdc ) . strategies for control and prevention may be quite different for various emerging infections. effective vaccinations are available only for some infections and are usually lacking for newly emerging infections (table . ). for the majority of emerging infections, control and prevention have to rely on information, education and exposure prophylaxis, interruption of transmission by vector control and control of reservoir hosts (e.g., rodents), and case finding with early diagnosis and treatment. for diseases and outbreaks caused by infections of public health relevance that are transmissible from person to person, containment procedures including isolation and treatment of patients under condition of barrier nursing as well as tracking and surveillance of contacts are warranted by national and international health regulations. here, international cooperation is essential to successfully contain outbreaks and epidemics such as the sars epidemic in . despite dramatic progress in their treatment and prevention, infectious diseases are still of enormous global significance with tremendous economic and political implications. emerging and re-emerging infectious diseases as well as emerging antimicrobial resistance are major challenges to all countries worldwide. for the management of current and future problems, it will be most important to counteract the imbalance between the industrialized world, new economies, and developing countries, and to adequately and timely react to new threats on a global scale. a new type of papillomavirus dna, its presence in genital cancer and in cell lines derived from genital cancer world health organization: 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hospitals: analysis of cases from a prospective nationwide surveillance study large outbreak of norovirus: the baker who should have known better epidemiology of drugresistant malaria nipah virus infection in bats (order chiroptera) in peninsular malaysia key: cord- - usagw authors: muntingh, lukas m title: africa, prisons and covid- date: - - journal: j hum rights pract doi: . /jhuman/huaa sha: doc_id: cord_uid: usagw africa’s prisons are a long-standing concern for rights defenders given the prevalence of rights abuses, overcrowding, poor conditions of detention and the extent to which the criminal justice system is used to target the poor. the paper surveys southern and east african countries within the context of covid- . between march and april covid- had spread to southern and east african countries, except lesotho. the overwhelming majority of these countries imposed general restrictions on their populations from march and nearly all restricted visits to prisons to prevent the spread of the coronavirus. the pandemic and government responses demonstrated the importance of reliable and up to date data on the prison population, and any confined population, as it became evident that such information is sorely lacking. the world health organization recommended the release of prisoners to ease congestion, a step supported by the un subcommittee on prevention of torture. however, the lack of data and the particular african context pose some questions about the desirability of such a move. the curtailment of prison visits by external persons also did away with independent oversight even in states parties to the optional protocol to the convention against torture (opcat). in the case of south africa, prison monitors were not listed in the ensuing legislation as part of essential services and thus were excluded from access to prisons. in the case of mozambique, it was funding being placed on hold by the donor community that prevented the human rights commission from visiting prisons. the covid- pandemic has highlighted long-standing systemic problems in africa’s prisons. yet african states have remained remarkably reluctant to engage in prison reform, despite the fact that poorly managed prisons pose a significant threat to general public health care. africa's prisons are a long-standing concern of human rights defenders. overcrowding, poor nutrition, illness, disease, and rights violations, to name a few concerns, characterize * the author is associate professor at the dullah omar institute, university of the western cape, south africa. he has been involved in criminal justice reform since ; his current focus is on the prevention and combating of torture and ill-treatment of prisoners and detainees. africa's prisons. the possibility that a highly infectious virus for which there is no vaccine becomes prevalent in africa's prisons is a scenario almost too disastrous to contemplate. many are familiar with the devastation that aids brought to africa's prisons and with underlying health conditions such as hiv/aids, tuberculosis (tb) and general poor nutrition, covid- does conjure up images of an unprecedented prisons health crisis, as both the infection rate (the proportion of people infected) and the infection fatality rate (the proportion of infected persons who die) may be higher in prisons than that which may occur among the general population outside prison. this essay reviews the situation regarding prisons and covid- in southern and east africa. there are many gaps in the information, which does point to long-standing issues on data reliability and accessibility. nonetheless an overview of prison numbers is provided, as well as some general comments on conditions of detention. this followed by a short description of covid- in africa and how different states have responded, imposing more or less severe restrictive measures. southern and east africa consist of internationally recognized countries and have a combined prison population of some , people. the average national prison population size for these countries is some , , with the average prison holding prisoners. there are, however, significant outliers with island states like the comoros having prisoners in three prisons and, at the other end of the spectrum, south africa with some prisons holding close on , prisoners at an average size of prisoners per facility. a further important variable is the proportion of prisoners who are awaiting trial. this is important for two main reasons. firstly, it indicates the efficiency and effectiveness of the criminal justice system, with a low percentage indicating that there is good reason for pretrial detention and that individuals do not remain in pretrial detention for an excessive time. secondly, a high percentage of pretrial detainees not only reflects inefficiency and ineffectiveness, but also results in more contact between the prison population and the outside world, because of remand prisoners' appearances in court and visits to them in prison, and this contact is relevant to the covid- discussion. in the southern and east african states surveyed, the highest proportion of pretrial detainees is found in madagascar at per cent and the lowest in rwanda at eight per cent. the average for all countries is per cent, meaning that nearly one-third of bed spaces in prisons are occupied by people presumed to be innocent. the last important variable to note is the level of occupancy. in uganda and zambia prisons are occupied at per cent and per cent respectively, meaning three people are using the space originally designed for one person. colonial-era laws as well as colonial-era modalities of policing have also shaped to some extent the profile of that segment of the population coming into (regular) contact with the criminal justice system. it is in particular in anglophone states of southern and east africa that a myriad of laws dating back to the previous century give the police wide discretion in arresting people for poorly defined offences such as loitering or being a rogue and vagabond (muntingh ; muntingh and petersen ) . these petty and outdated offences remain an affront to human dignity and perceptions of fairness, and need to be removed from statutes (achpr, principles on the decriminalisation of petty offences in africa). nonetheless, their continuous enforcement plays an important role in determining who is imprisoned. while there is much variation in the conditions of imprisonment in these countries, it can generally be concluded that there is significant room for improvement and, in some instances, prison systems are not able to meet even the most basic standards of humane detention with reference to accommodation, nutrition and health care. in some states prisoners are provided with only one meal per day of the most basic nature, resulting in malnutrition; illness and infectious diseases are common in the prison population; and prisoners are forced to sleep in cells filled to two or three times their capacity with the most rudimentary toilet facilities, and with limited capacity to maintain and keep ablution facilities sanitary. these conditions worsen health outcomes. poor conditions of detention and structural problems in african criminal justice systems are well documented and a number of efforts have been made at international and regional levels to enable, encourage and support prison and criminal justice reform. the african commission on human and peoples' rights (achpr) not only appointed two special mechanisms on the issue, but also adopted four soft law instruments to support reform. despite these efforts as well as general efforts to improve conditions of detention, the situation has not improved markedly. there are a few countries in east and southern africa that have been able to effectively maintain and replace (if not expand) prison infrastructure, such as south africa and botswana. but in most instances, the same infrastructure built by britain, portugal and france as colonial powers more than years ago remains in use and it is simply not possible to meet the minimum standards of humane detention (un standard minimum rules for the treatment of prisoners ). in many instances sentenced and unsentenced prisoners are not segregated, as is required by rule (b) of the un standard minimum rules, and this has implications for controlling infectious diseases. not only have post-independence governments largely failed to invest in criminal justice and prison reform; they have also failed to see prisons from a public health perspective and give recognition to the inescapable fact that prisons are vectors for disease. the first covid- case in africa was reported from egypt (bbc news ) and the second from algeria (who africa ). in southern and east africa, the first case was reported in south africa on march and the first prison system case (an official) was reported also in south africa on april (groundup ; graaff-reinet advertiser ). covid- came to africa through various entry points and most likely travel hubs like johannesburg and nairobi, from where it moved quickly to even the island states of the region, such as seychelles ( march the covid- pandemic and subsequent government responses again demonstrate the importance of reliable and up to date data on the prison population, and any confined population (such as police and immigration detainees). this not only concerns data on the health of prisoners, as well as more general data concerning the profile of prisoners, the reasons for their custody and so forth, but above all, if this information is available in the public domain those with an interest in prisoners' rights can make informed contributions to governments and other stakeholders. when the world health organization (who) recommended the release of prisoners to address overcrowding (who ) and this call was further supported by the un subcommittee on prevention of torture (spt) in its public advice to national preventive mechanisms (npms) (un spt : para (b)), it seemed in principle like an admirable idea, but reality demanded a more cautious approach, in africa at least. firstly, cognizance should be had for public safety and that it cannot merely be a case of opening the prison gates indiscriminately, not least because the person concerned may currently be infected. this means that there need to be clear criteria for eligibility, a confirmed and contactable address, and presumably consent from the household in which the person is intending to reside. moreover, should only deserving pretrial detainees be released or are sentenced prisoners also eligible prior to the expiry of their sentence? following from this, it must also be asked: how many people need to be released in order to have a protective impact for those that remain behind? secondly, in some instances, especially when an infection has not been recorded at a particular prison, it may in fact be a better option not to release prisoners since their basic needs are at least met in prison (this is assuming that basic nutritional and health requirements are complied with). thirdly, assuming that the preceding requirements are satisfied, the question becomes: where do released prisoners go to? they may not be welcome at their normal place of residence, or they may indeed have no place to go to, or their return may place additional socioeconomic strain on an already marginal household. with large-scale loss of income in the formal and informal sectors, and the absence of state-provided socioeconomic support, the large-scale release of prisoners may require a re-think in the african context. regardless of this, a number of southern and east african countries announced the release of prisoners to 'ease congestion', but the intended impact would be symbolic rather than real. seven countries announced significant releases with the highest number in south africa ( , ), ethiopia ( , ) and mozambique ( , ) (republic of south africa, the presidency ; ethiopian monitor a; daily nation ) and the lowest in botswana ( ). in the case of south africa, the releases would constitute per cent of the total prison population. however, in the case of ethiopia the prison system capacity is not known and the impact is thus uncertain, but the , releases constitute less than five per cent of the prison population. the , released in mozambique moved the occupancy level from per cent to per cent (world prison briefs ). with the exception of botswana, the releases effected did not move prison occupancy below the specified levels, and overcrowding remains present as ever. the releases should also be seen against the background of normal releases when prisoners are released conditionally (for example, parole) or on expiry of sentence. these figures are not in the public domain and it is therefore not known if the releases will have any meaningful and sustained impact on prison congestion. much as we would like to think that prisons are isolated from society, they are not. family and friends visiting prisoners are in many ways the lifeblood of the prison, bringing not only human interaction and contact with the outside world but also resources such as cash, food, bedding, toiletries and so forth. it is predominantly the poor who find themselves in prisons, but since the state cannot provide all the resources, prisoners are dependent on outside support (when they have such support) to make life in prison more bearable. in the end it is the poor who are subsidizing imprisonment in africa, picking up the tab where the state falls short in providing the basics to prisoners (muntingh and redpath ) . admittedly, visitors also bring contraband fuelling the carceral economy-which is often crucial for some prisoners to 'buy' their safety. contact with the outside world is vital for both physical and mental well-being. it is, however, not only prisoners' visitors who come to a prison. the staff working there as well as other officials also come to prisons on a daily basis. prisoners awaiting trial and sentenced prisoners with further charges also have to appear in court. in short, the gates of a prison are busy. this has obvious implications for virus transmission. of the countries surveyed in southern and east africa, only two could be confirmed as not having declared a state of disaster or emergency or lockdown: malawi and tanzania (new frame ). in the case of malawi, the government did declare a lockdown, but this was blocked in the high court (news ). eighteen of the states surveyed declared some form of a national restriction, such as a state of disaster or a state of emergency. this was then to a greater or lesser degree supported by a lockdown or curfew (terminology differs from one state to another). in some instances, this was announced for a very limited duration (such as days), but frequently extended. in ten states access to prisons by external visitors was prohibited (independent online b; all africa a; independent online c; ethiopian monitor b; icrc a; léger ; all africa b; icrc b) and in a further states this could not be confirmed. south sudan imposed light restrictions (that is, sign a register and wash hands) (undp south sudan ), and zambia prohibited visits but visitors could leave items for prisoners, such as food or clothing (global press journal ). while it must be appreciated that governments have an obligation to protect their citizens against public health threats, it must also be noted that the states surveyed have by and large shown a particular enthusiasm to restrict civil and political liberties and, further, to limit access to prisons. the guidelines from who made it clear that the 'covid- outbreak must not be used as a justification for objecting to external inspection of prisons and other places of detention by independent international or national bodies whose mandate is to prevent torture and other cruel, inhuman or degrading treatment or punishment' (who ). of the countries surveyed, six have ratified the optional protocol to the convention against torture (opcat) and two have signed it but not ratified. in the case of south africa, the judicial inspectorate for correctional services (jics) provides regular visits to prisons through its inspectors as well as community-based independent correctional centre visitors (iccv). however, the state of disaster declared on march and subsequent regulations ( march) closed all prisons to civilian visits (disaster management act regulations) and did not include the jics inspectors and iccvs in the definition of essential services; thus they were not permitted to conduct prison visits. the net result was that not only were visits by friends and families to prisoners stopped, but so were the visits by iccvs mandated under the correctional services act. moreover, this also prevented visits under the opcat, to which south africa is a party, since the jics forms part of the national preventive mechanism (npm), the south african human rights commission (sahrc), as designated by south africa in june . while officials of the department of correctional services (for example, prison warders) are exempted from the restrictions of the lockdown that commenced on march, the jics inspectors and iccvs are appointed under a different provision of the correctional services act resulting in them not being exempted from the lockdown. it then appears that a major victim of covid- was transparency of the prison system. south africa's neighbour, mozambique, declared a state of emergency on march (all africa c), but technically also a state of disaster in terms of a threat to public health or a natural disaster, and so which should be distinguished from martial law. the impact of restrictions imposed is less severe, and essentially, gatherings of more than people are prohibited, including in prisons. moreover, no restrictions, save for family members, are placed on who visits prisons and lawyers and the npm is free to conduct visits and even training programmes are continuing as long as groups remain under the -person ceiling (t. lorizzo, director: reformar, based in maputo, mozambique, interview with the author, may ). visits by the npm are, however, not taking place since the donors mozambique, south africa, madagascar, mauritius, rwanda and south sudan. angola and zambia. that would have supported the npm's visits to places of detention (and planning was reportedly well under way) placed all funding on hold due to the covid- pandemic. covid- has again highlighted the long-standing problems in africa's prisons, and these were noted above. as unpopular as this may sound, africa needs new prisons, not necessarily more prisons, because the basic infrastructure is so old and dilapidated that it is simply no longer possible to meet the minimum requirements of humane detention, let alone to have the capacity to deal with a health crisis. it is necessary to look beyond covid- and pose questions about long-term solutions. people should also not find themselves unnecessarily in prison and that means that reforms in law, policy and practice are needed, as has been advocated by many, including the african commission on human and peoples' rights. pretrial detention is very often the default position without any real exploration of conditional release mechanisms such as warning and bail. monetary bail is frequently set at amounts that are simply not affordable (such as equivalent to a year's income) that can only be regarded as punishing people for being poor. the statutes of many african states still contain colonial-era offences (such as rogue and vagabond) and in a more recent development, the creation of new petty offences, frequently under municipal by-laws, for which people are arrested and end up in custody. placing people in custody for petty offences is not only disproportionate, it places their health at risk and holds significant adverse socioeconomic consequences. these offences need to be decriminalized and/or declassified. prison overcrowding can to a certain measure be addressed by using non-custodial sentencing options, such as community service, or releasing prisoners prior to the expiry of sentence (for example, on parole). there are only a few african states where these measures are used on any significant scale. public health threats such as covid- or tuberculosis (tb) will always have particular significance in the prison environment, but also pose a particular threat to public health when prisons are poorly managed and resourced. in the end, the old dictum stands: good prison health is good public health. this work was supported by the open society foundation (human rights initiative) and the sigrid rausing trust. ouagadougou declaration and plan of action on accelerating prisons and penal reforms in guidelines on the conditions of arrest, police custody and pre-trial detention in africa-luanda guidelines, adopted at the th ordinary session of the achpr all africa. a. mozambique: visits to mozambican prisons suspended. march coronavirus: beijing orders -day quarantine for returnees daily nation. . virus fears: mozambique frees , inmates. april (a) and (b), published in government notice no prison commission blocks personal, legal visits over coronavirus fear now coronavirus: keeping zambia's prisoners healthy gets even harder women's prison in east london records positive cases of coronavirus covid- : call for minister to release prisoners judge shocked at the high number of deaths in sa prisons lesotho extends lockdown by two weeks, rolls out mass testing for covid- sa prisons suspend visits for days due to covid- outbreak eswatini suspends prison visits, restricts hospital visits as covid- fears mount kenya: red cross races to prevent spread of covid- to country's prisons. march b. sudan: helping prison authorities keep covid- at bay. april overcrowding and the risk of unmitigated spread of covid- in madagascar's prisons. amnesty international arrested in africa: an exploration of the issues punished for being poor: evidence and arguments for the decriminalisation and declassification of petty offences the socio-economic impact of pre-trial detention in three african countries tanzania's state response to covid- under fire malawi court indefinitely bars virus lockdown optional protocol to the convention against torture and other cruel, inhuman or degrading treatment or punishment the presidency. . placement on parole of selected categories of sentenced offenders un standard minimum rules for the treatment of prisoners (the nelson mandela rules), adopted by un general assembly resolution / undp supports prisons service of south sudan to protect inmates from covid- advice of the subcommittee on prevention of torture to states parties and national preventive mechanisms relating to the coronavirus pandemic frequently asked questions about prevention and control of covid- in prisons and other places of detention a second covid- case is confirmed in africa world prison briefs. . mozambique acknowledgements i wish to express my appreciation to t. lorizzo, j. mangwanda and j. redpath for their comments on an earlier draft of this paper. key: cord- - k vw d authors: georgiev, vassil st. title: niaid international research programs: global impact date: journal: national institute of allergy and infectious diseases, nih doi: . / - - - - _ sha: doc_id: cord_uid: k vw d niaid conducts and supports a global program of research aimed at improving diagnosis, treatment, and prevention of immunologic, allergic, and emerging infectious diseases. this research has led to new therapies, vaccines, diagnostic tests, and other technologies that have improved the health of millions of people in the united states and around the world (http://www .niaid.nih.gov/topics/globalresearch/default.htm) r tropical medicine research centers (tmrc). the tropical medicine research centers (tmrc) is a program that is intended to support foreign institutions-currently located in mali, china, colombia, and brazil-in conducting research of direct relevance to the health of the people in tropical environments and to promote collaborations and exchange of information between foreign and u.s. scientists (http://grants.nih.gov/grants/guide/ rfa-files/rfa-ai- - .html). this program was initiated in to support international centers located in disease endemic areas in conducting research in major tropical diseases. the initiative solicited applications in the areas of leishmaniasis, chagas' disease, and human african trypanosomiasis to facilitate translational research using the recently published genomes of the trypanosomatids. r international cooperative biodiversity groups program (icbg). the international cooperative biodiversity groups is a program with a threefold mission: conservation of biodiversity, economic growth for develop-ing countries (e.g., central and south america, nigeria, cameroon, madagascar, jordan, central asia, papua new guinea, laos, and vietnam), and discovery of pharmaceuticals from natural products. niaid, together with the national cancer institute (nci), national institute of mental health (nimh), national heart, lung, and blood institute (nhlbi), national institute on drug abuse (nida), fic, the national science foundation, and the usda, are the co-sponsors of icbg. the current awards are given to multidisciplinary research groups that also include in-country, research-capacity collections, and partnerships with a pharmaceutical company. the icbg program has been widely recognized as a model for research partnerships that acknowledge intellectual property ownership of indigenous communities. framework agreement between the u.s. government and the government of the republic of south africa concerning cooperation in scientific, technologic, and environmental fields, including areas of public health, was signed on december , . this agreement is still in effect. as operationally defined by who, the african region (who/afro) comprises countries. other countries in the african continent belong to another operationally defined region of who (http://www .niaid.nih.gov/ topics/globalresearch/africa/default.htm). as africa confronts the st century, it faces several challenges. some of the major challenges are in the interrelated areas of economic development and health. according to who, an estimated % of the population of africa lives below the poverty line, on less than us$ . per day. as who reports, life expectancy is only years, and people suffer from a wide range of diseases, several of which are niaid's highest priorities for research: r the majority of cases of malaria each year occur in africa, primarily in children under years of age r hiv/aids has had a more devastating effect on africa than on any other region of the world r tuberculosis (tb) is a major cause of death among people living with hiv/aids, and africa bears the brunt of the hiv-fueled tb epidemic african countries with current niaid-funded activities ( fig. additional countries where niaid is conducting and supporting research will continue to be added. however, this information is not meant to be a complete list of niaid research and niaid-sponsored activities. it is intended to serve as an overview. research focus. niaid has funded research activities in african countries, mostly in southern and eastern africa. however, niaid has also developed a major research presence in mali in west africa (http://www .niaid.nih.gov/ topics/globalresearch/africa/default.htm). hiv/aids, tb, and malaria are three of the most serious infectious diseases in africa, causing millions of deaths each year. these three diseases are a major cause of poverty through their debilitating impact on the workforce and significantly affect the economic development and stability of the region. niaid supports hiv/aids research in all of these countries, with most projects conducted in areas with the highest incidence of infection and disease, namely botswana, kenya, malawi, rwanda, south africa, zambia, and zimbabwe. the recent emergence of multidrug-resistant tb (mdr tb) and extensively drug-resistant tb (xdr tb), especially in the context of hiv/aids infection, is being addressed by niaid-funded projects conducted in south africa, tanzania, and uganda. malaria remains a major threat, and niaid conducts clinical, epidemiologic, drug, and vaccine research in east african countries such as kenya, malawi, tanzania, and uganda, and in mali, cameroon, ghana, and the gambia in central and west africa. neglected diseases such as filariasis and schistosomiasis are receiving renewed attention, with niaid projects in kenya, malawi, and south africa. diarrheal and respiratory diseases and vector-borne diseases, such as african trypanosomiasis (sleeping sickness), are also of concern. the largest niaid investment in the gambia is in malaria, particularly severe malaria in children, and methods of controlling mosquito larvae. niaid also has a program on helicobacter pylori and two programs on hiv/aids. a major program on a phase iii pneumococcal conjugate vaccine study in basse, the gambia, involved collaboration among niaid, the british medical research council (mrc), wyeth pharmaceuticals, who, the program for appropriate technology in health (path), and the united states agency for international development (usaid). this study was successfully completed in and has provided data to show that serious infections and deaths can be prevented by the incorporation of a pneumococcal conjugate vaccine into the local expanded program on immunization (epi) (http://www .niaid.nih.gov/research/topics/bacterial/ clinical/gambiapneumococcalvaccinetrial.htm). the mrc facility has offered the u.s. researchers the opportunity to undertake human clinical vaccine trials that comply fully with fda regulations. among these trials were a phase ii pneumococcal vaccine trial and a malaria vaccine involving the u.s. department of defense. vector-borne diseases, including dengue, crimean-congo hemorrhagic fever, and yellow fever, remain endemic. water-borne diseases include bacterial and protozoal diarrhea, hepatitis a, and typhoid fever. selected current and recent niaid-funded research (non-hiv/aids). the following information is not necessarily a complete list of niaid research and niaid-sponsored activities. it is intended to serve as an overview. kenya is a major site of niaid funding, with recently funded activities. the heaviest investments are in hiv/aids, malaria, schistosomiasis, and vector studies. there are opportunities for further research in tb (especially in the context of hiv/aids) and vector-borne diseases, especially rift valley fever (rvf), a serious zoonosis (a disease that primarily affects animals, but occasionally causes disease in humans) (http://www .niaid.nih.gov/topics/globalresearch/ africa/kenya.htm). according to who data, child mortality remains high in the country. kenya has a high risk of food-and waterborne diseases, particularly bacterial and protozoal diarrhea, hepatitis a, schistosomiasis, and typhoid fever. malaria is endemic in many areas, especially around lake victoria, and vector-borne diseases in general remain a threat, particularly rvf. hiv/aids prevalence is . % and, according to who, the incidence of tb is high. the appearance of mdr tb and emergence of xdr tb are potential threats. kenya reported two cases of polio in , although it is not regarded as a highly endemic country. selected current and recent niaid-funded research (non-hiv/aids). the following information is not necessarily a complete list of niaid research and niaid-sponsored activities. it is intended to serve as an overview. mali's climate is highly stratified: hot and arid in the north and wetter and more humid in the south. this affects vectorborne diseases such as malaria. food-and water-borne diseases, particularly associated with the niger river, include bacterial and protozoal diarrhea, hepatitis a, typhoid fever, and schistosomiasis. selected current and recent niaid-funded research (non-hiv/aids). the following information is not necessarily a complete list of niaid research and niaid-sponsored activities. it is intended to serve as an overview. mozambique suffers from high infant mortality, an expanding hiv/aids epidemic, malaria (plasmodium falciparum) as the primary cause of mortality among children under years of age, and recent severe outbreaks of cholera. extensive malnutrition among children and an increasing burden of tb, according to who, are also of concern (http://www .niaid.nih.gov/topics/globalresearch/ africa/mozambique.htm). all of niaid's current funding in rwanda involves hiv/aids-the adult prevalence rate in rwanda is approximately %. however, malaria is a major problem and probably contributes to the country's high infant mortality rate (who). there was a regional outbreak of meningococcus that caused as many as cases in , leading to a mass immunization program. as in many other countries in this region, water-borne diseases, such as bacterial diarrhea, hepatitis a, and typhoid fever, are prevalent. in addition, tb is a problem (who) that has remained steady over several years, with emerging mdr tb. immunization rates are generally low. currently, niaid is funding more than projects in south africa, most of them involving hiv/aids research. however, the institute is also supporting research on tb, malaria, and other diseases or vectors. these projects focus primarily on treatment and pathogenesis. niaid also supports some prevention and epidemiology studies in these areas and provides direct funding to seven institutions in south africa involving projects (http://www .niaid.nih.gov/ topics/globalresearch/africa/southafrica.htm). the incidence of tb in south africa is high, according to who. the recent emergence of mdr tb, and now xdr tb, is a major and urgent new challenge. better surveillance for drug resistance is urgently needed to determine the level and extent of mdr and xdr tb, especially in relation to hiv status. hiv-associated infections such as cryptococcus neoformans are increasingly found. drug-resistant staphylococcus aureus is a major health problem. there has been a rapid resurgence of chloroquine-resistant malaria strains, and schistosomiasis is endemic in rivers in eastern south africa. crimean-congo hemorrhagic fever is also endemic. despite a low life expectancy at birth (who), diseases such as diabetes mellitus and obesity are expected to increase significantly. selected current and recent niaid-funded research (non-hiv/aids). the following information is not nec-essarily a complete list of niaid research and niaidsponsored activities. it is intended to serve as an overview. the niaid influenza research effort covers the spectrum from basic research to clinical trials, leading to the discovery and implementation of influenza vaccines, therapeutics, and diagnostics. like research on other diseases, influenza research progress hinges upon collaboration and shared resources (http://www.usminstitute.org/spotlight .html). seasonal influenza is a fairly predictable annual occurrence. who estimates that influenza epidemics result in , to , deaths globally per year. in contrast, the impact of pandemic influenza, an unpredictable but historically proven threat, can range from fairly mild ( ) to catastrophic ( ) . an influenza virus that causes illness in humans, to which the majority of the human population has little or no immunity, and that is easily transmissible among humans, constitutes a pandemic virus. of the existing potential pandemic viruses, the highly pathogenic avian influenza (hpai) h n virus that has become endemic in poultry in southeast asia, eastern europe, and several countries in africa presents a source of concern to scientists and health officials around the world. not surprisingly, seasonal influenza preparedness and prevention are inherently linked to pandemic influenza preparedness and prevention. both seasonal influenza research and pandemic influenza research depend on collaboration, especially at the international level. niaid participates in several international influenza research efforts regarding pandemic preparedness. several international partners identified the need for a clinical research network focused on therapeutics. thus, in the niaid division of clinical research, with multilateral partners, established the southeast asia (sea) influenza clinical research network to advance the scientific knowledge and management of human influenza through integrated, collaborative clinical research. partners include hospitals and institutions in vietnam, indonesia, thailand, the united kingdom, and the united states. the network is committed to building independent research capacity within the sea countries involved. niaid and the wellcome trust provide financial support. initial clinical studies will evaluate appropriate dosage levels of the influenza antiviral drug oseltamivir in patients with severe seasonal or avian influenza. pharmacokinetics studies of oseltamivir in asian subjects began in autumn at the network pharmacokinetics unit at mahidol university in thailand. niaid research on sars. niaid maintains a longstanding commitment to conducting and supporting research on emerging infectious diseases, such as sars, with the goal of improving global health. in carrying out its global health research mission, the institute is supporting sars research, including intramural and extramural research and collaborations with international agencies and organizations, to rapidly initiate the development of diagnostics, therapeutics, and vaccines against sars. through a grant supplement to the chinese center of disease control (china cdc) and their collaborators, niaid has funded three different sars projects. approaches undertaken include: r developing immune correlates of protection through study of pediatric and adult serum, stool, and cellular clinical samples obtained longitudinally from sars patients r developing a panel of human sars-associated coronavirus (sars-cov) antisera that can be used to standardize diagnostic assays. this project will be a collaboration with fda and cdc r attempting to identify animal reservoirs of sars-cov through surveillance of live animal markets. niaid has assembled a multidisciplinary working group to develop a broad-based program that addresses the research needed to combat sars. key niaid intramural laboratories have begun to pursue a range of research strategies to develop a sars vaccine as well as therapeutics, including immunebased therapies, and the institute extramural programs are poised to help as well. niaid has also initiated and expanded collaborations with other federal agencies, academia, and private industry. in addition, niaid has released "sources sought" announcements, a special mechanism to rapidly identify contractors who can develop treatment strategies, vaccines, and antibody preparations to address sars (http://energycommerce.house.gov/reparchives/ / hearings/ hearing /fauci print.htm). niaid has purchased several hundred sars microarrays-essentially a reference strain of the sars coronavirus embedded in a quartz chip-and distributed the arrays at no cost to qualified researchers worldwide (http://findarticles.com/p/articles/mi pnih/is / ai ). seroprevalence studies. as part of the international avian influenza effort, niaid has funded several seroprevalence studies in southeast asia. a study of close contacts of infected individuals is being conducted by the china cdc. a case-control study of infected individuals is also planned to examine risks associated with infection. basic research on the cross-reactivity of immune responses to the influenza h n strain is also being carried out at the chinese academy of medical science. bird isolates will be evaluated at the chinese academy of science. in addition, a population-based seroprevalence study will be conducted in three provinces of vietnam. this study will be coordinated by the national institute of hygiene and epidemiology in collaboration with the afrims laboratory in thailand. enteric diseases. niaid has established an interagency agreement with the u.s. department of defense to support the afrims (armed forces research institute of medical sciences) site in thailand to develop a non-human primate model of shigellosis and to conduct clinical trials of vaccines against shigellosis and other enteric pathogens. r product development public-private partnerships (pdppps). in , a new initiative was announced by niaid that calls attention to the vital role played by pdppps in developing new products directed against the neglected tropical diseases. niaid is seeking to provide support to pdppps that have diagnostic or therapeutic products requiring additional targeted funding in order to complete the preclinical phase of development and enable an investigational new drug (ind) or investigational device exemption (ide) to be submitted for transition to clinical development. r the global alliance for tb drug development (gatb). gatb is a nonprofit organization involving many public and private partners, which is contributing to the development of new drugs to shorten or simplify the treatment of tb and facilitate tb control in high-burden countries. more than organizations are stakeholders in this public-private partnership, including the bill & melinda gates foundation, cdc, niaid/nih, the rockefeller foundation, usaid, the world bank, and who (http://www.tballiance.org/). of niaid. the niaid research conference also featured plenary lectures delivered by distinguished scientists, roundtable discussions on a wide variety of topics, and poster sessions open to all participants ( ) . prior to the conference (june - , ) , a satellite symposium was held on "grants opportunities and preparation" (grantsmanship, technology transfer, regulatory affairs, and fda regulations with concurrent workshops) and on training opportunities at nih by the fogarty international center. the training courses were conducted by staff members from the division of extramural activities at niaid and the nih offices of technology transfer and regulatory affairs ( ). about participants from countries in europe, asia, and north america have attended the niaid research conference. as a direct result of the conference, new collaborations in biomedical research were established by u.s. and foreign scientists. japan workshops in medical mycology: past, present and future r to enhance dialogue between niaid-funded scientists working on malaria and the implementing organizations of the president's malaria initiative (pmi), niaid convened a -day meeting in kampala, uganda this niaid-sponsored initiative addresses the interdependent issues of biodiversity conservation, economic capacity, and human health through discovery and development of therapeutic agents for diseases of importance in developing countries, as well as those of importance in developed countries. five comprehensive awards and seven planning grants were announced (http://www.nih.gov/news/pr/dec /fic- .htm). areas of research include discovery of natural products for treatment of hiv, tb, malaria, and other tropical diseases, with screening of extracts from uzbekistan, kyrgyzstan, papua new guinea, laos, vietnam, panama, jordan, and costa rica. two additional comprehensive awards co-funded by niaid were awarded in (http://www.nih.gov/news/pr/jan /fic- .htm) from the planning grants. r niaid research conference. as part of its mission to reduce the burden of human disease, nih-and niaid in particular-has committed to encouraging the accelerated translation of biomedical discoveries into new treatments outside the united states. one direction for niaid has been to broaden research opportunities and collaborations with scientists and research and educational institutions in europe and in particular of countries from central and eastern europe, the baltics, russia, ukraine, and other newly independent states of the former soviet union. to this end, the office of global research at niaid took the initiative to organize the niaid research conference in opatija, croatia (june - , ) (http://www .niaid.nih.gov/program/croatia).the scientific program of the conference covered a wide range of sessions by invited speakers on topics reflecting the broad scope of scientific activities key: cord- -p mbiq z authors: dawson, simon title: bushmeat date: - - journal: food ethics education doi: . / - - - - _ sha: doc_id: cord_uid: p mbiq z since homo erectus, an ancient ancestor of the modern human, was discovered to have evolved from africa million years ago, animals have been hunted for their skin and meat . animal meat is a nutritious, a convenient, and an easily accessible source of protein in the diet. however, over the turn of the last century, a sharp increase in widespread human populations, clusters of extreme poverty in areas surrounded by wildlife, and highly profitable trade revenues have exploited bushmeat at an unprecedented level. it is at a point now whereby some species are on the brink of extinction, and others will follow suit unless a drastic change occurs. this case study will focus on the ethical demand for bushmeat, focusing on the uk and european markets, and zoonotic diseases that have caused a major threat to the existence of human and animals alike. to obtain bushmeat species native to their homeland. to make matters worse, the increased wealth of consumers means traders are willing to go to extreme lengths in order to export/import bushmeat due to the financial incentives available. therefore, even the more resilient species may end up endangered, in order to supply this evergrowing demand (chaber et al. ) . the photograph ( fig. . ) below shows the remains of a giraffe slaughtered for bushmeat by two poachers, both of which were arrested (big life foundation ) . tracker dogs are often used by bushrangers to hunt for traps, injured and dead animals, and poachers. figure . is a photograph of the remains of wild animals loaded onto a truck, including a zebra caught in snares from poachers (big life foundation ) . there are many concerns regarding bushmeat consumption including eradication of species (john et al. ) , poor hygiene (federal department of home affairs, ), inhumane slaughtering (humane society international ), and spread of tropical diseases (fdha ; subramanian ; greger ) . bushmeat is predominantly obtained from areas of extreme poverty including africa, parts of south america, and asia. data provided by the world bank ( ) shows that in , of the top poorest countries in the world, of these are in africa. within these countries, moral principles governing the activities of a person and their behavior are lost in the need for survival. as a comparison, of the richest countries in the world are in europe (world bank ). criminal gangs have exploited the desperate need for survival by persuading natives in abject poverty to hunt wildlife for trade. endangered species are seen as being premium catches, procuring much higher markup prices; therefore natives receive incentives for obtaining these, even though this is completely illegal (file on ). a zoonotic disease is one that is transferrable between animal and human host. these can be caused by any microorganism, including bacteria, parasites, viruses, fungi, and prions. some of the most lethal diseases known to man have been the result of transference from animal to human, including anthrax, ebola, and variant creutzfeldt-jakob disease (vcjd). non-domesticated animal species have an intricate role in the spread of endemic and emerging zoonotic diseases throughout the world. since the turn of this century, international travel and migration, human encroachment and habitat expansion, and trade of live/dead animals have significantly increased (travis et al. ) . endemic and emerging tropic diseases have also followed suit. over the last years, the media has headlined emerging diseases such as severe acute respiratory syndrome (sars), ebola virus disease (evd), human immunodeficiency virus (hiv), and monkeypox, all of which originated from wild animals (doyle ; malone ; bbc news ). table . presents zoonotic diseases originated from wild animals, which have spread to humans through zoonosis. the microorganisms responsible for these diseases are not particularly heat resistant; therefore, thorough cooking is typically enough to destroy all of these. however, poor personal hygiene, cross-contamination during preparation, cuts, and exposed wounds are known routes that have allowed human infection. the handling and preparation of infected wildlife is therefore one of the critical transmission routes that must be carefully controlled. table . highlights examples of highly resistant diseases originated from wild animals, including those associated with bushmeat. the bacillus anthracis spores, responsible for anthrax disease, are resistant to sterilization temperatures, drying, and many disinfectants. these spores can easily be spread by release in the air, which is why the us military has viewed it as potential biological terrorism threat (inglesby ; fda ) . poisoning is widely used in many parts of africa as a means of killing wild animals. the chemicals are cheap, easily accessible, silent, and very effective (ogada ) . although illegal, they are often used to kill large carnivores such as lions, hyenas, and jackals as revenge attacks for killing farm animals. poisons are also used to kill wild animals for bushmeat. in - , samples of bushmeat were taken and analyzed by scientific officers of the ghana standards board. they found that % of samples contained chemical poisoning; all of which originated from locally sourced ingredients including residues of organochlorine, organophosphorus, and carbonates common in agricultural pesticides (fao ) . further to this, conservation international ghana found chemical poisoning to be the second most popular method of hunting in ghana (opare-ankrah ). during a case study in , involving traders and hunters from the mfantseman district in ghana, traders were asked about the severity to human health from the use of chemical poisons (opare-ankrah ). a general consensus was that no trader would buy or sell bushmeat that was believed to have been killed by poison. one trader stated that, "people will not buy from me anymore if… get sick when they eat from here so i have to make sure the meat is good" (opare-ankrah ). this is easier said than done though as animals brought in for sale by hunters are often shot after being poisoned to prevent suspicion. due to the covert nature of the business and the extent of illegal international trade, it is impossible to give a true estimation of global bushmeat distribution (smith et al. ) . what is known though is that almost three-quarters of emerging diseases are of zoonotic origin, predominantly due to contact with non-domesticated animal species (federal department of home affairs ; falk et al. ) . the parliamentary office of science and technology ( ) estimated that between and . million tons are harvested annually from africa alone. this includes approximately million bay duiker antelopes (cephalophus dorsalis) and over million red colobus monkeys (procolobus badius). meat, milk, and their products are banned from entering the european union (eu) from non-eu countries, even if imported in small quantities for personal consumption (ec regulation / ). there are certain exceptions to this; however, with countries endemic with diseases such as foot and mouth disease (fmd) including africa, the middle east, and parts of south america (fao ), the law is strict. in addition to this, many wild animals are regulated under the convention on international trade in endangered species of wild fauna and flora (cites) (cites a), an agreement which has been accepted throughout europe (cites b). inglesby et al. ( ) , fda ( ) and zumla et al. ( ) in spite of the abovementioned regulations and widespread media coverage relating to bushmeat, thousands of tons are illegally imported in to europe every year (chaber et al. ) . in france, for example, it is estimated that approximately tons of bushmeat are smuggled from africa through paris roissy charles de gaulle airport every week in personal luggage (fdha ) . of this, a third is estimated as being protected under cites (fdha ). it can be almost impossible to identify all meat products without dna testing due to the similarity in appearance of meat cuts, especially if bones, skin, or hair is removed (food inspectors ); therefore, this figure may be much higher. in november , two shopkeepers were caught trading bushmeat from their store in ridley road market in dalston, east london (vasagar a ). an environmental health officer, on a routine store visit, noticed a sign advertising bushmeat for sale (file on ). the price list contained cites listed endangered species including tiger (panthera tigris) and gorilla (gorilla gorilla), both of which are illegal to hunt worldwide (cites ). mobalaji osakuade and his partner rosemary kinnare told an undercover environmental health officer that they could get anything they wanted providing they were willing to pay for it. this includes whole lions at £ , lion and tiger heads at £ , and antelopes, goats, cane rats, porcupines, and live giant snails. the couple had also been smuggling illegal snakes and lizards, traditionally used within traditional african medicines. each was given jail sentences of months (vasagar a; vasagar b) . in december , dr. yunes teinaz, an environmental health officer for london borough of hackney, began an investigation into a shop in kejetia mini market on west green road, london (pointing and teinaz ) . during a routine inspection, dr. teinaz discovered meat products being prepared and sold in squalid, unhygienic, pest-infested conditions. the kitchen preparation area was so bad that an emergency prohibition notice was issued due to an imminent risk of injury to human health (pointing and teinaz ) . figures . , . , and . were taken by dr. teinaz during the inspection for evidence in court. the store was closed down and unable to reopen until substantial improvements warranted re-inspection and approval. however, paulina owusu pepra, the store owner, and her partner had reopened without approval. on nd october , dr. teinaz returned with police and found meat products again being prepared and sold in similar unhygienic conditions (pointing and teinaz ) . police officers seized over tons of rotten bushmeat including cane rat, giant snails that were decomposing in their own feces, pigs' feet, and a range of unidentified smoked meat, some with skin still attached. the owner, paulina owusu pepra, appeared in court in december and was given a -month prison sentence and lifetime ban for preparing food for sale. her husband, believed to have fled the country before sentencing, has not been found (pointing and teinaz ) . in , the british broadcasting corporation (bbc) launched a program on bbc radio about the potential illegal bushmeat trade in london markets (file on , ) . in the radio report, a senior environmental health officer stated "we have found it [bushmeat] on sale to some extent or another in almost every west african shop in the area [hackney] . we were finding forty, fifty kilos at a premises at a time. you could go back a month later and see exactly the same amount again. it's huge business." (file on ) in , the bbc received reports that shops in ridley road market, london, were being used as distribution points for illegal meat (bbc news ; lynn ) . undercover reporters, with hidden video cameras, were sent in to investigate further. during the report, dr. yunes teinaz stated "this is providing meat in to the human food chain which can carry infectious diseases. the people who are arranging this illicit trade are very dangerous. they only observe financial gains" (bbc news ). the undercover reporters enter a few shops, and after discussions with some butchers, one states "you tell me one day before, then you can have it ok? i can't keep it here too much. don't tell anyone… otherwise there will be trouble you know" (bbc news ). two years later, a uk television documentary, the food inspectors, conducted a follow-up investigation in to london markets looking for illegal meat (food inspectors ). in one video, a butcher, who sells a reporter bushmeat, tells the under reporter how it enters the country. he states "it's coming under the table. special. africa, france, coming dover under… underground" (food inspectors ). within the uk, the products of animal origin (third country imports) (england) regulations , as amended by the products of animal origin (third country imports) (england) (amendment) regulations , prohibits the importation and sale of any meats outside of the european union. however, with the strict regulations, government inspections, heavy fines, and potential jail sentences, this has not deterred the demand for this product. it is expected that in extreme poverty-stricken areas, such as parts of africa, south america, and asia, bushmeat consumption is a necessity. if wildlife is slaughtered only for these groups of people, and endangered species are left alone, this would become a sustainable option for the future. however, the majority of the world including the uk and europe do not fall within this poverty-stricken category. is bushmeat therefore essential to people living within these countries? no. are ethical considerations made when bushmeat is illegally imported, sold, and consumed? probably not. therefore, before the endangered become extinct, we need to decide on how to act for the future. instead of buying products that remind us of where we have come from, should we not be thinking more ethically and buy products that allow us to sustain for the future before it is too late? one approach to using this case study would be to have the students read the case and then pose the following questions to them: • how does this case encompass food ethics? • what do you think drives bushmeat consumption? • what are the risks involving bushmeat? [think ethics as well as safety] • what could been done to control/reduce bushmeat consumption? • what would you recommend going forward, and why? an alternative approach, instead of posing questions as above, would be to set students in to groups and have them role-play the part of the people involved in this case. using this method will both actively engage students and allow them to understand the viewpoints of the case characters. excursion up the river of cameroons and to the bay of amboises the african bushmeat trade -a recipe for extinction. fauna and flora international photos from big life kenya the scale of illegal meat importation from africa to europe via paris index of cites species. unep world conservation monitoring centre, cambridge doyle m ( ) the hunters breaking an ebola ban on bushmeat illegal import of bushmeat and other meat products into switzerland on commercial passenger flights food and agricultural organisation (fao) ( ) foot-and-mouth disease: frequently asked questions. fao/oie global conference on foot and mouth disease control the human/animal interface: emergence and resurgence of zoonotic infectious diseases get the facts about the wildlife trade anthrax as a biological weapon: medical and public health management international organization for migration (iom) ( ) guide to enhancing migration data in west and central africa bushmeat and food security in the congo basin: linkages between wildlife and people's future cane rat meat 'sold to public' in ridley road market secret-trade-monkey-meat-unleash-ebola-uk-how-appetite-african-delicacies-britishmarkets-stalls-spread-killer-virus.html national science foundation ( ) human disease leptospirosis identified in new species, the banded mongoose the power of poison: pesticide poisoning of africa's wildlife the bushmeat trade, livelihood securities and alternative wildlife resources. in: a case study of mankessim and its environs in the mfantseman district (ghana) bushmeat postnote: the bushmeat trade halal meat and food crime in the uk [presentation]. international halal food seminar, islamic university college of malaysia red list ( a) diceros bicornis gorilla gorilla equus africanus the spread of pathogens through trade in wildlife. scientific and technical review of the office international des epizooties zoonotic viruses associated with illegally imported wildlife products zoonotic disease risk and the bushmeat trade: assessing awareness among hunters and traders in sierra leone generation : africa. division of data, research and policy monkey meat dealers guilty of smuggling current concepts: tuberculosis. review article we would like to thank nick brandt and big life foundation for allowing us to use their photographs (figs. . and . ). we would also like to thank dr. yunes teinaz and, london barrister, john pointing for their assistance in sect. . bushmeat cases in the uk and for permission to use their photographs (figs. . , . and . key: cord- -ue azoyf authors: hardon, anita; desclaux, alice; egrot, marc; simon, emmanuelle; micollier, evelyne; kyakuwa, margaret title: alternative medicines for aids in resource-poor settings: insights from exploratory anthropological studies in asia and africa date: - - journal: j ethnobiol ethnomed doi: . / - - - sha: doc_id: cord_uid: ue azoyf the emergence of alternative medicines for aids in asia and africa was discussed at a satellite symposium and the parallel session on alternative and traditional treatments of the aidsimpact meeting, held in marseille, in july . these medicines are heterogeneous, both in their presentation and in their geographic and cultural origin. the sessions focused on the role of these medications in selected resource poor settings in africa and asia now that access to anti-retroviral therapy is increasing. the aims of the sessions were to ( ) identify the actors involved in the diffusion of these alternative medicines for hiv/aids, ( ) explore uses and forms, and the way these medicines are given legitimacy, ( ) reflect on underlying processes of globalisation and cultural differentiation, and ( ) define priority questions for future research in this area. this article presents the insights generated at the meeting, illustrated with some findings from the case studies (uganda, senegal, benin, burkina faso, china and indonesia) that were presented. these case studies reveal the wide range of actors who are involved in the marketing and supply of alternative medicines. regulatory mechanisms are weak. the efficacy claims of alternative medicines often reinforce a biomedical paradigm for hiv/aids, and fit with a healthy living ideology promoted by aids care programs and support groups. the aidsimpact session concluded that more interdisciplinary research is needed on the experience of people living with hiv/aids with these alternative medicines, and on the ways in which these products interact (or not) with anti-retroviral therapy at pharmacological as well as psychosocial levels. a large number of new treatments offered to people living with hiv/aids (plwa) have appeared over the last fifteen years in the therapeutic domain of aids. these med-icines are particularly heterogeneous, both in their presentation and in their geographic and cultural origin. they constitute a group of products with a therapeutic aim that occupies a space between the customary traditional, popular and biomedical sectors of health care [ ] . these products often mix reference to biomedicine and science with notions of traditional health culture and nature in a syncretic way. they consist mainly of herbs and nutritional substances and are packaged as 'modern' pharmaceuticals: capsules, tablets, and solutions. the names of these alternative treatments reflect their reference to biomedicine: immunocomplex, viralgic, virjint, etc. their accompanying leaflets provide detailed information on substance, as well as dosage, indications, and biomedical efficacy claims. their diffusion follows contemporary paths in the global economy and makes use of new information technologies. in this paper, we will use the term "alternative" to consider a generic category including medicines that recently appeared for aids which have not been authorised by drug regulatory authorities, nor recommended by who. other terms, such as neo-traditional or neo-phytotherapeutic, may be discussed for the characterization of some of these treatments, related to their local meanings or their social status. the emergence of alternative medicines for aids in asia and africa was discussed at a satellite symposium and the parallel session on alternative and traditional treatments of the aidsimpact meeting, held in marseille, in july . we were especially interested in the role of these medications since the introduction and rapid scale-up of highly active anti-retroviral therapy (haart) in resource poor settings. twenty anthropologists and health researchers attended the satellite session and presented exploratory findings from asia and africa (uganda, senegal, benin, burkina faso, china and indonesia). the aims of the satellite, the results of which were presented at the parallel session [ ] , were to ( ) identify the actors involved in the diffusion of these alternative medicines for hiv/aids, ( ) explore uses and forms of these medicines, and the way they are given legitimacy, ( ) reflect on underlying processes of globalisation and cultural differentiation, and ( ) define priority questions for future research in this area. we present here the insights generated at the meeting, illustrated with some findings from the studies that were discussed. there has been an increased professionalisation and commercialisation of traditional medicine in response to the development of biomedicine. this trend is not specific to aids and not necessarily a recent development. social scientists first noted this trend in the late s: charles leslie [ ] for example has shown how, in india, in response to an increased authority of biomedicine and the globalisation of health markets, unani and ayurvedic medicine production changed; and afdhal and welsch [ ] described the rise of 'modern' jamu in indonesia. jamu is the traditional term for indonesian indigenous medicines usually prepared from herbal medicines such as leaves, bark, roots and flowers. nowadays a multimillion dollar industry is involved in the production of ayurvedic and unani medicines in india, and of jamu in indonesia. a rapidly expanding assortment of powders, creams, pills, capsules and cosmetics has been manufactured both in small cottage industries as in large factories with increasingly sophisticated technologies [ , ] . the modernization of the manufacturing of these drugs has been accompanied with more modern biomedical modes of presenting their efficacy [ ] . under globalization, similar trends occurred in other regions and these products diffused more rapidly. at the seminars in marseille, we discussed the ways in which such alternative remedies operate in the therapeutic domain of aids care. in the first decade of the aids epidemic there was no effective treatment for hiv/aids and patients were faced with nearly certain premature death. at that time, there were regular hypes offering hope for life. but with the introduction of art, alternative treatments are now marketed for many additional purposes too: to prevent aids, to kill viruses, to delay the need for art, to restore and enhance health while on art, to treat opportunistic infections, and to alleviate adverse side effects of other treatments. biomedical practitioners generally discourage the use of alternative medicines, fearing interactions with art and also through the concern that patients may stop using art. at the aidsimpact sessions egrot and colleagues [ ] presented findings on the supply of what they label "neo-traditional medicines" to refer to the boundary-crossing nature of these treatments in west africa. the "designers" of the inventoried products are extremely heterogeneous. in some cases these people are nationals of african countries who present themselves as healers. some say they have undertaken "research" on the basis of therapeutic products that were already known locally. others refer to a dream revelation (classic in the universe of healers in africa) of a plant composition that is "efficacious" against aids, while yet others speak of a divine revelation. physicians, scientists and academics are solicitated, brought into involvement or spontaneously engage themselves in the exploitation of neo-traditional products. the case studies in west africa show that other treatments, such as immunicomplex or aloe vera, originate in europe and the usa. alternative medicines from europe and the usa occupy the same shelves in ordinary pharmacies as those originating from africa and china, often along with a few 'immune-boosting' food products (honey, olive oil). specialized "bio", "natural health" and "health food" shops make these products available to the more affluent. the distributors and marketing men of these products also target health workers and clinics directly. the west africa case studies noted that health workers also have started to prescribe alternative products such as immuboost (nhi t) or viralgic (pharma concept) (see figure ) . a case study from uganda showed how health workers operating an anti-retroviral treatment program adopted a locally available traditional ointment as an alternative medication for skins problems of people living with hiv and aids. the skin problems result from adverse effects of art or symptoms of opportunistic infections. the health workers obtained the recipe from local traditional healers (patients had told them that the cream works well), and the patients help collect the ingredients. they 'repackage' this traditional remedy into what is now called 'mobile cream' (to make clear it is produced by the so called 'mobile' art program). one of the nurses reports: "the mobile cream, which we ourselves prepare either at our chief nurse's home or here at the office depending on how busy we are at the office, is very efficacious for many kinds of skin related conditions. we are quick to prescribe it to the patients because we know it works and it is popular among patients too because it works for them [ ] ." content analysis of drug information leaflets, advertisements, product catalogues, and brochures distributed by medical representatives in the west africa case studies [ , ] casts light on the range of effects that are attributed to these drugs. most commonly cited (biomedical) properties are immune-stimulation and antioxidant. some manufacturers suggest that the products have antiviral properties as well. the antiviral dimension refers either to the opportunistic infections such as herpes (mentioned for example in the product information for immuboost) or eventually to the immunodeficiency syndrome itself. indeed, some products boldly claim anti-hiv activity as well, and are marketed as natural art (see figure ). however, such efficacy claims are not static. the producer of virusinest (nesto-pharma) recently withdrew the antiviral claim, stating in its information leaflet: "the analyses carried out among patients do not allow the anti-hiv assertion to be upheld". there may be also inconsistencies between various information sources. the brochure for viralgic (pharma concept) says that this is a product which renders the virus undetectable, but the website of the manufacturer presents the drug as immunostimulant (result of trials published on the web site), and present the product as treatment for opportunistic infections: "antiherpes...for healthy persons". a case study on indonesia [ ] dealt with the demand for alternative medicines among plwa. as afdhal and welsch noted two decades ago, indonesia has a thriving market for jamu. jamu are sold for a wide range of indications: common colds, influenza, headaches, aches and pains, high blood pressure, beauty, improvements in sexual performance, and recently to treat and prevent hivrelated health problems. aids prevalence is below % (i.e. this is a low prevalence area), but the disease is stigmatised, because of its association with intravenous drug use and prostitution. hardon and her colleagues conducted interviews with women and men who live with hiv and use anti-retroviral therapy, mainly intravenous drug users and their partners. all of them had better health since taking these modern drugs. nonetheless, all of them see the need to take jamu as well. they do so in tobacoak's, west africa part out of their intention to live positively (i.e. eating and sleeping well, and keeping a positive outlook on life), as promoted by many of the support groups in which plwa participate. the respondents do not make distinctions between modern medicines and jamu in these health maintenance and restoring practices. rather they distinguish the drugs by their effects. they use popular jamu to treat side effects of haart, such as itchiness. these jamus are not specifically promoted for hiv and aids in indonesia, perhaps partly because the disease is so stigmatised. however one neo-traditional preparation stood out in the narratives of our respondents as a product which can treat hiv/aids: virgin coconut oil. ceri, for example, started using coconut oil shortly after she found out she was hivpositive. she says: actually, the effect is not only for your immune system. so, i feel better, don't feel tired, and have more energy. i think what influences most is self-suggestion. it's self-suggestion that matters... mia (a year old woman from jakarta) was given virgin coconut oil by a friend from yogjakarta: i got boxes. a box contains capsules. it took it every day until i felt sick, but there was no effect. my cd level did not increase. three months, three months made me look like a coconut you just needed to squeeze (laughing). i became very oily. the good effect when you take vco is that your skin is silk smooth, your face is fairer and if you take a shower, you don't need any lotion, because your skin is naturally oily. that is the positive effect. your hair is also stronger. but buli, a -year-old ex-drug user from karawang, one of the most active members of the support group in karawang says: in indonesia, the drug sellers were not very willing to discuss the effects of vco. they would acknowledge that indeed these drugs are used by plwa, or they would deny knowing anything about the drugs. but their pharmacies are full of advertisements for the products and they have prominent positions on their shelves (see figure ). content analysis of the package information for vco in indonesia revealed that they are marketed as real 'curealls', i.e. to kill viruses and bacteria and/or strengthen the immune system, efficacy claims that we also found in west africa. for example the package leaflet for vicofit (manufactured by sumber dinamis in bogor) states that the drug has "a high content of lauric acid which has antivirus, anti-bacterials and anti-protozoa properties." and that it is "believed to help improve the health condition of those with cholesterol, diabetes, coronary heart disease, hepatitis c, hiv positive, cancer, prostate, uric acid, osteoporosis, influenza and weight problems". the package for virjint (produced by pt vermindo international) states that the medicine is safe for daily use and without side effects. it lists two dosages: one for prevention ( × capsules per day) and another for treatment ( × capsules per day). the leaflet stipulates that the indications are: -"to increase energy and body stamina -to increase body resistance (meningkatkan daya tahan tubuh) against bacterial, viral and fungal pathogens -to reduce weight -anti-oxidant, anticancer, and anti-hiv -to overcome uric acid, hypertension, stroke, heart disease, atherosclerosis, osteoporosis, influenza, hepatitis, chickenpox, herpes, tb, diabetes, epilepsy, eczema, liver, haemorrhoids, kidney, peradangan (burning sensation), infection, degenerative disease." the packages cite clinical research conducted elsewhere (philippines, usa) to give legitimacy to the products. for example the leaflet of holistic virgin coconut oil states: "based on research conducted in the philippines, holistic virgin coconut oil is very effective to fight against sars and aids". one of the key characteristics of alternative medicines in asia and africa is that they move from one cultural and geographic space to another, apparently without being constrained by trade-barriers, or regulatory mechanisms. some governments promote the production and diffusion of neo-traditional medicines. they do so for economic reasons: alternative medicines are big business, but they also do so for ideological reasons: neo-traditional medicines reflect an attractive hybrid of modernity and national heritage, providing a sense of national identity in the globalized health economy [ ] . the governments of india, china, indonesia, and some african countries support research programs to further advance these neo-traditional products, and facilitate market diffusion. while registered pharmaceuticals are regulated heavily upon market entry (proof of efficacy is assessed by national drug regulatory authorities), this is not the case for alternative medicines. art programs, which are sponsored by the same governments, usually discourage the use of alternative medicines, fearing the toxicity of the drugs, or that these medicines will interact with anti-retroviral medication and lead to discontinuation of art therapy [ ] . governmental agencies may have contradictory attitudes towards the use of alternative medicines for aids, discouraging it within art programs and supporting it within divisions of traditional medicine. an exception is the chinese government, which officially supports a complementary medicine program for aids care and research [ ] . mass-produced alternative medicines meet an increasing demand for health products, a trend which has been labelled the "commodification of health" [ , ] : from the slums of djakarta to rural settings in burkina faso, people believe more and more that they need pharmaceutical 'things' to protect their health and to treat illness symptoms. people living with hiv and aids are particularly uncertain about their health and their future: art may be accessible and improve health now, but they wonder if this will be the case in the future. this uncertainty makes them an attractive market for the 'best of both worlds', alternative medicines, which come with assertions of 'natural' safety and 'biomedical' efficacy [ ] . however the case studies presented in marseille suggest that people especially want to use alternative medicines to delay onset of art, treat opportunistic infections, restore health and alleviate adverse effects once on art. immuneboosters are popular, though our case studies suggest that plwa are often ambivalent about alternative medicines that claim anti-hiv efficacy. the case studies make clear that the market of alternative medicines for hiv/aids is dynamic. it adapts to progress in biomedicine, which has produced potent anti-retrovi-ral medications. in some cases, the efficacy claims for alternative medicines reinforce a biomedical paradigm for hiv/aids, and fit with a healthy living ideology promoted by aids care programs and support groups. more interdisciplinary research is needed on the experience of people living with hiv/aids with these alternative medicines, the ways in which the products and their representations move from one cultural setting to another, and on the ways in which these products interact (or not) with anti-retroviral therapy at pharmacological as well as psychosocial levels. more research is also needed to assess the economic impact of these therapies, since people seem to be spending much on these 'other' medicines while art is provided for free. a blanket denial of the relevance of these products for the quality of life of plwa does not make sense for patients, who need precise information that make clear which products are likely to have negative interactions with art, and which ones could be beneficial. unfortunately research on the interactions between alternative medicine and antiretroviral drugs is sparse [ ] . to be able to inform patients better, more clinical research is needed on the benefits and risks of those alternative medicines that are perceived to be beneficial by people living with hiv and aids. patients and healers in the context of culture: an exploration of the borderland between anthropology, medicine and psychiatry berkeley alternative and traditional treatments for aids in the time of art in resource-poor settings: a comparative analysis of recent anthropological studies abstracts aids impact th international conference indigenous pharmaceuticals, the capitalist world system, and civilization the rise of the modern jamu industry in indonesia: a preliminary overview ayurvedic and unani health and beauty products: reworking india's medical traditions an overview on neotraditional medicines for hiv/ aids in west africa. naarps workshop alternative and traditional treatments for hiv/aids staying healthy while on haart: the experiences of providers and patients on haart in uganda's resource limited settings. naarps workshop alternative and traditional treatments for hiv/aids non-conventional hiv/aids treatments in west-africa: based on the case of benin. proceedings naarps workshop alternative and traditional treatments for hiv/aids on coconut oil, buah merah and other treatments used by people living with aids in west-java neo-traditional treatments for aids in china: national aids treatment policy and local/global use of tcm (traditional chinese medicine use of traditional herbal medicine by aids patients in kabarole district, western uganda facettes de la recherche médicale et de la gestion du vih-sida dans le système de santé chinois: un autre exemple d'adaptation locale de la biomédecine' (an outline of aids medical research and management of hiv and aids in the chinese public health system: another example of biomedicine localisation) the anthropology of pharmaceuticals: a biographical approach. annual review of anthropology agenda for an anthropology of pharmaceutical practice use of traditional medicine by hiv-infected individuals in south africa in the era of antiretroviral theraphy the authors thank john kinsman for his editorial suggestions and rosalijn both for her assistance in preparing the manuscript. the authors prepared papers for a joint seminar held in aix-en-provence, see reference list for the titles of the contributing papers. a summary of the insights from the papers was subsequently presented at the marseille impact meeting, based on which a draft of this manuscript was written by ah and ad. all authors have contributed to the final manuscript. key: cord- -uoek pba authors: peset, josé l. title: plagues and diseases in history date: - - journal: international encyclopedia of the social & behavioral sciences doi: . /b - - - - . - sha: doc_id: cord_uid: uoek pba in spite of the development of the medical science, during the twentieth century, individuals have observed the spread of new or reemerging diseases, from plague, cholera, and flu; measles, cancer, and malaria; to acquired immune deficiency syndrome, west nile fever, resistant tuberculosis, virus of ebola, creutzfeldt-jakob disease, and others. as individual illness is rooted in society and the environment, human life is tied up with the history of main endemic and epidemic diseases. human health is very sensitive and adaptable to changes, so the history of disease and hygiene is the core of the new ecological history. the 'sweating sickness' (sudor anglicus) . on yet other occasions, these changes are merely due to cultural appreciations, as it has happened with certain sexual practices such as masturbation or homosexuality, which used to be framed as stigmatized diseases. on the other hand, disease is not always considered only harmful: thus it may be considered a distinction of the gods, as was the case of epilepsy in ancient times, or among some historical aboriginal tribes. nevertheless, the hippocratic text on the sacred disease established the natural condition of this illness, similar to other medical affections. the same disease was associated with the devil by the christians, and historically, it had always been a supposed distinction of great personages from caesar to napoleon. disease can also be considered a way toward perfection or transformations, leading to the creation of art or to the salvation of the soul, as melancholy or sorrow were for centuries. disease may also have political repercussions: it is claimed that george the third's madness gave rise to problems for the british crown, while roosevelt's fragile health was considered to have placed him in a weak position in the yalta negotiations. socially, disease has sometimes unjustly been considered the stigma of groups (as acquired immune deficiency syndrome (aids) for homosexuals, and poor or marginal groups, or alcoholism for black or aboriginal peoples). medicine and politics have endeavored to preempt social changes by means of the contested eugenic theories and practices of social engineering, inspired by francis galton at the end of nineteenth century, which began with recommendations or laws to avoid marriages entailing risks (real or imaginary), and went on to such processes as sterilizations. heredity is today considered an important predisposition for disease, but mostly not in a deterministic way. hereditary conditions are thus intertwined with cultural, social, religious, and moral ones. besides, in contrast with the stark determination of former times, there is today an attempt to draw new optimism from the possibilities of genetic modifications. yet, in this latter respect, there is fear of a future where such a formidable force could rest in the hands of the rich and powerful. an important renewal in the study of infectious diseases was driven by bacteriological discoveries, and the theories about infection and immunity. in this respect, hans zinsser in rats, lice, and history combined them with human history, proposing biographical interpretations of epidemiological history. the study of the transmission of pathogens through animals and human beings (as vectors and hosts), living in a physical, biological, social, and cultural environment, was crucial in bringing about a new history of disease and also much later in fueling the most recent ecological history. in the meantime, the essential contributions of historical demography and social history licensed the consideration of the history of diseases as 'biographies,' shared by human cultures, living beings, and natural environment. but with the development of accurate technologies of diagnosis, the real identification of old plagues is more and more demanding. paleopathology enables us to discover the high incidence of diseases in the early inhabitants of the earth, especially where such diseases left their mark on bones. it is thus possible to detect remnants of tumors, infections, necrosis, osteoporosis, and malformations, as also traumatisms, dental alterations, rickets, rheumatism, and other diseases of the bones. today, laboratory analysis allows the possibility of detecting remnants of other diseases, germs, or lesions, in animal or human remains, including of course the famous mummies. from the first settlements in the fertile crescent, changes have taken place in the relationship of man and animals with their environment and it is possible to establish an extensive catalog of diseases that have largely subsisted down to this very day. particularly significant are the forms of settlement, the crops and hunting, and the contact of man with cattle, pets, and parasites, as well as the relations between peoples, through mixing and trade, wars, and migrations. malaria originated in tropical africa, accompanying the dawn of humanity, from plasmodia infecting animals and hominids. caused by different plasmodia (plasmodium vivax and plasmodium falciparum among others, with different geographical distribution), its relation with human populations is shaped by migrations and deforestation, hunting and farming, climate and soils, crops, animals and foods, and a complicated immunity resulting from ancient genetic mutations and new infections. thus, with the early human emigrations, it expanded through eurasia, and in the third millennia bc, malaria had already set in the early civilizations in marshy areas where the water, the climate, and the crops provided the conditions for the anopheles mosquitoes to infect in crowded populations. evidence for the existence of intermittent fevers is already to be found in ancient cultures, finding suitable conditions along the yellow, indus, ganges, euphrates, or nile rivers. different interpretations considered the disease to originate from climatic or environmental factors, from particles or small animals, because of spirits or gods, or from unbalanced or disharmonic alterations. the connection between fevers, splenomegaly, and marshy areas appears in the hippocratic texts, such as on airs, waters and places. deforestation, agriculture, temperature, and a greater population density, as well as military and commercial movements, favor the spread of the disease. in italy, in republican times, the disease becomes acute; and it was recommended that the marshy lands be either abandoned or sold and that people should dwell on high groundthe latter being traditional advice and here defense reasons also counted. also, the cleaning and draining of swamps was considered, this being the origin of systems of engineering sanitation. the spread of malaria got worse and worse in rome owing to negligence and flooding, climate and agricultural changes, wars, travels, and migrations, and it reached its zenith at the time of the fall of the roman empire, a cataclysm to which it may have contributed. but when the old empire declined, another frightening ghost traveled through the mediterranean sea. plagues were considered in ancient cultures as diseases originating in god's punishment, with a violent pattern, and quick and terrible diffusion, affecting and killing a large number of persons. destructive epidemic catastrophes were narrated frequently in mesopotamian, biblical, egyptian, indian, or chinese sources, and in - bc, thucydides describes the plague of athens in the war against sparta, but it is doubtful that this case refers to the bubonic plague. this epidemic death is considered the beginning of the decline of athenian hegemony, the crisis of the democracy, and culture of the pericles era. fear, war, siege of the city, and its maritime port were accompanied by the death of the great ruler pericles. later on, the first reliable description of this disease is that given by rufus of ephesus in the ad first to the second century, in the epoch of trajan; and in the sixth century, the plague of justinian initiates the first great epidemic cycles of bubonic plague. soldiers and merchants, animals and merchandises, and slaves and prisoners all contribute to linking up the extremes of the known world. a consequence of this contact was the antonine plague in the second century. this plague -and othersis attributed to smallpox, a disease that had already existed as far back as years ago, as certain mummies show. in the middle ages, leprosy spread widely, allegedly as a result of the increasing east-west relations trough trade, travels, and wars. this biblical and present day disease is accompanied by social repulse and malignant connotations since dirtiness and overcrowding provided the conditions for the spread of the otherwise not extremely contagious mycobacterium leprae. in this respect, the way to santiago de compostela where pilgrims slept in groups and under unhealthy and dirty conditions provided a fertile ground for this disease. another markedly religious character is to be found in the 'sacred fire,' 'st anthony's fire,' or ergotism; a disease that developed in people eating rye infected by ergot, it was soon prevented, but reappeared during the course of severe famines. these diseases are linked to many others that owed their spread to squalor and poverty, for example, parasites and infections, scabies, mycoses and lice, anthrax and ophthalmia. natural catastrophes, wars, poverty, and famines were escorted by mental diseases, tuberculosis and pneumonia, traumatisms and poisonings, diarrheal diseases and fevers, as well as smallpox and measles. in the mediterranean basin, malaria continued to be endemic with the population tending to resort to residing on the hills and mountains, far from marshy lands. the extension of malaria involved south and southeast of asia, central china and japan, and also north europe. the plague set in the growing cities with the burden of rats and fleas, making this disease an explicative example par excellence of epidemic history. a second epidemic cycle began with the black death in . commerce and the cities collapsed, giving rise to the origin of the modern european kingdoms. at this time, venice established control over persons and ships, in order to avoid the spread of plague, arriving from distant lands. dark ages are ending, and new worlds are opening in culture and geography. european expansion meant a sudden traffic of diseases mostly toward the new world. the discovery of america, with its scattered population devoted to agriculture, where there were no dirty cities, and where the inhabitants were devoid of immunity to the diseases of old europe, produced an enormous demographic crisis. certain diseases, such as smallpox (and measles) ravaged the indigenous population; this very contagious and harsh illness was introduced in the caribbean and mexico, and destroyed american indigenous populations. syphilis came supposedly from america (although other human treponematoses were present in other continents), brought back by the spaniards and it caused havoc since renaissance in europe and soon all around the world. troop movements spread an unknown disease called 'tabardillo,' or 'typhus exanthematicus,' bringing about serious suffering for armies and poor people. sea voyages led to the development of scurvy, due to the lack of fresh food. other diseases also voyaged overseas, such as yellow fever; although it originated from africa, due to the commerce of slaves and merchandise, special temperature conditions and mosquitoes as vectors were required for the contagion. in the seventeenth century, it took root in brazil and also spread to the caribbean and throughout america, reaching new york and boston and likewise colombia, ecuador, and peru. it affected warm america and europe, through the iberian peninsula. immunity and cutoffs in commerce stalled the disease, but it remains endemic in tropical areas of america and africa. also, malaria arrived to america with the european conquest in sixteenth century, beginning in the caribbean and central america and soon spreading to south and north america, becoming endemic in hot, wet, and low lands. malaria was combated since the seventeenth century by the use of cinchona bark (peruvian bark), found in peru, as an indigenous medical practice. later on, the quininethe alkaloid obtained from the bark in french laboratoriesgave rise to rich industry and trade. trees were cultivated in british and dutch colonies, mainly in java. after being taken in the second world war by the japanese army, synthetic products such as atebrine and chloroquine were obtained. getting worse with agriculture, mining and livestock changes, settlements, and slavery trade, malaria becametogether with yellow fevera scourge along the warm and hot reaches. throughout the american conflicts between european empires, and later during the american independence wars, both diseases played an important role, infecting and killing nonimmune soldiers. plague slowed demographic growth in europe since the wars between modern and powerful nations, the crowded and dirty cities, and the developing trades impeded protection against the disease. the great writer daniel defoe remembered the terrible contagion in london in in journal of the plague year. after the great european plague of marseille in , the relative peace of the eighteenth century allowed western europe to set up sea and land defenses, with austria becoming a solid bulwark in the face of the ottoman empire, thus sealing off all possible spread of the plague. toward the middle of the nineteenth century, the third wave of the disease broke out and, with the exception of europe, it spread to all countries including asia, africa, and paradises like america and australia, leaving remnants in many places. the eradication of plague in europe was a result of the advent of public hygiene, immunity to disease, and the disappearance of rats and of the old and dirty wooden buildings. the great london fire in 'purified' the city, since the hygienic rebuilding was carried out in stone, eliminating animals and dirt. the disappearance of plague from europe was followed by the outbreak of cholera, which had been endemic in india for centuries. this disease was described by western travelers in the sixteenth century and its spread to europe and america was a consequence of pilgrimages, trade, and a lack of cleanliness in water. a great pandemic broke out in from india and spread through eastern africa and southern asia, arriving to china and the philippines, and in a second wave, it spread through persia reaching russia and poland in . then this second wave swept across europe and reached america by . throughout years, terrible waves spread from the east. however, the timely and necessary cleansing of urban water supplies helped to progressively stall its advance. nevertheless, as late as , the free hanseatic city of hamburg suffered an outbreak of cholera epidemic, while the neighboring altona, governed by the prussian reich, was able to avoid the disease, thanks to the successful filtering of its water. local and national governments advanced in hygiene and they attempted to bring about healthier cities by means of appropriate public health measures. the nineteenth century sees the beginning of the demographic revolution in europe, followed by developing countries, in america for example, with a sharp decline in mortality, especially maternal-infant mortality. old inoculation and the new vaccination proposed in by edward jenner fought smallpox successfully. studies about human immunity since the last decades of nineteenth century began a new medical approach to the prevention and understanding of illness, being successful in the contention of many diseases, which have a long record of burdens and deaths. mother care also advanced both throughout pregnancy and at childbirth and during lactation. the rise of great and industrial cities with low-grade outskirts and the emigration of peasants to the city favored the spread of maladies associated with poverty, hard work, squalor, lack of appropriate food, and exposure of people devoid of defenses. some of the diseases were strictly occupational as in the case of miners and textile workers who were exposed to injury, and to industrial poisons that affected the proletariat. sir percivall pott described in the eighteenth century the cancer produced in professional cleaners (chimney sweep) by chemical toxics contained in soot. many other diseases, such as cancers, will be attributed to chemical and physical aggressions, including radioactivity. other diseases were closely related to the harsh and dirty conditions of life such as spread of typhoid fever and pulmonary diseases. tuberculosis spread over the turn between the eighteenth and nineteenth centuries, and while it was represented as the disease in fashion, affecting notable and distinguished people, it struck the proletariat much more severely. the same can be claimed regarding the enormous spread of syphilis, and drug abuse, beginning with alcohol and continuing with cocaine and morphine. the discovery of the microbiological origin of infectious diseases, and of effective therapies against them, and the development of public health changed the pathological landscape in developed countries. the long way between ignaz semmelweis and alexander fleming arrived to the contention of infections in health care. the twentieth century marked the descent of the high mortality rates in countries that reached high standards of sanitary development, investing in health care and public health. such advances have been due to public health services, hospitals, antibiotics, surgery, and vaccination, and they have been reinforced by the developments in immunology and microsurgery, pharmacology, and biotechnology and with the promising future of genetic engineering. the international health solidarity promoted by the world health organization (who), and other governmental and nongovernmental organizations (ngos), including church missionaries, were accompanied by better governance of nations, and internationalization of information and resources. the twentieth century established a serious change in geopathology of diseases. smallpox is the first disease to be considered totally eradicated with only some samples of the virus being kept at a few laboratories for study purposes. a cuban doctor (carlos finlay) found the method by which yellow fever is transmitted through mosquitoes (aedes aegypti). after the cuban war and during the opening of the panama channel, yellow fever and malaria were studied and faced by us army and american sanitarians (walter reed, william gorgas), and later by the rockefeller foundation. impeding mosquito reproduction and avoiding bites and spreading chemical products were useful. fortunately, an effective vaccine against yellow fever was later discovered. during nineteenth century, malaria expanded all around the world, arriving to the central extensions of america and eurasia. emigrations and settlements, wars, famines, climate change, and revolutions in travels, such as railroads and steamships, contributed. during the napoleonic wars and the american civil war, malaria was seriously extended, as it was also during wars and revolutions in twentieth century. in the interwar years, the rockefeller foundation and the league of nations sponsored international campaigns against the disease. many governmental campaigns also fought against malaria; several national programs were effective, from taiwan and china to the united states, brazil, and argentina, passing across the mediterranean basin, from italy to egypt. opinions and campaigns oscillated between quinine treatment, fighting against mosquitoes (by dichlorodiphenyltrichloroethane (ddt)), and improvements in life, education, and land sanitation, clearing up the marshy areas. malaria has been eradicated from europe thanks to drainage, improvements in crop cultivation, mechanical barriers, quinine and modern drugs such as atebrine and chloroquine, and insecticides. colonial settlements entered tropical areas backed by quinine, nets in beds, hygiene, and sanitation, but transmissible diseases were continuously a serious burden for colonial armies, in america, africa, or asia. some chemical products such as ddt were a successful support for soldiers, travelers, merchants, or settlers. nevertheless, in , the world health assembly, meeting in mexico, warned against the resistance of the mosquitoes to insecticides. mosquitoes are still today carrying both diseases, and also dengue. chagas disease produced by trypanosoma cruzi is endemic in america, and sleeping sickness caused by trypanosoma brucei (rhodesiense and gambiense) occurs in africa. today, an effort is being made to involve governments in the fight against malaria, a disease that represents a danger to nearly half of the world's population. in africa, the situation is very serious due to the changes in agriculture and irrigation as well as in work and migrations, the political and economic problems, the severe droughts, famines and wars, the bad sanitary conditions following in the wake of housing expansion and deforestation, and harsh social and economic exploitation. together with the who and the united nations international children's emergency fund (unicef), regional institutions such as the pan american health organization and the us government are financing programs of eradication. the who, through the st world health assembly of , set up the program 'roll back malaria' and, with aid from unicef and the world bank, is endeavoring to bring about economic and sanitary improvements in developing countries. in twentyfirst century, the global fund to fight aids, tuberculosis and malaria is attaining important amount of resources and success. nets treated with insecticides are very useful for protection against mosquitoes. today, hope is also placed on vaccination and in the sterilization, or genetic modification, of the mosquitoes. yet, malaria continues to be endemic in warm zones of america, asia, and with severe cruelty, in africa. the rapid increase of world population in huge metropolitan areas was accompanied by new settlements and emigrations, wars, conflicts and revolutions, and marginalization of aboriginal cultures and disinherited peoples. throughout the past two centuries, economical, social, and political expansion of the west led to studies on tropical medicine, creating hospitals and laboratories and institutions on public health and sanitary departments. cholera continues to be feared in asia, between india and the far east, and also in warm zones in america and africa. wars and catastrophes, travels and migrations, as well as famines and unhealthy conditions allowed the expansion of the cholera germ, the vibrio cholerae isolated by robert koch in , as was the case of the recent tragedy of haiti. at the end of nineteenth century, the third outbreak of bubonic plague allowed its bacteriological and epidemiological description. the germ of bubonic plague yersinia pestis, discovered by yersin and kitasato, is still to be found throughout the world. the germ is carried by rats, rattus rattus: rat fleas are the arthropod vectors transmitting 'epizootic' plague to humans from rodent hosts, and related species, but transmission among humans is also possible. almost forgotten in the developed world, with several and very effective antibiotic therapies, there is, nevertheless, always the possibility that the devil may once more send his rats to the old, rich cities. but other viruses have taken its place in the twentieth century. thus the very old and common influenza caused several cruel and heavy outbreaks; among many others, influenza pandemics began in and reappeared in , , and : these were known, respectively, as the 'spanish flu,' which perhaps originated in the united states, the 'asian flu,' the 'hong kong flu,' and the 'avian flu,' mostly coming from asia. vaccines are very useful in its prevention, as they are also in the control of many infectious childhood diseases, such as measles, rubella, mumps, chicken pox, whooping cough, diphtheria, and so on. old diseases such as poliomyelitis exploded in the united states and europe, affecting nonimmune children, and this disease has only been controlled in developed countries by means of vaccination. during the past century, individuals have observed astonished the spread of new or reemerging diseases, from plague, cholera, influenza, measles, and malaria, to aids, west nile fever, avian flu, severe acute respiratory syndrome, resistant tuberculosis, hemorrhagic fever (ebola virus disease), transmissible spongiform encephalopathy (creutzfeldt-jakob disease), and others. unfortunately today, many frequent or rare diseases do not have adequate treatment, and many germs are developing resistance to antibiotics, a serious threat for its affectivity. aids has meant a development in the study of viral infections, and this disease has associations with the exploitation of poor people, unsafe sex, and drug trading, but it also affected an elite sector, which has sprung rapid research in the field. the world commotion surrounding this disease has served both to reveal human altruism on the one hand, and, on the other, contempt toward those infected by the disease, since aids became more and more the lot of the poor, mostly in large areas of africa, or india, and of downcast or marginal groups such as the chronic patients, drug addicts, prostitutes, and homosexuals. nevertheless, heterosexual transmission through unsafe sex and transmission from mother to child are today serious dangers. safe sex and antiretroviral treatment are the best contention, while a vaccine will be obtained perhaps in the coming future. mental affections were considered till modern times, as devilish, criminal, or vicious behaviors, more an ethical or social than a medical problem. in the eighteenth century, the natural explanation of mental disease was established, according to alexander crichton, or philippe pinel, and in the nineteenth and twentieth centuries, its psychogenic process, following sigmund freud. from pinel to freud, the possibility of treatment and remedy of mental disease was established, leading the soul of the patient with convictions and health measures to the cure. the discovery in recent times of some effective pharmacological drugs acting on human mind, and conduct, has allowed better treatment. reclusion was considered a doubtful possibility, restricted to some severe problems. the old lunatic asylums, founded since middle ages, were being abolished or completely renewed. nevertheless, mental illnesses wreak serious havoc at present times all around the world, affecting all ages, genders, and conditions, without any distinction. sometimes, the misunderstanding regarding mental diseases still produces cruel treatments, harsh restrictions, or punishment. during the past decades, economic and social improvements led to quick globalization and urbanization, with longer human life and changes in disease patterns. political, sanitary, and economic development managed to stamp out infectious morbidity, and forms of suffering or living illnesses are changing. unicef and who, in collaboration with governments, foundations, and ngos, promote successful campaigns of vaccination, especially focusing on children. the burden of infectious, parasitic, and transmissible diseases changed to chronic diseases and sufferings related with aging and lifestyles, likewise, nutritional disorders, cancer, or heart and brain vascular diseases. on the other hand, the increase in life expectation favors the development of alzheimer and other chronic and degenerative diseases, neurological and muscular diseases, mental affections such as schizophrenia, mania and depression, diabetes, vascular diseases, and of course, the terrible presence of cancer. accidents and traumatisms, due to traffic and sports, factories and radiation, or even home accidents, are something that the twenty-first century is inheriting. blindness, deafness, dumbness, and other frequent physical and mental disabilities, with multiple origins in traumatisms or accidents, genetic, metabolic and degenerative diseases, infectious diseases such as poliomyelitis, or cerebral and vascular affections, make daily life difficult and, at the same time, make economical, institutional, and social support necessary. incapacitating and chronic diseases lead to severe dependency and so the need for protection of disabled individuals is leading to the founding of patients' associations looking for help and justice, creating new rights and demands. ghettos and migrations, hard work, poverty and unemployment, and some of the old drugs such as alcohol, heroine, and tobacco or new synthetic ones are causing havoc even to the rich world. but in developing countries, the old morbidity due to transmissible diseases continues to exist, maintaining a very low life expectation. certainly, the increase of migrations and of urban population are requiring more water, food, and energy, producing climate warming, deforestation and agriculture changes, and dangerous issues such as waste, toxics, and pollutants. potable water, health services (medical care or medical drugs), sanitation and hygiene are urgently requested. environmental degradation and the confrontations between national, social, and ethnic groupings are a serious danger for healthy life. china, japan, and south korea and other expanding countries have lived through these challenges in different ways from diverse british colonies such as australia or india. different traditions and cultures are extremely important to understand the relations between peoples and diseases. death is most rampant amid the least protected and poorest people, especially women, children, and the elderly, with harsh sufferings such as wars, famine, and exploitation. under such circumstances, diseases caused by deprivation and infection continue to be the most rampant, causing high death rates among the population. old and new diseases, such as malaria and aids, are ruining great stretches of africa. leprosy and cholera, tuberculosis and tetanus, and many child diseases, such as mumps, measles, tetanus, or meningitis are in poor countries and populations the salt of the earth. private and public funds, and international solidarity, are always necessary for relieving these harsh sufferings. the united nations millennium development goals are also facing them. according to the who report global health risks ( ), the better or worse conditions for mortality and for the burden of disease are seriously conditioned by several circumstances, related to lifestyles: blood pressure, blood glucose, physical activity, alcohol and tobacco, weight, safe sex, safe water, sanitation, and hygiene. obviously, these circumstances and their consequences are very different, depending on the social level of individuals and the public health governance of nations and peoples. if developing countries are freeing themselves from transmissible diseases, now they are fighting against noncommunicable diseases, related to social level, health organization, and hygienic customs. some american, asian, and african countries are still supporting a terrible burden of disease, which is also shared by low-income population in developed countries. the rio political declaration in the world conference on social determinants of health (who-rio de janeiro, brazil, october ) is a new call looking for equity, justice, and universality of health. it has recommended adopting better governance for health and development; promoting information, justice, and participation in policy making and during the implementation process; including civil society like indigenous people; and reducing health inequities in the health sector. this declaration promotes research on the relationships between social determinants and differences (economic, ethnic, and gender inequalities) and health equity. we are all convinced about the relation between poverty, social discrimination, low education and low sanitation, and diseases and death. history of western; science, history of; welfare state, history of plagues in world history the great pox: the french disease in renaissance europe les hommes et la peste en france et dans les pays européens et méditerranéens, vols la malaria tra passato e presente the columbian exchange: biological and cultural consequences of médecins, climat et épidémies à la fin du xviiie siècle the cambridge world history of human disease public health in asia and the pacific. historical and comparative perspectives plague and the end of antiquity: the pandemic of - mosquito empires: ecology and war in the greater caribbean plagues and peoples inescapable ecologies: a history of environment, disease, and knowledge humanity's burden: a global history of malaria rats, lice and history. printed and pub. for the atlantic monthly press by little, brown, and company key: cord- -ezatw authors: vilakati, phesheya ndumiso; villa, simone; alagna, riccardo; khumalo, bongani; tshuma, sarah; quaresima, virginia; nieman, nicole rose; cirillo, daniela maria; raviglione, mario carlo title: the neglected role of faith-based organizations in prevention and control of covid- in africa date: - - journal: trans r soc trop med hyg doi: . /trstmh/traa sha: doc_id: cord_uid: ezatw the covid- pandemic has exposed health system weaknesses of economically wealthy countries with advanced technologies. covid- is now moving fast across africa where small outbreaks have been reported so far. there is a concern that with the winter transmission will grow rapidly. despite efforts of african governments to promptly establish mitigating measures, rural areas, especially in sub-saharan africa, risk being neglected. in those settings, faith-based and other non-governmental organizations, if properly equipped and supported, can play a crucial role in slowing the spread of covid- . we describe our experience in two rural health facilities in eswatini and ethiopia highlighting the struggle towards preparedness and the urgency of international support to help prevent a major public health disaster. since the first reported outbreak of the coronavirus disease in china, the disease has quickly spread across the globe and has reached africa where cases and deaths have increased by % ( new cases) and % ( new deaths), respectively, during the week between may and , . there is serious widespread concern about the lives and economic toll that covid- could claim across africa if the epidemic progresses with the same rate of devastation seen in the economically wealthier parts of the world. although several demographic or immune-related factors seem to play a role in mitigating the severity of cases in many african countries, there is serious concern about underestimation due to insufficient testing. especially in the sub-saharan countries, covid- may have devastating effects as the response required is challenged by inherent fragilities in the national health systems, high population density in metropolitan slums, a lack of services in rural settings, generally poor sanitation, food insecurity and undernutrition, as well as the high burden of comorbidities such as hiv infection and tuberculosis. in africa, faith-based organizations (fbos)-the values of which are based on religious and faith beliefs-which manage a vast number of health facilities in many low-income countries (for instance, approximately % of total health services and more than hospitals are managed by catholic fbos in africa), - play an essential role in providing healthcare and prevention services, community education, and financing. fbos are also undoubtedly crucial in promoting public awareness and addressing social and behavioral factors associated with covid- spread. however, due to their importance for local communities, fbos could become rapidly overwhelmed if the pandemic accelerates. we report here the status of preparedness to face covid- and the assessment of needs of two health facilities run by us, the missionary sisters of the sacred heart of jesus: cabrini st philip's clinic in the rural lubombo region of eswatini and st. mary's catholic primary hospital in the semi-rural area of dubbo in the southern nations, nationalities, and peoples' region of ethiopia (as displayed in table ). in both missions, we have developed strategies to identify suspected covid- cases and to isolate them in dedicated areas of the facility. in both, we have implemented a systematic triage at patients' point of entry and appropriate infection control measures. however, the existing shortage in supply may hinder the performance and sustainability of the response in the short term period, especially if the influx of patients intensifies. our hospital in ethiopia, staffed by a low number of healthcare workers (hcws) for the population served ( . hcws and . medical doctors per people, respectively), has at the moment very insufficient personal protective equipment (ppe) for both hwcs and patients, thus increasing the chance of nosocomial outbreaks. our rural out-patient clinic in eswatini, which has a higher ratio of hcws ( / people) but no medical doctor, has ppe estimated to last for about a month in the best-case scenario, which is however rapidly changing due to intensification of patient influx in recent days. key missing components in the preparedness of our two centers, besides ppe supply, are nasal swabs for molecular diagnostic tests and effective therapeutic options (e.g. oxygen support devices, anti-inflammatory and antiviral medicines commonly used in high-income settings, as well as broad-spectrum antibiotics). existing in-house basic laboratories cannot perform nucleic acid amplification tests on nasal swabs-both because these are technically challenging and are lacking in reagents . also, in normal circumstances, up to a week is required to obtain results from the referral laboratory, whose activities can be rapidly overwhelmed if cases increase, thus delaying diagnosis, isolation, and treatment. all these elements, together with the low availability of beds in the two health facilities-a limited number of beds in dubbo, and none in the out-patient clinic in eswatini-and the small number of well-equipped tertiary facilities nearby, suggest that effectively addressing covid- in these settings is a challenge. in the african continent, preparedness for a pandemic like covid- is a challenge given the need for rapid adaptation of already constrained health systems, scarcity of laboratories and reagents to test, limited training capacity, and poverty of resources in care provision and in general. yet, the simple transactions of the royal society of tropical medicine and hygiene administrative structure of fbos, with decision-making capacity at the grassroots level, makes them flexible and agile to rapidly adapt and respond to a health emergency, as long as fundamental tools are made available. however, due to the general shortage in ppe, diagnostic kits, and effective therapeutic options in countries like ethiopia and eswatini, most funds and key supply and equipment may be directed to governmental facilities rather than engaging the numerous fbos and other non-governmental organizations (ngos) providing care. in addition, many african governments will not be able to confront this pandemic alone and international support is urgently needed. this support, however, needs to be directed not solely to governmental facilities but also to the highly committed ngos and fbos that, operating at the grassroots level, are best placed to provide health services to people living in impoverished conditions, especially in rural settings. fbo and ngo facilities are often the only entry point for rural and semi-rural populations. they need to be engaged, urgently supported, and properly equipped to safely contribute to handle the pandemic and simultaneously manage the regular burden of the endemic diseases ravaging the continent. outbreak brief # : coronavirus disease (covid- ) pandemic the prospects for the sars-cov- pandemic in africa the role of faith-inspired health care providers in sub-saharan africa and public-private partnerships: strengthening the evidence for faith-inspired health engagement in africa. the international bank for reconstruction and development / the world bank world health organisation. the world health report : changing history. geneva building from common foundations: the world health organization and faith-based organizations in primary healthcare statistiche della chiesa cattolica critical supply shortages: the need for ventilators and personal protective equipment during the covid- pandemic essential care of critical illness must not be forgotten in the covid- pandemic keeping covid- at bay in africa africa prepares for coronavirus africa in the path of covid- authors' contributions: nrn, dmc, and mcr designed the study; pnv, st, and nrn implemented the study; sv, ra, and vq analyzed and interpreted the data: pnv, sv, ra, bk, and vq made major contributions to the writing of the paper; all authors read and approved the final version of the paper. competing interests: none declared.ethical approval: not required. key: cord- -rncleqqy authors: ramírez, j. martín title: long-lasting solutions to the problem of migration in europe date: - - journal: a shift in the security paradigm doi: . / - - - - _ sha: doc_id: cord_uid: rncleqqy this is the following of a previous publication on the refugee crisis in europe and its security challenges. here we suggest some long-lasting solutions to the problem of migration. these may be summarize in four points: dealing with the countries of origin and of transit, adequate control of borders, and positive measures to facilitate the integration of the newcomers in their countries of destination. in a previous publication on the refugee crisis in europe and its security challenges, i concluded that a global problem like this one could not be solved without an adequate orderly, and controlled immigration policy, creating systematic and controlled arrival and integration programs, because the mental structure of european societies is not prepared to face a disorderly increase in migration flows (ramirez (ramirez , . it is thus vital to regulate the arrival of migrants if we want to achieve their real integration in our culture (espaliú berdud ) . here i will try to go forward, pinpointing the terrible damage made by the massive escape of young people from countries that desperately need them in their struggle for development; their great problem is precisely the continuous loss of human capital. besides of that, who emigrate are not the "poor among the poor", but people with certain economic means to be able to afford the trip and contacts in the place they are going to. what is more important, according to me, is to argue that the best way would be to encourage migrants to stay home, preventing massive uncontrolled displacements, is addressing the factors that drive emigration of their own origin countries. to stop unwanted migration, the developed countries must promote a profound democratic and economic stabilization and development. we must always remember that the first right of every human being -after the right to live-is the right not to emigrate and to have the opportunity of living peacefully and prospering in our own home, as pope pius xii wrote in the apostolic constitution exsul familia: "all men have the right to a family living space in their place of origin". the right to emigrate is only subsidiary to the main right to have a family living space in the place of origin, when this cannot be assured. migration has been a sensitive and contentious topic for ages. escaping violence, war, poverty and environmental disasters, more people than ever are migrating worldwide. since it is not a cyclical, but a structural phenomenon, which means that whatever the method put forward migration cannot be stopped. currently, according to the uno estimates, million people live outside their country of birth ( . % of the world's population). in , about % of the world's . billion people lived abroad (unhcr ) . this figure grows due to inequality, climate change, conflicts, and the interconnectivity that facilitates the movement of people. migration itself affects values, identities, cultures, assimilation capacities of societies, and, far from being a problem in se, it may be a solution to many problems; e.g., benefits the demographic catastrophe present in the aging western societies. but it doesn't always engender positive changes; it may also show important disadvantages. this is why immigration must be orderly, capable of duly regulating the massive arrival of people; otherwise our social protection systems will not resist. the illegal immigration requires proper vetting to identify criminals and terrorists-the crime rates of the foreign immigrant population are significantly higher than those of the natives-, and sometimes, to put in metaphorical terms, surgical excision procedure without anesthesia will frequently induce pain. no country needs a trojan horse. but we will leave this so interesting aspect for another parliament. although mass emigration to developed countries is a global phenomenon -it happens even within each country, internally displacing for instance from rural areas to urban ones: china is a clear example-, the present chapter will be focused mainly on what would be the better long-lasting solutions to its present situation in europe, one of the leading destinations in the world in terms of migratory flows, with million migrants, russia included, according to the un's department for population. immigration is an irresolvable problem at short-term. migration policies should follow a long-term vision, addressing economic, security and sociological points of view (de la cámara ), creating systematic and controlled arrival and integration programs of security, trade, development and employment issues. but, being a global problem, migration will only be solved as a consequence of a frank and sincere joint co-responsibility between all countries of origin, transit and destination, sharing the burden of dealing with both regular and irregular migration whenever possible. this was the intention of the un global compact for safe, orderly and regular migration, signed at the end of by representatives of the countries of the united nations (uno) met in marraquesh, in a non-mandatory and rather controversial document that says, in an indirect manner, that for the entry to be safe, orderly and regular, the conditions of entry must be safe and not subject to the mercy of smugglers, seekers' and workers' entry profiles should be differentiated, and entries should be legal. its "objectives" were peppered with vague declarations, platitudes and split differences, such as the fight against the mafias that deal with human beings, the defence of the rights of immigrant workers or a change in narrative about migration towards a more positive approach. partly in the spirit of other global agreements like the paris climate deal, it encouraged states to co-operate on tricky cross-border matters without forcing them to do anything, and urged governments to treat migrants properly, but also to work together on sending them home when necessary. at least, it may help build the trust between "sending" and "receiving" countries that is the foundation of any meaningful international migration policy (economist ). let us offer some recommending ways of improving migration at four different levels: going to the roots in the countries of origin, dealing with the countries of transit, having an adequate control of borders, and suggesting some measures in the countries of destination. i have critized elsewhere (ramirez ) the saving buenist attitude of a migrationist maximalism that wants to open the doors, the ports, the windows and throw all the walls, in favor of a weberian realism (the ethics of convictions versus the ethics of reason) (leguina ): even if we would welcome forty or fifty million africans a year, africa will continue to have the same population. it would be good if they start helping africans in their own countries and avoiding as much as possible the reasons why they want to emigrate (ramirez ) . we want the potential migrants to have a better future in their countries. as ousman umar repeats like a mantra, "the solution is in the country of origin, not in the destination. you have to feed minds (well); if you feed the mind you are satisfying hunger for more than a hundred years" (umar ) . some african prelates within the catholic church are calling attention to the most forgotten aspect of this debate: the terrible damage made by a massive escape of young people from countries that desperately need them in their struggle for development. in a book released recently, cardinal robert sarah, currently prefect of the congregation for divine worship and the discipline of the sacraments, declares his personal position on immigration: "all migrants arriving in europe are crammed, without work, without dignity. is this what the church wants? the church cannot cooperate in this new form of slavery into which mass immigration has become" (sarah a, b; indelicato ). the european union (eu), thus, has to structurally turn over economic resources for the development of africa (and of middle east), tackling the problems that are the main cause of migratory movements, analysing them and offering real help in their own home. consequently, their priority has to be to invest in the countries of origin, because migration control has to be paid with money: financing, companies, information, facilitating their institutional, social, political and economic conditions in order that nobody will be obliged to leave their home, and creating sources of employment in those countries of origin. some political party has proposed in its program that the eu should prepare a sort of "plan marshall" for africa, similar to the one usa did for the post-war europe. according to the spanish royal academy (rae) dictionary, buenismo is the attitude of who reduces the seriousness of conflicts, acting with excessive benevolence and tolerance. this "goodism" is a demagogy destined to hold power through emotional blackmail, quite different to a real goodness, born of charity or philanthropy (robles, ) . cardinal robert sarah is a native of guinea guinean who grew up under a harsh marxist dictatorship and became archbishop at the age of with the task of guiding the diocese of conacry, when still in his country there was the socialist regime of sekou touré. so, i think he knows what he's talking about. in the forties of the last century, america passed the economic co-operation act, better known as the marshall plan, because its inspiration from a speech at harvard university by george marshall, america's secretary of state. the marshall aid, aimed to revive europe's war-ravaged economies, encouraged the europeans to quash inflation and to narrow their deficits while eventually dismantling price controls and import barriers. these reforms had enormous benefits. before fear of inflation and taxation prompted german farmers to feed their harvests to their cattle, rather than it is not enough with assigning cooperation funds. as de la concha stresses ( ), a proper management of migration flows requires working as much as possible in cooperation with the countries of origin taking into account, as appropriate, the various causes of migration (economic, security, political prosecution, climate, etc.). thus, a more ambitious measures are required, such as generating opportunities for the local population and offering fiscal incentives to the investments of european companies in those regions that seem to be condemned to diaspora. this move will also offer new markets for european products and services, as well as opening of eu markets to exports from these countries. and, what is more important, besides of contributing to the economic development of those countries, europe has to improve their social and political quality of life, which is precisely what they try to find in europe. our main objective, therefore, has to be to strength the production base and the creation of jobs in the countries of origin, the provision of basic services (health, education) to the local populations, and the literacy, ensuring that students in their countries have the tools to decide their future and thus avoid the temptation to migrate to europe, avoiding future victims (de la cámara ). either we offer them opportunities in their own countries, or they will come to ours looking for them zalba ( ). the best practical means for achieving it are probably inter-governmental agreements with the origin countries, giving them a generous economic aid. this is the stance taken by the visegrad group (v ) (check republic, hungary, poland, and slovakia): instead of uncontrolled massive immigration, we have to act in their origin countries; instead of importing problems, exporting help in situ. this attitude would also be "much more inexpensive", as is honestly admitted by juho eerola, a finn of the nordic freedom, or by the then slovak prime minister, peter pellegrini, during his first visit to brussels: "what we have to do is to invest in the countries where the problem is originated. each euro spent in northern africa is more efficient than spent in the migrants who arrive massively to eu" (eerola, april ). but, there is need to build up conditions to create secure environment within the transit african countries bordering the mediterranean sea. the north african governments are responsible for effective and transparent governance aimed at management of emigrants flows through their territories. eu's money poured into their accounts are wasted as they do not cooperate as they can. another effort to stem the flow of migrants to europe is "to save and protect the lives of migrants and refugees", motivating "operations of urgent evacuation" returning them to their origin countries through a repatriation programme that encourages those who have made it to northern africa to go home voluntarily, rather than risk sell it to the cities for money that might be diluted by inflation or seized by the government. its true significance laid not in the cash it provided but in the market-friendly policies it encouraged. to receive aid, european governments had to commit to restore financial stability and to remove trade barriers. we have a similar problem within our own countries, migration towards big cities is up siding the living in small rural areas; we have to stop it offering them "the needed modern technology to have the best of both worlds. it is not an easy problem, but i feel a deep analysis needs to be done so we understand more of the dynamics behind the movements"! (lindhard, ). a rickety boat across the mediterranean. this is what uno, eu and african union (au) jointly agreed in abiyan ( nov. ): people who turn back get a free flight-cutting out the need for a perilous return journey across the sahara. the programme has repatriated some , migrants to various west african countries, which barely scratches the surface because it reckons there are about m of them in the african shores, waiting for their risky jump to europe (economist ). the spanish government did this unilaterally in , after . immigrants arrived to the canary islands in open boats, known as cayucos: some direct forms of operative cooperation with those countries through which migrants come or transit, sending there some specific police units for working jointly with the local security forces with the aim of restraining subsequent invasions from other western african countries. since the devolution of immigrants to their origin countries is one of the best deterrent action to avoid the "calling effect", governments have to launch adequate information campaigns in their own origin countries to discourage potential migrants. the eu member states are africa's largest donors, supplying more than half the aid the continent receives. africa exported twice the value of goods to the eu as it did to china in . but it is not just a matter of addressing the factors that drive emigration. europe and africa share something much more fundamental: a future dependent on one another. as moroccan king mohammed vi pointed out in , solidarity between europe and africa has to be "built on shared responsibility and mutual dependence." the european continent is a global player worthy of genuine partnership of equals with africa that priorities concerning mutual interests through rapid funding in education, health and infrastructure for africa's youth would contribute to global growth. europe's investment must be bolder in terms of financing, policy and governance reforms than what is currently on the table (cole ) . economic development, government reforms, institutional strengthening, will result in common prosperity. europe, poor in natural resources and in demographic decline, desperately needs to contribute to the unblocking of the future of africa. up to now, the -economically important-european efforts have to qualify as at least disappointing. the eu needs to encourage, promote opportunities in africa, move from a policy built around aid to cement our relationships on trade and investment (palacio a) . cooperation between states that produce migrants and those that receive them can help to streamline migration flows. the european union has to structurally turn over resources for the development of africa and middle east, which are the main source of migrants nowadays, through agreements with extra communitarian countries for stopping irregular immigration towards europe. and this requires patience and diplomacy, treating the partner governments as equals. the optimism of the "refugees welcome" campaign in -wir schaffen esled towards an uncontrolled flood of refugees which destroyed the perception of order and stability. in june , there was a great turn in the attitudes of the rulers regarding immigration, with a broad consensus at the european council around much more restrictive. this practical agreement intended to hand over the decision-making capacity over who enters and who does not in the "fortress europe", strengthening the policies of controlling the external borders; fighting against traffickers; and more aid in the countries of origin instead of endless aid in europe. there is a need to strengthen collaboration with transit countries. it is necessary to prevent ships from leaving their points of origin. in cases where this is not possible, the practice should be implemented that those rescued at sea should be assisted and returned to the point of origin or departure of navigation. this is the specific task of frontex, the european border and coast guard agency: provide technical assistance and support to the countries of origin and transit to help strengthen border controls, even if it cannot replace national competence; it is converted into an authentic border police, but not in charge of rescuing. i will to come back to this point later. according to the ngo african center for strategic studies, there is a migratory flows that move . million people from one place to another from and within africa in the hands of traffickers; % of them are minors, and only % of those . million, will try to reach europe; the remaining % travel between african countries. in this context, i point out at a report by the department for human rights at the un, marking the horror of criminal smuggling networks which lead to humanitarian scandals such as: enslavement; imprisonment; rape; prostitution; the sale of organs; and camps, whose living conditions are beyond imagination. what alternative do citizens of many african countries have to come to europe? if the european states renounce their ethical convictions, delegating their responsibility, mafias and some connected "heroic" ngos will occupy the scene doing the dirty work. those still determined to reach europe may have to pay large sums to people-trafficking gangs and risk their lives in the sea (we may say the same about america, substituting the word "sea" by "desert"). the more borders, bureaucratic obstacles, closed routes and prohibitions the immigrant finds, the more profitable for the trafficker. no one moves as many people on the planet as immigration traffickers, nobody determines human flows as much as their implementation in a given territory, nobody has their flexibility to change plans and adapt to changing circumstances and nobody gets so many benefits as they do. their criminal business is more lucrative nowadays than drug or arms trafficking. some of those traffickers have changed tactics. before, they put hundreds of immigrants in old overloaded wooden boats with the aim of trying to reach europe. nowadays, after cashing from them, the immigrants are taken in safe boats from african territorial waters, until they know that the ship of some ngo is a few miles away. then, once in international waters, they put on life jackets, crammed them in zodiacs, which can barely sail a few hours and warn by radio that there are shipwrecked people in the area. the more rescue boats they have, the more immigrants will try to cross the mediterranean…, and the more deaths, drowning in the sea, those claimed heroes of the goodism will provoke. a ngo director denounced on television that although he had managed to rescue people from a zodiac, another had perished. what nobody asked was if he did not realize that by telling those who leave libya that there are boats a few miles away they are contributing to the death of hundreds of people who, for one reason or another, cannot be picked up. trafficking in human beings to the european destination is more profitable than drug trafficking: it moves around the mediterranean, according to the latest un report published last year, about billion dollars. just take the account: boats for people are used for , crammed, standing, and almost unable to move for hours. at , e per head, it gives , e per trip. it is paid in two parts: the first , e to take them from their country of origin to the ports of libya and the other , to move them to european port, in an offshore mothership, and then in small boats that launch into the sea in a point located by gps where they can be picked up by the rescue boats of the ngos, or by merchants, fishing or recreational. if they do not find this type of boats in the area, they make a distress call with a satellite telephone with the coordinates. if the trip is frustrated and they are returned to their countries, they try again when they have collected the money. and several thousand have not even had that opportunity because they have lost their lives. with that turnover, there is no problem in paying the corresponding bribes in each place (fernández arribas ). "the good trafficker tries not to lose the immigrants who have been his clients. his goal is to get them to europe and earn money. if they lose, e.g., a truck with immigrants between agadez and algeria or a boat that sinks with people, is not a problem, because they have already paid; but if they lose kg of cocaine or two boxes of kalashnikov, then they do have a serious problem. that is the difference". and how are these people's traffickers? "these gangsters are criminal entrepreneurs, but entrepreneurs. they must have many contacts, be credible, creative, charismatic, with the power of conviction, knowledge of the routes, the laws, the latest news… which make them very fast, elastic and flexible. they also participate in other businesses; f. inst., when the vehicles that bring immigrants back through the sahara return, they never make them empty: they carry weapons or drugs back to take advantage of the trip" (musumeci and di nicola ) . fernández arribas ( ) offers a very detailed description of how tens of thousands of human beings are stranded in territories dominated by mafias, in their expected way towards europe. although every corner of the world retains its specificities, the human traffic mafias analyzed by the un reflect some common patterns. all of them have recruitment agents from the main groups that are victims of extortion. a second level is that of the local mafias, who know the land and generally pay the collectors. one more step is that of small-scale service providers: trucks, boats and other means of transport. the most dangerous level is that of the big international mafias, who control the entire process and also add links to large international crime groups and use immigrants as a way to earn money quickly and easily. infrastructures built for the exploitation of the mineral resources of the desert, oil in libya and uranium in niger, facilitate trips through the desert. according to reports from the spanish police, nigeria and libya are the most active and most established bases of immigration mafias in central africa, with ramifications in other countries, where sudanese mercenaries act unscrupulously. in the waiting time, they live in abysmal conditions, suffering very serious violations of the human rights, such as abuse, harassment, violence, robbery, kidnapping, extortion, common torture and rape. in north africa they have their point of convergence in agadez, a town north of niger, or in sehba, south of libya, where control is exercised by heavily armed tribal groups. from that point of confluence, they are transferred to the coastal cities of the tripolitana region, where trips are negotiated and where part of the population collaborates with their garages as a temporary shelter at an abusive but obligatory price for those who see the end of your nightmare construction, agriculture or any job in order to get the money. the boats used are manufactured in libya and the fishermen always have on board some drum of gasoline, pure gold for the weak boats of the new slaves of the st century. in libya, each link in the chain receives its commission, especially those who seek protection and security, from militias to corrupt authorities. this action-paying poorer ones to set up vast holding-pens for humans in unhuman conditions-is a big business for a few behind the misery of many others, and involves something which would not be tolerated at home, but it seems somehow acceptable in these situations because it is out of sight. stopping these traffickers, which is the solution that many politicians in europe offer to regulate immigration, is almost impossible; they are always ahead of a european immigration policy, without the necessary coordination. a clear example has been the failure of the military operation eunavfor med sophia (from to ), which ambitious goal of dismantling the mafias that traffic with people from the libyan coasts to europe has not been fulfilled, partially because the closing of the italian ports to illegal immigrants has left it out of play. due to the fact that operation sophia no longer uses ships but only unmanned aerial vehicles, it cannot continue rescuing people at sea. federica mogherini, at that time high representative of the union for foreign affairs, explored a new mission, with more modest goals: to train the libyan coast guard to control their own waters and avoid the departure of irregular immigrants; but there were also no practical results. this shows the external and humanitarian action of the eu, as it really is: "lack of criteria, commitment and agreement on immigration issues…. public opinion will continue to show ships coming from the libyan coasts and criminal organizations will increase their profits" (de ramón-laca ; see also espaliu , espaliú berdud . as accurately pinpointed by bitzewski (personal communication), though, it is not the eu administration to blame but the heads of states not being willing to take the action. they point their fingers out towards the eu but, when the eu puts proposals on the table, they get reluctant to contribute to the common effort. it starts with the frontier countries, crying but doing very little to protect their own borders, and goes to the rest of europe raising any reason not to commit themselves to the program. the eu should be tougher on the north african governments, corrupted and ineffective. a carrot and stick should be one of the ways to start discussion with them. it's their obligation to control migrants movement within their territories but they make money on it! turkey and egypt are perfect examples of the game. when they want they can stop trafficking! but, obviously, the money is the main reason for action. the north african countries are interested in this business and it is up to us to give them a signal "do not be too smart". we deal with state controlled trafficking and we are very naïve not forcing these governments to take the responsibility. we can help them but we cannot work for them. a key move to avoid the "calling effect" is to guarantee security and economic agreements -migration control has to be paid with money-, with those countries migrants transit through in their way to europe, preventing them from leaving its coasts and returning to their country of origin those people whose asylum in the eu has been denied. in november the eu established the emergency trust fund for africa (eutf for africa) with an allocation of e . million covering algeria, tunisia, morocco and egypt, aimed "to contribute to safe, secure, legal and orderly migration from, to and within the region and support an effective management of migration flows that protects human rights" turkey is the main starting point for the arrival of potential refugees from middle east to europe. there are more than millions syrian refugees, and almost another one in lebanon. the repatriation agreement signed by brussels and ankara in march -entering , million euros annually in the turkish coffers + visa free travel for some turkish citizens-has been a quite good example of efficacy, convincing them to keep refugees from europe's shores: more than , migrants-three fifths of the detainees came from afghanistan and pakistan-have been detained in turkish territory since the document entered into force (turkish directorate general of migration management ). according to gerald knaus, leader of european stability initiative (esi), the entry of refugees into greece was reduced "by % and even higher in the number of deaths". and, in a more global view, the more than one million irregular migrants (mainly refugees) who arrived in europe in have fallen to . in . turkey thus has played a leading role as a dam to contain migration outside europe. in the future, eu will have to invest more in integration and public awareness programmes in turkey. erdogan himself has proposed resettling at least some of the refugees in a safe zone he wants set up in northern syria. all of this is legally possible. syrians in turkey do not enjoy formal refugee status, which would protect them from deportation, but "temporary protection", which does not. according to the high commissaire of united nations for refugees (acnur, in french), a turkish meltdown would send economic shockwaves or new surges of migrants onto the european mainland. erdogan has encouraged such fears (july nd, ), threatening the suspension of the migration deal over the eu's sanctions. another point for the arrival of potential refugees from africa is the maghreb. those eu southern members with close ties to it have an special interest in encouraging the reform of state structures, as well as working to reduce the socioeconomic disparities and lack of opportunities that remain the public's most pressing problems in those countries. two successful cases have been the attempts of cooperation of the eu with morocco and tunisia, as well as a. very important job in the control of migratory flows and the fight against mafias, terrorism and drug trafficking is due to the creation of a coordination authority for the gibraltar strait. by way of example, there is a positive counter-terrorism cooperation carried out by several eu countries working closely with northern africa on security, providing training and equipment for counter-terrorism and conducting some joint operations. morocco might be a capable security partner as the authorities closely monitor its population and controls its religious sphere. it has been successful in preventing attacks and obtaining information that can benefit its european partners, but its counter-terrorism efforts fit within a framework of conserving rather than transforming the state's unaccountable relationship with its subjects, which relies on a repressive political system and resists outside calls for reform. nato has also awarded us$ billion to turkey. four years later, just when this book is going to press, the crisis has returned. turkey does not seem proactive anymore. tayyip erdogan has called for more european support for ending the war in syria and for receiving millions of refugees. and as a pression measure, on february , , turkey decided to open its borders for migrants to move to the european union. this has brought together more than , migrants along the border with greece. three weeks later, though, following the strategies of the other countries to avoid a further spread of covid- , ankara has announced just the opposite: the closure of the eu's borders. the spanish authorities have observed with relief a downward trend in arrivals in mid-january , with a significant reduction of a % of the figures of irregular immigration: the entries, an average of about . a month, confirm that the flows have been considerably reduced since then and that they have fallen to levels below those registered the previous year, when spain became the main european gateway for irregular immigration. this proactivity of morocco, deploying agents to reinforce the fight against the mafias, stop the exits by sea and employed its coastguard in the rescues on the high seas, has been highlighted both by spain and by an internal report of the european commission as the most effective tool to contain migrants. this change of attitude coincided with the announcement of the visit of king philip vi to rabat, which was finally held on february , . on that trip, the spanish monarch asked mohamed vi to go "beyond" in the control of irregular immigration. later, the fisheries and agriculture agreements, signed by eu and rabat with an injection of million euros to contain migratory flows, have also been key to boost moroccan collaboration. besides of that, spain has approved to add the almost million that rabat asked last year to contain the exit of immigrants; that is to purchase surveillance equipment "to combat irregular immigration, immigrant trafficking and trafficking in human beings", as well as for fuel, maintenance of patrols, diets and salaries (palacio b) . the moroccan and sub-saharan return agreements are also praised as a "deterrent factor" to avoid the "call effect". morocco moves many sub-saharan people to the south, leaving them lying in the middle of the desert, or locked in small cells inside an illegal detention center in arekmane ( km from melilla) and then deported to their countries. tunisia has also made significant advances in its security policies, but it has yet to find balanced ways to deal with its porous borders and the disproportionately large number of radicalized people. unfortunately, the attempts to solve the problem of migration with libya have been rather frustrating. libya is a too fragile state, a territory without government since a few years ago, which is key in the irregular migratory flows towards italy and, in the late times, increasingly diverting the flow of west african migrants to spain, via new algerian routes (fernández-sebastián ). nowadays it is the largest and more serious migration corridor, due to the use of mafia "facilitators", as we had previously commented. in this context, some libyan militias behind much of the people-smuggling migrants across the mediterranean claim that eu and, more specifically, italy have given them money and equipment to improve the coastguard stopping migrant boats from setting sail. this may explain the falling of the number of migrants crossing the sea. finally, the european leaders seem delighted with the cooperation with egypt, where immigrants no longer arrive due to the decision of this country to prevent them from leaving its coasts. if all the countries of the south did like egypt, there would be no immigrants at sea. a punctual example of joint collaboration of countries of both sides of the mediterranean sea is the cross-border military exercise neptune, with the strategic objectives of unifying efforts and coordinating action plans among the mediterranean countries, especially in terms of detention and combating the movement of foreign terrorists through ports on both sides of the mediterranean. thus, passenger and freight transport vessels were included in the controls and the use of interpol databases could be activated participation. this activity has been developed between several ports such as tangier med, tangier city and bni-ansar (nador). in sum, the eu should remain committed to encouraging and supporting the most significant pressing remaining security challenges faced by those countries, such as: ( ) the reduction of the social frustrations, economic inequality, lack of opportunities, and governance problems that increase the likelihood that people will join extremist groups and recruit radicalized individuals; and ( ) the reform of state structures, especially in relation to: (a) improving security governance based in an adequate culture and professionalism of the security forces (f. ins., training of police officers, courts judges and staff, customs and coast guard officials); and (b) developing systematic approaches to prevent further radicalization and addressing conditions that facilitate it, such as: exploring better ways to handle radicalized individuals than large-scale incarceration; distinguishing between committed jihadists and those who are more open to reintegration into society; and developing programmes to promote religious education and awareness, gearing them towards pupils and their families from an early age, so relevant to the treatment of radicalized individuals and the prevention of further radicalization (dworkin and el malki ). although the priority has to be focused on the countries of origin and transit, the fact is that we have to face a massive amount of irregular migrants who are arriving to our borders, because a chaotic, uncontrolled immigration cannot be allowed. the main objective of eu policy in this topic should be to encourage legal and orderly immigration and deter illegal flows. what should be the european criteria for who is welcome to europe and who is not, to avoid an uncontrolled migration into our continent? how could be accomplished the aims to become a historic leap in the consolidation of a european area of freedom of movement without internal borders? a spanish writer, de prada ( ), has recently reminded the clairvoyant solutions offered by thomas aquinas already in the middle age on the obligations and limits of hospitality, making clear that the help demanded by those who suffer should not be confused with their unconditional reception. he refers to several possible types of peaceful immigrant: who passes through our land in transit to another place; who comes to settle in it as an outsider; and who wants to fully join the nation that receives it "embracing their religion" (their culture, we would say nowadays). he always puts the notion of common good, which requires a desire to integrate into the life of the host country; and he is inclined not to admit them until examining their degree of "affinity" with the nation that receives them. and, as a measure of legitimate defense, we should reject those immigrants considered hostile, understanding as such not only those who have the purpose of perpetrating crimes or violence, but in general those who harbor intentions contrary to the common good of the nation that receives them (see also : ramirez ) . the decision on who is welcome and who is not does not belong to the humanitarian people, even less to the people-smugglers, but to each state. security and protection of the borders is competence of each state member. without borders there are no states and no one else can supplant a state's right to manage and protect them, treating migrants humanely but also firmly, swiftly returning those who arrived illegally or whose claims to asylum have failed. even if the eu lacks competence over it, it does not preclude the convenience of an europeanization of the migration management, through a joint cooperation for specific purposes, even if it means losing part of the national authority over a very sensitive area of the territory. the political leaders of the eu must improve their coordination and develop common legislation on borders and immigration, creating systematic and controlled arrival and integration programs, focused on the new scenarios, such as the solution of the migratory crisis, with a common, effective, and decisive security policy, finding a balance between the implementation of measures that guarantee the security of the states, while respecting the rights of those migrants who no longer enjoy their protection in their respective countries of origin. the eu not only lacks competence over the management of the flow of refugees, but also lack of homogeneous response, as it is shown by of the dublin regulation (eu european parliament ), which has resulted an absolute failure, inept to establish a coordinated strategy with minimal effectiveness. the eu foreign policy remains hopelessly underpowered, limited to coaxing national capitals towards agreement and supporting their ad hoc initiatives (the economist economist a, b; niño ). it is good to remind again that it is not eu to blame but the states not taking actions. the dublin regulation ( ) determines the eu member state responsible for the examination of an application for asylum seekers of international protection under the geneva convention relating to the status of refugees of july , as supplemented by the new york protocol of january (eu ). according to this legislation, the first member state in which the asylum application is submitted will be responsible for the examination of the request for international protection and the asylum seekers have to stay there. this, the so-called "one stop one shop", burden the countries situated at the entry to europe, notably those in the south, and the individual preferences -that is, where people arriving into europe actually want to go to and where do they wish to live-are bound to not be properly taken into account. consequently, if they move later to another european country -known as secondary movements-, this second receptor may return them to the first state. this secondary migration penalizes those southern countries, because most refugees arrive to the coasts just as a transit towards other northern european countries, where many of the newcomers had linguistic and cultural or family ties. or with better job opportunities and welfare provision. as a matter of fact, most of them live already in germany. in front of this, the different eu member states have rather antagonistic approaches: (a) northern countries, preferential asylum for most of the refugees, are in favour of a quotes policy imposed by brussels' "eurocrats" for the reubication of refugees, and suggest an eu budget with more funds for those regions with higher number of asylum seekers. (b) mediterranean countries, plus portugal and france, suffering a heavy migratory pressure in their borders, have the feeling of being left alone to cope with immigrants, and reject the responsibility of attending by themselves everybody who arrives to their borders, because it would mean establishing a sort of sanitarian cordon with the rest of the communitarian block. their aim is a reform of the dublin regulation and the help of the other eu countries in the sharing of the irregular immigration arriving to the outer borders. for instance, the greek government and aid agencies argue that the eu must overhaul the dublin regulation, so that asylum-seekers are distributed more evenly. the current system, they say, is unfair. five countries-greece, italy, spain, france, and germanyreceived over three-quarters of europe's asylum applications in the first half of . greece has had to deal with times as many claims as hungary, a country of comparable size and wealth. the rules are also ineffective: eu money is not an adequate replacement for relocation. southern countries are also reluctant to expand frontex because this affects their rights to the sovereignty of control of the territory, but also concerns related to better registration of migrants…. this is the key problem! (c) the visegrad countries (v ) -poland, hungary, czech republic and slovakiaplus baltics (latvia and lithuania) and some recent addings (at least, austria, and partially italy), call for reform, and refuse to consider any binding sharing in , germany received . applications, almost double that of any other eu country, requesting the return of . refugees to other eu countries, but only managed to execute % of the returns of asylum seekers requesting from the eu. based on that, the german home minister, horst seehofer, wants to send tens of thousands of migrants to italy, and, on the contrary, italian home minister, feels legitimized to send those who arrive to the northern european countries; f.ins.,"france was to welcome , immigrants, but in reality accommodated only " (france has returned to italy , people in ). following the principle of solidarity, which is included in the lisbon treaty ( ), jean-claude juncker called on the member states of the eu to share refugee quotas according to the wealth of each country and population size, but it shattered and the european policy of immigration and asylum was marked by increased sovereignism in the states of europe. out of asylum-seekers. based on their right to security, they insist that their priorities are more about controlling europe's outer borders, in order to preserve the free movement of persons within the schengen space, than about managing the burden of refugees who cross them. what should be a reasonable attitude to avoid an uncontrolled moving of illegal migrants within the schengen area? the intended distribution of the burden of refugees imposing a quota system -i.e. every eu state had to admit a fixed amount of people-has not worked: only a % of the quota has been achieved by the different members. this system of quotes was firmly opposed by the central europe defence cooperation (cedc), arguing that the structures of their countries are not "ready" for supporting the social weight of the newcomers: it would be highly detrimental to the national security and sovereignty. they felt marginalized by angela merkel decision to keep germany's borders open to refugees at the peak of the crisis in , without any previous consultation; it seemed to them, the chancellor had turned them into transit corridors for undesirable migrants drawn by the promise of a cushy life there. they suggest as alternative to accept the free choice of country. following this rationale, the polish minister of foreign affairs in years - , witold waszczykowski, was backing the disagreement of his president, andrzej duda, to force the entrance of immigrants against the wishes of the polish people, asserts that "the security of poland is more important than the unjustified decisions of the european institutions on the issue of the refugees". viktor orban even dares to declare central europe a "migrant-free zone". the central european countries are pushing for the eu to get involved in the custody of the external borders and accuse the southern countries of letting irregular migrants pass unchecked through their territory to the rest of the eu, and ending up circulating in europe at will. for instance, sebastian kurz, at that time austrian kanzler and rotatory president of the council of the eu, told in a local newspaper "i am afraid that many are trying to avoid the high number of migrant records that they would have to do" (referred in abc, / , ) . his words suggested that national authorities sometimes turn a blind eye to not registering migrants and that, on the other hand, a community official who did not work directly for any state would not allow those distractions. the eu summit in brussels on june th , following a suggestion of angela merkel and horst seehofer, reached a transitory agreement based in two points: (a) bilateral agreements between different states, stopping secondary movements in their inner borders, i.e. sending the refugees back to the state in which their asylum application was first submitted, obviously with an economical compensation; and (b) more resources for setting up centres of transit (internment) or "landing regional platforms" with the task of reviewing asylum applications, "distinguishing between economic migrants and those needed of international protection". this move would speed up the deportations, disincentives dangerous adventures and reduce drownings at sea. this seems to partially accept sebastian kurz's proposal of a "copernican revolution" in asylum policy migratory model, as a new possible alternative similar to the one applied in australia: to implement the number of naval patrols for intercepting boats with refugees and confine them in islands like nauru o papua-new guinea": control first; then generosity. following this model means two things: first, taking tough action along borders, at sea and "upstream" (inside africa) to slash the number of asylum-seekers smuggled to europe; thwarting smuggling, the argument goes, would reduce drownings at sea, and reassure voters who might otherwise be tempted by the far right. second, striking deals with poorer countries to establish camps, run with un agencies, to receive, detain and, eventually, return migrants. it is a laudable but ill-defined goal, because it is unclear where to establish those camps. it was mentioned "in safe countries outside the eu". but where? some members want deals with north african countries to reduce departures, but it still unknown which non-european countries would be willing or able to host such centres. in front of this north african rejection, the danish prime minister at that time, lars lokke rasmussen, revealed that some communitarian countries are austria, which occupied the eu presidency that semester, hoped for a quick agreement to equip frontex with a supranational force of up to , members and to establish a landing platform for irregular migrants in north africa. algeria: just the day after the summit, algerian foreign minister abdelkader messahel said in an interview with the french broadcaster rfi: "i believe that europeans have enough capacity, means and imagination to manage these situations." "it is excluded that algeria opens any retention zone. "morocco: the next day, the moroccan foreign minister, naser burita, emphatically stressed that this country has always "rejected and rejected" in its territory the detention centers for foreign migrants. tunisia: for logistical and political reasons, it could be the ideal candidate to host this type of centers: its coasts are the closest to the maritime zone where the majority of migrants sailing from the western strip of libya are rescued; and, its democratic transition seems to be quite consolidated, being the country in the region that receives the highest volume of eu aid funds per capita. however, the tunisian ambassador to the eu, tahar cherif. abounded in categorical rejection by his political class and public opinion. "for tunisia, the creation of reception centers is a red line," says valentin bonnefoy, a researcher at the tunisian ftdes, a ngo specialized in migration. more than seven years after the revolution, this maghreb country does not have an asylum law, something that many observers attribute to a veiled strategy to avoid becoming a host country. egypt also rejected the possibility, although in a not-so-sharp way: "the eu migrant reception facilities in egypt would violate the laws and the constitution of our country," said parliament president ali abdel seeking to establish camps for failed asylum-seekers in a continental country, but out of ue, more specifically in the balkans. there is even a third possibility to consider: within the own eu border. jean-claude juncker, in his speech on the state of the eu, proposed to establish a more efficient control of the eu's external border, converting frontex, created in and reinforced in as a european guard of coasts and borders, into an authentic border police, but not in charge of rescuing. although still subject to the control of the national authorities, it is provided with broad competences in areas such as the control of irregular migratory flows from outside the eu, the return of irregular migrants to their countries of origin, the detection of illegal steps between countries of the club and the fight against the channels of transit in third countries. on november th , the eu decided to grow it from , s to a standing corps of , , with a % jump in funding next year, to m. e, for the first time, the eu will be able to dispatch gun-toting men and women clad in eu uniforms to patrol its fringes, without asking member-states to cough up guards. in this way, the surveillance capacity in european territory will be reinforced. this necessary hard-headed policy of tough border controls, swift return of illegal immigrants and encouraging would-be migrants to stay home obliges governments to work with others in the control of its migratory flows. europe cannot maintain the schengen system of internal free migration if it does not control its external borders. and, we have to admit it, it does not. the eu has so far failed in all its attempts to establish a common policy to address the problem; it has become impossible to have a level-headed conversation about managing migration in europe. the malta agreement (september rd, ) is a tentative deal, signed by a group of five eu interior ministers (germany and france, as well as finland, italy and malta), on a temporary scheme for a rapid relocation in other countries of asylum seekers, who are rescued from the mediterranean sea. it could open the way to a comprehensive overhaul of the dublin regulation by which the migrant's country of arrival is responsible for verifying the right to asylum of each person. it states that "the relocation member state will assume responsibility for the relocated person" and contemplates a quick procedure to say in advance the number of potential refugees each state is willing to host, setting a period of only four weeks to relocate rescued refugees in the mediterranean in other member states. this would allow the frontline first-arrival countries (the mediterranean), to be discharged from the responsibility of participating in their reception, quite heavy in periods of strong migratory pressure. in return, berlin and paris hope to achieve a reduction in the socalled "secondary movements" or movements of irregular migrants from the country of entry to other eu states. aal in welt am sonntag. in addition, aal said that his country already has millions of refugees from nearby countries, such as syria, yemen, iraq or sudan, so its reception capacity is at the limit. the eu ministers discussed on - - , in luxembourg this proposal to relocate asylum seekers rescued at sea, but they got a lack of solidarity of the whole european bloc, and the sole support of portugal, luxembourg and ireland. the agreement also speaks of a return protocol "immediately after landing", redoubling diplomatic pressure on migrant countries of origin, using "appropriate incentives to ensure full cooperation, including consular cooperation, from countries of origin", although at least it includes everyone passing a "medical and safety exam". it also underlines the need to "commit to improving the capabilities of the coastguards of mediterranean third countries". it is hoped that the deal will put an end to the game of pass-the-migrant spectacle of some countries squabbling over which should accept responsibility for small numbers of asylum-seekers, breaching in what until now has been a guiding principle: that irregular migrants must be dealt with by their country of first arrival. since participation in the system will be voluntary, much will now depend on how many countries will take part, how many asylum-seekers each will accept and whether penalties are to be imposed on those countries that refuse to co-operate (this last seems unlikely, given that such an idea would have to be approved by all the eu's members, including the countries liable to be affected (economist ). summarizing, there is a widespread perception that a series of instruments to control its external borders are not working well -the dublin asylum agreements, refugee quotas, frontex, return and development policies…-and that a lack of trust has grown not only between the member states, but also between the states and the european institutions, especially after the refugee reception crisis in . in few words, there is a deficient management of migration and a weak european solidarity on this issue (de la cámara ; de wenden ). the call thus is now for a joint cooperation towards a true common policy on asylum and immigration with a complete and efficient control of the eu's external border, reinforcing the role of frontex. everybody accepts this priority as the only possibility left for preventing a reinstatement of inner borders controls which would lead to the end of one of the most valued achievements of the eu, the schengen space. a positive step in this direction has just being announced, after the starting of their new mandate, by margaritis schinas, vice president of the european commission in charge of completing a new architecture that guarantees solidarity to the countries of the external border: the eu is going to make sure that there is a sufficient dimension of responsibility in terms of border control and returns. and as tangible measures in that direction, they promise an improvement of the management of external borders with , permanent staff; moving towards a federalization model of border management, this coming spring there will be the first community corps with their own boats and carry weapons, with the deploying the first european coastguards. the responsibility concerning the immigrants does not finish at the border. once accepted as our guests, we cannot forget about them. and, among our humanitarian obligations, we have to help properly integrating newcomers into our own society, avoiding their eventual fondness towards a multiculturalism, which only produces ghettos of their own culture, or wrongly thinking that the mere acceptance as migrants give them the right to have a claim to social welfare. and, on the contrary, who arrive without being invited cannot impose the host other people's rules. once they find a home in a new country, they have to accept the laws, rules, traditions and culture of the adopted society that welcomes them, learn the local language, mix with the natives, and be aware of the specific needs and priorities of their new home. in few words, they come to european territory with equal rights and obligations, but no more. whoever is not able to assimilate to their new society, should better return to their origin (ramirez (ramirez , . according to the dublin regulation, asylum-seekers are the responsibility of the first country to record their presence and, if they move later to another european country, this second receptor may return them to the first state, most of them arrive to the southern coasts heading north, trying to slip there unnoticed, as illegal paperless "invisible migrants", to avoid being picked up and returned to their first country of arrival. officials in the country of arrival can also use bureaucracy to slow the process of registration. and so, after six months, the new host state becomes responsible. this gives a strong incentive for foot-dragging. the recent malta tentative deal ( ) tries to partially solve this problem, allowing the frontline states to be discharged from the responsibility of participating in the relocation of the newcomers. once accepted as our guests, what to do with them? let us focus on the policy towards them in sweden and germany, preferential asylum of most migrants. strange enough, they are far from coincident at all. in sweden, immigrants received ample food and shelter, a generous welfare benefits, . times higher than the ones received by host taxpayers, as well as many facilities for family reunification, without any special focus on their social integration. even more, most of them are not allowed to work. this almost open bar policy, paying migrants to do nothing, has produced (a) an increment of the social expenses on the foreign population, with the consequent reduction of the benefits for the natives -the newcomers have priority to the swedish people; (b) a call effect on other tentative immigrants; and (c) increase of criminality and insecurity, which triggers the anti-immigrant feelings of host taxpayers who feel swamped. in my opinion, migrants should be encouraged to work, getting them language classes and education and offering job training, and introducing them into the labor market, meeting the main demands of the host country: f. ex, in nordic countries, anticipating a shortfall of geriatric nurses. in germany, the arrival of nearly one and a half million asylum seekers since polarized the country, with a consequent rise of a climate of political anxiety. it seems they have finally realized that the solution of the problem is to integrate into the labor market those who are already in the country, and relax the requirements to allow the entry of more workers. with this purpose, in december , the german government approved the fachkräfteeinwanderungsgesetz ("skilled workers immigration law"), an ambitious legislative package to attract qualified labor from non-eu countries and alleviate the pressing lack of workers in some sectors and regions of the country. this will extend the rules covering foreign graduates to vocationally trained workers, cautiously opening the door for rejected applicants for asylum, but who are already integrated into the labor market, and recruit more workers from outside the eu with medium and high education to find qualified work under certain conditions. germany economy enjoys enviable health, registering an unemployment rate of . %, the lowest since the reunification of the country. figures from the institute for employment research (iab), under the ministry of labor, estimate that there are about . million jobs vacancies, while posts actually registered in employment offices in november amounted to , ( , more than the same month of the previous year). however, one of the biggest concerns of the german businessmen, the so-called mittelstand, the motor of the exporting power and the backbone of the german economy, is the lack of skilled workers. unlike in other european countries, small and medium-sized german companies are distributed throughout the country, not necessarily concentrated in industrial centers. this often hinders the recruitment of workers who prefer to live in urban areas. there is a shortage mostly of workers with a level of professional training, such as plumbers, or drivers, and diploma courses, for example, of children's educators. elderly care and tourism, are also crying out for workers. this legislative text allows non-eu citizens to go to germany to seek work for six months provided they have the necessary training, know the language and have the means to survive during that time. in the case of persons with temporary permits, such as rejected asylum seekers, they must show that they have been working in germany for at least months and that they do not have a criminal record. the head of the employers' association, ingo kramer, recently indicated that , of the asylum seekers who arrived in are working or receiving some vocational training. in addition to the labour shortages, there are also demographic forecasts, which warn of a marked aging of the population. these projections will also affect eastern europe, where a good part of foreign workers in germany come from and whose arrival is expected to decrease in the coming years. according to thomas liebig, expert on migration issues at the oecd, "these countries are becoming places of immigration. we have to look for workers outside the eu". although the labor integration of immigrants advances, experts warn that it will take time. "it's a slow process; sometimes they are people who do not speak a word of german, and many of them come from afghanistan or somalia, where they have not had schooling" explains liebig ( ) . tangible achievements, indeed! milanovic and branco ( ) proposes an intermediate position between open to all or closed borders, under the name of "circular migration": to admit workers who cover specific positions, having salaries and work conditions similar to those of the locals, but with not vote rights, nor social benefits for children, retirement or free education; and at the end of their contracts, they will have to return to their countries. in few words, they will be partial citizens for a limited time, like it is already happening elsewhere: in gulf, singapore, iraq, usa, canada. perhaps one country may need extra workers and be in position of offering them stable working conditions; but this may not occur in other eu members. this is also suggested by alejandro portes, princess of asturias of social sciences award : offering a temporary, flexible and comprehensive program of visas to allow access to young people who want to come to work or study for a while, allowing a fruitful flow between countries. come in that way would also be much more economical, and would do a lot of damage to the traffickers, because those who come in that way would not have to pay them ( october ). psychological experiences of refugees and the response of the community in the lake chad region summa theologica (fathers of the english dominican province translation, prima secundae, question letter to the editor, the economist de la cámara m ( ) the eu migration challenge inmigración y cuestión religiosa, abc, ago de ramón-laca j ( ) operación sophia: paradojas de la acción exterior europea. análisis en minutos | nº a new european pact on immigration and asylum in response to the "migration challenge the southern frontline: eu counter-terrorism cooperation with tunisia and morocco the problem with eu foreign policy. too much historical baggage, the economist a migrant move in malta. the eu reaches a tentative deal to share out migrants rescued at sea. the economist taking european defence seriously: the naval operations of the european union as a model for a security and defence union, cuadernos europeos de deusto los buques de la operación sophia en el dique seco: elementos de un revés para la política común de seguridad y defensa regulation (eu) no / of the european parliament and of the council of maritime dimension in the fight against illegal migration on the western mediterranean route sbarchi? un nuovo schiavismo leguina joaquín ( ) migraciones sin respuestas alemania busca extranjeros para , millones de empleos, el país, dic how to stop migration towards big cities? research gate la inevitable migración hacia europa, el pais confessioni di un trafficante di uomini. reverse niño elena ( ) terrorismo e inmigración: cambiando el foco lazos y nudos con marruecos, el mundo europe's partnership with morocco. proyect syndicate apostolic constitution exsul familia nazarethana, castel gandolfo portes a ( ) princess of asturias of social sciences award buenismo ante el problema de los refugiados, migraciones en el siglo xxi: riesgos y oportunidades el terrorismo como desafío a la seguridad global the refugees issue in the frame of the european security: a realistic approach bondad y buenismo, abc, ago sarah r ( ) le soir approche et déjà le jour baisse turkish directorate general of migration management (turkish: göçİdaresi genel müdürlügü) ( ) migration management global compact for safe, orderly and regular migration. marraquesh global trends: forced displacement in he is member of the advisory board of the society for terrorism research and of the professors world peace academy. he has also chaired the complutense research group on sociopsychobiology of aggression and the departments of psychobiology at the seville and complutense universities, as well as being director of the rector office at the autonomous university of madrid. dr. martin ramirez was a humboldt and fullbright fellow but, let us close here our considerations, stressing that a revision of national and eu legislation is required, focused towards a cooperation with the countries of origin and transit; and that, instead of dreaming naively in a chimeric -non-existing-european eldorado, we have to promote the great possibilities that african continent has, knowing that, as the journalist lucia mbimio says, "we must not stop dreaming, but change the compass of dreams! returning from europe to africa is not a failure." ( , ). key: cord- -cdthfl f authors: burkle, frederick m. title: declining public health protections within autocratic regimes: impact on global public health security, infectious disease outbreaks, epidemics, and pandemics date: - - journal: prehospital and disaster medicine doi: . /s x sha: doc_id: cord_uid: cdthfl f public health emergencies of international concern, in the form of infectious disease outbreaks, epidemics, and pandemics, represent an increasing risk to the worldʼs population. management requires coordinated responses, across many disciplines and nations, and the capacity to muster proper national and global public health education, infrastructure, and prevention measures. unfortunately, increasing numbers of nations are ruled by autocratic regimes which have characteristically failed to adopt investments in public health infrastructure, education, and prevention measures to keep pace with population growth and density. autocratic leaders have a direct impact on health security, a direct negative impact on health, and create adverse political and economic conditions that only complicate the crisis further. this is most evident in autocratic regimes where health protections have been seriously and purposely curtailed. all autocratic regimes define public health along economic and political imperatives that are similar across borders and cultures. autocratic regimes are seriously handicapped by sociopathic narcissistic leaders who are incapable of understanding the health consequences of infectious diseases or the impact on their population. a cross section of autocratic nations currently experiencing the impact of covid- (coronavirus disease ) are reviewed to demonstrate the manner where self-serving regimes fail to manage health crises and place the rest of the world at increasing risk. it is time to re-address the pre-sars (severe acute respiratory syndrome) global agendas calling for stronger strategic capacity, legal authority, support, and institutional status under world health organization (who) leadership granted by an international health regulations treaty. treaties remain the most successful means the world has in preventing, preparing for, and controlling epidemics in an increasingly globalized world. “honesty is worth a lot more than hope…” the economist, february , . infrastructure, prevention, and preparedness, yet these protections remain far from being globally understood, available, practiced uniformly, or free of political control. what is increasingly common since the last one-third of the th century is the thread of public health emergencies permeating, and often dominating, the consequences brought on by wars, conflicts, and large-scale disasters. few are aware that wartime public health crises cause more deaths than weapons. , consistently in war, the public health protective threshold is destroyed and not recovered or maintained. recovery is purposely ignored, resulting in increasing post-crisis mortality and morbidity indices that are characteristically ignored or denied, especially if they negatively impact political, ethnic, or religious groups whose views are contrary to the newly installed autocratic regime. ruger reminds us that authoritarian regimes suppress political competition and tend to have an interest in preventing human development, because improved health, education, and economic security mobilizes citizens to advocate for greater participation and more resources. public health protections are literally invisible to populations; they are often taken for granted and applauded as great successes serving as propaganda ploys in public speeches. although there has been scant investment in public health infrastructure and protections in all parts of the world, those countries suffer the most under autocratic regimes, especially where they have failed to keep pace with population growth and density. currently, both the urban and rural environment of the st century are being defined by deficient dwellings, aged and inadequate infrastructure, and insufficient capacity to respond to crises, especially in ensuring access to safe water, food, sanitation, and energy. public health surveillance, the "continuous, systematic collection, and analysis of health-related data serve as an early warning system for impending public health emergencies, but compliance differs remarkably from one country to another." , indeed, the direct and indirect mortality and morbidity resulting from these tragedies are the responsibility of the government in power, but are often the first to be ignored. ecological and environmental protections and preservations, such as the continuous surveillance mandated by the world health organization (who; geneva, switzerland) of wet markets in china that launched sars (severe acute respiratory syndrome) in , is an example of a critical monitor that was ended prematurely. only the reporting of three diseases (yellow fever, plague, and cholera) are currently binding under the international health regulations, and then some countries are unwilling to notify who fearing economic and political consequences. stable and unstable political systems the processes of political development, primarily as they apply to stable and unstable political systems and change, have always been dynamic, especially in crisis situations such as outbreaks of infectious diseases in less-developed countries. crisis situations test the stability of political systems in revealing ways, placing extraordinary demands on the political leadership and the existing public health structure and processes of the country. in the absence of early and effective preparedness, societies may experience social and economic disruption, threats to the continuity of essential services, reduced production, distribution difficulties, and shortages of essential commodities. the who emphasizes a "whole-ofsociety" approach that emphasizes significant roles not only for the health sector, but also by all other sectors, individuals, families, and communities, in mitigating the effects of a pandemic. developing such capacities is at the heart of preparing the whole of society for a pandemic. i assert that it is the loss of the whole of society's concept, thinking, and participation that is systematically destroyed in autocratic regimes that contributes to why these political systems fail. they fail when citizens have no defined ownership, channels of communication, or are allowed to participate in any aspect of the disaster cycle (prevention, preparedness, response, recovery, or rehabilitation). they fail when citizens are not allowed a voice in the implementation of acceptable policies when the political system ceases to be viewed as responsive by individuals and groups making demands on it, and by what is considered inappropriate political behavior. infectious disease outbreaks have the uncanny capacity to question the status quo, catalyze smoldering unrest, and most importantly, reveal population-based public health imperfections. the "whole of society" which depends on a form of collaborative governance, which complements public policy, disappears and is seen only as the dictate of one person. indeed, the negative influence on society, what i refer to a "societal mental health," is out of proportion to their representation in society. the democracy index, compiled by the united kingdom's economist intelligence unit (london, uk) and published annually in the economist, ranks countries according to political and civic freedom using five criteria: whether elections are free and fair, whether governments have checks and balances, whether citizens are included in politics, the level of support for the government, and whether people have freedom of expression. nations are divided into "full democracies, flawed democracies, hybrid regimes [which include those exhibiting regular electoral frauds], and authoritarian regimes" where "political pluralism has vanished or is extremely limited." the edition is considered as having the "worst average global score since the index was introduced in , driven primarily by regressions in latin america and sub-saharan africa. globally, this is the first time in the modern era where we have the fewest democracies. by ranking on how functional their political systems are, less than five percent of the world's population live in a "full democracy." fewer countries can claim free and fair elections, checks, balances, and participation in their governments. fewer nations offer freedom of expression or political participation in established political cultures. rapidly established and increasingly prosperous autocratic regimes, many first drawn in by populist claims that enticed the masses of working-class and poor, are now firmly established by an economy ruled by dictators and oligarchs with unfettered political influence. the united states is now categorized as a "flawed democracy," experiencing both undeniable presidential claims for more authoritarian rule, a population that increasingly claims loss of traditional liberties, and low esteem in which us voters hold their government, elected representatives, and political parties. characteristics of autocratic regime leadership autocratic leaders demonstrate personality and behavioral characteristics that are remarkably consistent across borders and cultures. in great part, this is due to a common fault line from their adolescent development which becomes arrested cognitively and emotionally. while they may, at first glance, seems smart, they are not bright or capable of attaining abstract reasoning. this type of reasoning is required to formulate theories and understand multiple meanings crucial for reasoning. it demands generalizations, ideas, the ability to identify the relationship between verbal and nonverbal ideas, and to understand the multiple meanings that underlie an event, statement, or object; an example often cited is: "the liberty bell is not just a piece of american history, but is a symbol of freedom." concrete thinkers misinterpret many concepts like this and are compelled to reinterpret them in their own concrete manner in political speeches and legislative decisions. abstract thinking refers to a cognitive concept involving higherorder, or complex thoughts. to be able to think in an abstract manner implies that one is able to draw conclusions or illustrate relationships among concepts in a manner beyond what is obvious. often the terms "abstract thought" and "concept formation" are used interchangeably. in the past, the term "fluid intelligence" has been used to refer to the ability to reason. the generation of concepts, or abstract ideas, indicates an ability to progress beyond concrete thinking. the concrete interpretation of a concept involves a focus on the salient, obvious characteristics. progressing beyond the tangible characteristics in order to conceptualize theoretical relationships between items or processes involves abstract thought. deeper meanings such as "freedom," "equality," "charity," "love," and "democracy" express ideas, concepts, or qualities that cannot be seen or experienced. they are considered only in the concrete sense as it applies to autocratic thinkers. the us constitution would not be understood in the manner it was originally written as it is an example of a document that requires abstract thought and is either not read, understood, or interpreted concretely by a leadership that is completely self-serving. concepts such as freedom and equal rights interpreted concretely become self-serving. studies demonstrate that "persons with different value preferences apply different neurobiological strategies when facing a decision" and can help explain the fixed values that decisions are made that are independent of an actual situation. this stubbornness of thought and action is reflected in shared personality disorders of autocratic despots. brain areas beyond those activated in actual moral dilemma situations were found to be involved. they are psychologically fixed, as illustrated by muammar gaddafi when he was being beaten to death by his own people, claiming up to the last minute: "but the people love me!" some of the well-known behaviors include cover-ups, exaggeration, and fabrication; fraud, omission, half-truth, perjury, and lies that come in various types, conveyed to exaggerate one's credentials or get the attention that reflects their universal narcissistic disposition and constant needs. in great part, these behaviors are witnessed between all despots of the world. despite the bad press lies get, and that many press agencies tally the daily lie numbers, most are ignored by political supporters in every country, particularly the ones that have spoken to avoid conflict, and as a show of collective support. operationalization of narcissism is "dispositional" which accompany a "grandiose sense of selfimportance, exhibitionism, entitlement, interpersonal exploitativeness, and a total lack of empathy." autocratic leaders: [r]etain all power, authority, and control, and reserve the right to make all decisions; distrust their subordinate's abilities, closely supervise and control people under them; rarely delegate or empower subordinates; adopt one-way communication, do not consult with subordinates or consider their opinions; create a system of rewards and punishments; use threats and punishments and evoke fear; rarely concern themselves with developmental activities; and take credit for all the accomplishments. in truth, once in positions of power, only the most emotionally healthy and resilient can avoid the slide into psychopathology. for those with some of the personality attributes of sociopathy or psychopathy, the descent into deeper pathology may be beyond their ability to resist. even their followers can become pathologically dependent. democracies characterized by individual freedom and liberty are rare. throughout history, autocratic governments and tyranny have been the rule. their lack of conscience and an inability to feel remorse are the underlying factors that are often viewed initially as charming, but soon reveal uncanny skills as master manipulators, skillful at lying and cheating. they have no capacity to feel guilt. despite an incidence rate of three percent to five percent within the general population, and % of prison populations, it sometimes seems that they already rule the most despotic and populated areas of the world. part ii: pandemic status of countries under autocratic rule as of february , , nations have who-confirmed cases of covid- (coronavirus disease ) outside china. the global surveillance covid- database centralizes all covid- cases reported from outside china and is maintained at the who headquarters in geneva. their data analysis is conducted daily to: "follow the transmission of the disease between countries; describe the characteristics of human-to-human transmission within clusters of cases; describe the characteristics of affected persons and their exposure history; and support the evaluation of public health measures implemented in response to the epidemic." this study focuses only on countries under autocratic rule and describes the current status of public health preparedness and current responses. this review includes all countries run by one person or party with absolute power. autocracy is a system of governance headed by a single ruler called an autocrat. decisions made by the autocrat are not subject to legal restraints and the autocrat exercised unlimited and undisputed power. as of , nations are ruled by a dictator or authoritarian regime. admittedly, democracy remains unsure in many countries, especially africa, where dictators rising to power are increasingly likely. the study adds that: "europe is home to one dictatorship, while three of them can be found in latin america and south america. there are eight dictatorships in asia, seven in the eurasian region of the world, and twelve span territory from the northern parts of africa to the middle east." china i cut my humanitarian teeth in china in the s and s when an unprecedented % of the population was suffering from poverty and malnutrition, one of the highest in the world. i was one of the few foreign physicians continually invited back under mao's repressive regime. this allowed me an unprecedented view of china's attempt to re-define what is the anthesis to the established global who requirements that guaranteed population-based public health protections. i taught basic public health management and reforms and helped establish emergency services to many hospitals. i was engaged in these activities while the government emphasized unprecedented industrial and economic development that contributed to rapid and "remarkable achievements" in the overall social and economic health of the population. the incidence of poverty in china in declined from % to % in , a reduction of slightly more than million people, primarily accomplished through targeting rapid industrialization and village-based poverty. it also caused "twists and turns on the development of china's public health" requirements, which lagged vastly behind industrialization. public health was never given the same priority and failed to catch up with changes that required timely updating and adjustment of services. while it took time to recognize that china was on a path to also politically and economically redefine public health protections, infrastructure, and development, warnings directed at china's new regional centers for disease control (cdc; beijing, china) fell on deaf ears. that same lack of coordination and collaboration remains evident today, placing china under a different microscope, one of greater scrutiny and judgment from the global community who sees their many poor health outcomes. many of these poor outcomes are especially related to air pollution in re-defining hazardous air by who standards as "acceptable," and prompting many in china and the world to ask "at what price?" in , there was water scarcity in two-thirds of china's cities, % had no sewage treatment facilities, the food security program was unsustainable, % of groundwater was polluted, and major rivers had their downstream microorganism ecology altered by chemicals and fertilizers dumped by industry and cities into the water. this resulted in new and re-emerging diseases. after identifying sars origin from a wet market civet source in august of , president xi's economic address, tied to security concerns, called for "full protection of people's health, stressing that public health should be given priority in the country's development strategy." an independent survey of the chinese citizenry two months later revealed that while the chinese public agreed with xi's need to promote china's more influential role in the world, they raised grave concerns about environmental safety, numerous high-profile scandals regarding unsafe medical and food products, and water and air pollution. china's story mirrors that of other developing countries in asia, the fastest-growing region in the world, in that government spending on public health is inadequate and not focused on those who need it the most. studies in - confirm that % of china's groundwater is contaminated; tap water is not safe due to water contamination by the continued dumping of toxic human and industrial waste, because oxygen levels have obliterated normal organisms in all major rivers and only algae continue to flourish. air quality remains "very unhealthy" and continues to have a major toll on public health, resulting in , to , premature deaths. , it remains unclear whether china will ever meet its air pollution goals, let alone participate in global climate commitments to reduce carbon emissions. no one in global public health was surprised to learn that once again a wet market animal, not suited for human consumption, was probably responsible for this year's covid- pandemic. however, chinese researchers now stress that the virus did not originate in the wet market, but was transferred from elsewhere, on december th and again on january th. transmission could have begun in early december or late november, admitting the world-wide spread could have been limited had the earlier alerts been implemented. after sars in , external pressure has also impacted on the development of china's public health. during the sars outbreak, the who directly told the chinese government in its mission report in april that "[t]here was an urgent need to improve surveillance and infection control" in the country. two years later, in a joint report issued by state development research center (beijing, china) and who, the chinese government officially admitted its health care system was failing, and it needed to improve its disease surveillance system at the local wet market levels if they were to be seen as a "responsible state." in december of , the first cases of covid- were diagnosed in wuhan, the capital of hubei province, and rapidly expanded. for two weeks, the existence of a novel rapidly expanding virus was known to president xi. unconscionably, china arrested, jailed, and punished physicians and journalists who defied government attempts to silence the truth of the virus. moreover, the government ceased to enforce the timely flow of crucial public health information, delaying both critical medical care, its obligations to the who, and the sacred paradigm of human interaction with a disease that collectively defines "freedom of speech." andrew price-smith put the same point succinctly post-sars, stating that "while the sars epidemic may have generated moderate institutional change at the domestic level, it resulted in only ephemeral change at the level of global governance." in other words, national sovereignty is still of paramount importance for the chinese leadership. because of its sensitivity to foreign interference into its internal affairs, the chinese government has not yet formally or officially endorsed the notion of "human security." while china has embraced multilateral cooperation in a wide array of global health issues, its engagement remains "state-centric." , the sars event not only exposed a fundamental shortcoming of china's public health surveillance system, as well as its singleminded pursuit of economic growth since the late s, but also forced china to realize that, in the era of globalization, public health is no longer a domestic, social issue that can be isolated from foreign-policy concern. having no tolerance in ceding its supreme authority, the central government has adopted a multifaceted attitude towards its civil society organizations. while beijing shows its willingness to cooperate with a wide array of actors inside china, it refuses to let its domestic nongovernmental organizations (ngos) and activists establish direct links with their counterparts overseas. , china was openly accused of a cover-up with sars, and few professionals are confident that anything has changed. chan maintains that while "it is still uncertain whether this sovereign concern will trump the provision of global public good for health. nevertheless, in a highly globalizing world, infectious diseases know no border. while china is seeking to adhere as much as possible to the underlying norms and rules of global institutions," reemphasizing that china after sars "perhaps [needs] to reframe health as a global public good that is available to each and every individual of the world, rather than merely as an issue of concern to nation-states." in a rare openness, rarely seen before, the normally secretive xi admitted at a meeting to coordinate the fight against the virus that china must learn from "obvious shortcomings exposed during its response." yet given the second-guessing that always surfaces in these tragedies, "it cannot be denied that the chinese government tried to control the narrative, another sign of irrational hubris, and as a result, the contagion was allowed to spread, contributing to equally irrational fear." a china researcher for human rights watch (new york usa) noted: "authorities are as equally, if not more, concerned with silencing criticism as with containing the spread of the coronavirus. : : : repeating a pattern seen in past public health emergencies." although less clumsy than with sars, the government kept all non-party groups that could have helped prevent the spread of the virus out of the loop. , china's religious groups who "reflect the country's decades-long revival and feeling among many chinese that faith-based groups provide an alternative to the corruption that has plagued the government" are being ignored. will this just be a temporary stay as it was post-sars, or is china capable of adopting, without conditions, the who public health requirements they have ignored to date? north korea, the most sealed-off country in the world, has literally shut down all borders and communications on covid- , denying, according to their propaganda channels, the existence of any cases or deaths. this is unusual as it sits between china and south korea, which have recorded the largest numbers of cases. researchers state it is "unlikely that north korea is free of covid- ." south korean media reported that kim jong un, the north korean leader, had an official executed for violating the quarantine after the official returned from a trip to china. this may or may not be true since such reports have proved dubious in the past. north korea press outlets claim that "not one novel coronavirus has emerged;" yet south korea's unification ministry (seoul, south korea), in charge of inter-korean relations, reported to the who that north korea had tested suspected cases of coronavirus and all came up negative. nevertheless, south korean media, relying on anonymous sources, report cases of covid- in north korea, some of them fatal, according to john linton, head of the international health care center at severance hospital in seoul: "through private sources, they're asking for disposable gowns, gloves, and hazmat suits, which are undoubtedly lacking," he says. "so something is going on, otherwise they wouldn't be asking for this." north korea relies on china for more than % of its trade. researchers admit that while health indicators have improved in the two decades since the country's s famine, during which hundreds of thousands of people starved to death, but there are still major problems. in the s, amnesty international (london, uk) detailed a crumbling health care system in north korea, a nation unable to feed its population, and, in violation of international law. north korea refused to cooperate with the international community to receive food. levels of malnutrition, maternal health, and tuberculosis (tb) are chronic problems, but a lack of accurate data on hiv/aids and hepatitis b present cause for alarm. health indicators have improved in the two decades since the country's s famine, but major problems still exist. whereas communicable diseases account for a large proportion of the disease burden, there are very few opportunities to better understand and control them. while health infrastructure has improved, capacity is low and the health system is chronically under-resourced. north korea has allowed for united nation (un) interventions, primarily focused on sustainable development, but this has been on north korea's terms, a demand not unusual for autocratic regimes. in , the report of the un commission of inquiry on human rights in the democratic people's republic of korea (dprk) concluded that: " years after humanitarian agencies began their work in the dprk, humanitarian workers still face unacceptable constraints impeding their access to populations in dire need." the report found that the dprk has "imposed movement and contact restrictions on humanitarian actors that unduly impede their access." the dprk has "deliberately failed to provide aid organizations with access to reliable data, which, if provided, would have greatly enhanced the effectiveness of the humanitarian response and saved many lives." the north korean government "continually obstructed effective monitoring of humanitarian assistance, presumably to hide the diversion of some of the aid to the military, elite, or other favored groups, as well as to markets." in summary, the report stated: in this tightly controlled political climate, international humanitarian staff often have to make compromises. some point out privately that it is unrealistic to try to uphold humanitarian standards in an environment as difficult as north korea's. they try hard to come up with ways to make their aid sustainable for the north korean people, but their plans are not always accepted. although the knowledge of public health has improved in recent years, million people are dependent on a public distribution system of food rations and more than million are undernourished. , iran early in the coivid- crisis, iran introduced containment measures that china had instituted placing tens of millions of people under lockdown. yet, iran has confirmed infections and eight deaths, and appears to have entered the epidemic phase of the disease. pakistan and turkey announced the closure of land crossings with iran, while afghanistan said it was suspending travel to the country. four new covid- cases surfaced in tehran, seven in the holy city of qom, two in gilan, and one each in markazi and tonekabon. as of this writing, several reports from the cities in the south, west, center, and north of iran indicate cases testing positive for covid- . the iranian minister of health stated that the origin of the virus was in qom, where infected chinese nationals and iranians who traveled to china during its pandemic were diagnosed. reports suggest that a minimum number of cases is between , to , , with additional unofficial reports of deaths from hamedan, saveh, tonekabon, and tehran, suggesting that the government under-reports the number of positive cases. the health ministry ordered the closure of schools, universities, and cultural centers across provinces. all sport and cultural events were shut down for two weeks and all educational public exams were postponed. unfortunately, many health workers and physicians are among newly infected cases, including the deputy health minister. the country suffers a lack of basic equipment such as masks and disinfecting materials, even in health care centers. people are in a panic due to a lack of access to protective materials and angry over the government cover-up. , personal contacts in iran, unfortunately, report that: "there is a major concern of misinformation because people do not trust the governmental information, opening the doors for rumors and more misinformation." paul hunter, professor of medicine at britain's university of east anglia (norwich, england), said the situation in iran has "major implications" for the middle east. "it is unlikely that iran will have the resources and facilities to adequately identify cases and adequately manage them if case numbers are large." as of this writing, turkey has not reported any covid- infections. the government has closed its border with iran, introduced health checks from iran, and are turning back travelers. yet travel from turkey to iran continues. turkey is strategic in its geographic position. it is bordered by eight countries, is the intersection point of asia, europe, and africa, making it one of the most strategic countries in the world. with its geopolitical position, turkey is a unique bridge between eastern and western civilizations and between all religions. , i bring up turkey because that nation also has one of the most autocratic regimes in the world, which has mastered control over the population and media. the government has a pattern of undercutting critic's claims, accusing the opposition of having ulterior motives, and systematically undercutting the independence of the rule of law. recep tayyip erdogan's one-man rule-control all executive, legislative, and judicial functions by imprisoning critical journalists and destroying what was left of the free media. he has arrested teachers, police, and government workers. erdogan must be in control of the narrative on all issues, including health. after the lessoned learned in china with one non-medical voice controlling all news on covid- , a similar false narrative, seen with all dictators, may again occur. health differences with their northern european union (eu) neighbors were a concern that delayed accession talks for full membership in the eu in . one-half the population is made up of secular and liberal turks who wish to restrain erdogan and his abuse of power. african nations autocratic or authoritarian regimes-dictatorships-have been a dominant form of governance in africa for many years. in the second decade of the st century, one concern is that they may hinder the attainment of one of the un's crucial sustainable development goals. in the last three years, analysts say that african countries have registered an overall decline in the quality of political participation and rule of law. the british broadcasting corporation (bbc; london, uk) recently reported that "more and more elections are being held in africa." however, analysts dismiss many as being "lawful but illegitimate." although studies show a majority of africans still want to live in democracies, an increasing number are looking to alternative, autocratic models. african countries, in the last three years, have registered an overall decline in the quality of political participation and rule of law; analysts say: "today there are almost the same number of defective democracies ( ) as there are hardline autocracies ( ) , among the continent's states," nic cheeseman, professor of democracy at birmingham university (birmingham, england), concludes from his analysis of the last three years. nigeria is among those listed as a "defective democracy," which underscores the importance of recognizing fragile political parties in africa. recent elections in nigeria illustrates this. nigeria is seen as an emerging democracy often found in newly emerging states, and established democratic regimes existing in states with long traditions of uninterrupted sovereignty. most critically, many autocratic african countries have been thrown into an inescapable political mix with china because of china's close economic ties with multiple african countries. this economic dependence on china has grown so fast that it has critical future implications. the rapidity in which china has launched its massive continent-wide initiatives has been lost on many. the covid- pandemic has awakened scholars to revisit its impact on africa, where the world's most powerful autocratic regimes exist. as of , the african continent was home to more than . million chinese immigrants. from to , china's africa strategy began to solve overpopulation, pollution, and the poor economy in africa and other developing countries. china offered sizeable loans to finance infrastructure projects, which incurred major debts for many third world nations, but especially africa. these loans have changed the cultural and ethnic landscape of many struggling nations. the building of african ports, highways, and railways, all with chinese money, have primarily corporate-level intentions, not the daily welfare of the populations. on the surface, these sound infrastructure projects are what africa legitimately sees as necessary for progressing out of poverty. but on closer examination, they serve china's ambitions to write the rules of the next stage of what they define as "globalization." of major concern is that these african countries are now defaulting on the loans, primarily funded by countries other than china, for daily external assistance and survival. the very predictable failures of the african countries to pay back the loans have entrapped african nations even further: "china, as the only major creditor in africa, won't be far away from taking hold of virtually every industry in africa." according to the agreements set up by china, the african nations can repay loans with natural resources such as oil. yet, the defaulted loans made for constructing ports that were not productive are already owned by china. china's massive "belt & raid initiative" was designed to link up to countries, all tied to china's multiple infrastructure contracts and investments. overland routes for roads and rail transportation guarantee that most countries involved will never be able to fully pay the loans and will remain dependent on china for their trade economies in the coming years. this receives very little attention in the western press. in , forbes reported that china now owns international port holdings in greece, myanmar, israel, djibouti, morocco, spain, italy, belgium, cote d'ivoire, egypt, and about a dozen other countries. in , china took control of kenya's largest port after that nation defaulted on its unpaid chinese loans. china wants everything from africa-its strategic location, its rare earth metals, and its fish. this leaves african nations forever indebted to beijing. over one million chinese now work in africa, with one author citing that africa is "china's second continent," but the actual long-term impact of these many transient workers on african's future is mixed. one author summarized that "on closer examination, china's ambition is to write the rules of the next stage of globalization. this suggests that beijing will not accept anything less than being the dominant landlord, one that is autocratic and mimicking the current authoritarian regime in china. china wants africa's resources and its maritime roads for beijing's large military presence." this is evident from the fact that chinese troops and weapons outnumber all other countries, especially the us, which is decreasing its military footprint. china formally launched its first overseas military base in djibouti, where it constructed strategic ports, an electric railway, logistics, and intelligence facilities. but in all their projects, they focus on highways, ports, dams, and public networks, such as electric grids, not public health infrastructure. military might is their priority, a model taken from the us over the past two decades. while the us today is trimming down its military presence in africa, china is increasing theirs. from the outset, china and heads of state from african countries met to implement eight major initiatives to strengthen the cooperation between china and africa. some of the initiatives included industrial, trade, and cultural promotion, with public health ranking as a top priority for the china-africa health cooperation plans. in , there were , health professionals from china working in all african countries, focusing on public health training and disease-control programs centered on emerging infectious diseases, malaria, hiv/aids, and health informatics, in collaboration with africa cdc (addis ababa, ethiopia), us cdc (atlanta, georgia usa), and other global partners. what remains a contradiction is the strong health priorities of the china-african cooperation, which emphasizes many health initiatives that mainland china currently lacks. but china looks to the future and its survival. as they say in their next phase of "globalization," african economic dominance will be necessary for africa's survival. what political regime will rule at that time is questionable, but will probably be autocratic across china, africa, and other countries that currently face a potential military takeover by china, such as cambodia and myanmar. in the meantime, who and other regional and country public health experts are concerned the "fragile" health systems in most african countries will not be able to cope if coronavirus takes hold on the continent. even china, with its larger pool of technical and financial resources, appears to be struggling to contain the virus. , russia for all the advances in weaponry, including the first hypersonic missile, the poor-quality of public health directly "undermines the country's economic development." their aging population and declining birth rates contribute to the low overall health status and low life expectancy. more than two million russian men are considered to be hiv positive and extremely high multi-drug resistant tb persists. the direct connection between the public health crisis and russia's economic potential is clear. it is generally accepted that the highly productive educated soviets leave the country largely for reasons having to do with the deteriorating political freedoms in the country. failure to tackle russia's huge public health problems is likely to exacerbate the brain drain already underway. it is estimated that up to , more than . million russians emigrated. that represents an even greater number than those who left after the collapse of the soviet union. , russia reported its first two cases of covid- and said the infected people were chinese citizens who have since recovered. the first three russian citizens have also been infected with covid- onboard a quarantined cruise ship in japan. around , people arriving from china have been ordered/placed under quarantine for covid- and monitored by the russian capital's facial-recognition technology. their quarantine measures have mimicked other nations and appear robust, but remain challenging to the economy and sustainability. the one achilles heel in russia's public health is the abominable rise of infectious diseases such as tb and aids. public measures for their control in russia are insufficient, mainly because of the lack of funding for treatment, vaccine prophylaxis, and health education. tuberculosis has become an epidemic in a country where it was once a rarity. immunity is down because of poverty, too little food, and difficult access to health care. russian doctors are worried that the tb epidemic could lead to epidemics of another disease. today, tb is endemic in russia, and there is a rising incidence of multi-drug-resistant strains of tb. like other autocratic regimes, russia's "political model" of globalization that feeds transnational research and treatment of infectious diseases is seriously flawed and must take responsibility for the prevention of the spread of infectious disease beyond their borders accelerated by enhanced migration. what this reveals are cautious doubts about whether russia, combined with shortages of medical supplies and inadequate standards that further highlights a number of public health challenges for the country, has the public health and political capacity to manage a serious covid- epidemic. the borgen project, which addresses poverty and hunger, focuses on the leaders of the most powerful nations addressing the need to deal with poverty as a consequence of their dictatorial rule. it is repeated here as it serves as an objective measure of the consequences of a despotic rule, as well as an indication of the physical and emotional state of populations that might not survive the additional insult of an infectious disease: the united states, now designated a "flawed democracy," is showing increasing authoritarian rule and threats to basic health protections, especially in combatting communicable diseases. most concerning is the president's embrace of authoritarian leaders and the real possibility of major pandemic prevention funding, including the emergency reserve fund, which is designed to be "quickly deployed to respond to pandemic outbreaks." president trump has mimicked other autocratic leaders' positions in managing any serious outbreak. he has praised president xi's rulings and failed to comment on the chinese ruler's decision to punish physicians for grossly delaying international warnings and calling attention to the public health threat for which xi was totally responsible. trump's narcissistic personality will force him to be defensive and again lie to save face. peter navarro, trump's senior trade advisor, is quoted: "this delay allowed the virus to proliferate much faster than it otherwise would have and reach other countries that it might otherwise have not." trump does not possess the knowledge base or intellectual capacity to be the spokesperson for any north american outbreak. most critically, trump has set up a narrative that will impair the us's ability to manage any serious outbreak. he has argued for cutting spending for the cdc, national institutes of health (nih; bethesda, maryland usa), and medicare directly related to communicable diseases and will directly hinder any public health response. he is oblivious to the current status of emergency medicine departments in all hospitals, rural and urban, which are currently overloaded and have no beds for influenza patients. patients must remain in emergency rooms until critical care beds open somewhere in the system, and that may take days. in no manner is our current health system capable of handling a serious outbreak, and the failure to begin a dialogue with practicing medical professionals is being ignored. lipsitch predicts that some %- % of the world's population will be infected this year. despite political claims, a vaccine is more likely seen within a year or two at best. it is no longer realistic to expect the management of these gaps in infectious disease outbreaks, especially those that threaten to be epidemics and pandemics, are to be capably managed in their present state of willful denial and offenses by many countries, especially those that are ruled by authoritarian regimes. despite resistance to globalization's health benefits that would markedly benefit the global community during these crises by authoritarian regimes, in , i called for a new who leadership granted by the international health regulations treaty that has consequences if violated. i stated: the intent of a legally binding treaty to improve the capacity of all countries to detect, assess, notify, and respond to public health threats are being ignored. while there is a current rush to admonish globalization in favor of populism, epidemic and pandemics deserve better than decisions being made by incapable autocrats. during ebola, a rush by the global health security agenda partners to fill critical gaps in administrative and operational areas was crucial in the short term, but questions remain as to the real priorities of the global leadership as time elapses and critical gaps in public health protections and infrastructure take precedence over the economic and security needs of the developed world. the response from the global outbreak alert and response network and foreign medical teams to ebola proved indispensable to global health security, but both deserve stronger strategic capacity support and institutional status under the who leadership granted by the [international health regulations] treaty. treaties are the most successful means the world has in preventing, preparing for, and controlling epidemics in an increasingly globalized world. other options are not sustainable. given the gravity of on-going failed treaty management, the slow and incomplete process of reform, the magnitude and complexity of infectious disease outbreaks, and the rising severity of public health emergencies, a recommitment must be made to complete and restore the original mandates as a collaborative and coordinated global network responsibility, not one left to the actions of individual countries. the bottom line is that the global community can no longer tolerate an ineffectual and passive international response system. as such, this treaty has the potential to become one of the most effective treaties for crisis response and risk reduction world-wide. practitioners and health decision-makers world-wide must break their silence and advocate for a stronger treaty and a return of who authority. health practitioners and health decision-makers world-wide must break their silence and advocate for a stronger treaty and a return of who's undisputed global authority. will china's unilateral decisions just be a temporary stay as it was post-sars, or is china capable of adopting, without conditions, the who public health requirements they have so far ignored? autocratic leaders in history have a direct impact on health security. dictatorships, with direct knowledge of the negative impact on health, create adverse political and economic conditions that only complicate the problem further. this is more evident in autocratic regimes where health protections have been seriously and purposely curtailed. this summary acknowledges that autocratic regimes are seriously handicapped by sociopathic narcissistic leaders who are incapable of understanding the health consequences of infectious diseases or their impact on their population. they will universally accelerate defenses indigenous to their personality traits when faced with contrary facts, double down against or deny accurate science to the contrary, delay timely precautions, and fail to meet health expectations required of nations under existing international health regulations, laws, and epidemic control surveillance. kavanaugh's lancet editorial initially praised chinese tactics that reflected a level of control only available to authoritarian regimes. as days and weeks passed, it revealed a government that inherently became victims of their own propaganda based on "need to avoid sharing bad news." he concluded that authoritarian politics inhibited an effective response, and that openness and competitive politics favor a strategically fair public health strategy. democratic nations in comparison to autocratic regimes recognize that public health fundamentally depends on public trust. the who's china joint mission on coronavirus disease report has applauded china's eventual response capability and capacity with strict measures to interrupt or minimize transmission chains with extremely proactive surveillance, rapid diagnosis, isolation tracking, quarantine, and population acceptance of these measures, to implement the measures to contain covid- within the country. it must not be forgotten that china's authoritarian rule "put secrecy and order ahead of openly confronting the growing crisis and risking alarm or political embarrassment," arrested and compelled dr. li wenliang to sign a statement that his warning constituted "illegal behavior," all of which delayed a concerted public health offensive that led to his death. this was an "issue of inaction" that would have contained covid- within china and remains a potent symbol of china's failures. there is no evidence that the authoritarian regime has or will change to prevent this from happening again. i suspect china's sophisticated censorship and propaganda systems will outlast any public health improvements. world health organization research priorities in emergency preparedness and response for public health systems: a letter report wartime public health crises cause more deaths than weapons, so why don't we pay more attention? new security beat civilian mortality after the invasion of iraq interference, intimidation, and measuring mortality in war democracy and health democracy matters for health care report on global surveillance of epidemic prone infectious diseases: types of surveillance roles and responsibilities in preparedness and response development and change in political systems whole of society and whole of government approach. health and healthcare in transition: dilemmas of governance the economist intelligence unit the most authoritarian regimes in the world. business insider these are the best democracies in the world: and the us barely makes the list character disorders among 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concerns. live science seeing through the smog: understanding the limits of chinese air pollution reporting. feature article. china environment series wuhan seafood market may not be source of novel virus spreading globally research: virus did not originate at wuhan market china's engagement with global health diplomacy: was sars a watershed the sars epidemic and its aftermath in china: a political perspective disappearing the coronavirus truth tellers sars was a watershed for china public health domestically but not globally negotiating and navigating global health: case studies in global health diplomacy the guardian weekly. staff and agencies. china is accused of sars cover up coronavirus "rumor" crackdown continues with censorship, detentions. china digital times another citizen journalist covering the coronavirus has gone missing in wuhan the coronavirus outbreak exposes the truth about socialism with chinese characteristics religious groups in china step into the coronavirus crisis. the new york times north korea claims zero coronavirus cases, but experts are skeptical north korea isn't ready for coronavirus devastation the crumbling sate of health care in north korea humanitarian engagement with north korea sanctions hurt but are not the main impediment to humanitarian operations in north korea public health in democratic people's republic of korea why is iran's reported mortality rate for coronavirus higher than in other countries? nbo news now coronavirus: iran's deputy health minister tests positive as outbreak worsens world is approaching coronavirus tipping point, experts say. the guardian xi says china facing "big test" with virus, global impact spreads healthcare in overview of turkey how dictatorships take root in the st century a comparative analysis of the european union's and turkey's health status: how health-care services might affect turkey's accession to the eu is africa going backwards on democracy? bbc news june is now democracy day in nigeria. why it matters chinese immigration to africa: an essay countries jumped tenfold in the last five years what china wants from africa? everything how large chinese loans are entrapping african nations china's seaport shopping spree: what china is winning by one million chinese in africa perspectives china says it will increase its military presence in africa public health priorities for china-africa cooperation africa prepares for coronavirus some african countries at risk for the new coronavirus aren't prepared. the verge: science/health public health challenges facing russia today cripple its potential for tomorrow. the globalist: rethinking globalization the sickness of a nation. the yale global health review coronavirus in russia: the latest news. the moscow times top diseases in russia current dictators as of . the borgen project the coronavirus outbreak could bring out the worst in trump. virology isn't politics harvard scientist: coronavirus pandemic likely will infect %- % of world this year johns hopkins bloomberg school of public health usa: the international bank for reconstruction and development/the world bank global health security demands a strong international health regulations treaty and leadership from a highly resourced world health organization theme papers on global public health and international law authoritarianism, outbreaks, and information politics china's harsh response to the coronavirus has influential admirers, but western nations recognize that public health fundamentally depends on public trust report of the who-china joint mission on coronavirus disease as new coronavirus spread, china's old habits delayed fight. the new york times coronavirus weakens china's powerful propaganda machine. the new york times key: cord- -fwzm c authors: omorogiuwa, tracy be title: covid- and older adults in africa: social workers’ utilization of mass media in enforcing policy change date: - - journal: int soc work doi: . / sha: doc_id: cord_uid: fwzm c dominating headlines in the last few months, global attention has been fixed on the coronavirus pandemic given its rampaging impact on social events and human affairs. more than any other groups, older adults have been disproportionately affected by the deadly contagion. this situation poses legitimate concerns to the social work profession, whose mandate is to liberate vulnerable people and promote social development. although the covid- pandemic has continued to take a devastating toll on older adults in the short-term, its long-term consequences may be far more profound unless urgent attention is directed to mitigate this situation. given the promulgation of social distancing and shutdowns among a number of african countries, many social workers have found it increasingly difficult to address the difficulties faced by older adults. this article canvasses for the utilization of the mass media in initiating policy response to the challenges of older adults throughout the continent. commanding features over the most recent couple of months, worldwide consideration has been fastened on the coronavirus pandemic, given its rampaging sway on social events or get-togethers and human issues. more than some other gatherings, more seasoned grown-ups/elderly persons have been excessively influenced by the destructive infection. this circumstance presents authentic worries to the social work calling, whose order is to free powerless individuals and advance social turn of events. in spite of the fact that the covid- pandemic has kept on negatively affecting older adults, its long term impacts might be far significant except if critical consideration is taken. although studies abound as to the importance of the mass media in initiating policy change (de vreese, ; eveland, ; iyengar, ; jerit et al., ; lawrence, ; lee et al., ; schudson, ; walgrave and van aelst, ) , there is slim evidence in africa pointing towards social workers' usage of the media in policy advocacy for vulnerable groups (amadasun, a; international federation of social workers [ifsw] , ). before considering how social workers can 'activate' this powerful but often overlooked tool, we examine the grievous effects of the pandemic on older adults in africa. studies have shown that many older adults throughout the continent are dependent on their children and relatives, as well as reliant on the informal economy (such as the agriculture and fishing industries, including engaging in petty trade and menial jobs) for survival (omorogiuwa, ) . customarily, families are the bedrock of caregiving to older adults, but recent development, wrought by the forces of globalization, has collapsed africa's age-long kinship system, thereby elevating the vulnerability of this at-risk group all the more (omorogiuwa, ) . promulgations of social distancing and mandatory self-isolation (in a bid to curtail the spread of the contagion) have resulted in a negative trade-off, affecting the livelihood of older adults. this has been exacerbated in light of emerging reports attesting to inadequacy in palliative measures (human rights watch, ; okojie, ) , including the diversion of these limited resources by affluent officials (daily trust, ; hassan, ) . suffice to assert that this situation is trenchant owing to the non-inclusion of social workers in the administration of welfare packages. furthermore, as the global economy plummets, exceeding the great recession of - (gopinath, international monetary fund, ) , mass layoffs, including cuts in paychecks and unemployment, have ensued. implicit in the foregoing repertoire is that many families that hitherto had maintained the traditional values of kinship care may be forced to sever ties with their aged relatives and parents. equally, on perceiving the dire situation and the challenges their caregivers face, older adults may feel compelled to 'relieve' their relatives of caregiving duties. again, the largely dilapidated state of the public healthcare infrastructure suggests that many senior citizens will be unable to secure healthcare in emergency situations. this is aggravated by reports of grossly inadequate test kits, ventilators, personal protective equipment, and isolation centres -all essentials for treatment and recovery (finnan, ; médecins sans frontières, ) . disturbingly, the resultant effect of this situation is that many older adults may have contracted the virus but are unaware of such reality. this, on the whole, may spell doom for the general population. this means that, as core stakeholders, social workers have got more reasons to be worried (rightly so, since we are most affected by the pandemic) (amadasun, b) as we cannot afford to lose more of our highly resourced but undervalued citizens than we already have done. on a positive note, the covid- pandemic has brought to the fore, more vociferously than ever, the imperative of urgent policy response to the challenges of senior citizens in africa. pointedly, these challenges, as hinted earlier, range from lack of (in some cases) and inadequate (in many cases) social protection for older adults, to insufficient geriatric healthcare institutions and community-based care. these facilities are needed in abundance throughout the continent, and they require the services of multi-professionals, including social workers. in fact, given the biopsychosocial focus of the social work profession, many practitioners would be instrumental in this regard (amadasun and omorogiuwa, ) . it is against this background that social workers must be at the vanguard of promoting policy change in the context of the challenges faced by older adults in africa, through the instrumentality of the mass media. given the restrictions on social gathering, social workers can drive their actions through the tripartite (figure ) layer of the mass media. the overall aim of our actions should be premised on education, counselling and advocacy. via education, we can inform the public and policymakers about the plight of older adults, which is aggravated by the indiscriminate allocation of palliative measures, as well as their deprivation of access to medical care. through this role, social workers can restate their expertise in social welfare administration and reclaim their position in this regard. through the counselling role (abiodun et al., ; omorogiuwa, ) , we can consolidate the resilience displayed so far by older adults by emphasizing their strengths, while urging policymakers to step up action for service delivery. in the context of advocacy, social workers have an integral role to play and immense responsibility to assume. researchers have identified three policy fronts necessary for making an impact: ad hoc, intermediate and long-term (amadasun, b; amadasun and omorogiuwa, ; finnan, ; ifsw, ; omorogiuwa, ) . in specific terms, amadasun ( b) defined ad hoc policy action as designed to address the immediate needs of older adults, facilitated through cash transfers or in-kind services (e.g. food deliveries). intermediate policy response is aimed at evaluative action and corrective purpose (amadasun and omorogiuwa, ) . according to these researchers, social workers can set out to evaluate the effectiveness of ad hoc policy intervention with a view to consolidating achieved gains and/ or to making corrections in the event of shortfall in policy objectives. long-term policy response is construed as actions aimed at eliminating structural impediments (amadasun, b) . in this sense, social workers should advocate for alternative means of care (e.g. community-based approach to care, not as a replacement but as a complement to existing institutional care) in order to decongest the limited and overstretched public healthcare facilities, while canvassing for investments in socioeconomic and public health infrastructures. the coronavirus pandemic has restated the necessity of urgent policy response to older adults in africa. although the impact of the mass media in initiating policy change at both micro and macro levels is well noted, social workers, as agents of social change, have scantly deployed this channel to working with older adults in africa. this article has underscored the imperative of employing the mass media in ( ) supporting older adults, ( ) raising awareness about their challenges and ( ) engaging in policy change through investments in social protection programmes and alternative means of care to older adults. taken together, it is believed that social workers can play a pivotal role in improving the social conditions of older adults in africa, not only during the pandemic but also in its aftermath. print: writing opinion pieces in major national and local tabloids electronic: engagement in talk shows and utilizing jingles in national and local tv and radio stations social: employing internet channels (e.g. youtube, skype, zoom, hashtags, etc.) furthermore, this study has significant implications for social workers in the international arena and in healthcare settings. using the mass media, social workers can help empower the older adults not only in africa but also in other parts of the world, by striving to understand cultural diversity, appreciate cross-cultural knowledge and be open to indigenous ways to problem-solving. healthcare social workers should be sensitive to alternative models whose focal point is built around restoration through strengths and relationship promotion instead of depending solely on the overly formalized clinical outlook and its concomitant pathological and disempowering language. drawing on service-users' strengths by promoting collaborations, story-telling and knowledge sharing, especially in a group context, is one way practitioners worldwide can empower and help older adults recover from and/or cope with difficult times as typified by the current pandemic. the author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article. the author(s) received no financial support for the research, authorship and/or publication of this article. tracy be omorogiuwa https://orcid.org/ - - - counselling services for remediating the biopsychosocial challenges of the aged in nigeria social work for social development in africa social work and covid- pandemic: an action call coronavirus and social work: blueprint to holistic intervention nigeria: adamawa government, apc trade words over diversion of palliative news framing: theory and typology news information processing as mediator of the relationship between motivations and political knowledge lack of covid- treatment and critical care could be catastrophic for africa the great lockdown: worst economic downturn since the great depression federal government wants citizens to report diversion of palliative resources nigeria: protect most vulnerable in covid- response: extended lockdown threatens livelihoods of millions international federation of social workers (ifsw) ( ) statement on ifsw and covid- . available online at virus outbreak will slow global economic growth this year is anyone responsible? how television frames political issues citizens, knowledge and the information environment game-framing the issues: tracking the strategy frame in public policy news framing policy debates: issue dualism, journalistic frames, and opinions on controversial policy issues covid- will worsen access to healthcare in burkina faso % of nigerians say palliatives not sufficient for individuals, businesses amid lockdown the psychosocial problems of the elderly: implications for social work practice childhood experiences: an afro-centric perspectives on child labour international social work in perspective the contingency of the mass media's political agenda setting power: toward a preliminary theory tracy be omorogiuwa is a senior lecturer in the department of social work, university of benin, with research productivity in elite journals and three flagship texts which have continued to serve students and practitioners in nigeria. key: cord- - wk an authors: kalla, ismail s.; laher, abdullah title: covid- : the concept of herd immunity – is it a strategy for south africa? date: - - journal: nan doi: . / . .v nsia sha: doc_id: cord_uid: wk an nan we are currently in the midst of probably the greatest challenge our fledgling nation has faced since the abolition of apartheid. this threat does not discriminate on the basis of race, colour, religion, gender, age or socioeconomic status. the current outbreak of the novel coronavirus sars-cov- (covid- ) was declared a global health emergency by the world health organisation (who) in january , while the united nations has described this pandemic as the worst crisis that humanity has faced since the world war ii.( ) our president declared a state of disaster in south africa on march , enforcing a military-supported national lockdown. the concept of herd immunity was introduced with the widespread use of vaccines to protect against common, but severely debilitating illnesses, such as smallpox and polio, which are spread by human contact and for which humans, are a major reservoir of these viruses. herd immunity refers to the protection of populations from these infections and is brought about by the presence of immunity against these infections in individuals present within a community. it represents the balance between an at-risk population and the microorganism. conceptually, herd immunity is defined by a subpopulation of patients who have acquired active immunity from either previous infection or prophylactic immunization. these patients subsequently confer a degree of protection to the rest of the community by decreasing the burden of disease as well as the carriage of the organism within that population group. ( ) herd immunity has been an effective tool in the fight against infectious pathogens. the widespread use of vaccinations has eradicated smallpox from the world and probably polio as well. this has been achieved by the concept of introducing herd immunity artificially by immunization against these two diseases. this concept has been widely applied to many other infectious diseases such as measles, rubella, influenza and others. the effectiveness of herd immunity is dependent on several epidemiological principles which include the following: • the disease must carry a substantial health risk. • the risk of contracting the disease must be high. the covid- virus fits all the above principles, but there is currently no clinically proven vaccine against the virus. hence, what is all the fuss regarding herd immunity for covid- in the absence of an effective vaccine? the problem with covid- is that not only is it a highly infectious and contagious virus, but it is associated with a mortality of approximately . % ( april ) in confirmed cases.( ) dense communities are particularly at risk. the crowding together of human beings, coupled with poor socioeconomic conditions, potentially places the african continent at particular risk for covid- . additionally, very few african countries have sufficient and appropriate diagnostic capabilities. who has identified top-priority countries in africa which are at high risk for the spread of covid- infection. south africa, due to high volumes of international trade and travel, is also included in this list.( ) furthermore, evidence from china suggests that both health-care resource availability and health-care burden (number of patients presenting with disease) correlate with mortality.( ) in many parts of africa, including south africa, the health-care sector is overburdened. this is largely due to infectious diseases such as tuberculosis (tb) and human immunodeficiency virus (hiv). ( ) in response to this emerging health-care threat, most countries around the world began to lock down workplaces, schools and public gatherings. in contrast, the united kingdom instead opted to limit new infections through gradual restrictions, rather than adopting stringent lockdown measures. using mathematical modelling, they postulated a strategy with the aim of achieving herd immunity by allowing the disease to run rampant through their population. this strategy is similar to one that is achieved by a national vaccination programme in an attempt to build 'herd immunity'. the rationale behind this theory is that by allowing 'enough of citizens who are going to get mild illness to become immune', a national disaster may be averted. unfortunately, this strategy failed due to the high complication rates, as well as the short incubation period and lethality of covid- . the initial uk strategy led to high rates of hospitalization and intensive care unit admissions, thereby straining their current health service capacity beyond breaking point. ( ) our understanding of the early transmission dynamics of covid- and evaluating the effectiveness of control measures is crucial for determining the potential for sustained transmission to occur in new areas. ( ) among the first patients in wuhan, china, with confirmed covid- , the median age was reported as years, % were male and the mean incubation period was . days ( % confidence interval [ci], . - . ), with the th percentile of the distribution at . days. in its early stages, the epidemic doubled in size every . days. with a mean serial interval of . days ( % ci, . - ), the basic reproductive number was estimated to be . ( % ci, . - . ).( ) using a mathematical stochastic transmission dynamic model to multiple publicly available datasets on cases in wuhan and internationally exported cases from wuhan, it was estimated that just by introducing travel restrictions, the reproductive number would decline from . to . within week. ( ) with the aid of this data, many countries around the world have introduced national lockdowns, as well as the concept of social distancing and self-quarantine as appropriate measures to control the spread of covid- . the objective of this strategy is to potentially limit the strain on an already-overburdened health-care systemso-called flattening the curve.( ) south africa has followed suit with its lock-down measures. however, this strategy may not be potentially sustainable in a south african economy nearing collapse. in addition, upon the release of the national lockdown, there remains a high likelihood of a resurgence of newly diagnosed covid- cases ( figure ).( ) most of the available reports to date indicate that children infected with covid- are less symptomatic. recent data reported from the chinese centre for disease control and prevention indicated that among the , confirmed cases of covid- , as of february , ( . %) were aged - years and ( . %) were aged - years.( ) furthermore, in a study of , confirmed covid- cases of adults and children from china, south korea, italy and spain (as on february ), a total of ( . %) deaths were recoded, with only death in the - -year age group and no deaths in the - -year age group.( , ) the notable evidence form this data is that the burden of illness for covid- lies predominantly in the patient age groups ( )). a baseline simulation with case isolation only (red); a simulation with social distancing in place throughout the epidemic, flattening the curve (green) and a simulation with more effective social distancing in place for a limited period only, typically followed by a resurgent epidemic when social distancing is halted (blue). these are not quantitative predictions but robust qualitative illustrations for a range of model choices in these statistics quoted above may lie a potential solution for south africa. the median age of the south african population is . years with an average life expectancy of . years. currently, % of the population reside within an urban environment. ( ) this implies that we have a much younger population compared to countries such as spain, italy and england who have reported large numbers of covid- related mortality. in south africa, a hybrid model could be considered, wherein young children, adolescents and adults under the age of years, without any significant comorbidities, are allowed to return to schools or universities, and for employed adults to return to their places of employment. it is imperative that this should take place in a setting where the country continues to follow all the precautionary measures of testing, surveillance, quarantine of infected individuals, social distancing, hygiene and very close support of the elderly at-risk population. the potential benefit of targeting this approach is that the cohort of the population under years has the lowest case fatality rates for covid- . furthermore, easing the lockdown within this economically productive segment of the population will make a significant impact in mitigating the negative long-term financial impact of covid- on our fragile economy. this phased approach may also help us to mitigate against the potential of the 're-emergence phenomenon', where there is a sudden spike in the incidence of new covid- cases (figure ).( , ) the rationale of an approach of this nature would be for this young population of patients to acquire mild or asymptomatic disease with subsequent immune memory to covid- . this has the potential to disrupt the natural pattern of the spread of the illness within the population at large. in addition, this young population is less likely to pose a significant burden on the health-care sector as they have a high recovery rate and a very low case fatality rate.( ) a potential limitation to the implementation of this strategy is the unknown effect of covid- on persons living with hiv and tb. however, there are preliminary reports that countries with the widespread use of the bcg vaccine seem to have a lower morbidity and mortality from covid- , thus potentially protecting our population. ( ) unfortunately, the behaviour of sars-cov- has been unlike any other infection that we have previously been exposed to -and therefore there is no right or wrong answer. we can just postulate and hope for the best! early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia concepts of herd protection and immunity the covid- epidemic potential association between covid- mortality and health-care resource availability tuberculosis control has failed in south africa -time to reappraise strategy to beat covid- , we'll ultimately need it early dynamics of transmission and control of covid- : a mathematical modelling study how will country-based mitigation measures influence the course of the covid- epidemic? are children less susceptible to covid- ? novel coronavirus pneumonia emergency response epidemiology team the covid- risks for different age groups, explained south africa demographics (population, age, sex, trends) pneumococcal conjugate vaccines: what do we know and what do we need? procedia vaccinol pneumococcal vaccines who position paper - -recommendations can herd immunity really protect us from coronavirus? correlation between universal bcg vaccination policy and reduced morbidity and mortality for covid- : an epidemiological study key: cord- -jfm yvef authors: moodley, prevan; lesage, schvaughn sandrine title: a discourse analysis of ebola in south african newspapers ( – ) date: - - journal: s afr j psychol doi: . / sha: doc_id: cord_uid: jfm yvef the ebola outbreak in three african states transformed the virus into a social reality in which media representations contributed to globalised hysteria and had rhetorical effects. this study investigated representations of the ebola virus/disease in south african news reports (march –june ). four discourses were found to operate within the globalised social context: threat to humanity, predation, invasion, and conspiracy. the south african reportage framed ebola as a predator and criminal rather than using stock warfare imagery. representations indicated alignment with phobic high-income countries and colonial hegemony. these online posts, which represented public meanings in nigeria, kamalu ( ) found that posts actively evaluated government reaction and policy, circulated ethnic and racist discourse, and reinforced notions of ebola both as a form of terrorism and othering. online media thus played a role in public circulation of fear and hysteria, and also contributed to (improper) psychosocial management of affected persons. to demonstrate this, mondragon, de montes and valencia ( ) showed that laypersons' social representations depicted ebola as being definitively african (particularly in being linked to poverty), along with portrayals of dread about entering the affected countries and 'backward' africa lacking competence to manage the disease. localised social support for and stigma towards survivors added to the global fears originating in high-income countries, detracting from public education, as well as from the political and economic challenges in the affected regions (foster & dashwood, ) . the fear, which implicated stigma, showed that implementing just a clinical response to patients was insufficient (as the human immunodeficiency virus [hiv] crisis warned society previously) because psychosocial care was needed to help both stigmatised patients and their caregivers (davtyan, brown, & folayan, ; van bortel et al., ) . survivors were stigmatised through a contagion discourse because they were denied jobs by potential employers and refused treatment by health workers (mayhew, ) . the social problem that results from fear is one of positioning particular people as dangerous others, a common response in the history of epidemics. othering is fuelled by fear, and the dehumanising effect, which may ease the process of othering, leads to the blaming of infected persons and governments who fail to control the spread of the disease. such representations, with reference to ebola, depicted the african as the 'other' and therefore, inferior, further progressing to a discourse of hope for containing the infection through the superlative promises of biomedicine being delivered from the industrialised world (washer, ) . othering representations, however, have shifted from downward othering of marginalised groups towards upward othering of governments and organisations such as the world health organization (who) (joffe, ) . for the ebola crisis, such othering led to social representations of conspiracy. according to social psychology explanations, the ingroup (the affected group in this case) attributes the calamity to an act of government or to an outgroup because their sacred values are threatened (franks, bangerter, & bauer, ) . nevertheless, othering is appropriated within other discourses. in the discourse of hope (washer, ) , the risk of infection remains relegated to 'primitive' peoples, making this the west's way of talking so that it does not consider itself to be at risk as long as its borders are not transgressed. as conceptualised by aaltola ( ) , western lay people usually watch a scenario unfolding elsewhere and judge performers on a foreign disease stage. this reinforces the 'us' and 'other' distinction. the affected regions get viewed in western newspaper reports through colonialist images of africa as a jungle where people eat monkeys and fruit bats, and have cultural practices that promote disease transmission (abeysinghe, ) . olivier ( ) considers that any uncontrolled constituent of nature such as a virus (particularly when associated with an african jungle) represents a threat to humanity and civilisation, and is relegated to an 'abject' position. this threatens western capitalistic society's notion of taming nature and, in so doing, shows up the precariousness of a technological society whose survival is based on the idea that nature is controllable. historically, images have been used to construct particular versions of diseases, as sontag's classical theorising has shown. predominant explanations have used war metaphors. these have included notions of battle, combating of infection, counterattack, invasion, and fight (sontag, ) . metaphors function as a conduit to disseminate scientific knowledge to nonexperts, but they have discursive and sociopolitical consequences (larson, nerlich, & wallis, ) , contributing to particular media framings of disease, such as those of war or a plague in the case of ebola (vellek, ) . vellek's ( ) deductive content analysis shows that such images in reports in wide-reaching newspapers in the us, uk and singapore located ebola within a mutation-contagion frame. however, using war metaphors is a choice made by journalists. as larson et al. ( ) have shown, uk newspapers avoided war metaphors in reports on severe acute respiratory syndrome (sars), an emerging infectious disease (eid), just like ebola. even though war images add newsworthiness (larson et al., ) , the militarisation of illness creates stigma for those infected. sontag ( ) asserted that discourse of war and battle should be avoided because it promotes dread and stigma. popular culture and media have also extended the war metaphor to other-worldly battles of science fiction. diseases such as acquired immune deficiency syndrome (aids) were likened to alien invaders and envisioned as the alien 'other' (sontag, ) . the imagery of outer space further reinforces the otherness through visuals of hazmat suits that get likened to space suits and thus to science fiction (joffe & haarhoff, ) . common images about social, psychological, and national threats have been used in ebola discourse. predominantly, the ebola virus, based on the outbreaks occurring until , was subjected to a rhetorical construction of predation (weldon, a) . weldon argued that, in comparison to other deadly viruses, ebola does not kill millions of people and representations of the epidemic were based on misperceptions and, specifically, on predation images derived from a text, the hot zone (preston as cited in weldon, a weldon, , b ). weldon's ( a) analysis of the predatory discourse showed that 'the issue with ebola involves a rhetorical construction, in addition to a social construction' (p. ). the discursive construction of ebola functioned to detract responsibility from the problem of compromised medical practice for managing ebola. this shift, through personifying the virus that led to fear being elicited by this construction, removed focus away from the poor health systems and practices of the affected areas. movies and books, which capitalised on this image at that time, further shifted agency away from humans responsible for the spread (weldon, a) . images of war, fire, and mythical potency contributed to this predatory discourse. weldon ( a) argued that these were exaggerations because of the epidemiological fact that needle sharing at clinics in zaire and sudan led to fatalities in the earlier epidemics. in other words, governmental systems and human agency threatened the broader-accepted belief system that western medicine was infallible. as one epidemiologist and microbiologist also pointed out, the clinical picture presented in preston's book is inaccurate (t. c. smith, ) . weldon ( a) further speaks of ebola's representation within conspiracy discourses because of the global threat of bioweapons. besides state or us conspiracy, human blood was positioned as a coagent or as being in conspiracy with the virus. through this discourse, the sentient virus instructs the blood what to do, transforming ebola into a mythical entity that displaces the human medical practitioner as true agent of transmission in the epidemics that occurred until . whereas an 'objective' account would point out human mistakes and the health-practitioner carelessness, weldon ( a) attributes the dominating predatory discourse to preston's classic, purportedly nonfiction text. research into analyses of representations of the outbreak, even if it recognised the sensationalism effect (james, ) or used systematic empirical methods (e.g., paul, mahajan, & sahoo, ; s. smith & smith, ) , did not include in-depth analyses of the ideological and discursive portrayal of the disease, a gap addressed in this article. s. smith and smith's ( ) quantitative content analysis of four nigerian newspapers simply coded for reporting genre (e.g., editorial) and type of content (e.g., death rates) in articles; and paul et al. ( ) , despite confirming the globalisation of fear, presented frequency counts as opposed to showing how the fear was discursively constructed in their quantitative content analysis of three newspaper publications in india. in this article, we therefore aim to illustrate how fear was the effect of particular representations that emanate from cultural and metaphorical content in news reports in the ebola epidemic. put differently, we aimed to identify discourses that created a sociocultural reality about ebola. this final or refined sample consisted of news reports. these were labelled systematically for source tracking. we typed in the keywords 'ebola' and 'south africa' into the online news database south african bibliographic and information network (sabinet), where south african newspaper articles are archived. the date range was restricted from march , the date when the who officially announced the ebola outbreak, to june . june was chosen as the end-date because that was when data analysis commenced, despite the ongoing occurrence of ebola beyond this date. even so, news coverage of ebola became saturated and tailed off in november . the keyword search identified articles in full text (pdf) format. after reading all articles, a manual search excluded those that did not relate directly to the ebola virus. we removed articles because they did not discuss the ebola virus itself. the excluded articles either addressed the management of the epidemic or did not refer to explicit cultural representations of the virus. we were interested in how the disease itself had taken on a particular social and metaphorical reality. because we used archived published press reports, no ethical clearance was required. the data are in a public database domain. nevertheless, in the interpretation of data, we ensured we were transparent with the quoted extracts and made interpretations supported by textual evidence. we used parker's ( ) guidelines for analysis. keywords and phrases in the reports were subjected to a process of free association. in other words, shared social meanings were listed by free associating to words and phrases, but which were relevant to the research question. this led to describing how the ebola virus/disease was understood in the texts, making way for identifying discourses or the ways in which the disease/virus was constructed. both researchers critically reflected on the meanings arising from associations to ascertain if they contained unduly idiosyncratic or overpersonalised projections, and they validated each others' inputs throughout analysis. simply, they discussed associations and reached consensus by focusing on the relevance of meanings to the research question. because the meanings arose from the social worlds and culturally consensual realities of the researchers as south africans who wished to interrogate the representations of diseases, but who were also often sympathetic to african disasters and human loss, they acknowledge that, in line with discursive practice, their shared subjectivities are instrumental in making interpretations following a poststructuralist approach as opposed to aiming for an objectivist and realist encounter with the texts. four discourses have been selected for this article. these focus on social discourse, even though the expected medical discourse was also often represented in the texts. the medical discourse consisted of facts about the clinical picture and the transmission of the virus, in contrast to our focus on how the disease achieved a social and cultural reality, a version that contributed to barriers in better addressing the epidemic. we thus exclude the medical discourse in the reporting of our findings. the texts represented the ebola virus as a threat to humankind, transforming the epidemic into a pandemic. manifested through words such as 'epidemic', 'pandemic', 'threat', and 'devastating apocalyptic epidemic', ebola induced global panic and fear: senegalese president macky sall grabbed that ball and ran with it, chiming in that: ebola is not an african disease. it is necessary to confront ebola as a threat to humanity. (fabricius, ) the ebola outbreak in west africa is fast developing into the devastating apocalyptic epidemic mankind has feared for so long. ('help needed in ebola crisis', ) the reportage assumed that borders were permeable. the ebola epidemic moved from being a threat to specific populations (affected countries) to a collective threat due to globalisation. this was noted within the image of crossing of national borders: 'the ebola pandemic is a humanitarian crisis of tragic proportions . . . extending beyond these countries' borders' (serrao, ) . regarding the threat to south africa, reportage aimed to reassure citizens: 'south africa is capable of dealing with and containing ebola if the viral disease reaches our shores. this was the assurance from government as fears of a global ebola outbreak spread across the world' (mapumulo, ) . the virus was referred to as either a human or animal predator. personifications such as 'killer' and 'agent' implied murder. this suggests vigilance because reader-victims are unaware who and when this criminal will target next: the outbreak of ebola in west africa has seen, and rightfully so, a global response to a ruthless killer that science is yet to work out how to curb. ('educate nation on ebola', ) it is a scenario that science fiction writers often toy with -an infectious agent, lurking in the shadows, suddenly pouncing when an opportunity presents itself and wreaking havoc. ('nature's assailants ', ) [ebola has] slain more than all previous outbreaks put together. (vallely, ) headlines used the discourse of predation: nature's assailants these associations to crime ('steals', 'killer', 'lurking', 'slain') prefigured a forensic science narrative, so that the predatory discourse presented the movements of the virus as subject to surveillance and crime management. using crime associations to the virus, particularly within headlines, adds to newsworthiness and befits the news genre that needs to attract readership. lethality is made more frightening when the personification crosses over into the animal world. the press reports showed that evolved human rationality, now attributed to an animal, made the virus even more unpredictable. images such as 'molecular shark' ('guinea races to stop growing ebola epidemic', ), 'killer', and 'infectious agent' combine ideas about human and animal predators. the imagery of hunting and stalking represents the virus as purposeful agents intending to eliminate the human race. thus, ebola was accorded primitive but instinctive intentionality. like an animal hunting in wild africa, the ebola virus was represented as picking out vulnerable populations first and spreading thereafter to those who assist and care for affected groups. ebola was portrayed as an invading entity moving from country to country, leaving death and devastation in its wake. this was conveyed through the use of words and phrases such as 'sweeps', 'growing', 'fire', 'inferno', and 'raging out of control'. these images portrayed ebola as unstoppable, permeating borders at will: the government of guinea has raised the death toll in the ebola epidemic raging through its southern forests and capital to . ('nature's assailants', ) the ebola outbreak has become a tale of two diseases: one quickly controlled and cured in the case of two us aid workers, and another that is raging out of control in poorly prepared african countries whose infrastructure is either basic or nonexistent. (patta, ) the blame for this spread is distributed both to the industrialised, wealthy nations and to poor african countries. the west is implied as not doing enough for africans, mobilising quickly and effectively only when their own citizens are infected. in contrast, the poor african countries are seen as kindling the virus because their compromised infrastructure further spreads the disease. this leads to blaming the affected countries and their populace, creating an 'us' (enlightened and civilised persons) versus 'them' (primitive africans) mentality. the conspiracy discourse that constructed ebola as a fabrication occurred through reports using words such as 'lie', 'invented', 'fake', and 'hoax'. as a conspiracy, the virus was portrayed as arising in the racist west and directed at primitive africans. the primitive person was positioned by the developed world as having broken taboos and 'civilized' norms (e.g., eating bushmeat). meanwhile, marginalised groups in africa blamed the west for bringing the virus to africa and unleashing it on them: academic jules evariste toa said that in some rural communities, people continue to eat bush meat and tell themselves that ebola is a virus invented by white men to decimate the african population. ('caught between rumours, hard facts' ) one factor was that it is difficult to convince communities to go to a clinic when they are sick, because they believe they will die if they enter a clinic. 'many also believe the virus is fake or that we brought it here', he [doctor working for msf] said. (coetzee, ) and the conspiracy theory drumbeat is a little scarier when it comes from people who would seem to carry some more legitimacy -like the liberian-born us professor who recently wrote in a liberian newspaper that the ebola outbreak was the result of us bioterrorism experiments. ('spare us these idiots ', ) the second type of conspiracy theory is directed not at the outside western world, but at activities within the affected countries' borders, such as governments being blamed for lying in order to raise funds and so control them: cases were isolated at the public clinic and preparations made for transferring them to kenema's lassa fever ward. this is when the rumours started spreading to kono. outside our clinic, a woman yelled, 'ebola is a lie! they're sending people to kenema to die!' (frankfurter, ) in monrovia's largest slum, west point, angry protesters broke into an isolation ward this week, chanting 'ebola is a hoax' and accusing president ellen johnson sirleaf of using the disease as a scam to raise money. (patta, ) [t]he ebola outbreak is attracting conspiracy theories, with claims ranging from the unsubstantiated to the downright crazy . . . as the washington post reported, singer chris brown informed his twitter followers that ebola was some kind of population control plot. ('spare us these idiots ', ) the discourse of conspiracy, through the view that ebola is fabricated, detracts from a community's responsibility to address the seriousness of the disease. the discourse, for those who believe in its veracity, allows 'primitive' africans to believe they are safe and keep their integrity intact, given the history of colonialism and high-income countries' hegemony over cure of disease. this discourse thus serves as a barrier to medical management. as a psychological defence towards colonial oppression, conspiracy beliefs lead to an increase in political tension, both within international relations and the affected countries. the threat to humanity discourse found in the current study is typical of media representations of ebola outbreaks that occurred until (weldon, b) . the apocalyptic references in our findings were also invoked in nurses' utterances about ebola (broom & broom, ) . such discourse, however, is not limited to ebola: in an analysis of how british newspapers portrayed a particular agricultural threat, larson et al. ( ) found apocalyptic and providential references, with these metaphors complementing warlike responses to disease. however, the threat to humanity discourse can have an enabling outcome to motivate addressing the pandemic. weldon ( b) maintained that globalisation rhetoric was deployed to get the virus recognised, leading to renewed medical research. to get help to those most affected because of their less sophisticated health care systems, representation work must resort to personalisation of the threat, even though the discourse remains problematic. key to the threat to humanity discourse is the stock image of spread that is characteristic of pandemic risk. pandemics imply 'movement, directionality and contagious spread'; boundaries become porous, leading to zones cordoned off for containment (aaltola, , p. ) . this discourse was also found in vellek's ( ) content analysis of newspaper reports of ebola as a global threat, one made possible by easier travel options in the modern world. however, this discourse, when used in the earlier outbreaks in zaire and sudan, had the effect of protecting individual governments because it sidestepped the real factors that led to fatalities, that is, the economic and systemic constraints reflected in staff not being trained or enough supplies not being provided (garrettas cited in weldon, a) . kamradt-scott ( ) , therefore, in explaining the who's reform of global health security -although late for west africa -comments that the affected countries' governments should have been more proactive by asking for help because of the global risks. thus, the effect of the threat to humanity discourse is to detract from national governments' responsibilities and failures, allocating passivity and even invisibility to their actions and roles while uncontrolled agency is granted to the virus. the uncontrolled agency is also figured into the discourse of invasion which reveals the process that unfolds with graphic descriptions of territorial uncontainment. in other words, the threat to humanity discourse, which rests on the universal globalised fear, is the outer layer of the sinister (unseen) process of invasion. the discourse of invasion was similarly found in the theme of border control in abeysinghe's ( ) research of newspaper articles of the ebola epidemic in three countries. newspaper narratives of three western nations (australia, us, uk) focussed on ebola as a problem for the west and on how political governance could manage the ebola invasion. abeysinghe's ( ) study of news reports showed that ebola became written about not as an african problem or global problem, but as a problem for once safe and enclosed countries -a discourse also taken up by south african texts in our sample. the discourse of invasion by a force of nature feeds into political and psychological fears. consequently, australian health professionals experienced anxiety and were faced with moral challenges because they had to decide 'how benevolent they were, how much they would sacrifice, and the extent of their care' (broom & broom, , p. , italics in the original). furthermore, invasion discourse is key to militaristic metaphoricity. as larson and colleagues ( ) -referring to invasive species -explain, news reports, when allocating agency to an entity, are able to justify militaristic and nationalistic responses. the discourses of threat to humanity and invasion are also given an organic face and figuration, either human or animal, via the discourse of predation. the predation discourse is in line with positioning the virus as abject, through which the menacing potential of nature threatens the technophiliac illusion that a virus can be controlled by the achievements of western civilisation (olivier, ) . predatory images provoke fear about dangers of the natural world that need taming and control (olivier, ) . the social impact implied in the image of a killer, for example, and particularly when linked to a particular geographical location, is for othering to be increased (larson et al., ) . weldon's ( b) analytic work about the representations of ebola as an invisible predatorial virus in nonfiction accounts, such as in preston's the hot zone, shows that this imagery transforms the ebola hemorrhagic fever into a legend. when these images move from books to the news media, blurring occurs between the line of purportedly objective news representations and those descriptions aiming for literary and emotive value. similarly, ungar ( ) identifies the use of words such as 'assailant' and 'killer' in newspaper articles describing ebola, but within military discourse. the most widely used frame discovered in vellek's ( ) study even subsumes notions of a 'killer' alongside war and plague metaphors, rather than considering the killer from within a predatory model. the current study found greater reliance on the predatory model compared to militaristic images of the disease. this could be attributed to sampling because we selected news reports about the virus itself, rather than about how the disease is being managed. nevertheless, predatory images have rhetorical effects. weldon ( a) found that anthropomorphising of the virus through a predatory model downplays 'the extent of human involvement in the transmission of disease in favor of a much more titillating story of a predatorial virus' (p. ). such a discursive representation is dangerous because it adds to 'ignorance regarding our biological relationship with our world, especially as it is mediated by environmental explorations, coupled with scientific and medical interventions' (weldon, b, p. ) . the global public, as audience of this myth, is distracted from their role in taking responsibility for the spread and prevention of the disease (weldon, b) . another way of detracting from political and national responsibilities for managing disease outbreaks, whether as an intrapsychic coping strategy or a delineation of ingroup-outgroup distinctions and politics, was illustrated by the finding of the discourse of conspiracy. stigmatised groups redefine how they are represented (e.g., as unsanitary) through the use of conspiracy theories (joffe, ) . washer ( ) asserts that the aim of conspiracy theories is to direct blame back at the west, thereby challenging dominant medical discourses. our findings showed two types of conspiracy theories, based on whether agency was directed either to phobic high-income countries or within the affected countries. conspiracy notions led to an uncoordinated and slow response because, close to civil war zones, people in the outbreak area distrusted the government. infected people did not access treatment facilities (representing the untrustworthy government), and they died at home: this added to understaffed facilities not managing contagious dead bodies, resorting to sending the bodies back to their homes (brown, arkell, & rokadiya, ) . the conspiracy theme, represented in movies, mobilises global action (weldon, a) . thus, journalists' quoting of people's conspiracy ideas accentuates global attention. conspiracy theories also allow people to cope with collective trauma -particularly when attributing causes to outgroups and in doing so, they also problematise the dominant discourses (franks et al., ) which, in south african press reports, related either to medical understandings or predatory images. a limitation of this study is that, because sabinet relies on manual processing, it is possible that articles may have been mistagged and therefore did not appear in the search results. in addition, there may have been newspapers that were absent from the database. that the outbreak occurred years ago does not imply the current study is delayed or irrelevant. the - ebola outbreak was the largest, with approximately , cases (centers for disease control and prevention [cdc] , ). in comparison, approximately , cases were reported in all outbreaks before (cdc, ) . fatalities from the outbreak, as well as the media representations, point to lessons. the fear discourse spread worldwide, unlike the current - outbreak in the democratic republic of congo (drc) that has approximately , cases since august (who, regional office for africa, ) and no similar global hysteria. the drc outbreak has been difficult to manage partly because of violence stemming from the community's mistrust of western medicine and medical staff (who, regional office for africa, ). our study highlights discourses similarly contained in the social construction of disease, enhancing understandings about how epidemics are represented in the public sphere, and the findings suggest that media use alternative discourses that could bring social cohesion, social action, and organised medical management, rather than disease management being disabled by fear and conspiracy. this study illustrated the emotive impact that particular cultural representations of ebola have in newspaper reports. the consensus among the press reports was that south africa was not at risk, but the discourses have implications. first, reflected in this study through the threat to humanity discourse, africa's deviation from western norms was implied to be the cause of ebola, and this upholds colonial hegemony. second, the discourse of a human criminal who stalks victims seems more distinctive of south african news reportage compared to discourses in other studies' findings that relied instead on images of a predatory microorganism. crime headlines in south africa are not uncommon, and the ebola reportage deployed similar crime rhetoric. the more common image in other studies about diseases (e.g., aids, the plague, tuberculosis) was the waging of a war against an intruder. ebola, in our research findings, was represented not as a mere intruder but as a human predator. this shift could be considered within the context of individualisation of health risks rather than nationalistic protection because globalisation has removed borders; and readers, rather than nations that can wage war, are allocated responsibility for their health risks. the news reader is incited to be on the lookout for the lurking predator. in the st century and in a country at peace, crime against an individual elicits personalised fear, in contrast to the older image of a war that threatens national security. the fear that media incites only occurs because of flaws in health-risk communication, as well as in 'our fundamentally flawed human psychology . . . the real tragedy of this failure is in the consequences of that fear reaction, both intended and unintended' (james, , p. ) . even if fear discourse could help speed up medical research, the predatory discourse, according to weldon ( b) , is dangerous globally because it reveals an unsophisticated understanding about humans' biological relationship with the world through their environmental and scientific intrusions. poor disease control 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markotter, wanda; geldenhuys, marike; jansen van vuren, petrus; kemp, alan; mortlock, marinda; mudakikwa, antoine; nel, louis; nziza, julius; paweska, janusz; weyer, jacqueline title: paramyxo- and coronaviruses in rwandan bats date: - - journal: trop med infect dis doi: . /tropicalmed sha: doc_id: cord_uid: muxrxvyo a high diversity of corona- and paramyxoviruses have been detected in different bat species at study sites worldwide, including africa, however no biosurveillance studies from rwanda have been reported. in this study, samples from bats collected from caves in ruhengeri, rwanda, were tested for the presence of corona- and paramyxoviral rna using reverse transcription pcr assays. positive results were further characterized by dna sequencing and phylogenetic analysis. in addition to morphological identification of bat species, we also did molecular confirmation of species identities, contributing to the known genetic database available for african bat species. we detected a novel betacoronavirus in two geoffroy’s horseshoe bats (rhinolophus clivosus) bats. we also detected several different paramyxoviral species from various insectivorous bats. one of these viral species was found to be homologous to the genomes of viruses belonging to the jeilongvirus genus. additionally, a henipavirus-related sequence was detected in an egyptian rousette fruit bat (rousettus aegyptiacus). these results expand on the known diversity of corona- and paramyxoviruses and their geographical distribution in africa. bats (order chiroptera) account for % of all mammalian species and are distributed worldwide. with the advancement in detection techniques and increased surveillance, bats are being increasingly recognized as hosts for many zoonotic viruses [ ] , including filo-, paramyxo-, corona-and lyssaviruses [ ] [ ] [ ] [ ] . regions in africa are considered a hotspot for emerging infectious diseases with more than % of recently emerging diseases originating from wildlife species on this continent [ , ] . although several surveillance studies have been implemented to detect potential zoonotic viruses in bats, including from countries in the congo basin and east africa, limited information is available for rwanda. importantly, in the bordering democratic republic of congo and uganda, marburg and ebola disease outbreaks in humans have occurred [ ] , and corona-and paramyxoviruses have been reported to circulate in bats [ , [ ] [ ] [ ] . coronaviruses are positive-sense rna viruses with the potential to cause respiratory, gastrointestinal, hepatic, and neurological diseases in their hosts [ ] and are divided into four genera namely alphacoronavirus, betacoronavirus, gammacoronavirus, and deltacoronavirus [ ] . bats host a large diversity of coronaviruses and the expanding research can be largely attributed to the emergence of novel coronaviruses of public health and veterinary importance. three such viruses emerged in the last years, including the severe acute respiratory syndrome (sars) coronavirus in , middle east respiratory syndrome (mers) coronavirus in , and the swine acute diarrhoea syndrome (sads) coronavirus in [ , ] . bat coronaviruses have been shown to be associated with particular bat genera and similar viruses have been identified throughout the geographical distribution of their hosts [ , , ] . diverse bat coronaviruses related to sars coronavirus (now termed the sarbecovirus subgenus) have been identified from the rhinolophus bat genus (horseshoe bats) in asia, europe and africa [ , , ] . continued surveillance within these bats species in china identified lineages of recombinant sars-related coronaviruses nearly identical to human sars coronaviruses, capable of using the same receptor molecules [ ] [ ] [ ] . as a result, these viruses have therefore been postulated to be capable of direct human infection [ , ] . bats from various african countries, including kenya, ghana, nigeria, tanzania, uganda and south africa, have yielded a large diversity of novel coronaviruses [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . some of the bat coronaviruses identified have been shown to be genetically related to known human coronaviruses such as hcov- e, hcov-nl , and mers coronavirus [ , , [ ] [ ] [ ] . paramyxoviruses are negative-sense single-stranded rna viruses capable of infecting a diverse host range including mammals, birds, reptiles and fishes [ ] . the taxonomic classification of viruses in the paramyxoviridae family has recently undergone several changes [ ] . in an attempt to accommodate the rapidly growing number of paramyxoviruses described, the previously known avulavirus and rubulavirus genera were elevated to the sub-family level (avula-and rubulavirinae) each with two new genera. in addition, several unclassified rodent-borne viruses were classified to newly established genera (narmovirus and jeilongvirus) in the sub-family orthoparamyxovirinae to which the henipa-, morbilliand respirovirus genera belong. several zoonotic paramyxoviruses have emerged as important public health threats in the past three decades. the emergence of hendra and nipah viruses (henipavirus genus) during the s in australia and southeast asia respectively, marked the first report of zoonotic paramyxoviruses of considerable public health importance [ , ] . these viruses are characterized by high morbidity and mortality rates and outbreaks have been reported on a near annual basis. in addition, another paramyxovirus, sosuga virus (pararubulavirus genus), emerged as the etiological agent of a single non-fatal human infection contracted in uganda, africa [ ] . the natural wildlife reservoir for these zoonotic viruses was determined to be the fruit bat species occurring in these areas, i.e., flying foxes from the pteropus genus for the henipaviruses [ , ] , and the egyptian rousette bat (rousettus aegyptiacus) for the rubulavirus [ ] . viruses related to the henipaand orthorubulaand pararubulavirus genera as well as a number of unclassified viruses have been described from countries bordering rwanda as well as other african countries [ , , , [ ] [ ] [ ] . r. aegyptiacus, hipposideros spp. and miniopterus inflatus have tested positive for paramyxoviral rna that is closely related to known human pathogens including the henipaviruses, human mumps virus, human parainfluenza virus and human parainfluenza virus [ , ] . in this study, we report the detection of a novel betacoronavirus in rhinolophus clivosus sampled in the ruhengeri cave system in rwanda. in addition, we report on the detection of jeilongvirus and related sequences in hipposideros spp. as well as a henipavirus-related sequence in the fruit bat species r. aegyptiacus. these results expand on the known diversity of these virus groups and their geographical distribution in africa. in december , a team from the university of pretoria, national institute for communicable diseases, and rwanda tourism board and national park authority visited two cave sites in ruhengeri, rwanda (gps coordinates: • . " s • . " e; figure ) where bats were caught at night using mist nets in the surrounding areas, and two bank g forest strainer harp traps (bat conservation and management, inc., usa, australia) at the cave entrances. when collecting samples in the field, personal protective equipment used included tyvek suits (dupont tm , wilmington, de, usa), disposable over gowns (stylianou medisupplies ltd, middle east), m full powered air purifying respirators ( m, maplewood, mn, usa), gumboots (bata industries ® , pinetown, south africa), double layer nitrile gloves (lasec, cape town, south africa) and leather gloves (evrigard, johannesburg, south africa). in december , a team from the university of pretoria, national institute for communicable diseases, and rwanda tourism board and national park authority visited two cave sites in ruhengeri, rwanda (gps coordinates: ° ' . "s ° ' . "e; figure ) where bats were caught at night using mist nets in the surrounding areas, and two bank g forest strainer harp traps (bat conservation and management, inc., usa, australia) at the cave entrances. when collecting samples in the field, personal protective equipment used included tyvek suits (dupont tm , wilmington, de, usa), disposable over gowns (stylianou medisupplies ltd, middle east), m full powered air purifying respirators ( m, maplewood, mn, usa), gumboots (bata industries®, pinetown, south africa), double layer nitrile gloves (lasec, cape town, south africa) and leather gloves (evrigard, johannesburg, south africa). bats were placed in individual cotton bags before processing. bats were morphologically identified [ ] and data including sex, reproductive status, forearm length and weight were also recorded. samples collected from bats included fecal and oral swabs, wing biopsies in % ethanol and blood (serum) for use in viral surveillance studies. oral swabs were collected by gently swabbing the inside of the mouth (cheeks and tongue) with a sterile swab (vwr critical swab, atlanta, ga, usa). fecal material or swabs (vwr critical swab, atlanta, ga, usa) were collected from the bat or the cotton bag, when it was available. sterile foreceps were used to collect fecal pellet(s) and place them in ml microcentrifuge tubes (sarstedt, nümbrecht, germany). urine was collected with a sterile swab (vwr critical swab, atlanta, ga, usa) from individual bats as was available. in instances where bats died during processing, necropsies were performed and various organs and tissues, including kidney, spleen, heart, pectoral muscles, liver, lung, stomach, bladder, tongue, brain and lymph nodes, were collected and placed in ml cryotubes (sarstedt, nümbrecht, germany). all samples were collected in rnalater preservative inactivation solution (qiagen, hilden, germany), stored at °c, then transported to and tested in south africa at the national institute for communicable diseases (nicd) and university of pretoria. permits were obtained from the rwanda development board/tourism & conservation and animal ethics was obtained from the animal ethics committee, university of pretoria. for viral rna detection, rna was extracted from kidney, spleen, urine, fecal, rectal and intestinal samples (table s ). rna from kidney (n = ), spleen (n = ) and urine (n = ), were extracted using the bats were placed in individual cotton bags before processing. bats were morphologically identified [ ] and data including sex, reproductive status, forearm length and weight were also recorded. samples collected from bats included fecal and oral swabs, wing biopsies in % ethanol and blood (serum) for use in viral surveillance studies. oral swabs were collected by gently swabbing the inside of the mouth (cheeks and tongue) with a sterile swab (vwr critical swab, atlanta, ga, usa). fecal material or swabs (vwr critical swab, atlanta, ga, usa) were collected from the bat or the cotton bag, when it was available. sterile foreceps were used to collect fecal pellet(s) and place them in ml microcentrifuge tubes (sarstedt, nümbrecht, germany). urine was collected with a sterile swab (vwr critical swab, atlanta, ga, usa) from individual bats as was available. in instances where bats died during processing, necropsies were performed and various organs and tissues, including kidney, spleen, heart, pectoral muscles, liver, lung, stomach, bladder, tongue, brain and lymph nodes, were collected and placed in ml cryotubes (sarstedt, nümbrecht, germany). all samples were collected in rnalater preservative inactivation solution (qiagen, hilden, germany), stored at • c, then transported to and tested in south africa at the national institute for communicable diseases (nicd) and university of pretoria. permits were obtained from the rwanda development board/tourism & conservation and animal ethics was obtained from the animal ethics committee, university of pretoria. for viral rna detection, rna was extracted from kidney, spleen, urine, fecal, rectal and intestinal samples (table s ). rna from kidney (n = ), spleen (n = ) and urine (n = ), were extracted using the trizol reagent (invitrogen, carlsbad, ca, usa), and fecal material/swabs (n = ), rectal and/or intestinal samples (n = ) (table s ) were extracted using the duet rna/dna extraction kit (zymoresearch, ca, usa) from samples homogenized in µl of phosphate buffered saline (lonza, basel, switzerland). both extraction methods were performed according to the manufacturer's instructions without deviations. dna was extracted using the dneasy blood & tissue kit (qiagen, hilden, germany) from heart tissues. confirmation of species identification of bats, in which viral rna was detected, was performed by amplifying the cytochrome b (cyt b) or cytochrome oxidase one (coi) gene region and determining the dna sequence. selection of cytochrome region for amplification was based on availability of credible comparative sequences in public databases (ncbi genbank and bold). previously reported pcr primers targeting these two regions were used or modified [ ] [ ] [ ] . following the pcr analysis, reactions were subjected to agarose gel electrophoresis on a . % agarose gel (lonza, basel, switzerland) and pcr amplicons were gel-purified using the wizard ® sv gel dna clean-up system (promega, madison, wi, usa) according to the manufacturer's instructions and without deviation. all amplicons were subjected to sanger sequencing for both the forward and reverse reactions on an abi dna sequencer (ae applied biosystems) at the sequencing facility of the university of pretoria. host gene sequences were subsequently compared to bat sequences available in the public domain (on the ncbi genbank and bold databases), results were interpreted and compared with the respective morphological field identifications. fecal, rectal and/or intestinal samples from bats (table s ) were extracted and analysed for coronavirus rna. complementary dna (cdna) was prepared using ng random hexamers (ie hplc purified, integrated dna technologies, coralville, ia, usa) with u superscript iv reverse transcriptase (thermo scientific, waltham, ma, usa). additionally, cdna was treated with u rnase h (thermo fisher scientific) incubation at • c for min and inactivated at • c for min. presence of coronavirus rna was detected with a coronavirus genus-specific hemi-nested rt-pcr assay which targets the rna dependent rna polymerase (rdrp) gene for amplification as described in geldenhuys et al. [ ] . as the hemi-nested rt-pcr assay produced only short amplicons (approximately bp), the rdrp-grouping unit (rgu) assay was used to extend the sequenced region of the identified betacoronaviruses to bp [ ] . a hemi-nested rt-pcr assay was performed using the randomly primed cdna prepared as well as forward primers from drexler et al. [ ] (sp '-ctt ctt ctt tgc tca gga tgg caa tgc tgc- ' and sp '-ata ctt tga ttg tta cga tggt ggc tg- ') in combination with a reverse primer (p beta_rev '-cat crt cas dia rda tca tcat-' ) from the geldenhuys et al. [ ] assay. assay conditions from geldenhuys et al. [ ] were used with modifications to cycling conditions including longer annealing and extension cycles ( cycles of • c for s, • c for s and • c for s). agarose gel electrophoresis and purification of all pcr products were performed as previously described for molecular host species identification. kidney from insectivorous bats, spleen from frugivorous bats and urine from both groups (n = ; table s ) were tested with the use of two broadly-reactive assays targeting the avula-rubulavirinae (ar) sub-families, and the respiro-morbilli-henipvirus (rmh) genera. for both assays, published primers targeting the conserved polymerase (l) gene [ ] were used in combination with adapted two-step hemi-nested rt-pcr protocols. samples were tested with the ar assay as previously described [ ] . for the rmh assay, the samples were tested as previously described [ ] , with minor variations in the protocol. for the first-round pcr, mm mgcl (thermofisher scientific, waltham, ma, usa) was added and the nuclease-free water (ambion, foster city, ca, usa) was adapted for a final reaction volume of µl. all cycling conditions and the protocol for the hemi-nested pcr remained the same as for ar. agarose gel electrophoresis and purification of all pcr products were performed as previously described for molecular host species identification. sequencing was performed as previously described for molecular host species identification. sequences were viewed, edited and a consensus generated using the bioedit sequence alignment editor software version . . [ ] . cipres was used for clustalx alignments, determining the best dna substitution model for nucleotide sequence analysis using the jmodeltest software and for constructing bayesian phylogenies using the beast version . software [ ] [ ] [ ] . bayesian mcmc chains were set to million iterations, sampling every steps for optimal ess scores. output files were visually inspected to check for convergence using the tracer software version . [ ] . the final phylogenies were constructed in treeannotator with a burn-in value of %. for visualization and manipulation of the phylogenetic tree, the figtree version . . software was used. pairwise similarities between sequences were analysed in mega x with complete deletion [ ] . in total, samples from bats constituting five genera were tested for coronaviruses (table and table s ). of these, two samples contained coronavirus rna, originating from two individuals of the rhinolophus genus. barcoding and molecular identification confirmed the host species to be rhinolophus clivosus (table s ). coronavirus sequences were extended to bp with rgu assay primer sets [ ] . the two sequences (rh-btcov/ /rwanda/ and rh-btcov/ /rwanda/ ) share . % nucleotide identity; pairwise similarities and phylogenetic analysis group these sequences with other lineage b betacoronaviruses (figure ). the closest relative to the rwandan betacoronavirus was reported from kenya, btcovky (tao et al. unpublished; genbank accession number ky . ), though the rhinolophus species is not specified. the sequences share very close sequence similarities ( . % nucleotide identity and % amino acid identity), suggesting that similar betacoronaviruses may be harbored by both kenyan and rwandan rhinolophus bats. full genome comparisons will be able to determine if kenyan and rwandan rhinolophus bats are infected by the same betacoronavirus species. within the analyzed conserved rdrp gene segment, this rwandan rhinolophus betacoronavirus also shares pairwise similarities of % nucleotide identity ( . % amino acid identity) to the bulgarian betacoronavirus rh-btcov/bm - /bgr/ [ ] , as well as close similarities ( . - . % nucleic acid similarity and . - . % amino acid identity) to asian rhinolophus sars-related coronaviruses such as sarsr-rh-btcov/rp and sarsr-rh-btcovwiv [ , ] . other coronavirus surveillance in rwanda, and surrounding countries such as uganda and tanzania also report sars-related coronaviruses from the rhinolophus genus [ ] . unfortunately, the sequences cannot be compared as an assay targeting a different conserved peptide of the rdrp gene was used [ ] . boldface indicates positive samples. twenty-four samples from bats were tested for paramyxovirus rna (table s ), none of which tested positive with the avula-rubulavirinae (ar) assay. an overall percentage positivity for paramyxovirus rna, detected using the respiro-morbilli-henipavirus (rmh) assay, was found to be . % (n = ). three of the viral sequences were detected in the insectivorous bat species hipposideros ruber and otomops martiensseni, while one other sequence was detected in the frugivorous bat species rousettus twenty-four samples from bats were tested for paramyxovirus rna (table s ), none of which tested positive with the avula-rubulavirinae (ar) assay. an overall percentage positivity for paramyxovirus rna, detected using the respiro-morbilli-henipavirus (rmh) assay, was found to be . % (n = ). three of the viral sequences were detected in the insectivorous bat species hipposideros ruber and otomops martiensseni, while one other sequence was detected in the frugivorous bat species rousettus aegyptiacus. host identification of positive samples was confirmed using molecular analysis (table s ). phylogenetic analysis of the sequences indicated that the insectivorous bat-borne viral sequences grouped with the jeilongvirus genus as well as in a jeilongvirus-related clade (figure ). one of the h. ruber sequences (batpv/hip_rub/up /rwa/ ) described from this study potentially groups within the jeilongvirus genus. the second h. ruber-derived viral sequence (batpv/hip_rub/up /rwa/ ) grouped with a paramyxoviral sequence detected in a bat from the same genus sampled in cameroon in , however, was not identical. the detection of two diverse viruses from bats of the same species and same population has previously also been reported in insectivorous bats sampled in other african countries [ ] . these observations can in part be explained by the generation of viral quasi-species populations due to the high mutation rate of rna viruses as a consequence of rna proofreading deficiency of the rna dependent rna polymerase [ ] . a larger pool of diverse viruses within a bat population and the co-roosting of several cave-dwelling bat species may facilitate viral sharing between different bat species [ ] . however, ongoing biosurveillance in these cave-dwelling bat species will be required before active viral sharing can be shown. the paramyxoviral sequence detected in the o. martiensseni bat (batpv/oto_mar/up /rwa/ ) was near identical to the viral sequences previously described from several individuals of the same species sampled in kenya in [ ] . these sequences shared a . % similarity on both nucleotide and amino acid level. the r. aegyptiacus-derived viral sequence (batpv/rou_aeg/up /rwa/ ) grouped within a henipavirus-related clade and was near identical to a paramyxoviral sequence detected in the same host species previously reported from kenya [ ] . sequence similarity shared between these two sequences was found to be . % and . % on nucleotide and amino acid level, respectively. to our knowledge, this study reports on the first evidence of paramyxovirus rna in bats from rwanda. two of the four viral sequences detected in h. ruber, were not closely related to the paramyxovirus sequences previously reported (sharing nucleotide and amino acid similarities of less than % and . %, respectively) and might represent novel viral species. however, a more rigorous analysis with variable genes such as the fusion and hemagglutinin gene will be required before putative species can be inferred. as observed in previous studies, viral sequences from frugivorous bats were mostly found to belong to the henipavirus genus or a related clade, while insectivorous bat-associated viral sequences have been linked to other genera including morbilliand jeilongvirus [ ] . this observation was again reflected in the current study. the detection of highly similar viral sequences from bats in rwanda and kenya, which are more than km apart, can be explained by either the phenomena of metapopulations or the hypothesis of co-evolution of paramyxoviruses with their bat hosts [ , , ] . rna viruses have an exceptionally high mutation rate commonly associated with quasi-species populations and with the potential to cross the species barrier, among others. this is evident in the high diversity of paramyxoviruses described to date and the wide host range associated with these viruses [ , , , ] . additionally, due to the emergence of sars, mers and sads, it is widely accepted that coronaviruses are capable of readily adapting to new hosts [ ] . the rwandan caves are considered an ecotourism site and guano is also mined on a small scale, providing an ideal bat-human interface. several insectivorous bat species co-roost with the egyptian fruit bats in these caves and future studies should investigate viral sharing. the egyptian fruit bat also uses these caves as a maternity roost and studies have shown that increased viral shedding is linked to reproductive cycles [ ] . longitudinal biosurveillance studies can therefore identify high risk periods in the future. as such, the detection of a sars-related bat coronavirus potentially circulating within the rhinolophus population and a henipavirus-related paramyxovirus in r. aegyptiacus in the ruhengeri region may merit further investigation to determine exposure, and the potential for spill-over events to occur. to date, emphasis of paramyxovirus surveillance has mostly been placed on fruit bats, the henipavirus genus and related viruses due to the association of other henipavirus species with zoonotic events [ , ] . however, research regarding the zoonotic potential of the insectivorous bat-associated viruses is still lacking. one major aim regarding surveillance of wildlife populations is to identify potential zoonotic agents and to evaluate any threat to the public as well as domestic animal health. though these bat-borne viruses are unlikely to pose a significant threat, it still merits continued monitoring of the chiropteran species within these caves as well as mammalian species that inhabit the surrounding area. , however, was not identical. the detection of two diverse viruses from bats of the same species and same population has previously also been reported in insectivorous bats sampled in other african countries [ ] . these observations can in part be explained by the generation of viral quasi-species populations due to the high mutation rate of rna viruses as a consequence of rna proofreading deficiency of the rna dependent rna polymerase [ ] . a larger pool of diverse viruses within a bat population and the coroosting of several cave-dwelling bat species may facilitate viral sharing between different bat species [ ] . however, ongoing biosurveillance in these cave-dwelling bat species will be required before active viral sharing can be shown. the paramyxoviral sequence detected in the o. martiensseni bat (batpv/oto_mar/up /rwa/ ) was near identical to the viral sequences previously described from several individuals of the same species sampled in kenya in [ ] . these sequences shared a . % similarity on both nucleotide and amino acid level. the r. aegyptiacus-derived viral sequence (batpv/rou_aeg/up /rwa/ ) grouped within a henipavirus-related clade and was near identical to a paramyxoviral sequence detected in the same host species previously reported from kenya [ ] . sequence similarity shared between these two sequences was found to be . % and . % on nucleotide and amino acid level, respectively. for countries where the bat-human interface is more pronounced, as a result of ecotourism, guano mining or bat hunting and consumption, surveillance is key to identify the diversity of viruses present and their potential host species. 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of the southwest indian ocean we would also like to thank the staff of the rwanda tourism board and national parks and wendy white from the kwazulu-natal bat interest group for assisting in the logistics and fieldwork. the authors declare no conflict of interest. the funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results. key: cord- -citynr c authors: p. shetty, nandini; s. shetty, prakash title: epidemiology of disease in the tropics date: - - journal: manson's tropical diseases doi: . /b - - - - . - sha: doc_id: cord_uid: citynr c nan the study of epidemiology in the tropics has undergone major changes since its infancy when it was largely a documentation of epidemics. it has now evolved into a dynamic phenomenon involving the ecology of the infectious agent, the host, reservoirs and vectors as well as the complex mechanisms concerned in the spread of infection and the extent to which this spread occurs. similar concepts in the study of epidemiology apply to communicable as well as non-communicable diseases. the understanding of epidemiological principles has its origins in the study of the great epidemics. arguably, the most powerful example of this is the study of that ancient scourge of mankind, the so-called black death or plague. a study of any of the plague epidemics throughout history has all the factors that govern current epidemiological analysis: infectious agent, host, vector, reservoir, complex population dynamics including migration, famine, fi re and war; resulting in spread followed by quarantine and control. the world health report : 'fighting disease, fostering development', states that infectious diseases are the world's leading cause of premature death. infectious diseases account for % of deaths in low-income countries (figure . ) and up to % of deaths in children under years of age worldwide. africa and south-east asia carry the highest mortality due to infectious diseases (figure . ). in addition, new and emerging infections pose a rising global threat (table . ). no more than six deadly infectious diseases: pneumonia, tuberculosis, diarrhoeal diseases, malaria, measles and more recently, hiv/aids, account for half of all premature deaths, killing mostly children and young adults (figure . ). acute respiratory infections (aris) are the leading cause of death of infectious aetiology, killing more than million people a year, . million of which constitute children under the age of fi ve. among the countries of the world that carry % of the child mortality burden, - % of the under- mortality is due to pneumonia and nearly % of this pneumonia mortality occurs in the africa and south and south-east asia regions. the majority of this burden is borne during early childhood, with the greatest risk from mortality occurring during the neonatal period. the global incidence of ari in children is estimated to be million cases per year. this range of infections, which includes pneumonia in its most serious form, accounts for more than % of the global burden of disease. pneumonia often affects children with low birth weight or those whose immune systems are weakened by malnutrition or other diseases. caused by different viruses or bacteria, ari is closely associated with poverty, overcrowding and unsanitary household conditions. several other factors seem to exacerbate the disease. exposure to tobacco smoke increases the risk of contracting these infections, and many studies implicate both indoor and outdoor air pollution. indoor air pollution has been the focus of particular concern: specifi cally, the soot and smoke associated with the burning of biomass fuels such as wood, coal, or dung. many people in the developing world, mostly in rural areas, rely on biomass fuels for heating or cooking. a cause-and-effect relationship between indoor air pollution and ari has been diffi cult to prove. even so, the world bank estimated in that switching to better fuels could halve the number of pneumonia deaths. approaches to the management of childhood pneumonia in the tropics are hampered by lack of diagnostic facilities to identify the aetiological agent. the who has devised a simple algorithm for use in fi eld situations, by primary healthcare workers, using clinical criteria such as respiratory rate and indrawing of ribs to decide whether a child needs hospitalization. proper implementation of this strategy has been shown to reduce the mortality from childhood pneumonias by - %. however, implementation of community ari treatment programmes remains patchy and current rates of children with ari being taken to a health provider are ~ % in africa and south asia. in nearly half of the countries with available data, less than % of the children with ari were taken to an appropriate healthcare provider. the aids pandemic has emerged as the single most defi ning occurrence in the history of infectious diseases of the late twentieth and early twenty-fi rst centuries. according to the aids epidemic update of december (unaids and who), the epidemiology of hiv in the tropics varies enormously from place to place (figure latest estimates show some . million people ( million adult women) were living with hiv in , including the . million people who became newly infected in the past year. aids claimed some lives in . these estimates are in line with known risk behaviour in this region, where men account for the majority of injecting drug users, and are responsible for sexual transmission of hiv, largely through commercial sex. commercial sex accounts for a large part of the estimated % of hiv infections in china that are due to unprotected heterosexual contact. it also features in the transmission of the virus among men who have sex with men: a recent survey among male sex workers in the southern city of shenzhen found that % of them were hivpositive. however, it is the potential overlap between commercial sex and injecting drug use that is likely to become the main driver of china's epidemic. diverse epidemics are underway in india, where, in , an estimated . million indians were living with hiv. although levels of hiv infection prevalence appear to have stabilized in some states (such as tamil nadu, andhra pradesh, karnataka and maharashtra), it is still increasing in at-risk population groups in several other states. as a result, overall hiv prevalence has continued to rise. a signifi cant proportion of new infections is occurring in women who are married and who have been infected by husbands who (either currently or in the past) frequented sex workers. commercial sex (along with injecting drug use, in the states of nagaland and tamil nadu) serves as a major driver of the epidemics in most parts of india. hiv surveillance in found % of commercial sex workers in karnataka ( % in the city of mysore) and % in andhra pradesh were infected with hiv. the wellknown achievements among sex workers of kolkata's sonagachi red-light area (in west bengal, india) have shown that safe sex programmes that empower sex workers can curb the spread of hiv. condom use in sonagachi has risen as high as % and hiv prevalence among commercial sex workers declined to fewer than the combination of high levels of risk behaviour and limited knowledge about aids among drug injectors and sex workers in pakistan favours the rapid spread of hiv, and new data suggest that the country could be on the verge of serious hiv epidemics. most countries in asia still have the opportunity to prevent major epidemics. bangladesh, where national adult hiv prevalence is well below %, began initiating hiv prevention programmes early in its epidemic. indonesia is on the brink of a rapidly worsening aids epidemic. with risk behaviour among injecting drug users common, a mainly drug-injection epidemic is already spreading into remote parts of this archipelago. in malaysia, approximately people were living with hiv in , the vast majority of them young men (aged - years), of whom approximately % were injecting drug users. after peaking at % in , national adult hiv prevalence in cambodia fell by one-third, to . % in . the reasons for this are two-fold: increasing mortality and a decline in hiv incidence due to changes in risk behaviour. thailand has been widely hailed as one of the success stories in the response to aids. by , estimated national adult hiv prevalence had dropped to its lowest level ever, approximately . %. however, thailand's epidemic is far from over; infection levels in the most at-risk populations are much higher: just over % of brothel-based female sex workers were hiv-infected in , as were % of injecting drug users who attended treatment clinics. while cambodia and thailand in the s were planning and introducing strategies to reverse the spread of hiv, another serious epidemic was gaining ground in neighbouring myanmar. there, limited prevention efforts led to hiv spreading freely. consequently, myanmar has one of the most serious aids epidemics in the region, with hiv prevalence among pregnant women estimated at . % in . the main hiv-related risk for many of the women now living with the virus was to have had unprotected sex with husbands or boyfriends who had been infected while injecting drugs or buying sex. in japan, the number of reported annual hiv cases has more than doubled since - , and reached in ; the highest number to date. much of this trend is due to increasing infections among men who have sex with men. prevalence of hiv remains low in the philippines and lao pdr. the advance of aids in the middle east and north africa has continued, with latest estimates showing that people became infected with hiv in . approximately people are living with hiv in this region. an estimated adults and children died of aids-related conditions in . although hiv surveillance remains weak in this region, more comprehensive information is available in some countries (including algeria, libya, morocco, somalia and sudan). available evidence reveals trends of increasing hiv infections (especially in younger age groups) in such countries as algeria, libya, morocco and somalia. the main mode of hiv transmission in this region is unprotected sexual contact, although injecting drug use is becoming an increasingly important factor (and is the predominant mode of infection in at least two countries: iran and libya). infections as a result of contaminated blood products, blood transfusions or a lack of infection control measures in healthcare settings are generally on the decline. by far the worst-affected country in this region is sudan. in a country with a long history of civil confl ict and forced displacement, internally displaced persons face higher rates of hiv infection. for instance, among displaced pregnant women seeking antenatal care in khartoum in , hiv prevalence of . % was found compared with under . % for other pregnant women. the epidemic in latin america is a complex mosaic of transmission patterns in which hiv continues to spread through male-tomale sex, sex between men and women, and injecting drug use. sub-saharan africa has just over % of the world's population, but is home to more than % of all people living with hiv - . the rights and status of women and young girls deserve special attention. around the world -from south of the sahara in africa and asia to europe, latin america and the pacifi c -an increasing number of women are being infected with hiv. it is often women with little or no income who are most at risk. widespread inequalities including political, social, cultural and human security factors also exacerbate the situation for women and girls. in several southern african countries, more than three quarters of all young people living with hiv are women, while in sub-saharan africa overall, young women between and years old are at least three times more likely to be hiv-positive than young men (figure . ). in many countries, marriage and women's own fi delity are not enough to protect them against hiv infection. among women surveyed in harare (zimbabwe), durban and soweto (south africa), % reported having one lifetime partner, % had abstained from sex at least until the age of (roughly the average age of fi rst sexual encounter in most countries in the world). yet, % of the young women were hiv-positive. many had been infected despite staying faithful to one partner. diarrhoea remains one of the most common diseases affl icting children under years of age and accounts for considerable mortality in childhood. estimates from studies published between and show that there was a median of . episodes of diarrhoea per child-year in developing countries. this indicates little change from previously described incidences. estimates of mortality revealed that . children per /year in these countries died as a result of diarrhoeal illness in the fi rst years of life, a decline from the previous estimates of . - . per /year. the decrease was most pronounced in children aged under one year. despite improving trends in mortality rates, diarrhoea accounted for a median of % of all deaths of children aged under years in developing countries, being responsible for . million deaths per year. there has not been a concurrent decrease in morbidity rates attributable to diarrhoea. as population growth is focused in the poorest areas, the total morbidity component of the disease burden is greater than previously. diarrhoea remains a disease of poverty affl icting malnourished children in crowded and contaminated environments. efforts to immunize children against measles, provide safe water and adequate sanitation facilities, and to encourage mothers to exclusively breast-feed infants through to months of age can blunt an increase in diarrhoea morbidity and mortality. preventive strategies to limit the transmission of diarrhoeal disease need to go hand in hand with national diarrhoea disease control programmes that concentrate on effective diarrhoea case management and the prevention of dehydration. the factors contributing to childhood mortality and morbidity due to diarrhoea are described in table . . studies in asia and africa have clearly shown that establishment of an oral rehydration therapy (ort) unit with training of hospital staff can signifi cantly reduce diarrhoea case fatality rates. for instance, at mama yemo hospital in kinshasa, zaire, there was a % decline in diarrhoea deaths after creation of an ort unit. in may , the world health organization and the united nations children's fund recommended that the formulation of oral rehydration solution (ors) for treatment of patients with diarrhoea be changed to one with a reduced osmolarity and that safety of the new formulation, particularly development of symptomatic hyponatremia, be monitored. a total of patients, including children younger than months, were monitored at the dhaka and matlab hospitals, bangladesh. the risk of symptoms associated with hyponatraemia in patients diarrhoeal disease treated with the reduced osmolarity ors was found to be minimal and did not increase with the change in formulation. changing patterns in the epidemiology of diarrhoea have been noted in many studies. in matlab, bangladesh, acute watery diarrhoea accounted for % of diarrhoea deaths in under-fi ves, while the remaining % were related to dysentery or persistent diarrhoea and malnutrition. this pattern was age dependent, with acute watery deaths being more important in infancy, being associated with % of deaths, and less important in later childhood, being associated with % of deaths. rotavirus is the most common cause of severe diarrhoeal disease in infants and young children all over the world, and an important public health problem, particularly in developing countries where deaths each year are associated with this infection. more than million cases of diarrhoea each year are attributed to rotavirus. in tropical developing countries, rotavirus disease occurs either throughout the year or in the cold dry season. almost all children are already infected by the age of - years. although the infection is usually mild, severe disease may rapidly result in life-threatening dehydration if not appropriately treated. natural infection protects children against subsequent severe disease. globally, four serotypes are responsible for the majority of rotaviral disease, but additional serotypes are prevalent in some countries. the only control measure likely to have a signifi cant impact on the incidence of severe disease is vaccination. since the withdrawal from the market of the tetravalent rhesus-human reassortant vaccine (rotashield, wyeth laboratories) because of an association with intussusception, ruling out such a risk has become critical for the licensure and universal use of any new rotavirus vaccine. recent studies have shown that two oral doses of the live attenuated g p [ ] human rotavirus vaccine were highly effi cacious in protecting infants against severe rotavirus gastroenteritis, signifi cantly reduced the rate of severe gastroenteritis from any cause, and were not associated with the increased risk of intussusception linked with the previous vaccine. man is both the reservoir and natural host of shigella, the commonest cause of dysentery in the tropics. the most severe infections are caused by the s. dysenteriae type (also known as shiga's bacillus); it is also the only serotype implicated in epidemics. infection is by the faecal-oral route and is usually spread by personto-person transmission. it takes only - shigella organisms to produce dysentery, a low infectious dose, whereas million to million organisms may need to be swallowed to cause cholera. during the late s, shiga's bacillus was responsible for a series of devastating epidemics of dysentery in latin america, asia and africa. in , it was detected in the mexican-guatemalan border area and spread into much of central america. an estimated half a million cases, with deaths, were reported in the region between and . in some villages the case fatality rate was as high as %; delayed diagnosis and incorrect treatment may have been responsible for this high death rate. one particularly disturbing feature was the resistance of the bacteria to the most commonly used antibacterial drugs: sulfonamides, tetracycline and chloramphenicol. serious epidemics due to the multiple-drug resistant s. dysenteriae type have occurred recently in bangladesh, somalia, south india, burma, sri lanka, nepal, bhutan, rwanda and zaire. west bengal in india has always been an endemic area for bacillary dysentery. preventive measures include boiling or chlorination of drinking water, covering faeces with soil, protecting food from fl ies, avoiding eating exposed raw vegetables and cut fruits, and washing hands with soap and water before eating and after using the latrine. however, such measures are not easy to implement in most areas. consequently epidemics take their own course and subside only gradually. tuberculosis tuberculosis (tb) is the leading cause of death associated with infectious diseases globally. the incidence of tb will continue to increase substantially worldwide because of the interaction between the tb and hiv epidemics. in many developing countries, tb is mainly a disease of young adults affecting carers and wage-earners in a household, thus placing a huge economic burden on society as a whole. chemotherapy, if properly used, can reduce the burden of tb in the community, but because of the fragile structure of treatment programmes in many countries tb cases are not completely cured and patients remain infectious for a much longer time. another important consequence of poor treatment compliance is development of drug resistance in many developing countries. resistance to tuberculosis drugs is probably present everywhere in the world. worldwide attention was focused on south africa, when in october a research project publicized a deadly outbreak of xdr-tb in the small town of tugela ferry in kwazulu-natal. xdr-tb is the abbreviation for extensively drug-resistant tuberculosis (tb). this strain of mycobacterium tuberculosis is resistant to fi rstand second-line drugs, and treatment options are seriously limited. of tb patients at the church of scotland hospital, which serves a rural area with high hiv rates, some were found to have multi-drug resistance and of these, were diagnosed with xdr-tb. some of these patients died, most within days of diagnosis. of the patients, had been tested for hiv and all were found to be hiv-positive. the patients were receiving antiretrovirals and responding well to hiv-related treatment, but they died of xdr-tb. since the study, more patients have been diagnosed with xdr-tb in kwazulu-natal. only three of them are still alive (see: http://www.who.int/tb/xdr/xdr_jan.pdf). directly observed treatment, short course (dots), is the most effective strategy available for controlling the tb epidemic today. dots uses sound technology and packages it with good management practices for widespread use through the existing primary healthcare network. it has proven to be a successful, innovative approach to tb control in countries such as china, bangladesh, vietnam, peru and countries of west africa. however, new challenges to the implementation of dots include health sector reforms, the worsening hiv epidemic, and the emergence of drugresistant strains of tb. the technical, logistical, operational and political aspects of dots work together to ensure its success and applicability in a wide variety of contexts. million africans who die from malaria each year, most are children under years of age. in addition to acute disease episodes and deaths in africa, malaria also contributes signifi cantly to anaemia in children and pregnant women, adverse birth outcomes such as spontaneous abortion, stillbirth, premature delivery and low birth weight, and overall child mortality. the disease is estimated to be responsible for an estimated average annual reduction of . % in economic growth for those countries with the highest burden. of the four species of plasmodium that infect humans: p. falciparum, p. vivax, p. malariae and p. ovale, p. falciparum causes most of the severe disease and deaths attributable to malaria and is most prevalent in africa south of the sahara and in certain areas of south-east asia and the western pacifi c (figure . ) . the second most common malaria species, p. vivax, is rarely fatal and is commonly found in most of asia, and in parts of the americas, europe and north africa. there are over species of anopheline mosquitoes that transmit human malaria, which differ in their transmission potential. the most competent and effi cient malaria vector, anopheles gambiae, occurs exclusively in africa and is also one of the most diffi cult to control. climatic conditions determine the presence or absence of anopheline vectors. tropical areas of the world have the best combination of adequate rainfall, temperature and humidity allowing for breeding and survival of anophelines. in areas of malaria transmission where sustained vector control is required, insecticide treated nets are the principal strategy for malaria prevention. all countries in africa south of the sahara, the majority of asian malaria-endemic countries and some american countries have adopted insecticide treated nets as a key malaria control strategy. one of the greatest challenges facing malaria control worldwide is the spread and intensifi cation of parasite resistance to antimalarial drugs. the limited number of such drugs has led to increasing diffi culties in the development of antimalarial drug policies and adequate disease management. resistance of p. falciparum to chloroquine is now common in practically all malariaendemic countries of africa (figure . ) , especially in east africa. resistance to sulfadoxine/pyrimethamine, the main alternative to chloroquine, is widespread in south-east asia and south america. mefl oquine resistance is now common in the border areas of thailand with cambodia and myanmar. parasite sensitivity to quinine is declining in several other countries of south-east asia and in the amazon region, where it has been used in combination with tetracycline for the treatment of uncomplicated malaria. in response to widespread resistance of p. falciparum to monotherapy with conventional antimalarial drugs such as chloroquine and sulfadoxine-pyrimethamine, who now recommends combination therapies as the treatment policy for falciparum malaria in all countries experiencing such resistance. the preferred combinations contain a derivative of the plant artemisia annua, which is presently cultivated mainly in china and vietnam. artemisininbased combination therapies (acts) are the most highly effi cacious treatment regimens now available. resistance of p. vivax to chloroquine has now been reported from indonesia (irian jaya), myanmar, papua new guinea and vanuatu. urban and periurban malaria are on the increase in south asia and in many areas of africa. military confl icts and civil unrest, along with unfavourable ecological changes, have greatly contributed to malaria epidemics, as large numbers of unprotected, non- immune and physically weakened refugees move into malarious areas. such population movements contribute to new malaria outbreaks and make epidemic-prone situations more explosive. another disquieting factor is the re-emergence of malaria in areas where it had been eradicated (e.g. democratic people's republic of korea, republic of korea and tadjikistan), or its increase in countries where it was nearly eradicated (e.g. azerbaijan, northern iraq and turkey). current malaria epidemics in a majority of these countries are the result of a rapid deterioration of malaria prevention and control operations. climatic changes have also been implicated in the re-emergence of malaria. in the past years, the worldwide incidence of malaria has quadrupled, infl uenced by changes in both land development and regional climate. in brazil, satellite images depict a 'fi sh bone' pattern where roads have opened the tropical forest to localized development. in these 'edge' areas malaria has resurged. temperature changes have encouraged a redistribution of the disease; malaria is now found at higher elevations in central africa and could threaten cities such as nairobi, kenya. this threat has been hypothesized to extend to temperate regions of the world that are now experiencing hotter summers year on year. although substantial progress has been made in reducing measles deaths globally, in measles was estimated to be the fi fth leading cause of mortality worldwide for children aged < years. measles deaths occur disproportionately in africa and south-east asia. in , the african region of who, with % of the world's population, accounted for % of estimated measles cases and % of measles deaths; the south-east asia region, with % of the world's population and % of measles cases, accounted for % of measles deaths. the burden of mortality in africa refl ects low routine vaccination coverage and high case-fatality ratios. in south-east asia, where vaccination coverage is slightly below average worldwide levels, the large population amplifi es the number of cases and deaths resulting from ongoing measles transmission. the overwhelming majority of measles deaths in occurred in countries eligible to receive fi nancial support from the global alliance for vaccines and immunization's vaccine fund (who, unpublished data ). the majority of measles deaths occur among young children living in poor countries with inadequate vaccination services. like human immunodefi ciency virus, malaria, and tuberculosis, measles can be considered a disease of poverty. however, unlike these diseases, measles can be prevented through vaccination. , in much of the world, particularly sub-saharan africa, south-east asia, china and the pacifi c basin, infection with hepatitis b virus (hbv) is very widespread. the carrier rate in some of these populations may be as high as - %. in developing countries most hepatitis b transmission occurs during the perinatal period. infection between children is another common route of infection; it is not uncommon to fi nd up to % of -year-olds have serological evidence of infection with hbv. intermediate levels of infection ( - %) are seen in parts of the former soviet union, south asia, central america and the northern zones of south america. these high rates of infection lead to a high burden of disease, mainly from the clinical consequences of long-term carriage of the virus, which may include chronic hepatitis, cirrhosis and liver cancer. it has been estimated that hbv infection is the second most common cause of cancer deaths in the world (after tobacco consumption). in india hepatitis b is linked to % of cases of hepatocellular carcinoma and % of cases of cirrhosis of the liver. on the basis of disease burden and the availability of safe and effective vaccines, the who recommended that by the end of the twentieth century, hepatitis b vaccine be incorporated into routine infant and childhood immunization programmes for all countries. the effi cacy of universal immunization has been shown in different countries, with striking reductions of the prevalence of hbv carriage in children. most important, hepatitis b vaccination can protect children against hepatocellular carcinoma and fulminant hepatitis, as has been shown in taiwan. nevertheless, the implementation of worldwide vaccination against hbv requires greater effort to overcome the social and economic hurdles. safe and effective antiviral treatments are available but are still far from ideal, a situation that, hopefully, will be improved soon. with hepatitis b immunization, the global control of hbv infection is possible by the end of the fi rst half of twenty-fi rst century. tetanus is a vaccine-preventable disease that causes a total of deaths annually. of particular concern is maternal and neonatal tetanus (mnt), which can be prevented through immunization of the mother in pregnancy. in , neonatal tetanus alone was responsible for an estimated deaths. in addition, an estimated - non-immunized women worldwide die each year from maternal tetanus that results from postpartum, postabortal or postsurgical wound infection with clostridium tetani. while the focus is on priority countries, % of the neonatal tetanus deaths occur in countries. unicef spearheaded the effort to eliminate mnt by the year , with the support of numerous partners. mnt elimination is defi ned as less than one case of neonatal tetanus per live births at district level. the main strategies consist of promotion of clean delivery practices, immunization of women with a tetanus toxoid (tt) containing vaccine, and surveillance. maternal tetanus immunization is, in most developing countries, implemented as part of the routine immunization programme. however, large areas remain underserved, due to logistical, cultural, economical or other reasons. in order to achieve the target of mnt elimination by , and to offer protection to women and children otherwise deprived from regular immunization services, countries are encouraged to adopt the high risk approach. this approach implies that, in addition to routine immunization of pregnant women, all women of child-bearing age living in high risk areas are targeted for immunization with three doses of a tetanus toxoid containing vaccine (tt or td). by the end of vaccination against a range of bacterial and viral diseases is an integral part of communicable disease control worldwide. vaccination against a specifi c disease not only reduces the incidence of that disease, but it also reduces the social and economic burden of the disease on communities. very high immunization coverage can lead to complete blocking of transmission for many vaccinepreventable diseases. the worldwide eradication of smallpox and the near-eradication of polio from many countries provide excellent examples of the role of immunization in disease control. despite these advances many of the world's poorest countries do not have access to vaccines and these infections remain among the leading global causes of death. the special programme for research and training in tropical diseases (tdr) of the world health organization has designated several infectious diseases as 'neglected tropical diseases' (ntds) that disproportionately affl ict the poor and marginalized populations in the developing regions of sub-saharan africa, asia and the americas. infectious diseases are considered as 'neglected' or 'orphan' diseases when there is a lack of effective, affordable, or easy to use drug treatments. as most patients with such diseases live in developing countries and are too poor to pay for drugs, the pharmaceutical industry has traditionally ignored these diseases. ntds cause an estimated to million deaths annually and cause a global disease burden equivalent to that of hiv-aids. who estimates that at least billion people, i.e. onesixth of the world's population suffers from one or more neglected tropical diseases, while other estimates suggest the number to be much higher. some diseases affect individuals throughout their lives, causing a high degree of morbidity and physical disability and, in certain cases, gross disfi gurement. others are acute infections, with transient, severe and sometimes fatal outcomes. patients can face social stigmatization and abuse, which only add to the already heavy health burden. neglected tropical diseases are contrasted with the 'big three' diseases (hiv/aids, tuberculosis and malaria) which receive much more attention and funding. the current neglected diseases portfolio includes parasitic diseases of protozoan origin like kala-azar (leishmaniasis), african sleeping sickness (african trypanosomiasis) and chagas' disease (american trypanosomiasis) as well as those caused by helminths such as schistosomiasis, lymphatic fi lariasis, onchocerciasis (river blindness) and dracunculiasis (guinea worm). infestations due to soil transmitted helminths such as ascariasis, trichuriais and hookworm also belong to the latter category. other neglected diseases include those of bacterial origin such as leprosy, buruli ulcer and trachoma as well as those of viral origin like dengue fever which are vector-borne. even cholera and yellow fever are considered by some as ntds, while some include cysticercosis, hydatidosis and food-borne trematode infections. it is now believed that ramped up efforts against the 'big three', will yield far bigger dividends if they are coupled with concerted attack on ntds . evidence now points to substantial geographical overlap between the neglected tropical diseases and the 'big three', suggesting that control of the neglected tropical diseases could become a powerful tool for effectively combating hiv/aids, tuberculosis, and malaria. since , resurgent and emerging infectious disease outbreaks have occurred worldwide. in addition, many diseases widely believed to be under control, such as cholera, dengue and diphtheria, have re-emerged in many areas or spread to new regions or populations throughout the world (figure . ) . a growing population and increasing urbanization contribute to emerging infectious disease problems. in many parts of the world, urban population growth has been accompanied by overcrowding, poor hygiene, inadequate sanitation and unclean drinking water. urban development has also caused ecological damage. in these circumstances, certain disease-causing organisms and some of the vectors that transmit them have thrived, making it more likely that people will be infected with new or re-emerging pathogens. the existing public health infrastructure is already overtaxed and ill prepared to deal with new health threats. breakdown of public health measures due to civil unrest, war and the movement of refugees has also contributed to the re-emergence of infectious diseases (table . ). international travel and commerce have made it possible for pathogens to be quickly transported from one side of the globe to the other (figure . ) . examples of new and resurgent infections include ebola, dengue fever, rift valley fever, diphtheria, cholera, nipah virus infection, west nile virus infection, severe acute respiratory syndrome (sars) and avian infl uenza. in ebola (named after the ebola river in zaire) fi rst emerged in sudan and the democratic republic of the congo (formerly zaire). ebola virus occurs as four distinct subtypes: zaïre, sudan, côte d'ivoire and reston. three subtypes, occurring in the democratic republic of the congo, sudan and côte d'ivoire, have been identifi ed as causing illness in humans. ebola haemorrhagic fever (ehf) is a febrile haemorrhagic illness which causes death in - % of all clinically ill cases. the natural reservoir of the ebola virus is unknown despite extensive studies, but seems to reside in the rain forests on the african continent and in the western pacifi c. through the global prevalence of dengue and dengue haemorrhagic fever (dhf) has grown dramatically in recent decades. the disease is now endemic in more than countries in africa, the americas, the eastern mediterranean, south-east asia and the western pacifi c. south-east asia and the western pacifi c are most seriously affected. some million people -two-fi fths of the world's population -are now at risk from dengue. who currently estimates there may be million cases of dengue infection worldwide every year. in alone, there were more than reported cases of dengue in the americas, of which cases were dhf. this is greater than double the number of dengue cases which were recorded in the same region in . not only is the number of cases increasing as the disease is spreading to new areas, but explosive outbreaks are occurring. in , brazil reported over cases including more than cases of dhf. during epidemics of dengue, attack rates among the susceptible are often - %, but may reach - %. an estimated cases of dhf require hospitalization each year, microbial adaptation changes in virulence and toxin production; development and change of drug resistance; microbes as co-factors in chronic diseases of whom a very large proportion are children. without proper treatment, dhf case fatality rates can exceed %. with modern intensive supportive therapy, such rates can be reduced to less than %. the spread of dengue is attributed to expanding geographical distribution of the four dengue viruses and of their mosquito vectors, the most important of which is the predominantly urban species aedes aegypti. a rapid rise in urban populations is bringing ever greater numbers of people into contact with this vector, especially in areas that are favourable for mosquito breeding, e.g. where household water storage is common and where solid waste disposal services are inadequate. rift valley fever (rvf) is a zoonotic disease typically affecting sheep and cattle in africa. mosquitoes are the principal means by which rvf virus is transmitted among animals and to humans. following abnormally heavy rainfall in kenya and somalia in late and early , rvf occurred over vast areas, producing disease in livestock and causing haemorrhagic fever and death among the human population. as of december , who fi gures indicate that the outbreak continues to affect the north western provinces of kenya. in september who documented the fi rst ever rvf outbreak outside africa, in yemen and the kingdom of saudi arabia (ksa). rna sequencing of the virus from ksa indicated that it was similar to the rvf viruses isolated from east africa in . a total of suspected cases were identifi ed, of which ( %) persons died. of the , ( %) cases reported exposure to sick animals, handling an abortus or slaughtering animals in the week before onset of illness. the vibrio responsible for the seventh pandemic, now in progress, is known as v. cholerae o , biotype el tor. according to the who, it continues to spread in angola and sudan; more than cases have been documented with over deaths: a case fatality rate of . - %. cholera (biotype el tor) broke out explosively in peru in , after an absence of years, and spread rapidly in central and south america, with recurrent epidemics in and . from the onset of the epidemic in january to september , a total of cases and deaths (overall case fatality rate . %) were reported from countries in the western hemisphere to the pan american health organization. in december , a large epidemic of a new strain of cholera v. cholerae began in south india, and spread rapidly through the subcontinent (figure . ) . this strain has changed its antigenic structure such that there is no existing immunity and all ages, even in endemic areas, are susceptible. the epidemic has continued to spread and v. cholerae o has been reported from countries in south asia. because humans are the only reservoirs, survival of the cholera vibrios during interepidemic periods probably depends on low-level undiagnosed cases and transiently infected, asymptomatic individuals. recent studies have suggested that cholera vibrios can persist for some time in shellfi sh, algae or plankton in coastal regions of emerging and resurgent infectious diseases infected areas and it has been claimed that they can exist in a viable but non-culturable state. in early , health offi cials in malaysia and singapore investigated reports of febrile encephalitis and respiratory illnesses among workers who had been exposed to pigs. a previously unrecognized paramyxovirus (formerly known as hendra-like virus), now called nipah virus, was implicated by laboratory testing in many of these cases. as of april , cases of febrile encephalitis were reported to the malaysian ministry of health, including deaths. laboratory results from patients who died suggested recent nipah virus infection. the apparent source of infection among most human cases continues to be exposure to pigs. human-tohuman transmission of nipah virus has not been documented. outbreak control in malaysia has focused on culling pigs; approximately pigs have been killed. other measures include a ban on transporting pigs within the country, education about contact with pigs, use of personal protective equipment among persons exposed to pigs, and a national surveillance and control system to detect and cull additional infected herds. nipah virus cases and deaths have also been reported from bangladesh. since then, no more human cases have been reported. sars is due to infection with a newly identifi ed coronavirus named as sars-associated coronavirus (sars-cov). the source of infection is likely to be a direct cross-species transmission from an animal reservoir. this is supported by the fact that the early sars cases in guangdong province had some history of exposure to live wild animals in markets serving the restaurant trade. animal traders working with animals in these markets had higher seroprevalence for sars coronavirus, though they did not report any illness compatible with sars. more importantly, sars-cov-like virus detected from some animal species had more than a % homology with human sars-cov. the clinical course of sars varies from a mild upper respiratory tract illness, usually seen in young children, to respiratory failure which occurred in around - % of mainly adult patients. as the disease progresses, patients start to develop shortness of breath. from the second week onwards, patients progress to respiratory failure and acute respiratory distress syndrome, often requiring intensive care. in may , a -year-old boy in hong kong contracted an infl uenza-like illness, was treated with salicylates, and died days later with complications consistent with reye's syndrome. laboratory diagnosis included the isolation in cell culture of a virus that was identifi ed locally as infl uenza type a but could not be further characterized with reagents distributed for diagnosis of human infl uenza viruses. by august, further investigation with serological and molecular techniques in the netherlands and in the usa had confi rmed that the isolate was a/hong kong/ / (h n ), which was very closely related to isolate a/chicken/hong kong/ / (h n ). the latter virus was considered representative of those responsible for severe outbreaks of disease on three rural chicken farms in hong kong during march , during which several thousand chickens had died. molecular analysis of the viral haemagglutinins showed a proteolytic cleavage site of the type found in highly pathogenic avian infl uenza viruses. by late december, the total number of confi rmed new human cases had climbed to , of which fi ve were fatal; the case fatality rates were % in children and % in adults older than years. almost all laboratory evidence of infection was in patients who had been near live chickens (e.g. in marketplaces) in the days before onset of illness, which suggested direct transmission of virus from chicken to human rather than person-to-person spread. in december , veterinary authorities began to slaughter all ( . million) chickens present in wholesale facilities or with vendors within hong kong, and importation of chickens from neighbouring areas was stopped. knowledge of how humans are infected, the real level of humanto-human transmission, the spectrum of disease presentation and the effectiveness of treatment remains scanty. human-to human transmission is known to have occurred, but there is no evidence that transmission has become more effi cient. all the human-tohuman infections with h n to date seem not to have transmitted on further. therefore, although the case fatality rate for human infection remains high (around % for cases reported to who), it seems that h n avian viruses remain poorly adapted to humans. global prevalence studies (figure . ) indicate that indonesia is currently the most active site of bird to human h n transmission in the asia pacifi c region, and a large number of human cases have been detected here in - . china and cambodia have also reported human cases in . in south asia (india and pakistan), there have only been sporadic reports of infection in poultry to date. in vietnam and thailand there have been offi cial reports of poultry outbreaks; these show a decline since . surveillance in africa is especially weak, and there is evidence of widespread infection in domestic poultry in parts of north, west and central africa. prospects of control are bleak here because of weaknesses in veterinary services, and a number of competing animal and human health problems. the outbreaks in egypt have been well described. these involved both commercial and backyard fl ocks, with considerable impact on economic life and food security. it is probable that large numbers of people in african countries are at risk of h n infection. if that virus had pandemic potential then a pandemic arising from africa must be considered a possibility. non-infectious diseases take an enormous toll on lives and health worldwide. non-communicable diseases (ncds) account for nearly % of deaths globally, mostly due to heart disease, stroke, cancer, diabetes and lung diseases. the rapid rise of ncds represents one of the major health challenges to global development in the twenty-fi rst century and threatens the economic and social development of nations as well as the lives and health of millions of their subjects. in alone, ncds were estimated to have contributed to . million deaths globally and % of the global burden of disease. until recently, it was believed that ncds were a minor or even non-existent problem in developing countries in the tropics. a recent analysis of mortality trends from ncds suggests that large increases in ncds have occurred in developing countries, particularly those in rapid transition like china and india (table . ). according to these estimates at least % of all deaths in the tropical developing countries are attributable to ncds, while in industrialized countries ncds account for % of all deaths. low-and middle-income countries suffer the greatest impact of ncds. the rapid increase in these diseases is seen disproportionately in poor and disadvantaged populations and is contributing to widening health gaps between and within countries. in , of the total number of deaths attributable to ncds % occurred in developing countries, and of the disease burden they represent % was borne by low-and middle-income countries. it has now been projected that, by , ncds will account for almost three-quarters of all deaths worldwide, and that % of deaths due to ischaemic heart disease (ihd), % of deaths due to stroke, and % of deaths due to diabetes will occur in developing countries and the number of people in the developing world with diabetes is expected to increase by more than . -fold, from million in to million in . on a global basis, % of the burden of ncds will occur in developing countries and the rate at which it is increasing annually is unprecedented. the public health and economic implications of this phenomenon are staggering, and are already becoming apparent. it is important to recognize that these trends, indicative of an increase in ncds, may be partly confounded by factors such as an increase in life expectancy, a progressive reduction in deaths due to communicable diseases in adulthood, and improvements in case detection and reporting in the tropics. however, increase in the incidence of these chronic degenerative diseases is real. the complex range of determinants (below) that interact to determine the nature and course of this epidemic needs to be understood in order to adopt preventive strategies to help developing societies in the tropics to deal with this burgeoning problem. the determinants of non-communicable diseases in developing societies are as follows: • demographic changes in population • epidemiological transition • urbanization and internal migration • changes in dietary and food consumption patterns • lifestyle changes (changes in physical activity patterns, sociocultural milieu and stress as well as increased tobacco consumption) • adult-onset effects of low birth weight and the effects of early life programming • infections and their associations with chronic disease risk • effect of malnutrition and nutrient defi ciencies • poverty, inequalities and social exclusion • deleterious effects of environmental degradation • impacts of globalization. four of the most prominent ncds: cardiovascular disease, cancer, chronic obstructive pulmonary disease and diabetes, are linked to common preventable risk factors related to diet and lifestyle. these factors are tobacco use, unhealthy diet and lack of physical activity. interventions to prevent these diseases should focus on controlling these risk factors in an integrated manner and at the family and community level since the causal risk factors are deeply entrenched in the social and cultural framework of society. developing countries in the tropics have to recognize that the emerging accelerated epidemic of ncds is a cause for concern and that it needs to be dealt with as a national priority. they have to learn from the experience of industrialized and affl uent countries to tackle the emerging crisis of chronic diseases that they are likely to face in the near future. the emerging health burden of chronic disease affecting mainly the economically productive adult population will consume scarce resources. it is important, however, to realize that the poorer countries will be burdened even more in the long run, if attempts are not made to evolve and implement interventions to address these emerging health issues on an urgent basis. ensuring that health policies are aimed at tackling the 'double burden' of the continued existence of the huge burden of infectious/communicable diseases alongside the emerging epidemic of non-communicable diseases in developing countries of the tropics becomes a priority. the world we live in is constantly changing. in the past years, we have witnessed signifi cant progress in sustainable and technological development. however, increases in mass population movements, continuing civil unrest and deforestation have helped carry diseases into areas where they have never been seen before. this has been aided by the massive growth in international travel. effective medicines and control strategies are available to dra-matically reduce the deaths and suffering caused by communicable and non-communicable diseases. despite reduced global military spending many governments are failing to ensure that these strategies receive enough funding to succeed. who priorities for the control of infectious diseases in developing countries include childhood immunization, integrated management of childhood illnesses, use of the dots strategy to control tb, a package of interventions to control malaria, a package of interventions to prevent hiv/aids, access to essential drugs, and the overall strengthening of surveillance and health service delivery systems. over % of all preventable ill-health today is due to poor environmental quality-conditions such as bad housing, overcrowding, indoor air pollution, poor sanitation and unsafe water. the challenge of disease in the tropics has continued into the new millennium -never before have we been so well equipped to deal with disease threats. it remains for humankind to summon the collective will to pursue these challenges and break the chain of infection and disease. national and international surveillance of communicable diseases health report: fighting disease fostering development. geneva: world health organization acute respiratory infections. geneva: world health organization indoor air pollution energy and health for the poor estimate of global incidence of clinical pneumonia in children under fi ve years the global burden of diarrhoeal disease number evl- - . a global review of diarrhoeal disease control new parameters for evaluating oral rehydration therapy: one year's experience in a major urban hospital in zaire symptomatic hyponatremia during treatment of dehydrating diarrheal disease with reduced osmolarity oral rehydration solution diarrhoea mortality in rural bangladeshi children for the human rotavirus vaccine study group. safety and effi cacy of an attenuated vaccine against severe rotavirus gastroenteritis guidelines for the control of epidemics due to shigella dysenteriae . publication no. who/cdr/ . . epidemiology of dysentery caused by shigella. geneva: world health organization global tuberculosis control-surveillance, planning financing, geneva: world health organization who/international union against tuberculosis and lung disease global project on anti-tuberculosis drug resistance surveillance. epidemiology of antituberculosis drug resistance (the global project on anti-tuberculosis drug resistance surveillance): an updated analysis geneva: world health organization climate, ecology and human health global burden of disease and risk factors. geneva: world health organization update: global measles control and mortality reduction -worldwide towards the elimination of hepatitis b: a guide to the implementation of national immunization programs in the developing world. the international task force on hepatitis b immunization. geneva: world health organization global control of hepatitis b virus infection tetanus in developing countries: an update on the maternal and neonatal tetanus elimination control of neglected tropical diseases (ntd) incorporating a rapid-impact package for neglected tropical diseases with programs for hiv/aids, tuberculosis, and malaria emerging infectious diseases review of state and federal diseases surveillance fact sheet: ebola haemorrhagic fever. fact sheet no. . geneva: world health organization report of the public health laboratories division. who collaborating centre for research and training in viral diagnostics national institute of health update: vibrio cholerae o -western hemisphere, - , and v. cholerae o -asia update: outbreak of nipah virus: malaysia and singapore sars and emerging infectious diseases: a challenge to place global solidarity above national sovereignty world avian infl uenza update: h n could become endemic in africa global strategy for the prevention and control of non-communicable diseases. geneva: world health organization global comparative assessments in the health sector. geneva: world health organization life in the st century: a vision for all. geneva: world health organization life course perspectives on coronary heart disease, stroke and diabetes: key issues and implications for policy and research diet and life-style and chronic non-communicable diseases: what determines the epidemic in developing societies? in: krishnaswami k, ed. nutrition research: current scenario and future trends the double burden of communicable and non-communicable diseases in developing countries key: cord- - b authors: mok, chris ka pun; zhu, airu; zhao, jingxian; lau, eric h y; wang, junxiang; chen, zhao; zhuang, zhen; wang, yanqun; alshukairi, abeer n; baharoon, salim a; wang, wenling; tan, wenjie; liang, weiwen; oladipo, jamiu o; perera, ranawaka a p m; kuranga, sulyman a; peiris, malik; zhao, jincun title: t-cell responses to mers coronavirus infection in people with occupational exposure to dromedary camels in nigeria: an observational cohort study date: - - journal: lancet infect dis doi: . /s - ( ) - sha: doc_id: cord_uid: b background: middle east respiratory syndrome (mers) remains of global public health concern. dromedary camels are the source of zoonotic infection. over % of mers coronavirus (mers-cov)-infected dromedaries are found in africa but no zoonotic disease has been reported in africa. we aimed to understand whether individuals with exposure to dromedaries in africa had been infected by mers-cov. methods: workers slaughtering dromedaries in an abattoir in kano, nigeria, were compared with abattoir workers without direct dromedary contact, non-abattoir workers from kano, and controls from guangzhou, china. exposure to dromedaries was ascertained using a questionnaire. serum and peripheral blood mononuclear cells (pbmcs) were tested for mers-cov specific neutralising antibody and t-cell responses. findings: none of the participants from nigeria or guangdong were mers-cov seropositive. ( %) of abattoir workers with exposure to dromedaries, but none of abattoir workers without exposure (p= · ), ten non-abattoir workers or controls from guangzhou (p= · ) had evidence of mers-cov-specific cd (+) or cd (+) t cells in pbmc. t-cell responses to other endemic human coronaviruses ( e, oc , hku- , and nl- ) were observed in all groups with no association with dromedary exposure. drinking both unpasteurised camel milk and camel urine was significantly and negatively associated with t-cell positivity (odds ratio · , % ci · – · ). interpretation: zoonotic infection of dromedary-exposed individuals is taking place in nigeria and suggests that the extent of mers-cov infections in africa is underestimated. mers-cov could therefore adapt to human transmission in africa rather than the arabian peninsula, where attention is currently focused. funding: the national science and technology major project, national institutes of health. middle east respiratory syndrome coronavirus (mers-cov) is one of eight emerging pathogens identified in the who research and development blueprint requiring urgent action for development of effective vaccines and antiviral drugs. the emergence of severe acute respiratory syndrome coronavirus (sars-cov- ) as a pandemic virus emphasises the threat posed by zoonotic coronaviruses. mers-cov causes a zoonotic disease, middle east respiratory syndrome (mers), with out breaks in health-care facilities associated with trans mission between humans. as of november, , laboratoryconfirmed cases of mers, including associated deaths (case-fatality ratio of · %), were reported globally; the majority of these ( cases, including deaths) occurred in saudi arabia. travel-associated outbreaks led to cases and deaths in south korea. dromedary camels are the source of zoonotic mers-cov disease. the majority (> %) of dromedaries are found in africa. they have comparable seroprevalence and virus shedding to those in the arabian peninsula, but no zoonotic disease has been reported in africa. humans with prolonged close exposure to dromedaries in the arabian peninsula have serological evidence of mers-cov infection, sometimes having seroprevalence as high as %, , but serological evidence is rare in africa, even in dromedary-exposed individuals. , however, virologically confirmed infection, especially if it is asymptomatic or mild, might not lead to a serological response. thus, alternative and more sensitive methods for detection of past human mers-cov infection are needed. specific t-cell responses have been shown to be longlasting in sars-cov and mers-cov infected humans, , and persist longer than antibodies in sars. we therefore aimed to test peripheral blood mononuclear cells (pbmc) in workers from an abattoir in kano, nigeria, for mers-cov-specific t-cell responses to understand if the dromedary-exposed individuals in africa have been infected by mers-cov. in this observational cohort study, workers at an abattoir in kano, nigeria, consenting to participate in the cohort study in march - , , were recruited. nonabattoir workers were also recruited randomly from the city of kano during the same period, and blood donors aged - years sampled in may -aug , , at guangzhou blood center, guangzhou, china, were randomly included as healthy controls from a region with no dromedary camel exposure. convalescent blood samples collected from people with symptomatic or asymptomatic virologically confirmed mers-cov infections detected at the king abdulaziz medical city, riyadh, and king faisal specialist hospital, jeddah, saudi arabia, collected as part of a previously reported study were included as positive controls. the clinical, serological and t-cell responses (using only interferon [ifn]-γ as a readout of positive cells) of this patient cohort have been previously reported. pbmcs were collected at months (patients - , - , - as reported in the previous publication) or months (patients [ ] [ ] after infection. written informed consent was obtained from all study participants in nigeria and the study was approved by the health research ethics committee of the ministry of health, nigeria (moh/off/ /t.i/ ). we obtained institutional review board approval from the health commission of guangdong province to use the anonymised blood donor samples for this study. written informed consent was obtained from all recovered patients with mers to participate in this study and approval obtained from the institutional review boards of the national guard hospital, riyadh, and king faisal specialist hospital, jeddah. procedures ml of blood were collected from each study participant from the abattoir and from donors from guangzhou. pbmcs were isolated from blood using leucosep tubes (greiner, kremsmünster, austria) and ficoll-paque plus (ge healthcare, chicago, il) according to the manu facturer's instructions. pbmcs were stored in liquid nitrogen and plasma at - °c or lower before and during shipping before analysis. plasma was heat inactivated for min at °c before the serology testing. anti-mers-cov antibody titres were determined using plaque reduction neutralisation tests. , a set of -mer peptides overlapping by ten amino acids en comp assing the four mers-cov (hcov-emc/ ) structural proteins (peptides s , s , n, and me encompassing the n-terminal and c-terminal portions of the spike [ evidence before this study middle east respiratory syndrome coronavirus (mers-cov) is recognised as one of eight emerging pathogens of greatest threat to global public health, and dromedary camels are the source of human zoonotic infection. the emergence of sars-cov- highlights the pandemic potential of zoonotic coronaviruses. although zoonotic disease has been restricted to the arabian peninsula, the largest number (> %) of mers-cov infected camels are found in africa. we searched pubmed for articles published between nov , , and dec , , in english with the search terms "mers" and "coronavirus" and "human" and "africa" and manually screened all retrieved articles. there was one mers outbreak reported in tunisia initiated by a traveller returning from the arabian peninsula but no reports of zoonotic disease in africa. there were six sero-epidemiological studies of camel-exposed or other humans in kenya, egypt, nigeria, and morocco and only two (two of in kenya and three of tested in morocco) found any evidence of mers-cov infection. because there was evidence that serological assays for mers-cov had suboptimal sensitivity for past infection and because we had previous data showing that t-cell assays for mers-cov are specific and potentially more sensitive than antibody detection, we investigated t-cell responses in dromedary-exposed abattoir workers and controls in nigeria. we found that ( %) of abattoir workers with exposure to dromedaries had mers-cov specific t-cell responses, but of abattoir workers without exposure to dromedaries and ten non-abattoir workers from kano, none had such t-cell responses. no individuals with mers-cov t-cell responses had detectable antibody. by contrast, t-cell responses to endemic human coronaviruses were detected comparably in abattoir workers with and without exposure to dromedaries and control groups. we document that dromedary-exposed individuals in africa are frequently infected with mers-cov without evidence of severe disease. our findings indicate that there is substantial zoonotic transmission of mers-cov to people with dromedary exposure in parts of africa. the contribution of mers-cov to zoonotic respiratory disease remains to be established. our findings have implications for global mers-cov control policy. there is a need to confirm our findings elsewhere in africa and to include molecular testing for mers-cov in the investigation of patients with severe acute respiratory infections in dromedary-exposed populations in africa. orf b, orf and orf b) were synthesised by sino biological (shanghai, china), and used for stimulation of pbmcs. t-cell responses were measured using intracellular cytokine staining assays for interferon-γ (ifn-γ) and tumour necrosis factor (tnf). structural proteins peptide libraries of hku -cov, oc -cov, nl -cov, and e-cov were also synthesised by sino biological to detect viral-specific t-cell responses. to enhance specificity, only cells with dual expression of both ifn-γ and tnf after peptide stimulation were considered as positive. flow cytometry was used to determine the phenotype and function of t cells. the following anti-human monoclonal antibodies were used: bv -cd (hit a; bd, san jose, ca), percp-cy . in a previous study of dromedary abattoir workers in saudi arabia, ten of workers sampled had detectable t-cell responses to mers-cov. on the basis of this finding, and the assumption that abattoir workers without dromedary exposure and the other control groups would have no detectable t-cell responses, eight abattoir workers would be the minimal sample size required to detect a positive result with % probability, where the detection probability is given by: -( -p)n with p equivalent to / and n being the sample size. we aimed at sampling all abattoir workers who consented to participate, as long as we successfully sampled at least eight dromedary-exposed abattoir workers. association of t-cell responses with different exposure to dromedaries was done using fisher's exact test. in univariate analysis, we estimated the crude odds ratio (or) for each potential epidemiological exposure factor in relation to mers-cov t-cell positivity using a logistic regression model. independent risk factors for t-cell positivity were identified using multivariable logistic regression. we included a-priori variables, such as years of work in abattoir and whether other household members frequently visited camel farms, and other variables with a crude or of more than or less than · in the univariate analysis. due to small sample size and cross-related practices of drinking camel milk and camel urine, we first fitted a logistic regression model which considered all four combinations of the two practices (eg, drinking camel milk only, drinking camel urine only, drinking both camel milk and urine or not drinking either), adjusted for potential confounding factors (model ). then we further assessed the effect of drinking camel milk and camel urine separately in two models (models and ) . missing data were handled using multiple imputation with imputations by predictive mean matching using the aregimpute function in r. all statistical analyses were done using r version . . . the funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. the corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. we recruited volunteers working in an abattoir in kano, nigeria. dromedaries, sheep, goats, and cattle were slaughtered in different areas of this abattoir (appendix p ), and workers usually restrict themselves to work with one animal type. ( %) workers had occupational exposure to dromedaries, whereas ( %) were only involved in the slaughtering of sheep, goats, or cattle. ten people residing in kano not involved in abattoir-work and volunteers from guangzhou, china, with no exposure to dromedaries, were also recruited as additional controls. patients with confirmed mers from saudi arabia were included in this study as positive controls. all participants were adults (aged ≥ years). boots were the main protective equipment used by abattoir workers with ( [ %] of ) and without ( [ %] of ) exposure to dromedaries, whereas other protection, such as gloves, coveralls, masks, or goggles, were rarely used. there was no significant difference in the demographic characteristics between the three groups recruited in kano (table ) . none of the sera collected neutralised the nig virus (previously isolated at the same abattoir) at the dilution of : to levels of greater than % of control, the lowest threshold for a positive result (data not shown). pbmcs possessed good viabilities in all groups from which they were collected (appendix p ) and responded to anti-human cd stimulation (appendix p ). ( %) of samples from workers with exposure to dromedaries contained cd + or cd + t cells that responded to at least one peptide pool, particularly s and s pools ( figure a, b; appendix p ) . no mers-cov specific cd + or cd + t-cell responses were detected in the three groups without exposure to dromedaries ( figure c, d) . the proportion of individuals with both cd + and cd + t-cell responses was significantly larger among dro medaryexposed abattoir workers than in workers without exposure (cd + p= · ; cd + p= · ), non-abattoir workers (cd + p= · ; cd + p= · ), or the ghuangzhou control group (cd + p= · ; cd + p= · ). the magnitude of the cd + t-cell responses in abattoir workers with exposure to dromedaries was similar to individuals in the saudi arabian positive control group with a subclinical condition (p= · ), whereas the cd + t-cell responses were comparable to the symptomatic group (p= · ). for stimulation with peptide pools derived from mers-cov accessory proteins (orf , orf a, orf b, orf and orf b), pbmcs were available from workers with exposure to dromedaries who had t-cell responses to mers-cov structural proteins, from who had negative t-cell responses to mers-cov structural proteins, and from four each from abattoir workers without exposure to dromedaries and non-abattoir workers. eight of the dromedary-exposed workers who had t-cell responses to structural proteins also had t-cell responses to accessory proteins ( figure e ). none of the abattoir workers with dromedary exposure who did not have t-cell responses previously, nor those without dromedary exposure and non-abattoir workers had t-cell responses to accessory proteins ( figure e ). all the t-cell responses detected to accessory proteins were cd + t-cell responses and no cd + t-cell responses were detected (data not shown). taken together, of workers with exposure to dromedaries in our cohort, six had both cd + and cd + t-cell responses against mers-cov structural proteins, four had only cd +, and eight had only cd + t-cell responses. the mers-cov-specific cd + and cd + t cells were multifunctional with dual expression of two cytokines (ifn-γ and tnf). the majority of mers-cov-specific cd + t cells from dromedary-exposed workers were phenotypically effector memory (cd ra-ccr -) cells (figure f), whereas cd + t cells consisted of effector memory (cd ra-ccr -) and effector (cd ra+ ccr -) cells ( figure g, h) , comparable to the temra subset (effector memory t cells expressing cd ra) described in mers survivors. thus, these multifunctional cells are expected to rapidly and efficiently respond to subsequent mers-cov reinfection. ( %) of the participants had pbmcs available for additional testing for four endemic human coronaviruses ( e, hku , nl , and oc ), including dromedary-exposed workers positive and ten negative for a mers-cov t-cell response and from the negative control groups who were all mers-cov t-cell negative. ( %) of were t-cell positive to one or more of the human coronaviruses, with cd + t-cell responses being detected in all four groups (figure a), whereas cd + t-cell responses were found less often (figure b). in this group of people, mers-cov t-cell responsiveness was not significantly associated with t-cell responses to any of the other coronaviruses (fisher's exact test; e p= · , hku p= · , nl p= · , and oc p= · ). of the with t-cell response to any of the other coronaviruses, ten ( %) had t-cell responses to mers-cov. by contrast, seven ( %) of with no detectable t-cell response to any other coronavirus had t-cell responses to mers-cov, the negative association being statistically significant (fisher's exact test p= · ) . human coronaviruses did not differ between the exposure groups and this was in marked contrast with the observations with mers-cov, which was observed exclusively in the dromedary-exposed group. drinking unpasteurised camel milk (or · , % ci · - · ) and drinking camel urine ( · , · - · ) were significantly and negatively associated with t-cell positivity (table ). in the multivariate analysis, drinking both camel milk and urine was significantly negatively associated with t-cell responses ( · , % ci · - · ; model ; table ). similar findings were obtained from a model without adjustment for potential confounders (data not shown). we further assessed the effect of each practice separately (models and ; table ) and found that drinking unpasteurised camel milk ( · , · - · ) and camel urine ( · , · - · ) remained a significant factor for t-cell negativity. the two practices of drinking camel milk and camel urine were closely cross-related; ( %) of dromedary-exposed workers drank camel milk or urine, drank milk without drinking urine, and two drank urine without drinking milk. our results indicated that drinking camel milk or camel urine was associated with a protective effect against mers-cov infection, but we could not separate their independent effects in the analysis. dromedaries in africa have comparable seroprevalence of mers-cov and virus shedding to those in the arabian peninsula, but zoonotic disease has not been reported. , , even serological evidence of mers-cov infection in dromedary-exposed populations is uncommon. we previously found no serological evidence of mers-cov infection in dromedary-exposed abattoir workers in an abattoir in kano, nigeria, although virus rna was repeatedly detected in the camels slaughtered during the winter months, with a peak of % of animals shedding virus in some weeks. the negative serological results in workers from the same abattoir in this study were thus consistent with those of other studies of dromedary-exposed populations in kenya and egypt, which also did not find mers-cov-specific antibodies. , , one study in kenya found two seropositive individuals among people tested, and our study in morocco detected three seropositive individuals among people living in dromedary herding areas. because some patients with confirmed mers disease might not manifest neutra lising antibody responses and because such antibody responses can wane over time, serological studies could underestimate the extent of mers-cov infections in africa. furthermore, antibody responses might not be positive in those with mild or asymptomatic infection, , [ ] [ ] [ ] and t-cell responses are known to be more sensitive and long-lasting following sars-cov infections. we have therefore previously analysed t-cell responses to mers-cov. in these studies, both mers survivors (symptomatic and asymptomatic) and camel workers one abattoir worker with exposure to dromedaries had missing data for years working in abattoir, one for other household members frequently visited camel farms, two for travel outside kano in the past months, and one for participated in mass gathering. *mean for age was · years (sd · ). †mean for years working in abattoir was · years (sd · ). (asymptomatic) identified in saudi arabia were shown to have mers-cov specific t cells in their blood, and some of those with t-cell responses did not have neutralising antibodies. comparable findings were observed in the korean outbreak; some patients with mild mers did not produce neutralising antibodies but had mers-cov-specific t cells in their peripheral blood. we have shown that mers-cov-specific t cells were present in ( %) of dromedary-exposed workers but not in controls without exposure to dromedaries, and we conclude that mers-cov infections in people with occupational contact with dromedaries is underestimated in nigeria, and probably elsewhere in africa. t-cell responses in these workers recognised the highly variable s region and unique accessory proteins found in mers-cov, arguing for the mers-cov specificity of the t-cell responses. by contrast, t-cell responses to human coronaviruses nl , hku , e, and oc were found equally distributed in the dromedary-exposed worker group and the control groups (abattoir workers without dromedary exposure, non-abattoir workers, and ghuangzhou negative control). cross-reactive t-cell responses to other human endemic coronaviruses were not likely to be an explanation for the mers-cov t-cell responses in the dromedary-exposed workers, the association being a negative one. the observation that dromedary-exposed individuals with mers-cov t-cell responses did not have antibody responses is consistent with previous studies on mers and the underlying mechanisms needs further investigation. a question of relevance to public health is why no human zoonotic mers has been documented in africa even though zoonotic infection seems to be taking place as assessed by specific t-cell responses. the perception that mers does not occur in africa might reduce the use of mers-cov diagnostics in patients who have travelled to the arabian peninsula, precluding detection of zoonotic mers in africa. our finding that zoonotic mers-cov infection is occurring in dromedaryexposed populations in africa highlights that mers-cov needs to be considered in the differential diagnosis of patients with severe acute respiratory infections in these regions. an alternative hypothesis is that mers-cov strains in africa differ in pathogenic potential to those circulating in the arabian peninsula-ie, causing infection but less likely to cause severe disease. we have shown that mers-covs identified from africa (clade c), including those isolated in nigeria (clade c ), are phylogenetically distinct from contemporary viruses causing disease in the arabian peninsula (clade b). , , viruses from the african clade c -lineage were found to replicate less efficiently in human respiratory epithelial cell lines, in ex-vivo cultures of the human lung and in experimentally infected human dpp transgenic mice, possibly suggesting impaired pathogenic potential. the absence of antibodies in individuals with t-cell responses might also be indicative of less severe infections, because patients with mild or asymptomatic mers-cov infections often do not have detectable antibody in both the acute and convalescent stages of infection. , irrespective of whether mers-cov in africa is less pathogenic than the virus strains in the arabian peninsula, our findings argue for more intensive investigation of mers-cov in both humans and camels in africa. if repeated unsuspected zoonotic transmission of mers-cov continues to take place in africa as our findings indicate, given the much larger number of mers-cov-infected dromedaries in africa, the possibility of the virus adapting and efficiently transmitting between humans is probably more likely here than in the arabian peninsula where mers control efforts have been focused. the phylogenetic diversity of clade c viruses in africa suggests that these are the precursors that gave rise to the potentially more pathogenic clade b viruses currently enzootic in the arabian peninsula. , if so, similar pathogenic mers-cov might independently emerge in africa. overall, our findings suggest that the mers control in the arabian peninsula needs to be extended to africa. occupational contact with camels was found to be a key risk factor for mers-cov infection, as defined by the positive t-cell responses against mers-cov. a univariate analysis of exposure factors associated with mers-cov infection (ie, mers-cov t cell reactivity) in the dromedary-exposed worker group revealed that drinking unpasteurised camel milk and drinking camel urine for medicinal purposes were significantly and negatively associated with infection risk. because the practices of drinking raw camel milk and urine were often associated and because of the small sample size, it was not possible to estimate their independent effects in a multivariate analysis in which both factors were concurrent variables. the finding that drinking unpasteurised camel milk was negatively correlated with infection risk is surprising and requires independent confirmation. camel milk has been previously thought of as a potential risk factor for mers-cov infection because mers-cov virus has sometimes been detected in camel milk. however, camel milk contains high titre antibodies to mers-cov, which is likely to neutralise any infectious virus particles, and viable mers-cov was not isolated from milk samples in which mers-cov rna was detected. thus, mers-cov antibody present in camel milk could provide protection against mers-cov infection. our study had some limitations. exposure and risk factors associated with t-cell positivity were self-reported and the details on frequency or intensity for different modes of contacts with dromedaries were not collected. a small sample size reduced the power of the multivariable logistic regression analysis, although we were still able to identify a large protective effect of drinking unpasteurised camel milk or urine on t-cell positivity. in conclusion, we have shown that detection of virusspecific t-cell responses was a more sensitive method for detecting past infection compared with the serological tests being used hitherto, findings that may be also relevant to assessment of population-based infection attack rates of sars-cov- using seroprevalence that are currently under way. our findings suggest that the incidence of mers infections taking place in africa is underestimated. these findings have implications for policies on global mers prevention and control and highlight the need for attention towards camel-herding regions in africa as well as the arabian peninsula. ckpm, jincz, and mp designed the study. ckpm, joo, and sak coordinated and carried out the field work. az, jingz, and jincz designed and performed the experiments. jw, zc, zz, and rapmp participated in the experiments. ckpm, az, jingz, and mp analysed the data. ehyl and wl did the statistical analysis. yw collected pbmc from guangzhong blood donors. ana and sab provided mers patients samples from saudi arabia. ww and wt contributed new reagents. ckpm, az, jincz, and mp drafted the manuscript. all authors critically reviewed and commented on the manuscript. we declare no competing interests. review of emerging infectious diseases requiring urgent research and development efforts middle east respiratory syndrome coronavirus in dromedary camels: an outbreak investigation risk factors for mers coronavirus infection in dromedary camels in burkina faso presence of middle east respiratory syndrome coronavirus antibodies in saudi arabia: a nationwide, cross-sectional, serological study occupational exposure to dromedaries and risk for mers-cov infection no serologic evidence of middle east respiratory syndrome coronavirus infection among camel farmers exposed to highly seropositive camel herds: a household linked study middle east respiratory syndrome coronavirus (mers-cov) neutralising antibodies in a high-risk human population mers-cov antibody responses year after symptom onset, south korea lack of peripheral memory b cell responses in recovered patients with severe acute respiratory syndrome: a six-year follow-up study recovery from the middle east respiratory syndrome is associated with antibody and t-cell responses mers coronaviruses from camels in africa exhibit region-dependent genetic diversity seroepidemiology for mers coronavirus using microneutralisation and pseudoparticle virus neutralisation assays reveal a high prevalence of antibody in dromedary camels in egypt high prevalence of mers-cov infection in camel workers in saudi arabia who mers global summary and assessment of risk. world-health-organization lack of serological evidence of middle east respiratory syndrome coronavirus infection in virus exposed camel abattoir workers in nigeria mers coronaviruses in dromedary camels mers-cov antibodies in humans antibody response and disease severity in healthcare worker mers survivors transmission of mers-coronavirus in household contacts immune responses to middle east respiratory syndrome coronavirus during the acute and convalescent phases of human infection memory t cell responses targeting the sars coronavirus persist up to years post-infection middle east respiratory syndrome coronavirus (mers-cov) in dromedary camels in africa and middle east middle east respiratory syndrome coronavirus (mers-cov) in dromedary camels in nigeria enzootic patterns of middle east respiratory syndrome coronavirus in imported african and local arabian dromedary camels: a prospective genomic study middle east respiratory syndrome coronavirus (mers-cov) rna and neutralising antibodies in milk collected according to local customs from dromedary camels key: cord- -cd adns authors: thachil, jecko; owusu-ofori, shirley; bates, imelda title: haematological diseases in the tropics date: - - journal: manson's tropical infectious diseases doi: . /b - - - - . - sha: doc_id: cord_uid: cd adns nan haematological disorders are common in low-income countries. they make a substantial contribution to morbidity and mortality of individuals in these regions and have a negative impact on the growth and development of under-resourced nations. genetic red cells abnormalities are common in lowincome countries because they provide protection against malaria and they often co-exist with other causes of anaemia such as malnutrition and chronic illnesses. there is a close association between haematological abnormalities and infections which are a major cause of illness and death in these populations. morphological abnormalities of blood can often provide clues about the underlying diagnosis and blood film examination is particularly important where diagnostic facilities are limited. abnormal blood counts can manifest as various combinations of alterations of numbers of red cells, white cells or platelets. this section will outline some of the most common causes of abnormal blood counts likely to be encountered in clinical practice in low-income countries. anaemia is one of the most common causes of morbidity in the world and its impact is reflected in several of the health-related millennium development goals. although anaemia by itself is not a diagnosis, it suggests that there is an underlying disease state which needs to be recognized and treated. it is also a useful indicator of the general health of the population. the causes of anaemia may be identified systematically by considering the life cycle of the red cells (figure . ). nutrients necessary for red cell production are absorbed from the gastrointestinal tract and carried through the portal vein to the liver and ultimately reach the bone marrow where erythropoiesis occurs. this process is regulated by erythropoietin, a hormone released from the kidneys mainly in response to hypoxia. mature • africa and asia have more than % of the world's anaemic populations and anaemia burden is highest among children and women of reproductive age. • the accurate diagnosis of anaemia has been neglected; clinical assessment of anaemia is unreliable unless the anaemia is severe. • in low-income countries, anaemia in an individual is often due to multiple interdependent factors. removing or treating a single factor may not resolve the anaemia. • early diagnosis of sickle cell disease and rapid access to a specialist centre for emergencies such as severe pain crises, strokes and acute chest syndrome, can help to prevent permanent long-term complications. • beta-thalassaemia major is fatal in the first few years of life unless regular blood transfusions are given; unless they are accompanied by iron chelation, these transfusions will eventually cause death due to irreversible organ damage from iron overload. • malarial anaemia is a particular problem for children and pregnant women and severe anaemia can be caused by p. falciparum and p. vivax. malarial anaemia can be reduced with chemoprophylaxis and intermittent treatment, and by anti-mosquito measures such as insecticidetreated bed nets and vector control. • anaemia occurs in % of hiv-infected patients and is an independent risk factor for death. prompt treatment of factors associated with anaemia, such as infections and poor nutrition, and commencement of antiretroviral treatment will reduce deaths. • blood shortages are common in tropical countries. to increase the availability of blood, transfusions should be prescribed in accordance with guidelines and efforts made to encourage blood donors to donate regularly as repeat donors are the safest type of donor. reaction' , characterized by circulating myelocytes and metamyelocytes, can be mistaken for leukaemia but, unlike leukaemia, there is an orderly maturation and proliferation of neutrophils. leukaemoid reactions have also been described in patients with tuberculosis, juvenile rheumatoid arthritis and dermatitis herpetiformis. , decreased margination of neutrophils with egress of cells into the circulation can occur with exercise, adrenaline (epinephrine) injection, emotional stress and postoperatively or in response to drugs (e.g. steroids, β-agonists). other drugs, such as lithium and tetracycline, produce neutrophilia through increased production. neutrophilia is also a feature of bone marrow proliferation which occurs in myeloproliferative neoplasms, particularly chronic myeloid leukemia and myelofibrosis. teardrop cells and nucleated red blood cells are features of myelofibrosis on the blood film; basophilia and eosinophilia are common with chronic myeloid leukaemia. molecular testing for the jak- mutation or bcr-abl fusion gene can also help to differentiate between myeloproliferative neoplasms. rebound neutrophilia can occur following treatment of megaloblastic anaemia or after recovery from neutropenia induced by drugs. acute haemorrhage can cause neutrophilia, especially if bleeding occurs into the peritoneal cavity, pleural space, joints or adjacent to the dura. this is possibly due to the release of adrenaline and chemokines in response to local inflammation. the presence of neutrophilia can be useful in raising suspicions about the onset of complications in infections that are not primarily associated with neutrophilia. examples include meningitis in tuberculosis, orchitis in mumps, bowel perforation in typhoid fever and superadded bacterial infection in measles. the absence of neutrophilia can be helpful in differentiating typhoid and paratyphoid fever from pyogenic infections. neutropenia is defined as an absolute neutrophil count < . × /l. it is usually classified into severe (< . × /l), moderate red cells are released into the circulation from the bone marrow and percolate through the tissues and organs. anaemia can result from defects in any of these stages. inadequate production of red cells in the bone marrow can be due to lack of nutrients (e.g. iron, b , folate, vitamin a, copper or zinc), abnormal haemoglobin synthesis (i.e. haemoglobinopathies) or ineffective erythropoeisis from myelodysplasia or infections. red cells can be lost from the body (e.g. gastrointestinal bleeding) or removed prematurely if they are abnormal or the spleen is enlarged (i.e. haemolysis). kidney disease can result in decreased erythropoietin. anaemia of chronic disease (or 'anaemia of inflammation') is due to an inadequate response to erythropoieitin or to increased cytokine-induced hepcidin release in inflammatory states which interferes with iron absorption or iron utilization. diagnostic algorithms to determine the cause of anaemia are usually based on a combination of the mean cell volume of the red cells, the reticulocyte count and blood film appearance (figures . , . ). this approach is based on the availability of a haematology analyser and an experienced microscopist. several conditions which cause anaemia may co-exist in the same individual (e.g. intestinal parasites, malaria and sickle cell disease) and hence a thorough investigation is crucial to identify all potential causes of anaemia. neutrophils released from the marrow after maturation can either enter the 'circulating pool' or they can remain in the 'marginal pool' where they are loosely attached to the blood vessel wall. cells in the marginal pool are not sampled when blood is taken for a full blood count. neutrophilia can therefore result from increased bone marrow synthesis and also from decreased margination which increases the circulating pool. there are many causes of neutrophilia (box . ) but the commonest is bacterial infection in which there is increased bone marrow production of neutrophils and release of neutrophil precursors into the peripheral blood. this 'leukaemoid ( . - . × /l) or mild ( . - . × /l). the propensity to develop infections is related to the degree and duration of neutropenia, with higher risk associated with counts below . × /l. africans, african americans, yemenite jews, palestinians and saudi arabians generally have slightly lower neutrophil counts compared with other races. this is thought to be due to an increase in the bone marrow storage pool as ethnic neutropenia is associated with good neutrophil responses to infections. neutropenia can be due to impaired or ineffective (intramedullary death of neutrophil precursors despite normal bone marrow production) synthesis by the bone marrow (e.g. myelodysplasia, megaloblastic anaemia, treatment with phenytoin or methotrexate); a shift from the circulating pool to marginated pool (pseudoneutropenia) and increased peripheral destruction (e.g. secondary to antibodies against the neutrophils or increased reticulo-endothelial activity in sepsis or haemophagocytic syndrome) (box . ). increased consumption of neutrophils can result from increased attachment of cells to endothelium or other leukocytes in inflammatory states. neutropenia is often the result of a combination of several of these mechanisms. infants of hypertensive mothers may have moderate to severe neutropenia, which can last for several days. this is probably related to bone marrow suppression. moderate to severe neutropenia can also occur in newborn infants as a result of the transfer of maternal igg anti-neutrophil antibodies in a manner similar to rhesus haemolytic disease of the newborn. although neutropenia has been described with typhoid fever, minimum neutrophil count seldom falls below . × /l and the box neutropenia may not develop until after the first week of illness. infectious hepatitis and yellow fever can both cause neutropenia. overwhelming infections can lead to a failure of bone marrow production of neutrophils, especially in undernourished individuals and alcoholics. individuals with severe neutropenia can develop lifethreatening septicaemia, often from endogenous flora (e.g. oral cavity), and stringent measures should be taken to avoid situations which may predispose these individuals to infections. they may need prophylactic antimicrobials and should have rapid access to medical care. fungal infections are less common than bacterial infections in neutropenic individuals, and viral or parasitic infections rarely occur with isolated neutropenia. granulocyte colony stimulating factor (gcsf) injections can be helpful in raising the neutrophil count in patients with complicating infections since it stimulates the release of neutrophils from the marrow, but gcsf is only useful if there is some bone marrow reserve. patients with some congenital or immune forms of neutropenia can tolerate persistently low counts without any increase in the incidence of infections. monocytosis occurs in chronic infections and inflammatory conditions. protozoan infections such as typhus, trypanosomiasis and kala-azar may be associated with monocytosis. chronic and juvenile myelomonocytic leukaemias are malignant disorders in which monocytosis may be severe; acute monocytic leukaemias may present with mild to moderate monocytosis. monocytosis, and particularly a monocyte : lymphocyte ratio greater than . - . , may indicate active progression of tuberculosis and an unfavourable prognosis. the normal ratio of . or less is restored when the healing process is complete. a decreased absolute monocyte count occurs in bone marrow failure states such as aplastic anaemia or after chemotherapy. low monocyte counts can occur with overwhelming sepsis and with splenomegaly. monocytopenia is a characteristic feature of hairy cell leukaemia and is considered to be a diagnostic hallmark of this disease. peripheral blood contains only around % of the total body lymphocyte population since these represent the cells present in the blood during their transit into secondary lymphoid organs. wide variations exist in lymphocyte counts between individuals especially in childhood. lymphocyte counts exhibit a diurnal pattern; peaking at night with a nadir in the morning. lymphocytosis is characteristic of infectious mononucleosis and many atypical and large lymphocytes can be seen in the peripheral blood film. these atypical cells can also occur in cytomegalovirus infection and infectious hepatitis. absolute lymphocytosis can occur with chronic infections such as brucellosis and in the recovery stages of tuberculosis. lymphocytosis is unusual in bacterial infections except in the case of pertussis. heavy smoking is also an often overlooked cause of lymphocytosis and is probably one of the commonest reasons for a mild to moderate increase in the lymphocyte count. malignant bone marrow disorders, predominantly acute lymphoblastic and chronic lymphocytic leukaemia and non-hodgkin's lymphomas, can cause lymphocytosis. these lymphocytes may have characteristic morphological changes identifiable in the blood film (e.g. smear cells with chronic lymphocytic leukaemia) and the correct diagnosis can be confirmed by immunophenotyping for specific combinations of cell markers. lymphopenia is due to decreased production, redistribution or increased rate of death of lymphocytes. decreased production usually results from cytotoxic drugs and radiotherapy, while increased lymphocyte death can occur in infections such as influenza and hiv. occasionally, an isolated low lymphocyte count in the context of an otherwise normal full blood count can be a clue to the diagnosis of hiv. this reflects the destruction of cd + t cells by the virus although an expansion of cd + t cells may raise the total lymphocyte count to normal levels. redistribution rather than depletion of total body lymphocyte numbers occurs with steroid treatment or with endogenous secretion of corticosteroids during acute illnesses due to the retention of lymphocytes in secondary lymphoid organs. eosinophilia eosinophils are involved in innate immunity and hypersensitivity. their number in the circulation is relatively small compared to other leukocytes because they predominantly reside in tissues such as the gut, skin and lungs which are entry points for allergens and infections. the commonest causes of eosinophilia are helminthic infections, atopy and allergic diseases, and adverse drug reactions. less common causes are classified under the umbrella term of hypereosinophilic syndromes (table . ). since parasitic infections are likely to be the commonest cause of eosinophilia in the tropics and in returning travellers, an extensive search for such infections should be undertaken in patients with persistent eosinophilia; initial investigations should be determined by the patient's history of geographical exposure (figure . ) . [ ] [ ] [ ] the absolute number of eosinophils in the peripheral blood may not correlate with their tissue distribution or with their potential to cause tissue damage from their granule release. this is because the degree of eosinophilia depends on the extent of tissue invasion and is therefore modest with tapeworms and roundworms resident in the bowel but much higher where invasion occurs, for example with, toxocara canis or filaria. schistosomiasis almost always causes eosinophilia. strongyloides stercoralis has the capacity to remain in the host for decades after initial infection and causes varying degrees of eosinophilia, with or without other symptoms. steroid treatment, which may be necessary in cases of eosinophilic tissue damage, can exacerbate clinical problems in patients with strongyloides infection so this parasitic infestation should be excluded before starting steroids for hypereosinophilia. mild to moderate eosinophilia is common in asthma although a very high count should prompt a search for churg-strauss syndrome or allergic bronchopulmonary aspergillosis. most drugs including penicillins can cause eosinophilia but the diagnosis can only be made by noting recovery when the drug is discontinued. eosinophilia can be a feature of hodgkin's lymphoma. it signifies a more favourable prognosis and may precede the original diagnosis of lymphoma or relapses. in immunocompromised patients, such as those with hiv infection, the finding of eosinophilia may be crucial since the success of antiretroviral treatment may depend on concomitant eradication of parasites. thrombocytopenia is often discovered incidentally in patients during full blood count estimation. a platelet count above - × /l is usually not associated with any symptoms such as bleeding. if clinically evident haemorrhage does occur at counts above this level, other conditions such as coagulation defects, vascular problems or rarely platelet dysfunction should be suspected. although the prime role of platelets is in haemostasis, several other important roles have been recognized in recent years including wound repair, tissue healing, antimicrobicidal properties, lymphangiogenesis, tumour metastasization and maintenance of blood vessel integrity. congenital platelet disorders are often part of a syndrome. patients with wiskott-aldrich syndrome have small platelets in association with eczema and recurrent infections. other congenital platelet disorders, such as myh -related disorders, can present with deafness or cataracts while skeletal deformities and oculocutaneous albinism are common in other syndromic presentations. blood film morphology can provide important clues about the causes of thrombocytopenia (figure . ). fragmented red cells (schistocytes) increase the possibility of microangiopathic haemolytic anaemia, where an altered vessel wall and fibrin formation in the blood vessels shred the erythrocytes and consume platelets. thrombotic thrombocytopenia purpura, haemolytic uremic syndrome and disseminated intravascular coagulation can all present with thrombocytopenia. dysplastic red or white cells should raise the suspicion of myelodysplasia which can be confirmed by bone marrow examination and cytogenetic analysis. it is important to exclude in vitro platelet agglutination as a cause for apparent thrombocytopenia. this can be an anticoagulant (edta)-dependent phenomenon so a repeat sample should be examined using citrate anticoagulant. rarely, platelet satellitism where the platelets clump round the neutrophils, can cause artefactual thrombocytopenia. anaemia affects nearly two billion people globally with a much higher prevalence in developing countries compared with more wealthy nations ( % vs %). the continents of africa (highest prevalence) and asia (greatest absolute burden) account for more than % of the anaemic population. anaemia burden is highest among children and women of reproductive age. anaemia contributes to more than maternal deaths and perinatal deaths globally per year. who have defined anaemia according to various haemoglobin concentrations (table . ) but the appropriateness of these thresholds has been questioned because there are wide variations in haemoglobin concentration among people of different races. the prevalence of anaemia can be a useful indicator of public health status of a nation because: • the prevalence of anaemia is objective and quantifiable • anaemia is a major complication of several infections, including malaria, hiv, tuberculosis, and the neglected tropical diseases, which are among the commonest problems in most tropical countries • the incidence of anaemia changes in a predictable fashion with alterations in disease burden • the prevalence of anaemia can be used to assess whether an intervention has reached the poorest communities. haemoglobin concentration of < g/l has been recommended for disease surveillance in high-prevalence countries where changes in haemoglobin are used for monitoring the impact of interventions. anaemia in tropical countries (box . ) is often due to infections but chronic health problems, such as diabetes and chronic respiratory disease, and cancer and related complications are increasing as causes partly due to lifestyle changes. the body to compensate for the drop in haemoglobin content. for this reason the haemoglobin level can drop to extremely low levels before symptoms develop. anaemia presents with symptoms such as exertional breathlessness, palpitations and in some cases, syncopal attacks. patients with chronic anaemia may also have a multitude of nonspecific symptoms including poor concentration, decreased work performance and easy exhaustion (table . ). a thorough history and clinical examination may provide clues about the cause of anaemia but further investigations are often necessary to confirm the diagnosis and guide treatment. however, in many resource-poor settings, access to routine biochemical and haematological testing is scarce, so much reliance is placed on clinical examination. the international guidelines for the integrated management of childhood illness recommend that a diagnosis of anaemia in sick children is based on the assessment of palmar pallor. for pregnant women, symptoms of fatigue and dyspnoea, combined with signs of conjunctival and palmar pallor, and increased respiratory rate suggest anaemia. however, making a diagnosis of anaemia based on clinical assessment alone is unreliable unless the anaemia is severe. no specific anatomical site is particularly accurate for the prediction of anaemia though sensitivity may be increased by using multiple sites. most central laboratories in low-income countries have automated haematology analysers and several manual methods exist for assessment of haemoglobin concentration, which are suitable for rural areas where there is no mains electricity (e.g. haemoglobin colour scale; hemocue technique). [ ] [ ] [ ] haemoglobin colour scale principle. the colour of a finger-prick blood sample, soaked into special chromatography paper, is compared with the clinical symptoms and signs of anaemia vary and depend on the cause and the speed of onset. a rapid drop in haemoglobin is much more likely to cause symptoms of anaemia than chronic anaemia. slowly developing anaemia allows time for in many cases, there will be more than one of these conditions coexisting in the same individual. an adequate response to the treatment of anaemia requires management of all the contributory factors. intrauterine growth. thus, low birth weight and prematurity are both associated with iron depletion in the postnatal period. several interventions have been suggested to improve infantile iron deficiency, including: [ ] [ ] [ ] • delayed cord clamping at delivery; the short delay of - minutes allows a small but important amount of blood to continue to flow to the foetus from the placenta • improvement of infant feeding practices • prevention and treatment of infectious diseases • interventions to prevent low birth weight, such as maternal nutritional supplementation, the control of infections and chronic health problems in pregnancy. anaemia in young children can be due to increased nutrition requirements during periods of rapid growth; these requirements may be up to times higher per kilogram of body weight than that of an adult male. in addition, infant and toddler diets often lack bio-available iron. a case-control study of preschool children in malawi with severe anaemia (haemoglobin concentration, < g/l) identified bacteraemia, malaria, hookworm, hiv infections and deficiencies of vitamins a and b as the commonest causes of anaemia. lack of folate and iron were uncommon. in low-income countries multiple interdependent causes of anaemia often operate in one individual so rectifying a single factor is unlikely to make a big impact on resolving anaemia. interventions which are useful in preventing anaemia in younger children include micronutrient supplementation (food fortification), de-worming, prevention and treatment of infectious diseases, school nutrition programmes and community-based nutrition promotion. who defines anaemia of pregnancy as a haemoglobin level less than g/l, or haematocrit less than %, at any time during pregnancy. about one-fifth of maternal mortality is attributable to anaemia in pregnancy and anaemia affects nearly half of all pregnant women worldwide. maternal anaemia is associated with many factors that might also be causally associated with mortality including poverty, infections and inadequate health-seeking behaviour. globally, the most important cause of anaemia in pregnancy is iron deficiency although hookworm, malaria, hiv infection, and deficiencies in folate and other micronutrients may contribute. pregnancy-associated complications, including septicaemia, pre-eclampsia and other obstetric problems can precipitate anaemia. it is important to note that a diagnosis of iron deficiency in pregnancy which relies on ferritin measurements may be misleading because of high-quality digital examples of known haemoglobin concentration. the colours are represented in g/l increments from g/l to g/l. this method is inexpensive, does not depend on skilled scientists, is durable in dusty, hot, dry and humid conditions and is probably better than clinical diagnosis for detecting mild and moderate degrees of anaemia. the disadvantages are that it requires specific chromatography paper and good natural light and it cannot detect changes in haemoglobin less than g/l. this is a small battery-or mains-operated machine, which uses a drop of blood in a plastic cuvette to produce a direct read-out of haemoglobin in a few seconds. it is simple to use, produces accurate and consistent results to one decimal place and it has an in-built quality-checking mechanism. the hemocue hb- has been specifically designed for tropical conditions and operates in temperatures up to °c, in dusty and humid conditions. however the recurrent costs associated with disposable plastic cuvettes mean there is little opportunity for cost-saving with high-volume workloads. the iron status of an infant is directly proportional to its body mass and blood volume, both of which are reflections of the major cause of anaemia in most of these cases is iron deficiency. some of the effects have been described in individuals with iron deficiency without obvious features of anaemia. there are three intervention strategies recommended by who to prevent anaemia in pregnancy: . weekly iron and folic acid supplementation in women of reproductive age . daily iron and folic acid supplementation during pregnancy . presumptive treatment of hookworm infection during pregnancy in areas where hookworm infection is known to be endemic. several factors may interfere with the efficacy of these interventions. under-participation in antenatal care may be common due to factors such as geographic distance, low motivation and poor interpersonal skills of health staff, poor quality of supplies and facilities, insufficient supply of iron and folic acid pills and womens' poor understanding about the daily use of supplements, especially in the face of common side effects. in sub-saharan africa, the acute shortage and high turnover of health workers, and lack of time have also been shown to contribute to ineffective antenatal measures for reducing anaemia. interestingly, a study from bangladesh showed that the first pills (whether taken on a daily basis or less frequently) yielded most of the benefit for raising haemoglobin levels, which suggests that currently recommended doses may be higher than necessary to achieve optimal outcomes, except when anaemia is very severe. the global burden of iron deficiency has been estimated from anaemia prevalence surveys, which include many different causes of anaemia so data may be unreliable as they are often not based on proven cases of iron deficiency. who estimates that globally % of women and % of pre-school children are affected by iron-deficiency anaemia, making it number of selected risk factors for preventable death and disability worldwide. iron deficiency begins in childhood, worsens during adolescence in girls and is aggravated during pregnancy. poor iron stores at birth, low iron content of breast milk and low dietary iron intake throughout infancy and childhood result in high prevalence of anaemia in childhood. anaemia is exacerbated by increased requirements during adolescence and iron loss from menstruation and is often compounded by the lack of adequate nutrition. the situation is worsened by pregnancy when iron requirement is approximately two times higher than in a nonpregnant state. iron deficiency should not be considered a diagnosis but a secondary outcome due to an underlying medical condition. although it may be a physiological response to rapid growth or increased requirements during childhood and pregnancy, it still requires treatment due to potential deleterious consequences. many of the chronic effects of iron deficiency may develop before the clinical and laboratory evidence of anaemia becomes apparent. the biochemical evidence for iron deficiency occurs in several steps. initially, iron stores in the bone marrow are depleted as reflected by a decreased serum ferritin. the total iron-binding capacity then starts to rise, while the serum iron saturation begins to fall before microcytosis and a drop in haemoglobin ensue. there have been attempts to identify this early iron deficiency before anaemia develops in order to improve neurological and psychomotor functions in children and work performance in adults through widespread iron supplementation. however, there are concerns that iron excess may promote infections, especially in malarious areas. a range of laboratory investigations are usually necessary if iron deficiency is suspected (table . ) - because once the diagnosis is confirmed, a search for the precise cause is necessary. a systematic approach to the investigation of iron deficiency (see below) is required based on an understanding of alterations in the iron absorption and transport cycle. • deficient intake (cow's milk has poor iron content and can cause gut blood loss in some infants) • rare defects of haem biosynthesis and iron transport. iron-deficient individuals may have no symptoms. excessive fatigue and other nonspecific signs of anaemia become more pronounced as anaemia develops. consumption of unusual 'foods' such as ice and paint or 'pica' only occurs in a minority of individuals. physical examination may reveal stomatitis, glossitis, koilonychia (spoon-shaped nails) and hair loss. oesophageal webs have been described in the plummer-vinson syndrome but are rare and may respond to iron replacement. since iron is important in neuromuscular development, several features of anaemia described in table . may be related to iron deficiency. treatment of iron deficiency is with dietary modifications and oral or parenteral iron. blood transfusions should be reserved for those with severe symptoms especially if the anaemia developed rapidly. haemoglobin levels alone should not be considered as a criterion for transfusion since very low levels (e.g. - g/l) may be appropriately treated with oral iron if anaemia has developed slowly. intravenous iron should only be considered in cases of poor response or intolerance to oral iron. cereals, poultry and green leafy vegetables, contain non-haem iron, which is often poorly absorbed. if dietary history suggests a deficiency, diet with foods rich in haem iron, such as red meat or liver should be recommended if social and religious customs and financial status allow, ideally with a drink containing vitamin c to facilitate iron absorption. absorption is also facilitated by taking supplements on an empty stomach although side effects of dyspepsia may not always allow this strategy. heavy tea intake can interfere with iron absorption and should be avoided. multivitamin or dietary supplements containing calcium, zinc or copper can also interfere with iron absorption. absorption may be delayed by tetracyclines, milk and soft drinks. since acid is necessary for iron absorption, antacids may account for a poor response to oral iron. iron is usually prescribed as a daily dose of - mg of elemental iron, commonly ferrous sulphate, tablet three times daily. the dose in children is - mg/kg per day split into divided doses. assuming good compliance and absorption, this should result in an increase in haemoglobin within weeks. once the haemoglobin is normalized, iron should be continued for months to replenish the iron stores. the major problem with oral iron is upper gastrointestinal side-effects, which can be dose-dependent. a reduction in the dose or change in the formulation to gluconate or fumarate or even liquid forms, may be successful. liquid iron preparations may stain the teeth and should therefore be taken through a straw. oral iron can also cause constipation or diarrhoea which is not dose-dependent. parenteral iron is best given intravenously because intramuscular iron is painful and has been associated with development of soft tissue sarcomas. high-molecular-weight iron dextran carries a low but significant risk of anaphylaxis, but the newer formulations including low-molecular-weight iron dextran, iron sucrose, ferumoxytol and iron gluconate have minimal risks. vitamin b or cobalamin deficiency is a well-recognized cause of macrocytic anaemia (box . ). although some microorganisms can synthesize cobalamin, humans need to obtain this essential vitamin from foods, mainly meat, poultry and dairy products. vitamin b is an essential co-factor in dna synthesis, serving as a co-factor in two key biochemical processes involving methylmalonic acid and homocysteine as precursors. consequently vitamin b deficiency can interfere with dna synthesis. clinical manifestations include haematological (megaloblastic anaemia and pancytopenia), and neuropsychiatric disorders (paraesthesia, peripheral neuropathy, psychosis and dementia) and an increased risk of cardiovascular disease because of hyperhomocystinaemia. [ ] [ ] [ ] a systematic approach to the investigation of vitamin b deficiency requires an understanding of the absorption cycle. ingested vitamin b is broken down in the acidic environment of the stomach. it binds to r-binders in gastric secretions and saliva which stabilize the vitamin b . in the alkaline environment of the small intestine, vitamin b is released from r-binders to bind to intrinsic factor, synthesized in the gastric parietal cells. this vitamin b -intrinsic factor complex is absorbed from the terminal ileum. recently, an alternative absorption system independent of intrinsic factor and the terminal ileum has been postulated which provides a rationale for mean cell volume useful as a diagnostic clue but not confirmatory can also be low in thalassaemia, sideroblastic anaemia and rarely lead poisoning can be falsely normal in the presence of iron deficiency in older people or with coexistent megaloblastic anaemia anaemia of chronic disease can occasionally cause microcytosis serum ferritin the most useful laboratory measure of iron status low value is diagnostic in the presence of anaemia very high values (> µg/l) usually exclude iron deficiency' being an acute-phase protein, it increases in inflammatory conditions, and certain malignancies, making it unreliable also increased in tissue damage especially of the liver levels are falsely decreased in vitamin c deficiency and hypothyroidism erythrocyte zinc protoporphyrin an intermediate in haem biosynthesis and elevated concentrations indicate interrupted haem synthesis due to iron deficiency when zinc is incorporated in place of iron can be measured on a drop of blood with a portable haematofluorometer small sample size makes it very useful as a screening test in field surveys, particularly in children, and pregnant women where inflammatory states may not co-exist red cells should be washed before measurement (serum bilirubin and fluorescent compounds like some drugs can give falsely high values) although not often done lead poisoning can give falsely high values rarely acute myeloid leukaemia and sideroblastic anaemia give slightly high values useful in that it is not increased in thalassaemias who recommends normal level > µmol/mol haem iron studies serum iron concentration represents the iron entering and leaving the circulation. its range varies widely with age, circadian rhythm, infections and iron ingestion total iron binding capacity measures iron bound to transferrin. raised levels are suggestive of iron deficiency transferrin saturation is the ratio of serum iron and the tibc expressed as a percentage -it is probably more useful in detecting iron overload rather than low levels. sensitive indicator that falls within days of onset of iron-deficiency reduced levels shown to be predictor of iron deficiency especially in the setting of renal insufficiency false normal values can occur when mcv is increased or in thalassaemia serum transferrin receptor it is not increased in inflammatory conditions may be upregulated by increased erythropoiesis (haemolytic diseases) giving falsely high values -serum transferrin receptor to ferritin ratio has been suggested in these cases bone marrow examination with special iron staining (perl's) absence of stainable iron in a sample that contains particles can establish the diagnosis without other laboratory tests a simultaneous control specimen containing stainable iron should also be assessed useful in differentiating from anaemia of chronic disorders or α-thalassaemia or milder forms of thalassaemia can help in identifying the sideroblastic anaemias (ring sideroblasts with perls stain), and some forms of congenital dyserythropoietic anaemia which can also cause microcytosis. an improvement in haemoglobin and clinical symptoms with iron replacement is probably the simplest way to diagnose iron deficiency. peripheral smear may help by demonstrating pencil cells, anisopoikilocytosis and high platelet number in cases of blood loss. the treatment of vitamin b deficiency can be by the oral or parenteral route. increasing evidence suggests that oral supplementation may be adequate even in the presence of malabsorption or pernicious anaemia. , the recommended initial oral replacement dosage is - mg but higher doses may be needed for malabsorption or pernicious anaemia. for patients with severe anaemia and/or neurological disease, daily or alternate day intramuscular injections should be initiated for the first - weeks before reverting to the maintenance threemonthly dose. reticulocytosis is an early marker of response to treatment and is noticeable within - weeks. folic acid deficiency causes similar haematological manifestations to vitamin b deficiency though neuropsychiatric manifestations are less common. the ability of nerve tissue to concentrate folate to levels five times greater than those in the plasma has been suggested as a reason for the absence of neuropathy in folate deficiency. folic acid deficiency is associated with fetal neural tube defects, and possibly with an increase in atherosclerosis and arteriovenous thrombosis, dementia and colonic cancer. dietary folic acid is present in the form of polyglutamates, which are converted to folate monoglutamates by the enzyme folate conjugase in the intestinal brush border, prior to absorption. the monoglutamates function as a carbon transporter and are essential for dna biosynthesis. folate is found in green vegetables and fruits and deficiency can result from decreased intake, impaired absorption and increased utilization, although the commonest cause is dietary insufficiency. in some wealthy countries, cereals have been fortified with folic acid to successfully prevent vitamin deficiency. however folate deficiency continues to be a problem in less wealthy countries and particularly among children and pregnant women. , exclusive feeding of goat's milk to infants can lead to folate deficiency. other causes include alcoholism, excessive cooking of vegetables, and malabsorption (e.g. abnormalities of the small bowel). increased demand for folic acid occurs in pregnancy because the growing foetus has a high avidity for folate. for this reason, folate supplementation has been widely recognized as an essential part of routine antenatal care to reduce the risks of neural tube defects. high folate utilization also occurs in haemolytic anaemias such as sickle cell disease due to high red cell turnover and exfoliative dermatitis. several drugs, including sulfasalazine, trimethoprim, methotrexate, pyrimethamine and phenytoin, can also interfere with folate metabolism. folate-deficient individuals develop a macrocytic anaemia with peripheral blood and bone marrow findings similar to that found in vitamin b deficiency. diagnosis of folate deficiency is confirmed by the presence of low serum folate. red cell folate levels decrease more slowly than serum levels during the -day turnover of the red cells. red cell folate levels may be a better indicator of tissue folate levels than serum folate, although red cell folate can be more expensive and falsely low in vitamin b deficiency. , treatment of folate deficiency is with oral folate ( mg daily) which is sufficient even in malabsorptive states. it is crucial that any co-existing vitamin b deficiency is ruled out before initiating folic acid therapy, otherwise the neurological manifestations of b deficiency may deteriorate rapidly. it is also important increasingly popular oral replacement therapies. once absorbed, vitamin b binds to transcobalamin ii to be transported around the body. the diagnosis of vitamin b deficiency is based on the measurement of serum vitamin levels in a patient with clinical evidence of deficiency. a note of caution is that folic acid deficiency can cause falsely low serum vitamin b levels. diagnostic clues for vitamin b deficiency include marked macrocytosis (often > fl), neutrophil nuclear hypersegmentation and oval macrocytes in the peripheral blood film. blood tests may demonstrate increased lactate dehydrogenase and low haptoglobin levels due to haemolysis within the bone marrow. the cause of the macrocytosis can be confirmed by bone marrow examination which reveals a megaloblastic picture. although macrocytic anaemia is a typical feature of vitamin b deficiency, it can be absent in older individuals who may only have neuropsychiatric features. measurements of methylmalonic acid and homocysteine levels, two markers which are very sensitive for detecting b deficiency, have shown that vitamin b deficiency can occur with normal haemoglobin levels and without macrocytosis. pernicious anaemia is probably the commonest cause of vitamin b deficiency. the presence of parietal cell or intrinsic factor antibodies supports a diagnosis of pernicious anaemia. [ ] [ ] [ ] [ ] schilling tests are rarely performed because of the unavailability of the radio-labelled vitamin b and the difficulty in interpreting the results in the presence of renal insufficiency. • pernicious anaemia (begins after ), increased risk of gastric carcinoma and carcinoid tumours • rare congenital disorders, e.g. imerslund-grasbeck syndrome. the neglected tropical diseases are a group of infections which are endemic in developing countries. several of these neglected tropical diseases cause anaemia and many can be managed using inexpensive interventions to treat the underlying parasitic infections. the mechanisms of anaemia in these conditions are predominantly blood loss from the gastrointestinal or genitourinary tracts but also poor nutrition, bone marrow suppression, inflammation, hypersplenism and haemolysis. anaemia is a common consequence of infections with soiltransmitted helminths or schistosoma with a strong correlation between haemoglobin level and worm load or faecal egg count. even mild infections can lead to anaemia. polyparasitism (i.e. infection with several parasites simultaneously) can be responsible for unresponsiveness of the anaemia to eradication of one organism. treatment of communities at high risk of soiltransmitted helminths improves growth and iron stores in children and reduces anaemia in pregnant women. the treatment of anaemia due to neglected tropical diseases depends on eradication of the parasite with drugs such as albendazole and praziquantel though anaemia resolution may be less successful if it is due to trichuriasis. - the addition of iron to anthelmintic treatment has met with variable success rates probably because there is associated anaemia related to inflammation. however it is still generally recommended that iron supplementation should be included with anthelmintic therapy in treatment programmes for neglected tropical diseases. [ ] [ ] [ ] introduction haemoglobin s (hbs) has a prevalence of - % in many parts of africa and also some areas in the middle east ( figure . ). hbs tends to be common among ethnic groups that have traditionally had high exposure to plasmodium falciparum malaria. in sub-saharan africa approximately infants are born with sickle cell disease each year, mostly with hbss. sickle cell disease (scd) is an autosomal recessive disorder characterized by production of an abnormal haemoglobin, sickle haemoglobin. sickle haemoglobin (hbs) arises from a mutation in codon of the β-globin gene resulting in replacement of the normal glutamic acid residue by a valine. scd is most commonly caused by the co-inheritance of two sickle cell genes (homozygous hb ss disease) but patients who are heterozygous for hbs and for another haemoglobin mutation such as hbc (haemoglobin sc disease) or β-thalassaemia (sβ and sβ + ) can also present with features of scd. ss disease and sβ disease are more severe than sc disease and sβ + disease (box . ). scd can affect multiple organs and its clinical course is punctuated by episodes of acute illness on a background of progressive organ damage, especially of the central nervous system and the lungs. the first description of scd was in in an anaemic grenadian dental student and over the next years it was that the underlying cause of folate deficiency is identified and treated. vitamin a is important in erythropoiesis, iron metabolism (enhances iron absorption and its release from stores to the bone marrow) and for decreasing the risk of infections. vitamin a deficiency is a major public health problem in lowincome countries, with an estimated million preschool children affected. pregnant women and women of childbearing age also constitute high-risk groups for vitamin a deficiency. vitamin a given to thai school children with conjunctival xerosis led to a significant increase in haemoglobin level and in anaemic school children in tanzania, vitamin a supplementation produced a marked increase in haemoglobin which was enhanced by co-administration of iron. vitamin a can also improve anaemia in pregnant women, depending on the local prevalence of deficiency [ ] [ ] [ ] [ ] though the response may be suboptimal in pregnant women infected with hiv. copper is a trace element necessary for normal haematopoiesis and myelopoiesis. anaemia in copper deficiency is due to decreased activity of the copper-dependent enzymes, hephaestin, ceruloplasmin and cytochrome c oxidase. these are important in ferrous-ferric iron conversions and their decrease leads to abnormalities in iron absorption and its incorporation into the haemoglobin molecule. acquired copper deficiency occurs with malnutrition and gastrointestinal malabsorption syndromes. coeliac disease, cystic fibrosis and individuals who have had gastrectomy or surgery resulting in 'short bowel' are also at risk. copper deficiency has also been described in persons ingesting excessive amounts of zinc-containing supplements and those who have swallowed zinc-containing coins. , anaemia related to copper deficiency is normocytic or macrocytic and can be associated with neutropenia; thrombocytopenia is rare. bone marrow findings are characteristic with cytoplasmic vacuolization of both erythroid and myeloid precursor cells with ringed sideroblasts and an unusual finding of iron granules in plasma cells. these findings may be misdiagnosed as myelodysplastic neoplasm. measurement of serum copper levels is helpful in confirming the diagnosis although the test is fairly insensitive. since almost complete haematological recovery can occur with copper replacement, this may be a useful diagnostic test. oral copper supplements can be started with mg of elemental copper a day slowly decreasing over the next few weeks to mg until a good response is noted. although low zinc levels do not cause anaemia they have been linked to growth retardation, heightened susceptibility to infection and male hypogonadism in relation to sickle cell disease. zinc deficiency has been described in nearly half of children and % of adults with sickle cell disease possibly due to increased loss of zinc in the urine and high cell turnover with decreased dietary intake. in contrast zinc excess can cause anaemia through interference with copper absorption by sequestering it in the gut lumen. for this reason, zinc compounds have been used to treat wilson's disease which is characterized by copper excess. however repeated sickling and unsickling eventually causes irreversible changes, so early management to avoid repeated crises is important to prevent disease progression. polymerization, and therefore the clinical features of scd, are influenced by three main factors ; hypoxia, the intracellular hbs concentration and the co-existence of other genetic haemoglobin abnormalities (e.g. α-thalassaemia or hereditary persistence of fetal haemoglobin-haemoglobin f). sickled red cells lead to vaso-occlusion and haemolysis due to the entrapment of sickled erythrocytes in the microvasculature and upregulation of adhesion receptors. , , white blood cells contribute to this process by providing an inflammatory discovered hypoxia led to red cell sickling scd arises from the tendency of hbs to polymerize in hypoxic states. this phenomenon occurs where there is deoxygenation and is due to the binding between β and β chains of two haemoglobin molecules, a property unique to haemoglobin variants that have the glu- -val substitution. the polymerized haemoglobin fills the erythrocyte and deforms its architecture and flexibility to form a sickle shape. this alteration in the structure promotes cellular dehydration, , , upon reoxygenation, the polymers dissolve thus reversing the sickling process. exposure to cold, fever, menstruation, alcohol intake and dehydration can precipitate pain crises. unlike acute pain crises, chronic pain in scd usually has an identifiable basis such as femoral head necrosis, osteoarthritis or chronic skin ulcers. sickle erythrocytes have an average life span of days and anaemia can be due to several causes (box . ). red cell haemolysis causes anaemia and gall stones and can cause fatigue out of proportion to the anaemia. , there are suggestions that patients with low haemoglobin concentrations and high haemolytic rates are more likely to develop vascular problems compared with those with higher haemoglobin concentrations. splenic sequestration with a sudden rapid drop in haemoglobin occurs in those who have not yet developed autosplenectomy so it can occur in young children with hbss and adults with hbsc disease or sickle cell-β + -thalassaemia. treatment may require blood transfusion and in rare cases, sequestration can be fatal. splenectomy may be needed for recurrent severe sequestration. parents can be taught to feel their infant's abdomen for an enlarging spleen and report to hospital if there is a sudden increase in spleen size. red cell aplasia can develop due to secondary parvovirus infection which has a predilection for erythroid progenitors. alloimmunization is common in scd patients who have had frequent transfusions so, if possible, extended red cell phenotyping should be undertaken. hyperhaemolytic crisis is suspected when there is sudden exacerbation of anaemia with increased reticulocytosis and bilirubin level. infectious complications of scd are a major cause of morbidity and mortality, even with adequate vaccination and prophylactic antibiotic regimens. this propensity to infection is related to impaired splenic function although tissue ischaemia, especially in the lungs and renal system, can contribute. hyposplenism is demonstrable in the peripheral blood film by the presence of howell-jolly bodies. most children with scd have undergone autosplenectomy by the age of years and therefore have increased risk of infection from encapsulated microorganisms. typical infectious complications include pneumococcal sepsis, neisseria meningitis, osteomyelitis caused by salmonella species, urinary tract infections and pyelonephritis due to escherichia coli. anatomical abnormalities such as renal papillary necrosis can predispose to urinary complications which may require long-term antibiotics. acute chest syndrome (acs) is defined as a new pulmonary infiltrate on the chest radiograph combined with one or more environment. activation of platelets and the coagulation system also contribute to the vaso-occlusion in scd. [ ] [ ] [ ] [ ] [ ] infants with scd are protected during the first few months of life by the high levels of haemoglobin f in the red cells. anaemia usually develops by months. at all ages, chronic haemolysis of abnormal red cells means that scd is associated with steady state haemoglobin levels of - g/l. although any organ can be affected by scd and complications can occur at any age, certain features tend to predominate in different age groups (box . ). pain is the hallmark of scd and four different patterns of pain have been described with scd each with different underlying mechanisms: • vaso-occlusive (acute and intermittent) • pain from bone and tissue necrosis (chronic) • neuroplasticity (chronic, neuropathic) -functional brain changes • opioid-induced hyperalgesia (acute or chronic). painful crises often start in young children as dactylitis or handfoot syndrome, in which painful swelling of the hands and feet results from the inflammation of metacarpal and metatarsal periosteum. these crises are the result of vaso-occlusion of the bone marrow causing bone infarction and release of mediators that activate pain receptors. the number, severity and frequency of painful episodes vary widely in individuals. half may never have any episodes whereas about % may need hospital admission up to times a year. more than three pain episodes requiring hospitalization per year is associated with increased mortality among patients over years old. in under-resourced settings, hospital visits underestimate the frequency of pain box manifestations such as fever, cough, sputum production, tachypnoea, dyspnoea or new-onset hypoxia. acs is the most common cause of death in scd patients and a frequent cause of hospitalization, second only to painful crisis. mortality in patients with acs in a wealthy country setting is % in children and . % in adults. the peak incidence for acs is - years of age and gradually declines to . per patient-years in subjects older than years. , fever and cough are more common in children with acs and chest pain and dyspnoea are more common in adults. acs is often preceded by febrile pulmonary infection in children and by vaso-occlusive pain crisis and lung infarction in adults. it is important to note that although tachypnoea, wheezing and features of chest infection may be identified, a third of the patients may have a normal physical examination. more than one-third of patients with acs are hypoxaemic (oxygen saturation < %). chest radiography is essential although infiltrates may lag behind clinical symptoms by up to days. repeat chest x-rays are recommended if there is a strong clinical suspicion of acs. bilateral infiltrates or involvement of multiple lobes may predict a poorer prognosis. risk factors for acs (box . ) include fat embolus which can be confirmed by finding stainable fat in pulmonary macrophages. chronic complications such as pulmonary hypertension occur in as many as % of patients and do not appear to be associated with prior episodes of acs. high serum phospholipase a , and the surrogate marker c-reactive protein, have been noted in patients admitted with vaso-occlusive crisis - hours before the development of acs. , stroke neurological complications occur in at least % of patients with scd and scd is one of the most common causes of stroke in children. , in scd, the risk of having a first stroke is % by the age of , % by age years and % by age years. both thrombotic and haemorrhagic strokes occur, although the former is more common in children and those over years of age, whereas the latter is more common between the ages of and years. this age-specific pattern may be related to the higher cerebral flow rates in early childhood. although the prevalence of clinically overt stroke is of the order of %, clinically silent infarction, detectable by magnetic resonance scans, affect nearly double this number by the age of . silent infarcts are associated with cognitive impairment and the majority of these children require lifelong specialist care. cerebral thrombosis, which accounts for - % of all strokes in scd, results from large-vessel occlusion whereas silent infarcts are the result of microvascular occlusion or thrombosis or hypoxia secondary to large-vessel disease. in a third of scd patients, major-vessel stenosis is accompanied by collateral vessels that appear as 'puffs of smoke' (moyamoya) on angiography. risk factors for ischaemic strokes in scd include increased cerebral blood flow velocity, previous silent infarcts, nocturnal hypoxaemia, severe anaemia, acute chest syndrome and elevated systolic blood pressure. an elevated leukocyte count is a risk factor for haemorrhagic stroke. [ ] [ ] [ ] [ ] diagnosis often the family history and clinical findings clearly point towards a diagnosis of scd and during an acute crisis, abundant sickled red cells can be seen on a blood film. white cell counts are higher than normal in scd disease, particularly in patients under age years. the presence of sickle haemoglobin in different sickle syndromes (e.g. hbas, hbss, hbsc) ( table . ) can be confirmed by a simple sickle slide or solubility test. haemoglobin electrophoresis will distinguish between many of these variants but high-performance liquid chromatography and iso-electric focusing are preferred for a definitive diagnosis. haemoglobin mass spectrometry and dna analysis are being increasingly used. antenatal screening is available to women in some countries to help to identify couples who are at risk of having a baby with scd. community acceptance of reproductive genetic services however depends on the effectiveness of education and counselling. the use of prophylactic penicillin and the provision of comprehensive medical care during the first years of life have reduced mortality related to scd from % to less than %. management (box . ) individuals with scd are best managed by a multidisciplinary team as they may require a variety of specialist inputs including haematology, ophthalmology, nephrology, obstetrics, orthopaedics and physiotherapy. the cornerstones of scd therapy are disease modification and prompt and effective management of crises. severe pain crises generally require intravenous fluids and adequate, often opiate, analgesia (box . ), while disease modification is based on interventions to increase hbf levels. in steady state it is usual practice to give sickle cell patients folate supplements ( - mg/day) because their high rates of haemopoiesis put them at risk of deficiency. scd is associated with functional asplenia so patients should also receive prophylactic oral penicillin ( mg twice a day) and vaccinations against encapsulated organisms. hydroxycarbamide is the main agent used to increase hbf (box . ) and is associated with significant reductions in acute pain crises, hospitalization rate, time to first and second pain crises, episodes of acute chest syndrome, and the need for transfusions and the number of units transfused. other beneficial effects of hydroxycarbamide, which are independent of the increase in hbf, include reduced neutrophil count, increased cellular water content, decreased hbs concentration, changing expression of adhesion molecules and nitric oxide generation. hydroxycarbamide may also be an alternative to frequent blood transfusions for the prevention of recurrent stroke in children as it can lower transcranial doppler velocities. , under-use of this cheap, effective drug is related to concerns about leukaemogenicity but this has not been shown to be a problem when used for a non-malignant condition like scd. the two main approaches to transfusion in scd are simple top-up transfusion and exchange transfusion. target haemoglobin level in scd therapy is g/l or a haematocrit of %; higher target levels are associated with hyperviscosity and box . management of complications of sickle cell disease • inability to maximally concentrate urine (hyposthenuria) in response to water deprivation is an early finding • renal tubular acidosis • increased urinary tract infections • glomerular hyperfiltration, increased creatinine secretion, and a very low serum creatinine are characteristic of young patients with sickle cell anaemia, so renal dysfunction can be present even with normal serum creatinine values • microalbuminuria is common in childhood and up to % of adults develop nephrotic-range protein loss • gross haematuria can develop due to microthrombin in renal vessels, renal medullary carcinoma, and nocturnal enuresis • treatment is based on the early use of hydroxycarbamide and angiotensin-converting enzyme inhibitors in children with clinically significant albuminuria. • noted in up to % of scd cases • no relationship to acute chest syndrome (different pathophysiology) • mortality risk with even mild pulmonary hypertension is high • regular blood transfusions and long-term anticoagulation have been tried • hydroxycarbamide may decrease the risk • prostacycline analogues (epoprostenol, and iloprost), endothelin- receptor antagonists (bosentan), phosphodiesterase inhibitors (including sildenafil), and calcium channel blockers are being evaluated. • brief but recurrent (stuttering); may occasionally last for many hours and can lead to impotence • usually ischaemic, or low-flow, priapism • patients should be educated to seek medical attention if more than hours duration • detumescence within hours is necessary to retain potency • intravenous hydration and analgesia initially with consideration for α-adrenergic agonists (etilefrine or phenylephrine) • penile aspiration and irrigation with saline and α-adrenergic agents or shunting may be required in severe cases in combination with an exchange transfusion. • assess pain intensity • choose the analgesic, dosage, and route of administration • paracetamol and hydration should be considered in all patients • oral, sustained-release morphine is as good as intravenous morphine infusion in children and young adults • manage mild pain with rest, hydration, and weak opioids (such as codeine). admit patients in whom pain that does not subside promptly or require opioid treatment; fever, pallor, or signs of respiratory compromise; a low likelihood of receiving appropriate care at home • pain management should be individualized and dosing should take into account prior pain management and use of opioids • the pain pathway should be targeted at different points with different agents, avoiding toxicity with any one class • always look for a cause, e.g. infection, dehydration, etc. • education about avoiding exposure to precipitants • be empathetic, reassuring, and supportive • benzodiazepines may be helpful to reduce anxiety • re-examine the patient often to ensure adequate pain relief, to assess sedation and respiratory rate (to avoid opioid overdose). in assessing patient responses to conventional doses of analgesia, it must be remembered that those with sickle cell disease metabolize narcotics rapidly • re-search for evidence of any complications such as acute chest syndrome or anaemia • always look for a cause, e.g. infection. of multi-organ failure. both simple transfusion and exchange transfusions have been used and neither appears to be superior. a short course of steroids may attenuate acs but it may also increase the risk of re-hospitalization. bronchodilators may help patients with wheezing but inhaled nitric oxide has not shown any clear benefits. since coagulation activation is important in the pathophysiology of acute chest syndrome, treatment with low-molecular-weight heparin may reduce clinical complications. transcranial doppler measurement of cerebral blood flow has been a major step forwards in identifying individuals with an increased risk of ischaemic stroke. a value more than cm/ second imparts a % risk of stroke within the next years. regular blood transfusions can reduce the incidence of stroke in children. due to a high recurrence of stroke ( %) on stopping transfusions, continuation of transfusions should be guided by transcranial doppler measurements. , once a stroke has developed, the best therapeutic strategy is exchange transfusion which probably needs to be done monthly. , neurosurgical re-vascularization should be considered for moyamoya-like syndromes when new strokes occur despite transfusion. haemoglobin sc results from the co-inheritance of hbs and hbc and has its highest prevalence in west africa. clinical features and disease management are similar to those of hbss disease but splenomegaly, splenic infarcts and splenic sequestration may occur into adulthood. proliferative retinopathy necessitates regular ophthalmic review in those aged over years. compared with hbss, anaemia is less marked in hb sc ( - g/l) and there are fewer sickle cells and more target cells on the blood film. the diagnosis can be confirmed by haemoglobin electrophoresis, hplc or iso-electric focussing. worsening of complications. in exchange transfusion, the aim is to achieve an hbs% of < %. complications of transfusion in scd include alloimmunization, delayed haemolytic transfusion reactions and iron overload. the high rates of red cell antibody formation ( %) noted in wealthy countries are due to minor blood group incompatibilities between the recipient and the blood donor who is often of a different ethnicity. leukocyte reduction of transfused blood, routine abo, rh and kell matching for all patients and extended phenotype matching for those with alloantibodies may be useful for reducing transfusion reactions. treatment for acs is predominantly supportive and includes adequate pain relief, antibiotics (e.g. a macrolide with a cephalosporin), continuous pulse oximetry and delivery of supplemental oxygen to patients with hypoxaemia. incentive spirometry can prevent atelectasis and infiltrates and blood transfusion is indicated when a patient develops respiratory distress, a clinically significant fall in the haematocrit or signs the following predict a more severe clinical course and are additional reasons to consider offering hydroxyurea: hb < g/l, wbc > × /l, hbf < % and renal insufficiency due to scd. • start at - mg/kg per day (to the nearest mg/day) • if no or poor response, increase dose by increments of mg/ kg per day every weeks (max: mg/kg per day). most good responses require about - g/day in adults • monitor fbc, hbf%, and reticulocytes every or weeks initially, then every weeks when on a stable dose • monitor biochemistry profile (hydroxyurea has renal excretion and hepatic toxicity). • less pain • persistent increase in hbf (usually measured every - weeks) or mean cell volume • persistent increase in haematocrit if severely anaemic • decrease in ldh • acceptable toxicity. improvement in symptoms and blood parameters may take - months of therapy, but can be seen after approximately weeks. if the reticulocyte count is less than expected for the degree of anaemia, erythropoietin deficiency should be considered. • aim in all cases to reduce hbs level to < % • exchange transfusions may be considered in cases of stroke, acute chest syndrome not responding to top-up transfusion and major surgeries • target haemoglobin concentration of g/l may be considered in cases of organ failure and surgery. individuals with sickle cell trait (hb as) have -fold protection against severe malaria compared to individuals with normal haemoglobin (hbaa) probably due to both innate and immune-mediated mechanisms. individuals with sickle cell trait (hbas) are generally asymptomatic and they have a normal haemoglobin and normal life expectancy. uncommonly, complications such as poor perfusion of the renal papillae and increased bacteruria may occur. the blood film is generally normal and the diagnosis can be confirmed by haemoglobin electrophoresis, hplc or iso-electric focusing. the original descriptions of thalassaemia originated from areas round the mediterranean and the term derives from the greek thalassos (sea) and haima (blood). [ ] [ ] [ ] epidemiology thalassaemia is one of the most common single gene disorders and approximately - % of the global population are carriers. α + -thalassaemia occurs throughout the tropics, whereas α thalassaemia, which is responsible for haemoglobin bart's hydrops fetalis, is concentrated predominantly in south-east asia and to a lesser extent around the mediterranean. , β-thalassaemia is common in the mediterranean countries, parts of africa, throughout the middle east, the indian subcontinent and south-east asia. haemoglobin e prevalence is highest in cambodia, laos and thailand and can reach - % with lower prevalence rates in indonesia, malaysia, singapore and vietnam. β-thalassaemia β-thalassaemia is an inherited quantitative deficiency of β-globin chains which are required to make normal adult haemoglobin. more than mutations have been associated with the development of β-thalassaemia (a complete list is available at the globin gene server website, at: http://globin.cse. psu.edu) and they affect protein synthesis , leading to reduced (designated β + ) or absent (designated β ) production of the β-globin chains. the clinical severity of thalassaemia can be lessened by co-existing haemoglobin abnormalities such as the co-inheritance of α-thalassaemia and increased production of haemoglobin f. , α-thalassaemia normal α-globin synthesis is regulated by duplicate α-globin genes on chromosome . the genotype is usually represented as αα/αα and α-thalassaemia usually results from deletion of one or both α-genes. occasionally point mutations in critical regions of the α-genes may cause non-deletional α-thalassaemia (α t ). mutations can completely abolish expression of the αgenes (i.e. α -thalassaemia) or partially down-regulate expression (α + -thalassaemia). both α and α + thalassaemias can occur in the heterozygous or homozygous state or as a compound α /α + heterozygote form (table . ). underproduction of α-globin chains due to three or four gene deletions gives rise to excess γ (fetal) or β (adult) globin chains which form tetramers, called hb bart's (fetal) or hbh (adult). rare forms of α-thalassaemia occur in association with other conditions such as mental retardation and myelodysplastic/ leukaemia syndrome. , pathophysiology β-thalassaemia (figure . ) thalassaemias , , cause an imbalance of αand β-globin chain synthesis. in homozygous β-thalassaemia, excess α-chains precipitate in the red cell precursors and up to % of cells are destroyed in the bone marrow resulting in ineffective erythropoiesis and a shortened red cell survival. the red cells released from the bone marrow contain abnormal α-chains and these inclusions promote destruction of the cells by the spleen leading to clinical symptoms and signs of haemolysis. in heterozygotes, the α-chain excess and the degree of inadequate erythropoiesis is much less than in homozygous β-thalassaemia. hbf production normally tails off within a few months of birth but in β-thalassaemia hbf production can continue into adulthood. the effect of increased hbf production is to prevent precipitation of the excess globin chains and consequent ineffective erythropoiesis. however hbf has a high oxygen affinity, which can lead to increased erythropoietin production and thus, increased bone marrow expansion. the pathophysiology of α-thalassaemia, and hence the clinical manifestations, is quite different from β-thalassaemia. the excess non-α-globin chains form soluble tetramers rather than precipitates so there is only minimal ineffective erythropoiesis. the only clinical abnormality in those with hbh may be splenomegaly secondary to increased work load from destruction of red cells containing inclusions. rarely anaemia may be severe enough to require blood transfusions. classification of α-thalassaemia divide β-thalassaemia into thalassaemia major (transfusiondependent), thalassaemia intermedia (able to maintain adequate haemoglobin without transfusions or requiring less than units/year) and thalassaemia minor (asymptomatic). infants with β-thalassaemia are protected from severe anaemia by the presence of haemoglobin f and are usually asymptomatic. clinical manifestations of thalassaemia major depend on whether adequate blood transfusions are available and the stringency with which iron chelation is undertaken. untreated patients with thalassaemia major will die in late infancy or early childhood from the effects of severe anaemia. those who receive sporadic transfusions may survive longer but suffer from the secondary effects of anaemia, bony deformities and growth retardation. the clinical features of β-thalassaemia major are divided into those resulting from anaemia, bony changes and iron overload. anaemia from defective erythropoeisis, decreased red cell survival and increased haemolysis in thalassaemia major leads to cardiac decompensation, failure to thrive and growth retardation in children. splenomegaly, from the increased work load of culling red cells with inclusion bodies, can cause dilutional anaemia and a further drop in haemoglobin. compensatory extra-medullary haematopoiesis can lead to hepatomegaly and occasionally vertebral compression and neurological defects. haemolysis from increased red cell destruction is associated with gall stones in up to % of individuals with β-thalassaemia. another consequence of accelerated haemolysis is the increased incidence of thromboembolism ( % in thalassaemia major and % with intermedia) from the exposure of negatively charged phospholipids on the red cell membrane and the generation of red cell and platelet microparticles. splenectomy with postoperative thrombocytosis is a risk factor for thrombosis especially if combined with endothelial oxidative stress from iron overload, or procoagulant co-morbid conditions such as diabetes mellitus, hormone therapy, thrombophilic mutations and atrial fibrillation. folate deficiency, hyperuricaemia and occasionally gout have been observed in thalassaemia major due to the high turnover of red cells. the enhanced erythropoietic drive from anaemia in thalassaemia can lead to increased marrow expansion with in homozygous β-thalassemia, β-globin synthesis is markedly reduced or absent. the excess α-chains cannot form a tetramer but form a precipitate in the red cell precursors leading to intra-medullary destruction of these cells. this destructive process of the red cell membrane occurs from the formation of α-chain hemichromes (shown as red cell inclusions) and degradation products of the excess α-chains. the red cells which may be released from the bone marrow are destroyed by the spleen leading to clinical symptoms and signs of haemolysis. since only the β-chain is affected in these individuals, the synthesis of hbf and hba continues unabated. these haemoglobins have very high oxygen affinity, which can lead to increased erythropoietin production and thus, increased bone marrow expansion splenomegaly, which may be massive, and growth retardation in children. bony changes are unusual. other complications include infections, leg ulcers, gall stones and acute haemolysis in response to drugs and infections. the severity of the clinical features is related to the molecular basis with non-deletional types of hbh disease more severely affected. haemoglobin bart's (−/−) occurs almost exclusively in asians, especially chinese, cambodian and thai populations. an infant with hb bart's hydrops fetalis syndrome has pallor and gross oedema with signs of cardiac failure, marked hepatosplenomegaly and skeletal and cardiovascular deformities. there is often gross hypertrophy of the placenta. many of the clinical manifestations of this condition can be explained by the characteristic bossing of the skull and overgrowth of maxillary region, radiologically noted as 'hair on end' or 'sun-ray' appearance. metatarsal and metacarpal bones are the first to expand so measurement of the metacarpal bones has been considered a good indicator for initiation of transfusion therapy. other skeletal deformities include shortening of long bones due to early epiphyseal fusion and overgrowth of the maxilla causing dental malocclusion. the marrow expansion can also lead to pathological fractures, early bone thinning and osteoporosis , while ineffective drainage of the sinuses and middle ear from skull bone overgrowth can cause chronic sinus and ear infections. growth retardation is primarily the result of anaemia with contributions from iron overload, hypersplenism, deficiencies of thyroid and growth hormone, hypogonadism, zinc deficiency, chronic liver disease, malnutrition and psychosocial stress. patients with β-thalassaemia have increased iron absorption mediated by reduced hepcidin and those who receive regular transfusions may also develop transfusion siderosis if they are inadequately chelated. the iron is deposited in the parenchymal tissues with a variety of clinical consequences (box . ), [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] a process which may be modulated by variants in the haemochromatosis (hfe) gene. thalassaemia intermedia is characterized by haemoglobin concentrations of - g/l and children usually present at around - years of age with symptoms of anaemia, jaundice and hepatosplenomegaly. there may also be skeletal changes such as expansion of the facial bones and obliteration of the maxillary sinuses. several molecular factors including: (a) coinheritance of α-thalassaemia; (b) hereditary persistence of haemoglobin f; (c) δβ-thalassaemia and (d) the specific gγxmn polymorphism contribute to the 'conversion' of thalassaemia from major to intermedia type. in contrast to patients with thalassaemia major, iron loading in thalassaemia intermedia occurs mainly as a result of increased intestinal iron absorption rather than transfusion therapy. ineffective erythropoiesis with resultant chronic anaemia and hypoxia can suppress hepcidin, the regulator of iron metabolism, leading to increased iron absorption. the excess iron tends to accumulate in the liver rather than the heart. other clinical complications in thalassaemia intermedia include gallstones, extramedullary haemopoiesis leg ulcers, thromboembolic events and pulmonary hypertension, which is the major cause of heart failure in these individuals. although individuals with thalassaemia intermedia do not usually need regular blood transfusions, there is some evidence that complications, particularly later in life, may be less common in regularly transfused patients. α-thalassaemias , carriers of α-thalassaemia (traits, with loss of or α genes) are usually asymptomatic and may only be detected through a routine blood count which shows mild to moderate microcytic, hypochromic anaemia. antenatal counselling may be indicated if the mother has αα/− as there is a possibility that the fetus may be at risk of having haemoglobin bart's. haemoglobin h disease occurs mainly in asians and occasionally in the mediterranean population. it is the result of deletion of three α genes (α−/−) and can produce anaemia varying from - g/l. there is usually associated • hypogonadism is the most frequent complication in patients with prevalence over % in both males and females. it is usually hypogonadotrophic suggesting iron damage to the anterior pituitary or hypothalamus. the features range from total absence of sexual development to delayed puberty. in females with normal menstrual function, fertility is normal with the ovarian function preserved in most although secondary amenorrhoea can develop. damage of the ovaries is rare and is more likely to appear in older women (around ) because of high vascular activity on the ovaries at this age. secondary hypogonadism is common ( %) in older men. serum ferritin > ng/ml is a risk factor. • hypothyroidism is the second most common endocrine disorder (about %) although many of them may have the subclinical variety. most commonly hypothyroidism is of the primary type with secondary, central hypothyroidism increasingly being diagnosed in recent years. • the prevalence of diabetes mellitus is around % with the mean age of diagnosis being years. impaired glucose tolerance occurs first with microvascular damage like retinal changes being less common than the conventional form. erythroid precursor destruction. osmotic fragility is reduced, sometimes strikingly so since in some cases the red blood cells do not haemolyse even in distilled water. for this reason, if sophisticated tests are not available, osmotic fragility can be used as a screening test for thalassaemia trait. serum zinc levels may be low and this may be related to abnormal growth. vitamin c levels may also be low due to its increased conversion to oxalic acid in the presence of iron overload. care may be needed if folic acid is commenced on a background of bone marrow failure due to folate deficiency as it may precipitate painful erythropoietic crises. management a comprehensive management plan for patients with thalassaemia may involve transfusion therapy, iron chelation, splenectomy, prevention or early treatment of complications and stem cell transplant. the mainstay of treatment for the severe forms of thalassaemia is blood transfusion with the aim of reducing anaemia and erythropoietic drive. however, in many low-income settings blood supplies are inadequate and many thalassaemic patients are chronically under-transfused (table . ). transfusion frequency should be guided by clinical symptoms and signs such as poor growth and facial or other bone abnormalities, and should take into account any potential disease-modifying comorbidities. although the decision to transfuse should not be based purely on haemoglobin levels, a value of < g/l is often used as a trigger for regular transfusions. to prevent alloimmunization, extended red cell antigen typing for c, e and kell in addition to abo and rh(d) typing should be carried out prior to the first transfusion, and before each transfusion, full cross-match and screening for new antibodies should be undertaken. the risk of alloimmunization appears to be greater in patients who begin transfusion therapy after the first few years of life. development of alloantibodies and autoantibodies may result in increased transfusion requirements or haemolysis. use of leukodepletion techniques can result in less alloimmunization and fewer febrile transfusion reactions. since storage of red cells in anticoagulant solutions may decrease their efficacy, the use of blood that has been stored for less than - days may be beneficial for patients who require frequent transfusions. the use of st-degree relatives as blood donors should be discouraged, especially if the patient is a candidate for stem cell transplant. patients with thalassaemia major need lifelong regular blood transfusions, ml/kg per month or - units of blood every - weeks, to maintain the pre-transfusion haemoglobin level above - g/l. the clinical benefits of this regular transfusion programme include normal growth, suppression of erythropoiesis and bone marrow expansion, reduced hepatosplenomegaly and an overall sense of wellbeing, which allows normal age-appropriate activities. a higher target pretransfusion haemoglobin level of - g/l may be necessary for patients with heart disease or other medical conditions and for those patients who do not achieve adequate suppression of bone marrow activity at the lower haemoglobin level. shorter intervals between transfusions may reduce overall blood requirements but need to be balanced against the patient's work or school schedule and other lifestyle issues. iron chelation therapy , has improved survival rates for thalassaemic patients, and prevented hepatic fibrosis and ironinduced cardiac disease; most patients who are compliant with chelation therapy have normal growth and sexual development. iron chelators (box . ) are usually initiated in children over years who have received units of blood and/or have a steady-state serum ferritin level above ng/ml on at least two occasions. this level of iron overload typically occurs after - years of transfusions. desferrioxamine is started at - mg/kg per day in these children initially, to avoid toxicity due to over chelation. marked splenomegaly, often treated with splenectomy, was common in thalassaemia patients before the advent of regular transfusion programmes. severe haemolysis in thalassaemia is related to a hyperactive spleen, which aggravates anaemia and can increase transfusion requirements. although early the initiation of regular transfusion therapy for severe thalassaemia usually occurs in the first years of life. some patients with thalassaemia intermedia who only need sporadic transfusions in the first two decades of life may later need regular transfusions because of a falling haemoglobin level or the development of serious complications. haemoglobin should be monitored to assess the rate of fall in the haemoglobin level between transfusions and this can be used to indicate the frequency of transfusions. exchange transfusions have been tried as a way of reducing iron loading and are associated with a reduction in blood requirements by about one-third. (table . since each unit of red cells can contain up to mg of iron, cumulative iron burden is an inevitable consequence of a longterm transfusion programme. in addition there is increased iron absorption from the gut ( . - . mg/kg per day) as a response to severe anaemia and down-regulation of hepcidin. transfusion therapy can avert splenomegaly, hypersplenism still can develop, usually in children between and years of age. in these individuals, splenectomy can limit the complications from extramedullary hematopoiesis. splenectomy should be considered when the annual transfusion requirement reaches - ml red blood cells/kg per year and usually results in a halving of the transfusion requirements. splenectomy complications include opportunistic infections with encapsulated organisms. patients should therefore receive appropriate vaccinations preoperatively and should be advised to seek medical advice at the first sign of infection. it is advisable to delay splenectomy until patients are at least years old because of the increased risk of overwhelming sepsis below this age. thalassaemia patients can develop thromboembolic complications and pulmonary hypertension after splenectomy so partial splenectomy and splenic embolization have been attempted to minimize these complications but have not been studied in large trials. iron overload can occur in any organ in thalassaemia patients but particularly affects the heart, liver, the endocrine system, the bone and occasionally the pancreas and lungs. iron overload needs to be detected early and treated to prevent long-term damage. annual assessment of the iron loading of the liver and heart can be achieved using non-invasive methods such as magnetic resonance scanning to detect early changes. children should have regular growth and endocrine assessments and appropriate investigations should be carried out if there are any signs of developmental delay or hormonal deficiencies. osteoporosis is increasingly being recognized and should be prevented by ensuring adequate dietary calcium intake and sun exposure. vitamin supplementation with folic acid, zinc, vitamin e and vitamin c may be useful although the combination of vitamin c and desferrioxamine carries a risk of cardiac toxicity. allogeneic stem cell transplant , is currently the only means of curing thalassaemia. the outcome in carefully selected patients, measured by overall event-free survival, is around % with a transplant-related mortality of %. hepatomegaly, liver fibrosis, and inadequate iron chelation therapy predict a poor outcome. the best results from transplant have been obtained with hla-matched siblings. umbilical cord blood is a useful source of stem cells for young children. other potential treatment options for thalassaemia are outlined in box . . [ ] [ ] [ ] [ ] prevention of severe thalassaemia births by prenatal diagnosis and termination of pregnancies has been successful in countries with a high prevalence of thalassaemia. early identification of couples at risk and culturally sensitive genetic counselling facilitate decision-making for termination or continuation of pregnancy. the mean corpuscular haemoglobin (mch) is used to screen for the presence of thalassaemia using a cut-off of less than pg. rarely, silent β-thalassaemia mutation may present with an mcv over pg and should be considered in those with a positive family history. at-risk couples should be referred for detailed counselling on the options for prenatal diagnosis. these include chorionic villous sampling or amniocentesis, which are used to obtain fetal dna samples for genetic analysis. polymerase chain reactions and precise hybridization assays to detect single point mutations using very small dna samples have also been developed. a less invasive and less risky option is to isolate fetal dna circulating in the maternal blood for genetic analysis. pre-implantation genetic diagnosis is a newer technique where dna from the blastomere is used for genetic diagnosis. ultrasound can be used from the nd trimester for fetuses suspected of having α-thalassaemia to detect signs of hydrops fetalis and enlarged placenta (figure . ) . • hydroxyurea -helpful in some patients with β-thalassaemia intermedia, but not as effective in thalassaemia major • histone deacetylase inhibitors -derivatives of butyric acid; intermittent pulses with hydroxycarbamide has been tried • kit ligand • decitabine • knockdown of bcl a (regulator of γ-globin expression) • erythropoietin. • vitamins c and e • fermented papaya preparations. • successful in β-thalassaemia animal models using a retroviral vector transferring the human β-globin gene sequence and its promoter region into mice stem cells • β-globin gene transfer into progenitor hematopoietic cells of humans is also being studied • other molecular approaches being tried include using different mutations of stop codons and aberrant splicing. partner testing in all cases β-thalassaemia trait protecting red cells. red cells lack any other source of nadph and are solely dependent on the pentose phosphate pathway so g pd deficiency leaves these cells with no defence against oxidative damage. oxidative damage results in denatured haemoglobin aggregates which form heinz bodies (denatured haemoglobin precipitates). these damaged cells bind to the membrane cytoskeleton resulting in decreased cellular deformability, and are also destroyed in the spleen, resulting in haemolysis. the level of enzyme activity is higher in young erythrocytes than in more mature cells so older cells are more susceptible to haemolysis. the global distribution of g pd deficiency mirrors that of malaria, and where malaria has historically been prevalent, and it provides a degree of protection against malaria. • class iv -normal ( - % enzyme activity) • class v -increased activity (> % enzyme activity). g pd enzyme variants can be distinguished by their electrophoretic mobility. g pd b, the wild-type enzyme, and g pd a + , a common variant in populations of african descent, demonstrate normal enzyme activity and are not associated with haemolysis. g pd a − is the most common variant associated with mild to moderate haemolysis with approximately - % hb e is caused by a substitution of glutamic acid by lysine at codon of the β-globin gene. this causes reduced synthesis of the β-e chain and leads to a thalassaemia phenotype. hb e β-thalassaemia affects at least a million people worldwide and is an important health problem particularly in the indian subcontinent and south-east asia. in some areas, it has replaced β-thalassaemia as the most common thalassaemia disorder. the frequency of hbe reaches % in many regions of thailand, laos and cambodia with estimates of at least new cases of hbe β-thalassaemia expected in the next few decades in thailand alone. the natural history of hbe thalassaemia is highly variable; some patients are asymptomatic (e.g. heterozygotes, hbe - % or homozygotes hbe, - %) while others (e.g. hbe with β-thalassaemia) may be transfusiondependent. pathophysiology glucose- -phosphate dehydrogenase (g pd) deficiency was originally recognized through its association with haemolysis related to eating fava beans ('favism') and primaquine ingestion. g pd deficiency is the most common enzyme defect in humans and is present in about million people worldwide (figure . ). , it is an x-linked, hereditary defect caused by mutations in the g pd gene. g pd is an enzyme that catalyses the first reaction in the pentose phosphate pathway, to produce nadph, which is an important antioxidant used to preserve the reduced form of glutathione. , reduced glutathione acts as a scavenger for oxidative metabolites thereby < . % . - . % - . % - . % - . % - % of africans carrying this variant. g pd mediterranean, present in all countries surrounding the mediterranean sea, middle east, india and indonesia, has the same electrophoretic mobility as g pd b but the enzyme synthesis and catalytic activity are reduced. in several populations, g pd a − and g pd mediterranean co-exist. the clinical manifestations of g pd deficiency can be classified into: (i) asymptomatic; (ii) acute haemolytic anaemia; (iii) favism; (iv) neonatal jaundice; and (v) chronic non-spherocytic haemolytic anaemia. acute haemolytic anaemia in g pd deficiency can be secondary to infection (e.g. pneumonia, hepatitis a and b, and typhoid fever) or oxidant drugs, or may be precipitated by diabetic ketoacidosis, myocardial infarction and strenuous physical exercise. , a list of the drugs which may cause haemolysis in g pd-deficient individuals (table . ) can be obtained from: http://www.g pd.org/favism/english/index.mv. a drug which is deemed to be safe for some g pd-deficient individuals may cause haemolysis in others due to the heterogeneity of the underlying genetic variants. haemolysis typically occurs within - days after commencing the drug and can produce intense haemoglobinuria. fortunately, the disorder is self-limiting and most patients do not develop renal impairment or anaemia requiring transfusion. the spontaneous recovery reflects replacement of the older, enzyme-deficient red cells by younger reticulocytes which can withstand oxidative injury. if the precipitating cause has been removed the haemoglobin begins to recover after - days. acute renal failure due to acute tubular necrosis and tubular obstruction by haemoglobin casts can develop as a complication of haemolysis in g pd deficiency. this occurs more often in adults than children and may require haemodialysis. this occurs predominantly in boys aged - years in mediterranean countries, but it has also been observed in the middle east, asia and north africa. both intravascular and extravascular haemolysis, occasionally severe enough to cause renal impairment, can occur after eating fresh or cooked fava beans, and favism has been reported in breastfed babies of mothers who have eaten fava beans. divicine and isouramil have been implicated as the toxic components of fava beans. neonatal jaundice this occurs in one-third of male babies in areas where g pd deficiency is common and is likely due to g pd deficiency. it presents - days after birth and can lead to kernicterus. , maternal exposure to oxidant drugs, and even naphthalenecamphor mothballs, can precipitate haemolysis in affected babies. breast-feeding mothers should therefore be warned to avoid offending drugs, umbilical potions containing fava, triple dye or menthol, and should not apply henna to the skin or use clothes that have been stored in naphthalene. premature infants and babies who have co-inherited the mutation for gilbert's syndrome are at particular risk. phototherapy and exchange transfusion therapy may be required to reduce the level of unconjugated bilirubin. the diagnosis may be easily missed so assessment of g pd status should be undertaken for any jaundiced infant whose family history or ethnic or geographic origin suggest the likelihood of g pd deficiency, and in infants who respond poorly to phototherapy. this is an unusual manifestation of g pd deficiency and usually presents in childhood. , there may be a history of severe neonatal jaundice, episodic or worsening anaemia which requires blood transfusions, and complications from gallstones. although these individuals usually have a well-compensated anaemia, and require transfusions only for exacerbations, rarely some may become transfusion-dependent. antioxidants such as vitamin e and selenium may be of benefit in some cases. the haemolysis does not resolve following splenectomy. folic acid supplementation is necessary to support the increased compensatory erythropoiesis. the diagnosis of g pd deficiency is usually suspected when neonatal jaundice occurs in an area where g pd deficiency is drugs which may cause haemolysis in g pd-deficient individuals common or when an episode of non-immune haemolytic anaemia occurs in association with an infection or drug. the appearance of the red cells on the blood film is characteristic because denatured haemoglobin concentrates in one area within the cell creating 'helmet' or 'bite' cells. denatured haemoglobin precipitates in peripheral red blood cells as heinz bodies which can be detected by staining with methyl violet. definitive diagnosis of g pd deficiency is by quantitative spectrophotometric analysis of the rate of nadph production. point of care tests for g pd deficiency are being developed but have not yet been validated for routine use. measuring enzyme activity during an episode of acute haemolysis is not helpful since reticulocytosis, which is a feature of acute haemolysis, produces a false-negative result because of the high enzyme levels in younger erythrocytes. , management the most effective management strategy for g pd deficiency is to prevent haemolysis by avoiding triggering agents like infections, drugs and fava beans. for the milder variants (e.g. class iii and iv), drugs known to trigger haemolysis may be given to individuals with g pd deficiency if the benefits outweigh the risks and the blood count is closely monitored (e.g. use of low-dose primaquine for individuals with g pd avariant). screening programmes have been established in some mediterranean and other populations where g pd deficiency is prevalent. haematological complications of malaria (see chapter ) the pathophysiology of anaemia in malaria is multi-factorial and influenced by the age of the individual and their antimalarial immune status. anaemia mechanisms in malaria involve: • haemolysis with increased red cell destruction of both infected and bystander erythrocytes • dyserythropoiesis • hypersplenism • haemolysis • co-existent conditions which can cause anaemia. haemolysis is more common in non-immune individuals with acute malaria, whereas dyserythropoiesis is the predominant mechanism for anaemia in recurrent falciparum malaria. , haemolysis is the result of red cell phagocytosis by the reticuloendothelial system and is triggered by damage to the red cell membranes and exposure of abnormal surface antigens on their surface. [ ] [ ] [ ] [ ] ten uninfected red cells are removed from the circulation for each infected red cell destroyed, possibly related to loss of red cell complement regulatory proteins and increased levels of circulating immune complexes. this may partly explain the persistent or worsening anaemia following parasite clearance and the poor correlation between parasitaemia and the severity of anaemia noted in some studies. an increased incidence of anaemia has been noted in malaria vaccine trials possibly due to enhanced clearance of uninfected red blood cells. decreased erythropoeisis with abnormalities in red cell precursors and reticulocytopenia is found consistently on examination of bone marrow from malaria-infected patients. the decreased erythropoiesis is due to many factors including low levels of tnf-α, high levels of interleukin- , abnormalities of erythropoietin, a decrease in burst colony forming units, cytokine-induced suppression of red cell production and the inhibitory effect of the malarial pigment haemozoin. [ ] [ ] [ ] [ ] epidemiology malaria-related anaemia is most commonly seen in children and pregnant women. the prevalence of malarial anaemia in sub-saharan africa in children is - % and in pregnant women it is - %. the highest prevalence is in infants and children less than years of age. infants may acquire malaria through the placenta. , individuals living in malarious areas may have multiple reasons for anaemia such as bacteraemia, hookworm infections and vitamin a deficiency making it difficult to assign anaemia solely to malaria. however, animal studies and the fact that anaemia improves with anti-malarial treatment suggest a direct relationship between malaria infection and anaemia. , for example, in tanzanian children about % of anaemic episodes were thought to be caused by malaria. who defines severe anaemia attributable to malaria as: (i) haemoglobin concentration < g/l or haematocrit < %; (ii) parasitaemia with > parasites/µl of blood and (iii) normocytic blood film (to exclude other common causes of anaemia). however, aspects of this definition have been criticized because blood films are not examined routinely and parasite density varies with endemicity and age. although traditionally it is p. falciparum that has been associated with the most severe malaria-related anaemia, p. vivax is also a major risk factor for severe anaemia especially in young children or those with chronic and recurrent infections. p. vivax anaemia is associated with recurrent bouts of haemolysis of predominantly uninfected erythrocytes with increased fragility. symptoms of malarial anaemia can vary from negligible to profound depending on the degree of anaemia and the rapidity of onset. splenomegaly is a common feature of malarial anaemia because of the role of the spleen in the removal of both infected and uninfected red cells. blackwater fever, characterized by intense intravascular haemolysis with haemoglobinuria and occasionally renal failure in a patient with malaria, may be related to underlying glucose- -phosphate deficiency. , factors such as poor nutrition, deficiencies of vitamins and micronutrients, bacteraemia, and hookworm or hiv infection may co-exist with malaria and contribute to anaemia so nonmalarial causes of anaemia should be considered in patients whose anaemia does not respond to malaria treatment. the management of severe malarial anaemia involves supportive care and treatment of the malaria and any other underlying conditions. recovery from malaria-associated anaemia can be slow, taking weeks or even longer if there are episodes of re-infection. in children, blood transfusion is usually reserved for those with haemoglobin levels of less than g/l (< g/l if there are complications such as respiratory distress ). there of parasitized red cells and the release of von willebrand factor multimers which cause widespread platelet aggregation leading to thrombocytopenia , , platelet synthesis by the bone marrow is relatively well maintained during infection , but antiplatelet antibodies, immune complexes and splenomegaly all contribute to thrombocytopenia. thrombocytopenia occurs in - % of individuals infected with malaria irrespective of the species of plasmodium. , thrombocytopenia in febrile patients in an endemic area increases the probability of malaria by a factor of and in individuals returning from tropical countries with a fever, thrombocytopenia is highly specific for malaria infection. profound thrombocytopenia is unusual and malaria-associated thrombocytopenia is rarely associated with haemorrhagic manifestations. the clinical consequences of platelet aggregation and endothelial binding are primarily microvascular ischaemia. this may manifest as renal impairment, cerebral ischaemia, and occlusion of retinal vasculature or even in some cases, skin necrosis. bleeding is unlikely, although in severe thrombocytopenia, petechiae or purpura may develop which denotes extravasation of red cells into the subcutaneous tissue. continued platelet activation and consumption can exacerbate bleeding and decreased circulating platelets are associated with increased vascular leakage and the development of oedema. platelet transfusions are rarely required because the platelet count generally rises rapidly on treating the underlying malaria. coagulopathy is a disturbance of the whole coagulation system involving not just coagulation factors but platelets, anticoagulant factors, fibrinolytic system and, in the case of malaria, the parasitized red cells and the vascular endothelium. parasitized red cells induce expression of tissue factor on endothelial cells and monocytes, release of microparticles, cytokine release and platelet clumping, all of which initiate blood coagulation and tilt the balance towards the pro-coagulant state ( figure . ) . , [ ] [ ] [ ] [ ] [ ] [ ] anticoagulant factors are severely depleted in malaria. protein c and antithrombin levels are inversely correlated with severity of falciparum malaria and return to normal with treatment of the malaria. have been some concerns about a possible increased risk of infection associated with iron supplementation for children in malarious areas , but current recommendations advocate that where iron deficiency and malaria are common, iron supplements should not be withheld and appropriate anti-malarial treatment or prevention should also be offered. the best way to prevent malarial anaemia is to prevent malaria infection by avoiding mosquito bites (e.g. through the use of bed nets) or through chemoprophylaxis. malaria chemoprophylaxis during infancy can reduce both malaria and anaemia. children who have been hospitalized with severe malarial anaemia may benefit from intermittent preventive malarial therapy after discharge to prevent recurrence of anaemia. daily co-trimoxazole prophylaxis which is used for hiv-infected individuals has been shown to reduce malaria parasitaemia and anaemia. the normal platelet life span of - days is reduced to less than days in malaria infection. several factors are responsible for thrombocytopenia in malaria infection, the most common being increased platelet activation and aggregation ( figure . ). platelet activation is by parasitized red cells which express surface tissue factor and initiate coagulation and platelet aggregation. the resultant activated endothelium binds platelets and sequesters them in vascular beds including in the cerebral vasculature. , these platelets facilitate the adhesion and to % after a year. , although transfusions may be required in severe life-threatening cases of anaemia, aggressive transfusion therapy has been associated with fatal pulmonary emboli due to accelerated haemolysis and disseminated intravascular coagulation. in those who do not respond to art, erythropoietin may be considered since reduced responsiveness to this hormone and antierythropoietin antibodies have been noted in hiv patients. erythropoietin is particularly useful in individuals whose erythropoietin levels are less than iu/l because in addition to increasing the haemoglobin it can also improve the quality of life. erythropoietin may take several weeks to achieve full effect and patients should be replete in haematinics. erythropoietin can very rarely be associated with thrombosis or pure red cell aplasia. thrombocytopenia is a common finding in hiv-infected patients and it may be the initial manifestation of hiv infection in as many as % of patients. data from wealthy countries demonstrate platelet counts less than × /l in % of patients, and less than × /l in . %. overall the -year coagulopathy in malaria infection is unusual, occurring in less than % of cases. it appears to be most common in adults with cerebral malaria who may present with gastrointestinal bleeding or with microvascular ischaemia in the brain, kidneys, retina and occasionally, the dermal vasculature. prolongation of prothrombin time and activated partial thromboplastin time only occur in - % of patients with p. falciparum infection and coagulopathy does not appear to be a feature of p. vivax infection. since coagulation factors need to be depleted to less than % of normal to prolong the clotting times, these tests can be normal despite active coagulopathy. management of coagulopathy aims to restore the balance between pro-and anticoagulant processes. this is complex and requires input from a coagulation specialist and ideally, access to plasma, heparin and factor concentrates and a well-equipped coagulation laboratory. anaemia anaemia is very common in hiv-infected individuals occurring in up to % at initial presentation and about % at some stage during their disease. thirty-seven percent of patients with clinical aids have a -year incidence of anaemia (haemoglobin < g/l) and high rates of anaemia persist despite combination anti retroviral treatment (art). anaemia is directly related to mortality in hiv infection and is independent of other risk factors including cd count. there are multiple reasons for anaemia in hiv-infected patients (box . ), which often co-exist in individual patients. bone marrow infection by mycobacteria species, histoplasma, cryptococcus and penicillium marneffei can all decrease red cell production and can be detected by bone marrow examination and cultures. parvovirus has a predilection for the erythroid progenitor cells and can cause severe anaemia in hiv-infected patients. serological tests for parvovirus are unhelpful in hivinfected patients and viral polymerase chain reaction is needed to confirm the diagnosis. the likelihood of parvovirusinduced anaemia increases with the severity of anaemia and has been found in % of individuals with hiv and haemoglobin less than g/l. haemophagocytosis occurs in hiv infections and may be secondary to co-infection with mycobacteria, cytomegalovirus, epstein-barr or other herpesviruses. poor nutrition due to socioeconomic reasons, hiv-related anorexia, malabsorption from conditions affecting the gastrointestinal tract, and achlorhydria may contribute to anaemia. haemolytic anaemia occurs secondary to drugs or concomitant glucose- phosphate dehydrogenase deficiency and because reticulocytopenia is common in those with hiv infection, reticulocyte counts cannot be used to exclude haemolysis. although the direct coombs test may be positive in patients with hiv infection, autoimmune haemolysis is not a common cause of anaemia. a reduction in red cell precursors has also been noted in children in africa with severe anaemia. treatment of hiv-related anaemia should focus on starting art and eliminating any other factors, such as infections or vitamin deficiencies, which may contribute to the anaemia. in wealthy countries art has been shown to reduce anaemia prevalence from % to % within months of starting treatment, non-hodgkin's lymphoma (nhl) was noted to be associated with hiv infection early in the epidemic and is an aidsdefining illness. the incidence of nhl is up to times greater in hiv-infected adults than in those who are not infected, and it is responsible for nearly one-sixth of the deaths attributable to aids. since the introduction of haart, the incidence of all types of nhl has decreased by approximately - % , and the outcome of hiv-infected patients with lymphoma has improved. in the setting of clinical trials, the % -year survival rate is comparable to those without hiv infection. the incidence of hodgkin's lymphoma has increased in the post-haart era, possibly due to immune reconstitution and increased cd cells. , evidence of epstein-barr virus (ebv) infection can be found in virtually all cases of hodgkin's disease. hiv-related lymphomas (box . ) (see also lymphomas, below), are broadly divided into systemic lymphomas ( %) and primary central nervous system lymphomas. the incidence of highly aggressive lymphomas, either burkitt's lymphoma (approx. %) or diffuse large b-cell lymphoma (approx. %), is much higher in hiv-infected patients than in those without infection. although t-cell lymphomas are uncommon in hiv disease ( %), there has been an increase in recent years. the incidence of primary central nervous system lymphoma in hiv-affected individuals is - % and it is times more common than in the general population. the pathogenesis of nhl in hiv infection is related to the inadequate host immune responses to viruses with oncogenic potential, predominantly ebv and human herpesvirus (hhv )/kaposi's sarcoma-associated herpesvirus. this allows unregulated lymphoid growth and an accumulation of genetic abnormalities in b cells. markers of b-cell activation such as serum immunoglobulins and free light chains, and cd cell count have been suggested as predictive markers for the development of nhl in hiv infection. , extranodal and leptomeningeal involvement, and b-symptoms occur in the majority of hiv-infected patients with nhl and the bone marrow is commonly involved. the most common extranodal site to be involved is the incidence of moderate thrombocytopenia (< × /l) is . %, though this is higher in those with clinical aids ( . %). , thrombocytopenia is more common in those who abuse drugs, have opportunistic infections and malignant disorders of the bone marrow (e.g. lymphoma), and it may also be a side-effect of therapeutic drugs. the most common cause of thrombocytopenia in hiv infection is immune thrombocytopenia which may be associated with hepatitis c co-infection, and produces decreased platelet survival, particularly at cd counts below /µl. the anti-platelet antibodies, immune complexes and cross-reacting antibodies to hiv envelope proteins and platelets, which occur in hiv-associated thrombocytopenia , may also contribute to generation of reactive oxygen species. platelet production can also be affected in hiv infection and may explain the high levels of thrombopoietin that have been documented in hivrelated thrombocytopenia. some cases of hiv-related thrombocytopenia may undergo spontaneous remission so treatment of thrombocytopenia is usually only initiated if it is associated with bleeding, which is unusual. the first line of treatment involves antiretroviral therapy with the aim of achieving undetectable plasma hiv viraemia. , any drugs that may be associated with causing thrombocytopenia should be withdrawn and opportunistic infections or secondary malignancies treated. the treatment of immune thrombocytopenia is the same as in non-hiv cases and options include a short course of steroids, intravenous immunoglobulin (short-lived response), anti-d, interferon-α or splenectomy. although there are multiple causes of thrombocytopenia in hiv-positive individuals, one of the most devastating is the thrombotic microangiopathy of thrombotic thrombocytopenic purpura (ttp). this is because the combination of haemolytic anaemia and microthrombi has a very poor prognosis. symptoms are nonspecific and may include fever, headache, bleeding and changes in consciousness. if ttp is suspected, an urgent blood film should be requested and the combination of thrombocytopenia with red cell fragmentation is highly suggestive of ttp. ttp associated with hiv infection was more frequent before the introduction of art and is more common if adherence to treatment is poor or resistance to therapy has developed. ttp is thought to be due to endothelial damage, but unlike the situation in non-hiv-infected individuals, low levels of adamts- are not a useful predictor of outcome. treatment of ttp involves plasma exchange, and although refractoriness may occur, this can be corrected by art in some cases. if art is administered in these cases it is important to maintain adherence throughout the period of plasma exchange. if apheresis facilities are limited, plasma infusions alone ( ml/ kg per day) may also produce a response. art should also be administered immediately after plasma exchange to minimize drug removal. patients with a viral load of less than copies/ml generally require fewer plasma exchanges for remission than those with a higher load. survival of patients with hiv-associated ttp in the pre-art era was rarely longer than years, even with plasma exchange and steroid treatment, but for patients who are compliant with art the mortality is around %. which immediately limits the amount of blood loss. exposure of the subendothelial space releases factors such as von willebrand factor multimers which bind to platelets and initiate platelet adhesion to the endothelium. the adherent platelets release their granules and attract more platelets, which in combination with fibrinogen, form an aggregate. the activated platelets also attract coagulation factors thereby promoting the clotting process. the critical parts of clot formation are the conversion of prothrombin to thrombin and the thrombinfacilitated conversion of fibrinogen to fibrin (figure . ) . haemostatic control mechanisms operate throughout the clotting process to prevent excessive clot formation and involve proteins c and s, and anti-thrombin and antifibrinolytic systems. any alteration in these regulatory pathways can lead to either bleeding or thrombotic complications. bleeding can result from: • inadequate vasoconstriction, due to vascular problems which can be acquired (e.g. viral haemorrhagic fevers or immune vasculitis) or congenital (e.g. collagen vascular disorders) • qualitative or quantitative abnormality of von willebrand factor causing von willebrand's disease • decreased number or function of platelets which can be either acquired (e.g. aspirin, nsaids) or congenital (e.g. platelet function defects) • qualitative (e.g. caused by inhibitors to coagulation factors, commonly factor viii) or quantitative (e.g. haemophilia) abnormality of coagulation factors • increased fibrinolysis (e.g. viral haemorrhagic fevers, snake bites). acquired bleeding disorders are commonly caused by vitamin k deficiency, disseminated intravascular coagulation (dic) or platelet disorders (box . ) but may sometimes be due to acquired inhibitors of coagulation factors. the initial laboratory tests in a patient with excessive bleeding should therefore include a platelet count, clotting screen (prothrombin time (pt) and activated partial thromboplastin time (aptt)), and gastrointestinal tract, often the stomach or the perianal region. hepatic involvement, seen in a quarter of cases, is associated with a particularly poor prognosis. cns disease may be asymptomatic so diagnostic lumbar puncture may be required. hiv-related lymphomas frequently present with poor prognostic features such as elevated serum lactate dehydrogenase levels. , older age, lowest nadir cd cell counts prior to nhl diagnosis, developing nhl while on art, and cumulative hiv viraemia are also poor prognostic features. a formal prognostic scoring system has been developed which takes into account the cd count (< cells/µl). some types of hiv-related lymphoma are associated with characteristic clinical and laboratory features. primary effusion lymphoma is an aggressive lymphoma characterized by effusions in serosal cavities in the absence of any other tumour masses. , it is strongly associated with hhv infection and the virus can be identified in the nuclei of the malignant cells. plasmablastic lymphoma mainly affects the oral cavity and the mucosa of the jaw and is typically associated with epstein-barr virus. histological examination of biopsied tissue is necessary to confirm the diagnosis and type of lymphoma. diagnostic difficulties may arise because hiv-related hyperplasia in lymph node biopsies may be confused with lymphoma, the histological appearance of hiv-related lymphomas may be different from those of non-infected individuals and many opportunistic pathogens may mimic the appearances of nhl, or co-exist with it, and will need to be identified or excluded before making a diagnosis of lymphoma. prior to the widespread use of art, conventional lymphoma chemotherapy resulted in considerable toxicity, increased opportunistic infections and high mortality. art has facilitated the use of conventional doses of chemotherapy in conjunction with haematopoietic growth factor support. this has markedly improved the outcome of patients with hiv-related lymphomas who now have overall response rates of %. the concomitant use of art and chemotherapy is therefore recommended, especially in those with cd counts of less than /µl. anti-cd antibody is now included in treatment regimens for nhl, and studies that include patients with hivrelated lymphomas all report favourable outcomes. , some antiretroviral agents such as zidovudine are best avoided in combination with chemotherapy, because it adds to the myelosuppression of chemotherapy. didanosine may worsen the peripheral neuropathy caused by taxanes and vinca alkaloids. hiv-infected patients undergoing chemotherapy should receive adequate anti-infective prophylaxis due to the high risk of opportunistic infections such as pneumocystis, herpes simplex and zoster and candida. consolidation chemotherapy and stem cell transplant have been used successfully in relapsed hivrelated lymphomas. haemostasis is maintained by interactions between vessel walls, platelets and a balance between pro-and anticoagulant factors. although the process of haemostasis is usually considered to occur in a stepwise fashion, in vivo the steps happen virtually simultaneously. activation of the lining of the endothelium by trauma, cancer cells or cytokines triggers vasoconstriction, the tests for each pathway is given with arrows corresponding to each box complications, malignancies and infections and is a serious condition with a high mortality. patients present with spontaneous bruising or excessive bleeding from minor wounds such as venepuncture sites, and they may also have signs of complications such as renal failure, acute respiratory distress syndrome and microangiopathic haemolytic anaemia. dic is associated with a combination of depleted clotting factors (i.e. prolonged pt and aptt), a falling platelet count, red cell fragments on the blood film, raised d-dimers or fibrin degradation products, and reduced fibrinogen levels. management of disseminated intravascular coagulation includes treating or removing the underlying cause, and correcting the haemostatic abnormalities with combinations of platelets, cryoprecipitate and fresh frozen plasma. although bleeding due to thrombocytopenia is unusual unless the platelet counts falls below - × /l, bleeding may occur with a normal platelet count and normal clotting screening tests (i.e. pt and aptt) if platelet functions are impaired (e.g. myelodysplastic syndromes). platelet transfusions are generally not required unless there is active bleeding or prior to surgery. idiopathic thrombocytopenic purpura. idiopathic thrombocytopenic purpura is due to immune destruction of platelets. it is usually primary but can be associated with conditions such as lymphomas and infections including hiv. it may present incidentally or with petechiae, bruising or bleeding from the nose or gums, especially if the platelet count is less than × fibrinogen levels, which may be helpful in cases of excessive fibrinolysis (table . ). a difficult venepuncture can cause in vitro activation of the clotting system resulting in a shortened pt or aptt. similar findings may occur in chronic dic due to in vivo activation. the pt and aptt are not necessarily good predictors of the bleeding risk because some clotting disorders associated with thrombosis (e.g. anti-phospholipid antibodies) can prolong the aptt. a shortened aptt can be associated with marked elevation of factor viii levels (e.g. pregnancy) and may be a predictor of deep vein thrombosis. a prolonged thrombin time is caused by quantitative or qualitative fibrinogen deficiency, heparin and fibrin degradation products. reptilase time is helpful to distinguish between fibrinogen abnormalities (prolonged reptilase time) and heparin therapy (normal reptilase time). deficiency of vitamin k can be due to poor diet, small bowel disease or bile flow obstruction. clotting factors (ii, vii, ix and x) are dependent on vitamin k which is a fat-soluble vitamin. vitamin k deficiency therefore causes prolongation of the pt and aptt. in newborn infants, vitamin-k-dependent clotting factors can drop precipitously within a couple of days of birth. this causes haemorrhagic disease of the newborn which particularly affects infants that are premature, exclusively breast fed or have been exposed to drugs for tuberculosis, convulsions or anticoagulation in utero. these babies develop bleeding into the skin and gut, or bleeding from the umbilical stump or circumcision. vitamin k deficiency will respond to intravenous vitamin k ( mg/day for days orally or by intravenous injection) and in severe bleeding the clotting abnormality can be treated with fresh frozen plasma. haemorrhagic disease of the newborn can be prevented with mg of intramuscular vitamin k given at delivery. disseminated intravascular coagulation (dic) is characterized by activation of haemostasis with widespread fibrin formation, activation of fibrinolysis and consumption of platelets and clotting factors. it may be precipitated by tissue injury, obstetric desmopressin (ddavp) is a relatively inexpensive drug that increases fviii levels and vwf activity within minutes of administration. it is useful in mild haemophilia and mild von willebrand's disease. the major side effects are headaches and hyponatraemia so fluid intake should be restricted to . l/ day. tranexamic acid mouthwashes may be helpful for oral mucosal bleeding. danazol can increase both factor viii and ix levels within - days and has therefore been recommended for patients with recurrent haemarthrosis or with central nervous system bleeding which both carry a high risk of recurrence. most thromboembolic episodes are single events and may be associated with precipitating events or underlying risk factors. thrombophilia is the clinical state of hypercoagulability and should be suspected in patients who have a strong family history of thrombosis, or who have recurrent or unusual thromboses. increasing affluence and consequent lifestyle changes mean that the prevalence of thromboembolism is rising in some low-and middle-income countries. risk factors such as sedentary work, obesity, excessive alcohol intake, smoking and additional cardiovascular risk factors are compounded by other /l. spontaneous recovery occurs less commonly in adults than in children. it is important to exclude other causes of thrombocytopenia such as drugs, dic or sepsis. the diagnosis can be suspected from a bone marrow examination which shows increased numbers of platelet precursors. treatment with prednisolone ( . - . mg/kg) is usually only necessary if there is bleeding or excessive bruising and the dose should be reduced slowly once the platelet count improves. second-line treatments include immunosuppressive agents and danazol. splenectomy may also be beneficial but carries an increased risk of infection. platelet transfusions or intravenous gammaglobulin can temporarily increase the platelet count in an emergency or prior to surgical procedures. inherited bleeding disorders can be classified broadly into coagulation factor deficiencies (e.g. factor viii and factor ix deficiencies), von willebrand's disease and platelet disorders. the frequency of genes for inherited bleeding disorders is the same throughout the world. haemophilia a has a prevalence of about / , von willebrand's disease of > / and haemophilia b of < . / . these conditions occur more frequently among populations where consanguineous marriage is common and where prenatal diagnostic facilities are unavailable. in general, individuals with inherited coagulation factor deficiencies present with soft tissue bleeds such as haemarthroses or intramuscular bleeds. those with platelet disorders or von willebrand's disease tend to present with mucosal bleeds, however severe (type iii) von willebrand's disease can present with severe soft tissue bleeds. many of these conditions are diagnosed following excessive and uncontrolled bleeding after trauma or surgical procedures. menorrhagia and delayed severe postpartum haemorrhage may be presenting features of bleeding disorders, particularly von willebrand's disease or hypothyroidism, which can cause decreased synthesis of von willebrand factor. some inherited platelet function disorders are associated with characteristic syndromes (e.g. oculocutaneous albinism or skeletal defects) which may provide a clue to the diagnosis. early recognition of symptoms by clinicians, teachers and the public is important so that early treatment can be established. patients with inherited bleeding disorders are usually managed with blood products (box . ) or chemotherapy designed to reduce bleeding and associated complications. , , , clotting factor concentrates may be imported or produced locally by fractionation of plasma and are included in the who list of essential medicines. , one international unit (iu) of fviii clotting factor concentrate per capita is recommended as the minimum requirement for countries wishing to achieve optimal survival for their haemophilia population but only about % of the estimated people in the world with haemophilia receive adequate treatment. management of patients with bleeding disorders relies on a wellequipped and quality assessed laboratory for accurate diagnosis and monitoring of treatment and access to plasma and components for replacement therapy. appropriate support services such as physiotherapy, orthopaedics and counselling should also be available. in many countries inherited bleeding disorders are associated with stigma, which is particularly directed against the mothers of affected children, acute and chronic leukaemias are usually associated with a high white cell count but acute leukaemias can present with normal or even sub-normal white cell counts. morphology of peripheral blood and bone marrow specimens is crucial to confirm the diagnosis. this is particularly important in the case of acute leukaemia in children which may be mistaken for an acute viral infection. staining methods including sudan black b, myeloperoxidase and nonspecific esterase are important to distinguish between the different subtypes of acute myeloid and lymphoid leukaemias and therefore to guide treatment. acute myeloid leukaemia (aml). prevalence of this increases with age and the success rate with chemotherapy protocols is not high even in the most sophisticated centres. neutropenia and myelosuppression requiring intensive blood component support occur during chemotherapy and bone marrow transplantation offers the best option for cure for patients who relapse. management of aml is therefore complex and expensive. hydroxycarbamide or subcutaneous cytarabine may be used as a palliative treatment. acute promyelocytic leukaemia (aml subtype m ). this must be distinguished from other types of acute myeloid leukaemia because it has a high cure rate with early treatment. it predominantly affects young adults and it has a high incidence in certain ethnic groups especially those of latin american descent. a treatment protocol which includes all-transretinoic acid with combination chemotherapy has been developed which is feasible in low-income countries. , another regimen based on intravenous arsenic trioxide has been developed in india, , which has an % response rate with good diseasefree and overall survival. conditions that are associated with thrombosis such as hiv infection, and chronic infections including tuberculosis , and helminth-induced eosinophilic myocarditis. african americans are more likely to be diagnosed with pulmonary embolism rather than deep-vein thrombosis compared to other racial groups and african patients with thrombosis tend to be younger than those reported in literature with higher mortality rates (around %) possibly due to late presentation and poor access to health facilities. asian populations - seem to have a lower prevalence of symptomatic venous thrombosis compared to african americans. very little is known about the prevalence of prothrombotic factors such as mutations of the prothrombin gene or deficiencies of antithrombin, protein c and protein s in tropical countries, although high rates of factor v leiden, a risk factor for venous thrombosis, have been described in tunisia. , lupus anticoagulant and anti-phospholipid syndrome, which are associated with increased thrombosis risk, are increased in afro-caribbean populations, especially in the presence of hiv, and have also been described in nigerian women with pre-eclampsia. , the management of venous thrombosis is initially with heparin and then with warfarin for - months. compliance may be difficult in low-resource settings because of the requirement for regular monitoring of warfarin. it is therefore important to try to prevent thromboses by removing any underlying risk factors and by treating individuals at risk of thrombosis with a short course of prophylactic heparin to cover procedures known to be associated with thrombosis risk. this can present as venous or arterial thromboembolism and it may be inherited (e.g. deficiencies of thrombin, protein s or protein c) or acquired (e.g. antiphospholipids). the patient's personal and family history, and the results of clinical and imaging examinations to confirm thrombosis, may suggest the diagnosis. the laboratory tests needed to determine the cause and classify the type of thrombophilia, and their interpretation, are complex, so patients with recurrent or unusual thromboses should be referred to a specialist centre. haematological malignancies are predominantly leukaemias, lymphomas and myelomas. some of the general approaches for managing these conditions in low-income countries are outlined in box . but definitive treatment should be undertaken by a specialist haematology unit. leukaemias can be broadly classified as acute or chronic, and lymphoid or myeloid. the presenting symptoms and signs are related to the disturbed blood cell production from the bone marrow due to the effects of the malignant cell clone (box . ) . acute leukaemias are characterized by rapid progression and poor prognosis if left untreated whereas chronic leukaemias generally follow a much slower course. • mobilization of the community (especially parents and families) to raise awareness among local councils and government bodies about the treatability of the cancers and benefits from curing them • find an external partner unit locally, nationally or internationally which is already well-established and willing to help but will not dictate terms • improvement of supportive care facilities, especially protection from those with infectious diseases • development of a safe and reliable blood transfusion service • provision of subsidized travel, and satellite clinics to lessen the burden • development of appropriate protocols for each disease entity which is locally practicable with minimum cost and maximum efficacy • development of medical, nursing and paramedical expertise in the diseases to be treated -initially by offering visiting fellowships and in the long term for the trained individuals to arrange regional and local teaching programmes • formation of a cooperative group bringing together all the professionals involved in the speciality within a country or region to share expertise and develop training programmes. acute lymphoblastic leukaemia (all). this is the most common type of leukaemia in children. it has a good prognosis when treated with modern chemotherapy protocols with cure rates in the best centres exceeding %. in low-income countries, cure rates are much lower at around % primarily because of failure to complete therapy and deaths caused by treatment. considerable improvements in all outcomes have been achieved by twinning institutions in developing countries with specialist centres elsewhere in the country or internationally. measures that may improve outcomes focus on preventing abandonment of therapy (e.g. providing funding for transport, satellite clinics and support groups) and prompt treatment of infection. treatment in a dedicated paediatric oncology unit using a comprehensive multidisciplinary team approach and protocol-based therapy, is also associated with improved outcomes in resource-poor settings. chronic myeloid leukaemia (cml). management has been revolutionized by tyrosine kinase inhibitors (e.g. imatinib) which can produce complete remission in over % of cases. once the diagnosis of cml is established, hydroxycarbamide can be used to reduce the white cell count, followed by treatment with a tyrosine kinase inhibitor. manufacturers will provide the drug free of charge to patients in low-income countries with confirmed cml and generic forms of tyrosine kinase inhibitors are now becoming available. chronic lymphocytic leukaemia (cll). this occurs predominantly in older people and usually presents with lymphadenopathy and recurrent infections. treatment is with chlorambucil and prednisolone although aggressive forms require combination therapy with rituximab, fludarabine and cyclophosphamide. treatment is generally not curative but the disease may be indolent and drugs may only be required if the patient has symptoms or if there is a risk of hyperviscosity from a very high lymphocyte count. approximately cases of non-hodgkin lymphoma (nhl) occur in the equatorial belt of africa each year (table . ). there are marked geographical variations in prevalence but up to % are thought to be related to hiv infection. burkitt's lymphoma, a b-cell nhl, was originally described in children from africa and has an estimated incidence of - per million. lymphomas are broadly classified into hodgkin's lymphoma and nhl; nhl are divided into b-cell, t-cell and nk-cell, and immunodeficiency-associated types. the clinical presentation of lymphomas is characterized by enlargement of the lymphoid organs and subsequent compression of the adjacent structures, infiltration of organs by the malignant lymphoid cells and a dysfunctional immunological system which can manifest as immunosuppression or excessive but dysregulated immune activation associated with, for example, autoimmune conditions. the diagnosis and management of the various types of lymphomas are complicated and should be undertaken in a specialist box . clinical features of leukaemias • fatigue and cardiac symptoms from anaemia • bleeding from thrombocytopenia • increased risk of infections despite a higher number but dysfunctional white cells • lymphadenopathy and hepatosplenomegaly occur with all although lymphadenopathy may be observed in the monocytic variety of aml • blindness due to hyperviscosity from hyperleukocytosis • tumour lysis syndrome due to spontaneous cell lysis presents as renal failure • pustules or pyogenic infections of the skin from minor wounds • bleeding gums are a characteristic feature of acute monocytic leukaemia • disseminated intravascular coagulation can occur with acute promyelocytic leukaemia • gout can arise from breakdown of the excess white cells and release of uric acid • oral aphthous ulceration is seen with severe neutropenia in both aml and all • granulocytic sarcoma or chloroma represent extramedullary deposits of leukaemic cells in any organ but mainly the skin. this may occur in the absence of peripheral blood involvement and is more common with chromosomal translocation ( ; ) of aml • central nervous system manifestations due to sludging of the cerebral circulation by the malignant cells or increased intracranial pressure due to ventricular blockade can occur. monocytic myeloid leukaemia can also involve the meninges • intracranial haemorrhage can occur in all with very high white cell counts (> × /l) • bone pain and arthralgia can be a presenting feature of all in children in more than a quarter. these children may present with a limp or unwillingness to walk due to marrow infiltration by leukaemic cells. rarely, they may have normal blood counts delaying the diagnosis of all • anterior mediastinal mass (thymus enlargement) can also occur in children and young adults with all which may present as superior venocaval obstruction • painless enlargement of scrotum is a sign of testicular leukaemia or hydrocele from lymphatic obstruction. priapism can result from hyperleukocytosis rarely. • most often asymptomatic and usually suspected on blood counts • the chronicity of cml or cll tends to cause gradual-onset symptoms since the patients get adjusted to the slowly developing anaemia • abdominal discomfort and early satiety are a feature of cml due to excessive splenomegaly compressing the stomach and reducing the luminal volume • sternal tenderness may be noted in cml • hyperleukocytosis in cml can occur more often than with aml or all due to the gradual increase in white cells. this can cause symptoms like hyperuricaemia and gout, tinnitus, priapism or central nervous system disturbances • left shoulder tip pain can arise from splenic infarction from the massive splenomegaly in cml • cml can rarely present with features of thyrotoxicosis (heat intolerance, weight loss and excessive sweating) due to hyper-metabolism • cll is often associated with lymphadenopathy and rarely with mild to moderate splenomegaly. all, acute lymphoid leukaemia; aml, acute myeloid leukaemia; cll, chronic lymphocytic leukaemia; cml, chronic myeloid leukaemia. centre. diagnosis depends on clinical history and examination, radiological investigations to document the extent of disease, and morphology, immunohistochemistry and molecular studies on tissue samples to confirm the lymphoma subtype. guidance on the diagnosis and treatment of lymphoma in settings where resources are limited includes recommendations about panels of immunostains and chemotherapy regimens that minimize the need for supportive care. tele-pathology, which involves transmitting histological images via the internet to experts overseas, may be helpful in certain circumstances though it is dependent on the quality of the histology preparations and the images of appropriate diagnostic regions in the sample. treatment regimens for lymphomas differ according to the subtype but may involve chemotherapy and radiotherapy. high remission rates can be achieved in burkitt's lymphoma with a combination of cyclophosphamide, vincristine and methotrexate and progressive disease can be managed with ifosfamide, mesna and cytosine arabinoside. , adult t-cell leukaemia-lymphoma (atll) adult t-cell leukaemia-lymphoma (atll) is an uncommon lymphoid malignancy which occurs in patients infected with human t-lymphotropic virus type i (htlv-i). htlv- is endemic in the caribbean, western africa, peru and southern japan. less than % of those infected with htlv-i develop atll and up to years can elapse between the primary infection and the development of atll suggesting additional factors are needed for malignant transformation. atll presents acutely in approximately % of cases, although chronic forms have also been described. the clinical presentation is with generalized lymphadenopathy in most cases and hepatosplenomegaly in over half. atll is associated with a high risk of hypercalcaemia which occurs in more than two-thirds of patients during the course of their disease and may be associated with central nervous system disturbances and renal impairment. lytic bone lesions occur as a para-neoplastic types of lymphomas identified from selected countries in sub-saharan africa phenomenon due to production of parathormone-like peptides. as with other t-cell disorders, atll can involve the skin, producing, e.g. erythrodermic plaques. the diagnosis of atll can be suspected from a high peripheral blood white blood cell count in combination with hypercalcaemia and characteristic lymphocytes with convoluted and hyperlobulated nuclei. the diagnosis is confirmed by histological examination of a tissue (lymph node or bone marrow), immunophenotyping for specific cell markers and proof of htlv infection, usually by serological methods. management of atll is primarily with combination chemotherapy with intrathecal prophylaxis. , a combination of zidovudine and interferon, as agents against htlv, has also been tried with some success. hypercalcaemia and opportunistic infections should be sought and treated early in these patients. the high white cell count is associated with a significant risk of tumour lysis syndrome and should be prevented by adequate hydration and the judicious use of allopurinol and other urate-reducing agents. myeloma is a monoclonal proliferation of plasma cells and it particularly affects older people. myeloma appears to be less common in asian countries than elsewhere, although during the last years, an almost four-fold increase in incidence of myeloma has occurred in taiwan. in the united states, the incidence of multiple myeloma in the black population is twice that of the white population. the abundant plasma cells infiltrate the bone marrow and interfere with normal haematopoiesis. this leads to anaemia, which is a presenting feature in % of individuals. bony infiltration by the malignant plasma cells can produce osteoporosis, lytic lesions and pathological fractures in % of patients with myeloma. involvement of the bones can lead to hypercalcaemia, which may be a presenting feature, and vertebral fracture leading to spinal cord compression. the malignant plasma cells produce a paraprotein which can cause renal impairment in - % and hyperviscosity may ensue in % of patients if the paraprotein production is not controlled. patients with myeloma may need a variety of supportive interventions including management of anaemia, renal failure, hypercalcaemia, hyperviscosity, infections and bone pains. specific anti-myeloma treatment should be managed within a specialist unit and has undergone a radical change in the last decade with the use of thalidomide and its newer formulations, and the more expensive, proteasome inhibitors (e.g. bortzomib). thalidomide is relatively safe and effective although somnolence and constipation can sometimes be troublesome. there is a risk of thrombosis with thalidomide especially at the initiation of therapy, and prophylaxis with heparin, warfarin or antiplatelet agents, depending on an assessment of the risk, may be warranted. melphalan may also be useful, particularly if resources are limited and there is no specialist centre. however it is myelosuppressive, so regular monitoring of the blood count is essential. maintaining an adequate blood supply is a major challenge for low-income countries. only % of the global blood supply is donated in the poorest countries where % of the world's population lives. blood transfusion is a vital component of every country's health service. it can be a life-saving intervention for illnesses such as severe acute anaemia, but mistakes in the transfusion process can be life-threatening, either immediately or years later through transmission of infectious agents. clinicians need to understand how blood is acquired and its risks and benefits, and to use it appropriately. governments and transfusion services need to put measures in place to ensure that blood is safe for transfusion and that it reaches those who need it in a timely manner. only % of member states meet all the world health organization's (who) recommendations for a national quality blood transfusion system. at the national level the transfusion service should have a director, an advisory committee and clear transfusion policies and strategies (table . ). who recommend standardization of blood collection, testing and distribution. although centralization of these services may offer the best guarantee of quality, it is often not practical in countries with poorly developed communications and transport infrastructure. two systems, centralized and hospital-based, exist in lowincome countries for managing blood supply. in the centralized system, voluntary blood donors are recruited, screened and bled by regional centres and the blood collected is distributed to peripheral hospitals. hospital-based systems are the predominant source of blood across sub-saharan africa. hospital-based systems obtain blood predominantly from relatives of patients, and blood is screened and used within the local vicinity. blood from the centralized system costs at least three times as much per unit as that from a hospital-based system. although centralized systems can save costs through batching and bulk purchasing, the quality assurance processes and donor recruitment components are expensive and difficult to maintain without dependence on external funds. in hospital-based transfusion services, testing quality is variable and the families of patients bear the cost of finding blood donors. the vast majority of blood in low-income countries is transfused as whole blood. in high-income countries it is standard practice to optimize the use of each donation of blood by separating it into individual components but whether this approach is cost-effective in low-income countries, where indications for transfusion are different, is not known. these components, which may include plasma, platelets and cryoprecipitate, are prepared by centrifugation using a closed, sterile system and each component has different storage requirements. plasma and cryoprecipitate are kept frozen, red cells are stored at - °c, and platelets at - °c with constant agitation. recent evidence suggests that warm, fresh, whole blood may be better than component therapy for resuscitation of acidotic, hypothermic and coagulopathic trauma patients and for patients needing massive transfusions. many infections can be transmitted through blood transfusions and transfusion of infected blood causes morbidity and mortality in the recipients, and has an economic and emotional impact on their families and communities. those who become infected through blood transfusion are infectious to others and contribute to the spread of disease thereby increasing the burden on health services and reducing productive labour. strategies for recruiting blood donors have to provide blood for all who need it in a timely manner while ensuring that the blood is as safe as possible. the safest type of blood donor is one who donates regularly (i.e. repeat donors). who states that the safest source of blood is altruistic, voluntary, unpaid donors. only % of who member states report having at least % of their blood supply from voluntary donors, and low-income countries have not been able to increase the recruitment of voluntary donors for several years. recent evidence from sub-saharan africa indicates that the focus on voluntary donors may be misplaced since first-time voluntary donors have a similar prevalence of transfusion-transmitted infections as family replacement donors. in order to limit blood shortage and maintain constant blood supply in poorer countries, both voluntary and replacement donors should be accepted and encouraged to donate regularly. mechanisms to convert family replacement donors into repeating voluntary donors have the potential to significantly increase blood donations in africa. political will and open-mindedness about ways to improve the supply and safety of blood are essential to promote more evidence-based approaches to blood transfusion practice in poorer countries. supporting strategy in wealthy countries, the majority of transfusions are carried out electively. by contrast, in poorer countries, and particularly those where the malaria transmission rate is high, most transfusions are given for life-threatening emergencies. in low-income countries, - % of transfusions are administered to children, predominantly for malaria-related anaemia, and pregnant women. transfusion can significantly reduce the mortality of children with severe anaemia within the first days of hospital admission and successful malaria control can reduce paediatric transfusion requirements. in sub-saharan africa, % of in-hospital maternal deaths from severe bleeding were due to lack of blood for transfusion. other specialities which are significant users of blood are surgery, trauma, emergency medicine and general medicine. in low-income countries the most effective way to avoid transfusions is to reduce the prevalence of anaemia. more studies on the efficacy and cost of combinations of interventions including insecticide-treated bed nets, nutritional supplements and anthelmintic drugs to prevent anaemia are needed. when resources are very limited, governments may need to make some difficult decisions in order to achieve an equitable balance between investing in a transfusion service and public health measures to reduce anaemia. whether a patient needs a blood transfusion or not is ultimately a clinical decision. emergency transfusions can be lifesaving for patients in whom anaemia has developed too quickly to allow physiological compensation, as in severe malariarelated anaemia in children, and sudden, severe obstetric bleeding. in contrast, if the anaemia has developed slowly, for example due to hookworm infestation or nutritional deficiency, patients can generally be managed conservatively by treating the cause of the anaemia and prescribing haematinic replacements. iron supplements should be continued for at least months after the haemoglobin has returned to normal, so that body stores can be replenished. clinical guidelines. it is possible to avoid unnecessary transfusions by adhering to clinical transfusion guidelines. most institutions have developed guidelines to help clinicians make rational decisions about the use of blood transfusions (box . ) , and strict enforcement of transfusion protocols can significantly reduce avoidable transfusions. the principles underlying most transfusion guidelines are similar and combine a clinical assessment of oxygenation, with haemoglobin measurement being used as a surrogate measure for intracellular oxygen concentration. increasingly, transfusion guidelines are making use of evidence which shows that adequate oxygen delivery to the tissues can be achieved at haemoglobin levels that are significantly lower than the normal range. implementation of transfusion guidelines is particularly difficult if clinicians do not have access to reliable haemoglobin high-risk donors, such as commercial sex workers and their contacts, intravenous drug abusers, or those with an itinerant lifestyle such as traders, drivers and military personnel, should be deterred from donating. even in areas where hiv infection rates in the general population are high, donor deferral can be effective in excluding hiv-infected donors. the whole donation process, including tests for hiv and other infections, should be explained to the donor before blood is collected and donors should have the option of knowing the results and receiving counselling. it is imperative that complete confidentiality is maintained throughout all procedures. infections with organisms such as hiv, hepatitis viruses, cytomegalovirus, syphilis, lyme borreliosis, malaria, babesiosis, american trypanosomiasis (chagas disease) and toxoplasmosis can all be acquired through blood transfusions. some - % of hiv infections worldwide are thought to have been transmitted through the transfusion of infected blood and blood products. there have also been reports of transmission of variant creutzfeldt-jakob disease through blood transfusion and there is a theoretical risk of transmission of severe acute respiratory syndrome (sars). , who recommends that all donated blood should be screened for hiv, hepatitis b and syphilis and, where feasible and appropriate, for hepatitis c, malaria and chagas disease. malaria can be transmitted by blood transfusion and, depending on the local infection prevalence, - % of blood donors in africa screen positive for malaria. however, there is very little evidence to suggest that these donors transmit malaria to transfusion recipients. although who recommends screening donors in endemic areas for malaria, none of the screening methods that would be practical for transfusion services are sufficiently sensitive. furthermore, in some countries with high malaria transmission, exclusion of parasitaemic donors could result in deferral rates exceeding % which would have a major impact on blood supply. there is no evidence to support the widespread practice of routine treatment of transfusion recipients for malaria. fresh blood is potentially infectious for syphilis, but storage at °c for more than days can inactivate treponema pallidum. the high demand for blood in low-income countries means that blood is generally not stored for long enough to inactivate t. pallidum and syphilis seroconversion associated with transfusion has been reported from africa. globally, the prevalence of hepatitis c, htlv- and - and chagas disease is variable and the decision to introduce donor screening for these infections should be based on local assessments of the risks, benefits, feasibility and costs. blood should not be separated into components if the residual risk of infection is high, as this will increase the number of potentially infected recipients. a unit of blood is usually stored until screening tests for infections have been completed. this means that potentially infected blood may be mixed up with units that have already been screened, and costly blood collection bags are wasted. screening potential donors before venesecting a unit of blood may therefore be a more cost-effective way of ensuring safe blood. tests for screening blood donors need to be highly sensitive, and infected blood should be rejected. before informing the donor of the outcome, all positive results should be confirmed using a test with a high degree of specificity. where blood or that the blood may become infected with bacteria during the process. intraoperative blood salvage. this involves collecting blood lost during the operation and reinfusing it into the patient either during or after surgery. although this technique is practical and safe, and reduces the need for donor blood by - %, it requires specialized equipment and training, and may be more expensive than routinely donated blood. other measures. normal saline or intravenous replacement fluids can be used judiciously in acute blood loss, and in certain circumstances may be as effective as whole blood, red cells or plasma. erythropoietin, which stimulates endogenous red cell production is well-established for use in chronic anaemias such as those due to renal failure, cancer and hiv infection but its delayed action makes it unsuitable for use in acute anaemias. synthetic oxygen carriers, such as perfluorocarbons, are not yet routinely available. in low-income countries, the recommended haemoglobin threshold for transfusions is often well below that which would be accepted in more wealthy countries. randomized controlled studies in wealthy countries indicate that for most adults and children undergoing critical care, a haemoglobin threshold of g/l for transfusion is safe whereas paediatric blood transfusion protocols in sub-saharan africa often recommend transfusions for stable children only when the haemoglobin level is less than g/l. complications such as cardiac failure or infection may necessitate transfusion at a higher haemoglobin level. transfusion should be combined with adequate haematinic replacements and underlying conditions should be treated. early evidence suggests that intermittent preventive treatment with anti-malarials may reduce the high hospital readmission rates experienced by children post-transfusion. complications can occur immediately during transfusion, within a few hours of its completion, or be delayed for many years, as in the case of viral infections (box . ). measurements. when they doubt the haemoglobin result, clinicians rely entirely on clinical judgement to guide transfusion practice which can lead to significant numbers of inappropriate transfusions. a lack of investment in the quality of a critical test, such as haemoglobin measurement, can waste significant resources downstream in the transfusion process, and unnecessarily expose recipients to the risk of transfusion-related infections. minimizing surgical blood loss. where blood is in short supply, it is particularly important to ensure that the best anaesthetic and surgical techniques are used, to minimize blood loss during surgery. drugs which improve haemostasis or reduce fibrinolysis, such as aprotinin and cyklokapron, and fibrin sealants, can be effective in reducing perioperative blood loss. these drugs can therefore reduce the need for blood transfusion but they may be too expensive for use in low-income countries. a cost-effectiveness study of surgical bleeding in four sub-saharan countries indicates that the antifibrinolytic, tranexamic acid, could save lives in countries with blood shortages, reduce healthcare costs and prevent transmission of infections. preoperative autologous blood deposit. patients undergoing planned surgery who are likely to require a blood transfusion can have units of their own blood removed and stored in case they have significant intraoperative blood loss and need a transfusion. this process, known as preoperative autologous donation, can reduce the need for allogeneic transfusions by - % but it requires careful organization: the surgeon needs to predict how much blood will be required, the patient has to be fit enough to withstand removal of one or more units of blood over the weeks preceding the surgery and the surgery must take place within the shelf-life of the blood. as the blood has to be stored in the blood bank there is still a risk that the patient may receive blood which is not their own box . prescribing blood: a checklist for clinicians always ask yourself the following questions before prescribing blood or blood products for a patient: . what improvement in the patient's clinical condition am i aiming to achieve? . can i minimize blood loss to reduce this patient's need for transfusion? . are there any other treatments i should give before making the decision to transfuse, such as intravenous replacement fluids or oxygen? . what are the specific clinical or laboratory indications for transfusion in this patient? . what are the risks of transmitting hiv, hepatitis, syphilis or other infectious agents through the blood products that are available for this patient? bacterial contamination and should be investigated and managed accordingly. allergic reactions are due to infusion of plasma proteins and manifestations include erythema, rash, pruritus, bronchospasm and anaphylaxis. the transfusion should be stopped and the patient treated with antihistamines. if the reaction is mild and the symptoms and signs completely disappear, the transfusion can be restarted. if this type of mild reaction occurs repeatedly with more than one unit of blood, the red cells can be washed before transfusion. this should only be done if absolutely necessary, as it carries the risk of introducing potentially fatal bacterial infection. severe allergic reactions with evidence of systemic toxicity should be managed as acute anaphylaxis. blood should always be transfused slowly to avoid overloading the circulation, unless the patient has active and severe bleeding. fluid overload may be a particular problem when paediatric blood bags are not available, as children may be over-transfused due to miscalculation of the required volume, lack of accurate infusion devices or inadvertent administration of an adult-sized unit of blood. four units of blood contain the equivalent amount of iron stored in bone marrow (approx. g). repeated transfusions for chronic haemolytic anaemia, as in thalassaemia major and sickle cell disease, lead to iron deposition in parenchymal cells. eventually failure of the heart, liver and other organs supersedes. adequate doses of iron chelators, such as injectable desferrioxamine or oral deferiprone, are able to maintain acceptable iron balance in patients with chronic anaemia who need regular transfusions. it is not usually necessary to warm blood unless large quantities are transfused rapidly. this may lower the temperature of the sino-atrial node to below °c at which point ventricular fibrillation can occur. if blood needs to be warmed, an electric blood warmer specifically designed for the purpose should be used. this keeps the temperature below °c and avoids the haemolysis associated with overheating blood. graft-versus-host disease occurs when donor lymphocytes engraft in an immune-suppressed recipient. the lymphocytes recognize the recipient's bone marrow as foreign and induce aplasia. graft-versus-host disease is almost universally fatal and can be prevented by irradiating the donor blood, which inactivates the donor lymphocytes. transfusion of blood into a recipient who possesses antibodies to the donor's red cells can cause an acute, and occasionally fatal, intravascular haemolysis. this could occur, e.g. if group a cells are transfused into a group o recipient who has naturally occurring antibodies to group a cells. the profound haemolysis induces renal vasoconstriction and acute tubular necrosis. treatment involves stopping the transfusion, cardiorespiratory support and inducing a brisk diuresis. in addition to abnormalities indicating renal failure, laboratory findings include haemoglobinuria and haemoglobinaemia. proof of the diagnosis involves rechecking the whole transfusion process including all documentation stages, regrouping the donor and the recipient, and screening for antibodies on red cells with a direct antiglobulin test. these tests are usually available in any hospital laboratory capable of providing a transfusion service. delayed haemolysis has a similar physiological basis to acute intravascular haemolysis but it tends to be less severe, it occurs - days after the transfusion and it is less likely to present as a clinical emergency. limited data from sub-saharan africa show rates of bacterial contamination in donated blood of around % , but the clinical consequences for transfusion recipients are unknown. bacteria can enter the blood bag during venesection or if the bag is breached, e.g. when reducing the volume for a paediatric recipient or during component preparation. gram-negative bacteria, including pseudomonas and yersinia, grow optimally at °c and infected blood may not necessarily appear abnormal to the naked eye. reactions following infusion of infected blood are often due to endotoxins and may occur several hours after the transfusion has finished. although these reactions are rare, they can be severe and fatal. if bacterial contamination is suspected, the transfusion should be stopped and samples from the patient and the blood bag sent to the laboratory for culture. cardiorespiratory support may be needed and broad-spectrum antibiotics should be started immediately and continued until culture results are available. non-haemolytic febrile reactions are episodes of fever and chills associated with transfusion and for which no other cause can be found. they are due to the recipient's antibodies reacting against antigens present on the donor's white cells or platelets. these reactions are most common in patients who have had transfusions in the past and have therefore been exposed to allo-antigens. mild febrile reactions usually respond to simple antipyretics such as paracetamol. more 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placebocontrolled trial bacterial contamination of pediatric whole blood transfusions in a kenyan hospital bacterial contamination of blood and blood components in three major blood transfusion centres in accra, ghana access the complete references online at www.expertconsult.com key: cord- - skgb eu authors: chowell, gerardo; nishiura, hiroshi title: transmission dynamics and control of ebola virus disease (evd): a review date: - - journal: bmc med doi: . /s - - - sha: doc_id: cord_uid: skgb eu the complex and unprecedented ebola epidemic ongoing in west africa has highlighted the need to review the epidemiological characteristics of ebola virus disease (evd) as well as our current understanding of the transmission dynamics and the effect of control interventions against ebola transmission. here we review key epidemiological data from past ebola outbreaks and carry out a comparative review of mathematical models of the spread and control of ebola in the context of past outbreaks and the ongoing epidemic in west africa. we show that mathematical modeling offers useful insights into the risk of a major epidemic of evd and the assessment of the impact of basic public health measures on disease spread. we also discuss the critical need to collect detailed epidemiological data in real-time during the course of an ongoing epidemic, carry out further studies to estimate the effectiveness of interventions during past outbreaks and the ongoing epidemic, and develop large-scale modeling studies to study the spread and control of viral hemorrhagic fevers in the context of the highly heterogeneous economic reality of african countries. background a complex epidemic of zaire ebolavirus (ebov) has been affecting west africa since approximately december , with the first cases likely occurring in southern guinea [ ] . the causative ebola strain is closely related to a strain associated with past ebov outbreaks in central africa [ ] and could have been circulating in west africa for about a decade [ ] . however, the current epidemic was not identified until march [ ] , which facilitated several transmission chains to progress essentially unchecked in the region and to cross porous borders with neighboring sierra leone and liberia and seed a limited outbreak in nigeria via commercial airplane on july [ ] . the world health organization declared the ebola epidemic in west africa a public health emergency of international concern on august [ ] , with exponential dynamics characterizing the growth in the number of new cases in some areas [ ] [ ] [ ] [ ] [ ] . economic and sociocultural factors together with the delay in identifying the outbreak in urban settings have hindered a timely and effective implementation of control efforts in the region [ , ] . remarkably, the current size of the ongoing ebov epidemic far surpasses the total number of cases reported for all previous ebola outbreaks combined. a total of , cases, with , deaths, have been reported to the world health organization as of september . a serious shortage of timely resources in the region is the key factor responsible for the onset and disproportionate scale of the ongoing epidemic in west africa [ ] . in particular, the epidemic is unfolding in a region characterized by limited public health infrastructure including: ( ) a lack of essential supplies to implement infection control measures in health care settings; ( ) scarcity of health care workers and staff to manage a growing case burden and carry out essential contact tracing activities to find new cases quickly so that these can be effectively isolated [ ] ; and ( ) the absence of epidemiological surveillance for the timely identification of case clusters [ , ] . containing the ongoing epidemic poses an unprecedented challenge as the virus has moved from guinea to reach urban areas after crossing the unprotected borders of neighboring liberia and sierra leone. a major coordinated operation on the ground is needed to limit the geographic extension of the epidemic. the causative agent of ebola virus disease (evd) is an rna virus of the family filoviridae and genus ebolavirus. five different ebolavirus strains have been identified, namely zaire ebolavirus (ebov), sudan ebolavirus (sudv), tai forest ebolavirus (tafv), bundibugyo ebolavirus (bdbv) and reston ebolavirus (restv), with fruit bats considered as the most likely reservoir host [ ] . the great majority of past ebola outbreaks in humans have been linked to three ebola strains: ebov, sudv and bdbv [ ] . the ebola virus, ebov, (formerly designated zaire ebolavirus), the deadliest of the five ebolavirus strains, was first identified in in zaire (now the democratic republic of congo) and its name was derived from the ebola river located near the source of the first outbreak. past ebola outbreaks have been reported on average every . years [ ] , with a total of prior outbreaks generating over reported cases [ ] . a recent study has estimated million people distributed in areas of central and west africa to be at risk of ebola [ ] . ebola is characterized by a high case fatality ratio which was nearly % in a past outbreak [ ] . after an incubation period mostly ranging from to days, nonspecific symptoms appear, including sudden onset of fever, weakness, vomiting, diarrhea, headache and a sore throat. a fraction of patients may later develop severe internal and external hemorrhagic manifestations and experience multiple organ failures [ ] . except for restv, all other ebola strains are pathogenic to humans. human outbreaks may stem from direct human exposure to fruit bats or intermediate infected hosts that primarily comprise non-human primates (that is, gorillas, chimpanzees and monkeys). human epidemics subsequently take off by direct human-to-human contact via bodily fluids or indirect contact with contaminated surfaces. hence, stopping ebola transmission should be feasible when the cases are detected early and managed properly, because this virus is not transmitted through the air or water [ ] . nevertheless, ebola has been shown to spread through the air under carefully controlled laboratory conditions [ ] . hence, amplification of human-to-human transmission can result in the presence of suboptimal infection control measures in healthcare settings [ ] [ ] [ ] . unsafe burials that involve direct contact with ebola-infected bodies also pose a major infection risk [ ] . a review of key epidemiological parameters of evd and our current understanding of the transmission dynamics and the effect of basic control interventions against this disease would be useful for guiding and assessing the potential effectiveness of control interventions during ebola outbreaks. specifically, here we review epidemiological data from past ebola outbreaks including the basic reproduction number, the serial interval and the case fatality ratio. subsequently, we carry out a comparative review of mathematical models of the spread and control of ebola in the context of past and the ongoing epidemic in west africa. we show that mathematical modeling offers useful insights into the risk of a major epidemic of evd and the assessment of the impact of basic public health measures on disease spread. we illustrate the effects of demographic characteristics, such as the effective population size, size of spillover event (for example, details of initial conditions), baseline infection control measures in health care settings, and the timing of initiation of control interventions including enhancing the effectiveness of isolating infectious individuals, contact tracing to bring infectious individuals into isolation and social distancing interventions in the community. due to the relatively few past ebola outbreaks, available epidemiological data to infer the natural history parameters of evd remain limited. moreover, past outbreaks have been caused by different virus strains, making it difficult to judge whether a certain observed epidemiological characteristic is unique to the causative strain. here, we extract published evidence and review ebola epidemiological parameters from the literature, integrating estimates of the basic reproduction number, the asymptomatic ratio, the incubation period, the latent period, the symptomatic period, the infectious period, the serial interval and the case fatality ratio. the basic reproduction number, r , is interpreted as the average number of secondary cases caused by a typical infected individual throughout its entire course of infection in a completely susceptible population and in the absence of control interventions [ , ] . in the context of a partially susceptible population owing to prior exposure or vaccination, the (effective) reproduction number, r, quantifies the potential for infectious disease transmission. if r < , transmission chains are not self-sustaining and are unable to generate a major epidemic. by contrast, an epidemic is likely to occur whenever r > . when measured over time t, the effective reproduction number r t , can be helpful to quantify the time-dependent transmission potential and evaluate the effect of control interventions in almost 'real time' [ ] . in summary, r is regarded as a summary measure of the transmissibility of infectious diseases, playing a key role in determining the required control effort (for example, intensity of quarantine and isolation strategies). r could also be useful for guiding the numbers of antivirals and vaccines that would be needed to achieve control whenever these are available. r has been estimated for prior evd outbreaks in central africa using mathematical modeling and epidemiological data for two ebola outbreaks, namely the outbreak in democratic republic of congo and the uganda outbreak, respectively [ , ] . unlike the ongoing epidemic in west africa, past outbreaks in central africa have been confined to relatively rural and isolated areas without spreading to urban sectors which facilitated the effective implementation of control interventions. using a homogenous mixing seir (susceptible-exposed-infectious-removed) model that accounted for a gradual decay in the transmission rate at the start of interventions, chowell et al. [ ] estimated r at . [ ] : while allowing for homogeneous mixing, the study took into account three different transmission settings, that is, transmissions in community, hospital settings and during funerals. r was estimated at . for congo, and . for uganda, , but estimates showed substantial uncertainty. transmission from burials alone accounted for . secondary transmissions in congo while community transmission in uganda accounted for . secondary transmissions. variability in r estimates across studies can be attributed to differences in model structure and underlying assumptions. an assessment of r based on the growth rate of the ebola epidemic in west africa a quick look at the ongoing epidemic in west africa without delving into a too detailed analysis permits us to grasp the level of r for the ongoing ebola outbreak. assuming that the early epidemic data in sierra leone and liberia are sufficient to be characterized by exponential growth dynamics, with growth rate r, the incidence (that is, the number of new cases at calendar time t) is modeled as where k is a constant. as the observed data are cumulative i(t), we integrate the above equation from the starting time of exponential growth t to the latest time t, that is, it should be noted that the cumulative number of cases does not follow a single exponential growth term. assuming that the observed number of cases is poisson distributed, the maximum likelihood estimate for r for liberia is estimated at . ( % confidence interval (ci): . , . ). the growth rate in sierra leone is largely divided into two phases with a greater growth rate in the early phase (which could reflect initial case clusters in hospital settings). hence, r is estimated at . ( % ci: . , . ) and . ( % ci: . , . ) for the early and late phases, respectively (figure a) . assuming that the mean generation time is days (with standard deviation . days) based on contact tracing data from an outbreak in uganda [ ] (see below), r for liberia is estimated at . ( % ci: . , . ). for sierra leone, r is . ( % ci: . , . ) and . ( % ci: . , . ) for the early and late phases, respectively (figure b) . estimates in liberia and the late phase of sierra leone are roughly consistent with those published by chowell et al. [ ] . a comparison of the growth trends for past outbreaks in central africa (congo and uganda ) with the ongoing epidemic in liberia is shown in figure . recent studies have started to shed light on the transmission potential of the ongoing evd epidemic. specifically, three studies have estimated the basic reproduction number of evd in the range of . to . [ , , ] . althaus [ ] employed an seir model with the time-dependency of the reproduction number to capture effects of control interventions, following the model by chowell et al. [ ] ; analyzing the country-specific data independently for each country, the estimates were . for guinea, . for sierra leone and . for liberia [ ] . gomes et al. [ ] explicitly accounted for the risk of international spread, and the basic reproduction number ranged from . to . . more importantly, this study employed a global epidemic model with mobility data, indicating that the short-term risk of international spread to outside africa is small and that the expansion of the ongoing epidemic is more likely to occur in african countries [ ] . moreover, fisman et al. estimated r at . using a two-parameter mathematical model that describes the epidemic growth and control [ ] . real-time estimation of the effective (time-dependent) reproduction number revealed estimates in line with r estimates derived from other studies. for instance, by measuring temporal variations in the epidemic growth rate during periods of epidemic growth, the reproduction number was approximated based on a classic formula of r for the seir model, which provided estimates in the range of . to . [ ] . a different modeling study accounted for both local transmission and transnational spread across severely affected countries using a multivariate renewal process model which allowed the derivation of global and country-specific estimates of the reproduction number [ ] . this study indicated that the effective reproduction number r t from june to august ranged from . to . in sierra leone and liberia. hence, control could be reached by halting over half of the secondary transmissions per primary case whenever the reproduction number is below [ ] . moreover, it is worth noting that the exponential growth in ebola incidence is placing great pressure on healthcare facilities, which could affect time-and spacedependent variations in transmission dynamics and the surveillance system [ ] . the analysis of available data using mathematical modeling should, therefore, carefully assess the quality and consistency of the surveillance system employed to collect epidemiological data. hence, mathematical models should ideally be tied to characteristics of the surveillance system as much as possible to avoid potential bias [ ] . for comparison with other filoviruses, the r for the marburg fever outbreak in angola has been consistently estimated at . using two different statistical modeling approaches [ , ] . for comparison with other infectious diseases transmitted by direct contact, r has been estimated at . for an outbreak of acute hemorrhagic conjunctivitis in mexico [ ] . in contrast, for respiratory infections, the reproduction number has been estimated for the sars outbreaks in in the range . to . based on fitting transmission models to the progression of weekly cases prior to the start of control interventions [ , ] , in the range . to . for seasonal influenza [ ] , . to . for influenza pandemics [ ] [ ] [ ] [ ] [ ] [ ] , for pertussis, for measles [ ] and . to . for meningococcal meningitis [ ] . asymptomatic infection with ebola virus is known to occur in a certain fraction of exposed individuals [ ] . by analyzing the antibody responses among asymptomatic close contacts of symptomatic patients, leroy et al. found that ( . %) developed both immunoblobulin m (igm) and igg responses to ebola antigens. however, the study subjects were only those who experienced close contacts, and an estimate of asymptomatic ratio for the general population was not obtained. the majority of cases developed illness to days after infection. a classical study of the zaire strain [ ] indicated that the mean incubation period, that is, the mean length of time from infection to illness onset, is . days with the % quantile days. reanalyzing the data set of household contacts during the ebola outbreak in the democratic republic of congo in , eichner et al. estimated the mean incubation period at . days (with standard deviation . days) [ ] . the fitted lognormal distribution is redrawn in figure a the relationship between the exponential growth rate and the corresponding reproduction number for evd based on a weibull distributed generation time with shape and scale parameters of . and . , respectively. arrows indicate the uncertainty range ( % confidence interval) of the exponential growth rate estimated from the corresponding epidemic data. months of the ongoing ebola epidemic, a recent study estimated the mean incubation period at . days with no significant variation across the affected west african countries [ ] . the serial interval defined as the time from illness onset in the primary case to illness onset in the secondary case [ ] , has been relatively well observed for evd based on household or contact-tracing studies. a household study during the outbreak in drc indicated that the minimum serial interval was days, while the maximum was days [ ] . findings based on contact tracing data for the outbreak in uganda in were roughly consistent with those derived from household data [ ] : mean (sd) and median (quartiles) estimates for the serial interval were . ( . ) and . ( to ) days, respectively. figure b shows the serial-interval distribution along with a fitted weibull distribution with scale and shape parameters estimated at . ( % ci: . , . ) and . ( % ci: . , . ), respectively. the cramér-von mises goodness-of-fit test did not reveal significant deviations between the observed data and fitted model distribution (w = . , p = . ). this estimate is in good agreement with that derived from data of the first months of the ongoing epidemic in west africa, which has been estimated at . ± (sd = . ) days [ ] . this distribution is key to quantifying the reproduction number using the exponential growth rate of cases during the early stage of an epidemic, because the conversion from the growth rate of cases to the reproduction number requires estimates of the generation time distribution [ ] which is known to be informed by the serial interval and the incubation period [ ] . incidence data for the outbreaks in central africa are shown according to the dates of symptoms onset while the weekly incidence curve for the epidemic in liberia comprises total cases based on the daily epidemic curve estimated in [ ] . other parameters associated with the time course of evd have not been rigorously ascertained. however, according to bayesian model-based estimates from a past ebola outbreak [ ] , the mean latent and infectious periods have been estimated at . and . days, respectively, using a vague prior and . and . days, respectively, for an informative prior. these exponential distributions based on a mathematical modeling study are the only available empirical evidence for these two time periods. the mean length of time from illness onset to death is approximately days [ , ] , but the transmissibility from the deceased from ebola may account for a certain fraction of secondary transmissions [ ] . hence, the infectious period could be longer than the observable time to death if the burial is extended. the case fatality ratio (cfr) is calculated as the proportion of deaths among the total number of evd cases, thereby informing the virulence of the infectious pathogen. evd can be fatal, but it is important to note that the cfr being 'almost %' for evd in general does not rest on any empirical arguments. for the well documented outbreaks of ebola (excluding only isolated cases who are likely to have acquired infection from animal contact), the expected value of cfr has always been below % [ ] , with the range from % to %. the so-called zaire strain is considered to be slightly more fatal than the sudan strain. while the cfr for the sudan strain ranges from % to %, the cfr for the zaire strain ranges from % to %. considering that the corresponding quartile for the zaire strain, as determined by the distribution of outbreak-specific estimates, ranges from . % to . %, the cfr of the ongoing epidemic among cases with definitive recorded clinical outcomes for guinea, liberia and sierra leone has been consistently estimated at . % ( % ci: . to . ), which is in good agreement with estimates from prior outbreaks. nevertheless, it must be noted that earlier studies have not addressed ascertainment bias. it is important to follow up the reasons why the estimated % (as of august which involved an underestimation bias due to time delay from illness onset to death) in realtime has been much lower than the published estimate of . % among a portion of cases. given the potential presence of asymptomatic cases, addressing ascertainment error may be the key to appropriately capture the disease burden for the entire population. table summarizes key epidemiological parameters for evd. the transmission dynamics of ebola outbreaks in confined settings in central africa have been previously described using an seir epidemiological model [ ] with the goal of quantifying the effects of social distancing interventions. in this model, the time-dependent transmission rate parameter β(t) captures the effects of implementing basic public health interventions over time. for instance, once interventions are put in place τ days after the onset of the outbreak, the time-dependent transmission rate could be modeled to shift from a 'free course' baseline value β to a value β , where β < β . more realistically, one can assume that the full effect of interventions is not seen immediately but gradually takes hold in the population, as modeled in [ ] . in these models, the basic reproduction number, r , in a completely susceptible population and in the absence of control interventions is computed as the product of the mean transmission rate during the intervention-free course of the outbreak, β , and the mean infectious period, /γ . hence, r is given by: more detailed epidemiological data and information about the contributions of different settings to transmission could guide the design of more elaborate models that could be helpful to quantify the effects of more specific intervention strategies. legrand et al. [ ] developed a structured transmission model to describe ebola epidemics with contributions to the force of infection from the community, funerals and healthcare settings. the most distinctive feature of this model is that transmission during burial rituals is modeled by accounting for the duration of the burial and the intensity of transmission with infectious bodies. this model is comprised by six epidemiologically relevant states and thirteen parameters. the model was calibrated to data of the ebola outbreaks in the republic of congo in and uganda in by fitting three transmission rate parameters, one for each transmission setting and one parameter to quantify the effectiveness of interventions. the full model can be applied to the west african epidemic particularly for guinea, sierra leone and liberia where burial practices involve the touching of bodies of the deceased [ ] . but this feature is believed to be less influential in transmission in the context of nigeria where a limited outbreak developed. to illustrate the effects of control interventions during ebola outbreaks, here we only account for transmission in the community and in healthcare settings by adjusting baseline transmission rates, diagnostic rates and enhancement of infection-control measures (for example, strict use of protective equipment by healthcare workers and effective isolation of infectious individuals) (see for example, [ , , , , , ] ). in this simpler setting, the population is divided into five categories: susceptible individuals (s); exposed individuals (e); infectious and symptomatic individuals (i); hospitalized individuals (h); and removed individuals after recovery or diseaseinduced death (r). susceptible individuals infected through contact with infectious individuals (secondary cases) enter the latent period at rate β(t) (i + l(t) h) /n(t) where β(t) is the mean human-to-human transmission rate per day, l(t) quantifies the relative transmissibility of hospitalized patients compared to symptomatic patients in the community, and n (t) is the total population size at time t. thus, values of l(t) between and would reflect the effectiveness of hospital isolation measures that decrease ebola transmission probability below that seen in the community, and values above . denote increased transmission in the hospital relative to the community, potentially due to biological and/or epidemiological reasons (for example, exposure to body fluids). symptomatic infectious individuals i are hospitalized at the time-dependent average rate γ a (t) or recover without being hospitalized at the average rate γ i. individuals in the 'removed' class do not contribute to the transmission process. for simplicity, one can assume that the timedependent transmission rate β(t), relatively transmissibility of hospitalized patients, l(t), and the diagnostic rate γ a (t), remain constant values at β , l , and γ a prior to the implementation of comprehensive countermeasures. hence, in this model the basic reproduction number, r , is given by the following expression: in this equation, ( /(γ a + γ i ) is the mean infectious period of community cases, γ a /(γ a + γ i ) is the fraction of symptomatic cases that are hospitalized, and /γ r is the mean infectious period of hospitalized cases. this expression can be decomposed as the sum of the contributions of infectious individuals in the community and the hospital as follows: where r comm = β /(γ a + γ i ) and r hosp = β l ( /γ r )(γ a /(γ a + γ i )). importantly, the above components for the reproduction number underscore the fact that the actual reproduction number could vary across regions as a function of the local capacity public health context (for example, infection control practices and availability of personal protective equipment for health care workers) and any local cultural practices that may influence transmission infectious period . days (mean) [ ] serial interval . days (mean) [ ] generation time . days (mean) [ ] time from illness onset to death days (mean) [ , ] case fatality ratio % to % (sudan) [ ] % to % (zaire) (for example, funeral traditions). consequently, an outbreak may be very unlikely to unfold in developed countries simply as a result of baseline infection control measures in place (that is, r < ) whereas poor countries with extremely weak or absent public health systems may be unable to control an ebola outbreak (that is, r > ). this suggests that local socioeconomic and sociocultural conditions are key determinants of disease spread, particularly in the context of the transmission dynamics of evd. the impact of infection-control measures in health care settings is illustrated in figure for different initial values of baseline r . the combined effect of the effectiveness of isolation measures and the diagnostic rate of symptomatic individuals on r is given in figure . the natural reservoir hosts of the ebola virus have yet to be confirmed [ , ] , but laboratory studies point to fruit bats as the most likely culprit harboring the ebola virus in the natural habitat [ ] [ ] [ ] [ ] . ebola outbreaks among humans have been associated with direct exposure to fruit bats and mortality among other wild animals, which tend to succumb to the infection [ ] [ ] [ ] . epidemiological data support the notion that spillover events of ebola virus from a natural reservoir (that is, fruit bats) or an intermediate host, such as non-human primates, into human populations occur with a certain frequency (for example, [ , ] ), but only a small number of those introductions are ever correctly diagnosed and reported or successfully unfold human-to-human transmission chains that lead to outbreaks. this hinders our understanding of the frequency of spillover events as a function of time (for example, season) and its relationship with variation in climatological or socioeconomic variables. we note that two studies have associated the onset of ebola outbreaks with climatological variables [ , ] . specifically, pinzon et al. reported evidence that ebola outbreaks are correlated with drastic shifts from dry to wet conditions [ ] while a more recent study by ng et al. found lower temperature and higher absolute humidity associated with the onset of evd outbreaks during to [ ] . in the context of the ongoing ebola epidemic in west africa, a recent study suggests that people in sierra leone have been previously exposed to the ebola virus, but those introductions have not sparked major epidemics [ , ] . moreover, the ongoing epidemic may have been triggered by a single spillover event as suggested by limited epidemiological data indicating that chains of transmission of reported cases can be traced back to one or two individuals [ ] . this may be explained by the fact that table . the mean time from symptoms onset to diagnosis (γ a ) is assumed to be three days. the isolation effectiveness is given by *( -l ) where l is the relative infectiousness of infectious individuals in health care settings. baseline values of r are calibrated by adjusting the transmission rate β to achieve a given r . evd, ebola virus disease; r , basic reproduction number. three lines represent results for three baseline values of r : . , . and . . ebola introductions have historically tended to occur in remote, rural areas with sparse population structures characterized by higher disease extinction rates [ , ] . by contrast, the unprecedented size of the ongoing epidemic could have benefited from high population mobility across invisible borders, super spreading events [ ] and secondary transmissions linked to health care settings [ ] . figure illustrates the role of the size of spillover events (for example, the number of infectious cases initially introduced in the population) in triggering ebola epidemics in naive populations by showing that the probability that a major epidemic occurs rapidly increases as a function of the initial number of ebola cases. for instance, single-case introductions go extinct without developing into epidemics more than % of the time while five-case introductions lead to major epidemics more than % of the time. several factors hamper the timely identification of ebola outbreaks in africa. first, only a small number of ebola outbreaks have occurred in east and central africa since the first identified outbreak in relative to the regional burden of other endemic infectious diseases, such as malaria. moreover, some areas at risk of ebola have yet to experience ebola outbreaks, which severely limits community-level knowledge of the disease. for instance, the ongoing epidemic of evob is reportedly the first to occur in west africa [ ] . second, early symptoms of ebola virus disease tend to be nonspecific (for example, many cases are only febrile) [ ] , which increases the likelihood of misdiagnosing ebola with malaria or other locally endemic infectious diseases [ ] . unsuccessful treatment of febrile patients and/or the appearance of more specific symptoms during the course of the disease (for example, hemorrhagic manifestations) could increase the likelihood of an 'astute' public-health worker suspecting ebola or other viral hemorrhagic fever [ ] . third, lack of epidemiological surveillance systems and diagnostic testing in poor countries further exacerbates the delay in detecting outbreaks. consequently, the implementation of public health interventions may not start until case or death clusters start to be detected and investigated in the community by public health authorities. in general, the longer the delay in the implementation of control interventions, the higher the chances that the virus percolates from remote and sparsely populated areas into areas of high population density. the probability of observing major ebola outbreaks is highly sensitive to the timing of initiation of control interventions as illustrated in figure . figure the effects of isolation strategies and diagnostic rate on r . basic reproduction number as a function of the combined effect of the level of isolation effectiveness and the diagnostic rate. epidemiological mean parameter values for evd are shown in table . the mean time from symptoms onset to diagnosis (γ a ) is varied from one to three days. the isolation effectiveness is given by *( -l ) where l is the relative infectiousness of infectious individuals in health care settings. the baseline value of r is set at . . evd, ebola virus disease; r , basic reproduction number. this figure shows that a five-day delay is highly unlikely to result in major ebola outbreaks. by contrast, more significant delays exceeding two weeks are likely to lead to ebola outbreaks ( figure ) . basic infection control measures in health care settings are essential to avoid further spread of the disease to other patients, health care workers and visitors. unfortunately, under-resourced african regions not only suffer from a critically low ratio of health-care workers to total population, but also lack essential personal protective equipment (ppe) (for example, gloves, gowns, face masks) to practice standard infection control measures. they also often lack the infrastructure and local capacity necessary to effectively trace contacts and isolate infectious individuals. consequently, it is not surprising that ebola outbreaks have been amplified in health care settings [ , , , ] including the ongoing epidemic in west africa. indeed, a total of health care workers have developed evd as of september [ ] . fortunately, past experience also indicates that early and drastic enhancement of infection control measures in health care settings can substantially reduce the size and geographic scope of ebola outbreaks [ , ] . for instance, figure shows that the rising trend in infected health care workers during the ebola outbreak in congo rapidly declined following the implementation of control interventions. the combined impact of the rate of diagnosing symptomatic cases and the relative infectiousness of hospitalized cases on the probability of observing major epidemics is illustrated in figure . socio-cultural factors have not only contributed significantly to ebola spread, but have also complicated the implementation of control interventions. specifically, cultural practices involving touching the body of the deceased naturally (and greatly) contribute to the dissemination of the ebola virus [ ] . in particular, the potential for transmission to neighboring and distant areas by exposed funeral attendants could facilitate the development of major epidemics [ , ] . moreover, the lack of prior experience or knowledge of the disease can lead communities to deny its existence and to associate illness with witchcraft or conspiracy theories presumably created by governments to gain control of populations or attract resources from the international community [ , ] . for instance, during the ongoing size of spillover event (initial cases) probability of no major outbreak (%) figure the effects of size of spillover event on the likelihood of observing an outbreak. probability that no major outbreak unfolds as a function of the initial number of infectious cases introduced into the population. epidemiological parameter values for evd are shown in table . the mean time from symptoms onset to diagnosis (γ a ) is set at three days. the isolation effectiveness is set at (that is, l . = ). population size n is set at , . the baseline value of r is set at . . the curve corresponds to the mean of the results obtained from model simulations. evd, ebola virus disease; r , basic reproduction number. epidemic in west africa, a group of individuals looted equipment and potentially contaminated materials in an isolation facility in a quarantined neighborhood [ ] . finally, the stigma carried by ebola survivors and family members of ebola victims could exacerbate disease spread. in particular, uninformed families tend to hide relatives and friends infected with ebola to avoid being shunned by their own communities, which enhances transmission rates [ ] . the problem is compounded by the high case fatality ratio of evd whereby misinformed communities tend to associate case isolation with a death sentence. the ongoing epidemic in west africa offers a unique opportunity to improve our current understanding of the transmission characteristics of evd in humans, including the duration of immunity among ebola survivors and the case fatality ratio in the presence or absence of supportive therapy [ , ] , as well as the effectiveness of various control interventions [ ] . for this purpose, there is a critical need to collect detailed epidemiological data in real-time during the ongoing epidemic through the establishment of efficient epidemiological surveillance systems in the affected areas. in addition, we cannot overemphasize the importance of collecting data relating to population behaviors influencing disease spread and control and how these have changed over time. it would also be important to record the level of adoption of preventive and social distancing measures in the community and adherence to infection control measures in health care settings. detailed data regarding control interventions would also be critical to assess their effectiveness in reducing secondary transmissions including information on the changing numbers of isolation and treatment centers, healthcare workers, intensity of contact tracing activities and awareness campaigns in the community. table . the mean time from symptoms onset to diagnosis (γ a ) is set at three days. the relative infectiousness of hospitalized cases is given by l . population size n is set at , . the baseline value of r is set at . by adjusting the transmission rate. after the start of interventions, the transmission rate is reduced by % and the relative infectiousness of hospitalized individuals is reduced by % (that is, l = , l = . ). the curves shown correspond to the mean of the results obtained from model simulations. evd, ebola virus disease; r , basic reproduction number. there is a scarcity of empirical studies quantifying transmission and the effects of control interventions implemented during past ebola outbreaks [ , ] . further work is also needed to quantify the effects of various interventions put in place during the ongoing epidemic in west africa. specifically, careful mathematical and statistical modeling studies could help ascertain the role of social distancing interventions (for example, school closures and cancellation of mass gathering events), infection control measures in health care settings (for example, isolation and other infection control measures among health care workers) and contact tracing and quarantine efforts [ , , , [ ] [ ] [ ] [ ] [ ] . in addition to individual epidemiological data, the timing of such interventions should be recorded along with the scale and extent of interventions (for example, closure of class rooms or entire schools). intervention studies could reveal, for instance, whether effective infection control mechanisms in hospital settings could suffice to bring an epidemic under control or whether a combination of control strategies would be critical to ensure epidemic control (for example, r < ). while a significant number of computational models have been developed to inform preparedness plans against pandemic influenza [ ] [ ] [ ] , comprehensive modeling studies to examine the spread and control of viral hemorrhagic fevers, including ebola, in the context of the highly heterogeneous economic reality of african countries are yet to be developed. the shortage of modeling efforts could be explained by the fact that large ebola outbreaks affecting large population settings were largely unexpected until now. to start filling this gap, datasets comprising detailed demographic, socio-economic, contact rates and population mobility estimates in the region (for example, commuting networks, air traffic) need to be integrated. given that the disease is highly fatal, dynamic features of contact and mobility should also be closely investigated. modeling studies with local demographic characteristics and human movement could be useful not only to assess the likelihood of major epidemics and carry out sensible projections on epidemic outcomes, but also to guide control efforts in the field, such as the estimation of the number, size and location of isolation facilities, the number of health workers and staff and essential supplies that would be needed to respond to a particular outbreak scenario as well as to quantify the effects of potential quarantine efforts in certain areas, border closures and air travel restrictions. proven treatments or vaccines against ebola are still not available. hence, our current working toolbox available to control the spread of ebola still hinges on supportive medical care to increase the survival of those infected and basic non-pharmaceutical public health measures [ ] to prevent transmission, namely: ) infection control measures including standard precautions in health care settings; ) rapid contact tracing and isolation of infectious individuals; and ) social distancing interventions in the community which may include the dissemination of awareness campaigns to inform the population on how to avoid contracting the disease, quarantining individuals potentially exposed to infectious individuals and restricting the movement of communities exhibiting local transmission to prevent onward transmission. these actions must be conducted in close collaboration with local community leaders to effectively reach the population at large. with the ongoing epidemic in west africa, the development of treatments and vaccines against ebola is accelerating [ , ] . for instance, emergency use of a trickle of doses of an experimental drug with unknown efficacy or safety record in humans has been initiated during the outbreak [ ] . recent experiments in monkeys provide promising evidence that this experimental drug could have a significant impact on mortality burden during ebola outbreaks [ ] . furthermore, a promising bivalent ebola vaccine against the zaire and sudan ebola strains is entering human safety trials in september [ ] with an initial goal of building a stockpile of , doses by november . nevertheless, apart from pharmaceutical effects on the prognosis of infection, we have yet to examine how medication changes the transmission dynamics. hence, careful studies could be useful for assessing the impacts of treatment on contact, transmission and diagnosis as well as on the disease burden [ ] . if an ebola vaccine is developed successfully, one could assess the effectiveness of pre-emptive and reactive treatment and vaccination plans in the context of limited stockpiles. finally, it is worth noting that our efforts to prepare against current and future infectious disease threats should also include potential deliberate attempts to trigger epidemics, which are largely unexpected events figure the effects of size of baseline isolation effectiveness and diagnostic rate on the likelihood of observing an outbreak. probability that no major epidemic unfolds as a function of isolation effectiveness and time from symptoms onset to diagnosis. epidemiological parameter values for evd are shown in table . the mean time from symptoms onset to diagnosis (γ a ) is set at one, two and three days. the relative infectiousness of hospitalized cases (l ) is varied from to . population size n is set at , . the baseline value of r is set at . by adjusting the transmission rate. the curves shown correspond to the mean of the results obtained from model simulations. evd, ebola virus disease; r , basic reproduction number. but could pose high impact on public health and global economic activities. emergence of zaire ebola virus disease in guinea 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take full advantage of: key: cord- -etkhrgxp authors: meremikwu, martin; ezedinachi, emmanuel; ehiri, john e. title: malaria in women and children date: - - journal: maternal and child health doi: . /b _ sha: doc_id: cord_uid: etkhrgxp after reading this chapter and answering the discussion questions that follow, you should be able to: explain the global burden of malaria, discuss its clinical manifestations, and appraise its health impact on women and children. analyze the mechanisms and consequences of malaria and hiv co-infection and discuss current treatment, control and prevention strategies. describe the challenges posed by vector resistance to insecticides, parasite resistance to antimalarials, climate change, wars/conflicts, and hiv/aids to malaria control and prevention efforts. evaluate social, cultural, and economic limitations of community-based programs for malaria control and prevention. malaria is caused by plasmodium, a protozoan parasite transmitted through the bite of infected female anopheline mosquitoes. the four species of plasmodium known to cause malaria in humans are p. falciparum, p. malariae, p. ovale, and p. vivax. plasmodium falciparum is the most virulent of these species and is responsible for most cases of malaria infections and malaria deaths in sub-saharan africa. plasmodium vivax, the second most common species of the malaria parasite, is more prevalent in asia and is rarely associated with acute complications of malaria or fatality. box . presents definitions of some of the most commonly used terms in malaria epidemiology. figure . shows the global distribution of malaria transmission risk. malaria transmission occurs in africa, asia, and the americas, but sub-saharan africa bears over % of the global burden of malaria mortality (ehiri et al. ) . malaria is still a major public health problem in parts of southeast asia with foci of high p. falciparum transmission and high incidence of multidrug resistance. more than species of anopheles mosquitoes transmit malaria. anopheles gambiae, which is the most efficient and resilient vector, is the predominant vector in most parts of tropical africa, where it finds adequate rainfall, temperature, and humidity to support its breeding. figure . provides an illustration of the life cycle of plasmodium in the human and in the mosquito vector. spleen rates (percentage of the population with palpably enlarged spleen at any given time) and parasite rates (percentage of the population with malaria parasites in peripheral blood film at any given time) are traditionally used as malariometric indices to determine whether or not malaria is endemic in a given area. the entomologic inoculation rate (eir) is believed to be a better measure of malaria transmission and risk of infection than spleen or parasite rates. however, it is more difficult to assess. eir is the product of human biting rates (the number of mosquitoes biting a person over a given period of time) and the sporozoite rate (the proportion of vectors with sporozoites in the salivary glands) ). rupture and release the sporozoites, which then migrate into the mosquito's salivary glands, ready for injection into the human host. parasitemia: the presence of parasites in the blood. the term can also be used to express the quantity of parasites in the blood (e.g., 'a parasitemia of %''). phagocyte: a type of white blood cell that can engulf and destroy foreign organisms, cells and particles. platelets: small, irregularly-shaped bodies in the blood that contain granules. these cells are important components of the blood coagulation (clotting) system. presumptive treatment: treatment of clinically suspected cases without, or prior to, results from confirmatory laboratory tests. protozoan: single-celled organism that can perform all necessary functions of metabolism and reproduction. some protozoa are free-living, while others, including malaria parasites, parasitize other organisms for their nutrients and life cycle. residual insecticide spraying: treatment of houses by spraying insecticides that have residual efficacy (i.e., that continue to affect mosquitoes for several months). residual insecticide spraying aims to kills mosquitoes when they come to rest on the walls, usually after a blood meal. resistance: the ability of an organism to develop strains that are impervious to specific threats to their existence. schizogony: asexual reproductive stage of malaria parasites. in red blood cells, schizogony entails development of a single trophozoite into numerous merozoites. a similar process happens in infected liver cells. schizont: a developmental form of the malaria parasite that contains many merozoites. schizonts are seen in the liver-stage and blood-stage parasites. sequelae: morbid conditions following as a consequence of a disease. severe malaria: occurs when p. falciparum infections (often in persons who have no immunity to malaria or whose immunity has decreased) are complicated by serious organ failures or abnormalities in the patient's blood or metabolism, resulting in cerebral malaria, with abnormal behavior, impairment of consciousness, seizures, coma, or other neurologic abnormalities, severe anemia due to hemolysis (destruction of the red blood cells), hemoglobinuria (hemoglobin in the urine) due to hemolysis, pulmonary edema (fluid buildup in the lungs) or acute respiratory distress syndrome (ards), which may occur even after the parasite counts have decreased in response to treatment, abnormalities in blood coagulation and thrombocytopenia (decrease in blood platelets), cardiovascular collapse, shock, acute kidney failure, hyperparasitemia, where more than % of the red blood cells are infected by malaria parasites, metabolic acidosis (excessive acidity in the blood and tissue fluids), often in association with hypoglycemia (low blood glucose). splenomegaly: enlargement of the spleen, found in some malaria patients. splenomegaly can be used to measure malaria endemicity during surveys (e.g., in communities or in school children). sporozoite rate: the proportion of female anopheline mosquitoes of a particular species that have sporozoites in their salivary glands (as seen by dissection), or that are positive in immunologic tests to detect sporozoite antigens. sporozoite: a stage in the life cycle of the malaria parasite. sporozoites are produced in the mosquito and migrate to the mosquito's salivary glands. they can be inoculated into a human host when the mosquito takes a blood meal on the human. in the human, the sporozoites enter liver cells malaria transmission can be perennial (occurring throughout the year), high, intense, and/or stable, low, unstable, and seasonal. high stable transmission of mostly p. falciparum associated with high incidence of severe illness and mortality among preschool children is the predominant pattern of malaria in most of sub-saharan africa. the average malaria incidence rates across several parts of africa with high transmission are estimated at . per persons per year, . per persons per year, and . persons per year for age groups < years, - years, and ! years, respectively (snow et al. ) . in low transmission areas, incidence rates of malaria are much lower, and differ only marginally between the young and older age groups. malaria epidemics are more likely to occur in areas with seasonal and unstable transmission. figure . illustrates the various pathways by which malaria contributes to poverty, under-development, malnutrition, and maternal and infant mortality. some - million malaria episodes occur annually. children under years of age in sub-saharan africa and women who are pregnant for the first or second time bear the heaviest burden of malaria morbidity and mortality. an estimated million episodes of clinical malaria occur in young sub-saharan african children annually. about million cases are cerebral malaria, million cases are severe anemia, and approximately million result in death. estimates of malaria mortality show wide variation. a review of the literature on this subject shows that the number of deaths due to malaria in african children aged less than years where they develop into the next stage of the malaria parasite life cycle (the liver stage or exoerythrocytic stage). stable malaria: a situation where the rate of malaria transmission is high without any marked fluctuation over years though seasonal fluctuations occur. strain: a genetic variant within a species. sulfadoxine-pyrimethamine: a drug used against malaria. trophozoite: a developmental form during the blood stage of malaria parasites. after merozoites have invaded the red blood cell, they develop into trophozoites (sometimes, early trophozoites are called ''rings'' or ''ring stage parasites''); trophozoites develop into schizonts. uncomplicated malaria: the classical, (but rarely observed) uncomplicated malaria attack that lasts - hours. it consists of a cold stage (sensation of cold, shivering), a hot stage (fever, headaches, vomiting, seizures in young children), and finally a sweating stage (sweats, return to normal temperature, tiredness). the classical (but infrequently observed) uncomplicated malaria attacks occur every second day with the ''tertian'' parasites (p. falciparum, p. vivax, and p. ovale) and every third day with the ''quartan'' parasite (p. malariae). more commonly, the patient presents with a combination of symptoms that include fever, chills, sweats, headaches, nausea and vomiting, body aches, general malaise. unstable malaria: a situation where the rate of malaria transmission changes from year to year. vaccine: a preparation that stimulates an immune response that can prevent an infection or create resistance to an infection. vector: an organism (e.g., anopheles mosquitoes) that transmits an infectious agent (e.g. malaria parasites) from one host to the other (e.g., humans). source: malaria glossary -centers for disease control and prevention http://www.cdc.gov/malaria/glossary.htm could be between , and , , annually (breman et al. ) . about , of those that survive develop sequelae from neurological complications of p. falciparum malaria. pregnant women are more vulnerable to adverse consequences of malaria than other adults. an estimated million infections occur in pregnant women annually, resulting in , cases of severe maternal anemia and , low birth weight babies (greenwood et al. ) . in malaria-endemic countries of africa, up to % of all outpatient clinic visits and between and % of all hospital admissions are due to malaria (who ) . although the incidence of uncomplicated malaria is lower in adolescents aged - years than younger school aged and preschool children, the burden of malaria in this age group could be substantial in areas with high and stable transmission. a recent review of the epidemiology and pattern of malaria in adolescents estimates the clinical malaria rate in african adolescents aged - years to be . attacks per adolescent per year (lalloo et al. ) . results of analyses based on rainfall and temperature data and geographic information system (gis) population databases in areas with high and stable malaria transmission put the yearly estimate of the number of malaria attacks in children aged - years, - years, and - years at . million, . million, and . million, respectively. the clinical pattern and deleterious consequences of malaria infection vary, depending on the level of acquired malaria immunity of the individual and the pattern of malaria transmission in an area. in areas with high and stable malaria transmission, resident adults and older children acquire sufficient partial immunity to reduce the risk of severe and fatal malaria but younger children and pregnant women remain vulnerable to severe and complicated malaria. malaria infection may be asymptomatic or symptomatic. the majority of malaria infections in areas where transmission is high and stable are asymptomatic. even when malaria infection is asymptomatic, it is believed that the high prevalence of low parasitemic and asymptomatic malaria infections contribute to the high prevalence of mild and moderate childhood anemia. in these settings, young children who are less immune to the disease are more likely to have clinical malaria following infections. the common symptoms of uncomplicated malaria are fever, poor appetite, aches, malaise, nausea, and vomiting. uncomplicated malaria is the most common reason for which children and adults use the health service in sub-saharan africa. uncomplicated malaria accounts for about and % of outpatient attendance and hospital admissions, respectively. malaria is also a leading cause of absenteeism and poor performance at work and school. uncomplicated malaria is rarely fatal when treated promptly with effective antimalarial drugs. in preschool children, delayed treatment or failure to treat uncomplicated falciparum malaria could lead to rapid disease progression to severe and potentially fatal malaria within a period often less than h from onset of illness. plasmodium falciparum causes severe malaria through complex processes that involve immunological substances known as cytokines (john et al. ) leading to impaired perfusion and damage to tissues and organs. these pathological changes lead to clinical and laboratory features that are characteristic of severe and complicated malaria, namely cerebral malaria that is associated with impaired consciousness, repeated convulsions, severe malarial anemia, hypoglycemia, respiratory distress, and circulatory collapse. children that die from malaria would have one or more of these signs. the risk of death is higher in patients with multiple signs (schellenberg et al. ) . case fatality rate of complicated falciparum malaria is - %. about - % of those that survive cerebral malaria have residual neurological problems such as dyskinesia, cortical blindness, seizures, and learning disorders (meremikwu et al. ). most of these disorders are resolved within months but about % persist for longer periods of time causing varying degrees of disability and impaired intellectual development (murphy and breman ) . anemia childhood anemia in low-income countries is caused by multiple factors including poor nutrition, malaria, intestinal parasites, hiv/aids, and inherited blood disorders (e.g., glucose- -phosphate dehydrogenase (g- -p-d) deficiency and sickle cell disease). in areas with high transmission, malaria is the leading etiological factor for anemia. the processes by which malaria causes anemia are not yet fully understood; however, malaria-related toxins and immunological factors are believed to cause increased hemolysis, increased splenic clearance of infected and uninfected red blood cells, and impaired production of red blood cells in the bone marrow (dyserythropoeisis). in areas of africa with high malaria transmission, surveys have shown high prevalence rates of anemia (hemoglobin < g/dl) among infants and children under years of age (as high as - % in several areas). most of these cases of anemia go unnoticed and untreated because they are mild and cause no symptoms. although children with mild and chronic anemia do not feel distinct symptoms of illness, mild anemia is associated with chronic debility. it can cause such adverse effects as reduced activity and impaired cognition and learning. these chronic effects of malarial anemia in concert with malaria-related school absenteeism and neurological complications from cerebral malaria, adversely affect childhood development and education in sub-saharan africa (mung'ala- odera et al. ) . severe anemia (hemoglobin < g/dl) is a common acute complication of falciparum malaria. it is responsible for high case fatality and often follows massive hemolysis from a single episode of falciparum malaria. repeated episodes or poorly treated episodes of uncomplicated malaria are fairly common pathways to severe anemia in infants and young children who are residents of areas with high and stable malaria transmission. in many communities in africa where there are high levels of p. falciparum resistance to chloroquine and sulphadoxine-pyrimethamine, the continued use of failed drugs has resulted in an increase in the incidence of severe malarial anemia. case fatality from severe malarial anemia varies from % in treated cases to over % when associated with other complications of falciparum malaria, especially respiratory distress and deep coma (john et al. ) . many more children with life-threatening severe malaria anemia do not have access to formal health care where adequate treatment and blood transfusion are possible. this indicates that overall case fatality from severe malarial anemia is likely to be much higher than reported. blood transfusion for severe malaria-related anemia accounts for a remarkable proportion of new pediatric hiv infections in africa (crawley and nahlen ) . given the multifactorial nature of the etiology of childhood anemia, interventions to prevent or treat it should involve several approaches. for instance, mass de-worming of children and micronutrient supplementation programs are interventions that have the potential to reduce the burden of childhood anemia in developing countries (briand et al. ). insecticide-treated nets, chemoprophylaxis, and intermittent preventive treatment are malariaspecific interventions that have been shown to significantly reduce morbidity and mortality from malaria-related anemia (briand et al. ). malaria is a leading cause of hemolytic and vasoocclusive crisis in african children and adolescents with sickle cell disease. sickle cell disease is the most common inherited hematological disease among africans. the prevalence of the sickle cell trait (heterozygous inheritance on an abnormal and a normal gene) can be as high as - % in some parts of africa with - % affected by the disorder (inheritance of a pair of abnormal gene). a paradoxical relationship exists between the sickle cell gene and malaria. the sickle gene is believed to confer some measure of protection against malaria to those with the trait (one abnormal gene); however, it is a leading cause of morbidity and mortality among those with the disorder (two abnormal genes). two other notable chronic effects of malaria in children and adolescents include malarial nephropathy and hyperactive malarial splenomegaly. malarial nephropathy results from gradual damage of kidney cells by an antigen-antibody complex that is caused by previous malarial infection. there are no reliable data on the magnitude of renal morbidity which are caused by this malaria-induced pathology. however, it is believed that the problem is substantial. hyperactive malarial splenomegaly (also called tropical splenomegaly syndrome) is another chronic, but less common presentation of malaria among children and adolescents in the tropics. this condition is characterized by an enlarged spleen, high levels of malarial immunoglobulin (igm), sinusoidal lymphocyte infiltration, and resolution with prolonged antimalarial therapy. plasmodium falciparum and p. vivax are known to cause significant effects on maternal and child health during pregnancy. plasmodium falciparum exerts the worst effects among all the species of malaria parasite. in sub-saharan africa, the transmission of p. falciparum is predominantly high and intense with high levels of morbidity and mortality among infants and pregnant women. the major consequences of malaria infection during pregnancy are clinical episodes of malaria, maternal anemia (hemoglobin concentration < g/dl), or severe anemia (hemoglobin concentration < g/dl), placental parasitemia, intrauterine growth retardation, preterm births, and low birth weight. table . shows the contribution of malaria to adverse maternal and child health outcomes. malaria in pregnancy is estimated to account for up to % of cases of severe anemia, - % of babies born with low birth weight, and - % of neonatal and infant deaths are due to malariainduced lbw (greenwood et al. ) . the effect of malaria in pregnancy is influenced by the level of malaria immunity acquired by the mother before pregnancy. this depends on the pattern and intensity of malaria transmission. the parasite species, the number of previous pregnancies, and the presence of human immunodeficiency virus (hiv) also remarkably impact malaria morbidity and mortality during pregnancy. in areas with high and stable malaria transmission, the prevalence and intensity of p. falciparum parasitemia are higher in pregnant women than in non-pregnant women. the majority of malaria infections in pregnant women living in high transmission areas are asymptomatic because of immunity acquired from repeated exposure to malaria before pregnancy. the adverse consequences of malaria during pregnancy in areas of high transmission are anemia, placental malaria, intrauterine growth retardation, and low birth weight. in areas of low or unstable transmission, acquired malaria immunity is low in all age groups. pregnant women with malaria in this area are vulnerable to severe manifestation of the disease including cerebral malaria. the evidence that malaria and hiv co-infection increases morbidity associated with both conditions has been confirmed by several studies (snow et al. ) . impact of the complex interaction between malaria and hiv appears to be most profound in pregnancy and children. hiv infection in pregnancy is known to increase the risk of malaria infection (population attributable risk (par), - %), maternal anemia (par, - %), and low birth weight (par, - %) (steketee et al. ) . the mechanism by which hiv infection alters malaria morbidity is not well understood. it is believed to be due to systemic and placental immunologic changes that are induced by hiv. in a rwandan cohort study that included hiv-positive and hiv-negative participants, the incidence of malaria was almost twice as high in the hiv-positive group ( . per women-months) than in the hiv-negative group ( . per women-months) (ladner et al. ) . a review of studies on malaria and hiv coinfection shows that hiv infection in pregnancy significantly increases the risk of peripheral and placental malaria parasitemia. malaria in pregnant women infected by hiv is more likely to cause higher parasite densities, febrile illness, severe anemia, and low birth weight than malaria in those without hiv infection (snow et al. ) . in the absence of hiv infection, the deleterious effects of malaria in pregnancy, notably low birth weight and maternal anemia, were significantly worse in those pregnant for the first or second time than in those who have been pregnant for three or more times (ter kuile et al. ). with hiv co-infection, the pattern of malaria morbidity is similar across all categories of pregnant women (ter kuile et al. ) . a review of studies in areas of sub-saharan africa with high and stable malaria transmission shows that hiv- infection and clinically diagnosed aids increased the incidence of malaria . -fold and fold, respectively (korenromp et al. ) . in these high transmission areas, hiv- infection in children increased hospitalization for malaria and malaria case fatality -fold and . -fold, respectively. at the same time in low transmission areas, the incidence of severe malaria and malaria case fatality increased . -fold and . -fold, respectively. the effect of hiv on malaria incidence is worse in hiv patients with lower cd counts. in adult patients living in high malaria transmission areas, hiv increased the malaria incidence . -fold, -fold, and -fold when cd counts were ! , - , and < /ml, respectively (korenromp et al. ) . the increase in morbidity and mortality associated with hiv and malaria co-infection, both of which are highly prevalent in most parts of sub-saharan africa, calls for more focused research in this area and for integration of service delivery. one way of achieving greater impact is the integration of malaria and hiv/aids control activities within maternal and child health programs. achieving high coverage of insecticide-treated bed nets (itns) use and prompt access to treatment with artemisininbased combination treatments (acts) would contribute to the reduction in the morbidity and source: who-afro ( ) mortality attributable to hiv co-infection with malaria in high transmission areas. in areas of low intensity and unstable transmission, widespread and effective indoor residual spraying combined with effective treatment using artemisinin-based combination therapy (act) is cost-effective and has been shown to significantly reduce malaria morbidity and mortality (snow et al. ) . the following section provides a summary of the three-pronged approach to malaria control recommended by the world health organization's malaria control program (who ) . indoor residual spraying, environmental management to eliminate mosquito breeding sites, and use of larvicides are known to be effective in reducing malaria when used in combination. aerial and terrestrial spraying of insecticides is used in parts of south america and asia to control malaria. this intervention strategy is cost intensive and low in effectiveness. it is therefore, not an appropriate control measure for sub-saharan africa given the complex terrains and weak economies of these malaria-endemic countries. insecticide-treated bed nets (itn) have been shown by studies in a variety of settings to be effective in reducing the incidence of clinical malaria by half and fatalities by about a third (snow et al. ) . population coverage for itn in most parts of africa remains low (< %). the low re-treatment rate at the expiration of the usual period of potency ( months) was a major challenge, even in areas that achieved high itn coverage. the development and widespread deployment of factory-treated nets with lifelong protective effects (llins) has eliminated the need to re-treat insecticide-treated nets. the persisting challenge is how to improve access to itns by poor women and children who need to be protected from severe and fatal malaria. the global fund for tuberculosis aids and malaria is providing funding to countries in endemic low and middleincome countries to support this intervention. a systematic review of randomized controlled trials conducted in africa showed that itns used in pregnancy compared to ''no nets'' significantly reduced the risk of placental malaria in all pregnancies (relative risk . , % confidence interval . - . ). the review also showed that itns significantly reduced the risk of low birth weight (relative risk . , % ci . - . ) and fetal loss in the first to fourth pregnancy (relative risk . , % ci . - . ). however, this was not the case in women with more than four previous pregnancies (gamble et al. ) . in a large randomized controlled trial in communities with intense and perennial malaria transmission, itn use significantly reduced the risk of severe malaria anemia, placental malaria, and low birth weight among those pregnant for the first to fourth time, but not in those pregnant for five or more times (ter kuile et al. ) . the adherence to itn use in pregnancy was shown to be significantly lower in adolescent and young women, who are most at risk for the deleterious consequences of malaria (browne et al. ). this observation and the known risk of higher malaria morbidity associated with first pregnancy (involving mostly adolescent women) make it necessary to specially target this age group for intervention. in summary, the limited risk assessments undertaken so far with regard to the safety of itns suggest that they are relatively safe. however, a cautionary note regarding the need to monitor the health effects of long-term exposure to insecticides in resourcepoor settings has been presented by ehiri et al. ( ) . although the use of mosquito nets is not new, mass use of itns as a population-based malaria control tool is a relatively new technology, and some uncertainty remains about the potential for problems as their use expands (hirsch et al. ) . prompt treatment of malaria with efficacious and affordable antimalarials is a key component of the global malaria control strategy. the emergence and spread of malaria parasites (especially p. falciparum) resistant to the commonly used affordable antimalarials, like chloroquine (cq) and sulphadoxine-pyrimethamine (sp), hampered malaria control in africa and has deteriorated the malaria situation on the continent. the emergence of these multidrug-resistant malaria parasites led to the adoption of combination treatment options as the gold standards for treating malaria. the who ( ) recommends that the ideal drug combination should contain two drugs that are individually effective against the blood stages of the parasite and use completely different mechanisms to kill the parasite. based on results from several well-conducted studies, the who recommended that combinations that contain artemisinin (a drug derived from the chinese plant a. annua l.) or its derivatives and another structurally unrelated and more slowly acting drug provide the best therapeutic effects and are safe. this category of drug combinations is collectively known as artemisinin-based combination treatments (acts). the advantages of artemisinin-based combination treatments (acts) have been outlined by the who to include the following (who monotherapy with artemisinin derivatives requires multiple doses given for days due to their characteristic short half-life. the other key advantage of artemisinin containing combination treatments (acts) is the shortened duration of treatment ( days), with expected improvement in patient compliance to treatment. if the partner drug is effective, acts ensure prompt recovery and high cure rates. they are generally well tolerated. replacing the older failing or failed monotherapies with effective drugs will reduce morbidity and mortality. the challenge, however, remains how to deliver these drugs to the people that need them. implementation of this policy would put significant cost burdens on national malaria control programs. however, the costs of failing to change, such as an increase in childhood deaths and high cost of hospitalization, make it a necessary and cost-effective program. affordability of acts is a major issue affecting their effective deployment in malaria control programs in sub-saharan africa. acts are generally too expensive for most people in low-income settings where malaria is endemic. while drugs such as chloroquine and sulphadoxine-pyrimethamine (sp), which were previously used for treating uncomplicated malaria, cost only a few us cents, the new acts cost about $ -$ . and even higher when not discounted. international efforts to address this issue championed by the roll back malaria (rbm) partnership have yielded some positive results, especially through the global fund for tuberculosis, aids and malaria (brundtland ) . however, huge gaps still exist. unfortunately access to prompt treatment with effective antimalarial drugs remains very low in many sub-saharan countries, leading to the persistence of high malaria mortality rates. the reasons for poor access to treatment are mainly due to weak health systems that are poorly patronized by the populace and a lack of funds to procure and effectively deliver expensive artemisinin-based combination treatment (acts). acts are necessary since high levels of p. falciparum resistance have rendered chloroquine and sulphadoxine-pyrimethamine ineffective. these were the cheaper treatment options that have been used for several decades. most children who become ill with malaria in these areas are usually treated at home with poor quality or inappropriately administered medicines that were purchased from local, often untrained drug vendors. antimalarial treatment policies, adopted by each country, depend on the epidemiology of the disease, including patterns of transmission, drug resistance, political environment, and economic context. the adoption of acts in sub-saharan africa was preceded by establishment of local evidence on the effectiveness of existing first-and second-line drugs which have demonstrated consistently high treatment failure rates due to parasite resistance (snow et al. ) . the who ( ) also recommends that countries developing antimalarial treatment policies should strive to ensure that all populations at risk have access to prompt treatment with safe, good quality, effective, affordable, and acceptable antimalarial drugs and there is rational use of antimalarial drugs in order to prevent the emergence and spread of drug resistance induced by unduly high selection drug pressure on mutant malaria parasites. delivery of effective and safe antimalarial treatment to poor rural populations and those in difficult, hard-to-reach settings poses enormous challenges to malaria control programs in africa. in many endemic countries, the formal health system is weak. often the health system consists of a few ill-equipped health facilities run by inadequately trained and/or poorly motivated health personnel. the proportion of the people that access these services is so low that successful malaria treatment programs in africa would be impossible without community-based delivery mechanisms including adequately trained and equipped informal community-based providers and caregivers who provide treatment and preventive services as close as possible to where people live and work. delivering community health care such as malaria treatment services through primary healthcare centers has long been identified a big challenge by jeffery ( ) as summarized in box . . a careful appraisal of these factors in the context of the current situation of malaria control efforts in most endemic countries in sub-saharan africa shows situations that are as pertinent today as they were over two decades ago when they were highlighted by jeffery ( ) . home management of malaria (hmm), the strategy currently recommended by the who (mendie et al. ) as an effective community delivery mechanism for antimalarial treatment, is likely to address some of the limitations highlighted in box . . the hmm strategy entails educating community health workers, volunteers, mothers, and caregivers to recognize symptoms of malaria and treat with appropriate antimalarial drugs (mendie et al. ) . its goal is to ensure early recognition and prompt and appropriate response to malarial illness in under- children in the home and community by enabling health workers, mothers, and caregivers to recognize malarial illness early and take appropriate action. the who hmm strategy consists of four strategic components: . ensure access to effective and good-quality antimalarial drugs (preferably pre-packed) at community level. . ensure that community drug or service providers (e.g., patent medicine vendors, volunteer village health workers, community health extension workers) have necessary skills and knowledge to manage malaria. limitation of outreach capacity to geographically remote areas, and particularly to nomadic populations inability to make efficient use of community resources (both human and material) difficulty in achieving full community acceptance of chemotherapy insufficient training of local health workers lack of understanding of health problems and their solutions potential ineffectiveness of the curative drug or drug dosage used, usually through the emergence of parasite resistance to the drug undesirable side-effects of the drug source: jeffery ( ) . ensure an effective communication strategy to enable caregivers to recognize malarial illness early and take appropriate action. . ensure good mechanisms for supervision, monitoring, and communication activities. as shown in chapter , integrated management of childhood illness (community imci) also addresses both preventive and curative aspects of malaria control by seeking to improve community and family practices. giving prophylactic antimalarial drugs to prevent malaria is a routine practice for non-immune persons visiting malaria-endemic areas. malaria prophylaxis refers to daily or weekly administration of antimalarial drugs at a dose that is usually smaller than the therapeutic doses with a view to preventing clinical malaria. intermittent preventive treatment (ipt) refers to full therapeutic doses of an antimalarial given at specified time points to presumptively cure asymptomatic malaria and prevent clinical malaria or such other adverse consequences as anemia or placental malaria. usually, sulphadoxine-pyrimethamine (sp) is used for ipt as it requires a single dose and has a long half-life. the rationale is that intermittent treatment is likely to have fewer adverse events than prophylaxis because it is taken less often, and it is easier to deliver through clinics, reducing poor adherence with self-administration. chloroquine was the most widely used drug for malaria prophylaxis in pregnancy. the high prevalence of resistant strains, and the fact that most women adhered poorly to the weekly regimen required to achieve beneficial effects, rendered chloroquine chemoprophylaxis ineffective for malaria control in pregnancy. meta-analysis included in a cochrane systematic review of randomized controlled trials showed that ipt with sulphadoxine-pyrimethamine significantly reduced the risk of severe maternal anemia (relative risk . , % ci . - . ; , participants), placental malaria (relative risk . , % ci . - . ; , participants), and low birth weight (relative risk . , % ci . - . ; , participants) in women who were pregnant for the first or second time (garner and gu¨lmezoglu ) . ipt with sulphadoxine-pyrimethamine (sp) along with consistent use of itns are currently recommended as cost-effective and evidence-based interventions to prevent the deleterious effects of malaria in pregnancy and to reduce the associated maternal and infant morbidity and mortality. almost all the countries in africa with stable malaria transmission are already implementing intermittent preventive treatment in pregnancy (iptp) with sp (vallely et al. ). one of the key challenges with implementation of ipt is the high rate of parasite resistance to sp, and the lack of a safe and effective alternative to this antimalarial. in most parts of africa sp failure exceeds % and surveillance data on the trends are lacking in most cases. the effectiveness of this intervention in areas with high sp failure rates is yet to be adequately studied. the suggestion that two and three doses of sp, respectively, should be used in areas with sp resistance < and - % remains to be validated by robust research data. the continued use of ipt with sp in areas where sp resistance exceeds % also needs to be justified by research. there is also the problem of how to handle malaria co-infection with hiv in areas with high prevalence of hiv. a third dose of sp for ipt has been recommended for areas with high hiv prevalence but there is a need to monitor impact on such outcomes as severe anemia and low birth weight, and to study possible drug interactions in those receiving anti-retroviral treatment. in malaria-endemic communities, use of antimalarial drugs for prophylaxis or intermittent preventive treatment (ipt) is recommended for only pregnant women and special vulnerable groups such as children with sickle cell disease. several randomized controlled trials in malariaendemic communities have shown consistently that malaria prophylaxis and intermittent preventive treatment of infants (ipti) and young children are effective. a cochrane systematic review and meta-analysis (meremikwu et al. ) showed that receiving antimalarial drugs as prophylaxis or intermittent treatment reduced the incidence of clinical malaria episodes and severe anemia by about % in preschool children living in malaria-endemic communities. two main reasons are commonly given for discouraging widespread use of malaria chemoprophylaxis in preschool children in endemic communities. the first reason is the concern that giving malaria prophylaxis to infants and young children living in malaria-endemic areas will delay or minimize their chances to acquire protective immunity and result in a rebound rise in the incidence of severe morbidity and mortality later in life. the second reason is that poor compliance to weekly antimalarial drug prophylaxis could induce drug pressure and selection of mutant resistant strains of p. falciparum. intermittent preventive treatment of infants (ipti) with treatment doses of sp under direct observation at the time of routine immunization offers a better programmatic option, since it eliminates the problem of non-compliance and is expected to have little or no adverse effect or interfere with the child's ability to acquire malarial immunity. a major challenge to implementation of ipti, among others, is the rising incidence of sp resistance which is the principal drug currently used for this intervention. there has also been a concern about the possible interaction between sp and the routine infant vaccines but this has not been supported by any strong evidence. timely and efficient deployment of efficacious vaccines is widely accepted as an effective child survival strategy. the development of a successful malaria vaccine especially against p. falciparum would contribute remarkably to reduction of the unacceptably high childhood death from malaria. unfortunately decades of efforts at vaccine development have yet to meet this expected public health success. developing vaccines against parasitic infections poses greater challenges than developing vaccines for virus and bacterial infections because of their more complex nature and larger genomes. the multiple stages of the malaria parasite and the different proteins they express pose additional challenges to the development of a potent malaria vaccine. an allstage malaria vaccine capable of inhibiting growth or killing all of these different stages of malaria poses a complex challenge. researchers involved in development of malaria vaccine devote their efforts to three key strategies that target the preerythrocytic and erythrocytic stages of the life cycle in humans (fig. . ), and vaccines that induce antibodies in humans that can kill or prevent development of viable sexual forms ingested by the mosquito vectors. the pre-erythrocytic stage vaccines aim to prevent sporozoites (the stage of plasmodium that mosquitoes pass to humans) from invading and developing in the liver, while an asexual erythrocytic stage vaccine limits the invasion of erythrocytes or prevents their multiplication in the erythrocytes. the complete mapping of the p. falciparum genome with a better understanding of the organism at sub-cellular and molecular levels coupled with recent advances in genomic and proteomic science has led to a remarkable increase in the number of candidate malaria vaccines. there is no time better than the present to scale up support for malaria vaccine research and development. the goal of most of the initial efforts of malaria vaccine development is complete prevention of the disease with the hope of eliminating malaria. the disappointing results of early malaria vaccine trials appear to have diminished this enthusiasm. should efforts to develop a malaria vaccine capable of completely preventing clinical malaria fail, most public health experts and vaccine researchers advocate the goal of making malaria vaccines that ameliorate the severity of the disease and reduce the level of fatality. in africa, where pregnant women and children bear the greatest burden of severe malaria, such a vaccine will be a significant addition to maternal and child health services and will help to reduce the burden of childhood disability attributable to cerebral malaria. the opportunities provided by better research tools and a better understanding of the plasmodium and anopheles genome make the prospects and possibilities of a malaria vaccine better today than ever before. funding for malaria vaccine development and field trials has increased in recent years. however, it is still far short of the expected investment, given its huge potential for improving child survival and contributing to achievement of the millennium development goals (mdg). the inadequacies of health information systems and vital registration processes in most parts of sub-saharan africa make it difficult to obtain reliable records of malaria mortality. facility-based records of deaths, when available, are not representative of the situation in the larger population given that the majority of sick children do not use health facilities and most deaths occur outside the formal health facilities. most of the available mortality data from malaria-endemic areas are estimates and prospective mortality data from demographic surveillance systems validated by verbal autopsies . the inefficiency of health information systems and vital registration processes in sub-saharan african countries makes it difficult to obtain sufficient and timely information to track the performance of malaria control programs. the malaria situation globally deteriorated in the past three decades. this resulted in increased malaria-related morbidity and mortality, especially in sub-saharan africa where emergence and spread of multidrug-resistant malaria parasites and breakdown of malaria control programs were the leading reasons, among others (korenromp et al. ) . greenwood et al. ( ) have given an elaborate summary of the factors believed to have contributed to the deterioration of the global malaria situation in box . . while the discovery of additional malaria control measures such as a highly effective malaria vaccine should be expected to increase the gains of malaria control efforts, several appraisals and overviews of global malaria control efforts agree that the key reasons for the recent decline in the gains of malaria control efforts have not been the lack of effective malaria control measures. there is consensus that the four technical elements of the global malaria control strategy (box . ) affirmed by the international ministerial conference held in amsterdam under the auspices of the world health organization in have been essentially effective in the years preceding and succeeding the amsterdam conference. careful study of malaria control scenarios (mostly in sub-saharan africa) that have failed, or achieved only minimal success with these same strategies, shows that these control programs lacked the pre-conditions for effectiveness of the global strategy (box . ) as also outlined in the amsterdam ministerial conference on malaria. when the rbm strategy was established in , it was in response to these deficiencies. the rbm is a partnership between the who, other un agencies, bilateral aid agencies, nongovernmental organizations, and governments of climate instability: drought and floods increased malaria transmission in different epidemiological circumstances global warming may have led to increased malaria transmission especially in some highland areas civil disturbances and unrest have resulted in the collapse of malaria control programs and refugee situations with attendant effects on malaria transmission across epidemiological areas and increased risk of epidemics changes and increase in travel patterns within endemic areas and from non-endemic areas to endemic areas putting many non-immune people at risk hiv increases susceptibility to malaria and increases the burden on the health service emergence and spread of drug resistant p. falciparum has been a key reason for deterioration of malaria situation in especially africa and southeast asia insecticide resistance: resistance to pyrethroids used for treated bed-nets has emerged in anopheles gambiae (in west africa) and anopheles funestus (in southern africa). high vector resistance to anopheles funestus diminished the use of ddt for household spraying in southern africa. source: greenwood et al. ( ) malaria-endemic countries. the rbm has a longterm goal of reducing malaria morbidity and mortality by at least half by . rbm was not meant to be a new malaria control strategy but rather an organized global effort to facilitate the effective implementation of the global control strategy. the evidence that large-scale and effective use of itns can reduce the incidence of malaria and malaria-related deaths is both strong and consistent (lengeler ) . insecticide-treated mosquito nets (itns) can reduce all-cause childhood mortality by about a fifth; with about lives saved for every , preschool children protected with itn (lengeler ) . it is estimated that full itn coverage in sub-saharan africa could prevent , child deaths per year (lengeler ) . insecticidetreated nets are cost-effective, but endemic poverty and inadequate sensitization of people in malariaendemic areas remain the major reasons for low use (snow et al. ) . the cost-effectiveness of itns (us $ - per disability-adjusted life year (daly)) is similar to most childhood vaccines (who ) . when community coverage is high, itns not only protect those who sleep under them, but also those in the same dwelling (the home effect) and those living nearby (the community effect) (snow et al. ) . the year marked the end of the target set by african heads of state to achieve at least % access to prompt and effective treatment of malaria and % itn coverage for under- children and pregnant women. however, most countries in sub-saharan africa fell far short of these targets. it was also in the same year that rbm set the landmark target of halving malaria mortality by . appraisal of malaria control efforts at the end of uniformly indicated that resources available for procurement of malaria control commodities (acts, itn, and diagnostic kits) were grossly inadequate. the appraisal also showed that malaria control personnel at national and regional levels was inadequately equipped. donors and governments should develop effective mechanisms to monitor the access that children, adolescents, pregnant women, and children in difficult circumstances have to evidence-based to provide early diagnosis and treatment to plan and implement selective, multiple and sustainable preventive measures: including vector control; personal protection (notably insecticide treated nets); and chemoprophylaxis/intermittent preventive treatment. to detect early, contain or prevent epidemics; to conduct focused research, and to regularly assess the country's malaria situation, including ecological, social and economic determinants of the disease. source: who ( ) political will: sustained political commitment from all levels and sectors of government integration: malaria control should be an integral part of health systems, and be coordinated with relevant development programs in non-health sectors community participation: communities should be full partners in malaria control activities resource mobilization: adequate human and financial resources should be mobilized source: who ( ) treatment and preventive interventions for malaria. donor funds specifically tagged to providing resources and infrastructure for effective management of severe and complicated malaria have been grossly inadequate. supportive care for women and children with severe malaria is grossly impeded by weak health systems in malariaendemic countries. funds meant for providing adequate infrastructure and personnel for managing severe malaria should be tagged to bilateral and multilateral health system support grants. globally, women, children, and adolescents in sub-saharan africa are known to bear the greatest burden of malaria morbidity and mortality. list any six factors most peculiar to the region that account for this high burden. list five consequences of malaria infection in children and pregnant women. an integrated approach is advocated as an efficient and cost-effective strategy for the management of malaria co-infection with hiv/aids. briefly discuss what you understand by integrated management and describe how such an integrated approach might be operationalized in practice. what are artemisinin-based combination treatments (acts) and what are the advantages of their use in the treatment of malaria? what are the challenges of community delivery of malaria treatment through existing primary healthcare systems? is home treatment of malaria a better option? discuss the reasons for your position. list six factors that contribute to the worsening of the global problem of malaria? how can these be addressed? what should be the role of roll back malaria initiative in global malaria control? conquering the intolerable burden of malaria: what's new, what's needed: summary intermittent preventive treatment for the prevention of malaria during pregnancy in high transmission areas the impact of insecticide-treated bednets on malaria and anemia in pregnancy in kassena-nankana district, ghana: a randomized controlled trial external evaluation of roll back malaria prevention and treatment of malaria in young african children mass use of insecticide-treated bednets in malaria endemic poor countries: public health concerns and remedies insecticide-treated nets for preventing malaria in pregnancy drugs for preventing malaria in pregnant women programmatic environmental assessment for insecticide-treated materials in usaid activities in sub-saharan africa. agency for international development (usaid), office of sustainable development the role of chemotherapy in malaria control through primary healthcare: constraints and future prospects cytokine responses to plasmodium falciparum liver-stage antigen vary in rainy and dry seasons in highland kenya measurement of trends in childhood malaria mortality in africa: an assessment of progress toward targets based on verbal autopsy malaria attributable to the hiv- epidemic, sub-saharan africa hiv infection, malaria, and pregnancy: a prospective cohort study in kigali malaria in adolescence: burden of disease, consequences, and opportunities for intervention insecticide-treated bednets and curtains for preventing malaria effective delivery methods for malaria treatment. reducing malaria's burden: evidence of effectiveness for decision makers the pattern of neurological sequelae of childhood cerebral malaria among survivors in calabar chemoprophylaxis and intermittent treatment for preventing malaria in children the burden of the neuro-cognitive impairment associated with plasmodium falciparum malaria in sub-saharan africa gaps in childhood malaria burden in africa: cerebral malaria, neurological sequelae, anemia, respiratory distress, hypoglycemia, and complications of pregnancy african children with malaria in areas of intense plasmodium falciparum transmission: features on admission to the hospital and risk factors for death the public health burden of plasmodium falciparum malaria in africa: deriving the numbers. working paper , disease control priorities project the burden of malaria in pregnancy in malaria-endemic areas reduction of malaria during pregnancy by permethrintreated bed nets in an area of intense perennial malaria transmission in western kenya the burden of co-infection with human immunodeficiency virus type and malaria in pregnant women in sub-saharan africa intermittent preventive treatment for malaria in pregnancy in africa: what's new, what's needed world health organization ( ) ministerial conference on malaria cost-effectiveness of social marketing of insecticide-treated nets for malaria control in the united republic of tanzania a strategic framework for malaria prevention and control during pregnancy in the african region. who document: afr/mal/ / . brazzaville: world health organization regional office for africa world health organization guidelines for the treatment of malaria. who/htm/mal/ . . geneva: world health organizagtion international travel and health: situation as of key: cord- - qawjquv authors: lara, r.j.; islam, m.s.; yamasaki, s.; neogi, s.b.; nair, g.b. title: aquatic ecosystems, human health, and ecohydrology date: - - journal: treatise on estuarine and coastal science doi: . /b - - - - . - sha: doc_id: cord_uid: qawjquv this chapter treats two main topics: the relationship between human health, aquatic ecosystems, and water use; and the necessity of interdisciplinary approaches for the development of water management policies and disease control. main waterborne diseases, mostly affecting developing countries and relevant in terms of water management and changes in land use, such as malaria, schistosomiasis, or cholera, are discussed stressing links to the global water crisis. also, the role of artificial and natural wetlands in influenza epidemics is treated. the effects of increasing water use and scarcity on human health are discussed considering historical and contemporary incidence of diarrheal diseases in european and south asian megacities, relationships between dams and on waterborne diseases in asia and africa, and intensive agri- and aquaculture resulting in man-made ecotones, fragmented aquatic ecosystems, and pathogen mutations. it is emphasized that the comprehension of the multiple interactions among changes in environmental settings, land use, and human health requires a new synthesis of ecohydrology, biomedical sciences, and water management for surveillance and control of waterborne diseases in basin-based, transboundary health systems. surveillance systems should monitor changes in water management, ecotones, and hydrological cycles and shifts in, for example, the outbreak timing of strongly seasonal diseases. these indicators would provide criteria for the development of innovative water management policies, combining methods of vector control and the safe creation of water reservoirs, irrigation systems, and wetland habitats. this chapter is not intended to provide an extensive review of water-borne diseases, since there are already excellent examples of these in the literature. rather, the intention is to call atten tion to particular aspects of the principal water-borne diseases and related water management issues. the emphasis is often on controversial aspects which it is hoped will stimulate an open, undogmatic, and fruitful discussion on possibilities and cur rent and future challenges for ecohydrology in relation to human health. ecological integrity is central to health (epstein, ) . pollution, disturbed environments, habitat loss, and climate change promote disease emergence in a number of ways. threats to human health arising from man's interaction with aquatic ecosystems can originate from multiple factors, which can be broadly grouped into the following major categories: • natural biological cycles in which humans can act as hosts of pathogenic microorganisms (protozoans, bacteria, etc.); • consequences of the management of aquatic resources (e.g., wetlands drainage or creation, aquaculture, and dam construction); • effects of water pollution (chemical, microbiological, radio active, and thermal) on man and on the physiology of individual organisms; and • the impact of global changes affecting climate and hydrolo gical cycles (e.g., habitat degradation, warming, increased rainfall, and storms). clearly, these are interlinked and specific case studies are likely to present evidence of more than one causal factor. thus, an effort has been made to integrate these different topics into sections covering the most relevant factors related to diseases that can be considered indicators of determined hydrological processes. globally, approximately % of deaths due to infectious dis eases are water related. this amounts to . million deaths per year, % of which are caused by diarrhea, a disease killing around million people every year, mostly children in devel oping countries (wwd, ) . thus, it is crucial to develop an integrated water and health management system, as well as the tools required to identify and predict interconnected trends in the evolution of aquatic ecosystems and diseases. although the importance of integrating natural sciences with socioeconomic research is stressed and recommended in every forum dealing with sustainable use of natural resources, human health, one of the most valuable public goods, is seldom included as a significant issue in coastal or basin management programs. a frequent goal of cooperation between socioeconomic and natural sciences research is the evaluation of the sustainability of resource use and the vulnerability of the coastal zone. the seven step assessment framework of the international panel on climate change (ipcc, ) is the customary tool used for this purpose (figure ) . similarly, the health map program from the world health organization (who) provides criteria and a software platform for linking epidemiological data with layers of geographic information (who and unicef, ) . however, these two types of research programs mostly lack any substantial interaction. ecohydrology can provide the conceptual framework for establishing such links. this involves a scale (the river basin and the coastal zone), an integrative process (flooding dynamics), and an integrative tool such as digital elevation models (dem) of the study area (figure ) . high-resolution topography is essential for data integra tion in low-lying areas. for this purpose, a closer interaction of socioeconomic studies, climate, hydrology, ecology, micro biology, biogeochemistry, molecular biology, and medicine is required, as exemplified in the case of cholera (discussed in section . . . . ). further, it is necessary to generate a common language to facilitate and promote inter-and transdisciplinary communication. several concepts related to disease dynamics, such as outbreak, epidemics, and pan demics, are commonly used in a qualitative way. yet, the creation of interdisciplinary databanks or the compilation of information from diverse sources (e.g., hydrological events and outbreak intensity) including historical ones would ben efit from objective category definitions. in the following sections, some examples are dealt with, which will appear in this chapter and in other related literature. it is considered that an epidemic occurs when new cases in a given human population, during a given period, sub stantially exceed what is expected, based on recent experience (the number of new cases in the population during a speci fied period of time is called the 'incidence rate'). an epidemic may be restricted to one locality (an outbreak), be more general (the usual 'epidemic'), or even global (pandemic). common diseases that occur at a constant but relatively low rate in the population are said to be 'endemic'. an example of an endemic disease is malaria in some parts of africa, where a large portion of the population is expected to contract malaria at some point in their lifetime. these somewhat subjective definitions require more precisionand a wider diffusion among the populationwhen, for aquatic ecosystems, human health, and ecohydrology figure integration of socioeconomic, ecological, and medical research within the ecohydrology framework. example, public funds have to be allocated for prevention, alleviation, or fight against determined diseases or for insur ance policies. an increasing number of direct or indirect cases of water-borne diseases are due to global warming, increasing frequency and intensity of storms, flood control, and environmental management (dam construction, irriga tion, use of fertilizers, etc.), and this has greatly widened the spectrum of stakeholders with an interest in the use of water and its impact on health. this underlines the need for agree ment on and diffusion of definitions and criteria between users and managers to facilitate the quantification of impacts of disease, ecological damage, and poor sanitation, as well as for cost-benefit analysis of proposed prevention or remedia tion measures. the global burden of disease analysis (who, ) pro vides a comprehensive and comparable appraisal of mortality and loss of health due to diseases and injuries, and risk factors for all regions of the world. the overall burden of disease is assessed using the disability-adjusted life year (daly), a timebased measure that combines years of life lost due to premature mortality and years of life lost due to time lived in states of less than full health. worldwide, about million dalys per year are due to water-borne diseases (pruess et al., ) . a relevant specific example is the definition and evaluation of the impact of disease related to drinking water quality. this concerns the presence of chemicals or pathogenic microorganisms that are transmitted when contaminated drinking water is directly con sumed. if contaminated drinking water is used in the preparation of food, it can be the source of food-borne disease through consumption of the same microorganisms, often in the form of gastrointestinal illnesses. according to the who (who, a) , diarrheal disease accounts for an estimated . % of the total daly global burden of disease and is respon sible for the deaths of . million people every year. it is estimated that % of that burden is attributable to unsafe water supply, sanitation, and hygiene. at the national level, surveillance systems are the primary source of data concerning the scope and effects of water-borne diseases on persons. these data can be organized to provide information for political and administrative units such as counties or federal states, and/or geomorphological units, that is, basins. in the united states, since , the centers of disease control and prevention (cdc), environmental protection agency, and the council of state and territorial epidemiologists have maintained a collaborative surveillance system which monitors the occurrence and causes of water borne-disease outbreaks (wbdos) (calderon et al., ). the surveillance system includes data for outbreaks associated with drinking water and recreational water. state, territorial, and local public health departments are primarily responsible for detecting and investigating wbdos and voluntarily reporting them to cdc on a standard form. the unit of analysis for the wbdo surveillance system is an outbreak, not an individual case of a water-borne disease. two criteria must be met for an event to be defined as a wbdo. first, more than two persons must have experienced a similar illness after either ingestion of drinking water or exposure to water encountered in recreational or occupational settings. this cri terion is waived for single cases of laboratory-confirmed primary amebic meningoencephalitis and for single cases of chemical poisoning if water-quality data indicate contamina tion by the chemical. second, epidemiologic evidence must implicate water as the probable source of the illness. the integration of national information on water-borne disease incidence into collaborative regional, transboundary basin databank networks of open access is crucial to allow a fair and efficient implementation of water management regula tions related to, for example, dam operation and international irrigation agreements. this is particularly relevant in tropical countries where large river basins (e.g., amazon, nile, mekong, indus, ganges, and yarlong-brahmaputra) represent the main source of income, water, and food for millions of people. the rivers originating in the tibetan plateau ( figure ) are particu larly relevant as they flow through several, densely populated tropical and subtropical countries with quite different degrees of development. in general, water-borne disease can be caused by protozoa, viruses, or bacteria, many of which are intestinal parasites. in the following tables, some relevant examples of various disease types are grouped and summarized, including those which mostly affect developing countries, in many cases in tropical and subtropical regions. in the following sections, diseases have been selected that are relevant in terms of numerical incidence, water management, and changes in land use, parti cularly under the ecohydrological approach. these are malaria, schistosomiasis, lymphatic filariasis, onchocerciasis, cholera, spotted fever, and those illnesses induced by toxins produced during cyanobacteria blooms due to increased nutrient loads. we will provide a general overview of these diseases, stressing the links to the global water crisis, possible contributions of ecohydrology, and challenges to its classical approach. parasitic infections, particularly malaria and schistosomiasis, represent some of the most universal health problems. the who estimates that million people are infected and another million people are at risk of infection (who, ) . in fact, only malaria accounts for more cases of disease than schis tosomiasis, and both are closely related to water management (who, ) and will be extensively treated in this chapter. water scarcity and uncoordinated water management go hand in hand with poverty and disease. russel ( ) explains the links clearly: bilharziasis and malaria are both debilitating diseases and debility is not conducive to good farming. throughout history, malaria and bilharziasis have interfered with the use of arid land and indeed, calcified eggs of bilharzia worms were found in the kidneys of two mummies of the th dynasty - - b.c. there is a crucial chain reaction that in some instances has contributed to the virtual abandonment of irrigation systems: the more debility, the less canal maintenance, therefore the more anopheles mosquitoes and the more snails transmitting more malaria and more bilharziasis, thus leading to more debility, and so on…. (russel, : ) . table provides a summary of relevant water-borne diseases produced by protozoan parasites. in this section, we will con centrate on malaria, currently still the world's most important parasitic disease. today, malaria is one of the world's deadliest diseases and occurs mostly in tropical and subtropical countries, being transmitted from one person to another through the bite of female anopheles mosquitoes. the who estimates that there are - million cases of malaria, with over million deaths each year (who, a) . t he main burden of malaria (more than %) is in africa, south of the sahara. two-thirds of the remaining burden affects six countries: brazil, colombia, india, solomon islands, sri lanka, and vietnam. the ecology of the disease is closely associated with the availability of water, as the larval stage of mosquitoes develops in different kinds of water bodies. the mosquito species vary considerably in their water-ecological require ments (sunlit or shaded, with or without aquatic vegetation, stagnant or slowly streaming, and fresh or brackish; discussed in section . . . . . ), and this, to a great extent, determines the ecology of the disease. in many places, the nat ural habitat sustains intense malaria transmission; in others, the development of water resources (irrigation, dams, and urban water supply) has exacerbated the intensity of transmission and caused the disease to spread. in yet others, for example, the central asian republics of the commonwealth of independent states, malaria has returned as a result of a breakdown in water management and maintenance problems of local irrigation systems (who, ) . climate change (global warming) appears to be moving the altitudinal limits of malaria to higher elevations, for example, in the east african highlands and madagascar. further, in some of the tropical regions of the developing world, the incidence of malaria has increased in recent years as the mosquito and the malaria parasite it transmits have evolved more resistance to sewage, nontreated drinking water, flies in water supply (hand-to-mouth) untreated water, poor disinfection, pipe leaks, groundwater pollution, sharing of water source by humans and wildlife. beavers and muskrats create ponds that act as reservoirs for giardia (oral-fecal, hand-to-mouth) encephalitozoon intestinalis has been detected in groundwater chills, period fever attacks; debility, spleen and liver enlargement; anemia, jaundice; clogging of brain vessels can lead to death flu-like symptoms, watery diarrhea, loss of appetite, substantial loss of weight, bloating, increased gas, and nausea abdominal pain, fatigue, weight loss, diarrhea, bloating, and fever diarrhea, bloating abdominal discomfort, and flatulence diarrhea and wasting in immunocompromised individuals alternatives to dichlorodiphenyltrichloroethane (ddt) and to the medications used to prevent or treat the disease. in some regions (e.g., south africa), ddt is again increasingly used to control mosquitoes (thurow, ) . in general, land reclama tion for agriculture, deforestation, and changes in land use are probably the principal causes of the climatic and habitat changes responsible for these developments. yet, it should be borne in mind that it was the drainage of wetlands for agricul tural purposes in the nineteenth century which contributed most significantly to the eradication of malaria in europe (reiter, ) . these are crucial aspects to be carefully evaluated when wetland creation and management policy are being considered as an ecohydrological tool, for example, for sequestration of nutri ents in estuaries and for preventing toxic algal blooms. these issues will be discussed extensively in the following section (also discussed in section . . . ). it is often erroneously thought that larvae of malariatransmitting mosquitoes can only develop in freshwater. it is also frequently forgotten that malaria is not restricted to the tropics, and that only in did the who declare that europe was free of malaria. about years ago, malaria was a leading cause of death in many marshland commu nities along the coast of southern england. there, extensive salt marshes provided high-quality grazing for sheep and cattle, but were also a favored habitat for anopheles atroparvus, a highly effective malaria vector, which prefers to breed in brackish water along river estuaries and in the presence of abundant algae. until the nineteenth century, malaria was a major mortality factor in the netherlands. however, by the end of that century transmission had dropped precipitously in the more prosperous countries of north europe. a major factor contributing to this decline was that the mosquito habitat had been eliminated by improved drainage and extensive land reclamation. major epidemics still occurred in russia and poland in the s, with high death rates reaching regions near the arctic circle (wolanski et al., and references therein) . today, malaria is again common in many parts of central america, northern south america, tropical and subtropical asia, some mediterranean countries, and many of the republics of the former ussr. this spread of the disease has been attrib uted to, among other factors, forest clearance, irrigation, ecological change, population increase, deterioration of public health services, resistance of mosquitoes to insecticides, and resistance of the malarial parasite to antimalarial drugs (reiter, ) . thus, policies on wetland creation or restoration must take account of not only the benefits of the reestablishment of lost ecological services, but also the potential consequences of increased areas of slow-flowing or stagnant waters on disease vector proliferation, particularly under a scenario of increasing temperatures. the related ecohydrological concepts of system robustness and flushing dynamics can make a major contribu tion to the integrated analysis and handling of this issue, seeking equilibrium between the necessary water residence time, for example, efficient nutrient sequestration, and the minimization of mosquito reproduction. the choice cannot be formulated as 'mosquitoes in the basin' or 'toxic algal blooms in the estuary'. there are techniques such as 'runneling' that have been used with varying success to control mosquito proliferation in cre ated or natural wetlands. as mosquitoes can be vectors for several other diseases besides malaria, this will be treated in a separate section (discussed below in section . . . . . ). table provides a summary of relevant water-borne diseases produced by worm infections. in this section, we will concen trate on schistosomiasis, lymphatic filariasis, and river table main water-borne diseases produced by worms blindness because of their strong links to water management measures, such as irrigation and dam operation schemes. schistosomiasis is considered the second most important para sitic infection after malaria in terms of public health and economic impact. it is a chronic debilitating disease that is estimated to affect between and million people in countries. as many as million live in endemic areas. also known as bilharzia, bilharziosis, or snail fever, it is caused by several species of fluke (trematode) of the genus schistosoma. (gryseels et al., ; figure ) . infection with any of the five species of schistosome worms is rarely fatal. although it has a low mortality rate, schistosomiasis is often a chronic illness that can damage internal organs and, in children, impair growth and cognitive development. the urinary form of schis tosomiasis is associated with increased risks for bladder cancer in adults (hodder et al., ) . human infections are most common in asia, africa, south america, or the middle east, especially in areas where the water contains numerous fresh water snails, which are intermediate hosts, that is, may carry the parasite. however, trematodes can be found anywhere human waste is used as fertilizer. the disease affects many people in developing countries, particularly children who may acquire the disease by swim ming or playing in infected water, and field workers in arid or semiarid regions where agriculture depends heavily on irrigation. first infection with schistosomiasis usually occurs during the early school years and is a frequent cause of absen teeism. it is not uncommon for % of a school's student population to be infected in some highly endemic areas in africa. in addition to its effect on children, schistosomiasis has a major impact on the agricultural workforce and on national economic productivity. in egypt, where % of the people are infected, economic losses due to lost work are estimated to exceed $ million a year (anonymous, a) . development, both planned and unplanned, has resulted in a number of changes in the epidemiology of the disease that threaten to increase its spread and the number of people infected, reduce economic productivity, and compromise development gains. water development schemes, including dam building and irrigation systems, with slow water flows and aquatic vegetation, have created new breeding sites for snails. intensive agriculture has encouraged people to migrate to urban and peri-urban areas that are ill-prepared to meet their needs for sanitation and water. in these areas, snail-infested streams and canals are often the most convenient water sources. new agricultural systems that emphasize irrigation, double cropping, and other intensive cultivation practices have increased farmers' exposure to infection. the emergence or reemergence of schistosomiasis as a result of large-scale hydroprojects has been reported from the egyptian aswan high dam (khalil, ; strickland, ) , the sudanese gezira-managil dam (amin, ; omer, (teklehaimanot and fletcher, ) . in china, the danling dam in the province of sichuan and the huangshi dam in the province of hunan have all had adverse effects by increasing local schistosome transmis sion (zhang and guo, ) . however, not all dam regions suffer from schistosomiasis. for example, when the ertan dam in the province of sichuan became operational, local schistoso miasis control centers collaborated with dam management offices and government ministries to actively monitor and pre vent the spreading of schistosome worms. as a result of these efforts, potential schistosome transmissions in the ertan region were successfully averted (gu et al., ) . schistosomiasis infection in humans, the definitive hosts, is caused mainly by three species of flatworm, namely schistosoma haematobium, s. japonicum, and s. mansoni. infection occurs when free-swimming larvae penetrate human skin. the larvae develop in freshwater snails, which serve as intermediate hosts for the parasite. humans are infected when they enter larvaeinfested water for domestic, occupational, and recreational purposes and the larvae of the parasite penetrate the unbroken skin. the life cycle is continued when people infected with schistosome worms deposit urine or fecally borne eggs into the water. the disease particularly affects children who may acquire the disease by swimming or playing in infected water (hodder et al., ) . the life cycle of s. mansoni provides a simplified example for all species of schistosomes and helps understand the potential contribution of water management to snail proliferation. after the eggs of the human-dwelling parasite are emitted in the feces, into the water, the ripe miracidium hatches out of the egg. the miracidium searches for a suitable freshwater snail to act as an intermediate host and penetrates it. following this, the parasite develops, via a so-called mother-sporocyst and daughter-sporocyst generation, into the cercaria. the purpose of the growth in the snail is the numerical multiplication of the parasite. a single miracidium can produce several thousand cercaria, each one of which is capable of infecting humans. the cercaria propel themselves in water with the aid of their bifurcated tail and actively seek out their final host. when they recognize human skin, they penetrate it within a very short time. following a migration through the body within the bloodstream, they develop into sexually mature adults. the larvae enter through the skin, migrate via the blood vessels, and mature in the lungs. from there they travel to the veins of the upper or lower intestine or bladder and, if they find a partner of the opposite sex, they reproduce. there are specific host/parasite combinations that lead to typical forms of bilhar ziasis in endemic areas in different regions of the world, frequently associated with a particular economic activity. there are also region-specific control measures with positive and negative consequences or side effects (mannesmann and fuchs, ) as discussed in section . . . . . . in these regions, the snail bulinus truncatus, b. globosus, and b. forskali can be hosts of s. haematobium, which produces uro genital bilharziasis (lang, ) . the two clearest examples of large-scale irrigation systems spreading schistosomiasis are found in africa, especially in the nile valley. in upper egypt south of cairo, it has been known for a long time that the shift from basin irrigation by the floodwaters of the nile to perennial irrigation results in a dramatic increase in schistosomiasis. basin irrigation allows the land to dry out seasonally, killing almost all snails. under perennial irrigation, the land is wet all year round. soon after the construction of aswan low dam, four locations that changed irrigation methods in the mid- s experienced a surge in s. haematobium infections (khalil and abdel azim, ; khalil, ) . infection rates increased from - % in to - % in . urinary schistosomiasis had a pre valence at % in areas of perennial irrigation in upper egypt and only % in areas with basin irrigation (scott, ) . in the s, prevalence ranged from % to % in three districts with perennial irrigation, while in two districts with basin irriga tion, it was % and % (wright, ) . in the s, after the construction of the aswan high dam, the nile delta became a major breeding habitat for the snail hosts of both urinary and intestinal schistosomiasis. irrigation canals and drains ( figure ) harbored stable populations of these snails throughout the year. this resulted from the elimina tion in these canals of the so-called 'winter closure'. before the construction of the dam, the closure was enforced for about days, during which the canals were closed and dried up, and the silt deposited on their beds during the nile flood was dredged out together with the snails and aquatic weeds (malek, ) . the other large-scale nile valley irrigation system impli cated in schistosomiasis transmission is the gezira irrigation scheme in the sudan. the major increase in prevalence of schistosomiasis in gezira came after , when the cropping rotation changed to include 'winter' wheat. farmers kept the canals filled with water from march to may, when they were previously dry (fenwick, ) . another factor was the creation of the adjoining managil extension irrigation system which left tenants without adequate water supplies or sanitation facilities. also, there was an influx of migrant laborers in the original gezira scheme, who lived near irrigation canals, under very poor sanitary conditions, leading to the propagation of further water-borne diseases (tameim et al., ) . in north africa and the middle east, research has demon strated the association of even small-scale irrigation plans, decentralized at the village level, with increases in schistoso miasis transmission. malek ( ) reports that in sudanese villages along the nile, north of khartoum, prevalence of urin ary schistosomiasis in children was - %, compared to an average of less than % in other areas. wright ( ) reports that in the rural area around baghdad, iraq, prevalence of schistosomiasis increased from % to % following the installation of lift pumps. . . . . . asia in east and southeast asia, intensification and expansion of irrigated rice production systems over the past decades have increased the habitats for snail and schistosoma. the host/para site combinations tricula aperta/s. mekongi and oncomelania hupensi/s. japonicum produce intestinal bilharziasis predomi nantly in rural communities living close to irrigation ditches. the association of asian schistosomiasis with rice-growing areas has been reported by different authors. however, in many cases, rice fields themselves did not seem to be breeding habitats; rather snails found in the rice fields appeared to have spread from nearby irrigation canals. cattle and water buffalo can also be important reservoir hosts. various methods have been applied to substantially reduce schistosomiasis in rice agriculture, which will be discussed later in section . . . . . in this part of the world, it is mainly the combination of s. mansoni with biomphalaria glabrata snails that causes bilhar ziasis. brazil, with million people living in the endemic areas and million infected, is the most affected country in the americas (chitsulo et al., ) . however, it is not obvious to what extent hydrological factors, including large dams or irrigation systems, contribute to spreading schistosomiasis in brazil. the african slave trade was probably responsible for the introduction of schistosomiasis in brazil soon after the country was discovered by european explorers, and internal migration was responsible for spreading it from seashore to interior. nowadays, schistosomiasis transmission occurs over a vast endemic region, from maranhão to espírito santo, and minas gerais, and there are further areas with a high risk of endemic expansion (araujo, ; paraense, ) . there are also iso lated foci in the federal district and in the states of pará, goiás, rio de janeiro, são paulo, paraná, and rio grande do sul. some examples from the literature point to patterns of labor and household migration as significant factors in the incidence of disease in brazil, probably more than irrigation schemes. cases of disease importation from endemic areas have been registered over almost the entire country, mainly in the states that are considered migration destination areas, such as rondônia (coura and amaral, ) . a study involving irrigation projects in the semiarid region of five northeastern states of brazil (coutinho et al., ) found that schistoso miasis transmission was not a major problem in the areas studied. socioeconomic-sanitary analysis identified the pre sence of migrant farm workers coming from endemic areas of schistosomiasis and living in poor sanitary conditions in the irrigation areas as a main factor of epidemiological importance. however, continued epidemiological surveillance is essential in all irrigated areas of northeastern brazil if schistosomiasis control is to be maintained, as well as improvement in the water supply and sanitation measures for migrant workers (coutinho et al., ) . the potential association between irrigation levels and the occurrence and spread of s. mansoni infection was investigated (martins and barreto, ) in the state of bahia, where two forms of irrigation have been developed. the first is capital intensive and mechanized, requiring little manual labor. the second is labor intensive and characterized by limited mechan ization. according to the study, the municipalities with the largest irrigated areas are not the ones with the highest s. mansoni infection rates. in most of these counties, irrigation is capital-and technology intensive. according to these find ings, unlike africa, irrigation in the state of bahia has had little impact on the spatial profile of the schistosomiasis endemism. regarding the impact of schistosomiasis on labor-intensive irrigation schemes, some research points to the importance of the household in disease transmission, as a result of the cluster ing of domestic activities associated with water collection, storage, and usage. such activities can result in the sharing of water-contact sites and water-contact behavior, which expose all members of the household to an increased risk of infection. in previous studies in brazil (bethony et al., ) , it was deter mined that shared residence accounted for % of the variance in schistosoma fecal egg excretion rates. further, shared residence accounted for % of the variation in total water contacts per week. it also accounted for a large proportion of the variation in individual water-contact behavior: for example, agricultural con tacts ( %), washing limbs ( %), or bathing ( %). these results implicate the household as an important composite measure of the complex relationships between socioeconomic, environmental, and behavioral factors that influence water-con tact behavior and, therefore, the transmission of schistosomiasis. these results also support the idea of focusing on safe water supply and household density in the implementation of schis tosomiasis prevention and control measures. the role of aquatic animals in maintaining the schistosome life cycle in brazil requires further clarification. the influence of s. mansoni on a population of the water rat, nectomys squamipes, was studied at sumidouro, rio de janeiro, and brazil (d' andrea et al., ) . the population dynamics of parasites was studied. water contamination (i.e., the source of miraci dia), abundance of the intermediate host, and rodent migration were found to be related to schistosome prevalence. the n. squamipes population was not obviously influenced by the infection, as shown by the high number of reproductive infected females, high longevity of infected individuals, and the absence of a relationship between recruitment or survivorship rates and the intensity of schistosome infection. the data indicate that n. squamipes can increase transmission of s. mansoni in endemic areas and carry it to noninfected areas. furthermore, this rodent can be used as an indicator of trans mission foci. in the caribbean, b. glabrata can be found in shallow ponds with abundant vegetation or with fallen banana leaves. it has been also found in drains around banana plantations on the west indian island of st. lucia (sturrock, ) . this is a mosquito-borne parasitic worm infection, a debilitating parasitic disease, which affects million people in the tropical and subtropical areas of southeast asia, south america, africa, and the islands of the pacific. while filariasis is rarely fatal, it is the second leading cause of permanent and long-term disability in the world. a person with the disease tends to have more bacterial infections in the skin and lymph system. this causes hardening and thickening of the skin, which in its most dramatic form is expressed in the symptoms of elephantiasis, the accumu lation of lymph, usually in legs. it is not a killer disease, but causes severe debilitation and social stigma. the who has named filariasis one of only six 'potentially eradicable' infectious diseases and has embarked upon a -year campaign to eradi cate the disease. in addition to consistent long-term treatment by oral medicines, eradication efforts focus on controlling the pro liferation of mosquitoes in aquatic environments, which will help to reduce the transmission of lymphatic filariasis, as well as that of malaria, which is prevalent in many of the same communities in africa (cdc, ) . onchocerciasis or river blindness is the world's second leading infectious cause of blindness. it is found in countries in africa as well as in guatemala, southern mexico, some areas of venezuela, small areas in brazil, colombia, and ecuador, and in the arabian peninsula. a total of million people are affected worldwide. the disease is caused by onchocerca volvulus, a parasitic worm that breeds in water and that can live for up to years in the human body. controlling insect breeding sites in rivers is one of the pillars of prevention. the disease is trans mitted person to person by bite of a blackfly (simulium), which breeds solely in fast-flowing waters. symptoms of the disease in a person usually begin to show - years after infection. each adult female worm, which can be more than half a meter in length, produces millions of microscopic young worms (micro filaria). the microfilaria migrate through the skin and, upon death, cause intense itching and depigmentation of the skin (leopard skin), lymphadenitis, resulting in hanging groins and elephantiasis of the genitals, serious visual impairment, and blindness when they reach the eye. the disease blinds between % and % of its victims and seriously undermines the economic productivity of communities in endemic areas (who, b; figure ). figure onchocerciasis also affects the development of exposed children. their school performance is affected by the unrelenting itching associated with this disease. many youth are deprived of their childhood as they are often forced to guide and look after elderly relatives blinded by the disease. photo credit: bill vanderdecker in: http://www.pqmd.org/cms/node/ unlike malaria and schistosomiasis, transmission of river blindness is usually found along fast rivers or streams with white-water rapids and cascades. the species of blackflies, which transmit this blinding parasite, require well-aerated, high-velocity flow to deposit their eggs, usually on rocks or overhanging vegetation. the larval stages are filter feeders and need large flows passing their habitat to obtain sufficient food and oxygen for development. in many parts of africa, people living near rivers migrate out of the fertile river valleys because of the painful bites of the flies and the eventual blindness resulting from this parasite (kim and merritt, ) . river blindness has historically plagued the fertile valleys of west africa, but it was the arrival of europeans that unleashed the full force of the disease upon the region's inhabitants. traditional taboos had kept people from settling along river banks or visiting streams in broad daylight, when blackflies are most active. white colonists, however, insisted on recreating the riverside towns they remembered from home. by removing longstanding cultural prohibitions, they made onchocerciasis more prevalent than it had been before. by the s, several hundred thousand people had been blinded by the disease. also tragically for the region, the most fertile farmlandan area roughly the size of michiganwas abandoned due to the risk of contracting the disease (wong, ) . currently, river blindness has been eliminated as a major public health problem in west african countries. despite success in west africa, million people remain at risk of contracting river blindness in the countries of central, eastern, and southern africa (anonymous, ) . due to the tight connec tions between the dynamics of this disease and changes in flow velocity, we will return to it in section . . . in the discus sion of the effect of dams on human health. table provides a summary of relevant water-borne diseases produced by bacteria. we will concentrate on cholera and other vibrio illnesses for the reasons explained below. the case of cholera has been considered paradigmatic of the links between global climate change and infectious diseases. it offers an excellent example of how information about environ mental factors permits better understanding of disease virulence, transmission, and epidemiology. therefore, and due to the links to wetlands and other coastal ecosystems, aquaculture, and water management in megacities, this disease will be discussed in detail in this and the following sections, in relation to the dynamics of its causative agent in aquatic ecosystems. cholera is still an important cause of morbidity and mor tality in many countries in asia, africa, and latin america due to lack of safe water supply and poor hygienic practices (colwell, ) . cholera is endemic in the ganges and brahmaputra deltas. it was originally endemic to the indian subcontinent but spread worldwide along the trade routes, and mostly affects developing countries, particularly in coastal zones. in the last ∼ years, there have been seven pandemics and there is evidence of accelerated change of vibrio and disease dynamics as consequence of environmental changes and increased global connectivity (faruque et al., ) . the cur rent pandemic, which started in , is the most extensive in geographic spread and duration. cholera epidemics were reported from over countries during , the largest scale ever recorded in human history (who, ) . vibrio cholerae, a gram-negative comma-shaped gammapro teobacterium, is the causative agent of cholera ( figure ). vibrios are aquatic bacteria of marine and estuarine origin but can survive and be pathogenic in freshwater ecosystems. apart from v. cholerae, some other vibrios (v. parahaemolyticus, v. vulnificus, etc.) are also responsible for incidences of diarrhea, gastroenteritis, necrotizing fasciitis, and septicemia, which afflict human populations (table ) all over the world (chakraborty et al., ) . besides, many vibrios can also cause diseases in fish, shrimp, corals, and other aquatic organisms (thompson et al., ) . there are convergent approaches to the investigation of coral and human diseases. these include the research into the figure the causative agent of cholera, vibrio cholerae, is a faculta tively anaerobic bacterium, . - . µm to . - . µm, and a natural inhabitant of temperate/tropical estuaries, salt marshes, mangroves, coastal waters, and reefs. photo credit: moredun animal health, ltd/ science photo library/photo researchers, inc. same bacteria genus (vibrio), responsible for coral bleaching and for cholera, the use of remote sensing of ocean-surface temperature, climate research, and an emerging common cur rent of epidemiological thinking. traditionally, the association between water temperature and coral bleaching has been stressed, and only recently it has been discovered that this is probably triggered by a vibrio bacterium, and that it could be transmitted by a coral-feeding worm, acting as 'vector'. it is the first time a vector has been found for a coral disease (rosenberg and falkovitz, ) . table main water-borne illnesses produced by bacteria at the same time, the study of cholera disease has begun to encompass marine and estuarine research. the association of v. cholerae with plankton was established only recently, allow ing analysis of patterns of cholera epidemics, especially in those regions where it is endemic. the sporadic and erratic nature of cholera epidemics can now be related to climate-ocean coupling events, such as el niño (colwell, ) . since zoo plankton has been shown to harbor the bacterium and zooplankton blooms follow phytoplankton blooms, remote sensing can be employed to determine the relationship between cases of cholera and ocean chlorophyll concentration, as well as sea-surface temperature, ocean height, nutrient con centrations, salinity, and turbidity. during each pandemic, cholera has struck coastal regions before spreading inland. the principal agents responsible for cholera epidemics are the o and o serogroups of v. cholerae, of more than serogroups so far identified. within the o serogroup, the classical biotype caused the pre vious six pandemics, while the el tor biotype is associated with the present seventh pandemic. a coupling of vibrio dynamics to that of aquatic, brackish ecosystems is strongly suggested by the marked cholera seasonality in coastal villages of the bay of bengal (colwell, ) . the role of coastal areas in maintain ing endemicity is clearly a significant feature of cholera ecology. however, it was mainly laboratory research that provided evi dence for the existence of aquatic environmental reservoirs where v. cholerae survives for long periods of time and from which a toxigenic form may emerge to support epidemic con ditions (miller et al., (miller et al., , (miller et al., , barua and greenough, ) . the o serogroup emerged in the coastal zone in through a natural genetic alteration of the o el tor biotype. a survey in bangladesh established that this strain was mainly found in southern coastal marshes (faruque et al., ) . however, systematic, interdisciplinary field studies on the relationship between habitat characteristics and vibrio diversity and virulence are scarce. little has been done to widely monitor v. cholerae and study its ecology from a basin perspec tive in different related coastal environments such as mangroves, marshes, and estuaries, despite clear evidence that this could be one significant step forward for early warning and understanding human vulnerability to the disease (collins, ) . as early as , robert koch suggested that the bay of bengal, especially the sundarban mangrove forest, was the main source of cholera, noting that the combination of a brackish, organic-matter-rich environment, with a high den sity of human population represented the ideal conditions for the proliferation of v. cholerae (koch, ) . however, since then, there have been no extensive surveys of this transbound ary ecosystem (bangladesh and india), which represents the largest unitary mangrove and marsh system worldwide (akhtaruzzam, ) . difficult access, cyclones, floods, and the difficulty of obtaining funding for long-term research have precluded the systematic spatiotemporal monitoring of these habitats. most of the few available works are based on one-site samplings and do not provide information on seasonal trends. plankton is a significant marine reservoir of v. (huq and colwell, ) . in most cases, phytoplankton and zooplank ton are spatially and temporally associated (kiorboe and nielsen, ) and their abundance can be estimated by remote sensing, which has been related to cholera incidence in the bay of bengal region by lobitz et al. ( ) . living zooplankton can be a reservoir for vibrios, which attach them selves to the zooplankton's chitinaceous exoskeleton (kaneko and colwell, ) . nevertheless, watkins and cabelli ( ) found that growth and survival of v. parahaemolyticus was more stimulated by addition of pulverized chitin, than by living zooplankton, which however had a greater effect than the addition of sewage or other nutrients. in addition to salinity, nutrients, and plankton, suspended particle load and sediment resuspension also influence the vibrio amount in the estuary. recent investigations (lara, unpublished results) on seston size fractionation in sunderbans waters showed that the largest amounts of chitin and cultivable vibrio spp. were generally present in the fractions correspond ing to micro-, nanoplankton, microdetritus, and silt/clay particles, and not in zooplankton. it is still an open question whether the vibrio serotypes o and o , as well as the viable but not cultivable, and nonviable forms are preferen tially associated with determined seston size classes or wetland ecosystem compartments. better understanding of vibrio diversity in aquatic environ ments such as estuaries, marshes, and mangroves can lead to new insights into their genetic expression and co-regulation in the environment where they interact with each other. however, most vibrio studies treat species of pathogenic importance (e.g., v. cholerae, v. parahaemolyticus, and v. vulnificus) and not the diversity of the genus itself. a further key issue is the compre hension of the seasonality, life cycle, and dormant phases of bacterial population in nature. the environmental persistence of v. cholerae may be facilitated by entering a dormant state in which it remains viable but becomes nonculturable (vbnc) in conventional laboratory media (colwell et al., ) . the v. cholerae cells attached to plankton enter into the vbnc state as survival strategy (colwell and huq, ) . therefore, the detection of the nonculturable state is crucial to understanding v. cholerae ecology. however, the mechanisms that cause the organism to associate with plankton or other particles, to form biofilms, or to enter dormant or free-swimming phases are not yet completely understood. in the karnaphuli estuary, bangladesh, recent studies (lara, unpublished) showed that suspended particulate matter (spm) other than zooplankton contained significant amounts of chitin, especially in the size class < µm. the quantitative contribution of respectively nano-or bacterioplankton, microdetritus of biological origin, or resuspended sediment particles to the chitin pool in that size class is still unknown. particle load together with salinity significantly influenced estuarine vibrio distribution. we compared the microbial landscape dur ing a pre-monsoon situation and after a strong cyclone: the amount of cultivable vibrio, and its relative contribution to total aerobic bacteria, increased dramatically after the cyclone. amounts of spm also increased and there were higher salinities along the estuary. sediment resuspension and salt intrusion can thus strongly influence the abundance and distribution of estuarine vibrio population. the above findings call attention on essential questions relating estuarine dynamics and human health: are vibrios in sediment part of a benthic community with its own character istics or do they basically consist of a fraction of a pelagic population reaching the sediment after sedimentation of the particles to which they are attached? nair et al. ( ) also addressed the role of sediments as a possible vibrio reservoir in freshwater environments in calcutta. in florida, there was a predominance of non-o v. cholerae infections at the time the organisms flourished in the sediment (williams and larock, ) , which was detected down to -cm depth. higher sedi ment vibrio concentrations were associated with organic matter flocs occurring after the seasonal phytoplankton productivity maximum and during the zooplankton decline. this suggested that the flourishing of vibrio in the sediments was related to the presence of organic matter input from plankton detritus. thus, although plankton itself is an important aquatic vibrio reser voir, its relevance for fueling benthic vibrio seasonal cycles has probably been overlooked. the relevance of seasonally driven sediment resuspension in relation to annual cholera cycles in endemic regions deserves more attention. the incorporation of particle-bound vibrios and porewater nutrients into the water column could favor a sharp vibrio increase, even at otherwise unfavorable salinities (singleton et al., ) . future studies should investigate the links between the spatiotemporal estuarine variability and the ecology, diversity, and spreading mechanisms of vibrios including v. cholerae. a key question is how and to what extent these microorganisms persist in the transition from a brackish to a freshwater envir onment, involving strong gradients in salinity, ph, inorganic nutrients, dissolved and particulate organic matter, turbidity, plankton, and wetland vegetation. further, an ecohydrological research approach should focus on how the distribution of the above factors influences the relative abundance of v. cholerae compared to the total vibrio population and other bacterial groups in aquatic environments of west bengal, including water and sediment compartments. there have been efforts to predict cholera outbreaks through models relating disease incidence and environmental variables such as seawater temperature, chlorophyll content, height of the ocean surface, and rainfall, as well as by remote sensing (e.g., lobitz et al., ) . recently, an empirical model relating multiyear data of the number of cholera cases, rainfall, and chlorophyll was able to successfully reproduce outbreaks of cholera in kolkata and matlab over the time span of the data set (magny et al., ). yet, these authors stated that a finer temporal resolution (submonthly) in environmental data col lection was needed to improve mechanistic models and account for short-term variability, especially for the kolkata region. there is also evidence that cholera cases increased following a rise in ocean-surface temperature. however, a direct correla tion exists only for the spring peak, while during the rest of the year there are lags and even an inverse correlation between the two variables (colwell, ) . simple (lag) correlations between the seasonality of cholera and that of climate variables such as monsoon rainfall merely confirm that cholera is seaso nal (bouma and pascual, ) . these authors hypothesized that there would be two different aquatic habitats: the marineestuary type and the inland water bodies, with potentially different driving factors. although much has been speculated about possible ocean/ land interactions based on empirical correlations, the causal links between ocean parameters and cholera incidence in ripar ian inland villages are tenuous, as discussed in the following. zooplankton in freshwater has been considered a main trans mission means of v. cholerae to humans . although tidal transport of vibrio-carrying marine zooplankton toward the inland is likely and has been proposed by these authors as a possible infection source, until now there have been no studies demonstrating that marine copepods survive long enough to represent an infection source in freshwater, which is what people drink finally, and not seawater. simultaneous variation of two parameters does not imply causality and, although the existing mechanistic models can be useful as predictive tools, they have not significantly contributed to explaining the reasons for cholera endemicity or the existence of bimodal and unimodal occurrence patterns in the indian subcontinent. for example, sea-surface tempera ture in the bay of bengal shows a bimodal cycle similar to the seasonal pattern of cholera in dhaka, bangladesh (colwell, ; figure ) , and is therefore often used, directly or through covarying parameters, with success for such models. however, this seems to mask the fact that strong unimodal patterns are observed elsewhere in india (e.g., north bengal and vellore; jesudason et al., ; bouma and pascual, ) without any obvious relationship to the marine environment or even to temperature and rainfall. several studies found that the effect of rainfall on cholera incidence does not show any univocal pattern (glass et al., ; bouma and pascual, ; ruiz-moreno et al., ) . even in dhaka, which has a strong bimodal seasonality, there is no clear relationship between rainfall and cholera. the number of cases peaks before the monsoon (high rainfall period) and at its end, with a strong decrease in the middle of the monsoon. recently, hashizume et al. ( ) showed that the weekly number of cholera cases in the period - in dhaka did not show any direct relationship to rainfall, and suggested that river levelbelow flooding levelalso plays a role. river discharge is controlled not only by rainfall but also by snow melting in the himalayas and can control the survival of the bacterium through determining salinity and ph levels (bouma and pascual, ) . hashizume et al. ( ) stated that, because of the observed and potential effects of chemical changes in surface waters due to rainfall on vibrio survival and toxicity, it is necessary to quantify the level of v. cholerae in aquatic environments at the same time as measuring rainfall and river levels ( table ) . this section deals with examples of diseases derived from or influenced by high nutrient loads, particularly those derived from toxic algal blooms, as well as with the general effect of global changes in nutrient cycles on parasitic infectious diseases according to toxin type and exposure: skin irritation, stomach cramps, vomiting, nausea, diarrhea, fever, sore throat, headache, muscle and joint pain, liver damage, and kidney disease in the body nitrate is reduced to nitrite, which reacts with hemoglobin forming methemoglobin, and reducing blood ability to carry oxygen; affects mostly infants and old persons (pids). although arsenicosis affects millions of people, parti cularly in bangladesh, the problem arises from using water from wells reaching layers where groundwater naturally con tains high as levels and there is, to date, no obvious way that ecohydrological methods could help solve this problem. for this reason, we will not discuss this disease further in this chapter. eutrophication in water reservoirs or semi-enclosed water bodies leads to the formation of intensive phytoplankton blooms. during recent years, both the incidence and intensity of such blooms appear to be increasing, when examined at the global scale. this increasing severity of algal blooms may be a consequence of increasing levels of nutrient enrichment as a result of sewage disposal, increased agricultural runoff, and changes in hydrological regimes potentially related to climate change (unep, ) . blooms caused by toxic cyanobacteria (harmful algal blooms) lead to outbreaks of disease and dete riorated recreational and aesthetic values, causing both economic losses and illness and death of both humans and animals. in evolutionary terms, cyanobacteria are one of the oldest organisms on earth, dating back to more than ma (schopf, ) . they are oxygenic photosynthetic prokaryotes possessing the ability to synthesize chlorophyll a as their photosynthetic pigment. the nitrogen-to-phosphorus ratio (n:p) has been frequently used as a key indicator in predicting algal biomass and compositions, and its seasonal succession in lentic systems (tilman, ; kilham, ) . smith ( ) pointed out that bloom-forming cyanobacteria had a tendency to dominate in a lake when the n:p ratio was less than . the significance of the n:p ratio as a critical factor, however, is still controversial, due to the variability of the other chemical char acteristics and phytoplankton composition within a geographic region. for example, cyanobacteria blooms can be induced by increases in the phosphorus concentration instead of by a decrease in the n:p ratio (trimbee and prepas, ; sheffer et al., ) . cyanobacteria ( figure ) produce a variety of toxic com pounds known as cyanotoxins. the impacts of cyanotoxins on human health have been of increasing concern, as the impacts of cyanobacterial blooms on water supplies as well as nearshore marine ecosystems have become better understood. outbreaks of poisoning from cyanobacterial blooms can be catastrophic, such as the death of dialysis patients following exposure to inadequately treated water from the tabocas reservoir in brazil (pouria et al., ) or the hospitalization of children and adults who drank cyanobacterially contaminated water impounded by the solomon dam in australia (hawkins et al., ) . cyanobacterial toxins have also been implicated in mortality in wild fisheries and terres trial mammals, and can accumulate in the ecosystem . toxins are classified by how they affect the human body (who, c): hepatotoxins (which affect the liver) are produced by some strains of the cyanobacteria microcystis, anabaena, oscillatoria, nodularia, nostoc, cylindrospermopsis, and umezakia. neurotoxins (which affect the nervous system) are produced by some strains of aphanizomenon and oscilatoria. cyanobacteria from the species cylindroapermopsis raciborski may also produce toxic alkaloids, causing gastrointestinal symptoms or kidney disease in humans. not all cyanobacteria of these species form toxins and it is likely that there are other as-yet unrecognized toxins. further, cyanobacteria produce a wide range of secondary metabolites, among which new cya notoxins continue to be found. besides the recognized effects of the toxins mentioned above, a recent study opened up a discussion about possible new causes of known neurodegenerative illnesses. cyanobacterial strains were found to produce the neurotoxic nonprotein amino acid, β-n-methylamino-l-alanine (bmaa) (cox et al., (cox et al., , . the bmaa is considered a possible causative agent of human motor neuron disease, amyotrophic lateral sclerosis parkinsonism/dementia complex (als/pdc), and has been found to accumulate in brain tissues of patients with progressive neurodegenerative illness (murch et al., ) . this was first detected in humans as a consequence of dietary habits and biomagnification in terrestrial ecosystems in guam (cox et al., ) . however, sometime later, bmaa was detected in aquatic ecosystems, such as in seawater in the area of a trichodesmium bloom and in freshwater and brackish waterbodies (metcalf et al., ) . cox et al. ( ) isolated bmaa in several species of free-living cyanobacteria. possible implications of these findings (cox et al., ; ince and codd, ) are that bmaa of cyanobacterial origin might occur in diverse natural and controlled environments where massive cyanobacterial populations occur. because these environments can include waterbodies used for drinking and recreational use, bmaa in drinking water may contribute to chronic intoxication. this may involve incorporation of the neurotoxin into an endogenous protein reservoir with slow release (murch et al., ) and a possible lag between expo sure and effect of years or decades. since protein-associated bmaa can accumulate within food chains, it is possible that biomagnification of bmaa occurs in marine ecosystems in a way similar to that in terrestrial ecosystems (banack et al., ) . thus, production of bmaa by marine cyanobacteria may represent another route of human exposure to this neuro toxin. cox stated that the bmaa produced by the algae may act as a slow toxin. for these reasons, it would be advisable to monitor bmaa concentrations in drinking waters contami nated by cyanobacterial blooms and in fish and animals that may be ingesting the microbes, even at low environmental densities. this can be particularly relevant in semiarid or arid regions that are highly dependent for their drinking water supply on reservoirs, in which cyanobacteria can regularly occur on a seasonal basis, normally in summer. fertilizer use, widespread cultivation of leguminous crops, and fossil fuel burning have produced strong changes in the global n cycle (galloway et al., ) . more than half of all n fertili zers ever used in earth's history has been applied in the past two decades (howarth et al., ) . moreover, increased n loading in the environment often occurs together with that of phosphorus. in freshwater ecosystems in particular, a com bined increase in both n and p is highly likely to drive eutrophication and associated significant ecological change. mckenzie and townsend ( ) reviewed direct and indirect evidence that changing global nutrient cycles are influencing the dynamics and incidence of pids ( figure ). some of the disease agents discussed earlier in this chapter could react particularly sensitively to increased n and p loads. although generalizations are difficult, the evidence presented by these authors, together with past reviews by lafferty ( ) and townsend et al. ( ) , suggests a trend in which most asso ciations between increased nutrients and disease are positive. a parasite or pathogen may respond to nutrients directly, that is, without requiring an intermediate or vector host; or an inter mediate or vector host may respond to nutrients, mediating the overall disease response. there can be an increase in vector host population density as a result of increased primary productivity, or a decrease in population due to some disturbance related to nutrient addition, in both cases resulting in changes in transmis sion success of the parasite or pathogen (anderson and may, ; dobson, ; arneberg et al., ) . besides the above-mentioned increase in cyanobacterial blooms, increased nutrients could particularly affect ecological processes associated with, for example, malaria, schistomiasis, cholera, and filariasis, leading to a higher occurrence of these diseases. for example, vector-borne pathogens that cause malaria and schistosomiasis involve intermediate hosts (mos quitoes and snails) whose growth and reproduction depend on algae or weed abundance in their respective environments. where n additions cause greater plant growth and/or changes in plant species composition, the density of these intermediate hosts is also likely to be affected, with cascading consequences for the risk of disease. lafferty ( ) reviewed parasitic responses to a suite of environmental changes and found that, in most cases, eutrophi cation caused an increase in parasite abundance. johnson and carpenter ( ) suggested that planorbid snails in nutrient-rich environments grow faster. larger individuals are able to produce significantly more trematode cercariae at a faster rate. the avail able evidence suggests that, in general, nutrient additions should favor trematode development and increase disease risks. in the case of cholera, the bacteria display a strong associa tion with marine plankton, and, therefore, factors that cause increases in plankton primary productivity can also increase the prevalence of v. cholerae. thus, nitrogen-based eutrophication of coastal regions (nrc, ) has been linked to increased cholera risks (epstein, ; colwell and huq, ) , prob ably as an indirect response to plankton dynamics. changes in the n cycle are not globally uniform (galloway et al., ) . the largest changes have occurred in industria lized countries but the focus of global change is shifting to tropical and subtropical countries, where greatest relative changes in the n cycle over the next years are expected (galloway et al., ; dentener, ) . for example, the booming soybean agriculture in brazil in the last decade is leading to rapid increases in regional n deposition and nutrient loading to aquatic ecosystems (martinelli et al., ) . similar increases are occurring throughout tropical and subtropical portions of asia and central america. these same regions harbor the greatest diversity of human pids (guernier et al., ) , including those that currently cause the majority of pidrelated human deaths (who, b) . thus, the next decades will probably bring an increase in the potential for nutrients, especially n, to affect parasitic and infectious diseases in these regions. the changes in temperature and rainfall regime in temperate regions and the changes in land use resultant from them or from market shifts can exacerbate that potential. diseases produced by viral infections can emerge, reemerge, and be transmitted by several different, but often interlinked, mechanisms involving tight interactions between man and domestic and wild animals sharing artificial or natural aquatic systems. table summarizes some viral diseases of worldwide relevance. in the following section, we will focus on avian influenza due its multiple and complex connections with the dynamics and use of wetlands by man and animals. . . . . influenza: human and animal links between artificial and natural wetlands nutrient reduction in wastewaters or surface waters is a prior ity for reducing risks to human health. nevertheless, from the point of aqua-and agriculture, the nutrients contained in wastewater are a valuable resource, in particular in arid and semiarid regions. wastewater form has been used for aquaculture, for example, in duck ponds, in several countries, mainly in asia, for centuries to produce human food. organizations such as who, food and agriculture organization (fao), etc., have developed guidelines for the safe use of wastewater, excreta, and gray water in agriculture and aquaculture in order to provide a basis for the develop ment and implementation of health risk assessment and management approaches, including standards and regula tions, to address hazards associated with human waste-fed aquaculture (edwards, ) . however, wastes and fecally polluted surface water are often used without any pretreat ment or assessment of the presence of pathogens. various hazards are associated with waste-fed aquaculture: excretarelated pathogens (bacteria, helminths, protozoans, and viruses), skin irritants, vectors that transmit pathogens, and toxic chemicals. wastewater systems were also developed independently in india from the s, in china from the s, and in vietnam from the s onward, but they were designed primarily for aquaculture, not to treat wastewater. few engineered waste water-fed aquaculture systems have been developed recently. systems primarily engineered to treat wastewater that incorpo rated aquaculture were developed in germany from the end of the nineteenth century, but only the munich system remains, and only for tertiary wastewater treatment and currently as a bird sanctuary (edwards, ) . in this, the following aspects in the dynamics of bird popu lations are of ecohydrological and biomedical relevance. during migratory movements, birds carry pathogens that can be transmitted between species at breeding, wintering, and stopover places where numerous birds of various species are concentrated, such as wetlands. a study by jourdain et al. ( ) focused on bird migration routes to the camargue in relation to risk of pathogen dispersion into western mediterranean wetlands. they considered two pathogens clo sely associated with wild birds: avian influenza (ai) virus and west nile virus (wnv). the ai viruses have a water-borne transmission, and ducks are their main natural reservoirs (easterday et al., ; alexander, ) ; wnv has a vectorborne transmission, and passerines are believed to play a major role in the amplification cycle (hurlbut, ; malkinson and banet, ) . despite different transmission cycles and ecology, both viruses are known to be carried by reservoir birds during migration and have been associated with emer ging disease transmission risk for humans and domestic animals (rappole et al., ; reed et al., ; olsen et al., ) . environmental conditions, avifauna abundance, and diversity, as well as the interactions among birds from different species and departure sites in stopover wetlands, may be of key importance in terms of virus communication (hudson et al., ) . for water-transmitted pathogens such as ai viruses, the risk of transmission may be associated with the number of ducks congregated on the same water body, particularly in autumn and winter. this crowding of wintering species, in addition to the permanent presence of a transient population of birds using wetlands to stop off during migration, could provide the conditions for the circulation and rapid dissemi nation of ai viruses. for vector-transmitted pathogens such as wnv, transmission possibilities depend both on reservoir bird density and on the dispersion capability and activity periods of the arthropod vectors. the risk for interspecific transmission of disease is particularly problematic when wild and domestic species are involved. ducks are the aquatic birds most likely to come in contact with free-range poultry, especially because the presence of congeners can induce migrating wild ducks to make a stopover (jourdain et al., ) . the study by jourdain et al. ( ) showed that western mediterranean wetlands are a hub for birds from several differ ent origins in central asia, siberia, northern and eastern europe, western africa, and the mediterranean basin. as exam ple for the potential of wetlands for introduction or reemersion of these viruses, they state that wnv dispersion by birds migrat ing from sub-saharan africa might explain why an outbreak occurred in in the camargue, even though the virus had not been observed there since the s. besides migration, breeding ducks in the aquaculture ponds can increase virus circulation between ducks, water, sediment, fish, and man. in a study (markwell and shortridge, ) of the occurrence and persistence of influ enza viruses (hong kong type) within domestic duck communities, the virus was isolated throughout the year from feces or pond water or both, indicating a cycle of water-borne transmission. infection was asymptomatic and virus persistence in the duck community appeared to be dependent upon the continual introduction of ducklings sus ceptible to infection onto virus-contaminated water, since the feces of ducks - days old were generally virus-free despite the ducks' exposure to the virus in pond water. the normal practice of raising ducks of different ages on the same farm, where the water supplies are shared (figure ) , appears to be instrumental in maintaining a large reservoir of influenza viruses in the duck communities. domestic ducks may act as a silent reservoir for the h n ai virus. the concern is greatest in rural areas of affected countries, where traditional free-range ducks, chickens, and wildlife frequently share the same water source. domestic ducks can harbor the virus for long periods and without showing any sign of illness. an altered role for domestic ducks is further supported by evidence that the h n virus circulating in parts of asia has increased its virulence in chick ens and mice (a laboratory model for mammals), and has expanded its host range to include larger mammals (e.g., cats and tigers), not previously considered susceptible to infection (fao, ) . the assessment of respective roles of routes and timing of wild waterbird migration and poultry imports is of utmost importance in order to objectively identify the origin and pos sible evolution of an outbreak in a determined country. for example, the avian flu outbreak in nigeria in may have been caused by the supply of infected live poultry including day-old chicks from different sources, including east asia and turkey, and not by wild waterbirds. this is supported by sam plings of wild waterbirds in african wetlands, in which no evidence of the h n virus was found, indicting that wild birds probably played a relatively minor role in the spread of ai in that region. northward migration of wild birds from africa to europe in the northern spring of did not cause any major outbreaks. nor do wild birds seem to play a role in indonesia, where h n has been present for some years and several cases of human infections have been recorded. however, although not many major outbreaks took place in europe in , there is evidence to suggest that wild birds did play a significant role in spreading the disease on the european continent (aiweb, ). useand scarcityon human health: some examples from aquaculture, megacities, dams, and intensive agriculture aquaculture in or close to wetlands is increasing worldwide. besides being responsible for massive wetland destruction, aqua culture itself faces serious problems, arising from several diseases that can affect shrimp ponds. among the groups of microorgan isms that cause serious losses in shrimp culture, the best known are bacteria because of the devastating economic effects they have on the affected farms. as mentioned before, vibrio organ isms attach themselves preferentially to chitin surfaces, such as in zooplankton and shrimp exoskeletons. bacterial diseases, mainly due to vibrio, have been frequently reported in penaeid shrimp culture systems. at least vibrio species are implicated in disease outbreaks in shrimp, including vibrio harveyi, v. alginolyticus, v. vulnificus, v. parahaemolyticus, and v. cholerae (non-o ) (venkateswara, ; figure ). vibrios can produce different chitinases to degrade various chitin types (svitil et al., ) in marine, estuarine, and figure example of vibrio disease affecting shrimp. in such severe cases, extensively melanized black blisters can be seen on the carapace/ abdomen of the infected animals. copyright national institute of oceanography, dona paula, goa, india, . pond and irrigation canal next to live poultry markets. in http://www.eastwestcenter.org/index.php?id= &print= freshwater environments. further, meibom et al. ( ) found that v. cholerae can acquire new genetic material by natural transformation during growth on chitin. thus, natural compe tence occurring in chitin-attached bacterial communities can act as a powerful driver of v. cholerae evolution, which could be accelerated by environmental events such as high nutrient input, giving rise to copepod blooms. it is still unclear whether growth on a determined type of chitin substrateand the production of the corresponding specific chitinasespromotes the capture of external genetic material by vibrios. this empha sizes the need for biogeochemical characterization of different aquatic microhabitats, such as different types of chitin-contain ing particulate matter, besides living zooplankton, in environmental studies of vibrio diversity and virulence. as organic-matter-rich aquatic environments contain multiple microbial strains and species and high concentrations of bac teriophage and free dna, horizontal gene transfer (hgt) provides the most likely explanation for why vibrionaceae have developed high levels of genomic diversity (meibom et al., ) . interestingly, the cholera toxin gene (ctx) is a phage-mediated mobile genetic element that is transferrable to genetically closely related bacterial strains. in the aquatic environment, vibriophages can regulate seasonal disease out breaks, for example, seasonal cholera epidemics in dhaka were inversely correlated with the prevalence of environmental cho lera phages (faruque et al., ) . the v. cholerae (non-o ) is frequently isolated from sewage, estuarine waters, and seafood in cholera-endemic and noncholera-endemic countries. it has been associated with sporadic episodes of diarrhea worldwide, but has not caused pandemics. interestingly, in , there was the first report of an epidemic of diarrhea caused by v. cholerae non-o that produces heatstable toxin, affecting khmers in a camp in thailand. in con trast to the v. cholerae o isolated from the same camp, in % of the cases, the non-o were resistant to three or more anti biotics (bagchi et al., ) . this calls attention to several important aspects in relation to threats to human health. the fact that the toxin is heat stable could imply a higher diarrhea risk for humans consuming cultured seafood as cooking would not completely eliminate toxin activity. its higher resistance to antibiotics compared with v. cholerae o potentially increases the disease hazards associated with these non-o strains. further, as mentioned previously, the abundance of chitinac eous substrate can favor mutations. thus, just as v. cholerae o evolved from a nonpathogenic to a pandemic-causing form (faruque et al., ) , it cannot be excluded that the high individual density of aquaculturein the same way as megacitiescould be favoring the emergence of new and highly pathogenic vibrio types. in many of the world's cities, water management and sanitation are in crisis and will dramatically worsen with the continuing growth of cities and slums. sewage pollution is the largest and most common type of pollution and one of the most common causes of illnesses. illnesses caused by sewage pollution are estimated to affect the health of more than million people at any one time. contaminated water, inadequate sanitation, and poor hygiene cause over % of all disease in developing countries; diarrhea is the world's second most serious killer of children, but paradoxically in % of cases it could be easily prevented or treated. pollution of water sources by sewage contributes to billion cases of diarrhea in the world each year, killing some . million children under the age of . poor sanitation currently affects . billion people, % of the world's population, who lack access to even the most minimal toilet facilities. the number of people without sanita tion will double to almost billion in , as the world becomes more urbanized (anonymous, ) . some people are moving to cities from the country side every day. at least million people in africa, asia, and latin america now live in squatter settlements without any sanitation whatsoever. the pollution of rivers and groundwater by sewage spreads disease and causes environmental degrada tion. in latin america, as a whole, only % of sewage receives any treatment. in asia, the level of sewage in rivers is times higher than the united nations (un) guidelines. levels of suspended solids in asia's rivers almost quadrupled since the late s. every minute . million liters of raw sewage are dumped into the ganges river (vidal, ) . most megacities are in asia. dhaka's population rose from in the early s to ∼ million today, including the metropolitan area, and will probably reach million in . in the same time, kolkata's population grew from to million; including the metropolitan region, its population is million and is predicted to reach million in . pakistan experienced one of the highest growth rates of popu lation worldwide: it quadrupled in only years to over million in (prb, ) . according to the world bank, karachi is one of the fastest-growing megacities of the world and is expected to rank seventh by the year (kamal, ) . the country faces a serious situation in terms of water availability, depletion, and pollution of its water bodies and irrigation systems as well as a severe degradation of its coastal ecosystems. this complex and multifaceted setting will be clo sely analyzed in the following sections. it has been reported that at least of the towns of the city are supplied with water unfit for human consumption, in most cases infected with escherichia coli. only around % of the total sewerage generated by karachi at present is treated. the e. coli, found in human feces, and other bacteria found in drinking water could cause life-threatening diseases, including diarrhea and cholera. the bulk of the drinking water concerned is taken from the indus river. bacteria easily enter the drinking water as the pipelines are rusted and leaking (irin, ) . lowintensity seismic activity, though normally not felt by people, probably further damages worn-out pipelines. additionally, due to the water shortages, the pipelines remain empty for a considerable amount of time daily, during which time they develop negative pressure and absorb moisture and sewage that has leaked from the nearby, similarly worn-out sewers. additionally, after rains, rainwater mixes with sewage and gar bage can enter the pipelines through the leaks to contaminate the drinking water supply, making people vulnerable to numer ous health hazards (hasan, ) . karachi is situated in a desert. however, in a study by sheikh et al. ( ) the analysis of microbiological data for the period - showed the permanent presence of cholerawith seasonal periodicityin karachi. cholera cases peak each year between may and august in both epidemic and nonepidemic years. both v. cholera o and o serogroups were involved in the outbreaks in and ; o disappeared in . the role of rain in disease seasonality and incidence is not clear. rainfall is scarce and sporadic, usually only between june and august. in , the city could have been flooded, with wide spread overflowing sewers, whereas, in , there was virtually no rain at all. cholera appears each year before the rains, and epidemic years in the - data set appear to have occurred independently of rainfall. like most enteric diseases in an endemic setting, cholera in karachi is a disease of young children. the mean age of patients with acute cholera in karachi closely resembles that in the rest of the indian subcontinent where social conditions are com parable. despite this association with poverty, % of the patients in the study were admitted to expensive private rooms in good hospitals. this shows that, in a city with a sanitary infrastructure like that of karachi, personal wealth affords no protection (sheikh et al.. ) . visitors and tourists are also at risk. in the same context, despite the common perception that bottled water was safe and pure, microbiologi cal tests showed that about % of samples of water supplied in many bottled brands tested all over the city was unfit for human consumption (hasan, ) . according to the same above-mentioned study, in , the new strain of v. cholerae, serogroup o , established itself in karachi and during and karachi experienced over lapping, but distinct epidemics of both strains. the serogroup o never wholly replaced serogroup o , and by it had disappeared. at that time, it was still unclear whether the dis appearance would be permanent, or whether o would reemerge in subsequent epidemic years. karachi is in a semi desert area, and the strain may not be able to maintain itself outside the human host (sheikh et al., ) . this strain has also shown diminished ability to maintain its epidemic potential in bangladesh, and it has been suggested that one reason for this may be that it is less able to persist long term in the aquatic environment (faruque et al., ) . however, years later, in july and june , cholera outbreaks were detected by a diarrhea surveillance system in a fisher village near karachi (siddiqui et al., ) . the first outbreak was caused by v. cholerae o and the second one by serotype o . it would be erroneous to conclude that, because of the relatively small number of persons affected, these cases are not relevant in terms of public health. on the contrary, they should be considered extremely valuable indicators of environmental change, especially of aquatic systems, which provide an early warning of possible future trends for policymakers and sanitar ians. water source was a risk factor only in the first outbreak: a reservoir in the village containing brackish water was only used for washing utensils and clothes and for bathing. only illness caused by v. cholerae o was associated with the use of reservoir water, while o cases were not. washing the clothes of infected persons may have introduced the pathogen into the reservoir. this implies that v. cholerae o was probably able to survive for a time outside the body and in water long enough to infect other people. this may be partly because the water was salty and that v. cholerae is a salt-loving bacterium. in summary, fecal pollution, increased nutrients, turbidity, and sodium content create favorable conditions for the propagation of v. cholerae in pakistan's coastal zone, megacities, and irrigation systems. when the increasing pollu tantchemical and microbiologicalload reaches the coastal region, it encounters a disturbed wetland ecosystem (discussed in section . . . . ), where vibrios could potentially multi ply and mutate to new pathogenic types. a close regular surveillance of vibrios at basin level, including in the coastal region, rivers, and channels, and in humans is essential in this region, which has the potential to become an epidemic center. further, restoration of riparian forests and wetlands habitat should be a priority to avoid further habitat loss, and potential host shifts, although salinization would probably preclude the reinstallation of the same species existent before dam building and population explosion. the hoogly river is the most important source for the water supply of kolkata. through an agreement with bangladesh, only a determined amount of water from the ganges can be diverted into the hooghly river during the dry season. although this does not increase the amount of pollution in the river, it does increase its concentration. during the mon soon, rubbish and feces are washed out from the city into the ground and into the river (karthe, ) . around % of the water supply is lost through leakages in the obsolete distribu tion network, reservoirs, and public water tap connections. however, the disposal of sewage is an even greater threat to human health. reduced capacity of the inadequate sewer net work, aggravated by obstruction caused by mud or garbage, as well as flooding during the monsoon produces pollution of surface and groundwater with enteric bacteria. as in karachi, interruptions or shortages in the water supply produce a negative pressure in the pipelines, which then absorb polluted water that had leaked from sewers and the surface, especially during the monsoon season. before and after the monsoon, water quality increases, that is, bacterial load decreases. following several cholera epidemics, the chlor ination of unfiltered water supply began in . this reduced cholera incidence, but supply of potable water to many parts of the city is still insufficient. people in shanties frequently get untreated water from hydrants, or from the river (hensgens, ) . cholera seasonality in kolkata is further discussed in section . . . . . the situation in london years ago resembled current conditions in many megacities in developing countries. by , half of the population of britain was living in townsthe first society in human history to do so. over the previous years, britain's population had risen at an unpre cedented rate. large towns were desperately unhealthy, with death from sickness at a level not seen since the black death (daunton, ) . london had a large scavenger class living off the refuse of the citya group so numerous that it could have formed the fifth largest city in england. new epidemics affected the citiescholera and typhoid were carried by polluted water, typhus was spread by lice, and 'summer diarrhea' was caused by swarms of flies feeding on horse manure and human waste. london suffered from recurring epidemics of cholera and in - more than londoners were killed by the disease (johnson, ) . the frequent occurrence of cholera in london gave impetus to legislation, enabling the metropolitan board to begin work on sewers and street improvements. by most of london was connected to a sewer network brilliantly devised by joseph bazalgette (bbc, ) . the flow of foul water from old sewers and underground rivers was intercepted and diverted along new, low-level sewers, built behind embankments on the river front and taken to new treatment works. by , both the albert and the victoria embankments had been opened. the victoria embankment protected bazalgette's low-level sewer from the hydraulic pressure from the thames estuary. the chelsea embankment was completed in . the public health act of required local authorities to implement building regulations, or bylaws, which insisted that each house should be self-contained, with its own sanitation and water. this change in the design of housing complemented the public investment in sewers and water supply. cholera never reappeared in london after that. london was the largest city on the planet in , but now it is on the small side, in comparison to, for example, mexico city, são paulo, or mumbai. massive shantytowns have exploded at the margins of today's megacities. in such places, the water-borne diseasesincluding cholerathat plagued victorian london are still widespread, thanks to insufficient public health and sanitation resources. worldwide, up to a billion people live in shantytowns and according to some projections this will increase to a quarter of the world's popula tion by (johnson, ) . despite enormous progress in the molecular biology of v. cholera, still little is known about basic forces, such as spatial biogeochemical gradients, seasonal rainfall variations, or cyclones, driving its abundance, diversity, and virulence in the basins of rivers and estuaries of the indian subcontinent. the most recent detailed studies on seasonal variations of estuarine salinity and related urban cholera incidence are from the s (chatterjee and gupta, ) . these compare the river systems kolkata-hoogly (a main branch of the ganges) and london-thames (data from the nineteenth century), and are discussed in miller et al. ( ) . an important aspect of the s data is that minute but clearly delimited salinity oscillations (e.g., . - . and . - ppt) in the hoogly river tightly correlate with cholera incidence in kolkata. several authors reported significantly higher salinity ranges for the growth and persistence of v. cholerae in the environ ment, for example, . - ppt (miller et al., ) or - ppt (singleton et al., ; louis et al., ; randa et al., ) . salinities < ppt were considered suboptimal (miller et al., ) . however, kolkata's data clearly indicate cholera out breaks at much lower salinities. such oscillations could also be a proxy of other processes occurring at basin level, which were responsible for triggering the cholera outbreaks. vibrio survival at low salinities can be facilitated by adsorption onto algae, zooplankton, or by high nutrient concentrations. unfortunately, this information mostly originated from stag nant water bodies or short-term investigations (e.g., islam et al., , and references therein) , but no studies are available about the seasonality of hydrology, biogeochemistry, and vibrio dynamics in flowing waters of the large rivers in this region through which vibrios most likely spread from the coastal zone toward inland habitats. since the s, seven large dams for irrigation purposes have been constructed in india. the farakka barrage, complete in , diverts the ganges river water into the hooghly river during the dry season to flush out the accumulating silt in the port of calcutta. it cuts off bangladesh's water supply, elevating salinity, and has affected fisheries, caused desertification, and hindered navigation, and poses a threat to water quality and public health (wolf, ) . there is evidence of changes in cholera seasonality due to hydrologic disturbances. before the s, the peak cholera season in dhaka was november-february; now it is september-november. in kolkata, season ality has changed twice since the mid- s (niced, . these shifts may be related to changes in salinity, particle load, and associated estuarine biogeochemistry due to, for example, the construction of the farakka barrage on the river ganges (mirza, ) or increased melting of himalayan glaciers (unep, ) . more that years ago, miller et al. ( ) postulated that dam construction in india could influence vibrio dynamics by salt intrusion. these aspects deserve further investigation; apart from the s data, there are no other published data series systematically relating these parameters in the rivers of the region with cholera incidence. this informa tion is essential in order to evaluate the transboundary effects of dam construction and water management. dam construc tion in india has reduced riverine discharge in bangladesh, inducing desertification in its northern sector and facilitating salt intrusion into its estuaries, particularly in the southwestern region (wolf, ; adel, ) . this resulted in changes in land use from rice cultivation to shrimp farming in the southern bay of bengal (gebauer, ) (discussed in section . . . ). salinization of inland water bodies can facilitate the spreading of the halophilic vibrio organisms and affect drinking water availability. on the other hand, global warming increases glacier melting and associated riverine runoff. both factors, in a frame of increasing intensity and frequency of cyclones and flooding events, create an extremely complex situation in the coastal zone that could result in shifts in seasonal cholera patterns. despite the different overall climatic setting of pakistan as com pared to india and bangladesh, increasing water needs in pakistan are leading to a similar situation in the coastal zone, including increased cholera incidence. the common factors are the halophilic character of vibrio cholerae and other vibrios and the salinization of estuaries and inland waters. water needs for irrigation of desertic and semidesertic areas, as well as for drinking water supplies, mainly for karachi and islamabad, have led to the construction of several dams along the indus river. within the sindh province, there are three major barrages on the indus-guddu, sukkur, and kotri. severe reduction of water flow below the kotri barrage started affecting environments in the area from s onward, with the following consequences in the river basin: ( ) drying up and death of riparian forests, figure the indus delta faces major degradation threats, whose major cause is the reduction in the flow of freshwater from the indus river. as the delta dries up and the mangrove forests decline, the sea is slowly sweeping in. which occurred soon after ; ( ) reduction of the area under fruit and vegetable crops; ( ) destruction of natural pastures causing a reduction in animal populations; and ( ) desertifica tion leading to a shifting of human settlements. in the coastal region, intrusion of seawater in the river bed to a distance of km upstream from the shore, with percolation of saline water from the riverine areas into groundwater of adjoining irrigated areas, has turned shallow water lenses brackish ( figure ) . another reason for accelerated salinization in the indus river is the saline water discharges from the salinity control and reclamation program in the north-west frontier province, punjab, and india (hasan, ) . along the coast, the increase in salinity of seawater along the whole coastline of sindh has resulted in damage to man groves, colonization by other halophilic species, and the abandonment of ∼ ha of land reserved for shrimp farming by the government of sindh. sea shrimp can survive within salinity range of - of water, but in the space of years , salinity rose beyond the tolerance limit. water salinity in sea creeks and estuaries increased from ∼ to over ppt, making estuaries inhabitable for some shrimp and other species of commercial interest. in conditions of low salinity, shrimp farming could have been established all along km of seacoast. sea fish and prawn catch has declined considerably and severe erosion due to reduced sediment load occurs along the coast. in the coastal region, the livelihood of fishing communities and the fishing industry as a whole depends on ecosystem integrity. however, this has already been devastated by reclamation of former marine areas, and of mangrove marshes and mudflats. it desperately needs to be protected, for no city that destroys the ecology of the region where it is situated can be sustainable. the south asian tsunami gave ample proof of this and so did the flooding of karachi, much of which is the result of reclama tion from mangrove marshes, creeks, and natural drainage channels for elite real estate (hasan, ) . in addition to the deeply disturbed aquatic ecosystems described above, only % of cities with a population of over have wastewater-treatment facilities. of the wastewater generated daily, % is used in agriculture and % is disposed of into rivers or the arabian sea (iwmi, ) . directly or indirectly, % of the people of sindh, in rural or urban regions, drink water from the indus. salt content at kotri reaches . ppt in winter months, and supplies to karachi range from . to . ppt (panhwar, ) . the combina tion of a riverine environment with increasing salinity, growing populations, lack of sanitation, input of untreated sewage, drinking water contaminated with enteric bacteria, and rela tively high sodium content is very similar to that in london during the cholera epidemics in the nineteenth century (see section . . . . ). recently, a cholera outbreak in mirpur khas, a district of sindh province, has been reported (anonymous, ) . scientists at the university of health sciences found out that around % of the patients were affected by cholera instead, as was previously thought, by gastroenteritis. the authorities have been requested to pay particular attention to this outbreak of cholera, which could spread to the other areas of the province. mirpur khas has a population of ∼ , has successful agriculture, and is con nected to the indus via irrigation canals. the irrigation system of pakistan has been considered "one of the largest contagious systems of the world" by gachal et al. ( ) . the reservoir formed by the three gorges dam (tgd) is the largest in the world at over km in length. studies about the impact of parasite dynamics have been restricted to medically important species such as schistosoma japonica (zheng et al., ) . these studies have focused on the distribution of the intermediate host oncomelania hupensis within the tgd area and associated downstream water bodies. before construction of the dam, neither o. hupensis nor s. japonica occurred in the reservoir region. however, it is widely predicted that the dam will lead to the introduction of s. japonica into the tgd region, while downstream both positive and negative effects on schistosomiasis transmission will occur (zheng et al., ) . nevertheless, a survey of the recently filled reservoir (jobin, ) concluded that because of the very steep shoreline along most of its length and subsequent narrow photic zone, which provides only a limited area for the growth of plants, there was little chance of o. hupensis, principally a marshland snail, becoming established. however, these unfavorable topo graphic conditions do not preclude other mollusk species colonizing the shoreline (morley, ) . for example, former gravel quarries converted into lakes have a steep-sided profile with a narrow discontinuous zone of plant life but support a diverse molluskan-trematode community (adam and lewis, ; morley et al., ) . river blindness is an important parasitic disease around tropi cal dams in africa, along the red sea in arabia, in central america, and in parts of south america. the rapids of the upper nile river used to be a classic focus of this blinding parasite, spread by the bite of a species of blackfly, which breeds in white-water habitats and on dam spillways. in uganda (jobin, ) , the history of river blindness can be traced to the owen falls dam in the upper nile river. this dam flooded out owen falls and also ripon falls near the outlet of lake victoria. the history of the impact from the owen falls dam on onchocerciasis over the last years shows the importance of optimal water current velocity regulation for the avoidance of reduction of this and other water-borne dis eases such as schistosomiasis. prior to construction of the owen falls dam (figure ), river blindness was endemic among the buganda people, downstream along the nile. in , the prevalence of the parasite was %. to protect the workers, weekly applications of ddt were made at the outlet of lake victoria, treating the entire flow during the construction phase, and eliminating the blackflies for at least km downstream. after dam completion in and discontinuation of ddt applications, the black flies did not return to their former habitats downstream of the dam. by , the prevalence of the parasite had decreased to . % among the populations along the river. the fact that blackfly populations did not return to former levels indicates that there must have been a change in the basic habitat condi tions in the river. the dam had two major hydraulic effects on the river: one effect of turbine operation is a reduction of velocities downstream. the preferred range of water velocity for breeding of the east african species of blackfly involved in river blindness is between . and m s − . at present, the mean velocities downstream of owen falls dam are between . and . m s − , slightly less than the required velocities. prior to dam construction, the mean velocity was roughly twice the present, and thus highly suitable for blackfly breeding. yet, the major ecohydrologic effect of the dam reservoir was the complete submergence of owen falls and ripon falls upstream of the dam. these falls were preferential sites for blackfly breeding, and their permanent submergence eliminated the breeding completely. in west africa, dam construction has led to a significant switch in dominant water-borne diseases. the volta river basin extends over six west african countries ( % in burkina faso, % in ghana, and % in togo, benin, cote d'ivoire, and mali) and covers an area of about km . the volta lake is the largest man-made lake in the world, created after the construction of the akosombo dam in . the primary purpose of the project was to supply cheap electricity to smelt aluminum, other significant uses being transportation, fishery, water supply (commercial and domestic purposes), tourism, and irrigation. construction of the volta lake led to the resettlement of about people from several hundreds of villages. in the other riparian countries of the basin, small and larges dams have been built by governments, nongovernmental organizations (ngos), and local people to secure food produc tion after the severe droughts that occurred in the s and s. in the nakambe sub-basin (burkina faso) alone, more that small dams have been built, mostly during that period (barry et al., ) . there have been serious health issues associated with the volta lake, in particular with two major diseases: schistosomia sis and river blindness. before the creation of the volta lake, schistosomiasis was endemic in ghana; but endemicity was low along the volta river. according to an epidemiological survey done in - before the lake was formed, infection rates of schistosomiasis in the area had been - %, mostly affecting children. in the asukwakwaw area, north of the akosombo dam, the prevalence of onchocerciasis is now almost %. principal public health impacts of the formation of the lake have included reduced prevalence of river blindness, but increased incidence of urinary schistosomiasis and a mas sive increase in malaria, as discussed in the following paragraphs. the dam virtually halted the rate of flow in the volta river, increasing stagnant water conditions and consequently creating ideal breeding grounds for carriers of water-borne diseases. in the period following the construction of the dam at akosombo, there has been a steady decline in agricultural productivity along the lake and the associated tributaries (gyau-boakye, ). the land surrounding lake volta is not nearly as fertile as the for merly cultivated land residing underneath the lake, and intensive agricultural activity has quickly exhausted the already inade quate soils. without the periodic floodings that brought nutrients to the soil, before the natural river flow was halted by the dam, upstream agricultural systems are also losing soil ferti lity (van de giesen et al., ) . the growth of commercially intensive agriculture has produced a rise in fertilizer runoff into the river. this, along with runoff from nearby cattle stocks and sewage pollution, has caused eutrophication of the river waters (gyau-boakye, ) . this nutrient enrichment, in combination with the low water movement, has allowed for the invasion of aquatic weeds (cerratophyllum) (fobil and attaquayefio, ) . these weeds, associated with the aquatic snail, the 'intermediate host', together with mass migration into the fishing commu nities from regions in which the disease was endemic, have led to a great increase in the prevalence of schistosomiasis in many localities around the lake. the presence of aquatic weeds along the lake and within tributaries has resulted in even greater devastation to local human health as they provide an excellent habitat not only for snails but also for mosquitoes (gyau-boakye, ) . before the construction of the akosombo and kpong dams, malaria was not much of a problem along the swift-flowing volta river, but, when it became a stagnant lake, it became a greater public health problem in lakeside villages. by , urinary schisto somiasis had increased to become the most prevalent disease in the area, affecting some % of lakeside residents (gitlitz, ) and reaching a prevalence rate of % among children in certain localities. the problem of schistosomiasis in the lake basin must be seen as embracing both the lake and the volta delta. the migratory habits of the fishermen ensure the spread of the disease from endemic areas to other areas. in particular, resettlement villages have showed an increase in disease pre valence since the establishment of lake volta, and a village's likelihood of infection corresponds to its proximity to the lake. previously, the population in the basin generally lived away from the main watercourses because of the threat from water borne diseases. children and fishermen have been especially hard hit by this rise of disease prevalence (zakhary, ) . additionally, the degradation of aquatic habitat has resulted in the decline of shrimp and clam populations. the physical health of local communities has declined as a result of this loss of shellfish populations, as they provided an essential source of dietary protein (fobil and attaquayefio, ) . conversely, while leading to a dramatic increase in schisto somiasis, the lake has flooded out the riparian forests which constituted a breeding place for a species of tsetse fly, glossina spp. from the palpalis group, the vector of protozoan trypanosoma brucei gambiense, which causes the western african trypanosomiases (sleeping sickness) in people. the lake has also inundated and eliminated the major breeding sites of the onchocerciasis blackfly in rapidly flowing streams and rivers north of the akosombo dam. the construction of the second dam at kpong also eliminated the breeding sites downstream of akosombo and therefore stopped the transmis sion of river blindness in the vicinity. the main benefit to health because of the construction of the akosombo dam in and the kpong dam in is undoubtedly the reduc tion of the incidence of onchocerciasis in the volta basin. about fishermen living mostly in isolated villages around the lake were exposed to the riverine disease and did not have access to health facilities (jobin, ) . increased global demand for biofuels has incentivized sugar cane plantation in brazil, giving rise to several social and environmental modifications (martinelli and filoso, ) . the widespread occurrence of generalist animal species in sugarcane areas has been associated with public health pro blems. for instance, the population increase of the semiaquatic rodent, capybara (hydrochoerus hydrochaeris), in the piracicaba river basin has led to the spread of brazilian spotted fever (bsf) (labruna et al., ) . the bsf is the most important tick-borne disease in brazil and is caused by the bacterium, rickettsia rickettsii, and transmitted by the tick, amblyomma cajennense, its main vector, and capybaras serve as host for the ticks (estrada et al., ) . r. rickettsii infections can cause a wide range of clinical manifestations, ranging from asympto matic or mild febrile illness to overwhelming and fatal disease. failure in diagnosis and delayed therapy have contributed to hidden mortality, frequently a result of atypical fulminant forms of the disease (gonçalves da costa et al., ) and physician's lack of knowledge about the disease, which is exa cerbated by the difficulty of adequate confirmatory laboratory tests during its acute phase. mortality can reach % of the infection cases. the bsf has been known in brazil since . during the period between and the s there was a marked drop in the number of reported cases of bsf in brazil, as well as in the united states (angerami et al., ) . however, since the s an apparent reemergence of the disease has been observed with an increase in the number of reported cases in the southeast of brazil (angerami et al., ) . rickettsial diseases have been considered emerging zoo noses worldwide (raoult and roux, ) and should no longer be classified as rare diseases in brazil. despite the still moderate number of bsf cases, its increasing trend, together with high mortality rates, reflects and calls atten tion to deep changes in land use and habitat structure in brazil. increased fertilizer use, pollution, and soil erosion have caused deterioration of aquatic systems. as colluvium sediments are transported downhill across the landscape from sugarcane fields, they are deposited onto wetlands, and into small streams, rivers, and reservoirs. deposition affects water quality, and ecosystem biodiversity (politano and pissarra, ) and functions. high rates of n export into rivers draining watersheds heavily culti vated with sugarcane in brazil, such as the piracicaba and mogi river basins, have been reported (filoso et al., ) . the indus trial processing of sugarcane for production of sugar and ethanol is another source of pollution for aquatic systems with poten tially harmful effects for human health. waste products (vinasse) are rich in organic matter, and increase the biochemical oxygen demand (bod) of waters receiving these effluents, often causing anoxia (ballester et al., ) . with the boom of ethanol pro duction in brazil in the early s, new legislation was enacted to ban the direct discharge of vinasse into surface waters. since then, nutrient and carbon-rich vinasse has been mixed with wastewater from washing sugarcane and is recycled back to sugarcane fields as organic fertilizer (gunkel et al., ) , although this practice is still far from generalized. as a conse quence, high nutrient concentrations in these effluents also contribute to the problem by enhancing algal blooms and pro moting eutrophication of surface waters (matsumura-tundisi and tundisi, ) . the increase and dispersion of the capybara population and the associated health risk is most likely due to a strong anthro pogenic habitat modification caused by extensive monoculture. paradoxically, this situation could be aggravated by current efforts to restore aquatic ecosystems. typical capybara habitat is com posed of two main components: water and a patch of forest or woodland. in são paulo state, capybaras and ticks share a habitat component, the riparian vegetation called gallery forest. these forests form as corridors along rivers or wetlands and project into landscapes that are otherwise only sparsely wooded, such as savannas, grasslands, or deserts. the boundary between gallery forest and the surrounding woodland or grassland is usually very abrupt, with the ecotone being only a few meters wide. in são paulo state, capybaras shelter in the gallery forest and feed in the sugarcane fields adjacent to the ecotone ( figure ) . thus, the abundant food and lack of predators in this new habitat have led to a strong population increase (labruna, ). in the s, the capybara was considered in danger of extinction in são paulo state, where population can reach densities times higher than in natural environments in some areas, such as the extended wetlands of pantanal (verdade and ferraz, ) . this offers optimum conditions for the increase in the tick and rickettsia population. further, the capybara is a protected species and is gradually adapting to aquatic urban habitats with a larger spectrum of possible vertebrate hosts for ticks ( figure ). capybaras have been observed in the outskirts of são paulo city along the highly polluted pinheiros river (labruna, ) , which flows through the fourth largest metropolitan area worldwide, with ∼ million inhabitants. presently, a substantial cleanup pro gram for this river is underway and an increase of secondary vegetation and fragmented, regenerated systems is expected. with this, a further expansion of capybaras, ticks, and bsf toward anthropogenically modified habitats, including urban and suburban areas close to water sources such as rivers and lakes, is likely. in addition, it has recently been reported (meireles et al., ) that capybaras in the são paulo state were infected by cryptosporidium parvum, which is a protozoan pathogen that causes a diarrheal illness called cryptosporidiosis, an acute short-term infection that can become severe and chronic in children and immunocompromised individuals. despite not being identified until (meisel et al., ; nime et al., ) , it is one of the most common water-borne diseases and is found worldwide, being spread by direct ingestion of con taminated water or food and through recreational water activities. the finding of zoonotic c. parvum infection in this figure aerial photo of a sugarcane plantation and a small water body with highly fragmented remains of riparian forest, brazil. photo credit: geraldo arruda, jr. semiaquatic mammal that inhabits anthroponotic habitats raises the concern that human water supplies in brazil may be contaminated with cryptosporidium oocysts from wildlife. cryptosporidiosis is the most significant water-borne dis ease associated with the public water supply in western europe. when contamination occurs, it has the potential to infect very large numbers of people. some notable outbreaks of cryptos poridiosis have been associated with heavy rainfall events. in this chapter and elsewhere (despommier et al., and references therein) , there are indications that the boundaries between ecological systems play a role in some of the most important emerging infectious diseases, with a correspondence between ecotonal processes and the ecological and evolution ary processes responsible for zoonotic and vector-borne infections. terrestrial ecotones include forest-edge habitats, fragmented forest landscapes, and forest-grassland interfaces. terrestrial-aquatic ecotones are found in riparian habitats, riverine landscapes, freshwater and estuarine wetlands, and in the coastal zone. anthropogenic ecotones can include crop land/pasture-natural habitat and settlement-natural habitat, and a combination of these. processes in ecotones can contribute to the shifts or changes in hosts, vectors, or pathogens that produce disease emergence. these dynamics are associated with changes in land cover/use and with the changing nature of the land-water interface. anthropogenic influences can intensify ecotonal processes by increasing their geographic extent and overlap. various ecotone features can contribute to disease emergence. animals congre gate in ecotones. populations of species that normally are members of distinct ecological communities from different habitats or ecosystems overlap in ecotones, facilitating patho gen spillover. host-vector hyperabundance increases the potential for pathogens to achieve critical threshold density. enhanced dispersal conditions facilitate dispersal at a higher rate or over longer distances, along linear habitats defined by habitat edges, such as riverine or gallery forest, and flowing water in streams or rivers themselves. cropland-forest-river transitions appear particularly relevant as sensitive indicators of change in this context. for example, the transition between fragmented riparian habitats such as degraded gallery forests and, for example, sugarcane fields seems to be a priority sector for the control of rickettsia-related diseases since capybaras must cross the ecotone to feed on sugarcane, as described else where in this article. further, nutrient pollution, degradation of riparian habitat, and the loss of ecological functions involving assimilation of nutrients and pathogens, combined with high concentrations of domestic fowl and their waste, are commonly associated with human settlement/aquatic-terrestrial ecotones. the emer gence of ai involved the mixing of three different communities: wild migratory waterfowl (wetlands), wild local birds, and domestic fowl (ponds), and, later, also pigs. like influenza, the emergence of japanese encephalitis has involved transmis sion in the spatial area of overlap of human settlements, agriculture, and natural habitat (despommier et al., ) . while waterbirds and wetland habitat are implicated in influ enza, nonaquatic wild birds and irrigation systems provide the vector habitat for encephalitis. the intensification and expan sion of irrigated rice production systems in southeast asia over the past years have made an important contribution to the spread of this disease, which is produced by a mosquito-borne virus (see table ). the flooding of the fields at the start of each cropping cycle leads to a sizable increase in the mosquito population. domestic pigs and wild birds are reservoirs of the virus and transmission to humans may cause severe symptoms. japanese encephalitis is a leading cause of viral encephalitis in asia with - clinical cases reported annually (who, d) . in general, research in ecotoneparticularly terrestrialaquatic dynamicscan provide vital information about changes in climate, river hydrology, sea level (cohen and lara, ) , and land use (lara et al., ) . a strengthened integration of ecological and biomedical monitoring is essen tial for successfully restoring ecological functions and enhancing environmental and human health. globally, the surveillance of locally and regionally relevant ecotones could provide evidence of disease emergence related to environmen tal change. in this context, restoration of lost ecological functions, such as nutrient sequestration by wetland creation or regeneration of riparian vegetation, must be accompanied by careful monitoring of other changes in the surrounding land scape and in the connectivity between basin processes and land use. created or regenerated aquatic systemsindependently of their purposewill increment existing ecotonal processes or generate new ones. thus, surveillance of the created/recovered/ enhanced system ecological functions should include at least those disease agents (host, vectors, or pathogens) , which according to the present knowledge would have a higher prob ability of proliferation under modified or changing conditions (e.g., mosquito larvae in temperate wetlands and snails in tropical regions). floods and droughts will intensify with climate change and affect health through the spread of disease resulting from habi tat modification, with high risk of rapid increase in diarrheal and other diseases (lipp et al., ; ipcc, ) . there are many pathways through which hydrologically relevant events can affect health; notably when a river or stream bursts its banks producing changes in mosquito abundance (malaria, and dengue), or contamination of surface water with human or animal waste such as, for example, rodent urine (leptospiro sis). flooding may become more intense with climate change and can result in the spread of disease. conversely, droughts can produce changes in vector abundance if, for example, a vector breeds in ponds left in dried-up riverbeds (noji, ; menne et al., ) . coastal ecosystems and their basins are rapidly changing due to anthropogenic pressure and global warming, also inducing changes in patterns of resource use (lara et al., ) . integrative, comparative approaches are needed for the understanding of functional links between basin structure; morphology of different estuaries, marshes, and mangroves; flooding and biogeochemical regimes (lara and cohen, ) ; pathogen life cycles; and disease incidence (wolanski et al., ; lara et al., ) . for improved prediction of the dispersal of inundation waters, formation of drought ponds, or preventive identifica tion of vulnerable locations or sectors that could be used as drainage areas, it is crucial to have a detailed knowledge of the regional and local topography. the elaboration of highresolution topographic models (dem) of basins in connection with hydrology, meteorology, and biogeochemistry data will also allow the assessment of vulnerability descriptors such as soil moisture potential, salinity, or organic matter content, which can be crucial state parameters for the development of microorganisms and/or disease vectors. however, precisely in tropical coastal areas, where the impact of climate change on vector-transmitted diseases is of high concern, there is frequently a lack of topographic informa tion with an adequate resolution for low-lying sectors. in vulnerable regions, the combination of risks to both food and water can exacerbate the impact of even minor weather extremes (floods and droughts) on the households affected (webb and iskandarani, ) . a methodological approach including wetland basin microtopography and its relation with inundation dynamics and estuarine biogeochemistry is necessary for vulnerability assess ment and risk management. the use of geographic information systems (giss) provides an excellent basis for network coopera tion at the interfaces between environmental and biomedical research, adding a critical componenthuman healthto coastal management research. this is a major concern for the who, which also has set a priority on the link between gis and disease surveillance (who, ) . through the joint who/united nations children's fund (unicef) program health map, specific gis software was developed for that purpose, combining a standar dized geographic database, a data manager, and a mapping interface. however, although these concerns are closely linked to the subject matter of ecohydrology, they are not usually included in interdisciplinary research projects dealing with, for example, coastal wetlands. clearly, the only way to concretely reduce vulnerability is to ensure that infrastructure is in place for the removal of solid waste and wastewater and the supply of potable water. no sanitation technology is safe when covered by floodwaters, as fecal matter mixes with floodwaters and is spread wherever the floodwaters run (lara et al., ) . consideration should also be given to the deterioration of groundwater quality caused by salinity intrusion due to climate change and rising sea levels (e.g., sherif and singh, ) . thus, as stated in section . . . , such health issues clearly require a basin approach, that is, considering basins as a natural unit of territorial management. however, a usual shortcoming of gis-derived vulnerability studies is that data sources from official institutions are most frequently based on municipalities or counties as an administrative unit, whose limits do not necessarily coincide with basin boundaries. thus, this vision of the relationship between climate and sealevel change and effect on human health converges with zalewski's ( ) statement that: as a consequence, the issue of water quality at the basin scale cannot be resolved without a profound understanding of the effects of hydrology on biotic processes and of biota on hydrology. the frame work for developing the principles of ecohydrology is logically the water basin scale. (zalewski, : ) creation of wetlands for nutrient sequestration from surface waters requires the inclusion of measures for control of locally major and regionally relevant disease vectors such as snails or mosquitoes. the latter are relevant for disease transmission in several climatic zones besides the tropics, and global warming is widening their habitats with severe consequences for human health (e.g., the dengue outbreak in argentina in ) and will therefore be treated with some detail. early methods of managing salt-marsh mosquitoes have primarily focused on maximizing the reduction of mosquito populations, with mini mizing environmental impact as a secondary consideration. however, in the last few decades, there have been attempts to apply diverse water management models to marsh systems, especially in terms of vector control and habitat modification (dale and hulsman, ; wolfe, ) using programs with minimal environmental impacts. the success of these programs requires a thorough knowledge of mosquito developmental conditions, as well as potential impacts on adjoining ecosys tems. a deep knowledge of the local microtopography and tidal regimes is critical. marsh drainage and hydrological linkage to the tidal source are essential in the determination of what type of wetland occurs where, and for the development of appro priate wetland management measures. elevation of a few centimeters is more critical in the coastal wetlands than that of hundreds of meters in the mountains. in this section we cover not only well-established methods for mosquito control, but a series of successful methods for snail control derived from good agriculture practice, basically from techniques for rice cultivation. ecohydrology can contri bute to and learn from these experiences. water management, molluskicides, and chemotherapy have been the main instruments for preventing or treating schisto somiasis. biological control of snails through predators such as ducks, fish, turtles, crustaceans, water rats, leeches, and aquatic insects have been also used, as yet with very limited success. an interesting lesson on the potential for improved water management to reduce vector proliferation from the s can be drawn from the experience in the baluchi irrigation scheme in then tanganyika (sturrock, ) . this system was remark ably clear of snails, although several species occurred in small numbers. several factors may account for this. first, the water flow in the canal system was very rapid when it was in use, but the canals were completely dried out in the dry season. second, silt and vegetation were dug out of the canals twice a year. third, a complex system of rice husbandry was used in which the rice fields were ploughed, manured, and subjected to a program of alternate drying and flooding. consequently, neither the canal system nor the rice fields contained much in the way of snail habitats. snails were confined to temporary pool sites, filled with rain or seepage water. all these schemes were built on land with an appreciable slope and with relatively porous soils. even when irrigation was in progress, the field canals were not always in use and dried out rapidly. while snails are often able to withstand limited periods of drought, it is unlikely that any large snail populations could develop under these conditions in any one season. furthermore, on five of these schemes, field canals were often re-routed from season to season so that the establishment of suitable snail habitats was rendered even more unlikely. mobarak ( ) reported that after prevalence of urinary schistosomiasis in upper egypt reversed a previous downward trend and began to increase again because of the shift from basin to perennial irrigation. however, in any case, increased use of parenteral antischistosomal therapy (pat, injections of antimony-based drugs) was bringing schistoso miasis under control in egypt. in the northern part of upper egypt, prevalence dropped from . % in to . % in , while further south, prevalence reportedly fell from . % in % in to % in % in (who, . most experts agreed that applying the proper combination of sanitary engi neering, water control management, snail control, infection surveillance, and treatment drugs can avert adverse effects of irrigation on schistosomiasis. moreover, there was an impres sion that even without water control measures and environmental sanitation, chemotherapy with or without treat ing water to kill snails would adequately control schistosomiasis transmission. fenwick ( ) noted that in the newer rahad irrigation scheme, east of the gezira plain in the sudan, because of the use of drugs and snail control, the incidence of schistosomiasis remained very low, despite very poor sanitary conditions. it was predicted, however, that relax ing control measures would cause a surge in schistosomiasis. although oral drugs started to be used in egypt in the s, pat use continued into the mid- s. praziquantel, which also has a high cure rate for s. mansoni, became available in egypt in and has been the treatment of choice there since the late s. although the massive pat campaigns were successful in strongly reducing disease incidence, a study by frank et al. ( ) concludes that the intensity, widespread geographical coverage, and duration of the campaigns, together with unsafe injection practices (inappropriate sterilization pro cedures), have been responsible for the nationwide spread of hepatitis c in egypt in recent decades. the authors state that the enormous dimension of egypt's schistosomiasis problem and the sheer size of the antischistosomiasis effort, combined with the characteristics of pat, provided an effective mechanism for a massive increase and establishment of hepatitis c virus in the egyptian population. according to these authors, this is "the world's largest iatrogenic transmission of blood-borne patho gens known to date." moreover, it is probable that the heavy reliance on an effective chemical treatment also allowed the continuation of water management schemes that were contri buting to the maintenance of large numbers of snails in aquatic environments. the evolution of the schistosomiasis problem in egypt and sudan described above highlights the importance of developing water management programs able to keep vector proliferation under control. this lesson is also highly relevant to the construction of large-scale reservoirs and irrigation facil ities as in the case of the three gorges dam. in israel, biomphalaria alexandrina was eradicated through a combination of factors including chemical applications. as in all cases, snails return some time after the application of mol luskicides. some combined measures used for the control of snail vectors have been successful, such as increasing water currents to over cm s − , rapid emptying and drying up of water reservoirs, and weekly deflection of infested water courses along different routes (saliternik, ) . as stated previously, the success of chemotherapy in treating this disease and of molluskicides for eradicating snails does not imply that preventive measures should not be taken for avoid ing vector proliferation based on knowledge of their ecohydrological setting. all vector snails require water, at least for breeding. the management of water bodies is therefore a potentially powerful control method. for example, in the case of rice cultivation there are opportunities for vector control by changing the aquatic habitat of the snail in a way compatible with maximum crop production. infection of humans mostly takes place not in the rice field itself, but in irrigation canals and surrounding living quarters. different hydrological and rice husbandry approaches have been used in various countries. however, generalizations should be made with care because each snail species has its own preferences and tolerances regard ing shade, water velocity, the steepness of canal walls, and drought tolerance. rice cultivation by itself can be used as an environmental method of snail control in that it brings about ecological changes that can reduce snail habitat. the philippines has promoted more intensive scientific methods of rice cultivation to control schistosomiasis (hairston and santos, ) . snail control is achieved at different stages of rice growing in a number of different ways, for example, by deep plowing, which turns over the soil and buries the snails; or by draining the ricefield at harvest and keeping it dry until the next crop, which kills the snails and prevents them from breeding. in japan, s. japonicum eradication was accomplished by treatment, sanitation, control of animal reservoir host, educa tion, and elimination of most of the snail colonies (garcia, ) . the steepness of the walls of irrigation channels was increased and later they were lined with concrete and main tained clear of silt, vegetation, and debris to supplement the eradication of snails in the ricefields, which resulted from intensive cultivation. extensive rice-growing areas in china's mainland have been cleared of oncomelania snails (garcia, ) . the measures taken have included digging new water channels parallel to the existing snail-infested streams and using the excavated soil to fill the old ones, clearing streambeds, and removing vegetation. where the soil structure permits, the banks have been made steeper. in the philippines, similar measures have been taken as in china; in addition, converting undrainable swampy areas into fishponds and improving agricultural prac tices have successfully controlled snails in limited areas. thus, an integrated approach to drainage problems can result in increased production while reducing health risks. in the ecohydrology approach, it is essential to consider the whole basin in management policies, especially when a disease agent can be transmitted by different species of the same host (in this case a snail) that is differentially distributed along altitude gradients in river basins. both b. truncatus and planorbarius metidjensis are intermediate hosts of s. haematobium in southwestern morocco. a basin investigation (yacoubi et al., ) in five rivers identified sites colonized by these species and compared the habitats in which they were found. the p. metidjensis was observed in the upper valleys of three rivers, whereas b. truncatus was found in sites of lower altitude. a component analysis demonstrated that altitude (from to m), water ph (from . to . ), and electric conductivity (from to μs cm − ) were the main descriptors of environment. the p. metidjensis was associated to high altitude and low electric conductivity. however, b. truncatus was asso ciated to being found in lower altitude sites with medium electric conductivity in water. it has been mentioned above that periodic canal or field drying had been used successfully for snail control. nevertheless, before a control plan is adopted and implemen ted, the effects of drying out have to be monitored and thoroughly understood for each snail species: snails that are capable of undergoing diapause can circumvent unfavorable environmental conditions, including long periods of drought. cooper et al. ( ) found that diapause influenced the sus ceptibility of biomphalaria glabrata snails to s. mansoni infection. juvenile snails exposed just prior to diapause, or immediately following a diapause period of weeks, were highly susceptible to infection by s. mansoni miracidia. however, snails that underwent diapause produced compar able or only slightly fewer cercariae than did nondiapausing snails. these studies indicate that diapause in b. glabrata does little to decrease a snail's ability to act as an intermediate host for s. mansoni or to interrupt the development of the parasite. for these reasons, great attention should be given to diapausing snail populations when planning programs for mollusk control. thus, for snail control, it is important that not only the agricultural field but also irrigation and drainage channels, as well as the water source, be considered part of the agroecosys tem. this parallels the ecohydrology approach that considers the whole basin, from the river source to the wetlands, estuar ine, and coastal zone as an integrated management unit. both agricultural and ecohydrological models should converge in a new synthesis integrating their own tools with practices based on traditional knowledge, socioeconomical cost-benefit analysis of vector eradication, and agri-and/or aquacultural production. the type of wetland management approach, particularly when restoration or creation is planned, will require previous surveys of the mosquito species and their habitat types, locally and at basin level. in the following sections, we present a summary of main species/habitat combinations for different hydrological settings extracted from anonymous ( b) . relatively few mosquito species breed in running waters, such as streams. larvae can be flushed out when stream volume increases, and to remain in the stream requires a large amount of energy. the tropical genus, chagasia, and some anopheles species are stream breeders. stream breeders will find vegeta tion along banks with which to anchor themselves or attempt to remain away from the main flow of the stream by seeking isolated eddies. transient water sources, such as flooded areas and ditches, are used as breeding grounds for species whose eggs can with stand desiccation and whose life cycles require alternating periods of wet and dry, such as aedes and psorophora. the quality of transient water changes with time, which can result in a succession of different species using the same pool. transient waters include woodland pools created by spring rains (aedes stimulans), fresh floodwater (aedes canadensis), and tidal floodwater (aedes sollicitans). permanent or semipermanent waters support characteristic aquatic vegetation. cattail, rushes, and sedges are typical fresh water swamp vegetation. genera associated with permanent water are anopheles, culex, culiseta, coquillettidia, and uranotaenia, whose eggs are not desiccant resistant and must be laid directly on the water. aedes adults will oviposit near the edge of the swamp, or within tussocks of vegetation, requiring later flooding of the eggs for hatching. as with transient waters, there are seasonal changes in the vegetation, water quality, and mosquito species present. permanent waters can include fresh water swamps, such as, for example, tussock (aedes abserratus) or cattail swamps (coquillettidia perturbans), as well as brackish water swamps with salt marshes (culex salinarius). besides nat ural environments, polluted water with floating debris can be a habitat for species such as culex pipiens. container water habitat can be found in both natural set tings, such as water held by plants to artificial settings and water found in tires. container water is characteristically clear and many container species now also use artificial sites as they provide insulation against the weather and are more numerous (aedes aegypti and aedes albopictus). increasing dengue incidence in not only tropical but also subtropical countries requires a thorough elimination of such urban, man-made microhabitats. there are various techniques for mosquito control based on different principles. all involve modification of the hydrologi cal setting, ranging from total wetland drainage to an increase in their tidal flooding. a summary of these methods, including parallel grid ditching, open marsh water management, and runneling, is presented in the following paragraphs. parallel grid ditching consists in the physical removal of water from intertidal marshes and was one of the first largescale forms of mosquito control (lesser ( ) ; figure ). parallel grid ditches were dug in salt marshes, spacing these ditches about m apart to remove standing surface water where mosquitoes might breed. extensive ditching programs for mosquito control in north america were only moderately effective, since many breeding potholes were not drained dry, and there were long-term nega tive effects on wildlife and salt-marsh ecosystems. many nonmosquito breeding wetlands that provided wildlife habitat were unnecessarily drained and salt-marsh vegetation commu nities were changed into fragmented wetlands. birds were particularly affected through the draining of larger natural ponds. by the early s, there was an increasing awareness of wetland values and functions, and the value of parallel grid ditching was questioned. understanding of the drawbacks of the parallel grid-ditching technique led to the development of a new mosquito control source-reduction technique called open marsh water manage ment (omwm). it started in the late s and was further optimized until the early s. the goals of omwm are: ( ) control of salt-marsh mosquitoes; ( ) reduction of insecti cide applications; and ( ) habitat enhancement for salt-marsh fish and wildlife (ferrigno and jobbins, ; hruby et al., ) . the omwm method involves the selective installation of small, shallow ponds and interconnecting ditches superim posed on known mosquito-breeding habitats ( figure ). this aims to eliminate wet-dry-wet cycles necessary for determined species and any newly created permanent water habitats are unattractive for mosquito egg deposition. this simultaneously improves habitats for mosquito-eating larvivorous fishes which can quickly invade, via tidal flooding, any newly created omwm pond or ditch. scattered mosquito breeding depressions and sheetwater habitats are connected through pond and ditch excavations to allow unimpeded water flow and predatory fish movement, while isolated potholes are often filled with natural soils to eliminate these smaller-sized breeding depressions (lesser, ; figure ). the increase of tidal inundation frequency and predation by fish significantly reduce mosquito density. runneling is an effective method for controlling mosqui toes that breed in intertidal salt marshes through a type of habitat modification using shallow channels. this technique is based on omwm principles (wolfe, ) . it increases tidal frequency to a marsh and removes surface sheet water from low-lying areas high on the marsh. runnels are linked to the tidal source, promoting tidal exchange between graded regions of the marsh. they are conceived to allow transport of lowamplitude tides to areas of salt marsh in a way so that pools do not form, even after spring tides. runnels are shallow figure the omwm system, involving the selective installation of small, shallow ponds and interconnecting ditches superimposed on known mosquito-breeding habitats. (< cm deep) spoon-shaped channels constructed along nat ural drainage lines on the salt marsh ( figure ) to a maximum gradient of : (hulsman et al., ) . due to the slight slope, runnels enable slow water movement even during lowamplitude tides. the net result is a reduction in mosquito breeding areas, the modification of pools and edges for egg conditioning (the process involving flooding and drying events that prepares mosquito eggs for hatching), and larval development. there are few apparent negative impacts at the modified site (hulsman et al., ; dale and hulsman, ; dale et al., ; latchford, ) . further, like omwm, they allow water to drain from trap pools and permit predatory fish to gain access to the mosquito larvae, at least during high tide. in comparison to grid ditching and omwm, runneling is an environment-oriented approach to salt-marsh management for mosquito control that aims to alter the salt marsh as little as possible, while causing significant reductions in mosquito numbers. the main difference between the three approaches lies in the magnitude of the habitat modification. ditching involves the greatest alteration to the marsh, and runneling the least. runneling has a lesser effect on the estuarine environ ment as a whole than does either ditching or omwm. . . conclusions . . . some reflections on dams, water scarcity, ecohydrology, and health although the construction of reservoirs is controversial, the rising demand for water by an increasing human population makes more dams inevitable (jobin, ) . in a review, morley ( ) calls attention of the fact that most parasitological studies in relation to reservoir construction have been focused on schistosomiasis and other tropical diseases of humans (stanley and alpers, ; jobin, ) . in comparison, the impact of reservoir construction on indigenous aquatic parasite fauna of wildlife has been a subject largely ignored by the scientific community. however, reservoir formation can have profound effects on the parasite fauna of fish, birds in the reservoir, as well as up-and downstream of it. changes in host-parasite relationships and switches between animal and human hosts can occur (morley, and references therein) . the role of parasites in environmental monitoring is increas ingly recognized (lafferty, ; lafferty and kuris, ) . thus, the surveillance of the effects of reservoirs on parasite fauna of aquatic wildlife may provide important general infor mation on both short-and long-term changes that occur within and downstream of new reservoirs during the maturation pro cess of the reservoir. the above-described cases that show the effect of dam con struction on onchocerciacis and schistosomiasis call attention to the need to evaluate changes in flow power and velocity downstream of proposed dams, in order to assess their likely health impact. ecohydrological measures are required to improve the operation of existing dams to provide more effective control of disease vectors (see section . . . . ). the modeling of the effect of controlled flooding pulses on the plankton dynamics in the guadiana estuary (wolanski et al., ) is an outstanding example of the potential of the appli cation of ecohydrological principles for the control of toxic algal blooms. in arid and semiarid regions, the quality of water in artificial reservoirs is essential to human health, particularly in climati cally unstable regions. for example, recent el niño/la niña-southern oscillation teleconnections have produced a pro longed drought of ∼ years in south argentina. this has interrupted a period of about years of rainfall significantly above the historical average and produced a decline to critical levels in the reserves of drinking water reservoirs, which like other water bodies in the region, have suffered from recurrent summer algal blooms (kopprio et al., ) . however, the perception that cyanobacteria can represent a threat to human health only in connection with acute events such as blooms should be widened to consider the possibility of neurologic damage as consequence of chronic exposition to toxins such as bmaa via long-term ingestion of water or aquatic fauna. this should be taken into account when developing schemes for preventing cyanobacterial blooms by manipulating natural predator communities. the reduction of the nutrient load input to the water reservoir probably remains the best preven tive measure to prevent harmful algal blooms. water treatment should be regularly checked and improved to remove the organisms and their toxins from drinking-water supplies, where appropriate. water treatment by flocculation and sedi mentation, followed by sand filtration, is supposed to remove live cyanobacterial cells and debris. however, there is evidence that plants that are not working properly can actually increase cell counts of algae with potential toxicity (in this case, anabaena circinalis and microcystis aeruginosa) in the treated water (echenique et al., ) . throughout this chapter, examples have been referred to of actual and potential conflicts of interest between alternative uses of aquatic systems, for example, between the desire to restore degraded wetlands and the need to protect health of the human population living nearby. a relevant example of policy conflicts in an industrialized country is the experience of the tennessee valley authority (tva), where health concerns in the past gave rise to management measures that conflict with modern recreational interests (bos, ) . the meeting report of the ninth meeting of the who/fao/united nations environment programme (unep) panel of experts on environmental management for vector control in includes the following passage: as national and regional priorities change, so do policies, and there must therefore always be a provision for their reconsideration and modification. sometimes, though, the acute problems that led to the original priority setting might have become latent rather than have disappeared completely, and while public awareness and political pressure favour a policy change, the original goals of such policies should not be ignored. this was well illustrated by the water man agement policies including mosquito control established by the tva in the s. the standards of mosquito control maintained by tva equalled those maintained in privately owned river impoundments under prevailing public health regulations. the measures included the programmed fluctuation of water levels in the reservoirs, a practice that played a key role in reducing anopheles populations and eradicating malaria transmission from the valley. new uses of the reservoirs, including recreation and the promotion of nature conservation had led to a conflict of interests. for recreation, stable water levels during summer and early autumn were required; con servation of certain fish species and of waterfowl required higher water levels in spring to promote fish spawning and the rapid growth of aquatic vegetation for the fowl. such changes in water manage ment regimes would without doubt result in increased mosquito populations, yet the potential risk for the reintroduction of vectorborne disease was not appreciated after three generations of malaria free experience. in recent years much interest has been directed towards the protection and establishment of wetlands, without pay ing sufficient attention to their mosquito breeding potential. consequently, tva has been faced with a conflict of new policy directives concerning wetlands, existing mosquito control policies and state regulations for impounded water. the use of constructed (artificial) wetlands for the treatment of domestic waste water and its processing for reuse is of particular concern, since these could pro duce large quantities of potential disease vectors and they are often sited close to populated areas (peem/who, : - ). this stresses the necessity of harmonizing policies of reservoir management for vector control with other policies concerned with land use patterns, to ensure that areas of potential risk, such as artificial wetlands, are planned away from areas of human habitation. presently we face a complex environmental situation that seems to be changing at a much faster rate than our current capacity to revise and renew our intellectual schemes or to generate integrated management structures capable to enhance both ecosystem and human health. take, for example, the case of influenza virus. the loss of wetlands around the globe may force many wild birds onto alternative sites like farm ponds and paddy fields, bringing them into direct contact with domestic fowl and humans and providing greater opportu nities for the spread of the h n virus (anonymous, ) . poor planning in response to development pressures has led to the increasing loss or degradation of wild ecosystems which are the natural habitats for wild birds. the displaced wild birds increasingly seek to feed and live in areas 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control measures co occurrence of β-n-methylamino-l-alanine, a neurotoxic amino acid with other cyanobacterial toxins in british waterbodies cholera and estuarine salinity in calcutta and london response of toxigenic vibrio cholerae to stresses in aquatic environments cholera epidemiology in developed and developing countries: new thoughts of transmission, seasonality, and control the impact of physico-chemical stress on the toxigenicity of vibrio cholera diversion of the ganges water at farakka and its effects on salinity in bangladesh the schistosomiasis problem in egypt anthropogenic effects of reservoir construction on the parasite fauna of aquatic wildlife the role of bithynia tentaculata in the transmission of larval digeneans from a gravel pit in the lower thames vally a mechanism for slow release of biomagnified cyanobacterial neurotoxins and neurodegenerative disease in guam toxin profiles of vibrio cholerae non-o from environmental sources in calcutta national institute of 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to pesticide long banned in the west resource competition and community structure human health effects of a changing global nitrogen cycle evaluation of total phosphorus as a predictor of the relative biomass of blue-green algae with emphasis on alberta lakes guidelines for the integrated management of the watershed -phytotechnology and ecohydrology -newsletter and technical publications fast melting glaciers from rising temperatures expose millions in himalaya to devastating floods and water shortages competition for water resources of the volta basin vibriosis in shrimp aquaculture capybaras on an anthropogenic habitat in south eastern brazil disease stalks new megacities. guardian effect of fecal pollution on vibrio parahaemolyticus densities in an estuarine environment water insecurity and the poor: issues and research needs. zef discussion paper who, geneva. who, . the control of schistosomiasis: second report of the who expert committee strategy to rollback malaria in the who 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and control of schistosomiasis (bilharziasis) overview of disease fact sheets habitats of bulinus truncatus and planorbarius metidjensis, the intermediate hosts of urinary schistosomiasis, under a semiarid or an arid climate factors affecting the prevalence of schistosomiasis in the volta region of ghana ecohydrology -the use of ecological and hydrological processes for sustainable management of water resources impact of the three gorges dam construction on transmission of schistosomiasis in the reservoir area relationship between the transmission of schistosomiasis japonica and the construction of the three gorge reservoir key: cord- -d e zd authors: baldwin-ragaven, laurel title: social dimensions of covid- in south africa: a neglected element of the treatment plan date: - - journal: nan doi: . / . .v nsia sha: doc_id: cord_uid: d e zd nan mandela's triumphant release from prison years ago, those halcyon weeks in when we were hosts to the soccer world cup, or more recently siya kolisi's diverse team of players overcoming enormous odds to achieve a global rugby victory -the unity and transcendence of the rainbow nation largely have eluded us. while a pandemic is not the occasion to point fingers, it does expose the structural fault lines that undermine social cohesion. in "normal" times, these fissures are mostly tucked away safely in the recesses of our national collective consciousness. it is as if the virus, anthropomorphised, has pulled back the veil, baring the naked truth of our imperfect realities. there is no place to hide; and, to be totally honest, we are afraid. in south africa, with over total covid- cases and deaths at the time of writing, it is important to reflect on the intersections between the biomedicine of the novel coronavirus and its sociopolitical manifestations. while sars-cov- is clearly a biological phenomenon that clinicians and researchers are learning more and more about each day, we also observe that the disease plays out differently in different bodies and in different social-political realities. no two people, and no two countries, are living and dying from covid- in exactly the same way. while there are common threads of pathophysiology and constraints of health-care systems, the illness experiences of individuals, families, communities and countries are unique, based on underlying contextual factors that are embedded in culture, economics, politics and philosophy. as clinicians, what can we learn from such observations? how can south africa benefit from analysing what has happened in countries that are ahead of us in viral spread? is it possible to avert a future imperfect in our context that is already fraught with social upheavals and inequity? what will a post-covid- health-care workforce look like? these questions, and others, probably keep many of us up at night with good reason. as we struggle to plan for meaningful interventions, what social considerations need to be kept in mind? in the past month, vast amounts have been written capturing the south african experience of the sars-cov- adenovirus that causes covid- disease. from the social distancing necessary to reduce the speed of transmission and flatten the curve, to buying essential goods for the duration of a communal lockdown, to the suffering endured by not consuming alcohol and tobacco, to reports about the personal and collective economic costs, to the nightly release of case statistics by geographical region, to the biographies of those who have died, we have amassed a hefty repository of pandemic stories that are intended to reveal a shared humanity and promote common cause. yet, there is something that should niggle at us, a discomfort as we begin to realise that apart from the similarities, there are also major divergences in our narratives. while transmission is the same for everyone (droplet spread vs aerosolisation which only occurs during invasive medical procedures), we are told that the expression of symptoms can range from completely sub-clinical to severe respiratory failure and death. biomedically, these differences are accounted for by age and/or other comorbidities. in his daily broadcasts, minister of health dr zweli mkhize reassuringly informs the public that those who have died so far would have died anyway from their co-morbid conditions: those with hypertension, diabetes, obesity, chronic obstructive lung disease, end-stage cancer, underlying immunosuppression and the elderly (with the exception of two people under age ).( ) by implying that covid- was simply an added insult to an already-compromised human, he attempts to avoid panic by explaining that these people were already sick. he acknowledges that while the loss to each family is significant, the loss to the collective should be mitigated by this understanding. how true is this, however? it is certainly a more palatable explanation for the mounting death toll: weakened constitutions, people battling to stay alive anyway, a necessary culling of the herd. individual bodies live in communities with histories. these reveal the complex and less visible web of a person's or a community's inherent sociopolitical vulnerabilities that emerge as risk factors for poorer health outcomes. increasingly, it appears that someone's positionality on the uneven playing field of life will determine her prognosis in addition to biological factors for covid- .( , ) although there are well-established links between social positionality and the body's ability to mount an effective immunological response, the exact mechanism of these interactions remains elusive. ( , ) in the united states, we observe relationships between zip code, race and death from covid- , such as in new york city, where latinx people (those with latin american cultural or ethnic identity in the united states) make up % of the population but account for % of the death rate, a difference also seen with black new yorkers ( % of the population and % of the deaths). ( ) there is speculation that poorer access to the advanced technologies for heroic life-saving interventions was the reason; however, there is a growing body of evidence pointing to the intersectional stressors of living with inequality, racism, classism, marginalisation or being "othered" that act at a cellular level even in the presence of adequate medical care. ( ) this interplay between inherited and acquired vulnerability works its way into an embodied expression of disease at a granular level. however, there are ways to conceptualise some of the social and structural forces that increase risk (such as power and privilege) and simultaneously silence the expression and visibility of such suffering.( ) paul farmer points out, "structural violence is one way of describing social arrangements that put individuals and populations in harm's way. […] the arrangements are structural because they are embedded in the political and economic organization of our social world; they are violent because they cause injury to people … neither culture nor pure individual will is at fault; rather, historically given (and often economically driven) processes and forces conspire to constrain individual agency".( ) unlike the direct police violence resulting in the marikana massacre or the brutal rape and murder of uct student uyinene mrwetyana, structural violence is often invisible and has been likened to the unseen mass that lies beneath the tip of every iceberg exerting its influence by creating unequal life chances. structural violence is viewed as simply the way the world works, the natural order of things: entrenched power has become so normalised that it is often difficult to fathom where and how the injury came about. reflecting a recent episode of structural violence in our own health-care context, the life esidimeni tragedy comes to mind. as well intentioned as psychiatric deinstitutionalisation is in theory, economic expediency and a callous disregard for human life trumped professional ethics and the right to dignity. at least people died from hunger, starvation, hypothermia and neglect following the ill-conceived transfer of long-term mental health patients to community-based non-governmental organisations that were not equipped to care for them. what is striking about this disaster, however, is the role of those in the gauteng department of health who foresaw nothing unusual, or turned a blind eye to possible pitfalls, while executing the deinstitutionalisation plan. when reading out the findings from evidence presented to the arbitration commission he chaired, retired deputy chief justice dikgang moseneke commented about the sheer lack of official accountability for the life esidimeni tragedy: "senior provincial heath officials had lied‚ played the victim‚ abused their power and knowingly violated the rights of mentally ill patients and their families because the instruction had come from above". ( ) given that those who were directly responsible for the plan have not yet faced criminal prosecution, it remains whether this incident will be seen as a catastrophe of inordinate proportions or as a massive injustice perpetrated by particular individuals who benefitted. the late political theorist and legal philosopher judith shklar in her book the faces of injustice posits how accountability is apportioned according to how an incident is framed. if one interprets what has occurred as a "misfortune" or rather as an "injustice", there is an important distinction between whether and how accountability can be attributed. although people suffer either way, the depersonification of responsibility for that suffering in the case of a misfortune -a tsunami, landslide, tornado or other natural disaster -assumes that it is the invisible hand of fate at fault. according to shklar, however, a calamity is rarely neutral: scratch deeply enough and there will be an injustice where someone or something has behaved with culpability.( ) returning to our current crisis of covid- , we actually have a choice in how our own responses will be judged by history. like famine, pandemics can either be mitigated or exacerbated by the political leadership and the decisions they make. ( ) in fact, as many have argued, the root causes of mass starvation are wholly human-made. ( ) although extreme weather events such as drought or flooding or a scourge of locusts or other blight may destroy food crops, theorists of the politics of famine argue that it is human beings who first determine their degree of responsiveness to climate change that actually results in such "natural" disasters and after, the nature and extent of food distribution that has been banked for emergencies, often privileging one group over another as food becomes weaponised. the national department of health in its covid- infection prevention and control guidelines for south africa states an obvious truth about combatting the spread of the virus in our particular situation: "south africa has a unique challenge of a large vulnerable immunocompromised population living in overcrowded conditions".( ) over the past years, prior to being hit by the sars-cov- virus, this is a frank admission that we have been sluggish in our duty to address the needs of the masses. despite constitutionally enshrined guarantees to housing, sanitation, nutrition, education, recreation, gender equity and protection of those most vulnerable, progress on these fronts has been achingly slow. while pandemics are the ultimate litmus test of a nation's health system, the social determinants of health have never been more meaningful in our context. the minister of health, dr zweli mkhize, made it clear, "at this point … this is collaborative work. we did say [that] to defeat covid- , it's no longer an issue of a nurse and a doctor. it's actually about society…about going into a combat zone to fight this infection". ( ) attention to the social determinants of health, those underlying predictors of life and death, should give us pause to realise that no amount of ventilators and hospital beds can in fact stem the ravages of a virus that only knows a single pathway, that of vulnerability. we have ignored engaging with them at our peril. stats sa data from / indicate that almost half of the adult population (men and women over age ) were living below the upper bound poverty line, the cut-off point at which there is just enough money for basic nutrition and other essential non-food items such as soap, clothing and sanitary pads. ( ) in , that amount was r per person per month, with women experiencing % higher rates of poverty ( %) than men. ( ) as regards changes in housing value over a year period, the statistics are also grim: "more than half of south african households headed by black africans lived in dwellings that were valued at less than r […] [in contrast], most households headed by indians/asians and whites lived in properties valued at r or more". ( ) in terms of both the number of rooms in these dwellings -and by implication size -"there has been a shift between and towards more rooms in formal dwellings and changes from multiple rooms in informal housing to one to two rooms" (italics added for emphasis). ( ) in another report released by stats sa in february explaining income inequality, there is the stark finding that the poorest % of south african households are now relying more on social grants than paid employment to attain overall household income. this intervention prevents an even greater "income inequality gap between the bottom and top deciles". ( ) despite this attempt at economic stabilisation, the divide between rich and poor is so wide that south africa carries the dubious honour of being the longest running most unequal country on the planet from . ( ) now it seems we must pay the price as the virus threatens to run its course along the fault lines of poverty and inequity. therefore, adherence to world health organisation directives like social distancing is impossible for large swaths of south africans who, through no fault of their own, lack the necessary infrastructure for such adherence. in an ironic twist, a resident of a rural community in mpumalanga expressed his "thanks" to the coronavirus for water. commenting on the installation of "six boreholes [with running taps] and six , litre water tanks" in the space of a week after years of waiting for access to fresh water, another resident pointed out that, "[al]though they (government) had promised us water a long time ago, […] now that we have this virus, we see fast delivery". ( ) ongoing service delivery protests bear testament that in other parts of the country, after decades of neglect, improving access to water and sanitation has not been as successful. similarly, sheltering in place takes on new meaning across the inequality divide. given the challenge highlighted by stat sa ( ) in that % of the country's population live in informal dwellings, corresponding to million people, ( ) physical distancing in such conditions becomes next to impossible. there are substantive differences in self-isolating with a fridge and freezer full of food, opportunities for recreation on one's own lawn or swimming pool or tennis court versus the informality and overcrowding that are daily realities for much of the population. in the early days of the lockdown, we recall the images of law enforcement officials acting with zealousness to confine people to their shacks. as the bbc reported, "the police and army have, at times, acted with thuggish abandon in their attempts to enforce the […] lockdown, humiliating, beating, and even shooting civilians on the streets of the commercial capital, johannesburg, and elsewhere". ( ) similar reports from front-line colleagues providing primary medical care in the townships expressed exasperation that the mall in ebony park remained open, or that it was "business as usual" with informal traders and food vendors in daveyton.( ) despite application of the siracusa principles (see table ) during the declaration of a national disaster to ensure that any limitations of human rights are the least restrictive possible and affect all members of the population without discrimination, is it really possible to apply these principles equally if we live in such an inequitable society? these principles are not explicitly discriminatory against the poor. yet, the lockdown disproportionately affects low-wage workers in precarious employment. during and after the -week lockdown, the consequences of staying home are substantively different on the one hand, for a person with no guarantee of sustainable income or paid sick leave and on the other, for a person with job security or a stable business. can we blame the population for wanting to leave their overcrowded homes and travel to the local clinics during the lockdown to consult on previously neglected health matters? can we blame a parent who, because of lockdown, is not working at her usual three jobs and sees it as an opportunity to catch up on delayed immunisations for children, to extract a tooth that has been bothersome for months or to pass by for a social visit with the staff or other patients? the experiences of confinement and boredom are psychological for those of us with adequate housing. in the townships and informal settlements, these experiences are spatial and material. davis and others have described such toxic urban environments as "… a dumping ground for a surplus population working in unskilled, unprotected and low-wage informal service industries and trade". ( ) in such contexts, does the restriction of rights to freedom of movement and employment carry the same meaning or intention? the current national debates about whether to extend the lockdown, and for how long, reveal the tensions between competing agendas. although few people are explicit about the trade-offs in terms of lives worth sacrificing as opposed to lives worth preserving, experts speak as if we inherently share the same belief that some lives are more precious, or at least worth saving, than others. further signalling the contingencies that will sway the balance between human life, and the survival of the economy is the personification of corporations and businesses: how long can the engines of industry remain moribund without suffering terminal complications? the flip side of this, however, is that there have been some very brave public health-motivated decisions taken by president cyril ramaphosa and his cabinet to regulate industry and repurpose manufacturing to address the pandemic. although the "combat zone" war metaphor may be problematic, it invokes powers for the executive to act in ways that place health at the centre of a societal agenda, something that we have not seen during peacetime. it opens up certain possibilities that are at odds with "getting back to normal", such as the mining industry is keen to do. ( ) embedded in this calculus is what number of human beings can be forfeited to get the stock exchange up and running again -so that the poor can get back to work and not starve; because without employment and in the absence of a meaningful social safety net they will die anyway. we are told that actuarial scientists are key to resolving these equations, presumably relying on a common understanding of what utilitarianism means in our context. while it is acknowledged that we will all take a hit, certain among us must pay with our lives as well as our purse. so, what will be our levels of complicity with managing these "surplus people", those who in the best of times die from falling into a pit latrine, or a delayed cancer diagnosis, or at the hands of a violent partner or from a gang rape for being queer? in conversations with gauteng colleagues regarding their role in the covid- pandemic, they recall the trauma of working or training in apartheid-era segregated hospitals or wards with woefully inadequate resources and security police monitoring, or the overwhelming helplessness in the pre-antiretroviral days when aids patients lay dying on stretchers everywhere. other colleagues are more in tune with the fluidity of this crisis: "well, we are rationing all the time", which is probably a more honest appraisal of the resource constraints (structural violence) we have come to accept as a normal condition of practising in south africa's public health sector in the st century. whether we support national health insurance as the realisation of universal health coverage or not, we are now confronted with a number of questions that will determine our post-pandemic future. what is our appetite as clinicians to tackle these underlying sociopolitical issues, recognising their inexorable links to the current best medical and scientific management of covid- ? it is not a one or another choice. traditionally, clinicians have been averse to engaging in such issues because they are not regarded as purely "medical", but rather political, something that i have written extensively about in the past. yet, these are exceptional and truly ominous times. a set of agreed-upon foundational principles when human rights are temporarily restricted and subject to ongoing review and appeal in so far as • the restriction is provided for and carried out in accordance with the law; • the restriction is in the interest of a legitimate objective of general interest; • the restriction is strictly necessary in a democratic society to achieve the objective; • there are no less intrusive and restrictive means available to reach the same objective; • the restriction is based on scientific evidence and not drafted or imposed arbitrarily i.e. in an unreasonable or otherwise discriminatory manner. ( ) in thinking about what instructs and informs physician advocacy, we can turn to various guidelines. first, the world medical association statement on patient advocacy and confidentiality advises, "medical practitioners have an ethical duty and a professional responsibility to act in the best interests of their patients. this duty includes advocating for patients, both as a group (such as advocating on public health issues) and as individuals".( ) (italics added for emphasis) the canmeds health advocate role, adopted by the health professions council of south africa, states, "as health advocates, physicians contribute their expertise and influence as they work with communities or patient populations to improve health. they work with those they serve to determine and understand needs, speak on behalf of others when required, and support the mobilization of resources to effect change". ( ) (italics added for emphasis) inherent in these professional statements is a divide between the doctor and the patient or community, which recognises both the power differential and a need for therapeutic distancing that is purported to allow objectivity and reason to prevail. this divide also confers an element of safety, a recognition that doctor and patient are not in the same boat, at least not in that exact moment. covid- has changed that equation. now, it is not safe to be caring for patients with sars-cov- , especially in an environment where access to appropriate personal protective equipment may be restricted. st augustine's hospital in durban is closed indefinitely due to an outbreak of covid- at the facility, where nurses and patients who tested positive are being kept in quarantine. ( ) the media coverage of both famous and ordinary doctors from around the world who have died in the line of duty caring for covid- patients makes us question our own mortality and realise that, in this instance, nothing separates us from our patients really, except if fortunate, a medical or n mask. even the retreat to the sanctuary of our own homes is fraught with the risk of unwittingly bringing the virus, trojan horse-like, into our most sacred of spaces. patients are us. we are them. yet, not really. the repercussions of the pandemic will exact a high toll on our collective psyche and on the public's trust in medicine, nursing and the health-care system. clinicians can choose to exhibit leadership in opening up difficult conversations that frame a set of questions about the value of life in principle and about the underlying and obvious value chains of who deserves human rights. we can advise on how to "get people to stay home" by giving them the resources to make that possible. or, we can usher in a police state that will further violently punish poor people for existing while we do nothing to help stop the spread of the virus. community engagement, public education, housing and financial support are required to help people practise physical distancing. our treatment armamentarium for covid- needs to expand if we have a hope of coming through this alive. coronavirus deaths in south africa rise to being a person of color isn't a risk factor for coronavirus. living in a racist country is -the boston globe vulnerable groups. world health organization world health organization perceived discrimination, race and health in south africa racism and health: evidence and needed research new york city's latinx residents hit hardest by coronavirus deaths on suffering and structural violence: a view from below pathologies of power: structural violence and the assault on human rights full: life esidimeni arbitration handed down by moseneke the faces of injustice from cholera to corona: the politics of plagues in africa africa is a country the political economy of famine. a preliminary report of the literature, bibliographic resources, research activities and needs in the uk. institute for research in the social sciences covid- infection prevention and control guidelines for south africa -draft v . department of health covid- recovery patients quadruple: report. sabc news -breaking news, special reports, world, business, sport coverage of all south african current events africa's news leader statistics sa. men, women and children: findings of the living conditions survey national poverty lines. pretoria, gp: isibalo house ghs series volume vii: housing from a human settlement perspective in-depth analysis of general household survey ( - ) and census ( - ) media statement inequality trends in south africa: a multidimensional diagnostic of inequality world bank we thank virus for water', say grateful mpumalanga community we thank virus for water', say grateful mpumalanga community. sowetanlive [internet]. sowetanlive; south africa's ruthlessly efficient fight against coronavirus personal oral communications with clinical colleagues siracusa principles on the limitation and derogation world health organization. who guidance on human rights and involuntary detention for xdr-tb control world health organization planet of slums amcu rules out mines returning to limited operations business day world medical association-wma statement on patient advocacy and confidentiality [internet]. the world medical association royal college of physicians and surgeons of canada. canmeds role: health advocate the royal college of physicians and surgeons of canada durban hospital closed indefinitely due to covid- outbreak i am thankful to antje schuhmann, sanele sibanda, zimitri erasmus and sarala naicker for rich conversations that have assisted in converting my thoughts and ideas around the covid- pandemic into something coherent. i am grateful to my daughter shanthi samara ragaven for a careful read of the text as well as her assistance with putting the references into vancouver citation style. finally, many clinician colleagues from south africa and internationally have generously shared their own frontline experiences which have broadened my own understanding of the challenges we are facing. key: cord- - w elfro authors: tambo, ernest; ugwu, emmanuel chidiebere; ngogang, jeane yonkeu title: need of surveillance response systems to combat ebola outbreaks and other emerging infectious diseases in african countries date: - - journal: infect dis poverty doi: . / - - - sha: doc_id: cord_uid: w elfro there is growing concern in sub-saharan africa about the spread of the ebola virus disease (evd), formerly known as ebola haemorrhagic fever, and the public health burden that it ensues. since , there have been , suspected and laboratory confirmed cases of evd and the disease has claimed , cases and fatality in west africa. there are certain requirements that must be met when responding to evd outbreaks and this process could incur certain challenges. for the purposes of this paper, five have been identified: (i) the deficiency in the development and implementation of surveillance response systems against ebola and others infectious disease outbreaks in africa; (ii) the lack of education and knowledge resulting in an evd outbreak triggering panic, anxiety, psychosocial trauma, isolation and dignity impounding, stigmatisation, community ostracism and resistance to associated socio-ecological and public health consequences; (iii) limited financial resources, human technical capacity and weak community and national health system operational plans for prevention and control responses, practices and management; (iv) inadequate leadership and coordination; and (v) the lack of development of new strategies, tools and approaches, such as improved diagnostics and novel therapies including vaccines which can assist in preventing, controlling and containing ebola outbreaks as well as the spread of the disease. hence, there is an urgent need to develop and implement an active early warning alert and surveillance response system for outbreak response and control of emerging infectious diseases. understanding the unending risks of transmission dynamics and resurgence is essential in implementing rapid effective response interventions tailored to specific local settings and contexts. therefore, the following actions are recommended: (i) national and regional inter-sectorial and trans-disciplinary surveillance response systems that include early warnings, as well as critical human resources development, must be quickly adopted by allied ministries and organisations in african countries in epidemic and pandemic responses; (ii) harnessing all stakeholders commitment and advocacy in sustained funding, collaboration, communication and networking including community participation to enhance a coordinated responses, as well as tracking and prompt case management to combat challenges; (iii) more research and development in new drug discovery and vaccines; and (iv) understanding the involvement of global health to promote the establishment of public health surveillance response systems with functions of early warning, as well as monitoring and evaluation in upholding research-action programmes and innovative interventions. please see additional file for translations of the abstract into the six official working languages of the united nations. the growing public health concern and the burden of ebola outbreaks in the absence of an effective drug and vaccine for the dreadful and deadly outbreak caused by the ebola virus disease (evd), formerly known as ebola haemorrhagic fever, there is growing concern for its public health burden in sub-saharan africa. since , there have been , suspected and laboratory confirmed cases of evd, including cased on the ongoing disease outbreak has claimed lives in west africa [ ] . this part of the world is persistently confronted with this fatal disease which has an incubation period of two to days (averagely - days). symptoms range from, firstly, fever and fatigue before descending into headaches, vomiting, violent diarrhoea, then multiple organ failure and massive internal bleeding [ , ] . ebola typically begins in remote places and can be distributed via hospitals/ healthcare centers or within the community as it takes several infections before the disease is ascertained. the prevalence, morbidity and case fatality of chronological evd outbreaks showed the persistent resurgence in different regions in sub-saharan africa (see figure ) . ebola outbreaks have a case fatality rate of - %, yet no specific drug or vaccine is available for people and/or animals hosts. as of august , the cumulative number of cases attributed to evd in the four countries stands at including deaths. the distribution and classification of the cases are as follows: guinea, cases ( confirmed, probable, and suspected), including deaths; liberia, cases ( confirmed, probable, and suspected), including deaths; sierra leone, cases ( confirmed, probable, and suspected), including deaths and nigeria, cases ( confirmed, probable, and suspected) including death. between the and july , a total of new cases (laboratoryconfirmed, probable, and suspect cases) of evd, and deaths, were reported from the four countries as follows: guinea, new cases and deaths; liberia, new cases and deaths; sierra leone, new cases and deaths; and nigeria, new case who died [ ]. the outbreak is expected to last longer if proper diagnostic tools and rigorous integrated active surveillance response systems are not rapidly established and instituted [ ] . therefore, the following requirements for rapid, scalable and sustainable responses to evd and other outbreaks across african countries, and globally, have been identified. first, the need to urgently recognise and coordinate outbreak action-responses in affected african countries and in cross-border neighbours, as well as collaboration with those that experienced outbreaks in the past, is vital. overall, ebola virus socio-ecology systems have shown to be linked by direct and indirect transmission through contact with objects from patients. for example, the blood or secretions of an infected person or objects that have been contaminated with infected secretions can reach humans from a variety of hosts/sources: naïve infected populations, infected wildlife, fruit and vegetable bats and the handling of infected fruit bats, monkeys, chimpanzees, gorillas, forest antelopes and porcupines are all possible natural hosts (whether ill or dead or found in the jungle or rainforest) [ , ]. thus, tracking, mapping, reporting and documenting veterinary public health zoonosis surveillance responses, the behaviour and medical history of butchers and poachers, as well as agro-livestock business trading are imperative to be able to establish integrated community-based and national comprehensive early warning and outbreak surveillance response systems. second, understanding the unending transmission dynamics and resurgence is essential to actively identify and map transmission foci and local micro-epidemiological situations, which can lead to implementing prompt, effective response interventions tailored to specific local settings. hence, active early warnings approach under the framework of a surveillance response system both for veterinary and human public health should be established and implemented. this system could include, for example, a ban on bush meat consumption, a ban on public places and markets, a reinforcement of safety and inspection regulations on food and fruit eating bats and examining bat migration as well as other animal-household drivers and risk factors [ , ] . third, instituting electronic-based reporting systems based on advances in information and communication technologies (icts) is crucial as already about % of the west african affected populations use mobile phones (mhealth or ehealth). building a local network (e.g. whatsapp) or crowdsourcing data for targeted active responses, as well as the implementation of a geographical information system (gis), are necessary spatial-temporal mapping and decision-making support systems to contain ebola outbreaks. lessons learnt from other outbreaks including cholera, h n and h n avian influenza, severe acute respiratory syndrome (sars), lassa fever, the middle east respiratory syndrome (mers), dengue pandemic and the human-animal with environmentalclimate interface in africa and elsewhere can assist in setting benchmarks for monitoring epicentre/focal early warning alert, incidence and prevalence as well as effective surveillance response interventions measures [ , ] . meanwhile, modelling factors and trends in different changing transmission scenarios could also yield better tactics, as well as strategic evidence not only for policy support, but also for direction, planning and implementation of national and regional early alert and surveillance response systems to control and prevent sentinel sites [ ] . following from the aforementioned three challenges and requirements to respond to evd outbreaks in africa, the following actions are recommended to combat evd as well as other emerging infectious diseases. ebola was first reported in in sudan and congo and named after the river where it was identified. it was later reported in gabon, central africa. the genus ebolavirus is one of three members of the filoviridae family (filovirus), along with the genus marburgvirus and the genus cuevavirus, and comprises five distinct species, of which zaire ebolavirus, sudan ebolavirus and bundibugyo ebolavirus are mostly associated with the major evd outbreaks in africa. reston ebolavirus and taï forest ebolavirus are mostly reported in the asia-pacific region, especially philippines and the people's republic of china, but no symptoms or deaths in humans from these have been reported to date [ ] . the disease outbreak has persisted over the years across central, east and southern africa. on march , , the first case of an outbreak was identified in guinea, west africa, witnessing a total of cases with fatalities, as it spread beyond the remote rural areas to the capital city of conakry. soon after the outbreak was identified, it appeared across the border in the small nation of liberia on march , . this country was the least hit with cases and fatalities thus far. later, it was also identified in sierra leone in late may , just as it appeared the outbreaks in guinea and liberia were winding down. it has since spread to at least two sierra leone districts with cases claiming at least lives, including deaths of new cases within just four days. similarly, between and july , new cases and deaths were reported from liberia and sierra leone. in guinea, new cases and deaths were reported during the same period and one death in nigeria [ ] (see table ). understanding african cultural and customs practices and how they affect psychosocialbehavioural attitudes towards ebola outbreaks african economic community according to the world bank, . each country consists broadly of two distinct zones: a sahelian zone (north), largely landlocked, and a more humid, forested coastal zone (south), with the literacy rate varying from - % (see figure ). similar to the conception and spread of the hiv/aids pandemic in africa, one of the main obstacles in reducing the distribution of ebola has been the widespread ignorance, lack of knowledge and potential panic over evd, considered to be a 'satanic or bewitched' disease, leading to trepidation, isolation, dignity impounding, stigmatisation and ostracism from associated socio-ecological and public health consequences. recently, local residents of the sadialu village in sierra leone were sheltering those infected with ebola, refusing to go to or escaping from hospitalisation referred as "death sentence", and hiding from the local health centre due to circulating beliefs, myths and rumours that the interventions being administered to patients were actually causing the disease (see figure ). such consequences and misconceptions are proscribed in the international health regulations (ihr), human rights laws, as well as the helsinki and the who declarations. these detail the challenges and opportunities that ebola and other infectious diseases are currently facing, including neglected tropical disease (ntd) prevention, control and management, as well as health system coverage and service delivery bottlenecks. harnessing all stakeholders' collaboration, communication and networking, including communities, is essential for improving and nurturing community participation, informal and formal health education, ownership and empowerment of the programmes, and patient independence and dignity, as well as ensuring human rights for all ages at all levels in order develop a productive and sustainable african continent and achieve the millennium development goals (mdgs) and global health. hence, accelerating the response through provision of minimum essential information on risk communication for behavioural impact, developmental communication and health promotion/education personnel and community, working in multidisciplinary to respond to the disease outbreak, will be very useful for adequate and appropriate national staff and other national resources to the field operational epidemiologists, clinicians, and public health officers in fostering positive behavioural changes while respecting cultural practices, and impact on local contexts and outbreak dynamics, prevention and control interventions and scaling up outbreak containment measures, especially effective contact tracing. unfortunately, several countries in africa, as well as governmental and research institutions, are inadequately equipped in diagnostics, tracking, active reporting, prompt healthcare delivery, and accessible and affordable treatment to combat the ebola infection and other emerging infectious diseases. the development of new tools, strategies and approaches, such as improved diagnostics and novel therapies including vaccines, is needed to prevent, control and contain ebola as well as sars, bird flu, lassa fever, dengue and mers outbreaks. hence, the urgent need to develop and implement early warning alert and active surveillance response systems for emerging infectious diseases and the control and elimination of ntds, as well as early warning and emergency systems, cannot be overemphasised. the prerequisites for fighting and containing the transmission and saving lives include concerted actions to empower communities through mobilisation, communication and participation; formal and informal education; and training of community and environmental health professionals. timely and effective reporting, documentation and communication of incidence and prevalence by all stakeholders including the health ministries, international and local ngos, un agencies, religious leaders, who regional and partners (cdc, msf, unicef, ifrc) continue to work together through the sub-regional ebola outbreak coordination center (seocc), global health institutions and other stakeholders are paramount in early containment response [ ] . who does not recommend any travel or trade restrictions is applied to guinea, liberia, sierra leone or nigeria, based on the current information available. moreover, people who don't have the knowledge should be educated on how to protect themselves. also important is the prompt quarantining of the sick and the dead in line with the african customs and burial traditional, cultural myths and practices, as it is believed in such cultures that corpses are still contagious and customary transmits the disease. there is an urgent necessity to strengthen the primary healthcare system, and develop more sensitive serological and molecular diagnostic tools, as well as innovative methods and approaches to assess vulnerability in agreement with current practices (see figure ). this requires further research and development (r&d), capacity building based on international best practices for containing public outbreaks, the drafting of standard processes and operating procedures, biorisk management as samples from patients and animals are an extreme biohazard risk, thorough adherence to the who global alert and response operations, and outbreak communication guide-lines. moreover, maximizing the advances in genomic, biotechnological and communication technologies provides efficient and improved surveillance tools for early warning system prognostic, monitoring and evaluation control and prevention of outbreaks; these should be based on preventing the source as ascribed in the 'one world-one health' standpoint [ , ] . in addition, intensive efficacy and pharmacovigilance assessment of these interventions including diagnostics, drugs and vaccines against ebola and other emerging infectious diseases including ntds must be carefully re-evaluated, and the cut-offs determined and monitored over time, in addition to enhance cross-border collaboration and strengthen effective coordination across african government and populations [ ] [ ] [ ] . real-time active surveillance response systems, research priorities and innovative mechanisms for outbreaks include the development of tools targeting early active diagnosis especially at the onset and during the low level of transmission; tracking and mapping; monitoring human and host population migration; forecasting outbreaks based on risk factors; assessment of indicators and minimal essential datasets to guide evidence decision making; strategic planning and effective control; and prevention programmes and response packages tailored to local settings [ , ] . experiences and lessons learnt from outbreaks in developed nations could be shared with limited-resource countries so that they can to establish early warning and surveillance response systems [ ] . irrefutably, national and regional inter-sectorial and trans-disciplinary approaches must be adopted and related to ministries and organisations in order to build innovative early warning system surveillance response systems through fostering capacity building and training on outbreaks and emerging infectious disease prevention, control and elimination. it is also imperative to understand global health involvement and governance, establish monitoring and evaluation (m&e) of research for action programmes, as well as increase funding to support efforts of existing and new consortiums and research projects in africa. furthermore, there is need to analyse the socio-economic and cultural factors, the status of prevailing health systems, and the risk factors and determinants of the emergence and spread of outbreaks in africa. reliable and well-organised monitoring, the establishment of giss and appraisals of cost-effectiveness in an integrated national health system (with a care management approach) will eventually improve evidence information for policy-makers [ ] . in turn, they can make decisions and guide implementers of health programmes to achieve beneficial and innovative sustainable global public health interventions, quality healthcare outcomes and economic prosperity. consolidating and harmonizing the technical support at local, country, regional, and international level is required in mobilizing the international community in support of national efforts in epidemic and pandemic prevention and control. hence, developing, scaling up and strengthening all aspects of the outbreak surveillance response system including contact tracking, public information and community mobilization, case management and infection prevention and control, and effective coordination. references . who: ebola virus disease, west africa-update disease outbreak news elimination of tropical disease through surveillance and response surveillance-response systems: the key to elimination of tropical diseases improving the performance of outbreak detection algorithms by classifying the levels of disease incidence prioritizing research for "one health -one world need of surveillance response systems to combat ebola outbreaks and other emerging infectious diseases in african countries no funding body supported this study. additional file : multilingual abstracts in the six official working languages of the united nations. the authors declare that they have no competing interests.authors' contributions et conceived, collected and analysed the data, and drafted the manuscript. et, ecu and jyn provided additional information. all authors read and approved the final manuscript. key: cord- - tp ig o authors: hayman, david t s title: african primates: likely victims, not reservoirs, of ebolaviruses date: - - journal: j infect dis doi: . /infdis/jiz sha: doc_id: cord_uid: tp ig o nan ebola virus disease (evd) kills almost half those people infected. four different viruses from ebolavirus species have caused evd in africa: zaire ebolavirus (ebov), sudan ebolavirus (sudv), bundibugyo ebolavirus (bdbv), and tai forest ebolavirus (tafv), with all but tafv causing fatal human disease. outbreaks have been sporadic and unpredictable, but the frequency and size of outbreaks appear to be increasing [ , ] . the ongoing outbreak in the democratic republic of the congo (drc) is the second largest on record, with > cases and > deaths reported from health zones [ ] . the largest evd outbreak, originating in guinea, west africa, in [ ] , ended in after cases and deaths [ ] . preventing evd outbreaks is challenging because the "reservoir hosts" of the viruses that cause the disease are not known. the weight of evidence suggests that fruit bats are the natural hosts, but this is uncertain [ ] . the uncertainty is partially because most outbreaks in people are not directly linked to bats. circumstantial evidence linked bats to the west african outbreak [ ] , but index case exposure to bats has only once been reported with any confidence [ ] . in contrast, hunting or butchering primates has been linked to several evd index cases. in particular, africa's great apes, gorillas and chimpanzees, have been sources of human infection, and human evd outbreaks have occurred concurrently with outbreaks in apes in central and west africa [ , ] . high case fatality rates among apes [ ] [ ] [ ] , however, suggest they are not maintenance reservoir hosts [ ] . wildlife mortality events during evd outbreaks have involved other mammals, including monkeys, pigs, and antelope [ ] . contact with monkeys has been reported in human outbreaks in central africa [ , ] and chimpanzees in ivory coast [ ] . monkeys themselves appear to be susceptible to ebov infection, at least experimentally [ ] . outside of africa, reston ebolavirus (restv) has been linked to monkeys, with macaques imported to the united states from the philippines infected [ ] , but the mammals linked to restv in asia are similar to africa, with pigs, monkeys, and bats all implicated as hosts [ ] [ ] [ ] . serological data may be well suited for surveillance studies, because antibodies are longer lasting than viral infection and provide evidence of survival. experimental evidence suggests that ebov infection in bats may be acute, nonfatal, and short-lived, but induces antibodies [ ] . this experimental work is supported by field data from related marburg viruses, first identified after african monkeys infected people in europe [ ] , which apparently persist within large colonies of cave-dwelling egyptian fruit bats, and restv in asian bats. in both cases, viruses or viral rna and antibodies were detected in apparently healthy bats [ , ] . just study has detected ebov rna in bats, but anti-ebov antibodies are widespread in african bats and the rna-positive bats were, again, apparently healthy [ , [ ] [ ] [ ] [ ] . in contrast, while anti-ebov antibodies have been observed in african apes and monkeys [ , ] , suggesting that nonlethal infections might occur, the prevalence of antibodies is low (similar to those reported for restv in asian macaques [ ] ), and ebov rna has been isolated from dead apes [ ] . thus, together the evidence for bats being the true reservoir host for evd causing viruses is convincing, but relies on serological evidence of infection rather than virus detection, and the role of nonhuman primates as reservoirs remains uncertain. the role of primates in evd epidemiology has been unclear largely because study sample sizes have been small. serology is further complicated by different methodologies and antibody-positive sera cross-reacting among different evd-causing viruses. a report by ayouba et al, in this issue of the journal of infectious diseases, has taken a significant step toward addressing these problems [ ] . the team utilized a large sample (n = ) of tissues from multiple species of african primates, collected from to from ivory coast in west africa and drc and cameroon in central africa. the study more than triples the number of all previous primate samples reported and is similarly powered to some studies showing high seroprevalence of anti-ebov antibodies in certain african fruit bat species [ , ] . a single luminex-based serological assay that included antigens from viruses (ebov, sudv, bdbv, and restv) was used, and the team discovered that none of ape samples and only of monkey samples met their seropositive criteria. the data strongly suggest that the primates sampled are unlikely reservoir hosts. the work highlights the importance of multiyear, multisite empirical studies and archiving samples. specimen collection in general has created some controversy in areas such as conservation biology [ ] , but for epidemiologists tissue archives may enable us to better understand the epidemiology of infectious diseases. here, the primate samples were collected for lentivirus research (eg, human immunodeficiency virus [hiv] and its relatives), then repurposed for evd research. in other systems, archived sample banks have helped identify middle east respiratory syndrome coronavirus-seropositive camels in east africa over -year (kenya) and -year (sudan and somalia) periods, suggesting extensive virus circulation in camels prior to the first human outbreaks [ ] [ ] [ ] [ ] . some impressive examples of using archaeological samples have led to the sequencing of yersinia pestis genomes from black death victims in london, england, dated to - [ ] , and bronze age hepatitis b viral dna [ ] . the instability of rna viruses will prevent paleovirological studies on these timeframes, though gene sequencing from archived samples has helped identify hiv type (hiv- ) sequences predating the first aids diagnosis, with hiv sequences from and in drc informing our understanding of pandemic hiv- origins and evolution [ , ] . ideally, evd-causing viruses themselves will be isolated in space and time through wildlife surveillance to understand viral transmission dynamics. phylogenetic models that estimate the relationship between genetic sequences have been used with sample location data to place the first case from drc near the root of the ebov phylogenetic tree, suggesting that all other known outbreaks descended from a closely related virus [ ] . although the analysis contained just a few viral fragments, it suggested that later outbreaks were epidemiologically linked and occurred in a wave-like pattern, spreading at approximately km per year. once ebov rna fragments were discovered in bats, the same team used similar models to reconstruct the ancestry of ebov, including fragments of viral rna from bats [ ] . their analyses suggested that all of the genetic variation present in ebov, including from fruit bats, was the product of mutations accumulated within a -year time period, supporting the ancestry of ebov in bat reservoirs and the role of bats in ebov epidemiology. the absence of robust data on ebola virus reservoirs makes forecasting when and where outbreaks may occur difficult, limiting preventive measures [ , ] . the lack of data relating to bats themselves led researchers to characterize the traits of all filovirus-seropositive and virus-positive bat species to predict potential undetected bat species [ ] . putative bat hosts have been included in models to predict the spatial risk of human outbreaks [ ] . similar modeling approaches have been used to model the spatial and temporal risk of human and ape evd, finding the greatest risk during wet to dry season transitions in sparsely populated regions of tropical africa [ ] , supporting previous work [ ] . all of these studies are limited by data, but ayouba et al's comprehensive study supports the assumption that bats, not primates, are likely reservoir hosts and that nonhuman primates may be viewed as both sentinels for human infection and victims of evd [ , , , ] . these are important findings because they can inform field and surveillance studies, which are costly and difficult in most areas where evd outbreaks occur and for the species linked to evd. to really manage and prevent evd, however, we also need to understand why outbreaks appear to be increasing in frequency. recent analyses of forest fragmentation and evd emergence suggest there may be links [ , ] . if so, there may be management options that can be implemented alongside human and wildlife surveillance and public health interventions to reduce the risk of human and, potentially, primate evd emergence in the first place. financial support. the author was supported by the rutherford discovery fellowship (award number rdf-mau ) and the marsden fund (award number mau ). potential conflicts of interest. author certifies no potential conflicts of interest. the author has submitted the 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transferred to the united kingdom from the middle east a draft genome of yersinia pestis from victims of the black death ancient hepatitis b viruses from the bronze age to the medieval period direct evidence of extensive diversity of hiv- in kinshasa by an african hiv- sequence from and implications for the origin of the epidemic wavelike spread of ebola zaire recent common ancestry of ebola zaire virus found in a bat reservoir field investigations of an outbreak of ebola hemorrhagic fever, kikwit, democratic republic of the congo, : arthropod studies search for the ebola virus reservoir in kikwit, democratic republic of the congo: reflections on a vertebrate collection undiscovered bat hosts of filoviruses mapping the zoonotic niche of ebola virus disease in africa spatiotemporal fluctuations and triggers of ebola virus spillover trigger events: enviroclimatic coupling of ebola hemorrhagic fever outbreaks multiple ebola virus transmission events and rapid decline of central african wildlife habitat fragmentation, biodiversity loss and the risk of novel infectious disease emergence the nexus between forest fragmentation in africa and ebola virus disease outbreaks key: cord- -mqbud t authors: tambo, ernest; madjou, ghislaine; khayeka-wandabwa, christopher; tekwu, emmanuel n.; olalubi, oluwasogo a.; midzi, nicolas; bengyella, louis; adedeji, ahmed a.; ngogang, jeanne y. title: can free open access resources strengthen knowledge-based emerging public health priorities, policies and programs in africa? date: - - journal: f res doi: . /f research. . sha: doc_id: cord_uid: mqbud t tackling emerging epidemics and infectious diseases burden in africa requires increasing unrestricted open access and free use or reuse of regional and global policies reforms as well as timely communication capabilities and strategies. promoting, scaling up data and information sharing between african researchers and international partners are of vital importance in accelerating open access at no cost. free open access (foa) health data and information acceptability, uptake tactics and sustainable mechanisms are urgently needed. these are critical in establishing real time and effective knowledge or evidence-based translation, proven and validated approaches, strategies and tools to strengthen and revamp health systems. as such, early and timely access to needed emerging public health information is meant to be instrumental and valuable for policy-makers, implementers, care providers, researchers, health-related institutions and stakeholders including populations when guiding health financing, and planning contextual programs. in recent times, the persistence and unprecedented emergence of rising epidemics and infectious diseases in africa and worldwide triggered numerous public health declarations of international concern . these local and global uncertainties and potential consequences have prompted questions and reflections on the usefulness and implications of unlocked and unprocessed available massive database resources from different national, regional and international funded projects overtime in low and middle income countries (lmics) and particularly in africa. can free open access (foa) to these valuable resources improve evidence-based decision making policies, health planning and adequate funding allocation, innovative programs and strategic interventions performance and effectiveness to most vulnerable populations' health and socio-economic benefits? emerging and re-emerging infectious diseases epidemics are rampant, ranging from ebola, influenza, lassa fever, hiv sars and mers-cov, zika to other zoonotic diseases existing as potential threats with sporadic epidemics in old and new regions , . there is a need for availability of data and information on humanvector-pathogen-ecosystem interfaces, drugs and vaccines development as well as diagnostics techniques and tools from preclinical to clinical levels. it is critical that the information is used in an equitable, ethical and transparent manner. operational research projects in libraries, national archiving, journals, local and international , scholarly institutions and centers are partially or yet to be fully tapped into maximizing and ensuring improvements of health and disease information, knowledge and empowerment for all generations . previous literature reviews have shown that open access data and information are of great importance and valuable assets in information sharing, education exchanges and capacity development. this foa necessity has practically been laid bare by the recent from west africa ebola to zika epidemics crisis where experts across fields including clinical ' neonatal and pediatrics have been challenged. henceforth, academic journals, libraries sources, local and internal non-governmental organizations (ngos) data, data from research funded or non-funded projects, centers and institutions should be committed to foa data and results sharing relevant to the current zika public health crisis and future emergencies for rapidly emergency mobilization and response. moreover, the approach has proved to be useful in translation and application of proven and reliable knowledge in guiding effective decision making policies, lifestyle adaptations and contextual programs and strategies in improving public health social economic development and well-being of local and global community , , , . most data and information often used in global policies and initiatives are either guaranteed as free by the world health organization (who) and partners philanthropic organizations, whereas the bulk of support references and documents are not readily accessible to most african scholars, but mainly to policy-makers and implementers . equally, limiting access to younger generations of researchers and students who cannot afford the fee to access publication in high impact placed journals, provide highly condensed information not easily informative to those in much need. the free open access core concept can be characterized by removal of price barriers, no subscription fees and permission barriers, no copyright and licensing restrictions to royalty free literature, to make data and information available to all populations , . "fee free open access to health data and information for all generations offers a new public health paradigm shift and opportunities to meet the knowledge, lessons learnt and experiences gaps and needs in africa. advocacy and mitigation on lack to limited access of existing and emerging data, and information sharing is necessary in embracing regional and global open access. these novelties in information sharing approaches towards collective learning and participative engagement for sound knowledge and empowerment for better health, information exchange for equity in quality education and utilization are paramount for human and societal benefits. it is of fundamental importance to increase multi-disciplinary and inter-sectoral partnerships and collaborations not only to understand and fill the gaps through joint or independent research, but also to be able to use and mine unrestricted data and information for public health good, economic growth and sustainable development , . although decades of funded and non-funded programs and projects in both developed and developing countries have generated millions of publications and databases on emerging and infectious diseases of poverty , , . the impact of policy-translation of lessons learnt and experiences gained are seldom and limited in applications mostly in developing countries. as most lmics are still challenged with weak health systems and low literacy mainly in remote rural areas and areas of political instability, inadequacies in health funding allocation and resources capacity, poor accountability and governance are present. moreover, inefficiencies in management and lack of a multi-sectoral approach to access and use local or national data repositories in a structured manner prevent both mainstream national and regional economic development . furthermore, the usefulness in forecasting, prevention and management or smart response of emergency situations and disasters are yet to be fully documented and demonstrated in africa. foa viability and benefit in most tropical endemics and epidemics-prone developed and developing countries affirmed that the vast majority of metadata and database platforms are still locked (inaccessible and unavailable) for public use and untapped to global community multi-dimensional gains. increasing unrestricted and foa use or reuse as well as timely reporting or communication capabilities strategies are urgently needed in promoting and scaling up data and information sharing and exchange between african researchers, partners and collaborators , , , . the strength of scaling foa in developing countries will entail but not limited to: ) increasing real time and effective knowledge-or evidence-based translation of proven and validated approaches, ) strategies and tools in strengthening health systems and revamping early and timely access to much needed information by policy-makers, and ) enhanced guided health financing and capacity development by health institutions and related stakeholders, and strengthening contextual programs and activities planning, transparency and accountability. this paper assesses the values and benefits of open, free of charge data and information access and availability in strengthening health systems policies, financing, promoting knowledge-based programs and targeted interventions directed to forecast, prevent, reduce and/or manage the growing emerging threats and epidemics as well as infectious diseases of poverty in lmics, especially in africa. the growing burden of emerging epidemics and infectious diseases have been documented in demoting health systems in rural and urban settings in africa. it is important to assess and understand why and how open data and information access is needed in the context of health and diseases epidemics. also, what capacity development and training are needed to translate these various valuable datasets and database assets if freely available into knowledgebased innovations needed to revolutionize africa and global health capabilities, and opportunities to prevent and control emerging epidemics and infectious diseases of poverty , , , . the current trends of globalization of trade and travel, intense urbanization, economic slowdown are coupled with rising of double epidemics burden (emerging infectious diseases and chronic diseases). thus, there is an urgent need for open data and information access promotion, advocacy and awareness. this is critical in strengthening and improving the strategic value and usefulness of knowledge-based innovations, teaching and learning, key sources and assets of policy transformation oriented research and primary care innovations (e.g., routine to universal immunization, essential medicines and nutrition). adopting and adapting open access proven lessons learnt and experiences to alleviate sufferings and poverty, health literacy access and delivery inequities amongst vulnerable populations in africa is very important , , , . the evolving use of electronic data and digital delivery platforms to support open access interactive literacy, communication and empowerment of health is a vital need in increasing care acceptability, uptake and scaling up positive cultural ad behavioral changes relevant for communicable and non-communicable diseases vigilance and resilience , , . however, with restricted content access, such anticipated evolution in terms of accurate timing and relevant knowledge among experts remains to be a blatant wish as technology and information are not mutually exclusive. digital technology is only but a driver of available content and hence it thrives, and finds usefulness in the context of information, particularly transformative evidence for universal global health resources access and sharing benefits for all. health financing or national resource allocation requires as much open data and information access, analysis, effective and reliable interpretation for outcomes-based sustainable and equitable early decision health financing and funding in achieving local and regional universal health coverage (uch) and sustainable development goals (sdgs). moreover, this new paradigm has the capacity to strengthen and allow exploration of potential local and national health systems, insurance schemes implementation, uptake and coverage impacts as well as legislative and institutional reforms and regulations to enable community and stakeholders commitments and investments , . proactive efforts in promoting radical data and information openness and defining criteria tailored to sharing capabilities and transparency are critical and innovative approaches to create monetary and non-monetary benefits , . data-driven approaches and strategies provide an immense opportunity to understand, define and generate databases that can be used for predictive primary care and innovations in the short-and long-term in diverse scenarios , . in order to attain and optimize the pan-africanism aspiration to foa to current findings and evidence that help shape our decision making process, it is imperative to consolidate online platforms and resources to one stop shop for evidence in different genres. since timely access to accurate data and information are essential to improving the quality of knowledge and intervention effectiveness, to information scientists alongside librarians globally. predominantly, with the challenges of electricity shortage and costly internet services, most open access african users' tendency is increasingly familiar with google and other internet search engines to discover or access information. hence, any foa platform should be user-friendly, non-bias choice, interoperability and flexible. that is, accessibility should not depend on articles being accessed via a special portal or proxy server or publishing platforms, or via complex authorization systems, but should be readily and freely available to all re-users or users consumers and redistribution within the ethical and legal framework. information should be readily reached without barriers targeting all cadres of technocrats from those with basic training and skills to the advanced. tested models have proved this relevance and lesson for progressive improvement can be adopted , , . one of the implications of not doing so is not being able to find information easily using online systems , , . consequently, researchers and policy-makers and implementers in lmics have to spend enough time to be informed, consolidate and synthesize what types of information and knowledge can be adaptable, scalable, cost-effective and translated in intervention and best practices , , . as a way out in many occasions, when we develop policies for research and programs delivery, we as institutions or individuals take slightly different routes to find the evidence that helps shape our decision making. we often end up relying on a restricted range of platforms, consortia systems and institutional networks that are only readily available small scale data and database evidence online . hence, without objectivity and in absence of credible context relevant platforms, we are prone to use biased and/or misplaced approaches policies particularly in the health systems improvement endeavor , , . foa platforms prospects are multiple to african scholars, researchers and their collaborators real time and frontline data and other research outputs contextual determinants and scenarios will preferentially entail consolidating r&ds that are alternatives to the prevailing publishing proprietary models to support open access to health resources. for instance, prioritization databases combine available genomic, genetics and bioinformatics data for each priority genre with automatically extracted and manually curated information for genetic counseling to personalized medicine. also, in questioning or responding to further literature and other databases research gaps relevant to clinical and analytical practices, putative drug and vaccine target(s) discovery for threatening chronic diseases. investing substantial efforts in open database mining also permits prioritization, actionable and customized evidence, potential drug and vaccine targets discovery , , , . such harnessing may entail the development of research and innovation portfolios focusing on critical public health gaps where traditional approaches are failing, and leveraging proven evidence and lessons learnt on what works and what does not work. as such, the aim would be to attain a long term health agenda and capacity building mitigation via research approaches, cost-effective, timely and progressive innovations , . authors advocate to governments, policy-makers and implementers, researchers, academicians, health professionals and other stakeholders including the community to endorse open access public health resources platforms implementation at all levels. there is also need to develop appropriate mechanisms and strategies to promote open access capacity building and empowerment, enhanced health and disease literacy and education through sharing and exchanges, innovative policies and frameworks with advances in digital technologies, establishment of data and information quality control and assurance principle and guidelines, well-coordinated and coherent metadata and database management for evidence operational research and clinical decision making interventions , . the value and credit of foa does not only promote health and disease literacy, but offer opportunities for mutual sharing of various educational materials, learning and empowerment on maximizing on the use or reuse of the data mining and managed for short-and long-term public health benefits, global health security and wellbeing. foa agenda to health workers, professional and providers and communities offers new opportunities in providing affordable, robust, real time and free user friendly and sustainable datasets and databases , , , . while proactive efforts in reducing or minimizing the various barriers and challenges of foa uptake and implementation capacity including intellectual property rights, confidentiality, legislation and data use agreements amongst stakeholders (including the lay communities, institutions of learning and studentships) still persist, the value of open access is real , , , . the value of freely accessible and available scarce and/or other profuse data, database and information through foa for public health systems offers tremendous opportunities to strengthen and fasten emerging threat and epidemics including persistent infectious diseases of poverty modeling in preparedness, prevention and control. moreover, promoting robust evidence-based health and disease surveillance, response planning and funding underscore the social, ecological and economic burden, and opportunities for governments, stakeholders and vulnerable populations , , , , , . nonetheless, foa and information sharing potential benefits and gains should include but not limited to: ( ) enhancing new public health paradigm and innovations in collective and participative education, timely reporting and increasing dissemination and effective trans-boundary risk communication towards democratization of heath data and information for quality health and wellbeing. ( ) accelerating proven acceptability and uptake tactics and sustainable mechanisms such as expanded vaccine(s) immunization or mass drug administration in scaling up the coverage and effectiveness to prevent disability and death; uses of wearable technology and sensors in early detection, tracking and monitoring of vectors and/or pathogens and management of associated diseases including non-communicable diseases mitigation and lifestyle adaptations strategies. ( ) upholding continuous open access resources advocacy, education and awareness for all in securing universal health coverage, sdgs and "foa health information for all generations". ( ) nurturing new commitment and investment in novel proven approaches, methods and tools in strengthening local and regional health systems capacity development (infrastructures and resources) in operational and translation research from diverse resources and sources. ( ) promoting the value of free, real-time data and information access and availability to all parties in transforming knowledge-based translation into health policy decisions and guiding health priorities financing and public health actions. ( ) improving integration and use of information to support evidence-based integrated public-private health and related sectors partnerships (local private sector, bilateral and multi-international) and community-based programs and projects participative ownership. ( ) fostering innovative interventions and best practices amongst professional, health workers and the community resilience and participative engagement in response to emerging threats and disasters. ( ) facilitating lifetime interactive learning, increasing knowledge, empowerment and resilience in emerging epidemics and infectious diseases vulnerability surveillance and monitoring measures. ( ) promoting ethical, legal and international regulations and by-laws applications in safety and security. ( ) promoting local, national and regional "one health" approach in tackling in integrated manner regional and global epidemics of zoonotic infectious diseases prevention, preparedness, control and elimination agenda integration, uptake and utilization for impact. author contributions et conceived the idea, researched the literature and initiated the primary draft of the manuscript. et, gm and ckw contributed to review the literature. et, gm, ckw, ent, oao, nm, lb, aaa and jyn provided further inputs. all authors read and approved the final manuscript. no competing interests were disclosed. the author(s) declared that no grants were involved in supporting this work. the authors have addressed the highly important issue of free open access (foa) as a means of tackling emerging epidemics and infectious diseases burden in africa. they argue that unrestricted open access and free use or reuse of relevant and appropriate data together with sharing of data among african researchers, international partners, policy makers and the community will help limit the effect of burden of infectious disease epidemics in africa. availability of real time information on virtually all aspects of infections and diseases is required for timely action and response needed to ensure that public health events do not escalate to international concerns with grave consequences. it must be however observed that unrestricted free open access to data may lead to users being overwhelmed and unable to make sense out of the data, unless there is available capacity and capability for appropriately analysing and synthesizing the data into valuable information for policy-makers, implementers, care providers, researchers, health-related institutions and stakeholders including the community. this requires increasing and improving human resource capacity side by side with the call for unrestricted free open access. i find the review stimulating and challenging, with title and abstract matching the contents and conclusions which focuses on the benefits of foa. as they call for foa, they also call for the need for unrestricted but planned collaboration between all stakeholders under the "one health" umbrella. no competing interests were disclosed. competing interests: are press depictions of affordable care act beneficiaries favorable to policy durability? cumulative environmental impacts: science and policy to protect communities open access to research for the developing world lessons learned from scaling up a community-based health program in the upper east region of northern ghana pubmed abstract | publisher full text | free full text active patients in rural african health care: implications for research and policy improving online access to medical information for low-income countries health professionals for a new century: transforming education to strengthen health systems in an interdependent world organization wh: strengthening health systems to improve health outcomes. who's framework for action which knowledge? whose reality? an overview of knowledge used in the development sector promoting open access to research in academic libraries open access in south africa: a case study and reflections research evidence and policy: qualitative study in selected provinces in south africa and cameroon version this article was carefully thought of by the authors in relation to the current disease burden faced by the world and its people. the concept of foa as a driving force for better networking on the knowledge of disease burden, has been an area of concern by researchers, health organizations and the various government bodies around the world. research based information generated by different labs using high throughput information has been the driving force for obtaining large funding, reasons why the published information cannot be freely accessed in some journals. the resulting challenge is the lack of implementation of the right approaches to disease outcomes in lmics due to low comprehension of the disease epidemiology and genetic factors. there is actually need for world governing bodies to sit at their conferences and make foa a priority so that researchers in lmics, through documented information in accessed journals, could collaborate with authors who have published widely in related fields of interest, helping them contain the disease epidemic using the right approaches before it spreads. the world now is a global village and should be treated as such, hence institutions at all ends of the globe should be able to create some form of partnerships for training and sharing data for the advancement of better health for all.the authors actually focused on their indicated topic and brought out related challenges, which suggests reasons for poor approaches to the current disease burden. their proposals highlight steps which every player involved in decision making at various levels of the disease burden for better health, need to consider for us to attain the health goals put in place.i recommend this article as a document for all involved in the research and health field. no competing interests were disclosed. key: cord- -z kvf n authors: rogerson, stephen j.; beeson, james g.; laman, moses; poespoprodjo, jeanne rini; william, timothy; simpson, julie a.; price, ric n. title: identifying and combating the impacts of covid- on malaria date: - - journal: bmc med doi: . /s - - -x sha: doc_id: cord_uid: z kvf n background: the covid- pandemic has resulted in millions of infections, hundreds of thousands of deaths and major societal disruption due to lockdowns and other restrictions introduced to limit disease spread. relatively little attention has been paid to understanding how the pandemic has affected treatment, prevention and control of malaria, which is a major cause of death and disease and predominantly affects people in less well-resourced settings. main body: recent successes in malaria control and elimination have reduced the global malaria burden, but these gains are fragile and progress has stalled in the past years. withdrawing successful interventions often results in rapid malaria resurgence, primarily threatening vulnerable young children and pregnant women. malaria programmes are being affected in many ways by covid- . for prevention of malaria, insecticide-treated nets need regular renewal, but distribution campaigns have been delayed or cancelled. for detection and treatment of malaria, individuals may stop attending health facilities, out of fear of exposure to covid- , or because they cannot afford transport, and health care workers require additional resources to protect themselves from covid- . supplies of diagnostics and drugs are being interrupted, which is compounded by production of substandard and falsified medicines and diagnostics. these disruptions are predicted to double the number of young african children dying of malaria in the coming year and may impact efforts to control the spread of drug resistance. using examples from successful malaria control and elimination campaigns, we propose strategies to re-establish malaria control activities and maintain elimination efforts in the context of the covid- pandemic, which is likely to be a long-term challenge. all sectors of society, including governments, donors, private sector and civil society organisations, have crucial roles to play to prevent malaria resurgence. sparse resources must be allocated efficiently to ensure integrated health care systems that can sustain control activities against covid- as well as malaria and other priority infectious diseases. conclusion: as we deal with the covid- pandemic, it is crucial that other major killers such as malaria are not ignored. history tells us that if we do, the consequences will be dire, particularly in vulnerable populations. the impact of the covid- pandemic on the control of infectious diseases is substantial, undermining established programmes addressing hiv, tuberculosis and malaria and childhood vaccination. this opinion piece focuses on the threat covid- poses to the control of malaria and the steps that can be taken to mitigate these impacts. over the past years, major gains have been made in reducing the global burden of malaria, with countries achieving malaria elimination. these gains are largely attributable to expanding the distribution of insecticidetreated bed nets (itns), indoor spraying of residual insecticides (irs) and other vector control strategies; access to early diagnosis (e.g. rapid diagnostic tests (rdts)); and more effective antimalarial treatments [ ] , together with targeted interventions such as intermittent preventive treatment in pregnancy (iptp) and seasonal malaria chemoprevention (smc). this multipronged approach has been enabled by a greater political, financial and global commitment to malaria elimination, encouraged by ambitious targets, such as reducing malaria globally by > % by (compared to ), eliminating malaria from the asia pacific by and africa being largely malaria-free by . however, in recent years, progress in reducing the global burden of malaria has stalled. in , there were an estimated million cases, compared with million in , and over , deaths [ ] . challenges in achieving malaria elimination include the emergence and spread of drug-resistant parasites and insecticideresistant mosquitos, suboptimal rdts, lack of universal access to malaria prevention and treatment and the lack of a highly effective vaccine. malaria funding is below what is required to achieve global goals, and many countries face competing health priorities in the context of severely constrained resources [ ] ; tuberculosis, human immunodeficiency virus (hiv) infection and other diseases face similar challenges. in this environment, the emergence and spread of covid- presents a huge threat to malaria control that could reverse recent gains in many malaria-endemic countries. historically, curtailing malaria control activities has been followed by resurgence in malaria morbidity and mortality [ ] . this has occurred when programmes were reduced due to funding constraints or disrupted by war, disaster or conflict [ ] . following the termination of a dichlorodiphenyltrichloroethane (ddt) programme in indonesia in the s, annual malaria cases rose from < to , . between and , sri lanka reduced malaria cases from . million to just , but experienced a massive resurgence to over , cases per year [ ] . while sri lanka has now successfully eliminated malaria, other asian countries that are approaching elimination face similar risks of resurgence if current programmes are substantially disrupted by the covid- pandemic. economic collapse and health system failure are known to be critical causes of rising morbidity and mortality from infectious diseases, and this commonly spreads beyond national borders. in venezuela, the recent economic crisis has been accompanied by population movements and major increases in vector-borne diseases, including a fivefold increase in malaria cases [ ] ; venezuela now has over half the malaria cases in the americas [ ] , and in adjacent regions of colombia and brazil, up to % of malaria cases are attributed to recent migration [ ] . covid- has already caused major disruption to economic activity, which could contribute to malaria resurgence. during the ebola fever crisis in west africa, excess malaria deaths outnumbered total deaths from ebola [ ] . deaths from hiv infection and tuberculosis also surged [ ] . contributing factors, including deaths of health care workers, overwhelmed health facilities and fear of contracting disease at health services [ , ] , are relevant to covid- . the ebola epidemic disrupted distribution of itns and resulted in increased malaria transmission, while poor access to malaria treatment led to dramatic increases in deaths in children [ ] . subsequent modelling studies indicated that additional itn distribution and introduction of safe monthly mass drug administration (mda) [ ] with dihydroartemisinin-piperaquine each had the potential to reduce malaria deaths during the epidemic by approximately two thirds [ ] . although international donors pledged support for ebola, significant delays occurred in getting funds on the ground and this contributed to the severity of the epidemic [ ] . likewise, the magnitude and timing of additional support to covid- -affected countries is critical. support for the management of covid- must be combined with support for malaria treatment and prevention programmes; it is likely that this will need to be sustained for years until covid- is brought under control. key interventions and innovative approaches, such as targeted mda programmes and enhanced distribution of itns, will be critical in preventing dramatic increases in malaria deaths [ ] , but their implementation and prioritisation will bring logistic and financial challenges given covid- disruptions and the competing needs of other health issues and services. while covid- is less often severe in children and pregnant women [ , ] , these groups would bear a disproportionate burden of excess malaria mortality arising from covid- -related disruption of health systems and malaria control programmes, particularly in sub-saharan africa. recently, the malaria atlas project modelled these potential impacts in africa for the world health organization's (who) global malaria program [ ] . a range of scenarios were considered, such as ceasing itn distribution campaigns planned for , reductions of routine itn distribution and reduced access to effective antimalarial drugs. in the worst-case scenario, a % decrease in itn distribution coupled with a % decrease in access to artemisinin combination therapies (acts) was predicted to result in a % increase in malaria cases, and doubling of malaria deaths within a year to , [ ] , % of them in children under . these models do not include additional increases in malaria that could result from disruptions in distribution of smc (which currently protects million children in countries) and iptp (which protects pregnant women and their babies in african countries from malaria in pregnancy and low birth weight) [ ] . neither do they include the potential impacts of decreasing irs and other vector control strategies, or the consequences of reassigning malaria personnel to covid- -related activities. the future severity of the impact of covid- in africa is unknown. at the time of writing, africa has % of the world's covid- cases, and % of its deaths [ ] , with around , infections and , deaths reported [ ] . these numbers are likely to be underestimates due to limited testing being undertaken in some regions. these rising numbers are occurring despite many countries taking early, decisive steps to lockdown borders and implement social distancing in crowded environments and other preventive measures. if these measures, or the disease itself, substantially impede normal functions of the health system, this could result in delayed treatment for young children, in whom severe malaria develops rapidly, even with prompt treatment - % of children with cerebral malaria die. if treatment is not available, staggering numbers of young children may lose their lives from malaria. covid- -related lockdowns threaten the livelihoods of the many africans who work in the informal sector, affecting their ability to pay for transport and for health care services when these are not free [ , ] . preventive and therapeutic maternal child health services such as antenatal clinics and childhood vaccination programmes (with > million infants at risk) are at risk, and economic disruptions may exacerbate child undernutrition [ ] . continued provision of chronic medications for tuberculosis and hiv (there are > million people living with hiv and aids in africa) and access to malaria treatment and prevention services (such as itn distribution, iptp and smc) collectively threaten major increases in infectious disease morbidity and mortality. while the greatest burden of malaria is in sub-saharan africa, two billion people in the asia pacific region remain at risk of malaria [ ] . this region has been the global hotspot for emergence of plasmodium falciparum resistant to drugs, including chloroquine, antifolates and mefloquine. the spread of chloroquine and antifolate resistance to africa reversed gains of intense malaria control activities undertaken between and , leading to increasing mortality and morbidity [ ] . in the s, the prospect of untreatable malaria was averted by the introduction of acts, which have now been adopted as first-line treatment by almost all malariaendemic countries [ ] . over the last decade, artemisininresistant p. falciparum, originating from western cambodia, has spread across the greater mekong subregion (gms). the efficacy of a key partner drug, piperaquine, has also declined dramatically [ , ] , causing the efficacy of dihydroartemisinin-piperaquine to fall below % in cambodia, thailand and vietnam [ ] , once again raising concerns of resurgent and untreatable malaria. while new antimalarial agents are urgently required, these are unlikely to be available for several years [ ] . who has a detailed strategy to contain artemisinin resistance, and substantial resources have been made available to eliminate drugresistant malaria before it spreads beyond the gms. from to , across who's south east asian region, there was a % reduction in malaria morbidity and a % reduction in mortality. these gains remain fragile and depend on robust health systems achieving early diagnosis and treatment of symptomatic patients and clearing parasite reservoirs from asymptomatic populations. if efforts to eliminate drug-resistant p. falciparum from the gms falter, resurgence is highly likely to be followed by the spread of resistance into south asia, increasing the risks that resistant malaria will spread to africa. in many places, community-based malaria workers work in close proximity to febrile patients and are at high risk of covid- . despite the risks, adequate personal protective equipment is often lacking, and workers suffer the stigma of being potential sources of viral infection. funds and personnel are being reassigned from malaria and other programmes to enable covid- response efforts. malaria elimination campaigns must reach marginalised groups living in remote and border areas [ ] , but these programmes are at particular risk of being scaled back for logistic or economic reasons associated with covid- , putting communities at risk. together, these complex issues are compromising the provision of health care and surveillance for malaria and threatening elimination efforts. to reduce the impact of covid- disruptions, it is essential that the supply of diagnostics and treatments for malaria are maintained and that there is strong support of itn distribution, irs and other preventive interventions. maintaining drug quality is also critical, with potential proliferation of substandard and falsified medicines and diagnostics when supply chains for established suppliers are disrupted [ ] . furthermore, companies may switch from producing drugs or diagnostics for malaria to covid- , driven by higher profit margins [ ] with clear negative consequences for malaria treatment and control. community education and engagement will be important to reinforce messages regarding malaria prevention, diagnosis and treatment. provision of health services that can provide prompt diagnosis and treatment of malaria is critical, together with professional support of health workers to ensure safe working environments and properly resourced facilities. ideally, these activities would be integrated within the covid- response [ ] . where adequate personal protective equipment or rdts are not available, presumptive malaria treatment may be required (based on symptoms of fever without another obvious cause) [ ] . this brings risks of confounding malaria and covid- and of missing other key diseases like childhood pneumonia. if health systems are not able to maintain malaria control interventions while managing the response to the covid- emergency, they are highly likely to be further impacted by additional malaria cases. a series of case studies prepared for the who in by the university of california san francisco [ ] documented effective strategies used to re-establish malaria control and support progress towards elimination in countries. political will is a critical component, with programmes supported by national governments, although implementation may be also be coordinated at local levels. while some countries are able to self-fund flexible programmes, many rely on donor support, particularly from the global fund for aids, tuberculosis and malaria, to assist with procuring diagnostics, drugs and itns. distribution channels must be strengthened, and capacity building is required to ensure that a skilled and adaptable workforce can deliver interventions. integrated approaches to control vector-borne diseases are essential, with cadres of health care workers benefiting from donor-supported malaria-specific training and other professional development [ ] . with regard to service delivery, strengthening the treatment and prevention of malaria must go hand-in-hand with overall health systems strengthening, as part of integrated models of primary health care. in areas of heterogeneous transmission, robust surveillance and targeted control activities can be highly effective. in countries approaching elimination, such responses will need to include localised vector control responses with focal irs campaigns and potentially other measures such as environmental management [ ] . intensified passive case detection and prompt disease notification can in turn facilitate targeted screening and active case detection programmes. a combination of reactive focal mass drug administration with artemether lumefantrine and reactive irs with primiphosmethyl was recently trialled in a low transmission area of namibia; each intervention halved clinical malaria cases, and the combination reduced malaria by % [ ] . management of malaria in border areas requires special initiatives. in some island nations, all arrivals from endemic countries are recorded and monitored, while countries in the end stages of elimination, such as bhutan, turkey and turkmenistan, have developed systems to track and identify infections in mobile populations including cross border traders, migrant workers and refugees. transnational cooperation around borders is key to tackling malaria in undocumented migrants, seasonal workers and marginalised populations in remote border areas. economic disruption following the covid- pandemic is likely to lead to increases in malaria cases or changing patterns of population movements in these groups. in high transmission areas, continuing malaria surveillance combined with real-time reporting will allow the prompt detection of hotspots of transmission. itn distributions and irs campaigns combined with mda hold great potential for bringing malaria under control. technical advances such as geographical information system (gis)-based case mapping and electronic reporting of cases can provide real-time data on numbers and locations of cases and tailored responses to high burden areas. in the context of covid- , surveillance may be difficult due to multiple factors, including restrictions on movements, concerns about field worker exposure, requirements for additional ppe or resource constraints. therefore, integrated, population-wide approaches that include itn distribution and mda and/or irs for malaria with treatment of neglected tropical diseases, and community health education, may be more practicable to maximise population protection. many successful malaria elimination campaigns have had a strong focus on community awareness and community participation. the latter may extend to active involvement in environmental management and breeding site interventions (as in réunion), and there is great potential to integrate community education and health promotion on malaria with covid- activities. recent years have seen the emergence of civil society organisations such as the civil society for malaria elimination [ ] and campaigns such as #zeromalariastartswithme, which are empowering community and civil society to work for effective, sustainable and inclusive malaria control solutions. close engagement with local community is integral to the implementation of high-impact programmes. private sector involvement is important on several levels. private clinics, pharmacies and local drug sellers have crucial roles in ensuring accurate diagnosis and prompt effective treatment of malaria. in many settings, these services also have important roles in reporting malaria infection [ ] . large enterprises in extractive and agricultural industries may house great numbers of workers and families, sometimes on a seasonal basis. these can be sources of local disease outbreaks or can help to strengthen the surrounding health care system and work jointly on malaria control activities. irrigation schemes require ongoing maintenance and oversight to prevent the development of vector breeding sites. partnerships between successful local companies and local health authorities can help to support specific malaria control activities of mutual interest, to "give back" to their home community. following the first covid- epidemic peak in malariaaffected countries, reinvigoration of malaria control will be needed in many regions (table ) , and steps will need to be taken to prepare for further waves of infection. strengthening surveillance for malaria is crucial together with campaigns to ensure sustainable provision of antimalarials and itns, while strategies are explored to allow community-based malaria programmes to continue. these efforts will inform health system responses. lessons can be learnt from childhood immunisation programmes, which have achieved significant successes in increasing immunisation coverage following disruptions through programme intensifications, outreach activities, community engagement and political support and leadership. transnational and regional initiatives, including operational research, will help to identify strategies for subsequent malaria control activities. as we struggle with covid- , we call on the leaders of countries across the world to recommit to malaria elimination as an achievable and enduring public good. the broader goal of malaria eradication remains highly attractive. an estimated us$ -$ billion investment would unlock over us$ trillion in economic benefits [ ] . if we reduce our focus on malaria, it will resurge, bringing a terrible death toll and even greater economic hardship. if efforts to eliminate drug-resistant p. falciparum malaria from the gms falter, resistant malaria will likely spread to africa, an outcome that could lead to a dramatic increase in childhood deaths [ ] . the world's most affluent countries are already grappling with the challenges of delivering health care and responding to the secondary social and economic costs of the covid- pandemic. in malaria-endemic countries, it is vital that measures are taken both to protect health workers and maintain malaria control activities. the global community cannot afford to cut aid to established programmes that have contributed significantly to the major progress made against malaria and other diseases; we must continue to look outwards, rather than turning inwards at the expense of the world's most vulnerable. successful malaria programmes that are depleted by the covid- epidemic must be rebuilt as quickly as possible to prevent a novel pathogen from giving a new lease of life to an old one. table priorities for combating malaria ensure the safety of health care workers and the populations they serve through adequate provision of personal protective equipment, hand hygiene and ability to practice social and physical distancing. provide resources to enable national malaria control programmes to continue to carry out established programmes. maintain campaigns and systems to procure and distribute itns, ensuring continuing coverage of high-risk populations. secure ongoing production and supply chains of quality-approved malaria diagnostics, treatments and preventives. ensure the timely delivery of these essential supplies to all health facilities. consider safely implementing campaigns of mass drug administration, especially during periods of peak malaria risk. support malaria-endemic countries both in fighting covid- disease and in controlling malaria through an integrated health care programme and community engagement. resume, and maintain funding for, non-covid- research, from 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middle-income countries: a modelling study measurement of trends in childhood malaria mortality in africa: an assessment of progress toward targets based on verbal autopsy world health organization. guidelines for the treatment of malaria. geneva: world health organization spread of artemisinin resistance in plasmodium falciparum malaria evolution and expansion of multidrug-resistant malaria in southeast asia: a genomic epidemiology study determinants of dihydroartemisinin-piperaquine treatment failure in plasmodium falciparum malaria in cambodia, thailand, and vietnam: a prospective clinical, pharmacological, and genetic study the antimalarial pipeline malaria elimination in remote communities requires integration of malaria control activities into general health care: an observational study and interrupted time series analysis in myanmar signatories from c. covid- and risks to the supply and quality of tests, drugs, and vaccines demand for coronavirus tests raises concerns over hiv and malaria the guardian novel coronavirus disease (covid- ) mitigation steps provide a blueprint for malaria control and elimination effectiveness of reactive focal mass drug administration and reactive focal vector control to reduce malaria transmission in the low malaria-endemic setting of namibia: a cluster-randomised controlled, open-label, two-by-two factorial design trial civil society for malaria elimination nonessential research in the new normal: the impact of novel coronavirus disease (covid- ) from aspiration to action: what will it take to end malaria? springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations the acreme investigators who contributed to this article include prof nicholas anstey, menzies school authors' contributions sjr and jgb conceived the article. sjr, jgb, jas and rnp drafted the article with input from tw, jrp and ml. all authors read and approved the final version. acreme investigators provided comments and contributed to discussion. key: cord- -ubw mdzi authors: colebunders, robert; siewe fodjo, joseph nelson; vanham, guido; van den bergh, rafael title: a call for strengthened evidence on targeted, non-pharmaceutical interventions against covid- for the protection of vulnerable individuals in sub-saharan africa date: - - journal: int j infect dis doi: . /j.ijid. . . sha: doc_id: cord_uid: ubw mdzi since many sub-saharan african countries started easing their lockdown measures, covid- cases have been on the rise. as covid- transmission may be difficult to stop in these settings, we propose to complement the existing covid- prevention strategies aiming at reducing overall transmission with more targeted strategies to protect people at risk for severe covid- disease. we suggest investigating the feasibility, acceptability, and efficacy of distributing covid- prevention kits to households with persons at increased risk for severe covid- disease. a curious imbalance exists between the research and development (r&d) efforts dedicated to pharmaceutical versus non-pharmaceutical interventions in outbreak control. the scientific output as well as the associated r&d investments for pharmaceutical interventions are often a factor higher than those for non-pharmaceutical interventions, even though the latter commonly represent a cornerstone of outbreak control. this seems no different in the case of the coronavirus disease- j o u r n a l p r e -p r o o f pandemic: at the time of writing, a pubmed search indicates that the number of published peer-reviewed articles on covid- and treatment/vaccination is approximately double that of covid- and containment/prevention. pharmaceutical interventions such as treatment or vaccination benefit -rightly -from calls for innovation, extensive investigations, rigorous monitoring and evaluation, and the best that evidence-based medicine has to offer. in contrast, while nonpharmaceutical interventions such as physical distancing, lockdowns, contact tracing, facemask promotion, and others have been implemented almost ubiquitously as a measure to stem covid- transmission, they have tended to be implemented as a blanket approach, with limited monitoring and evaluation, and limited generation of evidence to adapt strategies as they go along. here, we call for the generation and strengthening of evidence to guide non-pharmaceutical interventions for covid- , which we illustrate with a practical proposal for assessing the impact of targeted protection of at-risk individuals in settings in sub-saharan africa. the sub-saharan africa region was touched relatively late by covid- , with the first case occurring in nigeria in late february (nigeria centre for disease control ). while implementation of general preventive measures in sub-saharan africa may have slowed down the pandemic, it seems it cannot be stopped: by august th , there were more than one million covid- cases in africa, with more than , deaths (africa cdc ). as covid- diagnostic capacity remains limited in the region, the reported numbers of covid- cases and deaths are likely an underestimation of the true disease burden. moreover, since many african countries are now easing lockdown measures, the number of covid- cases is likely to increase rapidly. a sharp increase has already been observed in south africa, which now accounts for more than % of the continent's total confirmed cases (who ). despite the increasing community spread of covid- in sub-saharan africa, mortality rates reportedly remain low in most countries. this may be related to the relatively younger demographic j o u r n a l p r e -p r o o f in the region: the proportion of persons age and over was estimated to be . % in and is expected to rise to . % in (velkoff and kowal ) , compared to approximately % in e.g. western europe currently. nevertheless, the region is home to more than million elderly (aged and over) (united nations ), who can be considered at elevated risk for severe infection. additionally, the continent has seen a steady increase in non-communicable diseases (ncd) such as diabetes (ojuka and goyaram ) and hypertension (bigna, noubiap et al. ) , which have been linked to covid- severity (rastad, karim et al. , zhou, chi et al. , and additionally carries a high burden of infectious diseases such as hiv and tuberculosis, which have been speculated to represent particular risk factors for severe covid- infection as well (davies ). with covid- gaining ground in sub-saharan africa and the sizeable population of vulnerable individuals at risk of severe covid- , the often already-fragile health systems in many african settings risk being dramatically outpaced by the pandemic. at the onset of the covid- pandemic, lockdowns were swiftly recommended as strategy for covid- prevention. such interventions were typically modelled on the covid- outbreaks in high-income countries and were subsequently replicated in other settings, such as sub-saharan africa (hodgins and saad ) . concerns have however been raised that the pandemic follows very different trajectories in different contexts, and that a "one size fits all" approach for nonpharmaceutical interventions may not be appropriate, as the risk-benefit balance of such interventions may vary across settings (hodgins and saad , van damme, dahake et al. ) . although the early implementation of lockdown measures for covid- control may have contributed to the (initially) low mortality observed in most sub-saharan africa countries, the collateral damage resulting from this strategy is becoming increasingly apparent. lockdown measures have resulted in major economic losses, loss of jobs (yaya, otu et al. ) , increase of poverty (yaya, otu et al. ) , food shortages (mclinden, stover et al. ) , mental health problems (guessoum, lachal et al. , joska, andersen et al. , domestic and other forms of violence (joska, andersen et al. ) , and disruption of health services through drug shortages and an overall negative impact on the quality of non-covid- healthcare. moreover, it is expected that post-lockdown, there will be an increased burden of malaria, tuberculosis (nghochuzie, olwal et al. ) and of neglected tropical diseases resulting from the suspension of control programs. in addition to the fact that lockdown measures are more detrimental to those with the least resources, they are unlikely to be sustainable for the stretch of time required to fully curtail covid- transmission in the long run. we therefore propose to complement the extant containment measures in sub-saharan africa with more targeted protection strategies, aiming at protecting people at risk of severe covid- disease. a targeted strategy may be more efficient to decrease covid- related mortality and to prevent health systems from being overwhelmed by cases in need of resource-demanding intensive support. if implemented together with the general measures to limit the spread of covid- in the population such as physical distancing, universal facemask use and frequent handwashing, such a strategy may provide authorities with the means to selectively relax population-wide measures in favour of these more targeted approaches. protecting persons at risk of severe covid- disease may however be challenging. in high-income countries, where inter-generational mixing within households is less common and where many elderly reside specifically in long-term care facilities, protection was ostensibly straightforwardhowever, few countries failed to safeguard these populations (ecdc public health emergency team, danis et al. , miller . in sub-saharan africa, where elderly family members generally live together with the rest of the family or in close contact with them, this challenge may be further compounded. additionally, one's ncd status may be less well documented in african contexts, j o u r n a l p r e -p r o o f prohibiting self-identification as vulnerable. we propose to develop and test different targeted covid- prevention strategies adapted to the sub-saharan african context. one strategy could be to distribute covid- prevention kits to households with persons at increased risk for severe covid- disease. hygiene kits or prevention kits have been used successfully in other outbreaks, commonly for fecoorally transmitted diseases such as cholera or ebola, as stopgap measure when population-wide prevention tools. we surmise that basic kit items will include fabric facemasks, soap, water storage capacity, alcohol-based hand gel, and health education materials. these materials should ideally cover topics such as respecting at least . m distance from the person at risk for severe covid- disease, always wearing a facemask when interacting with these persons, having these persons wear a facemask when in the company of others, and limiting human interactions with these persons until covid- is eliminated. moreover families could be given access to a phone help-line for more personal advice and support. experience with such kits exists, but needs to be contextualised to covid- (lewnard, ndeffo mbah et al. , yates, allen et al. , ali, benedetti et al. , d'mello-guyett, greenland et al. . different ways to identify families with persons at risk for severe disease should be explored. identification could be integrated within a contact tracing programme, whereby a symptomatic person suspected to have covid- is investigated as to whether there is a person at risk for severe covid- disease in her/his household. this approach may be logistically easier to implement, as it j o u r n a l p r e -p r o o f would allow centralised distribution of kits, but risks coming too late as the person at risk could already be infected. in communities where there is high ongoing covid- transmission, it may be preferable but more costly to offer prevention kits to all those with a household member at risk, irrespective of any suspicion of active covid- in the family, since it is becoming increasingly clear that asymptomatic infected subjects can also spread the infection. such an approach could be aided by demographic records that indicate the ages of residents in the different households and/or medical records from local ncd programmes, and safe and efficient distribution models to realise this approach would need to be tried and tested. another entry point for the distribution of kits could be clinics attended by persons with co-morbidities such as diabetes, hypertension, hiv and tuberculosis. in rural areas, community health workers could play a key role in identifying vulnerable persons, health education and distribution of kits. who should be the focus of the targeted intervention needs to be investigated in each setting taking into account the phase of the covid- epidemic, the commonness and types of vulnerable people, whether they are known in the community, the ability of the local community health workers to recognise vulnerable people, the cultural context, and the financial resources. the easiest way is to consider all persons older than years at risk for severe covid- disease. recently, a frailty scale was shown to be more predictive of covid- disease outcome than age and co-morbidities (hewitt, carter et al. ) . however, it needs to be investigated whether community health workers will be able to categorize persons using such a scale and how much resources (time, finances) this will require. formative research will be necessary to explore the composition of the prevention kit; this will depend on local needs and resources. the distribution of the kits will need to be pilot-tested for feasibility and acceptability. to minimize cost, we recommend large scale local production of fabric face masks. an important component of the intervention would be the counselling of the families by the community health workers. while the exact cost for the production and dissemination of the j o u r n a l p r e -p r o o f prevention kits (including the incentives for the community health workers) may be difficult to evaluate, the proposed targeted approach appears to be more cost-beneficial than all-inclusive strategies such as providing face masks to the entire population and enforcing strict contingency measures, with the associated economic backlash. this model of targeted intervention should be compared with interventions focusing mainly on decreasing overall covid- transmission. there is thus an urgent need to upscale research capacity, in order to appropriately address these questions. currently, a large proportion of the covid- research funding for the prevention covid- transmission is being directed towards the development of a vaccine. it is however unlikely that an effective vaccine will be available very soon in all covid- transmission foci in sub-saharan africa. therefore we recommend that well-designed studies, including randomised trials, be planned and conducted in sub-saharan africa to identify the most cost-efficient ways to decrease the covid- disease burden, while at the same time mitigating collateral damage of prevention measures. hygiene kits may be one such measure worthy of investigation. in collaboration with somalian investigators, we have submitted a research proposal for a cluster randomised trial among camps for internally displaced persons in somalia to compare a targeted covid- prevention programme to reduce severe covid- related disease and mortality with a standard covid- prevention program to reduce overall covid- transmission. for the moment, such a targeted intervention using prevention kits in is only possible in somalia with external funding. however, we hope that if a significant difference in severe disease and mortality is shown, governments, non-governmental organisations and funding agencies will try to scale up and sustain similar interventions in other settings. j o u r n a l p r e -p r o o f distribution of household disinfection kits during the - ebola virus outbreak in monrovia, liberia: the msf experience prevalence and etiologies of pulmonary hypertension in africa: a systematic review and meta-analysis distribution of hygiene kits during a cholera outbreak hiv and risk of covid- death: a population cohort study from the western cape province, south africa high impact of covid- in long-term care facilities, suggestion for monitoring in the eu/eea adolescent psychiatric disorders during the covid- pandemic and lockdown the effect of frailty on survival in patients with covid- (cope): a multicentre, european, observational cohort study will the higher-income country blueprint for covid- work in low-and lower middle-income countries? covid- : increased risk to the mental health and safety of women living with hiv in south africa dynamics and control of ebola virus transmission in montserrado, liberia: a mathematical modelling analysis hiv and food insecurity: a syndemic amid the covid- pandemic protecting and improving the lives of older adults in the covid- era pausing the fight against malaria to combat the covid- pandemic in africa: is the future of malaria bleak? first case of corona virus disease confirmed in nigeria increasing prevalence of type diabetes in sub-saharan africa: not only a case of inadequate physical activity risk and predictors of in-hospital mortality from covid- in patients with diabetes and cardiovascular disease world population prospects the covid- pandemic: diverse contexts; different epidemics-how and why? aging in sub-saharan africa: the changing demography of the region. aging in sub-saharan africa: recommendation for furthering who coronavirus disease (covid- ) dashboard short-term wash interventions in emergency response: a systematic review globalisation in the time of covid- : repositioning africa to meet the immediate and remote challenges obesity and diabetes as high-risk factors for severe coronavirus disease (covid- ) the authors have no conflict of interest no ethical approval is required key: cord- -vzmn zep authors: mougeni, f.; mangaboula, a.; lell, b. title: the potential effect of the african population age structure on covid- mortality date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: vzmn zep currently (mid may ), most active cases of covid- are found in europe and north america while it is still in the initial phases in africa. as covid- mortality occurs mainly in elderly and as africa has a comparably young population, the death rates should be lower than on other continents. we calculated standardised mortality ratios (smr) using age-specific case fatality rates for covid- and the age structure of the population of africa and of other continents. compared to a european or northern american population, the standardised mortality ratio was only . and . , respectively, corresponding to reduction of deaths rates to a quarter. compared to the asian and latin american & caribbean population, the smr was . and . , respectively, corresponding to half the death rate for africa. it is useful to quantify the isolated effect of the african age-structure on potential covid- mortality for illustrative and communication purposes, keeping in mind the importance of public health measures that have been shown to be effective in reducing cases and deaths. the different aspect of age pyramids of a european and an african population are striking and the potential implications for the pandemic are often discussed but rarely quantified. public health measures that have been shown to be effective in reducing cases and deaths. the different aspect of age pyramids of a european and an african population are striking and the potential implications for the pandemic are often discussed but rarely quantified. currently (mid may ), most active cases of covid- are found in europe and north america while it is still in the initial phases in africa. it is unclear what death rates can be expected for this continent. on one hand, african health care systems are weak and therefore many severely ill patients will not be able to receive ventilation and other highend health care in intensive care units. on the other hand, covid- mortality occurs mainly in elderly and as africa has a comparably young population, the proportion of deaths among the population should be lower than on other continents. as age-specific case fatality rates for covid- are available, and the age structure of the population of africa and of other continents is known, it is possible to calculate the comparative effect of age using methods known from indirect age adjustment. age-specific case fatality rates (cfr) published in march were used.( ) these were based on data mainly from china and were calculated using a model correcting for biases such as the preferential detection of severe cases early in the epidemic, and the delay in time from detection to outcome. although there since have been over ten times the number of cases since these calculations were published, they are still likely to be best currently available estimates and no updates on age-specific case fatality rates are . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint available. two sets of cfr were used and compared, the crude cfr and the cfr adjusted for censoring, demography and under-ascertainment. the population estimates of the "united national world population prospects" were used to find the proportion of each population within each age group. ( ) indirect age adjustment was performed by multiplying the case fatality rate with the proportion of the population within an age group. the ratio of the sums, which corresponds to the standardised mortality ratio (smr) in indirect age adjustment show the relative number of deaths in equally sized populations. we use the term standardised mortality ratio, as it closely corresponds to indirect age adjustment procedure. however, we use it to calculate relative number of deaths rather than comparing predicted versus actual deaths. the formula used for the calculation of the smr is as follows: the proportion of population within each of the age groups are designated pai for africa and pci for comparator populations. the age-specific case-fatality rate is designated di. confidence interval were calculated with a bootstrap method in r using the 'rsample' library. ( ) the crude and adjusted cfr and the proportion of population in each age group for different regions are shown in table . . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint covid- mortality is strongly age-dependent and africa has a young population compared to other regions. we show that its isolated effect is quite strong in comparison to europe or northern america, and one can expect only around a fourth of the death rate simply due to the age effect. in comparison, latin american and asian populations have a higher proportion in younger age groups, but the effect is still clear when compared to africa, with a reduction of around %. . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint the number of covid- deaths varies considerably from country to country and from district to district within countries, due to differences in e.g. public health measures, and restrictions taken by the authorities. our results should therefore not be interpreted as predictive. authors of mathematical models predicting covid- mortality in africa acknowledge the strong effect of age in the african population. ( , ) however, it is useful to quantify the isolated effect of the african age-structure on potential covid- mortality for illustrative and communication purposes. the different aspect of age pyramids of a european and an african population are striking and the potential implications for the pandemic are often discussed but rarely quantified. estimates of the severity of coronavirus disease : a model-based analysis world population prospects -population division -united nations bootstrap confidence intervals for ratios of expectations the relatively young and rural population may limit the spread and severity of covid- in africa: a modelling study. medrxiv response strategies for covid- epidemics in african settings: a mathematical modelling study. medrxiv key: cord- -snkdgpym authors: ackermann, klaus; chernikov, alexey; anantharama, nandini; zaman, miethy; raschky, paul a title: object recognition for economic development from daytime satellite imagery date: - - journal: nan doi: nan sha: doc_id: cord_uid: snkdgpym reliable data about the stock of physical capital and infrastructure in developing countries is typically very scarce. this is particular a problem for data at the subnational level where existing data is often outdated, not consistently measured or coverage is incomplete. traditional data collection methods are time and labor-intensive costly, which often prohibits developing countries from collecting this type of data. this paper proposes a novel method to extract infrastructure features from high-resolution satellite images. we collected high-resolution satellite images for million km $times$ km grid cells covering african countries. we contribute to the growing body of literature in this area by training our machine learning algorithm on ground-truth data. we show that our approach strongly improves the predictive accuracy. our methodology can build the foundation to then predict subnational indicators of economic development for areas where this data is either missing or unreliable. the efficient allocation of limited governmental funds from local governments as well as international aid organizations crucially depends on reliable information about the level of socioeconomic indicators. these indicators (e.g. income, education, physical infrastructures, social class etc.) are critical inputs for addressing the socioeconomic issues for researchers and policy-makers alike. although data availability and quality for the developing countries has been improving in recent years, consistently measured and reliable data is still relatively scarce. numerous studies have documented specifically the problems of aggregate economic accounts, in particular to africa, where the data suffers from various conceptual problems, measurement biases, and other errors (e.g. chen and nordhaus ; johnson et al. ; jerven and johnston ) . researchers have probed into alternative options in the absence of reliable official statistics. among this newer generation of alternative economic data research, a burgeoning literature has emerged that uses satellite imagery of nighttime luminosity as a proxy for economic activity. work by sutton and costanza ( ) , elvidge et al. ( ) , chen and nordhaus ( ) , henderson, storeygard, and weil ( ) , sutton, elvidge, and tilottama ( ) and *contributed equally. work in progress. hodler and raschky ( ) documents a strong relationship between nighttime luminosity and gross domestic product (gdp) at the national and subnational levels. this allows researchers to generate information for any levels of regional analysis and also the likelihood of strategic, human manipulation is limited with satellite generated data. however, luminosity data as a proxy for economic activity is not free from concerns. satellite sensors have a lower detection bound and nighttime light emissions below this bound are not captured by the satellites' readings. this leads to bottom-coding problem and this is particularly an issue in low-output and low-density regions (chen and nordhaus ) , which are very often regions and countries (e.g. africa) where official macroeconomic data is missing or unreliable as well. over the past few decades, some parts of the african continent have witnessed large increases in economic development. nevertheless, the majority of regions within african nations still lacks behind. the continent faces further challenges due to localized conflicts (berman et al. ) , rapid urbanization (moyo et al. ) as well as the impacts of the covid- pandemic ), among others. a key pre-requisite in formulating adequate strategies to address these challenges, is reliable socioeconomic data at a spatially, granular level. as of now, even data about basic infrastructure such as roads and buildings is not consistently collected across the african continent. the purpose of this project is to overcome this data problem, by applying machine learning and artificial intelligence tool to a vast amount of unstructured data from daytime satellite imagery. ultimately, this project aims to go beyond the use of nightlight luminosity as a proxy for economic development data and use high resolution, daytime satellite imagery to predict key infrastructure variables at national and subnational levels for less developed countries like in africa. daytime images contain more information about the landscape that is correlated with economic activity, but the images are highly complex and unstructured, making the extraction of meaningful information from them rather difficult. our approach builds upon and further expands the work of (jean et al. a ). the standard approach in the literature is to learn a representation out of satellite images, that allow an interpretation of pixel activation that are important for predicting night time light or other target. this represen-tation is then used to predict an aggregated wealth index. instead, we directly predict infrastructure measures on the ground, albeit knowing that there is a wide spread scarcity of ground truth data. existing solutions for policy makers in developing countries often rely from traditional data gathering processes (i.e. surveys), which are costly and infrequent. given the high costs, this data does not cover an entire country but only a subsample of geographic units. our solution provides a lowcost method to collect valuable insights about economic development for every location in a country. our methodology provides relevant decision makers in developing countries as well as ngos and international organizations with very accurate counts of buildings and the length of roads for an entire country and continent. for example, accurate building counts and density can be used in natural hazard preparedness tools as an indicator for an areas vulnerability against natural disasters. information about roads and settlement helps infrastructure agencies to quickly identify areas that lack market access, a key determinant for economic growth in developing countries. although relatively new, recent studies have begun to use different daytime satellite images to conduct novel economic research (donaldson and storeygard ) . daytime images contain more information than night-time images and are thus a good alternative data source for empirical economics. marx, stoker, and suri ( ) used daytime images to analyse the effects of investment on housing quality in the slums of kibera, kenya. investment was calculated based on the age of a households roof. the results showed that ethnicity plays an important role in determining investment in housing and belonging to the same tribe as that of the local chief has a positive effect on household investment. (engstrom et al. ) used daytime satellite imagery and survey data to estimate the poverty rates of , km subnational areas in sri lanka. using a convolutional neural networks algorithm, they identify object features from raw images that were predictive of poverty estimates. the features examined by the study included built-up areas (buildings), cars, roof types, roads, railroads and different types of agriculture. the results showed that built-up areas, roads and roofing materials had strong effects on poverty rates. a suite of related work has used satellite images to predict population density (e.g. simonyan and zisserman ; doupe et al. ), urban sprawl (burchfield et al. ) , urban markets (baragwanath et al. ) electricity usage (robinson, hohmans, and dilkina ) , as well as income levels (pandey, agarwal, and krishna ) . more broadl, we also relate growing body of literature that uses other passively collected data to measure local economic activity (e.g. abelson, varshney, and sun ; blumenstock, cadamuro, and on ; chen and nordhaus ; henderson, storeygard, and weil ; hodler and raschky ) , methodologically, our paper contributes to the large remote-sensing literature that applies high-dimensional techniques to extract features from satellite imagery (e.g. jean et al. b jean et al. , yeh et al. ; ronneberger, fischer, and brox ) . in general, reliable data at a more granular spatial level is very scarce for the african continent. this poses a particular challenge if the researcher wants to apply machine learning tools that require some form of ground truth data. to overcome this problem, we accessed data from two open-data sources. the first one is open street map, a collaborative project allowing volunteers around the world to contribute georeferenced information in an open-source gis. we utilized http://download.geofabrik.de/ to retrieve a complete snapshot of all geo-located objects africa in . in general, osm coverage for africa is very sparse and often non-existent outside urban areas. our strategy to mitigate this issue, was to build an iterative procedure that would help us select areas ( × km) with good osm coverage. we were then able to convert the geometric osm data into an image mask. our image data was collected in via the google maps api following the exact procedure as in jean et al. ( b) . this data set has be used in various studies (e.g. jean et al. ; sheehan et al. ; uzkent et al. ; oshri et al. ) . again the same pattern as with osm data emerges, the image quality of these freely available african images is not as good as in other places around the world, see figure . in the absence of reliable ground truth data, we selected the architecture based on data that we could make look like as if it would be from our target domain. for buildings, we employ imagery collected by drones in africa from the "open cities ai challenge: segmenting buildings for disaster resilience" , with the corresponding ground truth data provided and re-scaled and blurred the drone imagery. for roads, we build a model to select images with almost complete masks, albeit having missing roads and errors. we benchmark our proposed methodology against the latest publication of poverty predictions in africa using their provided wealth index based on dhs cluster data (yeh et al. ). as it is common in this literature an index is created with a principal component analysis (pca) out of survey respondents. again, due to data limitations, research in this area always only performed a in-sample validation. a true out of sample comparison would require a strict separation between the train and test set, something that is not possible if the pca is calculated over all data points across all countries and therefore inflating the prediction results. as such, (yeh et al. ) also provided an index that is based on within country survey respondents. this enables us to benchmark against both indices. in principle, we follow the outline of the well known u-net architecture for medial images (ronneberger, fischer, and brox ) and modify it for satellite images creating a satellite-u-net (sat-unet). figure provides a general overview of our approach. the network contains layers in total, with major blocks of types: convolution / down-sampling block, intermediate convolution block and the de-convolution/up-sampling block. the convolution block, shown in figure , consists of a batch normalization layer, two convolution layers with the kernel of ( , ) and a dropout layer. the dropout layer is not used in the first down-sampling block. the number of filters in downsampling blocks (encoder part) starts from and doubles every time in the following block reaching in the intermediate convolution block, and then decreases in the upsampling blocks (decoder) with the coefficient . . the core difference from (ronneberger, fischer, and brox ) is that instead of up-sampling layers, we are using transposed convolution layers, which performs the reverse convolution operation (dumoulin and visin ) . in addition, we added drop-out layers after each convolution and de-convolution block. in a x image the number of pixel belong to a house or a road, class one, vs the number of pixels of zero-class (non classified space) is up to times higher, creating a severe class imbalance. we address this issue with a hybrid loss function. first, we use the loss of the sum of binary cross entropy ( ) and the sorensen-dice coefficient: combined. as metric we used the intersection over a union (the jaccard index) data pre-processing to make image input size is x , compatible with a factor of to conform the shape reduction coefficients of the network, we added a padding of . on average across our images, the rgb colours maximum was around - out of the maximum of . color channels re-scaling has been implemented to intensify colors before feeding the image into the network. for augmentation we used rotation by , and degrees. the main difficulty in choosing the exact architecture for the road network was the lack of a sufficiently large amount of, error-free, ground truth data. therefore, we used the following iterative strategy: . create an initial mask with osm data and train on them. . filter out masks, where the model predicts significantly more objects than the osm mask has. . retrain the model on the filtered data-set. due to the large possible set of images to train from, around million, we first selected a subset based on osm data. as our main focus is to get an indicator of the economic development, the best case would be to find areas of economic activity. osm has a classification for commercial buildings, which is rarely used ( / mil). we selected areas in the same adm regions of those images based on descending order of square meters occupied by buildings on a uniform grid, until we had selected a base set of masks. next, we trained our sat-unet model for roads on all masks as labels we had created from osm. the judge: for filtering purposes the sat-u-net based model judge has been created with an additional input for the osm mask. using transfer learning the weights of the pretrained sat-unet model have been transferred to the bottom layers of the judge for the mask creation from the original image, and top layers perform the calculations of the index of validity, using the calculated mask and the osm mask as inputs. combining everything in a single gpu model allows to achieve more than x increase in performance comparing to cpu-based technique. . the index of validity is where i,j-pixel values of predicted mask and the osm respectively. the resulting filtering model decreased the dataset approximately by %, filtering out instances like those presenting in figure . furthermore, as our network predictions had very low values caused by model uncertainty, we re-trained several sat-unet model on the selected images with different random seeds. this ensemble learning significantly increased our predictive performance, as shown in figure . the top three are predictions on the test set, while the last image is the combination of all three with the pixels reduced to the skeleton for counting. for building recognition, we used open cities ai challenge data set as ground truth data set. this data set contains imagery of several african cities in a ultra high resolution of up to cm per pixel. each city is split by square areas and for each image there is a geojson file with vector data describing contours of the buildings. out of these geometric data, we created a contour layer and a centroid layer, which represents the center of every building structure. we down scaled the images to the scale of . pixel/meter to match google this high-quality ground-truth data further allowed us to experiment with different architectures. we replaced the encoder part in the sat-unet model with the inception v (xia, xu, and nan ) and the resnet (he et al. ) . in every instance we reset all the weights to random before training but we did not make use of any transfer learning. table presents the evaluation results on our test set. we also compared how well the network performs in counting the correct house based on the jaccard index, visually shown in figure . the performance of the incep -unet and resnet -unet was quite similar. for the final model selection we trained both architectures on the previous selected masks out of osm, and compared their performance in terms of their predictability on a test set. table demonstrates the effect of different thresholds on the performance.the threshold is in color intensity units (range - ), tp is true positive, when the predicted centroid is located inside the building contour of the mask, pred-to-mask coefficient is the ratio between predicted number of houses and the ground truth number, and false positives (fp): f p ← · t otalp red − t p t otalp red ( ) figure : the filter removes incomplete osm masks. from left to right: original image, osm mask, prediction of the trained model on the stage . figure : africa, building model stage, contour-in-contour evaluation. buildings that were predicted correctly are in blue, not predicted in orange. orange areas of random shapes inside building blocks are usually courtyard areas and not considered as a wrong prediction. a threshold of has the closest prediction-to-mask score, acceptable tp and fp rates. therefore, we picked this threshold for further modeling. the final model resnet -unet has layers. to avoid the vanishing gradient problem with the depth of hundreds of layers resnet uses skip connections, it adds input information of the convolution block to its output. in addition skip connections give the model the ability to learn the identity function which guarantee the similar performance of the lower and higher layers (he et al. ) . we compare our prediction results of buildings and roads to the latest benchmark study in the field of poverty prediction based on dhs data (yeh et al. ) . the dhs data is collected in various waves across countries and years. for the comparison use of the most recent wave available for a country and use the aggregated wealth index data. two indices are provided, the first wealthpooled is the pca calculation across all years, while the second index wealth, is calculated (yeh et al. ) did not provide any out of sample estimates, therefore we fully replicated their method by getting all their images they used for their location and trained their combined cnn model of multi-spectrum and night lights images to determine economic well-being in africa, with wealth as label for the last of their training folds (d). the performance results are almost identical in terms of rsquared. in their study they also found a high correlation of the measures to other type's of aggregation, such the sum total of all assets. using their wealthpool predictions as predictor for wealth, the r-squared is around . vs . for wealthpool. the dhs location data from (yeh et al. ) has , unique cluster location in the last wave of each respective country. we use a km radius corresponding to the possible displacement of survey measurements, as selection criteria to select our images. for every square km we predict the number of buildings, the number of roads as well as calculate the night time light (elvidge et al. ) by grid cell. we then aggregate the roughly . million images into features, by building the sum, averag and quantiles by cluster across all input variables. in total, this leaves us with , locations. we perform loocv cross validation by country, as figure : ensembling: the first three are predicted masks based on different random seeds, the last one is the resulting mask. we are interested in predicting the marginal unit if we would use the model to get data for one extra country. we also iterate over standard machine learning algorithms without any hyper parameter tuning, by only using the default settings. table and table present the results for out of sample and out of country predictions, respectively. as expected, using a normalized outcome measures across all samples, inflates the performance. in comparison to the previous literature, our predictions show an increased predictive performance, both in and out of sample. this paper introduces a novel and scalable method to predict road and housing infrastructure from daytime satellite imagery. compared to existing approaches, we achieve higher predictive performance by training a u-net style architecture using ground-truth data from a subset of images. using satellite images from african countries we show how our method can be used to generate very granular information about the stock of housing and road infrastructure for regions in the world, where reliable information about the local level of economic development is hardly available. consistently measured and comparable indicators about local economic development are crucial inputs for governments in developing countries as well as international organizations in their decision where to allocate scarce public funds and development aid. the predictions generated by our method can be directly included in existing decision support systems. for example, international organization such as the red cross are using similar data at the local level to evaluate an area's vulnerability against natural hazards. our data can be considered as more granular complements to existing measures of the local stock of physical infrastructure. numerous charitable organizations already rely on satellite imagery to identify districts of african countries that are among the least developed (e.g. abelson, varshney, and sun ) . our approach provides a low-cost and scalable alternative to identify areas that are in need. in addition, the open street map mapping community would benefit from our findings as well. the road prediction model could be used worldwide to help completing the road network or help narrowing down possible errors in the data. finally, our approach is an important methodological contribution to the large group of scholars from varying disciplines working in the area of poverty measurement. the majority of the existing research focuses on predicting poverty based on aggregate household wealth. this paper shows that predicting poverty measures can also be viewed as a simple high dimensional feature representation problem. our study is a proof-of-concept exercise to show that combining daytime satellite imagery, open source ground truth data and machine learning tools can translate unstructured image data into valuable insights about local economic development at an unprecedented scale. table : predictive performance of satellite predictions, r-squared based on loocv on out of country predictions by country using wealthpooled targeting direct cash transfers to the extremely poor detecting urban markets with satellite imagery: an application to india this mine is mine! how minerals fuel conflicts in africa predicting poverty and wealth from mobile phone metadata causes of sprawl: a portrait from space. the quarterly using luminosity data as a proxy for economic statistics the view from above: applications of satellite data in economics equitable development through deep learning: the case of subnational population density estimation a guide to convolution arithmetic for deep learning viirs night-time lights a global poverty map derived from satellite data evaluating the relationship between spatial and spectral features derived from high spatial resolution satellite data and urban poverty in colombo, sri lanka deep residual learning for image recognition measuring economic growth from outer space regional favoritism combining satellite imagery and machine learning to predict poverty combining satellite imagery and machine learning to predict poverty tile vec -unsupervised representation learning for spatially distributed data statistical tragedy in africa? evaluating the database for african economic development is newer better? penn world table revisions and their impact on growth estimates the economics of slums in the developing world african cities disrupting the urban future infrastructure quality assessment in africa using satellite imagery and deep learning multitask deep learning for predicting poverty from satellite images a deep learning approach for population estimation from satellite imagery u-net: convolutional networks for biomedical image segmentation predicting economic development using geolocated wikipedia articles very deep convolutional networks for large-scale image recognition estimation of gross domestic product at sub-national scales using nighttime satellite imagery global estimates of market and non-market values derived from nighttime satellite imagery, land cover, and ecosystem service valuation the nextgencities africa programme learning to interpret satellite images using wikipedia. ijcai inception-v for flower classification using publicly available satellite imagery and deep learning to understand economic well-being in africa key: cord- - q authors: malherbe, petrus; smit, pierre; sharma, kartik; mccaul, michael title: guidance we can trust? the status and quality of prehospital clinical guidance in sub-saharan africa: a scoping review date: - - journal: afr j emerg med doi: . /j.afjem. . . sha: doc_id: cord_uid: q introduction: prehospital care is integral in addressing sub-saharan africa's (ssa) high injury and illness burden. consequently, robust, high-quality prehospital guidance documents are needed to inform care. these guidance documents include, but are not limited to, clinical practice guidelines (cpgs), protocols and algorithms that are contextually appropriate for ssa. however, ssa prehospital guidance mostly originates from the ‘global north,’ with limited guidance for africa by africans. to strengthen prehospital clinical practice in ssa, we described and appraised all prehospital ssa guidance documents informing clinical decision making. methods: we conducted a scoping review of prehospital-relevant guidance documents, including cpgs, algorithms, protocols and position statements originating from ssa. we performed a comprehensive literature search in various databases (pubmed and scopus), guideline clearing houses (scottish intercollegiate guidelines network, trip, and guidelines international network), journals, various forms of grey literature and contacted experts. guidance document screening and data extraction was done independently, in duplicate and reviewed by a third author. guidance quality was then determined using the agree ii tool and data were analysed using simple descriptive statistics. results: we included guidance documents from countries across ssa after screening potential documents. the majority of guidance documents lacked an evidence foundation, made recommendations based on expert input, and were predominantly end-user presentations such as algorithms or protocols. overall, reporting quality was poor, specifically for critical domains such as rigour of development; however, clarity of presentation was generally strong. guidance topics were focused around resuscitation and common diseases (both communicable and non-communicable) with major gaps identified across a variety of topics; such as mental health for example. conclusion: the majority of prehospital clinical guidance from ssa provides clinicians with excellent ready to use end-user material. conversely, most of the guidance documents lack an appropriate evidence foundation and fail to transparently report the guidance development process, highlighting the need to strengthen and build guideline development capacity to promote the transition from eminence-based to evidence-based guidance for prehospital care in ssa. guideline developers, professional societies and publishers need to be aware of international and local guidance document development and reporting standards in order to produce guidance we can trust. as a region of mostly low-and middle-income countries (lmics), sub-saharan africa (ssa) experiences a high volume of injury and illness requiring a robust system of emergency medical services [ ] . emergency medical services, and the prehospital care delivered, provide access to timely interventions and transportation of those in need. this plays an important role in reducing mortality and morbidity in the region. emergency medical services in ssa are growing as more regions across ssa establish basic services by building and expanding formal prehospital service delivery infrastructure. this is often supported by organisations such as the african federation of emergency medicine (afem). additionally, various countries such as rwanda and zambia are establishing training programmes for emergency medicine specialists [ ] . emergency medicine as a whole can be found in both the in-hospital and pre-hospital environments, often with overlap of intended treatment goals and outcomes. however, irrespective of a country's level of prehospital services (whether it be first aid responders in a volunteer capacity, or formal emergency medical services staffed by health care professionals), prehospital care should be guided by the best available evidence. as the best available evidence could potentially be aimed at the early management goals of the emergency centre in-hospital, these goals and recommendations can sometimes be extrapolated to the prehospital environment. local contexts and, ideally, patients' preferences should also be considered. these form the components of evidence-based healthcare (ebh), where guidance and recommendations for healthcare decisions or interventions are based on the best-available evidence [ ] . in the past two decades, despite africa's high disease burden and health system challenges, progress has been made in accepting, adopting and implementing ebh principles [ ] . an example of this is the clear recommendations about stopping bolus fluids in shocked children produced by the paediatric association of kenya -recommendations that the world health organisation (who) is still to adopt [ ] . indeed, high-quality guidelines play an essential role in bridging the gap between current best available evidence and clinical practice. concerns have been raised regarding the quality and availability of emergency care or prehospital clinical practice guidelines (cpgs) [ , ] . high-quality guidelines are especially important in lmics as policymakers and healthcare providers can ill afford to make healthcare decisions based on outdated evidence, considering that it may lead to wasteful or less-efficient expenditure of finite resources. resource limitations are quite well-known in lmics and across ssa. a question that is raised, however, is whether implementing ebh increases cost-effectiveness in emergency medicine, or whether the opposite is true. this association is not yet clearly understood. several tools exist to aid in the critical appraisal of various study types. these tools are designed to standardise and improve the efficiency of the appraisal process and can either be qualitative or quantitative in nature. an example of such a tool is the appraisal of guidelines for research and evaluation ii (agree ii) tool which serves to assess the quality and variability of cpgs across various domains, including methodological rigour [ , ] . in a landscape analysis of global emergency care clinical practice guidelines (cpgs), less than % of cpgs originated from lmics [ ] . furthermore, the authors concluded that 'although some highquality cpgs exist relevant to emergency care, none directly address the needs of prehospital care in lmics, especially in africa' (p ). this paints a concerning picture of the current status of african prehospital guidance and evidence informing downstream practice. however, the landscape analysis by mccaul et al. [ ] excluded any other form of guidance documents such as algorithms, patient care pathways or clinical care protocols, potentially missing prehospital guidance documents that do not conform to the strict definition of a cpg, as set by the institute of medicine [ ] . guideline quality in prehospital care was also raised as a concern, a sentiment prevalent across various disciplines, from primary health care to allied health [ , , ] . furthermore, a similar landscape analysis conducted of only south african guidance documents highlighted the lack of emergency care guidance available [ ] . guidance document quality seems to be a concern for lmics, possibly due to their lack of formal guidance document organisations, technical capacity, or collaborations to develop evidencebased guidance documents [ , ] . this potential lack of available upto-date high-quality prehospital guidance is not just a major concern for clinicians, but for guideline developers as well. in prehospital care, the most common form of cpg development is de novo, whereby guidance documents are newly produced [ ] . however, an alternative method is to adapt already published, high-quality evidence-informed cpgs to a particular setting [ , ] . these methods, often termed guideline adaptation, have been successfully showcased in various healthcare settings [ ] , including the african prehospital setting [ ] [ ] [ ] . in general, they are considered more efficient than de novo development. however, guidance developers who use adaptation methods are dependent on up-to-date high-quality cpgs to adapt to their local settings. without a clear picture of the availability and quality of local guidance documents, guidance developers may need to resort to de novo development. failing that, they would need to spend more time and resources contextualising guidance from high-income countries, where the recommendations might not be transferable. very little is known about the scope and quality of prehospital guidance in ssa. therefore, this study has aimed to describe and appraise all prehospital-relevant guidance documents in sub-saharan africa. this paper describes and appraises current sub-saharan african guidance documents to inform regional guidance developers and clinical decision making. a scoping review was chosen as the method of choice, as it allows the authors to map the spectrum of prehospital guidance documents available in ssa. it is also useful in describing scope, locale, methods, target audience and guidance quality (using agree ii). in contrast to systematic reviews, which synthesise available evidence to answer a focused research question, scoping reviews attempt to map available literature, often utilising a broad study question to identify gaps in knowledge [ ] . the study was reported according to the prisma extension for scoping reviews checklist [ ] . the study protocol was approved by the stellenbosch university health research ethics committee (u / / ). we included any prehospital-relevant guidance documents (considering the broadest definition, e.g. protocols, patient care pathways, standard operating procedures) published either in english or french since , and published in countries within ssa as stipulated by the united nations (un) [ ] , listed in appendix . we excluded healthcare infrastructure, administrative guidance and medical textbooks. the date of publication restriction was introduced to ensure that we captured the most up to-date guidance documents, likely used in current practice. guidance documents related to covid- were not considered. we conducted a comprehensive and broad search on july (updated june ) of databases (pubmed and scopus), guideline clearing houses (scottish intercollegiate guidelines network, trip, and guidelines international network), and google scholar. the search strategy was created with the assistance of an information technologist. the search strategy for pubmed can be found in appendix . . we searched grey literature, such as hand-searching journals not indexed in pubmed/scopus, prehospital society websites, local ministry of health websites for each country and hand-searched conference proceedings (also updated june ). additionally, we contacted experts, policymakers and clinicians for unpublished guidance documents (see appendix . for list of all databases, journals and websites searched). we identified various experts working in ssa prehospital settings by way of societies and published works. they were contacted to seek counselling on guidance potentially missed during formal and grey literature searches. experts merely suggested articles of interest to the authors that they may have potentially missed, and in no way influenced the development or results of this study. we merged the results of the searches using reference management software and removed duplicate records. two authors (pm and ps) independently, and in duplicate, examined titles and abstracts to remove obviously irrelevant reports and retrieved full text of potential relevant documents. full text was then screened for eligibility and prehospital relevance in duplicate and independently (pm and ps). in both title/abstract and full-text screening, any disagreements were resolved by consensus with a senior author (mm). we created a flow diagram to show the process of inclusion and exclusion of documents; potentially eligible studies that were excluded are noted in fig. . three authors (pm, ps and ks) independently extracted data from documents using a data extraction form, developed a priori by the authors. data were collected for the following information: country, date of publication, guidance type, producer, target audience, subpopulation, health service area, health discipline, method of development, and evidence grading. guidance quality was assessed with agree ii. the maximum score for each agree domain, of which there are six, is %. landmark reference standards include the agree ii tool [ ] , or the right extension (reporting items for practice guidelines in healthcare) for alternative guideline development methods [ ] . at face value, both tools assess similar components of the guideline development process, which are considered indicators for quality. agree ii was chosen as the preferred method of appraisal as two authors had better familiarity with it. in addition, it had a better quantitative representation of the appraisal scores for each included guidance document. it is worth noting that no reporting or quality checklist exists for end-user documents such as protocols or algorithms, even though these should be based on clear parent cpgs or systematic reviews. in light of this, agree ii was used as a benchmark for all included study types, to improve comparability in appraisal impressions. four authors (pm, ps, ks and mm) independently, and in duplicate, assessed the quality of included guidance documents using agree ii. any major discrepancies in scores were resolved by discussion amongst all four authors. data were extracted from the data collection forms to a microsoft excel spreadsheet (microsoft corporation) and imported into stata (statacorp) for analysis. spatial mapping was presented graphically to summarise the number of guidelines by country. continuous data (agree ii scores) were assessed for normality, determined using the shapro-wilk test and reported appropriately using medians and interquartile ranges. descriptive statistics was the primary method of analysis. the electronic search identified documents in total after removal of duplicates. documents were identified through databases, documents identified through guideline clearing houses and additional documents through grey literature sources. potential full text articles remained after removing duplicates and obvious exclusions. guidance documents were included in the scoping review, following the exclusion of articles with reasons provided. in the updated searches, no new documents were found that could be included, and fig. was updated to reflect the latest information. only two updates of previously included documents were found, but no changes were made to the original methods or process of development. thus, their original agree ii scores remained unaffected. the majority of included guidance documents were identified via grey literature, hand-searching journals and government websites. the search flow diagram can be seen in fig. . ssa countries contributed prehospital clinical guidance documents included in the scoping review. approximately % (n = ) of guidance documents were published from onwards. south africa produced the largest portion of guidance documents at % (n = ). kenya produced % (n = ) and tanzania produced % (n = ). see fig. for the guidance documents distribution across ssa. the largest proportion of guidance documents were algorithms ( %, n = ), % (n = ) were cpgs, clinical protocols represented % (n = ) and review documents represented % (n = ) of the total. only documents were position statements ( %). more than half ( %, n = ) of the guidance documents were produced by professional societies (e.g. afem or the south african trauma society), while national departments of health and clinicians/ academics produced % (n = ) and % (n = ), respectively. international organisations contributed only one guidance document ( %). guidance documents in ssa targeted a wide array of subpopulations. subpopulations consisted of pregnancy and childbirth with % (n = ), neonatal with % (n = ), mixed paediatric with % (n = ), and adults with % (n = ). furthermore, 'mixed populations' (applied to multiple, but not all subpopulations) comprised % (n = ) of the total, 'all populations' (applied to all subpopulations) represented % (n = ) and 'unspecified' subpopulations represented % (n = ). while no explicit themes emerged within the subpopulations, topics were largely dictated by the document type. disease-based guidance (malaria, heart failure, hiv, etc.) existed mostly in the form of stgs while symptom-based guidance (choking, tachycardia, stab wounds, etc.) existed mostly in the form of algorithms. only guidance documents addressed mental health issues ( % (n = )). while all guidance documents included were pertinent to prehospital care, only % (n = ) were written primarily for prehospital providers. the majority of guidance documents ( % (n = )) in prehospital care in ssa were written for mixed primary target audiences (prehospital and in-hospital). ranked by their agree ii domain scores, quality varied across producers, as presented in table . on average, domain and (scope and purpose, clarity of presentation) scored the highest, with % and %, respectively. domains and (stakeholder involvement and editorial independence) scored % and %, respectively. the most important domain when considering scientific rigour, domain (rigour of development), scored on average % across all guidance documents. when stratified by producers, clarity of presentation scored high, whereas rigour of development scores showed a greater degree of variance. for example, professional societies scored poorly ( %) compared to national departments of health-( %) and academic-produced guidance documents ( %). refer to fig. for a representation of agree ii scores by country. as shown in fig. , there is significant variance amongst agree ii scores when stratified by country of origin. south africa scored the lowest overall, even though articles such as the afem cpg (produced in south africa) had the highest attributed average score ( . %). this is due to the higher number of total studies produced, most of which were protocols and algorithms that generally had lower agree ii scores on average. several countries scored very high as they only had a single (or relatively few) articles published, generally of a higher quality. no guidance documents included in our study were developed de novo, while only one guideline used clearly specified guideline adaptation methods. additionally, % (n = ) of guidance documents were based on a combination of unstructured literature reviews and expert opinion, while the majority ( %, n = ) did not specify any methods of development at all. cpgs' overall agree ii scores (and especially domain : rigour of development) were significantly higher than other types of guidance documents. however, only two cpgs specified an evidence grading system for recommendations. additionally, overall guideline quality differed significantly between guideline producers. only % (n = ) of guidance documents were recent (published from and onwards) and quality was rated as poor (agree ii score of < or < %). our results reveal that the majority of guidance documents for prehospital providers in ssa, lack appropriate methodological reporting and transparency. this sheds doubt on the scientific validity and rigour of recommendations from these guidance documents. more than % (n = ) of included guidance documents did not specify any methods of development. this is a concerning observation as the potential impact of life-saving care not being based on the best available evidence is unknown. considering the overall poor rigour of development, especially from professional societies, there is a clear need for building awareness of guidance development principles. in addition, promoting the use of quality reporting tools such as agree ii or the right statements [ , ] , might improve the quality of guidance documents produced. guidance development literacy, as a component of evidence-based decision making, is an essential competency for healthcare providers, decision makers and healthcare managers. without this competency, it is likely prehospital guidance documents will continue to be developed through eminence-based as opposed to evidence-based methods [ ] for the foreseeable future. the majority of guidance documents available for prehospital providers in ssa are algorithms or protocols. these end-user-centric guidance documents usually provided little to no detail regarding their development process, nor what the underlying evidence-base was (i.e. the rigour of development). however, many are excellent examples of user-friendly and pragmatic clinical decision-making tools. noteworthy examples include the emergency medicine clinical guidance for the western cape (south africa), the emergency medicine kenya foundation emergency care algorithms [ ] , and the resuscitation council of southern africa algorithms [ ] . agree, appraisal of guideline research and evaluation; sp, scope and purpose; si, stakeholder involvement; cp, clarity of presentation; rd, rigour of development; apl, applicability; ei, editorial independence; overall judgement; sd, standard deviation. given the significant resource constraints in lmics, and especially ssa, it is understandable that some guideline developers do not have the means to develop guidance documents with excellent transparency on development. however, considering this, every possible effort to improve reporting on methods within these guidelines should be encouraged. transparent reporting of guidance document development is essential, as without this users or policymakers have no means of judging whether recommendations provided are trustworthy or valid. our results revealed unacceptably poor scores for editorial independence (such as reporting funding and conflicts of interest), stakeholder involvement and most importantly, rigour of development. all these elements are essential components of producing guidance documents we can trust. overarchingly, professional societies produced the least transparent, and therefore least trustworthy guidance documents. this reflects similar results seen at a global and regional level [ ] . developers of cpgs and end-user documents can learn from organisations such as the belgian red cross's centre for evidence-based practice (cebap). they developed basic and advanced first aid manuals for first responders in africa in an end-user document format. these manuals provided clear evidence for their de novo guidance development methods, without compromising on the usability of the clinical decision tool [ , ] . our results indicate such transparency in reporting, and acknowledgment of the original evidence base or source guideline, is lacking in the vast majority of end-user documents produced in ssa. a wide array of topics were represented within guidance documents, though major gaps were identified. infectious diseases (especially ebola, malaria and other endemic infectious diseases) were fairly well described amongst a number of included articles. similarly, toxicology, trauma, cardiology, cpr, metabolic diseases and endocrinological diseases were well represented. primary health care was especially well described in guidance documents self-labelled as "standard treatment guidelines" (stg). these stg documents covered a wide array of responses and recommendations to healthcare burdens commonly associated with the region or country for which they were developed. the protocols and algorithms included were predominantly focused on streamlining the management of certain patient presentations in the emergency setting. they tended to focus on a single disease process or management strategy, whereas standard treatment guidelines resembled cpgs in method of development, and user-presentation. while % of guidance documents were written for 'all populations', existing mostly in the form of national stgs, a disconcertingly low proportion of guidance documents were written with the primary focus on 'pregnancy and childbirth' or 'neonatal' populations. furthermore, only two of the guidance documents identified mentioned mental health-or psychiatry-related events, both from kenya. this is of concern due to the fact that % of countries in africa have no formal mental health policies [ ] . in addition, across the continent the number of disability-adjusted life years attributed to mental health, nearly equalled the number of disability-adjusted life years attributed to infectious diseases [ ] . increased awareness is required in order to improve implementation of health services for mental health; prehospital guidance documents are no exception. mental health emergencies often require prehospital providers to serve as the first point of contact. it is therefore crucial that prehospital guidance pertaining to mental health in ssa be created. de novo guidance development is considered time-consuming, expensive, and often out of reach for lmics, especially in africa. of the cpgs produced in ssa, none used de novo methods. the majority used literature reviews, expert input or informal guideline adaptation methods, as opposed to formal adaptation methods such as adolopment [ ] , adapt [ ] , or others [ , [ ] [ ] [ ] . considering the international standards in guidance development and the continuous movement toward evidence-based decision-making [ ] , we argue that if any guidance in prehospital care is to be developed, the methods of development should be transparently and clearly reported [ ] . this would be recommended irrespective of whether guidance takes the form of formal cpgs, protocols, or algorithms. where methods and transparency are unclear, there is potential for various forms of bias to creep into the guidance development process. this undermines trust in guidance, and ultimately affects patient outcomes. as a consequence, when evidence is open to misinterpretation [ ] , recommendations are open to conflicts of interest [ ] and undue influence, especially, in situations where decisions are being made by various stakeholders on how recommendations should be implemented [ , ] . considering how important locally appropriate guidance is to clinicians in day to day practice, it is essential that african guidance developers are aware of international standards when developing and reporting clinical guidance. in light of this, african journals and societies are increasingly requiring authors to adhere to quality standards set out by the international community, in order to publish guidance documents [ ] . of the documents we included, the largest portion of included documents came from grey literature sources. overall, we found it quite challenging to find documents on ssa in general, and especially in grey literature sources. we presume it will likely be even more challenging for clinicians seeking best practice advice. finding trustworthy guidance documents should not be a difficult process. considering this, key priorities that require attention include the need to improve guidance document access, as well as increasing guidance document quality and transparency, by considering central coordination of guidance documents in ssa. the african federation for emergency medicine is well placed to spearhead such an initiative in ssa, where a prehospital or emergency medicine guidance repository can be hosted. this repository would require adherence to international guidance standards (such as agree ii) and improve access to guidance documents in ssa. such an initiative will require a consolidated regional effort, of which the first step is adherence to international guidance document development and reporting standards by all stakeholders involved. considering limitations, we made concerted efforts to comprehensively search for all available prehospital guidance in ssa. however, it is likely we have missed potentially important documents which were not available electronically, or open to the public. the majority of prehospital clinical guidance from ssa provides clinicians with excellent end-user material. conversely, most material lacks an appropriate evidence foundation and fails to transparently report the guideline or guidance development process. this highlights the need to strengthen and build guidance development capacity, to promote the transition from eminence-based to evidence-based guidance for prehospital care in ssa. guidance document developers, professional societies and publishers need to be aware of international guideline development and reporting standards in order to produce guidance we can trust. to improve access to clinical guidance and enduser documents in ssa, and improve the development thereof, a guidance coordinating centre should be considered. supplementary data to this article can be found online at https:// doi.org/ . /j.afjem. . . . pm presented on the findings of this study at the emergency medicine society of south africa conference in november . authors contributed as follow to the conception or design of the work; the acquisition, analysis, or interpretation of data for the work; and drafting the work or revising it critically for important intellectual content: pm contributed %; ps and mm %; and ks %. all geneva: world health organization emergency medicine residency training in africa: overview of curriculum evidence based medicine: what it is and what it isn't series: clinical epidemiology in south africa. paper : evidence-based health care and policy in africa: past, present, and future immediate fluid management of children with severe febrile illness and signs of impaired circulation in low-income settings: a contextualised systematic review clinical practice guidelines within the southern african development community: a descriptive study of the quality of guideline development and concordance with best evidence for five priority diseases. health research policy and systems global emergency care clinical practice guidelines: a landscape analysis scoping studies: advancing the methodology agree ii: advancing guideline development, reporting and evaluation in health care clinical practice guidelines we can trust the national academies press series: clinical epidemiology in south africa. paper : quality and reporting standards of south african primary care clinical practice guidelines south african clinical practice guidelines: a landscape analysis use of evidence for clinical practice guideline development building capacity for development and implementation of clinical practice guidelines adaptation of clinical guidelines: literature review and proposition for a framework and procedure to adopt, to adapt, or to contextualise? the big question in clinical practice guideline development clinical practice guideline adaptation methods in resource-constrained settings: four case studies from south africa prehospital providers' perspectives for clinical practice guideline implementation and dissemination: strengthening guideline uptake in south africa developing prehospital clinical practice guidelines for resource limited settings: why re-invent the wheel? south african pre-hospital guidelines: report on progress and way forward systematic review or scoping review? guidance for authors when choosing between a systematic or scoping review approach prisma extension for scoping reviews (prisma-scr): checklist and explanation about sub-saharan africa; c [accessed extending the right statement for reporting adapted practice guidelines in healthcare: the right-ad@pt checklist protocol a reporting tool for practice guidelines in health care: the right statement consortium of universities for global health (cugh) competency sub-committee. cugh global health education competencies tool kit nairobi: emergency medicine kenya foundation randburg: resuscitation council of southern africa evidence-based african first aid guidelines and training materials development of evidence-based first aid guidelines for laypeople in flanders mental health in africa grade evidence to decision (etd) frameworks for adoption, adaptation, and de novo development of trustworthy recommendations: grade-adolopment manual for guideline adaptation adapting a large database of point of care summarized guidelines: a process description contextualizing western guidelines for stroke and low back pain to a developing country (philippines): an innovative approach to putting evidence into practice efficiently a user-friendly clinical practice guideline summary for managing low back pain in south africa strengthening prehospital clinical practice guideline implementation in south africa: a qualitative case study the interpretation of systematic reviews with meta-analyses: an objective or subjective process reassessment of clinical practice guidelines: go gently into that good night submissions guidelines for authors the authors would like to acknowledge anel schoonees (centre for evidence-based health care, stellenbosch university) for her support in developing the search strategies, including support from stellenbosch university faculty of medicine and health sciences library. furthermore, the authors would like to thank the regional guideline experts who provided support for finding grey literature. key: cord- -opvs ejd authors: masiira, ben; antara, simon n; kazoora, herbert b; namusisi, olivia; gombe, notion t; magazani, alain n; nguku, patrick m; kazambu, ditu; gitta, sheba n; kihembo, christine; sawadogo, bernard; bogale, tatek a; ohuabunwo, chima; nsubuga, peter; tshimanga, mufuta title: building a new platform to support public health emergency response in africa: the afenet corps of disease detectives, – date: - - journal: bmj glob health doi: . /bmjgh- - sha: doc_id: cord_uid: opvs ejd public health emergency (phe) response in sub-saharan africa is constrained by inadequate skilled public health workforce and underfunding. since , the african field epidemiology network (afenet) has been supporting field epidemiology capacity development and innovative strategies are required to use this workforce. in , afenet launched a continental rapid response team: the afenet corps of disease detectives (acodd). acodd comprises field epidemiology graduates and residents and was established to support phe response. since , afenet has deployed the acodd to support response to several phes. the main challenges faced during acodd deployments were financing of operations, acodd safety and security, resistance to interventions and distrust of the responders by some communities. our experience during these deployments showed that it was feasible to mobilise and deploy acodd within hours. however, the sustainability of deployments will depend on establishing strong linkages with the employers of acodd members. phes are effectively controlled when there is a fast deployment and strong linkages between the stakeholders. there are ongoing efforts to strengthen phe preparedness and response in sub-saharan africa. acodd members are a competent workforce that can effectively augment phe response. acodd teams mentored front-line health workers and community health workers who are critical in phe response. public health emergence response in sub-saharan africa is constrained by inadequacies in a skilled workforce and underfunding. acodd can be utilised to overcome the challenges of accessing a skilled public health workforce. to improve health security in sub-saharan africa, more financing of phe response is needed. the risk that infectious agents will continue to kill humans in the st century is highest in africa. according to the who, africa experiences more than disease outbreaks and other health emergencies annually. from the beginning of , african countries have been facing one of the greatest challenges: the covid- pandemic. the covid- pandemic started in china in december and rapidly spread across the globe. such public health emergencies (phes) expose the fragility of emergency response systems in africa. for example, the ebola virus disease (evd) epidemic in west africa claimed > lives and cost billions of us dollars in socioeconomic losses. for an effective phe response, the global health security agenda recommends countries to have at least one field epidemiologist (trained at the advanced or intermediate levels) per population. other authors have suggested a coverage three to five field epidemiologists per million population. however, data at the african field epidemiology network (afenet) show that the sub-saharan region summary box ► innovative strategies can be applied to leverage the inadequate public health workforce to address public health challenges including emergencies. ► acodd was established to support ministries of health to overcome the challenges of rapidly mobilising and deploying adequate and skilled public health workforce. ► public health emergency response in sub-saharan africa is still constrained by underfunding. ► it is feasible to mobilise and deploy acodd member within hours to support ministries of health to respond to emergencies. ► lack of effective community engagement can result into violence against the rapid responders. ► psychosocial support can be a game changer in addressing difficult situations faced by rapid responders such as distrust. has only % of the required number of field epidemiologists. afenet was established in to support field epidemiology workforce development in sub-saharan africa. during the ministerial round acodd's organisational structure is summarised in figure . there are three levels of acodd management; the afenet secretariat, regional and country levels. at the afenet secretariat, the head of afenet (who reports to the afenet board of directors) provides overall strategic leadership, the head of programmes provides overall technical leadership and the acodd focal person (fp) coordinates operations across the network. at regional level, acodd operations are led by the afenet regional technical coordinator (rtc). at country level, the acodd operations are led by the country fp who is the fetp resident advisor. details of the acodd management team responsibilities are summarised in table . acodd has supported response to several emergencies including disease outbreaks, mass gathering event-based surveillance, polio surveillance and natural disasters such as cyclone idai in the southern africa region. outlined below are the key disease outbreaks where acodd members were deployed. the ninth ebola virus disease outbreak in the democratic republic of the congo, may-july soon after acodd was launched, afenet received a request from the drc ministry of health to support the response to the evd outbreak in Équateur province. this evd outbreak had been declared on may . between may and july , afenet, in collaboration with the us centres for disease control and prevention (cdc), deployed a team of acodd members to support the national rrt contributing a total of person-days of deployment. acodd members investigated alerts of which were confirmed with evd, identified contacts of which were followed up, mentored front-line health workers and conducted a total of community sensitisation sessions. other acodd members were involved in screening of passengers at five priority points of entry (poes) and points of control (pocs) to identify suspected cases of evd surveillance. the acodd conducted data analysis and compiled and presented daily updates that helped inform the outbreak response strategies. this outbreak was quickly contained and the minister of health announced its end on july . the outbreak had a total of evd cases of which were confirmed, were probable, died (case fatality ratio: %). of the cases, occurred in bikoro health zone, occurred in iboko health zone and occurred in wangata health zone. as part of the mohcc rrt, acodd teams investigated cholera cases, identified cases through active cholera case search and participated in outbreak data analysis. acodd members with clinical background supported case management teams at health facilities and assessed compliance to treatment protocols by case management teams. a team of acodd participated in conducting risk communication, community a total of acodd members were deployed in rotations for days contributing a total of person-days. once in the field, acodd members had a meeting with the field incident commander and the district health leadership to get an understanding of the outbreak and to finalise the terms of reference. acodd teams investigated alerts none of which was confirmed with evd and listed contacts of which ( %) were followed up and tested negative after completing the follow-up period. the acodd reviewed medical records at health facilities to identify suspected evd cases and out of these records nine suspected cases were identified and all tested negative for evd. in addition, the acodd screened travellers at poes, participated in community-based and event-based surveillance, community sensitisation, psychosocial support and data analysis. the response team initially found surveillance and contact tracing difficult due to community mistrust and false information. for example, there was information that suspected patients with ebola admitted to the etu and their contacts are killed by a 'lethal injection' in order to prevent further transmission of evd. these rumours made one of the high-risk contacts to go into hiding. when the high-risk contact was traced in one of the remote locations, he rejected ebola vaccination despite several visits by the teams. however, after days of counselling by the psychosocial team, the high-risk contact eventually accepted evd vaccination. because of the community mistrust and misinformation, the rrt adopted a community-led surveillance and contact tracing strategy. under this approach, community health workers known as village health teams (vhts) were trained. the vhts conducted contact tracing under the close supervision from the contact tracing teams. during field activities, acodd teams mentored health workers and vhts. this evd outbreak involved three confirmed cases, all of whom died (case fatality ratio, cfr: %) and all had an epidemiological link to a confirmed case who died in drc. many of the acodd teams faced community resistance and constant security challenges, amidst the increase in the spread of the outbreak, which had a negative impact on the response. on july , who declared this outbreak as a public health emergency of international concern. afenet received grants from the us cdc and the world bank to enhance response efforts. these funds were used to implement surveillance training to enhance ebola response and readiness (steer) for the front-line health workers, community health workers and acodd deployment. steer focused on building the capacity in evd surveillance, ipc and risk communication. a total of health workers and community health workers in evd affected health areas were trained. by december , the rrts were starting to register success with new evd cases reported during the week of november to december compared with cases during the week of - september . by march , there was no new confirmed evd case since february , and a total of evd cases had been reported of which were confirmed cases, probable cases and cases had died (case fatality ratio of %). as of march , there were signs that the epidemic had been contained with the last cases all reported from a small geographical area within beni health zone. acodd response to the covid- pandemic as soon as the chinese government declared the covid- outbreak, countries on the african continent activated their emergency preparedness and response mechanisms. by january , who declared the pandemic a phe of global emergency of international concern. in early february , the acodd fps started working with afenet to mobilise acodd members to be on stand-by to support ministries of health and technical bmj global health agencies/networks such as the who, us cdc, global outbreak alert and response network and africa cdc. acodd teams across afenet member countries supported various activities including ( ) coordination and planning, ( ) development of the national response plans, ( ) adapting the who covid- case definition to country contexts, ( ) investigation of suspected cases, ( ) poe screening, ( ) contact tracing, ( ) training of rrts and screeners at poes, ( ) risk communication and ( ) supporting the development of protocols and standard operating procedures (sops). afenet supported africa cdc to recruit acodd epidemiologists to strengthen covid- capabilities among african countries. these volunteers supported coordination and planning, building capacities for surveillance, laboratory, ipc and case management, policy development and provided technical support to public health emergency operation centres to develop incident action plans and sops. acodd teams faced four key challenges during deployment and these are highlighted below. the bulk of afenet operations are supported by the us cdc and the united states agency for international development. between august and march , afenet received requests for acodd support from member countries of which ( %) were funded. acodd deployments were largely supported using the funds generated from indirect project costs while some deployments received direct support from the us cdc. although afenet uses a cost-effective model for acodd deployment, available funding has been insufficient to meet the growing demand for acodd support. a more sustainable strategy for funding of phe response should be led by the african governments. however, investigations have shown that the majority of countries in africa allocate below % of their total budget to the health sector. availability of acodd for deployment because majority of acodd are not employed by afenet, their availability to support phe response depends on their release by employers. during deployments, some of the acodd members could only serve a short duration in the field which presented a challenge of recruiting and orientation of new volunteers. although afenet has been able to mobilise adequate numbers of acodd members during emergencies, mobilisation is anticipated to be difficult in large-scale phes which require a bigger workforce. the safety of rrts is one of the critical elements for an effective response. overall, acodd and other responders operated in a safe and secure environment in most of the deployments. however, the response to the evd outbreak in drc was substantially hampered by insecurity. acodd teams in insecure areas always operated in constant fear of being attacked by the armed groups. on april , a doctor who was deployed by who was brutally murdered at the butembo university hospital. on the night of november , armed rebel forces attacked a camp at biakato mines and killed four health workers. the deteriorating security situation led to the evacuation of several rrt members, including acodd members, to goma city on december . resistance to interventions and distrust of the responders although the acodd participated in community sensitisation during the tenth evd outbreak in drc and the sixth evd outbreak in uganda, community resistance and distrust remained a key challenge. in both outbreaks, lack of trust was primarily driven by false information, misperceptions and ignorance about control strategies. whereas in uganda the distrust was easily controlled through community engagement, the responders in drc faced a more complex situation. a mob attacked one of the etus in drc resulting into patients and caregivers fleeing and one of the caregivers was killed. activities such as identification of new cases and safe, dignified burials were dangerous to implement in some areas because of violence from the residents. community resistance and distrust was also documented during the response to the west africa evd outbreak. lessons learned although fetps started over two decades ago in sub-saharan africa, the region is still faced with a scarcity of field epidemiologists. during acodd launch, the participants were engaged in discussions about the anticipated challenges related to acodd deployment. the key anticipated challenges elicited from participants included difficulty in mobilising adequate numbers of acodd members, lack of interest in responding to outbreaks due to highly infectious pathogens such as evd, and delays or non-release of the acodd members by their employers. our experience showed that its feasible to mobilise and deploy adequate numbers of acodd members within hours after receiving requests from ministries of health. many acodd members felt motivated to participate in rapid response within their countries and beyond. the acodd members employed within government ministries were easily released compared with those in the private health sector. all acodd deployments were approved and effected by the ministries of health. before field deployment, predeployment briefings were conducted with a special focus on discussing the terms of reference. acodd members were integrated into the national rrt and their daily operations were under the direct supervision of ministries of health. although the deployments were largely successful, sustainability will rely on establishing strong linkages with organisations that employ the acodd members. afenet is continuously sensitising and engaging the organisations that employ the acodd members to ensure that they release them during emergencies. the final key lesson learnt was that phes were effectively controlled when the responders were rapidly deployed and when there was strong collaboration between the key stakeholders. an analysis of the evd outbreak in west africa showed that a well-coordinated faster response would have halted the propagation of the outbreak. opportunities considerable efforts are ongoing in the sub-saharan africa region to strengthen preparedness and response to phes. from its founding in afenet, in collaboration with the us cdc, universities and other technical partners, has been contributing to health systems strengthening. acodd members are a skilled workforce that can be utilised to support emergency response. the afenet cost-effective strategy for acodd deployment is centred on in-country field epidemiologists; with recruitment from other countries only done once the in-country acodd have been exhausted. the recruitment strategy provides an added advantage in that the acodd members are well versed with the country context and can easily communicate to the target populations as opposed to recruiting external acodd members. during deployments, acodd teams interacted, worked with and learnt from other experienced responders. furthermore, in areas where the acodd members were deployed, they were involved in mentoring the front-line health workers and community health workers. effective public health preparedness and response in sub-saharan africa is constrained by inadequate skilled human resources and underfunding. the acodd platform is afenet's innovative strategy to deploy the existing field epidemiology workforce to support phe response. experience from these deployments has shown that the acodd can be rapidly mobilised and deployed to the field. the contributions of the acodd since its establishment is a clear demonstration of leveraging the existing workforce to solve the complex public health challenges that threaten health security in sub-saharan africa. the deficiencies in financing the health sector in sub-saharan africa emphasise the need for african governments to devote more financial support and resources for phe response. african field epidemiology network, kampala, uganda global public health solutions, atlanta, georgia, usa african field epidemiology network, harare, zimbabwe twitter notion t gombe @gombent contributors bm participated in conception of the manuscript, supervision of acodd deployments, synthesis of field experiences and writing all the drafts of the manuscript. sa participated in conception of the study, supervision of deployments, writing and reviewing of the manuscript and approval of the manuscript. hbk participated in conception and supported manuscript writing at all stages. on wrote the field experiences from the uganda acodd deployment and participated in reviewing and writing of the manuscript at all stages. ntg wrote the field experiences from zimbabwe, supervised acodd deployment and participated in writing of the manuscript at all stages. anm wrote the field experiences from drc acodd deployments and participated in writing of the manuscript at all stages. pmn participated in writing and reviewing of the manuscript at all stages. dk wrote supervised acodd deployment in drc and participated in writing of the manuscript at all stages. sng, ck, bs and atb participated in writing and reviewing of the manuscript at all stages. co participated in conception of the study, supervision deployments and reviewing of the manuscript. pn participated in study conception, writing and reviewing of the manuscript at all stages. mt participated in conception of the study, supervision deployments, writing and reviewing of the manuscript and gave final approval of the manuscript. funding the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. competing interests none declared. patient consent for publication not required. provenance and peer review not commissioned; externally peer reviewed. open access this is an open access article distributed in accordance with the creative commons attribution non commercial (cc by-nc . ) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. see: http:// creativecommons. org/ licenses/ by-nc/ . /. ben masiira http:// orcid. org/ - - - x emerging infectious diseases in africa in the st century world health organization. who health emergencies programme in the african region: annual report available: http:// apps. who. int/ ebola/ current-situation/ ebola-situation-report the economic and social burden of the ebola outbreak in west africa global health security agenda: ghsa workforce development action package (ghsa action package detect- ) strengthening public health surveillance and response using the health systems strengthening agenda in developing countries afenet. ministerial resolutions on african field epidemiology network (afenet) democratic republic of congo: ebola virus disease -external situation report ebola virus disease democratic republic of congo: external situation report / democratic republic of the congo. external situation report promoting equitable health care financing in the african context: current challenges and future prospects world health organization. state of health financing in the african region responder killed in attack on the butembo hospital armed groups kill ebola health workers in eastern dr congo msf suspends congo ebola effort after deadly clinic attacks an epidemic of suspicion -ebola and violence in the drc social and cultural factors behind community resistance during an ebola outbreak in a village of the guinean forest region the health impact of the - ebola outbreak field epidemiology training programmes in africa -where are the graduates? post-ebola reforms: ample analysis, inadequate action key: cord- - o n authors: amewu, sena; asante, seth; pauw, karl; thurlow, james title: the economic costs of covid- in sub-saharan africa: insights from a simulation exercise for ghana date: - - journal: eur j dev res doi: . /s - - - sha: doc_id: cord_uid: o n globally, countries have resorted to social distancing, travel restrictions and economic lockdowns to reduce transmission of covid- . the socioeconomic costs of these blunt measures are expected to be high, especially in sub-saharan africa where many live hand-to-mouth and lack social safety nets. social accounting matrix multiplier model results show that ghana’s urban lockdown, although in force for only three weeks in april , has likely caused gdp to fall by . % during that period, while an additional . million ghanaians temporarily became poor. compared to the government’s revised gdp growth rate of . % for , the model predicts a contraction of . to . % for , depending on the speed of the recovery. the us$ million budgeted for ghana’s coronavirus alleviation program will close only a small part of the estimated us$ . billion gdp gap between the fast recovery scenario and government’s revised gdp trajectory. as the covid- pandemic spreads across sub-saharan africa, the region's political leadership faces an almost impossible policy dilemma. in the absence of a vaccine and amidst concerns about precarious health systems, severe shortages of intensive care beds and ventilators, and the underlying poor health of the population (the economist ; bishop ), it is imperative for countries to slow down the viral spread to ensure that health systems can cope with rising patient numbers and that mortality rates are kept as low as possible. however, the instruments available to policymakers to reduce the spread of the virus are blunt, and basically entail measures that restrict the movement and physical interaction of people, or in extreme cases, force certain sectors to shut down. apart from skepticism about how well such measures would work in densely populated informal neighborhoods, they can be extremely costly from a socioeconomic standpoint. with many people in sub-saharan africa living hand-to-mouth, a sudden income shock can have devastating consequences for people's food security and health. for this reason, government stimulus programs and social support packages should ideally complement social distancing and economic lockdown measures. these support measures can be costly, especially when considering that governments themselves can anticipate deep cuts to tax revenues as economies grind to a halt. borrowing may be an option to some governments, but with more than half the countries in sub-saharan africa already exceeding the international monetary fund's (imf) % debt-to-gdp threshold (onyekwena and ekeruche ) , the ability of countries to provide such support is severely hamstrung. the policy dilemma is perhaps best articulated by hausmann ( , p. ) , who remarks "the flatter you want the contagion curve to be, the more you will need to lock down your country-and the more fiscal space you will require to mitigate the deeper recession that will result". while government has some control over these tough domestic decisions, it can do little to prevent external shocks associated with the covid- pandemic. with around two-thirds of the global economy under some form of lockdown or quarantine (deloitte ) , global supply chains are disrupted, demand is weakened, and commodity markets are in turmoil. countries in sub-saharan africa may be particularly vulnerable given low levels of economic diversification, their relative openness, and an overreliance on a limited range of export commodities for foreign exchange earnings and government revenue. with disruptions to international travel, tourism revenues in sub-saharan africa are expected to decline by % (unwto ), while foreign direct investment could drop to % (unctad ). households in sub-saharan africa may be directly impacted by the predicted % decline in private remittance receipts this year (world bank ). in parallel to concerns about health and socioeconomic costs, a concern globally is the impact that covid- may have on food supply chains, whether as a result of global trade restrictions, disruptions to domestic agricultural input-and output supply systems linked to restrictions on economic activity, or rising food prices as consumers stock up or resort to panic-buying (gakpo ; glauber et al. ). there have also been concerns about diet quality as income losses or relative price shocks push consumption away from vegetables, fruit, and animal-source foods towards less perishable, calorie-dense staples (headey and ruel ) . for this reason, global actors have been closely monitoring food trade flows and commodity prices, while governments are encouraged to ensure that restrictive measures do not adversely affect agri-food systems. the objective in this paper is to estimate the economic costs of covid- policies and external shocks in a developing country context, with a focus on agri-food system impacts. ghana is selected as a case study. ghana recorded its first two cases of covid- infection on march . the government responded by gradually introducing social distancing measures, travel restrictions, border closures, and eventually a two-week "partial" lockdown in the country's largest metropolitan areas of accra and kumasi. social distancing measures have been enforced nationwide and include bans on conferences, workshops, and sporting and religious events, as well as the closure of bars and nightclubs. all educational institutions were also closed. the partial lockdown measures in urban areas directed all residents to remain home except for essential business, prohibited non-essential inter-city travel and transport, and only essential manufacturing and services operations were permitted to continue (the presidency ). at the time the lockdown was announced, ghana's ministry of finance revised its gdp growth estimate for downwards from . to . % (mof ), although the minister warned that growth could fall further if lockdown measures were extended. the lockdown was initially extended for a third week but was officially lifted on april. many social distancing measures remain in place nationwide, although a gradual easing of restrictions commenced in june. ghana's borders also remain closed at the time of writing. we estimate the economic costs of covid- using a social accounting matrix (sam) multiplier model for ghana. sam multiplier models are ideally suited to measuring short-term direct and indirect impacts of unanticipated, rapid-onset demand-or supply-side economic shocks such as those caused by the covid- pandemic. through capturing the complex linkages between various economic sectors as well as household employment and consumption patterns, sam multiplier models can be used to simulate the direct and indirect effects of economic shocks on domestic production, value-added (gdp), employment, and household income and poverty. since the preliminary estimate by the ministry of finance ( a, ) focused only on gdp, and given the extension of the lockdown, our results add value to our understanding of the wide-ranging effects of covid- in ghana. the remainder of the paper is structured as follows. "ghana's covid- outbreak" section provides information about ghana's covid- outbreak; "simulating the economic impacts of covid- " section introduces the sam multiplier model and the simulation approach; "model results and discussion" section presents the model results; and "conclusions" section concludes. technical information about the model is provided in "annex". ghana began preparing for the spread of covid- in january with the establishment of a national technical coordinating committee tasked to review the country's resilience and preparedness to manage an outbreak (moh ). by early march, president nana akuffo-addo committed gh¢ million (us$ million) towards a coronavirus national preparedness and response plan, which sought to strengthen the capacity of health facilities, laboratories, and points of entry to detect and control viral spread and to create public awareness. although a world health organization report (who ) described ghana's readiness to deal with the covid- pandemic as "adequate", global statistics on covid- hospitalization rates are sobering (cdc covid- response team ): with an estimated intensive care unit beds and ventilators available at private and public facilities in ghana (arhinful ; ghanaweb ) , the country can ill afford active infections rates to spiral out of control. figure provides a timeline of policy measures against cumulative confirmed covid- cases. ghana recorded its first two cases of covid- infection on march . soon thereafter, president akufo-addo announced nationwide travel and social restrictions effective from march (the presidency ). these measures included a ban on entering the country for foreign nationals travelling from countries with more than covid- cases; a ban on public gatherings, such as conferences, workshops, political rallies, and (some) religious activities (funeral attendance was to be limited to people); and closure of universities, senior high schools, and basic schools. businesses, retail outlets, restaurants, hotels, transport operators, and local markets could continue to operate but had to adhere to social distancing and enhanced hygiene measures. ghana only started relaxing some of these social distancing measures at the beginning of june . although by march ghana had only recorded cases (gss ), ghana's international borders were closed, initially for a two-week period, but several further extension have been announced since then and borders remain closed at the time of writing. on march, a partial lockdown was announced in ghana's largest metropolitan areas, namely accra (including neighboring tema and kasoa) and kumasi (the presidency ). the lockdown was extended for one week until april. all residents were directed to remain home, only leaving for essential purchases (food, medicine, water) or essential services (banking transactions, use of public toilet facilities, or medical care). the lockdown further prohibited inter-city movement of vehicles and aircrafts for private and commercial purposes, except for those providing essential services and moving cargo. within city limits, passenger vehicles and taxis were instructed to reduce their numbers of passengers, resulting in an estimated to % reduction in capacity (ayamga ) . workers in certain categories were exempt from the stay-at-home directives. these included: (i) members of the executive, legislature and the judiciary; (ii) production, distribution and marketing of food, beverages, pharmaceuticals, medicine, paper and plastic packages; (iii) environmental and sanitation activities; (iv) staff of volta aluminum company, an aluminum smelter; (v) road and railway construction workers; (vi) mining workers; (vii) fisherfolk; (viii) members of the security agencies assigned lawful duties; (ix) staff of electricity, water, telecommunications, e-commerce and digital service providers; (x) staff of fuel stations; (xi) health workers; (xii) media; and (xiii) persons in the food value chain (the presidency ). the lockdown was formally lifted after three weeks primarily due to concerns about its devastating socioeconomic impacts (the presidency ). as noted, social distancing measures were gradually lifted from the beginning of june, but the country's borders remain closed. ghana's ministry of finance conducted an early rapid assessment of the likely budgetary impacts of covid- . on the revenue side, government expects to lose gh¢ . billion in oil revenue due to the two-thirds decline in crude oil prices. non-oil revenues are expected to fall by gh¢ . billion due to the slowdown in economic growth (mof ) (fig. ) . government also faces significant unforeseen costs associated with the covid- response programs, including the national preparedness and response program (gh¢ million), and the coronavirus alleviation program (gh¢ . billion). the latter makes provision for various stimulus and support measures, including gh¢ million in the form of soft loans to small and medium enterprises, to which private sector banks will contribute a further gh¢ million; gh¢ million to supplement healthcare workers' incomes; and gh¢ million for household water supply subsidies, food packages, and public grain procurement from smallholders (mof ). in order to finance these costs and to cover losses in revenue, government obtained an imf loan of us$ billion (gh¢ . billion) (imf b). interest on the loan of around gh¢ . billion will become payable this year (fig. ) . in summary, revenue losses and unforeseen program costs related to covid- are estimated at around gh¢ . billion, which raises the fiscal deficit from . % of projected gdp to . % of revised gdp. the new imf loan, which comes at a time when ghana's debt stock is already gh¢ billion or % of gdp (mof ), will cover about half of the covid- costs and revenue losses. government further proposes to defer interest spending on existing loans from the bank of ghana and to temporarily reduce or suspend payments to sovereign investment funds, such as the stabilization fund and the heritage fund. it also plans to reduce planned capital and current expenditure by gh¢ . billion this year (mof ). in recognition of the socioeconomic importance of the agricultural sector and the vulnerabilities of the agri-food system, the minister of agriculture released a press statement on march explicitly exempting the agri-food system from domestic covid- related restrictions (mofa ). this meant (i) all farmers could continue their farming activities; (ii) input suppliers and retailers could continue distribution and sales of farm inputs; (iii) the transportation of farm inputs within lockdown zones and in the rest of the country could continue uninterrupted; (iv) food processing companies could continue production and distribution of their products; and (v) subsidized fertilizer and seed subsidies would continue to be provided through the planting for food and jobs program. despite this pronouncement, the ministry of food and agriculture ( ) acknowledged reports of unavailability of food in some markets, instances of government security personnel restricting movements of traders of farm inputs and food despite their exempt status, increases in food prices in some markets, and increased food losses in producing areas and at markets due to supply chain challenges and low patronage of markets. there are several reports of local authorities temporarily closing markets or restricting trade because patrons or traders failed to adhere to social distancing protocols (ifpri ). supply chain challenges have also been reported. for example: the cocoa sector anticipates significant losses due to a lack of access to credit and the global market contraction (ayitey ); cashew farmers experienced a % price drop in the first quarter of as foreign investors were unable to travel to ghana to procure nuts (b&ft online ); and with the planting season approaching, some analysts are concerned about commercial farmers plant less crop area than normal in anticipation of a decline in consumer demand (goldstreet business ). globally, international commerce is expected to contract between and % in as a result of covid- (walker ) . if these disruptions spill over into food supply chains, it may have important implications for ghana. first, it may affect food availability directly. as elsewhere in africa, ghana's food needs are increasingly met through imports, with rapid increases recently being seen in processed food imports especially (aragie et al. ). this places ghana in a vulnerable position should it be required to shift to domestic supply chains on short notice. second, it could affect the availability of farm inputs. should the global fertilizer supply chain be affected by covid- , the timing could be disastrous for ghana since, on average, % of annual fertilizer needs are imported in the first two quarters of the year in time for the planting season (africa fertilizer ). moreover, almost % of that fertilizer is procured through the planting for food and jobs program, which subsidizes % of the retail price (mofa ; africa fertilizer ). given the precarious financial position of government due to covid- , fertilizer suppliers may be cautious about delivering inputs on credit (gyasi ) , especially given the experience in when government cash flow problems led to fertilizer suppliers not being paid. none of these agri-food system impacts are intended consequences of domestic policies. as such, we do not directly simulate supply-side restrictions on the agrifood system in the modeling exercise. however, we do measure and decompose the indirect effects of covid- within the broader agri-food system. generally, the discussion here demonstrates the importance of continually monitoring the situation on farms and in retail and wholesale markets as the agricultural sector may be impact indirectly despite policies implemented to protect the sector from the adverse effects of covid- . social accounting matrix (sam) multiplier models are ideally suited to measuring short-term direct and indirect impacts of unanticipated, rapid-onset demand-or supply-side economic shocks, such as those caused by the covid- pandemic (breisinger et al. ; round ) . at the heart of the multiplier model is a sam, an economywide database that captures resource flows associated with all economic transactions that take place in the economy, usually over the course of a financial year. as such the sam represents the structure of the economy at a point in time, showing the relationships between actors (i.e., productive activities, households, government, and foreign institutions) in terms of how they interact and transact via commodity and factor markets (round ) . the sam multiplier model in this study is calibrated with a sam for ghana, which is an update of a sam developed jointly by ghana statistical services, the institute of social, statistical and economic research, and ifpri (gss, isser & ifpri ). whereas the macro-framework for the sam draws on such data sources as national accounts (gss ) and global trade and balance of payments statistics (unctad ; imf a) for , the sector-and microlevel structure is constructed from a variety of sources from different years, including crop production estimates for (fao ), household survey data from to (gss ), and a supply-and-use table from (gss ). the latter remains the latest available data on input-output relationships in ghana. while the updated sam has a base-year, multiplier results are applied to national accounts, household income, and population data for to permit an assessment of the likely impacts of covid- in , relative to values. this ensures comparability with current economic growth forecasts and other economic aggregates. the sam multiplier model provides a mechanism for estimating the effects of an external shock, typically an exogenous change in final demand for goods and services (e c ), on total supply (z c ) of commodities (c , … , c n ) . through capturing input-output, employment relationships, and the functional distribution of income, the model also generates results on domestic production, employment, and changes in household incomes. final demand (e c ) typically includes government consumption demand, investments, and exports. household consumption demand may be treated as endogenous or exogenous in sam multiplier models, depending on preferences. for the analysis here, we assume household demand is exogenous, i.e., a change in income will not result in a secondary round of consumption demand shocks. this is consistent with the short time horizon of our simulations, accounts for the ability of (some) households to maintain consumption levels in the shortrun by drawing down savings, and ultimately avoids over-estimation of the multipliers, which is a common concern in fixed-price multiplier models with endogenous household consumption (haggblade and hazell ) . a commonly used variant of the standard sam multiplier model is a "semiinput-output" or "supply constrained" sam multiplier model. under a semiinput-output specification, supply in one or more sectors (e.g., z k , k ∈ c , … , c n ) is treated as exogenous, with the associated final demand component ( e k ) becoming endogenous. theoretically, such a model "closure" can be used to simulate a supply-side shock, e.g., a reduction in supply due to a mine or factory closing, but implicitly then demand would be satisfied through a reduction in net-exports (or, essentially, imports). however, this is not realistic in a covid- context where global supply chains are also constrained. since many of the restrictive covid- measures are simultaneously supply-and demand-side measures, i.e., supply is constrained through restrictions imposed on productive activities, while demand is reduced through limitations on what consumers may purchase, we apply changes to the exogenous demand component (i.e., Δe c ) as a proxy for shocks to either supply and/or demand. at least one potential limitation to our simulation approach relates to the fact that supply constraints cannot be imposed on sectors through forward linkages. for example, if a sector a supplies intermediate inputs to a downstream sector b, and sector a's output is reduced through a negative shock to its exogenous demand component, sector b's output will not automatically be constrained. even if the exogenous shock exceeds the initial value of exogenous demand, the model will treat negative exogenous demand (say, exports) as a positive shock to supply (i.e., via imports), thus ensuring that sector b's output is not constrained by a lack of intermediate input supply. a way around this problem is to directly shock demand for sector b's output. note, however, that the model does capture the effect of backward linkages. thus, a decline in downstream sector b's output resulting from a shock to its exogenous demand component will lead to a decline in demand for upstream sector a's output. a final point worth noting is that the short-run analysis period assumes that technical input-output relationships, output choices of producers, and consumption patterns of households do not change in response to the simulated shock. sam multiplier models therefore assume prices are fixed, which is generally considered a drawback of these models. since flexible prices and behavioral responses are incorporated into general equilibrium models, such models are often thought to be superior to fixed-price models. however, considering that the covid- shocks constitute an almost catastrophic lockdown of demand and economic activities, rather than a shock to equilibrium where adjustments work through price-endogenous market mechanisms, the sam multiplier framework is appropriate in this context, at least in the short run. for more on the equations making up sam multiplier models, please refer to "annex". we distinguish between domestic policy-induced impact channels and external impact channels. as explained previously, all shocks are imposed via changes to the exogenous demand component (Δe c ) of a sector. as such, our impact channels, listed in table , are defined along individual sectors or clusters of sectors that are affected by the various covid- related policy measures or external shocks. the model defines sectors that can be mapped to impact channels, although not necessarily uniquely so-for example, the construction sector is impacted directly via the partial lockdown of the construction sector as well as via reductions in government revenue and foreign direct investments which impacts physical infrastructure spending. underlying the sectors are more detailed supply-and-use data for economic sectors in ghana. therefore, in defining sector-level shocks across the sectors we consider implications of policy prescriptions at a more detailed sector-level and estimate a weighted average shock that is applied to the relevant sectors in the model. as shown in table , potential impact channels are identified, although policy directives in ghana means four of those, namely farming, mining, water and energy, and health, are fully exempt from lockdown measures. these sectors may, of course, be impact indirectly due to shocks entering the model via the remaining impact channels. our assessment of policy measures allows us to classify shocks to impact channels as being: (i) "extreme" in the case of manufacturing, hospitality, and foreign remittances (i.e., supply shock imposed are in excess of % during the lockdown period); (ii) "high" in the case of construction, trade, transport, education, sports and entertainment, and private services ( to % supply shock imposed), and (iii) "moderate" in the case of business services, government services, exports, author's compilation government revenue and foreign direct investments (supply shock less than % imposed). more detailed information about the shocks applied at the -and -sector levels are available from the authors. we define shocks as a percentage decline in domestic supply or in one of the final demand components. while the model is calibrated to national data, some measures only apply within the lockdown zones. in those instances, shocks are adjusted for the lockdown zone's share in sector-wide national gdp (see final column in table ). accra and kumasi are important commercial hubs in ghana. census and labor force data show that the specific districts affected by lockdown measures are home to % of ghana's population and a similar share of the workforce. however, due to the higher-skilled nature of urban jobs, workers in the lockdown zone earn a significant wage premium over those in other urban or rural areas. based on labor force survey data (gss ), we estimate that the lockdown districts account for between and % of gdp in industry and manufacturing (average %) and to % of gdp in services (average %). we first report on the anticipated impacts of covid- during the lockdown period, which in the case of ghana was in force for three weeks from march to april. when calculating percentage losses in national or sectoral gdp or in household income, the denominator (baseline value) is scaled to the lockdown period and adjusted for seasonal fluctuations based on historical quarterly gdp data. the second set of results looks at the impacts over the calendar year, starting in quarter one (i.e., before covid- ) and extending through quarter four. following the lockdown period, we assume policy measures are either lifted quickly, resulting in a fast recovery, or gradually, resulting in a slow recovery ( table ). the fast and slow recovery scenarios may equally represent a scenario where economic actors, due to concerns for their own health, are slow to return to a business-as-usual scenario even as restrictions are fully lifted. we first consider the impact during the three-week lockdown. figure shows the impact on aggregate gdp and its components. the largest losses, in absolute and relative terms, are recorded in the industrial (− . %) and services (− . %) sectors, which contribute over % of the recorded . % loss in national gdp during the lockdown period (left panel). this is equivalent to gh¢ . billion or us$ . billion in lost gdp during the three-week period (right panel). ghana's lockdown period was relatively short; should it become necessary to reintroduce the lockdown again in future-a notion that is floated from time to time as the country battles to bring infections under control-every additional week figure provides a breakdown of the contribution to total gdp losses of several of the impact channels described in table . the relative contributions of these impact channels depend on the severity of the lockdown measures, the geographical scope of their implementation, the relative size of the sectors within each impact channel, and the extent of the economic linkages that exist between affected sectors and other sectors. -$ . bil. -$ . bil. -$ . bil. -$ . bil. the severe restrictions imposed on non-essential manufacturing operations in accra and kumasi contribute about one-fifth to overall losses. restrictions in the hospitality and transport sectors and domestic limitations imposed on construction activities contribute a further two-fifths. the construction sub-sector also suffers additional losses via the government and foreign direct investment impact channels, which lead to falling private and public capital stock formation. although primary agricultural activities are excluded from direct restrictions, the agricultural sector is not shielded from adverse effects of the lockdown, with agricultural gdp falling . % (see fig. earlier) . these unintended knock-on effects of covid- related policies highlight the importance of using a model framework that explicitly captures inter-industry linkages and measures indirect effects. to understand the significance of these inter-industry linkages better, it is useful to consider effects along the entire agri-food system (afs). the afs accounts for . % of gdp in ghana and consists of primary agriculture ( . % of gdp), agroprocessing ( . %), food services (hotels and restaurants) ( . %), and food trade and transport services ( . %). figure shows that afs gdp losses amount . % or us$ million in value terms during the lockdown period. with respect to losses within each afs component, we find that the food services sector, which is affected directly by social distancing measures and reduced patronage due to the fall in tourism, not only declines significantly in relative terms (- . %), but also accounts for a large share of overall afs gdp losses, despite being a relatively small subsector. figure provides a breakdown of the contribution of different impact channels to gdp losses in ghana's agri-food system and reconfirms the substantial effect restrictions on hotel and restaurant operations have on the food system. we next turn to household incomes. given the nature of the lockdown measures introduced, household incomes are affected primarily via employment income losses and, to a lesser extent, via falling foreign remittances. as shown in fig. , total household income falls . % during the lockdown period as livelihoods are temporarily lost. if household demand were assumed endogenous, these first-round income losses would have resulted further in declines in demand and employment, and hence larger household income losses, but the distributional pattern of these losses would have been similar to what is shown the figure. in this regard, we find that higher-income households suffer greater income losses than lower-income households, which reflects their stronger ties to formal sector job markets, particularly in the manufacturing and services sectors, which are the sectors most severely affected by lockdown measures. although the lockdown primarily targets urban households and, to a more limited degree, rural non-farm households, rural farm households are affected by social distancing measures and transport restrictions imposed nationwide, as well as indirectly via spillover effects of urban lockdown measures into the agricultural sector. figure presents the effects on poverty due to the lockdown. in generating poverty estimates, we assume that a production slowdown translates into a decline in employment income. in reality, some employers would have continued to pay workers during lockdown or households would have been able to draw on savings to sustain consumption. as such, our result may overstate the actual experience of being poor, i.e., from the perspective of people's ability to access food. but, it nevertheless demonstrates the impact of the shock in terms of wage incomes and/ or profits foregone. we find that the national rate of poverty increases . percentage points from a base of . % to . %, which equates to . million additional people falling below the poverty line during lockdown. rural farm households are somewhat shielded from negative income shocks, but they still account for % ( . million) of those that fall into poverty. this is because many rural farm households have levels of consumption just above the national poverty line, so are more vulnerable to falling into poverty due to adverse income shocks. whereas the earlier results report on the shocks experienced during ghana's threeweek lockdown period, we also measure the likely annual impacts of covid- under two scenarios: a fast recovery scenario, which assumes restrictive measures are quickly lifted and business activities rapidly return to pre-crisis levels, and a slow recovery which assumes a more gradual easing of restrictions and a tentative return to business-as-usual (see table ). gdp results are shown in fig. . with the full lockdown only commencing towards the end of the quarter one (q ), the loss in that quarter is minimal (− . %). the biggest impact is felt in q when the actual lockdown is imposed, with an average loss of . to . % in quarterly gdp. (note that these percentage losses are slightly lower than those reported in fig. , because we account here for some restrictions being eased in the immediate post-lockdown period that still falls in q ). further easing of restrictions in q and q result in losses ranging from . to . % and . to . %, respectively, depending on the speed of recovery. our estimated weighted average loss in gdp for the calendar year ranges from . to . %, which translates to a year-on-year real gdp contraction of . to . % for . government's own expectation is a slowdown in growth from . to . % this calendar year (fig. ) . these results suggest the gdp revision may have been too optimistic, although the projection by government was done at a time when the lockdown was planned to last for only two weeks. moreover, that our model framework captures both direct and indirect effects of covid- may also explain the less optimistic outlook shown in our projections. compared to the . percentage point decline in the poverty rate during lockdown, fig. shows how the poverty rate gradually returns to the baseline (or precrisis) poverty rate during the period from q to q . by the end of the calendar year, the poverty rate will likely be between . and . percentage points higher than in the baseline. however, it is evident that millions of ghanaians will suffer deprivations during q and q and will require government support. future analyses should consider the mitigating effects of the household support programs that government has established as part of its coronavirus alleviation program, which include availability of government-backed soft loans, subsidized water rates and income supplements to healthcare workers (see "financing and budget considerations" section). not much is known about the targeting of these measures or the rate at which funds are being disbursed. however, the us$ million budgeted for the coronavirus alleviation program will close only a small part of the estimated us$ . billion gdp gap between our fast recovery scenario and government's revised gdp trajectory, and unless very well targeted may do little to alleviate the short-term poverty effects of covid- . following the example of countries across the globe, ghana responded to the covid- outbreak by introducing nationwide social distancing measures and travel restrictions, closing its international borders, and implementing a three-week lockdown in the country's largest metropolitan areas of accra and kumasi, which restricted the supply and marketing of non-essential goods and services. the objective of these restrictive measures was to limit the importation and spread of the coronavirus. as elsewhere, concerns about the economic implications of these measures were widespread and certainly not unfounded. in addition to domestic policy impacts, the global pandemic is disrupting global supply chains and economic activity, which could translate into falling exports and sharp reductions in government revenues, foreign direct investments, and private remittances. the objective of this study is to estimate the economic costs of covid- vis-à-vis output and value-added, employment incomes, household income, and poverty using a social accounting matrix (sam) multiplier model for ghana. sam multiplier models are ideally suited to measuring short-term direct and indirect impacts of unanticipated, rapid-onset demand-or supply-side economic shocks. results from the multiplier model show that ghana's partial lockdown, despite being implemented for a relatively short period and only in ghana's major urban areas, will impose heavy economic costs. national gdp is estimated to fall by . % during the three-week lockdown period, while agri-food system gdp losses are estimated at . %, even though the food sector is largely excluded from the restrictive covid- related measures. even as lockdown measures are now gradually being lifted, some restrictions (e.g., social distancing or border closures) are expected to remain in place for longer, while business may be slow to restart operations and reach pre-crisis production levels. under our fast and slow recovery scenarios, we estimate that annual gdp will be . to . % lower, respectively, than the baseline due to covid- . this implies a contraction in the gdp growth rate of between . and . % in , which is significantly less optimistic than the official revised growth target of . %. with respect to poverty, and assuming the production slowdown during lockdown translates into a proportionate decline in employment income, we find that the national poverty headcount rate increases by . percentage points during the lockdown period from a base of . %. this substantial increase, albeit temporary, translates into an additional . million people falling into poverty during lockdown. since some employers continued to pay workers during lockdown, and since some households may have had savings to fall back on to sustain consumption, our result may overstate the actual experience of being poor. nevertheless, the results demonstrate the severity of the shock in terms of wage incomes or profits foregone. during the rest of , as households' current incomes recover to (almost) pre-crisis levels by the end of the fourth quarter, the national poverty rate will be between . and . percentage points higher than at the start of the year. while the expected recovery is good news for most households, millions of people will experience temporary hardships, especially during the second and third quarter, and will require significant and targeted government support. further analysis is needed to assess the impact of household support measures that have already been announced. however, many of these tend to be biased in favor of urban households, whereas our results show that around % of households that become poor during the lockdown period are rural farm households. special support measures for the food system are also warranted, not only to protect rural farm livelihoods, but to ensure stable and safe food supply across all markets. conflict of interest on behalf of all authors, the corresponding author states that there is no conflict of interest. the economic costs of covid- in sub-saharan africa: insights… following the example in breisinger et al. ( ) , consider a simple two-sector sam multiplier model represented by two demand equations, where supply ( z andz ) equals the sum of intermediate input demand, private household demand, and final demand ( e ande ), assumed here to include government demand, investments, and exports. intermediate input demand is expressed as a function of domestic production, x and x and the relevant technical coefficients,a ij , denote demand for commodity i required per unit of commodity j produced. household demand, in turn, is a fixed share (c i ) of income . thus: supply is made up of domestically produced and imported goods and services. we assume that domestic production x i is a fixed share (b i ) of income z i : households derive income from employment, by assumption, a fixed share (v i ) of output: substituting ( ) into ( a) and ( b) yields the following equations: rearranging so that domestic supply components are on the left and the exogenous demand components are on the right and simplifying further yields the multiplier system of equations: this can be expressed in matrix format as follows: the first term in ( ) is the identity matrix (i) minus the coefficient matrix (m) , while its inverse (i − m) − is known as the multiplier matrix. thus, in matrix notation with vectors z and e , the final multiplier equation becomes: ( a) z = a x + a x + c y + e ( b) z = a x + a x + c y + e ( ) this allows us to calculate the change in domestic supply (z) for a given change in exogenous demand (e) . output multipliers (derived from the output vector, x ), employment multipliers, and income multipliers (derived from the income measure, y ) are calculated through substitution. equation ( ) is generalizable for a sam of any dimension. note when household demand ( ) is treated as exogenous, this component of demand forms part of final demand (e) and the coefficient matrix (m) simply excludes the various share parameters ( c i , b i and v i ). africa fertilizer. . fertilizer statistics overview ghana strategic public spending: scenarios and lessons for ghana covid- : ghana has ventilators-health minister coronavirus: trotros to carry just passengers per row from today tumble of global cocoa price causes ghana $ bn deficit-cocobod coronavirus: local cashew industry suffers % price drop covid- -"enormous gap" in ventilators for africa-the worry is no one is sure how big social accounting matrices and multiplier analysis: an introduction with exercises. food security in practice technical guide severe outcomes among patients with coronavirus disease (covid- )-united states economic impact of the covid- pandemic on the economy of ghana: summary of fiscal measures and deloitte views fao statistical databases (faostat) covid- virus spread prompts food insecurity fears in africa icu beds ready to contain critical coronavirus cases-oppong nkrumah covid- : trade restrictions are worst possible response to safeguard food security covid- pandemic: how prepared is ghana's rice sector? supply and use table for ghana / ghana living standards survey round (glss ): main report gss. . labor force report. accra: ghana statistical service (gss) rebased - annual gross domestic product ghana covid- monitoring dashboard ghana statistical services (gss), institute of statistical, social and economic research (isser) and international food policy research institute (ifpri) fertilizer statistics expert agricultural technology and farm-non-farm growth linkages flattening the covid- curve in developing countries the covid- nutrition crisis: what to expect and how to protect ifpri. . covid- policy response (cpr) portal. international food policy research institute balance of payments and international investment position statistics request for disbursement under the rapid credit facility-press release planting for food and jobs campaign: implementation modalities and campaign impact budget highlights of the government of ghana for the financial year statement to parliament on the coronavirus alleviation programme press statement by hon. minister for food and agriculture on the distribution and marketing of food items during the period of restriction press release: update on preparedness on novel corona virus ( -ncov) outbreak is a debt crisis looming in africa? social accounting matrices and sam-based multiplier analysis africa is woefully ill-equipped to cope with covid- the presidency. . speeches. march coronavirus could cut global investment by %, new estimates show trade analysis information system impact assessement of the covid- outbreak on international tourism coronavirus: 'drop in global trade to be worse than who african region covid- readiness status v world bank predicts sharpest decline of remittances in recent history key: cord- -n lttt authors: balsari, satchit; dresser, caleb; leaning, jennifer title: climate change, migration, and civil strife date: - - journal: curr environ health rep doi: . /s - - - sha: doc_id: cord_uid: n lttt purpose of review: in this article, we examine the intersection of human migration and climate change. growing evidence that changing environmental and climate conditions are triggers for displacement, whether voluntary or forced, adds a powerful argument for profound anticipatory engagement. recent findings: climate change is expected to displace vast populations from rural to urban areas, and when life in the urban centers becomes untenable, many will continue their onward migration elsewhere (wennersten and robbins ; rigaud et al. ). it is now accepted that the changing climate will be a threat multiplier, will exacerbate the need or decision to migrate, and will disproportionately affect large already vulnerable sections of humanity. worst-case scenario models that assume business-as-usual approaches to climate change predict that nearly one-third of the global population will live in extremely hot (uninhabitable) climates, currently found in less than % of the earth’s surface mainly in the sahara. summary: we find that the post–world war ii regime designed to receive european migrants has failed to address population movement in the latter half of the twentieth century fueled by economic want, globalization, opening (and then closing) borders, civil strife, and war. key stakeholders are in favor of using existing instruments to support a series of local, regional, and international arrangements to protect environmental migrants, most of whom will not cross international borders. the proposal for a dedicated un agency and a new convention has largely come from academia and ngos. migration is now recognized not only as a consequence of instability but as an adaptation strategy to the changing climate. migration must be anticipated as a certainty, and thereby planned for and supported. people have always been on the move in search of a better life and often simply for survival. population movements, both voluntary and involuntary, have been of interest to those in power and especially so in the last years, coinciding with the period of great explorations, wars of extensive scale, accelerated population growth, and increased control of political borders. the international legal regime created in the years after world war ii, when at least million refugees were stranded in europe and uncounted millions rendered homeless in africa and asia, established rules and regulations relating to definitions and options for people who had left one country for any reason and desired entry into another. these rules have been used to establish the legitimacy of an individual's claim to be a refugee. in the decades since the end of wwii, these rules have proved insufficient to capture the needs and motives of desperate people on the move [• • , ] . migration has now become the reality for nearly one billion people. on a seasonal basis, the numbers are larger, although on smaller temporal and spatial scales. in this paper, we use movement and migration interchangeably to mean displacement, whether voluntary or forced, temporary or permanent, and across spatial scales. diverse political, economic, and environmental causes have triggered large migrations in the past five decades (see table ). a surge in human population creating rising resource demands, an explosion in industry and technology with heavy reliance on fossil fuels, and many different kinds of wars and ethnopolitical conflicts have brought us to this point: nearly one billion people live away from their places of birth, among whom about million (or . % of the global population) have crossed international borders. those on the move include people seeking work, collective groups of people fleeing war and oppression, environmental and climate refugees, and many who fit several of these categories [• • , - ] . in the first half of the twentieth century, migration into wealthy countries of the north and west was driven by major wars and the collapse of countries. in the s, however, the influence of environmental degradation and then climatechange-induced distress began to emerge in the scientific and policy discourse [ ] . this phenomenon is not new-periodic shifts in environmental conditions or sheer over-population of fragile ecosystems have prompted migration for centuries. advances in remote-sensing and surveillance capabilities that have tracked population displacements in recent years have generated strong empirical evidence that migration is a key survival mechanism in the face of extreme weather events, including floods and droughts; that most climate-related migration takes place across short distances within countries or across contiguous borders; and that households which lack migration options are inherently more vulnerable and less adaptable to the impacts of climatic variability [ ] . the drivers of migration are complex and there is now growing recognition that climate change is a threat multiplier, meaning that while it may not directly cause conflict, it can significantly exacerbate the conditions that lead to conflict, destitution and displacement [ ] . until recently, large migrations usually resulted in the eventual integration of people into the social and economic lives of communities and states in their path. the processes were complicated and much hardship and suffering were often experienced by the first generation who made the move. in recent decades, however, the international and regional responses to migration have become much less welcoming and non-porous, requiring large swathes of people to undertake perilous and often fatal journeys by road or by sea to find a route into some country that might allow them entry. popular discourse has often reduced the complexity underpinning the decision to migrate to a tussle over resources between those native to the land and those that have arrived from elsewhere. over the course of this century, it is expected that heat and irregular rainfall will render many agricultural lands infertile and contribute to land degradation, the expansion of deserts, food insecurity, and permanent alteration of many regional economic systems [•• ] . there is an extensive history of how prolonged episodes of severe drought in many regions of the world have caused hardship for pastoralists and farming populations whose lives and livelihoods depend upon periodic rains. in general, several years without rainfall are required before these populations decide they must leave [ ] . they sell assets to try to survive until the rains come and then over time their animals, and table notable international migrations in the past five decades (nonexhaustive list), reconstructed from "migration waves," national geographic, august when fully impoverished, they then abandon home [ , ] . where people choose to go depends upon location and custom, and their ability to leave; movements may be to urban areas, coastal regions, or adjacent lands which remain fertile. these paths out inevitably lead to social collisions with other populations, and again, consequences vary considerably. the world community has had more experience with periodic drought in sparsely settled rural areas than in dense cities where, in general, wealth and infrastructure have buffered urban populations from the direct effects of decreased rainfall. with accelerating climate change, however, the intensity and duration of droughts are likely to increase, impacting urban water supply [•• ] ; urban heatwaves will also become more frequent [ ] . as greenhouse gas concentrations continue to rise, regional warming will intensify [• • , ] ; models suggest that alterations in atmospheric dynamics may lead to large changes in precipitation, particularly in subtropical and mid-latitude regions. [ ] [ ] [ ] . the ipcc report forecasts that, by the late twenty-first century, intense heat and dryness will affect countries extending across north africa into egypt and sudan and northeast to saudi arabia, the levant including syria, iraq, and iran [ ] , to parts of india and china in asia, and across the southern united states and mexico [ ] [ ] [ ] . intense regional heat may render some areas uninhabitable [• ] . a model suggests that business-as-usual approaches to climate mitigation and population growth may expose one in three humans in this belt to high temperatures currently found only on . % of the earth's surface [ ] . these environmental conditions raise fundamental concerns about the viability of agriculture in these important regions, as they are seen now to be forcing millions of farmers, pastoralists, and smallholders into increasingly precarious livelihoods and worsening food insecurity [• • , ] . in iran, models suggest that soil may be increasingly infertile by mid-century, contributing to increased dust storms and falling agricultural output [ ] [ ] [ ] . in wealthier settings, such as australia, high transition costs may occur as commercial farmers seek to control additional resources and invest in more efficient systems to maintain agricultural output [ ] . an additional risk factor may be the habitation of regions that will become more desirable as a result of climate change and may become the object of resource competition with adjacent states or populations [ ] . dependence on water from transboundary rivers that upstream political entities may seek to control also creates inherent vulnerability and opportunities for conflict [ ] . other impacts of climate change will impose similar migration choices. evidence of accelerating sea-level rise due to climate change is now extensive. mainstream estimates range from . to . m by the end of the twenty-first century [ , ] , and higher rates are possible if ice sheet and permafrost melting occur faster than anticipated [ ] . displacement of populations whose dwellings are inundated is the most obvious concern and is already occurring in some low-lying islands and river deltas. displacement from these areas will be a widespread issue within a few decades [ ] [ ] [ ] . in addition, repetitive instances of saltwater intrusion from sea-level rise and storm surges will render well water non-potable and farmland infertile, causing livelihoods stress even for people whose dwellings are not directly affected by rising waters [ ] [ ] [ ] . storms will increase in severity and frequency as a result of climate change [ ] [ ] [ ] . high winds, hail, and heavy rainfall can directly damage crops and can lead to extensive surface flooding, landslides, and structural damage; in the case of tropical cyclones, these may also be accompanied by deadly coastal storm surges causing millions of dollars in damage [ ] [ ] [ ] . the resulting physical and emotional trauma, in addition to damage to individual livelihoods, businesses, and entire sectors of the economy can be substantial and, in some cases, accelerate emigration of affected persons or even lead to abandonment of heavily damaged locations [ ] [ ] [ ] . in the arctic, melting permafrost and sea ice are fundamentally altering transportation systems and rendering some subsistence-based lifestyles unsustainable, as maritime resources are harmed by warming, acidifying oceans [ , [ ] [ ] [ ] [ ] . wildfire has become a new hazard in the region, threatening settlements in the tundra and boreal forest and in some cases permanently altering the ecosystem [ ] . this threat is not limited to the far north; inhabitants of some regions in california may soon be unable to purchase fire insurance, suggesting significant actuarial concern about the longterm habitability of certain fire-prone locations [ ] . current economic and political systems ensure that these slow-moving but inevitable changes will force millions to move for reasons not envisioned in the legal regimes instituted in the s and s [ ] . how migrants are received in host communities however has profound and long-lasting implications on the future of both. migration affects most aspects of human social interaction and in itself imposes environmental change when large influxes of refugees lead to increased demands on ecosystem services as well as on space, food, and shelter [ ] . in the face of inevitable large-scale migration expected within and from the weak economies of latin america, africa, the middle east, and south asia, the current xenophobic approach to keeping out migrants ensures devastating and destabilizing consequences for humans and the planet. a full review of specific vulnerable populations in the face of climate change projections has been extensively explored by other authors [ , ] . here, we focus on four regions at the confluence of climate-related hazards noted above: the african sahel, the middle east and north africa (mena), the "dry corridor" in central america, and south asia, as together they host the world's most vulnerable billions. . the sahel: migration and conflict related to climate change and resulting agricultural and ecological problems are increasingly prominent issues in the sahel, a semi-arid region stretching across africa from ethiopia to senegal. smallholder rainfed agriculture and herding are becoming increasingly difficult due to unpredictable availability of water and in some locations expansion of the sahara desert [ , , ] . these stressors and competition for available resources may have contributed to conflicts in nigeria [ ] , uganda [ ] , sudan [ ] , and kenya [ ] , although the relative causal contributions of climate change, governance, population pressures, and preexisting sectarian divisions to outbreaks of organized violence remain a subject of intense debate [ , , ] . many people facing unpredictable weather, food insecurity, and in some cases violence have left their land for urban centers in african nations, where conflict with existing populations and discord over space and essentials may occur [ ] [ ] [ ] . others have followed longer, more dangerous migration routes across the sahara and the mediterranean in hopes of reaching europe. these routes are characterized by conflict with populations and governments along migration routes and substantial hazards during transport across desert and ocean [ , , ] . even after arrival in host countries, migrants remain a source of intense political tension and experience a variety of forms of discrimination and violence [ , ] . . the mena region: climate models for the rcp . (business-as-usual emissions trajectory) in the middle east and north africa estimate that by there will be at least a days a year (and by , over days) when temperatures will cross into the th percentile for the region, with the hottest temperatures exceeding °f [ , • ] . the same models suggest that in the same time frame ( ) the heat stress on the soil in many areas would desiccate organic life to as much as inches deep, precluding crop growth even if adequate irrigation were provided. although there is some disagreement, the preponderance of the literature suggests that climate change has contributed to civil strife in syria [ ] [ ] [ ] . there, a prolonged drought in the east and northeast linked to climate change forced pastoralists and farmers to abandon their land, sell their animals, and trek to the cities in the western region of syria. in - , it is estimated that approximately one million people migrated to these urban centers, including the seat of the assad government in damascus [ , ] . underlying political grievances in these urban areas, already stretched for resources by . syrian government in the spring of led rapidly to an outright civil war [ ] . that war, now in its tenth year, has killed approximately , people, created . million refugees and at its peak - million internally displaced persons. the ongoing ramifications of this conflict are undermining stability in much of the middle east as well as europe. . central america: in central america, another pattern of climate change, drought, livelihood collapse, discord, and distress migration leading to conflict has occurred [ ] . since , the "dry corridor" in nicaragua, honduras, el salvador, and guatemala has experienced a series of devastating multi-year droughts [ ] . this series is consistent with the predicted effects of climate change in the region, and there is now substantial evidence linking drought and agricultural hardship to the effects of climate change [• • , , ] . according to the food and agricultural organization (fao) of the united nations, crop losses in the region from to range from to % and left . million people in need of humanitarian assistance [ ] . these losses have had a profound effect on the viability of agricultural livelihoods, with the majority of households resorting to crisis coping methods such as selling agricultural tools for food. even so, as of the last quarter of , more than % of the population in the dry corridor are without sufficient income to purchase necessary food [ ] . facing uncertainty about future rainfall, many have chosen to leave, with emigration from the region increasing by % between and [ , , , • ] . the majority of people moved overland along this "dry" corridor to seek better prospects northwards. this trek has resulted in increasing conflict between migrants and authorities in transit nations and along the southern border of the usa. this border, historically the final destination and hopeful push-off point in the usa for many of those attempting to escape the worsening conditions to the south [ ] , has for the last five years now been effectively closed [ ] . . south asia: the densely populated gangetic plains in south asia also fall in the zone that will experience high temperatures as a result of climate change in the coming decades. a model suggested that extremes of wetbulb temperature in south asia, under the representative concentration pathway . (rcp . ) scenario, are expected to approach or exceed the critical temperature of °c ( °f), considered an upper limit of human survivability [ ] . in addition, bangladesh will face the consequences of rising sea levels and coastal flooding that is already imperiling millions of coastal dwellers. the south asia region has already experienced severe heat waves in recent years, including the fifth deadliest heat wave in recorded history killing people in pakistan in . per the world bank report, by , south asia could see - million climate migrants in scenarios under models of urgent climate mitigation, and up to million under a more pessimistic scenario [ ] . the population is highly dependent on the summer monsoons and rainfed agriculture, making it particularly vulnerable to temperature and rainfall changes. the region is likely to have the highest number of foodinsecure people by mid-century [ ] . the southern indian highlands between chennai and bangalore (containing many densely populated cities), parts of northwest india, and nepal may see in-migration, while bangladesh and the gangetic corridor from lahore to delhi will be hotspots for out-migration. coastal cities such as mumbai, dhaka, and chennai are likely to reel under the burden of continued rural to urban migration, until intensifying heat, and worsening flooding and coastal storm surges make life untenable for most of the millions who live at the economic margins of these megalopolises, compelling them to move again. models estimate that the number of people trying to live in the flood plains of south asia may rise from million in to at least million by , even as climate change renders these regions more hazardous [ ] . growing religious and ethnic intolerance in south asia does not bode well for the region when the overwhelming survival need for populations in this century will be more movement not less. rohingya refugees from myanmar are trapped in what is now the world's largest refugee camp in coastal cox's bazar in bangladesh, where they are denied formal refugee status, and remain stateless, unable to seek formal work, advance educational opportunities, or do much more than barely survive [ ] . in neighboring india, the government launched an attack on its minorities by re-defining citizenship, arresting dissenters, and beginning to build detention camps for muslims and unregistered populations in the northeast of the country [ , ] ; the border with neighboring bangladesh, a likely source of climate refugees, is now heavily militarized [ ] . india is currently the greatest exporter of migrants-nearly million-to the gulf states, the usa, the uk, and elsewhere. the experience of populations in the sahel, mena, dry corridor, and south asia, where the climatologic roots of their displacement may overlap considerably with conflicts arising from deep-seated political enmities, suggests patterns of mixed climate change and social crises now occurring in many regions. as they seek stability, livelihoods, and food in new locations, the implications of these movements for affected populations and host regions have become a topic of increasing concern in policy circles although few robust response strategies have emerged from these deliberations. these patterns are expected to intensify and occur more frequently as climate change becomes more extreme in the coming decades. a vexed question over the last years for social scientists and demographers has been whether uprooted populations contribute to intra or inter-group conflict during migration or in the host country. the expert consensus from the late s through early s was that societies could adapt, migration was not clearly caused by climate change, and there was little to no evidence for the influence of environmental stress (let alone climate change) on the incidence or persistence of armed conflict [ ] . shifts in these arguments began to emerge in the mid- s, as the effects of climate change became more marked [ ] , the number of resource wars increased with surges in forced migration [ ] , and research and policy analysis contributed to enhanced understanding of the pivotal negative roles played by internal social fragilities and incompetent or malicious state leaders in the setting of external economic and agricultural shocks [ , ] . at present, available evidence indicates that distress migration from climate-induced environmental crises does sometimes lead to intense social conflict and in certain instances contributes directly to armed conflict. there are however numerous mediating variables: the capacity of the host government and its economy to absorb the incoming population, the extent to which the incoming population is related politically or socially to another population threatening the state's internal order, and the underlying historical vulnerability of this society to civil war or armed conflict all play a role [ ] [ ] [ ] . these variables are crucial in all assessments of these interrelationships and the most pivotal of these is the fragility of the government and its recent conflict history. to put the empirical findings positively, a flexible and robust system of governance with a strong economy can respond to an influx of large numbers of people without deep social distress or conflict-provided sufficient foresight and resources are devoted to advance planning and mitigation. for decades, however, migration was not high on the global political agenda, and not imagined beyond the contours of movements of political refugees. the millennial developmental goals do not pay particular attention to migrants. this stance has changed rapidly in the first ten years of the twenty-first century, as evidence as well as the experience has accumulated to focus attention on the increasing numbers and kinds of distressed migrants moving within countries, within regions, and to europe and the usa. some are fleeing extreme weather events or slowonset but cumulatively dramatic environmental change. some are fleeing conflicts, exacerbated by climate change and resource tensions. a watershed moment in global political discourse around climate change and migrants occurred in - , when a series of international initiatives acknowledged not only the urgent need to address climate change but also the intersection of climate change and human mobility (see table ). in stark contrast to the mdgs, the sustainable development goals (sdgs) called for the "facilitation of orderly, safe, and responsible migration and mobility of people, including through implementation of planned and well-managed migration policies." the sendai framework for disaster risk reduction recognized climate change as a driver of human mobility. the world bank report and the atlas of environmental migration authored by the iom and others conclusively recognize the salience of "environmental migrants." there are to date no international conventions that explicitly address migration from environmental or climate-related causes, and no single un agency responsible for them. proposals for treaties and legal instruments focusing on climate refugees have largely originated from academia and ngos and are summarized in table . the iom does not favor a separate category of "climate refugees" or new treaties to address them, arguing that international attempts at controlling such flows will clash with current notions of national sovereignty [ ] . migration is now recognized not only as a failing consequence of myriad and intersecting determinants, including the failure to adapt to environmental changes, but also as a useful climate-adaptation strategy-if managed, planned, facilitated, and well prepared for in advance [ ] . most migration will continue to occur within countries, and will largely involve rural to urban population flows, mediated by a complex intersection of political, demographic, socioeconomic, and environmental drivers [ ] . while transient shocks like the nationwide lockdown in india amidst the covid- pandemic the conference also established a process for least developed countries (ldcs) and other interested developing countries to formulate and implement national adaptation plans (naps) to identify and address their medium and long-term adaptation needs. it proposed the idea of a climate risk insurance facility, and sought "ways to address rehabilitation from the impacts of such climate change-related events as sea-level rise [ ] ." the nansen initiative, [• • ] in response to cop , the nansen initiative, launched by switzerland and norway, was a state-led consultative process, which recognized that while most movement will take place within countries, there remains a significant protection gap (both legal and operational) for those who cross an international border. based on these consultations, the initiative published a consensus "agenda for the protection of cross-border displaced persons in the context of disasters and climate change," which was endorsed by states in [ ] . the protection agenda supports the integration of effective practices by states and (sub-) regional actors into their own normative frameworks, rather than calling for a new binding international convention on cross-border disaster displacement [ ] . the wim created a legitimate policy space to discuss and address the negative consequences of climate change if society's efforts to mitigate and adapt are not sufficient. it sought to implement approaches to address climate change associated loss and damage and recognized migration as an adaptation strategy. the paris agreement seeks to strengthen the global response to the threat of climate change by keeping a global temperature rise this century well below °c above pre-industrial levels. to strengthen the ability of countries to address the impacts of climate change, it seeks to facilitate appropriate financial flows, a new technology framework, and an enhanced capacity-building framework to align action by developing countries and the most vulnerable countries, with their own national objectives. to date, of the parties to the convention have ratified it. having notified intent, the usa can officially withdraw from the agreement on or after november , . many of the nationally determined contributions, as required by the paris agreement, from africa, asia pacific, and oceania refer to human mobility and its role as an adaptation strategy [ ] . sendai framework for disaster risk reduction, [•• ] the sendai framework adopted at the world conference on disaster risk reduction and endorsed by the unga in recognizes that population movements produce risk but can also serve as an adaptation strategy [ ] . the text however emphasizes disaster-related displacement and avoids explicit inclusion of mobility from conflict and violence, to gain member state consensus. agenda for humanity, [ ] the third of five principles, articulated in this political communique led by the un secretary general, as an output of the world humanitarian summit (whs) in istanbul, is titled "leave no one behind" and addresses displacement, migration, and statelessness. the platform on disaster displacement, [ ] the goal of the platform also launched at the whs is to follow-up on the protection agenda published by the nansen initiative. it explicitly recognizes the intersection of environment and climate change, and displacement. its four strategic priorities include addressing knowledge gaps, promoting identified effective practices, promoting policy coherence and mainstreaming of human mobility challenges, and promoting policy and normative development in gap areas [ ] . assembly and addresses migration due to environmental and/or climate change, as well as the environmental impacts of migration, large population movements, and the environmental sustainability aspects of migration. it notes that environmental factors drive both internal and international migration the global compact for safe, orderly and regular migration, [ ] the compact is an intergovernmental negotiated, non-binding, un global agreement initially adopted by countries that seeks to address concerns of state sovereignty and responsibility-sharing while upholding human rights and principles of non-discrimination as societies undergo demographic, economic, social, and environmental changes that may have implications for migration or result from it. the global compact for refugees, [ ] the compact seeks to invest in host communities to provide better education, healthcare access, and livelihood opportunities, moving away from contemporary dominant encampment policies [ ] . resulted in return migration to rural areas, we find that the current literature suggests overwhelming net rural to urban migration. the foresight commission report from the uk government cautioned against trying to prevent such migration (although it might lead to increased vulnerability of new urban migrants) because preventing them from leaving highly stressed or insecure environments could lead to graver outcomes for those trapped in rural areas with even less access to food and water [ ] . it recognized that the cities receiving these migrants were also particularly vulnerable to environmental change and without adequate preparation would also suffer the consequences of extreme heat and depleted water resources. now, almost a decade later, this scenario is already evident: rural populations moving into vulnerable urban cities, finding no sustenance are on the move again. a recent model developed jointly by the new york times magazine and propublica, and published in july , estimates that the number of migrants arriving at the us border from central america and mexico may rise to . million a year by , from about , a year in , in the absence of climate mitigation or adaptation strategies [ ] . the current international agreements are not remotely adequate to address ongoing and projected levels of human migration, regardless of how and how much climate change may influence it, nor are the decades-long and still current trajectories of industrialization, globalization, and development providing any signs of serious commitment to climate adaptation. realistic global and regional planning should therefore assume the worst-case scenarios under rcp . and begin immediately to prepare to make life tenable for the hundreds of millions that will urbanize and then attempt to move again as life becomes unendurable when the urban centers themselves exhaust resources and opportunities: the migration in the dry corridor heading toward the us border, or the perilous journeys over the mediterranean, are examples of migration patterns when the first stop of refuge is no longer a sustainable option. the wall-building, xenophobic, and insular strategy embraced by the usa, europe, china, and india to deal with the greatest challenge of our times is regressive, violent, and profoundly ignorant, in that it denies the core reality that for millennia, under threat, humans have moved to escape. it dismisses recent and strengthening scientific evidence that stability and security for hundreds of millions in latin america, africa, and asia will depend on the opportunity to relocate, even if seasonally, for work. facilitating visa, employment, and remittance arrangements can complement urgently needed climate mitigation strategies. water management in agricultural lands and in urban areas is likely to become critical to any adaptation plan. host communities, including the transition cities and towns we have examined and final destinations whether in-country or across borders, must start preparing now for the increased demand for food, water, shelter, services, and jobs that will arrive with these migrant populations. there is little indication table key legal instruments that have been proposed in the twentyfirst century mostly based on the premise that current options are not sufficient or are failing. the summaries here are based on [ ] draft convention on the international status of environmentally displaced persons, . [ ] university of limoges the principles underlying the convention include the principle of solidarity, common but differentiated responsibilities, effective protection, non-discrimination, and non-refoulement. the specific rights guaranteed to persons threatened by displacement include rights to information and participation, displacement, and the right to refuse displacement. the rights guaranteed to persons already displaced include those common to inter-state and internally displaced persons. the convention would include a world fund for the environmentally displaced that would provide financial and material assistance for the receipt and return of the environmentally displaced. proposal for a convention on climate change refugees, [ ] harvard university the authors argue for a new, independent convention that allows for the instrument to be creatively tailored to the complexity of the problem and to take a broad-based and integrated approach, on the basis that the problem of climate-induced migration "is sufficiently new and substantial to justify its own legal regime," instead of being forced within legal frameworks that were not designed to handle it. [ ] university of western australia the convention would assign rights and protections through a process of "request and determination" that would be based on scientific studies and the particular situation of the community. under the convention, displacement would be viewed as "a form of adaptation that creates particular vulnerabilities requiring protection as well as assistance through international cooperation." thus, the emphasis of this convention would be on the duty of a particular state to provide protection and humanitarian assistance to climate change displaced persons within its jurisdiction and to support governments, local communities, and agencies in fulfilling that duty. climate exile treaty, [ ] iit, madras, india the authors distinguish between "luxury" emissions referring to those associated with wasteful lifestyle choice and "survival" emissions that are associated with subsistence living. they invoke the "beneficiary pays" principle, which states that "countries that undertook and benefited from emissions activities are liable for the costs of combating negative externalities that resulted from them." that any of this preparatory action will happen: the pandemic has reaffirmed that the current global approach to solving intractable challenges does not embrace cooperation, mutual interest, and scientific rigor but instead retreats to adamant rejection of a future that is upon us. the post-wwii international regime sought to rescue, provide refuge, and rehabilitate millions rendered homeless by the wars and post-colonial independence struggles that followed. but in recent decades, large pulses of migration along the dry corridor in central america, the sahel, the middle east, and asia, some in the context of protracted wars, have culminated in a regime of reneged promises to protect, refusal to let the vulnerable in, and attempts at repatriation or worse, forced refoulement [ ] . these responses have followed the ascendancy of inwardlooking nation-states in the north and west who have observed explosive population growth elsewhere and interpreted this phenomenon as a threat to their own internal resources and stability. consequently, international borders have become increasingly tightly regulated and hostile to foreign entrants. complex visa arrangements are now a key driver of who can cross international borders, and under what conditions, inflicting with their harsh differentiating categories particularly punishing effects on women, children, and the elderly [ ] . the regressive treatment of refugees at the us-mexico border and at the gates of europe (with the exception of germany) is diametrically opposite to what is needed. weaker economies like turkey, jordan, lebanon, and even bangladesh have been kinder to the millions that have poured across their borders, albeit with wide variation in permitted integration. unless the most powerful governments around the world change course nowand they are showing little signs of doing so-over this century, the evidence shows, the impact of climate change on the hundreds of millions who will nevertheless move, on those in regions that will receive them, and on those who will not find any remedy through migration, will be impossible to bear. acknowledgments we thank abhishek bhatia for the assistance with editing the manuscript. dr. balsari and dr. dresser's research is supported, in part, by the living closer foundation consortium on climate and health. author's contribution the manuscript was jointly developed and written by sb, cd, and jl. all authors read and approved the final manuscript. conflict of interest the authors declare that they have no conflict of interest. open access this article is licensed under a creative commons attribution . international license, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link 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safety and dignity: addressing large movements of refugees and migrants: report of the secretary-general human rights of refugee and migrant women and girls need to be better protected. human rights comment-the council of europe commissioner for human rights publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations key: cord- -byjyqisn authors: asiedu, edward; sadekla, sylvester s.; bokpin, godfred a. title: aid to africa’s agriculture towards building physical capital: empirical evidence and implications for post-covid- food insecurity date: - - journal: world dev perspect doi: . /j.wdp. . sha: doc_id: cord_uid: byjyqisn the formation of physical capital in sub-saharan africa (ssa) in agriculture is imperative to help the continent ( ) overcome the effect of the covid- pandemic on food insecurity and ( ) still be on track towards achieving the sustainable development goals (sdgs) of “no poverty” and “zero hunger” in the midst of the covid- pandemic. using country-level data on ssa countries from to and rainfall deviations as an instrument for agricultural official development assistance (oda) in fixed-effect estimation settings, this paper examines the ‘instantaneous’ impact of agricultural oda on agricultural fixed capital formation in ssa. the question here is whether aid to agriculture does translate instantaneously to building fixed capital urgently needed to address the effect of any potential crisis on food insecurity. measuring agricultural fixed capital as fixed investments in farm machinery, dams, industrial buildings for agricultural and agro-processing, fences, ditches, drains, etc., we find that capital formation in ssa agriculture improves instantaneously with agricultural oda inflows. second, we find that even though rainfall deviations are associated with agricultural oda inflows to ssa, institutions particularly those designed to control corruption and strengthen rule of law, do matter for agricultural aid inflows to ssa. these results suggest that agricultural oda is necessary to accelerate agricultural investments and achieve food security. our results are robust to sensitivity analysis on the specification of the instantaneous model. the paper studies the instantaneous impact of agricultural official development assistance (oda) on agricultural gross fixed capital formation (gfcf) in sub-saharan africa (ssa). over the past decade, oda to sub-saharan africa (ssa) has increased significantly. in , the amount of oda flows to the region was $ billion and rapidly reached $ billion in (mccloskey, ; ogundipe et al., ) . in , data suggest that total oda to ssa increased to $ . billion (mccloskey, ) . in general, over the past five decades, ssa has received about $ trillion in foreign aid. the broader question here is whether the oda to ssa has had significant impacts on receiving countries. the more specific question is whether agricultural oda to ssa has had significant and instantaneous impacts on the formation of agricultural physical capital and for which reason, in the midst of crisis, can be used as a tool to address vulnerabilities in the food system. thus, in the era of possible food insecurity in ssa due to the increasing threat of climate change and the aftermath effect of the covid- pandemic, it is important to examine whether aid can have immediate impacts and as such help to create the needed fixed capital required in the shortest possible time (see sasson, for elaboration on pre-pandemic food insecurity in ssa). importantly, in the midst of any crisis, be it climate-induced or pandemic-induced, it is important to explore both the short-term as well as long-term solutions. resolving the problem of food insecurity induced by climate change or by a pandemic is crucial to development in lowincome countries. anecdotal evidence so far shows rising food insecurity due to the covid- lockdown in a number of ssa countries. although the aftermath of the covid- pandemic could heighten food insecurity in many ssa countries, we argue that an instantaneous improvement in agricultural physical capital formation could lessen the impact. thus, in this paper, we explore the instantaneous impacts of agricultural-specific aid on the formation of agricultural fixed capital in the form of farm machinery, dams, industrial buildings for agricultural and agro-processing, fences, ditches, drains, etc., in ssa's agriculture sector. we consider the associations between current agricultural oda and current levels of agricultural fixed capital formation. oda to ssa based on the motive for the support can be categorized into social (education, health, water, and sanitation), economic (transport, communication, energy, and banking) , production (agriculture, industry, and trade), humanitarian, multisector. general program aid and debt (see oecd, ) . while there is a general greater understanding of the impact of aid at the national and sub-national level (see (alesina and dollar, ; arndt et al., ; qian, ; briggs, briggs, , masaki, ) , nonetheless there is scanty empirical evidence on the impact of sector-specific aid, particularly aid to the agricultural sector of ssa countries. traditionally, agriculture in ssa had been largely traditional with limited use of productivity-enhancing machinery such as tractors, plows, harvesters, etc. (see daum and birner, ; benin, ) . support for agricultural mechanization has increased significantly since the last food price crisis in , culminating in the introduction of policies including subsidies on farm implementsto ease access to farm implements and increase food production (benin, ) . the need for increased capital formation in agriculture to increase food production, and reduce food insecurity and hunger particularly in ssa is heightened by the daunting effect of climate change and the coronavirus outbreak. scholars argue that food insecurity and hunger can lead to social upheaval and can create a new 'security' threat for ssa (hendrix and brinkman, ; brown et al., ; paarlberg, ) . for completeness, we also examine the long-term impact of agricultural aid, one of the ways to still be on track towards achieving the sustainable development goals (sdgs) of "no poverty" and "zero hunger in the midst of a pandemic and climate change is to aggressively increase access and use of agricultural machinery, in order to increase food production. improving capital formation is therefore imperative for agricultural development. agricultural development is a goal in itself, and if reached can help to reduce poverty and hunger in ssa. it can also help ssa countries to be resilient in terms of food security in the face of any crisis such as the covid- pandemic. there exist very few country-specific studies that have examined the impact of agricultural oda in developing countries. the preponderance of evidence has focused on project and country-specific oda. for example, nkonya et al. ( ) have shown that a multilateral agricultural aid programme that was initiated in nigeria led to the neglect of investment in postharvest technology, leading to increased storage losses. abdulai et al. ( ) examined the effect of food aid on household-level food production. they find no effect of food aid on food production. investment in infrastructure and other capital goods is particularly crucial in the development process of developing countries. dams, warehouses, farm machinery, etc., can enhance agricultural productivity. fixed capital formation in agriculture is therefore imperative for pro-poor growth and poverty reduction. the theoretical argument is that oda has the potential of augmenting scarce domestic resources to aid the formation of fixed capital needed for economic growth. nonetheless, oda can also be a disincentive to wealth building by depressing governments' motivation for revenue generation and thereby impeding capital formation. against this backdrop, we contribute to the literature by focusing on a sectoral analysis of official development assistance, and to the best of our knowledge, this study is one of the few studies that examine the impact of agricultural-specific oda on agricultural fixed capital formation in ssa. we draw on data across forty ( ) ssa countries from to and address the endogeneity of agricultural oda received by a country through an instrumental variable (iv) estimation an approach. we instrumented agricultural oda by countries' (lagged) rainfall deviations from their own long-run average rainfall. for comparison purposes, informed by the literature on aid competition, we use the countries' yearly rainfall deviations from the ssa continental average rainfall also as an instrument for agricultural aid. lahiri and raimondos-møller ( ) noted that recipient countries use their domestic situation and policy instruments in competing with each other for foreign aid. thus, we argue that countries with relatively higher deviations from the ssa average, compared with those with smaller deviations, are more likely to receive more agricultural oda. our main results are the following: we find an association between oda received in the current period and agricultural capital formation in the same period. the coefficient on the agricultural oda variable in the fixed capital formation model is positive and highly significant at the % level. our finding is consistent even if we model the instantaneous effect of agricultural oda with a one-year lag. the short-run elasticity of capital formation in agriculture with respect to agricultural oda ranges between . and . . this economic significant effect is non-trivial, and consistent with the view that agricultural oda stimulates agricultural capital formation in ssa. our two-stage least squares ( sls) estimation approach adopted also allows us to probe the drivers of agricultural aid to ssa. we find that even though some part of agricultural oda inflows is driven by the recipient country's need, in our case measured by the extent of rainfall deviations, the quality of recipient country's institutions still matters for agricultural aid. generally, we find that agricultural aid is directed to well-governed countries, countries in periods of high rainfall deviations, and high exchange rates. in a nutshell, we find that agricultural aid is useful for building agricultural fixed capital and that countries can attract more agricultural oda if institutions are strengthened. the rest of the paper proceeds as follows; section briefly presents a review of previous works on aid and investments. section presents a conceptual framework and empirical issues in assessing the impact of agricultural oda. section presents the data used for our analysis and time period under consideration. section presents and discusses the empirical results whereas section concludes. the impact of aid on investments has been previously examined by lensink and morrissey ( ) , hansen and tarp ( ) , gomanee et al. ( ) , boone ( ) , and gang and khan ( ) , etc.. for example, using data on developing countries and ssa countries, lensink and morrissey ( ) find that aid has a significant positive effect on the volume of investment. hansen and tarp ( ) find similar results for a sample of countries with being ssa countries. precisely, they conclude that aid continues to impact on growth via investment. gomanee et al. ( ) in their study which focused entirely on ssa countries ( countries) reinforced the positive relationship between aid and aggregate investment. the insignificant link between aid and government consumption is articulated as one of the key reasons for the positive relationship between aid and investment/capital accumulation (see gang and khan, ) , however, a number of empirical studies particularly carried out in the s on aid effectiveness find no impact of aid on investment but rather aid increases the size of government (see boone, white, ) . obstfeld ( ) qualified the results by boone ( and , by arguing that aid raises both consumption and investment, as well as the growth rate, provided the economy is initially below the steady-state. the studies by hadjimichael et al. ( ) , durbarry et al. ( ) , and burnside and dollar ( ) have all questioned the findings by boone ( . aside from the impact of aid on investment, in terms of the impact of aid on economic growth and poverty reduction, while a number of still inconclusive evidence on the causal effect of aid on growth (see galiani et al., ) this is approaching unity. studies (levy, ; arndt et al., ; hansen and tarp, ; lensink and morrissey, ; burnside and dollar, ; karras, ; galiani et al., ) find evidence for the positive impact of foreign aid on economic growth and poverty reduction. interestingly, a similarly large number of studies also find evidence for the opposite (bräutigam and knack, ; javid and qayyum, ; tracy, ; and uzonwanne & ezenekwe, ) . another group of researchers finds evidence for aid neutrality (jensen and paldam ( ) ; djankov et al. ( ) suggest that aid has effects that are analogous to a natural resource curse (see also arndt et al., ) . thus, the empirical aid effectiveness literature has produced mixed results and is inconclusive about the usefulness of general aid. beyond examining the impact of aid on investment and growth, quite a number of studies have also examined the patterns and drivers of aid giving across the world. shafer ( ) argues that the presence of corrupt, abusive, or ineffective government can undermine or nullify efforts to enact change through aid. broadly, the reasons for sending and receiving aid in the literature range from the desire to help other countries (neumayer, ) , good governance and strong institutions in the recipient country (alesina and dollar, ; neumayer, ; shafer, ; wright and winters, ) , cultural closeness measured by religious closeness (shafer, ; alesina and dollar, ) . historical closeness measured by colonial relationships (arndt et al, ; alesina and dollar, ) , to food insecurity in the recipient countries (abdulai et al., ) . alesina and dollar ( ) argue however that the major donors also give aid to just about every developing country, indicating that some donors like to be involved everywhere. in terms of agricultural specific aid, there is very little evidence across countries, and particularly for ssa africa. country-level programmes such as the multilateral aid for nigeria's agricultural development have found weak impact of the "national fadama development programme" on infrastructure (post-harvest technologies and irrigation) and assets accumulation in nigeria (see nkonya et al., ) . they find that the project succeeded in targeting the poor and women farmers in its productive asset acquisition component. one of perhaps the most closely related studies on the impact of aid on agricultural-related activities is the study by miller ( ) . in this study, the authors examined the extent and trends of international aid to biodiversity conservation and development goals from to in countries. the study using an ols multivariate multiple regression model finds that biodiversity aid generally was directed to biodiversity-rich and well-governed countries. abdulai et al. ( ) also examine the impact of food aid in ssa. the authors find no disincentive effects of food aid on recipient food production. in this study, we fill the gap in the literature by focusing on the effectiveness of agricultural specific aid in promoting the building of fixed capital, which is imperative for poverty reduction. in attempting to estimate the effect of aid on investments and growth, issues of endogeneity, or selection, are important to consider, and therefore attempts need to be made to mitigate these issues. first, aid is not sent randomly to countries, and therefore it is possible that receiving countries are different from non-receiving countries. importantly, if aid sending countries send aid in response to a certain observable recipient country characteristic (s), then aid will be endogenous. one way to address the endogeneity problem regarding aid is to use instrumental variable (iv) techniques relying on external instruments (see maruta et al, ; galiani et al., ) . others have used ordinary least squares (ols) as well as a generalized method of moments (gmm) estimators (see lensink and morrissey, ; hansen and tarp, ; gomanee et al., ; boone, gang and khan, ) . maruta et al., ( ) instrumented foreign aid with recipient and donor countries similar voting positions in the un general assembly. galiani et al. ( ) instrumented general foreign aid based on the fact that, since , eligibility for aid from the international development association (ida) has been based partly on whether or not a country is below a certain threshold of per capita income. in this paper, we instrumented agricultural aid flows partly by rainfall deviations, and partly by domestic institutions. in order to reduce the high poverty levels that continue to plague many rural areas in ssa, it is imperative to find innovative and sustainable ways to increase capital formation in agriculture. doing so, and doing it rapidly, can help to hasten recovery from the covid- pandemic and remain on track to still to achieve the sustainable development goals (sdgs) of "no poverty" and "zero hunger" in ssa. agriculture still remains the backbone of the majority of economies in africa (gabre-madhin & haggblade, ; fao, ; godfray et al, ) . as of , the sector contributes an average of . % to gross domestic product (gdp) with the minimum contribution being . % in botswana and a maximum of . % in chad (world bank, ). diao et al ( ) argue that the growth of the agricultural sector triggered by increased fixed capital formation is more pro-poor than growth in other sectors. a lump-sum gift of aid should have a positive effect on agricultural investments. the consensus is that aid allows countries to expand public spending (see doucouliagos and paldam, ) . foreign aid flows therefore once received by a country adds to their existing capital stock. however, doucouliagos are paldam ( ) from a meta-analysis of aid studies that conclude that only about a quarter of aid is invested. they argue that aid generates dependency by replacing domestic savings. consider the following simple model (eq. ( )). let gfcf it be a gross fixed capital formation (investments) in agriculture -the value of agricultural investment-of country i at time t. gfcf it include the value of land improvements (fences, ditches, drains, etc), livestock that is used continuously in production year to year (breeding stock, dairy cattle, sheep reared for wool and draught animals.), tree stock (trees cultivated in plantations and yields year to year such as fruit trees, vines, rubber trees, palm trees, cocoa trees), farm machinery such as tillers, fertilizer spreaders, harrows, harvesters; plants and equipment such as cages for fish farming; and also roads, railways, dams, industrial buildings for agricultural and agro-processing purposes. according to the system of national accounts (sna) of the united nations statistics division (unsd), net acquisitions of valuables are also considered capital formation. let oda it equal the value of agricultural oda received by country i at time t, thus exploring the instantaneous effect of oda. in other specifications, we include a one-year lag of the agricultural oda variable. we however still consider the one-year lag as an immediate impact of oda. there may also be some random factors that cause gross fixed capital formation in agriculture to differ and we denote these as ε it . in this study, the parameter β captures unbiased estimate of the effect of agricultural oda on agricultural fixed capital formation, provided that it is uncorrelated with ε it . this would be true if agricultural oda were randomly distributed to countries in ssa. however, this is unlikely to be true. in this case, eq. ( ) will generate biased estimates of β because the assumption underlying the regression analysis, that e a better representation of the relationship between current agricultural oda and current gross capital formation is, therefore: here, x it is a vector of control variables in-country i at time twhereas ν t are fixed-time effects to capture the impact of worldwide business cycles. the choice of controls to include in this model is informed by the literature on investments across developing countries (see bleaney and one-year lag of oda on fixed capital formation is also estimated. greenaway, ; bleaney and greenaway, ; hadjimichael and ghura ; greene and villanueva, , servén, ) . our control variables include a one-year lag of real gdp per capita, the real interest rate, the inflation rate, and volatility of the real exchange rate. thus, as is common in the literature we control for the one-year lag of gdp per capita. thus, we allow agricultural gross capital formation (agricultural investments) in period t to depend on the one-year lagged gdp per capita i.e., initial real gdp per capita or gd per capita at the beginning of the period. we expect the coefficient on the one-year lag gdp per capita to be positive, with a higher gdp in the previous year expected to have a positive impact on the current year's agricultural investments. bleaney and greenaway ( ) also included a two-year lag of gdp per capita in the investment model. as argued by alesina and perotti ( ) and levine and renelt ( ) , empirically gdp enters a cross-country investment model with a consistently positive sign, suggesting that the convergence in gdp per capita occurs through channels different from increases in physical investment. here, we also control for gdp per capita in the oda model. with regards to the inclusion of real interest rate, inflation, and real exchange rate as part of the controls in the agricultural investment (agricultural gross fixed capital formation) model, serven ( ) documents how recent investment theory have paid attention to uncertainty and instability as important drivers of investment. the theoretical argument is that, if the investment is costly or difficult to reverse (as in the case for many fixed capital investments), investors have an incentive to postpone commitment and wait for new information in order to avoid costly mistakes. and this "value of waiting" can be quite considerable, especially in highly uncertain environments. for example, scholars conjectured that a higher interest rate can lead to "investment pause". thus, higher interest rates and for that matter higher inflation may delay investment (serven, ) . in terms of the effect of exchange rate devaluation on investment, as noted by bleaney and greenaway ( ) , in general, a lower real exchange rate stimulates investment, and this implies that real exchange rate overvaluation is bad for investment. in general, rodrik ( ) argues that overvalued currencies are associated with foreign currency shortages, rent-seeking, unsustainably large current account deficits, balance of payments crises, and stop-and-go macroeconomic cycles, all of which are damaging to investment and growth. others argue that the optimal response to a lower exchange rate will depend on the country's reliance or otherwise on imported inputs and the level of foreign export. a country that is more dependent on imported inputs will have an increase in variable costs and therefore a reduction in the marginal value of capital (see nucci and pozzolo, for detailed theoretical exposition). but for a country with a larger share of revenues from the export markets, exchange rate devaluation is likely to increase the expected value of its capital and therefore in its level of investment (campa and goldberg, ; nucci and pozzolo, ) . a number of empirical literature have demonstrated a relationship between s africa's poor investment, inflation, and exchange rate depreciation (see bleaney and greenaway, ; serven, ; bleaney, ; hadjimichael and ghura, ; aizenman and marion, ; baldwin and krugman, ) . these listed studies provide enough justification for the inclusion of these variables in the agricultural gross fixed capital formation model. in addition to these general conceptual considerations, we also acknowledge that receipt of agricultural oda is not random i.e., other factors may drive differences in agricultural oda receipts. also, there could be the issue of reverse causality, in that, higher (lower) gross fixed capital formation in agriculture in a particular country could trigger lower (higher) agricultural oda inflows. thus, in our modeling, and to enhance the robustness of our estimates, we also consider agricultural oda to be endogenous. we estimated a two-stage least-squares ( sls) regression, instrumenting agricultural oda with country-level rainfall deviations from the regional ssa mean rainfall. increased deviations in rainfall could lead to erratic rainfall patterns affecting the planting and harvesting patterns of farmers. severe deviation does indeed have the tendency to reduce food production and heighten national food insecurity, and therefore, increase the likelihood of a country receiving oda. the inclusion of rainfall deviations in the agricultural oda equation is consistent with earlier works on aid, which finds that donors to developing countries do indeed respond to recipient need (see harrigan and wang, ; miller, ) . the yearly country-level rainfall deviations are computed from the ssa mean rainfall over the period of the study. an alternate approach will be to use the rainfall deviations from the country's own long-term mean rainfall. for the purposes of a robustness check, we also provide estimates for the latter. in all cases, we include a one-year lag of the rainfall deviation variable in the agricultural oda equation. in addition, to further strengthen the achievement of identification we include a composite governance indicator in the agricultural oda equation as an instrument to capture the strength of local institutions on aid receipt. burnside and dollar ( ) in a neoclassical growth model postulates that the impact of aid will be greater when there are fewer policy distortions affecting the incentives of economic agents. they also argue that effects may work either through increased productivity of capital or via a larger fraction of the aid flow is actually invested. murata et al. ( ) found that foreign aid is improved by the level of institutional quality. the good governance composite variable used was derived from the worldwide governance indicators (wgi), which captures six dimensions of governance. elaboration on the six governance indicators is presented in the data section. as found by dollar and levin ( ) and miller ( ) , aid targets developing countries depending on how well-governed they judge the recipient country to be (see also neumayer, , wright and winters, ) . wright and winters ( ) argue that donors may avoid politically unstable countries, or they may deliver emergency aid rather than make longer-term infrastructure investments in response to corruption, inefficiency, or antidemocratic behavior. thus, we build the specification of the agricultural fixed capital formation equation drawing on the large empirical literature on investment and the literature on aid allocation. the simple bivariate simultaneous equation model which treats agricultural oda as an endogenous variable is written as follow: a. data a. agricultural official development assistance (oda) official development assistance is defined as all resources such as physical goods, skills, technical know-how, financial grants and/or loans (at concessional rates) transferred by donors to recipient governments (riddell, ) . in addition, technical co-operation costs are included as oda, but grants, loans, and credits for military purposes are excluded. transfer payments to private individuals, public donations, commercial loans, and foreign direct investment (fdi) are not also regarded as oda. in general, the fao classifies agriculture oda as financial supporteither grants or "concessional" loans from organisation for economic cooperation and development (oecd) member countries to developing countries for the purpose of achieving food security, nutrition, and agriculture, and rural development. the data on agricultural official development assistance (oda) is obtained from the oecd creditor reporting system which aggregates the data to reflect the over faorelated subsectors, such as agriculture, forestry, fishery, rural development, agricultural policy and management, cooperatives, etc. it must be noted that the new food and agriculture organization (fao) aid database "aidmonitor" also contains the same data, extracted from the oecd creditor reporting system. data on the agricultural gross fixed capital formation (gfcf) is obtained from the food and agriculture organization (fao) faostat database. fao publishes country-by-country data on physical investment in agriculture, forestry, and fishery and measured by the system of national accounts (sna) concept. gross fixed capital formation (gfcf) is measured as the total value of agricultural acquisitions, fewer disposals, of fixed assets during the accounting period plus certain specified expenditure on services. gfcf also includes improvements to existing fixed assets, such as buildings and structures, that increase their productive capacity, extend their service lives, or both. in the case of land, improvements are treated as the creation of a new fixed asset and are not regarded as giving rise to an increase in the value of the natural resource. however, if the land, once improved, is further improved, then the normal treatment of improvements to existing fixed assets applies. the fao agricultural gfcf data consolidates the gfcf data from the united nations statistics division (unsd) and the organisation for economic co-operation and development oecd. previous studies on trends in agricultural capital formation have used this data (see butzer et al., ; larson et al., ) . the rainfall deviations data used to instrument for agricultural oda was derived from the weatherbase website. the data has been used extensively in the area of crop science, environmental science, and climatology to examine the impact of rainfall variability in agricultural production (see covarrubias and thach, ; larson, and lohrengel, ; yukimura et al., ) . to capture deviations in rainfall over time, we computed the country's own average rainfall over the period of the study, from to , and examined each year's deviation from the long-run average country rainfall. we argue that deviations from the country's own average could signal country 'need', and therefore drive oda inflows. for completeness and also as a robustness check, instead of the year-by-year country deviations from the country's own average rainfall, we alternatively generated the yearly rainfall deviations from the ssa average over the period of the study. the estimated results from the latter are presented in the appendix. deviations from the ssa average are in line with the argument that aid will go to countries with the most need (dipendra, ; lahiri and raimondos-møller, ) . these rainfall indicators assume that donors would respond to huge deviations from either rainfall deviations from the country's own average rainfall or that of the ssa average. we obtained the recipient institutional quality indicator variables from the world bank's world governance indicators (wgi). the data have been used by a number of related studies on aid effectiveness (see akanbi, ; miller, ; pinar, ) . as an indicator of the quality of local institutions, countries are ranked on six dimensions of good governance: government effectiveness, control of corruption, voice and accountability, rule of law, political stability, and regulatory quality. as can be seen, all the six indicators are clearly linked to good local institutions, and scaled in units of the standard normal distribution, with mean zero, the standard deviation of one, and a range from - . to . (see miller, ; kaufmann et al., ) . higher values indicate higher governance effectiveness, less corruption, higher voice and accountability, better law and order enforcement, stronger political stability, and higher regulatory quality. we compute a composite institutional quality indicator (labeled ave_wgi) by averaging the six indicators to reflect the overall quality of institutions. as explained in the previous section, we control for oneyear lag of gdp per capita in the agricultural gross fixed capital formation model. we used gdp in purchasing power parity (gdp ppp) per capita which corrects for differences in cost of living and differences in total population for each year for each country. with regards to examining the effect of real exchange rate (rer) distortions, we follow the three-step methodology as rodrik ( ) to obtain a ppp-based index of rer undervaluation (see also rapetti et al., ) . our index of undervaluation is a measure of the domestic price level adjusted for the balassa-samuelson effect. precisely, we first computed the real exchange rate (rer) as the ratio between the nominal exchange rate (xrat) and the purchasing power parity conversion factor (ppp). both xrat and ppp are expressed as national currency units per u.s. dollar with values of rer greater than suggesting that the value of the currency is lower (more depreciated) than indicated by purchasing power parity. however, since ppp is calculated using the entire gdp including non-tradables and non-tradables are also cheaper in poorer countries, we adjust for this balassa-samuelson effect. we adjust for the balassa-samuelson effect by regressing rer on real gdp per capita (rgdpch): where f t accounts for time fixed effects and μ is the error term. this regression yields an estimate of β of − . , which is significant at the % level. the estimated coefficient for rodrik ( ) and rapetti et al. ( ) was − . for all developing countries. percent. our estimated coefficient is in line with balassa-samuelson's prediction. in our case, a % increase in rgdpch is associated with a . % real appreciation. following rodrik ( ) we estimated the undervaluation (underval) as the difference between the actual real exchange rates and balassa-samuelson-adjusted real exchange rates: lnunderval it = lnrer it − lnrer it . when underval exceeds unity, it means the currency is undervalued, and that domestically produced goods are relatively cheaper in dollar terms. the advantage of using the index is that it is comparable across countries and over time. for our sample, underval index has a mean of zero and a standard deviation of . . the data for the the the real interest rate, inflation, and for the computation of the real exchange rate undervaluation measure were obtained from the world bank's world development indicator (wdi) database. our sample consists of ssa countries that have received agricultural oda within the period of the study, from to . table presents the descriptive statistics for the key variables. the mean interest rate in the sample over the period of the study is . % with the mean inflation being %. the mean governance indicator (ave_wgi) of − . on the scale of − . to . , suggests that on average ssa countries have weak institutions over the period of the study. the mean of the individual components of the governance index mirrors that of the index. on average, ssa countries rank low on voice and accountability, political stability, governance effectiveness, rule of law and controlling corruption. the standard deviation of these governance indicators shows, however, variability across countries. in terms of the rainfall deviation variable, we find higher deviations from the ssa average rainfall compared to the within-country deviations. precisely, the high average rainfall deviation suggests high variability in rainfall across countries, whereas countries do not deviate so much from their own long-run rainfall. fig. depicts a positive cross-country association between average agricultural aid and average agricultural gross fixed capital formation in the period - . even though we find a positive correlation, in the next section, we systematically investigate the effects of agricultural aid on agricultural gross fixed capital formation using econometric techniques and controlling for other factors, country-and time-specific effects, and possible endogeneity of agricultural aid. our hypothesis is that agricultural-specific oda increases agricultural fixed capital formation. thus, the paper estimates agricultural fixed capital formation as a function of agricultural-specific oda controlling for several core country characteristics as delineated in the previous section. our relatively long panel dataset of years for the forty ( ) countries allows us to control for time-invariant omittedvariable bias. our first model examines the instantaneous impact of agricultural oda (level effect) on agricultural fixed capital formation. our estimated fixed-effect reduced-form model is presented in table . the fixed-effects technique assumes that the individual-specific effects are correlated with the regressors and therefore the approach removes the effect of the unobserved time-invariant characteristics in order to assess the net effect of the independent variables. the fixed effects in panel data permit us to control for each country's idiosyncratic features and, therefore, to account for their heterogeneity. thus, including both the individual-and time-specific effects into the specification can eliminate a larger portion of the omitted-variable bias. the randomeffect models on the other hand assume that all covariates are uncorrelated with the unobserved effect. this is unlikely to be true. hausman's test justifies the use of the fixed-effects model. we, therefore, present the results from the fixed effect. column reports our specification for agricultural fixed capital formation (investments) and agricultural oda in the same period, whereas column presents the results for a one-year lag of agricultural oda. both models, we argue capture the instantaneous effect of agricultural oda on fixed capital formation in ssa. the coefficient on the agricultural oda variable in period t, is positive and significant at the % level. we find almost similar results if we lag the agricultural oda variable by one year, as shown in column . the only difference is the magnitude. we show that the marginal effect for the impact of agricultural oda in period t on the agricultural fixed capital formation ( . ) is larger than that of the one-year lagged agricultural oda ( . ). the results are consistent with the findings of earlier studies on the general impact of oda on the capital formation (see alvi and senbeta, ) and contrary to studies that find no impact of oda on investment (boone, . it is also contrary to studies that find that aid replaced domestic savings and planned domestic spending (see doucouliagos & paldam, ) . thus, in both regression models in table , we find a significant positive association between agricultural aid agricultural fixed capital formation. one can argue that, because aid to the agricultural sector is partly driven by recipient country's needspotential and/or urgent food insecurity and vulnerabilitiescountries must apply the aid urgently in a manner to address the underlying vulnerabilities. hendrix and brinkman ( ) have shown that food insecurity can indeed trigger political instability and therefore receiving agricultural aid must be properly invested in tangle inputs. thus, in all from our fixed-effect models, we find that agricultural aid either model at time t, or with a one-year lag impacts physical capital formation in agriculture in ssa. in addition, we report strong accelerator effects, as shown by the positive coefficient for the initial income per capita (lnpcgdp (t- )). thus, higher real gdp per capita in the previous year impacts positively on fixed capital formation in agriculture in the current year. it seems agricultural aid receiving countries that perform well in terms of gdp growth are rewarded with more agricultural aid. with respect to the other control variables, interest rate and inflation have no significant impact on fixed capital formation. the results on the interest rate and inflation are consistent with findings by bleaney and greenaway ( ) for general investments. in terms of the effect of undervaluation, an increase in undervaluation in the real exchange rate is associated with an increase in agricultural investments or gross fixed capital. therefore, our findings support the theoretical proposition that countries with a larger share of revenues from the export markets , an exchange rate devaluation is likely to increase investments, and therefore increase the expected value of its capital. the estimate suggests that a percent undervaluation is associated approximately . percent increase in agricultural fixed capital formation during the same period. as noted by rajan and subramanian ( ) , if aid is spent on the production of tradable goods such as agricultural products produced by ssa, the more the supply of factors of production and non-traded domestically produced goods respond to aid inflow. also, as noted by rodrik ( ) , for most countries, periods of rapid growth are associated with undervaluation. in general, our fixed effect models show that foreign agricultural aid affects agricultural fixed capital positively and the effect is very much instantaneous. aside from our basic reduced-form model, we do acknowledge that agricultural oda to a country is not random. thus, oda could be driven by other factors that are not captured by the model as presented in eq. ( ), and as such any observed effect of oda without accounting for this non-randomness cannot be interpreted as causal effects of oda. this raises a typical issue of omitted variable bias. there could also be an issue of reverse causality, in that, higher fixed capital formation in agriculture in a country could trigger lower agriculture oda inflows. we therefore in addition to the simple fixed-effect model, present the results for the estimated agricultural fixed capital formation equation by the fixed-effects instrumental variable (iv) method (using the two-stage least-squares estimator). in explaining the allocation of agricultural aid to ssa, as indicated earlier, we use 'good governance index' and rainfall deviation variables as external instruments for agricultural aid. table presents the -stage least-squares ( sls) fixed-effects results. to examine the instantaneous effect of oda (as done also in the fixed effect model), model includes oda in time, t, whereas model captures the effect of the one-year lag of oda i.e., oda in time t- . columns and present the results first-stage agricultural oda models which while columns and present the results for the second-stage agricultural fixed capital formation models. for the sls estimation, under each model, we first examine the impact of our external instruments on agricultural oda in the first stage, and then the subsequent impact of agricultural oda on fixed capital formation in the second stage. in all estimated models, we find a positive impact of lagged gdp per capita on agricultural oda. thus, the coefficient on the initial real gdp per capita is positive and highly significant in the oda model, as found under the fixed effect model as well. this result could suggest that for poor ssa countries receiving aid, improvement in economic performance is rewarded with more agricultural aid. in terms of the other determinants of agricultural oda to ssa, from robust standard errors in parentheses. *** p < . , ** p < . , * p < . . robust standard errors in parentheses. *** p < . , ** p < . , * p < . . columns and , the coefficients on the two instruments (rainfall deviations from ssa mean and the governance index) are assessed. estimated results using rainfall deviations from the country's own mean rainfall are qualitatively similar and are presented in the appendix. in all both models the coefficients on the composite good governance indicator are positive and significant at the % level. the results imply that a one percentage point increase in governance quality is associated with the range of to percent increase in agricultural oda. note, however, a percentage point increase in governance quality will require a substantial improvement in governance effectiveness, reduction in corruption, improvement in voice and accountability, improvement in law and order enforcement, improvement in political stability, and higher overall regulatory quality. the descriptive statistics as presented in table on a scale of − . to . show that the levels of these governance indicators are quite very low for the average ssa country. thus, an improvement in governance can increase agricultural-linked oda. in addition, we find that rainfall deviations, just like governance are very important for agricultural aid inflows to ssa. the coefficients on the rainfall deviation variable (rfd (t- )) in the first-stage equations in both sls models as presented in table are positive and significant at the % level. our instruments are reasonably strong according to the first stage regression results. according to staiger & stock, ( ) , an ftest statistic of at least shows that the endogenous regressor is not weakly identified. the cragg-donald wald f statistic test for a weak identification test shows that our instruments are plausible, and the estimates are robust across both specifications. thus, overall, we find that recipient countries' institutions and weather situations matter for agricultural oda receipts in ssa. one more factor which matters for agricultural oda receipts is the recipient countries' exchange rate devaluation. we find a negative association between the real exchange rate devaluation and agricultural oda inflows to ssa. exchange rate overvaluation is expected to shrink the tradable goods sector, reduce revenues from exports, and worsen the wellbeing of people who live in the country. deteriorating economic situations will, therefore, drive the need for aid inflows. in terms of other possible drivers of agricultural oda, we don't find any association between agricultural oda inflows, on one hand, domestic interest rate and inflation on the other. we now turn our attention to the second stage gross fixed capital formation (gfcf) regression equations. the estimated results are presented in columns and . the second stage results from the sls estimations confirm that the exogenous component of agricultural oda has agricultural capital formation-enhancing effects. as the results from the reduced-form fixed-effect model presented in table , the coefficient on agricultural oda variable, in the current term, time t and the oneyear lagged term of the variable are both positive and significant. thus, both the current level and the one-year lagged level of agricultural oda have significantly positive coefficients. comparing the simple fixed-effect model results to that of the sls, the key difference is the magnitude of the agricultural oda impact. the coefficient on the agricultural oda as presented in columns and of the sls regressions are quite similar to the fixed-effect model estimates, but they tend to be somewhat higher and closer to one. for example, the sls estimates of β are . and . , compared with the fixed effect estimates of . and . . the evidence-based on these elasticities support the preposition that most agricultural aid intended for fixed capital formation over the period of the study is indeed invested. in summary, the overall instantaneous effect of agricultural oda from both the fixedeffects and the sls regressions is positive: a change in the agricultural oda moves agricultural fixed capital formation in the same robust standard errors in parentheses. *** p < . , ** p < . , * p < . direction. in terms of other controls in the agricultural fixed capital formation models, consistent with the estimated results for the fixed-effect model, we find that gross fixed capital formation is associated positively with real exchange rate undervaluation. thus, overvaluation negatively impacts the formation of agricultural fixed capital. the explanations presented under table for the impact of real exchange rate undervaluation on agricultural fixed capital formation still holds here. the domestic interest rate and inflation have no impact on agricultural fixed capital formation, consistent with the results under the fixed-effect model and that found by bleaney and greenaway ( ) . lastly, while there is a greater understanding of the role of institutions in aid inflows (see maruta et al., ; nunnenkamp et al., ; jones and tarp, ; Ö hler and nunnenkamp, ; akanbi, ; bräutigam and knack, ; , there are important gaps in our understanding regarding which institutions actually matter. for example, Ö hler and nunnenkamp ( ) found that countries with better governance practices, for example, received higher aid allocation. nunnenkamp et al. ( ) in their study on sub-national governments india however did not find any evidence that aid projects by the world bank went to areas with less pervasive corruption for example. we, therefore, examine the associations between the various components of good governance, agricultural aid, and agricultural fixed capital formation. precisely, we explore the impact of government effectiveness (goef), control of corruption (coc), voice and accountability (vaa), rule of law (rol), political stability (ps), and regulatory quality (regq) on agricultural aid flows to ssa. in order to avoid over-identification, we examine the institutional variables as instruments in pairs. the results are presented in table . in model of table , we instrumented agricultural oda with the rule of law and control of corruption, while in model , we used voice and accountability and political stability as instruments for agricultural oda. in model of table , we instrumented agricultural oda with government effectiveness and regulatory quality. some key findings are noteworthy from these regression models. first, we find that agricultural oda inflows into recipient countries depend positively on the and rule of law and control corruption (see model of table ). the coefficient of control corruption and rule of law are positive and significant highly significant. the cragg-donald wald f statistic test for a weak identification test shows that these two instruments are plausible (f-stat. = . ). also, in column of model , the coefficient on the agricultural oda variable in the gross fixed capital formation equation is positive and significant at the % level. contrasting the findings in model with that of model and , we find that voice and accountability, political stability, government effectiveness, and regulatory quality do not strongly correlate with agricultural aid flows to ssa. the coefficients on these variables are positive in all models are positive but not significant. the coefficients on the agricultural oda in the gross fixed capital formation in both model and are also not significant. thus, the key institutional variables critical for agricultural aid flows to ssa are the rule of law and the control of corruption. these findings regarding the specific institutions that matter for agricultural oda suggest that, for ssa countries to attract agricultural aid to boost their capital formation and reduce food insecurity, there must be conscious efforts towards improving the rule of law and controlling corruption. we now turn our attention to the empirics that help answer the question of whether oda has a long-term growth effect on agricultural fixed capital formation. this, even though we are mainly interested in the instantaneous impact of agricultural oda, for completeness, we also examine the long-term growth effect. as noted by mogues & benin ( ) , this estimation is more indicative of the longer-term trajectory that agricultural fixed capital formation may undergo as a result of the inflows of official agricultural development assistance. hence, a growth model is estimated as: in the growth model, a possible path-dependency of growth in agricultural fixed capital formation is accounted for by including each country's past growth of fixed capital formation as an independent variable. allowance is also made for the possibility that low-income countries may have a different growth trajectory than high-income countries by including the lagged level of fixed capital formation; this variable clarifies the nature of convergence or divergence of each country's fixed capital formation over time. thus, the model estimates growth or changes in agricultural fixed capital formation Δ[ln(gfcf it )] as a function of changes in the first lag of agricultural fixed capital formation Δ[ln(gfcf it− )] by following the lagged-investment in the fixed capital concept of eberly et al ( ) and mogues & benin ( ) . in eq. ( ) above, although the objective of the study is to estimate β , the difficulty is to estimate β accurately because the lagged growth term of fixed capital formation correlates with the stochastic error term. for simplicity, rewriting eq. ( ) as; where π it = ν i + ε it , it is evident that both Δ(lngfcf it ) and Δ(lngfcf it− ) depend on the time-invariant effects, ν i . thus, the introduction of the lagged dependent variable makes ols estimation inconsistent and bias (nickel, ; jones & tarp, ) . the ols estimate of β is upward- biased, because Δ(lngfcf it− ) is positively correlated withπ it = ν i + ε it . to avoid the inconsistent estimates of the pooled ols estimation of an ar ( ) process caused by endogeneity, the difference (arrelano and bond estimator) and system-gmm (blundell and bond estimator) estimation techniques are used. the techniques remove the unobservable, time-invariant country fixed effect ν i among other corrections, so as to eliminate the inconsistency caused by the dependence of Δ(lngfcf it− ). thus, the rationale for the differencing is that time-invariant country fixed effects are purged from the data. for the analysis of the results, we will focus on the system gmm. a number of empirical simulations have shown that the system gmm estimator has a lower bias and higher efficiency than the standard first-differences gmm estimator particularly in finite samples (see blundell and bond, ; blundell et al., ) . for robustness purposes, we present both results. column of table reports the result for the difference gmm (arrelano and bond estimator) while column reports that of the system gmm estimator. we find that both the difference and system gmm estimated effect show a positive impact of agricultural aid on capital formation in ssa's agriculture as shown by the coefficient on the agricultural oda variable. however, the coefficient on the agricultural oda in the 'difference model' presented in column is not statistically significant. the coefficient on the agricultural oda variable in the system gmm model is however significant at the % level. our system gmm estimates show evidence that agricultural oda to ssa is associated with growth in agricultural capital formation. the estimated result under the system gmm regression model indeed confirms our findings using external instruments under the sls estimation approach. aid effectiveness still remains a contentious area of debate. sub-saharan africa (ssa) has received a substantial amount of aid, and therefore it is important to understand the impact of such aid. considering the perception that aid has been ineffective (see boone, , we have estimated the instantaneous effect of agricultural aid on agricultural fixed capital formation using a panel of countries in sub-saharan africa (ssa). precisely, we explored whether agricultural aid given to ssa's agriculture does have instantaneous impacts on building the needed physical capital. even though the covid- pandemic and climate change could heighten food insecurity on the african continent, we argue that an instantaneous improvement in agricultural physical capital formation could lessen the impact. it is important to note that, a very long lagged impact of agricultural aid on the agricultural capital formation (more than years) will challenge the ability of ssa countries to deal with the impact of any crisis, such as that of the covid- pandemic or the potential threat of climate change. using a fairly standard investment/agricultural capital formation model that addresses the endogeneity of agricultural oda, with both within-country and cross-country rainfall deviations, and the strength of domestic institutions, and also relying on a comprehensive data on agricultural aid receiving countries, we find that agricultural fixed capital formation depends on aid received for agriculture in the same year (contemporaneous effect). we also find a positive effect of the one-year lag of aid on gross agriculture fixed capital formation. both empirical results suggest an instantaneous effect of agricultural aid on the formation of agricultural capital, which is needed to address any global shocks to food security. this finding has powerful implications for the way we fight crisis-induced food insecurity both in the shortterm and in the long-term. estimates from fixed-effects and sls are quite similar. our findings on agricultural aid are therefore contrary to studies that find that aid, in general, replaced domestic savings and planned domestic spending (see doucouliagos & paldam, ) and supports studies that have found a positive relationship between general aid on investments (lensink and morrissey, ; ) , gomanee et al., ; gang and khan, ) . we argue that since food insecurity could give rise to hunger and political instability as articulated by hendrix and brinkman ( ) , and smallholder farmers constitute over % of the workforce in many ssa countries, it is in the best interest for political leaders to use agricultural aid effectively and instantaneously to maximize the wellbeing of their people. thus, in this study, we do not find strong evidence to support the assertion that agricultural oda replaces domestic savings and spending. we also contribute significantly to the literature on the drivers of aid. in terms of the drivers of agricultural aid to ssa, we find that deviations in rainfall from both country and continent's average rainfall are positively associated with agricultural oda inflows. however, we also find that even though agricultural oda is given to countries to build food production capacities and help such countries better deal with food insecurity, countries with stronger institutions are more likely to receive more agricultural oda. thus even though the recipient country needs are important for agricultural aid receipts, institutions do matter for agricultural aid flows. ssa countries can attract more agricultural oda if particularly, institutions that are responsible for the control of corruption and the enforcement of rule of law are strengthened. good institutions regularly emerge as significant in aid and investment equations (pinar, ; jones and tarp, ; bräutigam and knack, ) , 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isolated from arctic terrains: implications for long-range transportation of microorganisms key: cord- - ozoq hb authors: togun, toyin; kampmann, beate; stoker, neil graham; lipman, marc title: anticipating the impact of the covid- pandemic on tb patients and tb control programmes date: - - journal: ann clin microbiol antimicrob doi: . /s - - - sha: doc_id: cord_uid: ozoq hb the covid- pandemic has currently overtaken every other health issue throughout the world. there are numerous ways in which this will impact existing public health issues. here we reflect on the interactions between covid- and tuberculosis (tb), which still ranks as the leading cause of death from a single infectious disease globally. there may be grave consequences for existing and undiagnosed tb patients globally, particularly in low and middle income countries (lmics) where tb is endemic and health services poorly equipped. tb control programmes will be strained due to diversion of resources, and an inevitable loss of health system focus, such that some activities cannot or will not be prioritised. this is likely to lead to a reduction in quality of tb care and worse outcomes. further, tb patients often have underlying co-morbidities and lung damage that may make them prone to more severe covid- . the symptoms of tb and covid- can be similar, with for example cough and fever. not only can this create diagnostic confusion, but it could worsen the stigmatization of tb patients especially in lmics, given the fear of covid- . children with tb are a vulnerable group especially likely to suffer as part of the “collateral damage”. there will be a confounding of symptoms and epidemiological data through co-infection, as happens already with tb–hiv, and this will require unpicking. lessons for covid- could be learned from the vast experience of running global tb control programmes, while the astonishingly rapid and relatively well co-ordinated response to covid- demonstrates how existing programmes could be significantly improved. every year, march th is celebrated as annual world tb day. this is usually acknowledged across the world by a wide range of activities, to highlight the unsettling fact that mycobacterium tuberculosis, a human-specific pathogen, is still a scourge after millennia of coexistence. it has recently reclaimed top spot as the infectious disease that kills more people in the world than any other infectious pathogen. this year, however, its show was stolen by a newlyemerging pandemic caused by a novel pathogen, severe acute respiratory syndrome coronavirus- (sars-cov- ), which has jumped from animals to humans and causes the disease named covid- -a flu-like disease characterised by severe acute respiratory distress in its most severe form. by the first week of april , a million cases of covid- disease had been diagnosed worldwide, including at least , deaths since the beginning of the epidemic in january . world tb day itself was eclipsed, with events cancelled throughout the world, including our own annual london symposium [ ] . in an extraordinarily short time, covid- has supplanted everything-normal activity, annals of clinical microbiology and antimicrobials so, what about tb when covid- is so front-andcentre globally? clearly tb has not disappeared, but does anyone still care? and if so, are we able to do more than watch as an existing global health problem becomes increasingly neglected-leading to predictable outcomes? on the plus side, with such a long history of intense research and infectious disease management, can tb teach the world anything about how we should deal with covid- ? tuberculosis remains a global health emergency and needs our attention more than ever, given that significant resources are now being diverted to covid- management. to lose sight of the unfinished business of tuberculosis control will jeopardise important milestones, gains and ambitions, and we believe that now more than ever is the time to care about tb in adults and children . in this manuscript, we cover areas of particular concern for both epidemics facing us today. this reflection was developed from a video conversation held by the participants on march and posted online following the cancellation of our world tb day event [ ] . we discussed issues of how covid- would affect control programmes: prioritisation of services, availability of drugs, the effect on hard-to-reach and low-income communities and the role of stigmatisation, how paediatric tb disease might be affected, the possibility of increased disease transmission or disease susceptibility, and the problems caused by likely co-morbidity. we thought it important to look at the situations in both high-income countries (hics) and low and middle-income countries (lmics), and we used the uk and africa as exemplars with which we are most familiar. we also reviewed how control programmes for each disease could learn from each other. we are of course not the only people reviewing and comparing these two pandemics, and we acknowledge the contributions by wingfield et al. [ ] who discussed the negative effect of covid- on tb patients and control programmes, and the union supported by tb alert [ , ] who actively compared and contrast the two diseases, and focused on ways in which tb expertise can be useful for covid- control. as an example of an hic, the uk has a significant tb problem with approximately new cases a year, particularly in london [ ] . there is a specific integrated tb control programme with allocated staff managing all aspects of diagnosis, treatment, contact tracing, outbreak investigation, latent disease, dialogue with communities, and linking to other relevant charities and organizations. in recent years, the numbers of cases have fallen, and multiple and extensively drug-resistant cases have been successfully treated. this tb control programme lies within a single national health service, administered through separate trusts, with healthcare free at the point of care for all citizens. at the time of our video discussion, the uk was in the middle of the first wave of covid- , with the population under lockdown, number of cases and deaths still rising-putting a tremendous strain on the nhs as it struggled to cope with this, and much of normal clinical practice put on hold. london was the uk's epicentre. governmental loans to businesses and freelance workers, and paid sick leave in a high proportion of cases, was put in place to minimise short-term economic damage. working from home was encouraged for many through a good internet structure. africa has a much greater tb burden. in , africa had an estimated % of the million global incident cases of tb and the region also has the smallest rate of decline of tb globally [ ] . although every country within africa will have a different health system, they are limited and quality of tb care is sub-optimal. a -country patientpathways analysis that included six african countries with the highest tb burden on the continent found that less than % of estimated tb patients had documented treatment success [ ] . also, a cascade of tb patient care analysis in south africa reported that only % of tb patients in south africa were diagnosed and successfully treated [ ] . by st april, the covid- pandemic had started in africa, with cases and deaths [ ] . a large rise in cases of covid- was expected as countries ramped up their testing and diagnostic capacity for covid- [ ] in the context of already stretched and poorly-resourced health care systems. it's already apparent that there will be a need to prioritise the care that tb services can deliver. tb control will focus on tb disease rather than prevention (such as the management of latent, non-transmissible tb infection). this arises in part because of a tb workforce being redirected to manage covid- , others being off sick or self-isolating (up to % of healthcare staff ); and the concern that too much social contact within a clinic is likely to result in more viral transmission. the need to reduce contact with patients who see their tb service as a source of both social and medical support may result in reduced adherence and worse outcomes. this will affect those who are least able to self-care-in other words the very people who most need tb services. a potential unintended consequence of the uk and many other government's promotion and enforcement of isolation is that socially-disadvantaged and homeless populations may be more likely to come together in hostels or other settings and hence increase their risk of acquiring and passing on infection. they are also perhaps less able to protect themselves from contact transmission by regular hand washing and use of sanitizers. in households who are self-isolating, a coughing adult may have a viral infection, though could have tb that is then inadvertently passed on to other family members. pre-covid- and brexit, there were regular anti-tb therapy stock-outs. this is likely to get worse as supply chains become harder to sustain during a time of prolonged infection, illness and economic shut down. as a result, not only will tb services have to modify treatment regimens in line with what drugs are available, but there will also be errors in prescribing-leading to more adverse effects and treatment failures. these are issues that every high income country affected by covid- faces. one of the cardinal objectives of the who's end tb strategy [ ] , which proposes the target of ending the tb epidemic in the next years, is the provision of highquality and patient-centred care for tb patients based on the their human rights [ ] . this very ambitious target requires sustained political and financial commitment from african countries toward the provision of basic essential universal health care, and specifically for tb diagnostic, prevention and treatment services. however, the studies cited earlier suggest that, even prior to the onset of the covid- pandemic, the quality of tb care in africa is sub-optimal. covid- will potentially worsen patient care and tb control efforts in africa, given the likely negative impact of the pandemic at the macroeconomic, health system and individual levels in africa. covid- is expected to result in a global economic recession in with the economic downturn particularly worse for the emerging markets and low-income countries, as recently communicated by the international monetary fund [ ] . without gainsaying, the impact of the global economic recession will be worse on the lmics of africa-many of which were either in borderline or full economic recession prior to the coronavirus pandemic. while hics are now releasing economic stimulus packages, this will be practically impossible in african lmics, who often depend on donor funds and natural resources from extractive industries. as these countries are now setting up and/or ramping-up their covid- responses in the midst of a global economic downturn, we have already seen the diversion of political will, scarce financial and the limited human resources in the hitherto weak health system to the covid- responses. as an example, nigeria that has the largest burden of tb in africa and is one of the high tb burden countries globally recently announced that genexpert machines in the country will be diverted to efforts to scale-up covid- diagnosis [ ] . this will definitely have a huge negative impact on basic and essential tb control efforts, including routine diagnosis of tb cases, treatment monitoring by direct observation, provision of tb preventive therapy, and contact tracing among others. tuberculosis in africa is a disease of poverty as in all lmics, most often afflicting the poorest people in the society who also have the least access to basic health care. we also know that socio-economic circumstances are a crucial determinant of health outcomes, in particular for people with tuberculosis. many of the socioeconomic and behavioural factors that could enhance transmission of coronavirus in africa are also the recognised factors that enhance transmission of m. tuberculosis. while patients with chronic cough might hesitate to seek care due to the 'new' stigma and fear associated with covid- , they are very likely going to meet an unprepared and overwhelmed health system when, or if, they do. on the other hand, the interventions proposed to "flatten the curve" in covid- responses e.g. physical distancing, regular handwashing, whole community lockdowns, etc. are going to be disproportionately more challenging for the poorest who most often live in overcrowded conditions, with no or limited access to drinking water, and earn meagre incomes from daily wages. furthermore, very little is known about the pathobiological mechanisms of the covid- caused by the novel sars-cov- especially in populations in africa with a relatively higher prevalence of hiv infection, tb, anaemia and malnutrition, as well as in patients with significant post-tb lung damage. taken together, it is clear that the impact of covid- in africa is going to be disproportionately worse on the very poor and the least-advantaged people, who already bear the largest burden of both communicable and noncommunicable diseases, and also have the least access to basic healthcare. these will include many undiagnosed and current tb patients who are, as a result, very likely to have worse outcomes from their tb. amongst the . million annual deaths from tb, an estimated , occur in children with the majority occurring in resource-poor settings [ ] . child survival from tb depends on timely diagnosis, prompt initiation of treatment, community and health systems support for continuous availability of child friendly medication as well as prevention of transmission from sputum-smear positive index cases-usually adults-to vulnerable young children in households. these important elements of the cascade of care are at stake at a time when resources will be focused on providing care for individuals affected by covid- . the diagnosis of childhood tb is not only made at dedicated clinics of national tb control programs but equally in generic child health clinics and hospital wards. many of these facilities will be closed or overwhelmed with other tasks, and as a result diagnostic opportunity in children will be missed. the majority of children in lmic are not seen by dedicated paediatric specialists, and many general physicians and nurses usually available for their care will be seconded to dealing with adult patients affected by severe respiratory symptoms of covid- instead. available specialist expertise in respiratory medicine switched to diagnosing and treating this new viral disease, which does not appear generally to have similarly severe manifestations in children compared to adults. hence it will be assumed that children will cope better and do not need similar attention from the health services during the covid- pandemic. we are already witnessing this trend in hic where routine clinics are cancelled and paediatric intensive care beds are handed over to adult services. laboratories are likely to be overwhelmed with analyses of respiratory specimens sent for covid- rather than m. tuberculosis or other pathogens, and once the eagerly anticipated xpert cartridges for covid- are rolled out it is easy to imagine that genexpert platforms will be seconded for covid- diagnostics. these issues are not specific for childhood tb as adult tb services are likely to be similarly affected. however, the timely diagnosis of tb in children is even more essential to prevent deaths. families are reluctant to bring unwell children to the hospitals for investigation as everyone is discouraged from using health services at this stage, unless severely unwell. apart from tb meningitis, tb rarely presents as an acute, severe illness in children but progresses silently until tipping points are reached. such subtle presentations are likely to be missed if children cannot be reviewed regularly. given the overlapping presentations of tb and pneumonia in children in the first place, many children are initially placed on a trial of antibiotics but ought to be reviewed in a timely fashion. this does not happen with severely-stretched health services. another important part of services for children is the provision of preventive therapy (ipt) for tb infection in the community, which requires resources to contact trace, screen and eventually implement drug therapy. these services are rudimentary in lmics at the best of times. ipt works, and given that the under year olds are particularly at risk of progressing to tb disease in its absence, the number of cases of childhood tb will most likely rise as a consequence. whether such figures can even be captured when services are near to breaking-point remains to be seen. as most tb in young children is acquired in their own household, social distancing measures that keep a family together for long periods of time are likely to result in more exposure of children to infectious tb index cases. contact screening for covid- should therefore include questions about tb in the household in order to protect young children from additional risks. tuberculosis stigmatisation is a problem in many settings, though more so in lmics. it is likely to rise and be confounded by covid- . stigma is associated with fear, and fear of covid- will increase. this has already been seen in the cases primarily imported into africa-with stigmatization being directed not only at the affected patients but also their carers and family. this applies equally to healthcare workers who are likely to be managing both covid- and tb. the world tb day had an emphasis on destigmatizing tb, but we should be de-stigmatizing any infectious disease. people do not go around spreading disease deliberately within their communities. as such, there is the need for stronger community engagement, including families and community-based groups being enabled to act as advocates. the symptoms of tb and covid- can be similar, with for example cough, fever, breathlessness and malaise being common in both. not only can this create diagnostic confusion, but tb patients who are already stigmatized for coughing will be even more likely to be viewed with concern in lmics, given the fear of covid- . this could result in people being afraid to present to healthcare services when they have such symptoms that in fact result from tb. in a minority of patients, mainly elderly adults and/or those with underlying comorbidities, covid- leads to severe pneumonitis and possibly long-term lung damage. we have much to learn about the long-term effect of this virus on lung function. the clinical presentation of lung disease in tb can be different, yet important interactions between the two diseases can be anticipated and need to be understood. to be diagnosed with covid- does not exclude underlying tb, and in tb endemic settings particular attention should now be paid to this. there are no data currently to inform us of the outcomes of co-infection, or that of covid- in known tb patients. this information will emerge once the covid- pandemic reaches the tb endemic areas of africa and asia. data on long term sequelae for lung health in tb patients are sparse, and going forward, research studies (both laboratory and clinic-based) need to take covid- into account as a possible co-factor in the interpretation of their results. post-tb lung damage was an area that was until recently largely ignored. hopefully this will now change given the potential for such patients to do worse with covid- disease. similar considerations need to be given to covid- / hiv co-infections or underlying tb/hiv co-infection. there needs to be a particular emphasis on possible drug-drug interactions in individuals on medication for tb and/or hiv, who also may be using additional antivirals and immune-modulating agents which show promise against covid- . the impact of covid- on populations and health systems in africa will be very broad. the response, therefore, needs to be equally comprehensive and long term, rather than focused on just covid- . countries in africa will no doubt need help from the rich nations to mount a robust, sustained and regional response. therefore, "it is time" for african countries to galvanize global attention and advocacy right now to substantially increase their investments toward the provision of universal health care, and to comprehensively strengthen their national health systems, with a particular focus on the primary health care and provision of essential diagnostics to the poorest and the least advantaged in society. this should be a wake-up call for countries in africa to substantially increase their investments in health. tuberculosis control has only been possible through robust and consistent diagnosis, accompanied by contact tracing, including in households. this has also been implemented in the early stages of the covid- pandemic in many-but by no means all-countries in order to minimise spread. the associated social distancing has helped to "flatten the curve" in china, south korea and will hopefully be successful in all of the settings where it is currently followed. much depends on it right now. the covid- pandemic reminds us of the importance of this approach to tb too-with prevention being better than cure. community engagement has proven essential in tb control to address stigma, which has already been associated with covid- . mitigation strategies that proved to be successful in tb might also assist in the community control of covid- although the infection dynamics are very different. the incredibly rapid and fruitful interactions of the scientific community to address the covid- epidemic show what can be done when an emergency arises and scientists are focused and work together, with serious research funds being provided over a short time frame. it is encouraging to see the many new initiatives that have already arisen from the covid- pandemic, be it in modelling, artificial intelligence for clinical algorithms to predict disease severity, international clinical trial platforms, or drug and vaccine developments. neither covid- nor tb respect geographical or scientific borders. lessons learnt from this emergency need to be applied to other infectious diseases of global importance, including tb, where a similar emphasis on clinical and research activity would no doubt have a very large impact. without it, we will never control tb. one positive from the covid- pandemic may be that the world becomes more aware of the need to control and eliminate infections through sustained and joined-up working. let's keep the momentum going and not forget tb! tuberculosis is just one of many areas in global public health that will be sidelined and adversely affected by the covid- pandemic. it is important to start thinking critically about these effects, and develop comprehensive mitigation plans where possible. if not addressed, the million incident tb cases and > million deaths from tb that occur annually worldwide will increase, with the negative impact being worst in lmics. a positive aspect to these two pandemics colliding is that people-communities, public health how will covid- affect tb patients and control? tackling two pandemics: a plea on world tuberculosis day covid- and tb: frequently asked questions world health organization. global tuberculosis report . geneva: world health organization finding the missing tuberculosis patients the south african tuberculosis care cascade: estimated losses and methodological challenges covid- pandemic in west africa world health organization. the end tb strategy world health organization. a patient-centred approach to tb care. geneva: world health organization joint statement world bank group and imf call to action on debt of ida countries fg to convert tuberculosis testing machines to covid- 's-minister publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations the cancelled world tb day event, from which this manuscript arose, was organised by ucl tb, lshtm tb centre, the francis crick institute and birkbeck, university of london. received: april accepted: may professionals and policy makers-can learn from each other. perhaps we can look forward to a time when infectious diseases are taken even more seriously and the link between infectious disease and poverty is further recognised such that increased investment in their control results in societal structural changes that benefit all. hics: high income countries; ipt: infection preventive therapy; lmics: low and middle income countries; tb: tuberculosis. all authors contributed equally to the conception, writing, and refinement of the article. all authors read and approved the final manuscript. not applicable. not applicable. not applicable. not applicable. the authors declare that they have no competing interests. key: cord- -neqycg v authors: sewlall, nivesh h.; richards, guy; duse, adriano; swanepoel, robert; paweska, janusz; blumberg, lucille; dinh, thu ha; bausch, daniel title: clinical features and patient management of lujo hemorrhagic fever date: - - journal: plos negl trop dis doi: . /journal.pntd. sha: doc_id: cord_uid: neqycg v background: in a nosocomial outbreak of five cases of viral hemorrhagic fever due to a novel arenavirus, lujo virus, occurred in johannesburg, south africa. lujo virus is only the second pathogenic arenavirus, after lassa virus, to be recognized in africa and the first in over years. because of the remote, resource-poor, and often politically unstable regions where lassa fever and other viral hemorrhagic fevers typically occur, there have been few opportunities to undertake in-depth study of their clinical manifestations, transmission dynamics, pathogenesis, or response to treatment options typically available in industrialized countries. methods and findings: we describe the clinical features of five cases of lujo hemorrhagic fever and summarize their clinical management, as well as providing additional epidemiologic detail regarding the outbreak. illness typically began with the abrupt onset of fever, malaise, headache, and myalgias followed successively by sore throat, chest pain, gastrointestinal symptoms, rash, minor hemorrhage, subconjunctival injection, and neck and facial swelling over the first week of illness. no major hemorrhage was noted. neurological signs were sometimes seen in the late stages. shock and multi-organ system failure, often with evidence of disseminated intravascular coagulopathy, ensued in the second week, with death in four of the five cases. distinctive treatment components of the one surviving patient included rapid commencement of the antiviral drug ribavirin and administration of hmg-coa reductase inhibitors (statins), n-acetylcysteine, and recombinant factor viia. conclusions: lujo virus causes a clinical syndrome remarkably similar to lassa fever. considering the high case-fatality and significant logistical impediments to controlled treatment efficacy trials for viral hemorrhagic fever, it is both logical and ethical to explore the use of the various compounds used in the treatment of the surviving case reported here in future outbreaks. clinical observations should be systematically recorded to facilitate objective evaluation of treatment efficacy. due to the risk of secondary transmission, viral hemorrhagic fever precautions should be implemented for all cases of lujo virus infection, with specialized precautions to protect against aerosols when performing enhanced-risk procedures such as endotracheal intubation. viral hemorrhagic fever (vhf) is an acute systemic illness classically involving fever, a constellation of initially nonspecific signs and symptoms, and a propensity for bleeding and shock. vhf may be caused by more than different viruses from four taxonomic families: arenaviridae, filoviridae, bunyaviridae, and flaviviridae. transmission of hemorrhagic fever viruses is through direct contact with blood and bodily fluids during the acute illness. although patient isolation and specific vhf precautions (consisting of surgical mask, double gloves, gown, protective apron, face shield, and shoe covers) are advised for added security, experience has shown that routine universal and contact precautions are protective in most cases [ ] . aerosol precautions, such as the use of n particulate filters, are only recommended when performing specific potentially aerosol-generating procedures, such as endotracheal intubation. south africa has often played a role of ''sentinel'' for vhf in countries further to the north through the travel and admission of undiagnosed patients to south african hospitals, often with subsequent nosocomial transmission to healthcare workers. for example, cases of marburg and ebola hemorrhagic fevers have been reported in johannesburg in persons initiating travel in zimbabwe [ ] and gabon [ ] , respectively. in a nosocomial outbreak of five cases of vhf occurred in johannesburg [ , ] (figure ). the primary patient was a tour operator who was evacuated from lusaka, zambia. the etiologic agent was determined to be a novel arenavirus and the name ''lujo virus'' was proposed. the source of the patient's infection is unknown, but assumed to be a rodent, as with all other pathogenic arenaviruses. recent field studies of small mammals in zambia did not result in isolation of lujo virus, although another novel arenavirus was discovered [ ] . arenaviruses are divided into two groups: the new world (or tacaribe) complex, and the old world (or lymphocytic choriomeningitis/lassa) complex, with various members of both groups causing vhf in south america and africa, respectively [ ] lassa virus, the distribution of which is confined to west africa, is the only other old world arenavirus associated with vhf [ ] . lujo virus is only the second pathogenic arenavirus to be recognized in africa and the first in over years. some arenavirus infections, especially lassa fever, have shown benefit with the use of the nucleoside analogue ribavirin [ ] . because of the remote and resource poor locations where lassa fever typically occurs, as well as the history of civil unrest in west africa in recent decades, there have been few opportunities to undertake in-depth study of the clinical manifestations or pathogenesis of lassa fever or other vhfs, or the response of these infections to treatment options typically available in industrialized countries. we describe the clinical features of the five recognized cases of lujo hemorrhagic fever (lhf) in the outbreak in south africa and summarize their clinical management, as well as providing additional epidemiologic detail, with a focus on the risks for secondary transmission. the initial description of the outbreak [ ] was published primarily under the auspices of the south african national institute for communicable diseases, which had a blanket ethics author summary viral hemorrhagic fever is a syndrome often associated with high fatality and risk of secondary transmission. in , an outbreak of a novel hemorrhagic fever virus called lujo occurred in johannesburg, south africa, with secondary transmission from the index patient to four healthcare workers. four of the five patients died. lujo belongs to the arenavirus family and is only the second pathogenic arenavirus, after lassa virus, to be recognized in africa and the first in over years. because most viral hemorrhagic fevers occur in remote, resource-poor settings, few in-depth controlled studies of their clinical manifestations, transmission dynamics, pathogenesis, or response to treatment options are possible. we describe the clinical features of the five cases in this outbreak and summarize the clinical management, as well as providing additional epidemiologic detail. lujo virus causes a clinical syndrome remarkably similar to lassa fever. the treatment options used in these five cases are discussed as well as the recommended precautions to prevent secondary transmission. approval for use of all the patients' data. the same data set has been used for this publication, with ethics committee approval, with the exception of further data collated on the one survivor, who provided written consent for use of data and images related to her illness. case descriptions case . the initial case and primary patient (patient ) was a year old white female who lived on the outskirts of suburban lusaka, zambia. she kept horses, dogs and cats at her house and evidence of rodents was found in her stables (personal communication, r. swanepoel). the patient fell sick on september (illness day [id]- ) with the abrupt onset of fever, myalgia, sore throat, and headache, for which she took over-the-counter antipyretics and analgesics. the next day she described nonbloody diarrhea and vomiting. a mild erythematous rash appeared on id- on her chest and upper arms. fever up to uc continued intermittently, escalating on id- , accompanied by retrosternal chest pain and worsening sore throat, after which she presented to a clinic in lusaka (id- ), where she was given broad spectrum antibiotics. by id- the rash covered her entire body. myalgias became more prominent and her face was noticeably swollen. rapid deterioration occurred on id- with progressive confusion and generalized tonic-clonic seizures. she was intubated with some difficulty using only succinylcholine and started on further antibiotics, including ceftriaxone, ciprofloxacin and ampicillin. the patient was evacuated by air ambulance to a private tertiary care hospital in johannesburg on september (id- ). the glasgow coma score was / , with contracted non-reactive pupils and absent corneal reflexes but no papilledema-findings consistent with transtentorial brain herniation syndrome and damage to the pontine tegmentum from diffuse cerebral edema. generalized edema, including of the face and neck, was present. there was no visible hemorrhage. a fine macular rash was observed over her torso and legs. an eschar resembling a tick bite was visible on her right foot. diffuse interstitial infiltrates with bibasal atelectasis was noted on chest radiography. the patient received a tentative diagnosis of tick bite fever (rickettsia africae) and was started on intravenous (iv) cefepime, clarithromycin, and linezolid, along with lactated ringers solution and dobutamine. mechanical ventilation was continued (fio . ; bipap / mmhg; rate ). the p a o /f i o ratio was . on id- progressive organ failure occurred. oliguria was followed by a high anion gap metabolic acidosis and worsening generalized edema. continuous veno-venous hemodialysis was commenced. a ct scan of the brain showed extensive cerebral edema with compression of the brainstem ( figure ). an eeg showed diffuse slowing. blood tests on id- demonstrated leukocytosis ( /l), thrombocytopenia ( /l), elevated hepatic transaminases (ast , iu/l, alt iu/l) and lactate dehydrogenase (ldh , iu/l), and mildly elevated c reactive protein (crp) ( mg/l). the wbc rose to /l the next day . blood cultures remained negative, as well as tests for malaria, typhoid fever, brucellosis, syphilis, and autoimmune disease. rapidly progressive hemodynamic collapse and death occurred on id- despite inotropic and vasopressor therapy. case . patient , a year old white male, was the paramedic who accompanied patient on the medical evacuation flight from zambia to johannesburg, subsequently returning to lusaka. he participated in the intubation of patient at the referring hospital wearing disposable gloves but no gown, mask or face visor. no specific exposure to blood or other bodily fluids was noted. on september (id- ), nine days after last contact with the index case, patient noted the abrupt onset of fever, headache and myalgias. three days later (id- ) he was admitted to a hospital in lusaka for a possible upper respiratory infection and treated with oral amoxicillin and antipyretics. on id- he developed a diffuse, erythematous skin rash, sore throat, and worsening myalgia and his fever rose to uc. intravenous fluids and antibiotics were begun. on id- he was transferred to the same hospital in johannesburg as patient . initial evaluation showed him to be fully awake and alert with a diffuse maculopapular eruption on his chest, arms, legs and back, sub-conjunctival hemorrhage, face and neck swelling, and pharyngitis, with ecchymoses on the hard and soft palates. he began to have non-bloody diarrhea. clinical laboratory examination revealed thrombocytopenia ( , /ml); leucopenia ( /l); elevated transaminases (ast iu/l, alt iu/l), ldh ( iu/l), and procalcitonin ( , ng/ ml); marginally elevated crp ( ) ; a positive d dimer (. mg/ ml); and microscopic hematuria. the inr was . and the partial thromboplastin time. (ptt) was elevated to seconds. tests for malaria, rickettsia, and salmonella were negative. a presumptive diagnosis of thrombotic thrombocytopenic purpura was made and plasmapheresis initiated on id- . prominent bleeding from the central vein insertion site was noted. on id- the patient was seen by the intensive care unit (icu) physician who cared for patient and an epidemiologic link was noticed. vhf precautions were immediately implemented. given the history, possible filovirus infection was considered and contact tracing of the first patient was commenced by members of the hospital infection control team. modest improvement in patient 's condition was noted after plasmapheresis, with the platelet count increasing to , /ml. however, rapid clinical deterioration began on id- , including altered mental status, oliguria, metabolic acidosis, and progressive generalized edema. sustained low efficiency dialysis was begun and the patient was intubated due to worsening ards (p a o / f i o ratio ). fulminant hepatitis (ast , iu/l; alt , iu/l; ldh , iu/l), encephalopathy, and shock ensued and the patient died on id- despite inotropic and vasopressor support. case . on october , the day of patient 's death, contact tracing revealed that an icu nurse (patient ) who cared for patient was admitted to a private hospital west of johannesburg, close to her family home. patient was a year old black female who became ill on september (id- ), nine days after caring for patient (a previous publication on this outbreak erroneously cites this patient's first day of illness as september ) [ ] . she was primarily involved in turning and cleaning patient , including washing the corpse and removing the dialysis catheter after her death. infection control precautions in the care of patient included providing care in an isolation room and wearing of surgical gowns, latex gloves, surgical masks, and plastic visors. no needle stick injuries or splashes of blood or bodily fluids were reported. patient 's illness began with headache and myalgia followed by sore throat, high fever, and rigors on id- . oral amoxicillin and antipyretics were started by her general practitioner. worsening headache and fever prompted hospitalization and isolation on id- , where nausea, abdominal cramps, non-bloody vomiting, and dysphagia were reported and a fine, macular rash noted on her trunk. (nb: although paweska et al. [ ] reported that no rash was seen in the black patients with lhf, subsequent review of the treating physician's notes confirmed that a rash was indeed seen in this patient.) clinical laboratory testing on admission was limited but demonstrated thrombocytopenia ( , /ml) and normal transaminases (ast iu/l, alt iu/l). renal function was normal. initial therapy consisted of iv fluids and ceftriaxone, fluconazole, and omeprazole. the patient's condition worsened on id- with non-bloody diarrhea, worsening rash, and peri-orbital and facial swelling. subconjunctival hemorrhage was noted. clinical laboratory analysis showed leukocytosis ( , /ml), worsening thrombocytopenia ( . /ml), and drastic elevations of liver enzymes (ast , iu/l; alt iu/l; ldh , iu/l). the quantitative d-dimer was markedly elevated(. . ug/l). oral ribavirin ( , mg loading dose followed by mg q hours) and iv gancyclovir ( mg/kg q hr) were begun, the latter to cover the possibility of disseminated herpes virus infection. nevertheless, the patient's condition worsened on id- , with continued diarrhea and facial edema, progressive mental obtundation, thrombocytopenia ( , /ml) and persistently elevated transaminases (ast , iu/l; alt iu/l). a decision not to institute intensive care was taken collectively by the provincial outbreak investigators given the circumstances at the time and the facilities available at the hospital. the patient became comatose and died on id- . case . patient was a year old black female with a history of aids and a cd count of . she worked as a cleaner and was involved in the disinfection of the hospital room where patient died, which was performed wearing a scrub gown, surgical mask, plastic visor and surgical latex gloves. no specific exposures to blood or bodily fluids were reported. patient fell ill on september (id- ), days after cleaning patient 's room. initial complaints included headache, dry cough, rhinitis, sore throat, myalgias and left sided chest pain. she visited her general primary care practitioner where a fever of . uc was recorded and amoxicillin and diclofenac were prescribed. five days later (id- ), she presented to the infectious disease clinic at her local hospital. on the basis of fevers, sweating and an abnormal chest radiograph, outpatient therapy for tuberculosis was started. however, her condition continued to deteriorate and she was admitted to her local hospital on id- . at this point, the contact tracing team had located her and she was transferred to a tertiary academic hospital where she was noted to be confused with photophobia, nausea and vomiting. physical exam showed candidiasis and generalized lymphadenopathy. lumbar puncture and cerebrospinal fluid analysis showed five neutrophils and no lymphocytes, markedly elevated protein (. g/dl) and elevated glucose ( mmol/l), which were considered consistent with a diagnosis of tuberculous meningitis. clinical laboratory analysis revealed thrombocytopenia ( , /ml), elevated transaminases (ast iu/l, alt iu/l), mild renal dysfunction, a high anion gap metabolic acidosis, and a positive hepatitis b surface antigen. the patient's confusion worsened and fatal cardiac arrest occurred on id- . case . patient was a year old white female who worked as an icu nurse caring for patient from september - . she had significant exposure to blood and bodily fluids, including cleaning up vomitus and changing bloody dressings over the insertion site of the central catheter on september . although there was not yet a particular concern of vhf when the nurse was caring for patient , she reported wearing plastic aprons, disposable gloves, and surgical masks, although she admits to potential lapses in the consistent wearing of this apparel. along with other contacts, patient was placed on twice daily temperature monitoring. on october (id- ), ten days after her last exposure to patient , she noted a temperature of . uc along with retro-orbital headache, nausea, and significant anxiety and was admitted to the hospital. blood tests revealed thrombocytopenia ( , /ml), leucopoenia ( , /ml), normal levels of hepatic transaminases and an elevated d-dimer ( . mg/ml). a diagnosis of probable vhf was made (this was days before an etiologic agent was identified). since iv ribavirin was not available, oral ribavirin ( g loading dose followed by g q hrs) was begun on id- along with atorvastatin ( mg qd) and nacetylcysteine ( mg q ), both for their immunomodulatory and anti-inflammatory effects [ , ] , and anxiolytics. on id- myalgias became prominent and thrombocytopenia worsened ( , /ml). on id- the temperature was . uc and non-bloody diarrhea and vaginal bleeding began, despite the patient being midcycle. laboratory tests on id- show a leukocyte count of , /ml, elevated transaminases (ast iu/l, alt iu/l), and a prolonged ptt of seconds (control seconds). drowsiness and exudative pharyngitis, including a peritonsillar pseudo-membrane, were present. on id- the patient complained of odynophagia and facial edema and a resting tremor were noted ( figure a ). despite being clinically hypovolemic, relative bradycardia (hr /minute) was present. thrombocytopenia ( , /ml) and transaminitis (ast iu/l, alt iu/l) worsened. intravenous recombinant factor viia ( . mg q hrs) was begun and the n-acetylcysteine was switched to iv administration ( g q hrs). on id- , the facial edema was slightly improved but palatal ecchymoses were noted along with conjunctival injection. to cover possible bacterial or fungal superinfection, iv cefepime ( g q hrs) and fluconazole ( mg q hrs) were started. non-bloody diarrhea and hypotension (bp / mmhg) with relative bradycardia (hr /min) persisted on id- . the patient became tachypnoeic, with basilar crackles noted on auscultation. a decision was made to intubate the patient but the procedure, although ultimately successful, proved difficult due to the swollen airway with a pseudo-membrane extending to the glottic folds. multiple, coalescent hemorrhagic areas were present in the hypopharynx. minor contact bleeding followed suctioning. a central line was inserted, with significant bleeding around the insertion site. ribavirin was continued via naso-gastric tube until a supply of iv ribavirin was finally obtained and administered at mg/kg q hrs in place of the oral drug. the patient's condition improved on id- , with better hemodynamic parameters and reduction in mechanical ventilation (fio . ). no focal neurologic deficits were noted on interruption of sedation. subconjunctival hemorrhage was noted and a fine, blanching, erythematous, maculopapular rash appeared on her trunk, arms and legs, sparing the palms and soles ( figure b and c). the patient continued to steadily improve, with the nadir of thrombocytopenia on id- ( , /ml) coinciding also with the peak transaminase level (ast iu/l, alt iu/l). the rash resolved by id- . distal neuropathic weakness appeared on id- and hepatomegaly and splenomegaly on id- . she was weaned from mechanical ventilation on id- . however, on id- she developed sinus tachycardia ( /min) associated over the following four days with basal crackles and an s gallop rhythm treated with diuretics and carvedilol. this finding was attributed to myocarditis, a conclusion supported by the finding of an elevated nt-pro bnp level ( pg/ml). on id- , the ten day course of iv ribavirin was completed and ribavirin, recombinant factor viia, and n-acetylcysteine were stopped. no further bleeding was noted. thrombocytopenia improved ( , /ml) and the ast was down to iu/l, although the ptt was still elevated ( sec) on id- . the russell's viper test for lupus anticoagulant was weakly positive. the patient recovered slowly and was discharged from hospital on november (id- ). neurologic features were prominent during the patient's recovery. anxiety, mood fluctuation, and confusion were considered consistent with post-traumatic stress disorder for which she was treated with antidepressants and anxiolytics, which were slowly weaned after one year. distal critical illness peripheral neuropathy and myopathy, tremors, and weakness persisted for at least months after hospital discharge. no hearing loss was noted, although formal audiometry was not performed. her sinus tachycardia resolved by id- . complete nonscarring alopecia developed from id- and resolved slowly over a four month period. repeat tests for lupus anticoagulant were negative. the five patients' ages ranged from to years. there were two white females, two black females, and one white male. the incubation periods of the secondary and tertiary cases ranged from - days. four of the five patients died (cfr %). signs and symptoms. the signs and symptoms of the five patients are presented in table . in all cases, the clinical illness began with the abrupt onset of common and nonspecific symptoms, including fever, malaise, headache, and myalgias, that would not particularly raise suspicion of vhf. sore throat (in one case accompanied by pharyngeal exudates), non-bloody diarrhea, and nausea and vomiting readily ensued, sometimes accompanied by retrosternal or epigastric pain. a blanching erythematous maculopapular rash on the torso extending to the limbs, but sparing the palms and soles, appeared toward the end of the first week of illness in / patients and seemed to coalesce before fading and disappearing in the sole survivor by id- . subconjunctival injection or hemorrhage and swelling of the face and neck appeared slightly after the rash in most cases, around the end of the first week of illness. neurological signs were less frequent, but included tremors and seizures, the latter in the end stages of disease and accompanied by cerebral edema noted on ct scan. hepatomegaly and splenomegaly developed in the survivor by id- persisting until id- . no episodes of major hemorrhage were noted, although minor hemorrhage was common in the later stages of disease, including the aforementioned sub-conjunctival hemorrhage, palatal ecchymoses, and bleeding at injection sites. rapid clinical deterioration consistent with shock and multi-organ system failure was noted between ids - , with death a mean of nine days (range - days) in the four fatalities. the simplified acute physiology score ii (a predicted mortality score derived from measurement of various physiologic parameters hours after icu admission) for the four fatal cases ranged from . % to %, compared to . % for the surviving patient. convalescence was protracted for the survivor. clinical laboratory findings. clinical laboratory findings for the five patients are presented in table . typical findings included early leucopenia and lymphocytopenia followed later by leukocytosis, thrombocytopenia, and elevated ldh and transaminases, with ast generally - times greater than alt. elevated d-dimer levels and prolonged ptt consistent with disseminated intravascular coagulopathy (dic) were noted in three patients. no red cell fragmentation was seen but microscopic hematuria was documented in / patients. other notable laboratory results included mildly elevated bun ( / patients) and creatinine ( / patients) and normal or slightly elevated levels of crp and procalcitonin. clinical management. although epidemiological links were made between many of the patients as the outbreak progressed, the diagnosis of arenavirus infection was not made until october (id- of patient 's illness). furthermore, the five patients were hospitalized at three different centers in south africa and treated by different healthcare workers. thus, there was little opportunity for uniformity of clinical approach. management of the nonsurvivors included iv fluids ( / ); broad spectrum antibiotics ( / ); transfusion of packed red blood cells, platelets, and fresh frozen plasma ( / ); hemodialysis ( / ); mechanical ventilation ( / ); plasmapheresis ( / ); and oral ribavirin ( / , but the patient received only three doses before death). the surviving patient received many of these same treatments. distinguishing characteristics of her care which could have played a role in her survival include rapid commencement of ribavirin (oral ribavirin was begun on id- with conversion to iv on id- ), and the administration of recombinant factor viia, n-acetylcysteine, and atorvastatin on id . based on the five cases of lhf recognized to date, the clinical disease associated with lhf is remarkably similar to lassa fever [ ] . surprisingly, the two viruses are genetically quite distinct (up to . % on the nucleotide level), with lujo virus grouping much closer genetically to old world arenaviruses not associated with vhf [ ] lassa fever classically begins with non-specific signs and symptoms including fever, general malaise, headache, myalgia, chest or retrosternal pain, and sore throat with progressive diarrhea and other gastrointestinal involvement [ , ] . severe cases may progress to a capillary leak syndrome with septic shock, rash, facial and neck swelling, and multi-organ system failure. the facial and neck swelling seen in both lhf and lassa fever appear to be specific to old world arenavirus infection and may help differentiate it from other african vhfs. like in lassa fever (and despite the slight misnomer ''vhf''), major bleeding was not a prominent feature in the patients with lhf, although minor bleeding was common. the ast and alt are typically elevated in lassa fever, with ast much greater than alt and high levels of ast associated with a poor prognosis [ ] . this same pattern was seen in all five patients with lhf, with the only survivor manifesting the lowest peak ast and ast: alt ratio. some distinctive features of lhf relative to typical lassa fever were the abrupt disease onset (typically indolent in lassa fever) and the presence of dic, which is generally not considered to be part of the pathogenesis of lassa fever, although the matter has not been extensively studied [ ] . although rash is consistently seen in light-skinned persons with lassa fever, for unknown reasons it is almost never seen in blacks. all of the white patients and one of the two black patients with lhf manifested a very prominent rash. interestingly, the black patient without rash was hiv infected, suggesting that the rash of lhf may be immune mediated. patient also had relative bradycardia, an interesting finding given reports of depressed cardiac function in an animal model of arenavirus infection [ ] . the cfr associated with this outbreak of lhf was %. the cfr of hospitalized patients with lassa fever is typically in the - % range, ranging up to % in some nosocomial outbreaks [ ] . however, mild and asymptomatic lassa virus infection is thought to be common, with mortality rates less than % when infection in the community is considered [ , ] . no antibody survey of case contacts or community members in the region of origin of the index case in zambia has been conducted to determine if mild or asymptomatic infection with lujo virus occurs. the four nosocomial infections of lujo virus illustrate the risk to healthcare workers. although no specific exposures were reported and some degree of personal protective equipment was worn by all four secondary or tertiary cases, it appears that strict barrier nursing practices were not always maintained and full vhf precautions were often implemented late in the course of treatment, if at all. furthermore, the four infected healthcare workers generally had very close and sometimes prolonged contact with the patient, including in closed settings, such as the medical evacuation flight of patient , augmenting the possibility of exposure to blood and bodily fluids. they also performed procedures that are often considered to be high risk, such as endotracheal intubation, insertion of indwelling intravascular catheters, and dialysis. the transmissibility of other emerging viruses such as sars and mers coronaviruses has similarly been enhanced when such procedures have been performed [ ] . in addition to the secondary/tertiary cases, another persons were identified as contacts and monitored, including support staff (kitchen, laundry, cleaning), laboratory and radiography technicians, and nursing staff. we did not categorize contacts in terms of risk at the time, but now estimate that at least of these would be reasonably categorized as high risk. nevertheless, no suspected cases of lhf were noted in this group. we suspect that the degree of transmissibility of lujo virus is likely analogous to that of lassa virus, for which, although reliable reproduction numbers and secondary attack rates are difficult to ascertain, they are generally thought to be low. nevertheless, occasional outbreaks with secondary and tertiary cases are sometimes seen, especially when barrier nursing practices are not maintained [ , ] . until the matter can be studied more thoroughly, vhf precautions should certainly be implemented for all suspected and confirmed cases of lhf, with specialized precautions to protect against aerosols when performing endotracheal intubation [ ] . despite the high prevalence of hiv infection in many areas of sub-saharan africa, including some areas where vhf is common, data are scarce on hiv and hemorrhagic fever virus co-infection, such as was the case with our patient . she was also infected with hepatitis b virus. a year old sierra leonean man with a history of hiv infection and chronic progressive neurological deterioration was infected with lassa virus in [ ] the patient survived despite severe disease requiring intubation and mechanical ventilation. in the - outbreak of ebola virus in uganda, the cfr was not statistically different between those who were hiv positive and negative [ ] . the samples were anonymously tested and no clinical data were reported. although the clinical data on patient are also sparse, there were no obvious differences in the clinical manifestations of lhf in this patient compared to the others, with the exception of the aforementioned absence of rash. it is also interesting to note that her peak fever ( . uc) and leukocyte count ( /l) were not particularly high, consistent with her compromised immune system. there have been very few controlled studies on the management of vhf. most recommendations represent the informal consensus of experienced clinicians and investigators. supportive therapy is the mainstay [ ] . the pathogenesis of severe cases of vhf is thought to be similar to severe sepsis, with a severe inflammatory response syndrome mediated in part by various soluble cytokines and chemokines and nitric oxide [ ] . therefore, the basic management principles of shock are also recommended for vhf [ , ] however, since most vhfs occur in resourcepoor areas with little access to advanced icu medicine, opportunities to use and make observations on the efficacy of these or other advanced treatment options are rare. although obviously not a controlled trial, we were nevertheless able to make some detailed observations on the management of five patients with lhf, who were often treated in more advanced healthcare settings. the most detailed data are from patient , who was the only patient for whom a specific diagnosis of vhf was considered and confirmed early in the course of disease. despite receiving ribavirin at disease onset, patient 's clinical status deteriorated and her illness was severe and prolonged. although these results could be interpreted as lack of efficacy of ribavirin against lujo virus, this is unlikely considering the drug's proven efficacy in other arenavirus infections [ , [ ] [ ] [ ] of greater importance was probably the fact that ribavirin was administered orally for the first days of treatment. efficacy of oral ribavirin for arenavirus infection has not been definitively shown and, in light of the significant first-pass hepatic metabolism resulting in an oral bioavailability of only , %, it is unlikely that oral administration reliably reaches the minimum inhibitory concentration for arenaviruses in serum [ ] serum levels are undoubtedly further diminished by decreased gut absorption, vomiting, and diarrhea in these severely ill patients. various adjunctive therapies with demonstrated or theoretical efficacy in severe sepsis were administered to patient and a few of the other patients, including hmg-coa reductase inhibitors (statins), n-acetylcysteine [ , ] , recombinant factor viia, [ , , ] mechanical ventilation, plasmapheresis, and hemodialysis. animal models of sepsis have suggested that statin drugs may improve outcomes in septic shock [ , ] . furthermore, a large, population-based cohort analysis in canada showed reduced risk of sepsis in patients with cardiovascular disease who were treated with statins [ ] . patient enrolment is currently ongoing for prospective trials of statin therapy after the development of sepsis. n-acetylcysteine is an antioxidant and free radical scavenger that resulted in decreased nuclear factor-kb and interleukin- in patients with sepsis, suggesting a blunting of the inflammatory response [ ] . recombinant factor viia is a prohaemostatic agent thought to act at the local site of tissue injury and vascular wall disruption by binding to exposed tissue factor to promote generation of thrombin and platelet activation. [ ] . the drug has been used in hemophilia and other coagulation disorders, as well as in liver disease, reversal of anticoagulant therapy, and for episodes of excessive or life threatening bleeding related to surgery or trauma [ , ] . other therapies being explored for sepsis and, in some cases specifically for vhf, such as the recombinant inhibitor of the tissue factor/factor viia coagulation pathway, rnapc , and activated protein c, were not used in this outbreak due to lack of availability and/or risk of bleeding. the seemingly counterintuitive use of anticoagulants like rnapc stemmed from work with an ebola virus animal model to ameliorate the effects of tissue factor resulting in dic [ ] . it is difficult to assess the contribution of the various therapies to the patient outcomes. although hemofiltration has been suggested in patients with refractory hemodynamic septic shock, with a significant decrease in icu mortality in responders [ ] , and plasmapheresis appeared to have a brief positive effect in patient , we are reluctant to advocate treatments or procedures that potentially increase healthcare worker exposure to blood. in fact, one explanation for the high secondary attack rate associated with this outbreak could be that such high-risk procedures were frequently undertaken. many of the drugs employed in the management of patient are already clinically approved. investigation of many of these compounds in animal models of vhf is warranted, including in lhf model using strain /n guinea pigs [ ] . ideally, controlled clinical trials in humans would also be undertaken, although the feasibility of this is dubious for most vhfs, with the possible exception of lassa fever, for which many infections occur across west africa, or perhaps through a ''multicenter'' approach through advanced planning with ministries of health and other partners in endemic areas for vhfs [ , , ] . until controlled efficacy data are available, and considering the high cfr often associated with vhf, we feel that it is both logical and ethical to explore the use of these approved compounds in treatment of patients with vhf when possible. treating clinicians should make a concerted effort to collect and publish detailed, repeated, and systematic clinical observations to facilitate objective evaluation of their efficacy. the pace of discovery of arenaviruses has increased considerably in recent years, with over ten new viruses being isolated since . pathogenic arenaviruses will almost certainly continue to be discovered. furthermore, rapid population growth, especially in africa, and incursion for both economic and leisure activities into natural habitats harboring rodents will likely put humans at risk. the clinical findings and management experience reported here will be of use to clinicians faced with patients with arenavirus infections and as well as other vhfs. the day of illness that the value was noted is in parentheses. *patients , , and received transfusions of packed red blood cells, platelets, and fresh frozen plasma during the course of their illnesses. abbreviations: alt-alanine aminotransferase, ast-aspartate aminotransferase, crp-c reactive protein, esr-erythrocyte sedimentation rate, hb-hemoglobin, hcthematocrit, inr-international normalized ratio, ldh-lactate dehydrogenase, nd-not done, pct-procalcitonin, ptt-partial thromboplastin time, wbc-white blood cell count. doi: . /journal.pntd. .t infection control for viral haemorrhagic fevers in the african health care setting outbreak of marburg virus disease in johannesburg unexpected ebola virus in a tertiary setting: clinical and epidemiologic aspects nosocomial outbreak of novel arenavirus infection, southern africa genetic detection and characterization of lujo virus, a new hemorrhagic feverassociated arenavirus from southern africa novel arenavirus, zambia arenavirus infections lassa fever. effective therapy with ribavirin a case-control study of the clinical diagnosis and course of lassa fever hmg-coa reductase inhibitor simvastatin profoundly improves survival in a murine model of sepsis statins and sepsis in patients with cardiovascular disease: a population-based cohort analysis physiological and immunologic disturbances associated with shock in a primate model of lassa fever lassa fever, a new virus disease of man from west africa. i. clinical description and pathological findings a prospective study of the epidemiology and ecology of lassa fever aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review an outbreak of lassa fever on the jos plateau review of cases of nosocomial lassa fever in nigeria: the high price of poor medical practice lassa fever in france ebola hemorrhagic fever: novel biomarker correlates of clinical outcome : viral hemorrhagic fevers treatment of marburg and ebola hemorrhagic fevers: a strategy for testing new drugs and vaccines under outbreak conditions surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock treatment of bolivian hemorrhagic fever with intravenous ribavirin brief report: treatment of a laboratory-acquired sabia virus infection treatment of argentine hemorrhagic fever review of the literature and proposed guidelines for the use of oral ribavirin as postexposure prophylaxis for lassa fever mechanism of action and value of n-acetylcysteine in the treatment of early and late acetaminophen poisoning: a critical review the effect of n-acetylcysteine on nuclear factor-kappa b activation, interleukin- , interleukin- , and intercellular adhesion molecule- expression in patients with sepsis the activation of factor x and prothrombin by recombinant factor viia in vivo is mediated by tissue factor efficacy and safety of recombinant factor viia for treatment of severe bleeding: a systematic review low-dose recombinant factor viia for trauma patients with coagulopathy simvastatin decreases nitric oxide overproduction and reverts the impaired vascular responsiveness induced by endotoxic shock in rats highvolume hemofiltration as salvage therapy in severe hyperdynamic septic shock severe hemorrhagic fever in strain /n guinea pigs infected with lujo virus new opportunities for field research on the pathogenesis and treatment of lassa fever lassa fever in guinea: i. epidemiology of human disease and clinical observations the authors would like to thank cecilia gonzales, landon vom steeg and rene kleyn for assistance preparing the manuscript. checklist s strobe checklist. (pdf) key: cord- - t gyy authors: john, nitin ashok; john, jyoti elgiva title: implications of covid- infections in sickle cell disease date: - - journal: pan afr med j doi: . /pamj. . . . sha: doc_id: cord_uid: t gyy sickle cell disease is a major concern of public health significance in africa. nearly / (rd) of the global burden of sickle cell disease (scd) is found to be in sub-saharan africa. there is increased mortality risk in sickle cell disease patients in africa due to associated complications such as acute chest syndrome, asthma, pulmonary emboli and sepsis. sickle cell disease management is the major contributor of financial burden on the government. moreover, there is a shortage of medical specialists in africa. covid- pandemic has further led to devastating impact on economy and health globally. the chances of scd patient contracting covid- infections are higher as these patients are immunocompromised and may be at a higher risk of mortality. practicing preventive measures including isolation and social distancing by these patients will prevent mortality rates as well as economic burden on government in the present unprecedented covid- pandemic. world health organization has identified sickle cell disease (scd) as a major concern of public health significance. it has been estimated that around % of the global population carry sickle cell trait genes. around / rd of the sickle cell disease patients of the global burden reside in sub-saharan africa [ ] . scd has been a neglected cause of childhood mortality in african countries. in view of the huge population of scd patients in africa, the government has to bear large financial burden for management of this haemoglobinopathy. governments in africa have to struggle while addressing health concerns in scd by regularly screening all newborns for hbs, providing hydroxyurea therapy and prophylactic medication for pneumococcal infections as public health measures. the perpetual problem of acute shortage of medical specialist across the region adds to further woes of the governments [ ] . covid- pandemic caused by corona virus (sars cov ) is having a devastating effect on socioeconomic and health indicators in counties worldwide as well as in africa. the additional financial burden of supporting health care management system in tackling covid- impact at the same time preventing mortality rate of covid- deaths is a matter of great concern in africa [ ] . pathophysiology of sickle cell disease: the pathogenesis of the sickle cell disease is attributed to the polymerization of the deoxygenated hbs. the polymerization leads to alteration in the normal biconcave shape of the red blood cells making them rigid and more prone for intravascular haemolysis. as a consequence of repeated hypoxia driven polymerization of hbs there is development of cyclic cascade leading to blood cell adhesion, vaso-occlusive crisis and ischemic reperfusion injury. scd patients may develop complications such as acute chest syndrome, pulmonary embolism and stroke [ ] . hbs/beta+thalassemia has been observed in west africa [ ] , scd has been a neglected disease in africa for many years and had led to the death of about - % of the affected as the disease remains undiagnosed during the childhood. the various studies done in africa were found that scd patients have higher mortality rates [ , ] . the development of knowledge of understanding the pathology and management protocol of scd has been helpful in management of disease but application of these protocols in africa are limited due to shortage of trained medical personnel and health care facilities such as indoor hospitals, medications and diagnostic facility for newborns hbs screening [ ] . the presence of malaria, undernutrition and other infectious diseases are also contributors towards mortality rate in africa. of late, it has been seen that because of the devoted and dedicated health care services provided by the health personnel, the mortality rates are declining and this life-threatening disease of children is now progressing to chronic disease of the adult. the study carried by researchers in kilfi area of kenya compared the incidence of specific clinical outcomes in children with and without sickle cell disease in age groups between newborn to years. they found that though morbidity and mortality were higher in children with sickle cell disease, these were reduced by early diagnosis and supportive care management. the authors recommended that early detection will help preventing long term complications [ ] . still, till date genetic and infectious diseases in africa are of public health significance and needs to be addressed by adequate government funding for their effective management. pulmonary complications in sickle cell disease: it has been observed that pulmonary functions are decreased in scd. in our previous study also, we found that lung functions were compromised in patients of sickle cell disease and sickle cell trait (sct). our finding was attributed to the fact that repeated chest infections in scd and sct leads to alteration in geometry of lung parenchyma and physical properties of elastic and collagen fibres thus decreasing pulmonary function parameters such as forced vital capacity, forced expiratory volume and forced expiratory volume %. moreover, the pulmonary vasculature is highly sensitive to hypoxia driven micro-occlusion of pulmonary vasculature which along with cell adhesive changes may cause pulmonary hypertension and further compromise lung functions [ ] . the research studies have pointed out that patients with scd have an increased susceptibility to infection. the impaired leucocyte function and humoral and cell-mediated immunity loss have been reported to account for the immunocompromised state in patients with sickle cell disease [ ] . the scd patients being immune compromised are more prone for recurrent chest infections. the major cause of mortality in patients of scd is acute chest syndrome, pneumonia and acute respiratory distress syndrome [ ] . the severity of pneumonia manifests with dyspnoea and tachyponea [ , ] . exacerbate the pulmonary manifestation in scd patients especially in those having pulmonary complications such as acute chest syndrome, pulmonary hypertension and ards. covid- infections in scd can also increase morbidity and mortality risk in these patients [ , ] . the main cause of concern in patients of scd is that these patients are immunocompromised and may suffer from both acute and chronic complications which require hospitalization and close contact with the medical system. there is overlap in clinical manifestations of fever and lung disease in covid- and scd. the increased complications will amplify health care utilization. the shortage of medical specialists catering towards health care will further hamper and hinder the diagnostic, management and logistic challenges in africa. in view of the above facts it is necessary for health care workers to educate scd patients registered in their areas regarding care and precautions to be taken during covid- pandemic to prevent getting affected with covid- infection [ , ] . sickle cell disease in africa: a neglected cause of early childhood mortality mitigating the effect of the covid- pandemic on sickle cell disease services in african countries ahmed al-jabir, christos iosifidis et al. the socio-economic implications of the coronavirus and covid- pandemic: a review lung functions and oxidative status in sickle cell disease and sickle cell trait the natural history of sickle cell disease. cold spring harb perspect med the epidemiology of sickle cell disease in children recruited in infancy in kilifi, kenya: a prospective cohort study reduced levels of cd + cells and t-cell subsets in patients with sickle cell anaemia raffaela di napoli. features, evaluation and treatment coronavirus (covid- ). statpearls [internet covid- infection in patients with sickle cell disease medical and research advisory committee sickle cell disease association of america (adapted for sub-saharan africa) the authors declare no competing interests. both authors have read and agreed to the final manuscript. key: cord- -bj ebk s authors: binagwaho, agnes; frisch, miriam f.; ntawukuriryayo, jovial thomas; hirschhorn, lisa r. title: changing the covid- narrative in africa: using an implementation research lens to understand successes and plan for challenges ahead date: - - journal: annals of global health doi: . /aogh. sha: doc_id: cord_uid: bj ebk s despite predictions that the number of deaths in africa due to covid- will reach million, overall, the continent has reported relatively few cases compared to the rest of the world. many african countries have been successful in containing initial outbreaks by rapidly using evidence-based interventions through implementation strategies adapted from other countries’ covid- response as well as from prior epidemics. however, it is unclear whether these interventions will lead to long-term and complete success in stopping covid- spread. implementation research is a tool that can be used by countries to learn how to identify and understand contextual factors impacting covid- prevention and control and select evidence-based interventions and strategies known to reduce spread of the virus. we identify seven key contextual factors that are facilitators or barriers to implementation of these interventions, and several strategies that can be leveraged if the factor is present or ones to strengthen if weak to improve implementation. these factors are: a culture of accountability, national coordination, financial stability of the population, culture of innovation, culture and capacity for research, health systems strength, and cross-border economies. implementation science methods can serve to develop knowledge at a country and regional level on how to identify, utilize, and address these and other contextual factors, and inform relevant evidence-based interventions and implementation strategies. this approach can support african countries’ ability to address key challenges as they arise, both in fighting covid- and future health systems challenges. despite predictions that the number of deaths in africa due to covid- will reach million, overall, the continent has reported relatively few cases compared to the rest of the world. many african countries have been successful in containing initial outbreaks by rapidly using evidence-based interventions through implementation strategies adapted from other countries' covid- response as well as from prior epidemics. however, it is unclear whether these interventions will lead to long-term and complete success in stopping covid- spread. implementation research is a tool that can be used by countries to learn how to identify and understand contextual factors impacting covid- prevention and control and select evidence-based interventions and strategies known to reduce spread of the virus. we identify seven key contextual factors that are facilitators or barriers to implementation of these interventions, and several strategies that can be leveraged if the factor is present or ones to strengthen if weak to improve implementation. these factors are: a culture of accountability, national coordination, financial stability of the population, culture of innovation, culture and capacity for research, health systems strength, and cross-border economies. implementation science methods can serve to develop knowledge at a country and regional level on how to identify, utilize, and address these and other contextual factors, and inform relevant evidence-based interventions and implementation strategies. this approach can support african countries' ability to address key challenges as they arise, both in fighting covid- and future health systems challenges. rwanda and uganda are two countries that took early and strong approaches before reporting their first cases of covid- . as a result, both countries have successfully prevented and mitigated the spread of the virus [ , ] . rwanda began implementing evidence-based interventions including airport screenings in january [ ] . these practices continued after rwanda confirmed its first cases in mid-march, with systematic contact tracing according to world health organization (who) standards, and national lockdowns. similarly, uganda initiated preventive measures such as social distancing and travel restrictions four days before registering their first case, while implementing additional interventions including lockdowns once cases were confirmed [ ] . the responses in these countries show that effective outbreak prevention is not due to the strength of the health system, but more the ability to identify and address the right contextual factors, with strong leadership, when rapidly and effectively implementing evidence-based interventions [ , ] . while african countries vary in their ability to contain the pandemic, there is a need to assess whether the high prevalence of asymptomatic and mild cases found in other parts of the world is also true in africa [ ] . current data suggests that while there is now community spread and growing challenges in a number of countries in africa, other countries have still continued to have success in preventing the widespread infection predicted [ , ] . it is unclear whether these prevention interventions, when effectively implemented, will lead to long-term and complete success in stopping covid- spread. interventions, including border closings and social distancing, can only go on so long. reopening requires strategic and evidence-based actions. evidence shows that even some countries with early successes are now struggling when community spread takes off, such as ghana, which, as of june th, is experiencing a spike in infection after reporting lower case numbers since its first cases in mid-march [ ] . implementation research is a tool that can facilitate continued success for countries performing well. it provides methods to evaluate the use of strategies to integrate interventions into real-world settings to improve health outcomes, to understand the contextual factors that need to be addressed, and to inform adaptation of these strategies. this tool can also accelerate the production of knowledge needed to contain outbreaks in countries with less successful responses, while suggesting informed approaches to maintain pandemic control [ ] . using the methods in implementation research, countries can understand their successes and challenges by identifying not only what strategies to use, but also identifying how contextual factors can serve as either facilitators or barriers to implementation [ ] . countries can use that knowledge in their decisions to adapt strategies to implement evidence-based interventions, meet local needs, and inform effective and equitable infection prevention and control measures. following is a number of contextual factors that are emerging as important facilitators and barriers in response efforts. there are also outlined implementation strategies that can be chosen to address or mitigate factors if weak, and leverage when strong, for effective implementation of evidence-based interventions for pandemic response (and other recurrent outbreaks such as ebola or cholera) as well as in maintaining primary care. [ , ] . . culture of accountability: the presence of an existing chain of accountability for any health threat is a major contextual factor to be regularly assessed for covid- . this culture will make implementation strategies such as developing national policies more effective and easier to adapt with new scientific findings and changes in the pandemic status. a culture of accountability can also facilitate the integration of these interventions into existing systems for sustainability [ ] . . national coordination: a culture of partner and sectoral coordination is a preexisting facilitating factor needed to develop a national covid- response. government leadership can build up a strong national coordination through using a multisectoral approach as a strategy to change this factor from a barrier to a facilitator. ministries of health can strengthen communication with other ministries including labor, education, internal security, and immigration, to ensure effective and coordinated outbreak preparedness and response, and economic recovery. strategies of donor coordination and stakeholder engagement can help facilitate a comprehensive implementation of evidence-based interventions, including to the most vulnerable populations, and to map and understand where resources are available (i.e. laboratory capacity to conduct tests or provide oxygen to patients) and where additional resources are needed. integrating these strategies to build coordination can be further facilitated by a culture of accountability, which is important for successful and timely implementation. . financial stability of the population: populations living in poverty or employed through the informal economy need special consideration when additional lockdowns or plans for phased reopenings are made because of their limited financial safety nets and higher risk of covid- due to their need to work outside the home. governments need to acknowledge and address this contextual barrier by adapting implementation strategies such as a focus on equity and community engagement and providing support to reduce socioeconomic hardships related to covid- response. ignoring this factor, however, can result in an inability for populations to adhere to lockdowns or strict social distancing interventions. . culture of innovation: the growing culture of innovation across the african continent is a facilitating contextual factor that can be leveraged as part of response efforts through implementation strategies such as support for rapid development, early adoption, and scale-up of innovations. innovations that have recently been developed, or are in development throughout the covid- pandemic, include low-cost rapid testing kits, web-based alerting systems to counter misinformation, and locally manufactured ventilators, all to meet the needs of low-resource settings [ ] . this culture can be leveraged through the use of community health workers by providing them with appropriate protection and training for education and engagement. . culture and capacity of research: the lack of investment in building a culture of research remains a barrier in many countries. strong internal research capacity is important for generating context-specific understanding and adaptations of both existing and new evidence-based interventions, such as those for phased re-opening of society. identifying areas where local research is needed, drawing on the existing research capacity, and building new research capacities are strategies which can accelerate the most effective response for pandemic recovery, and prepare for future health system shocks. generating and using data for decision making and focusing on equity also helps guide policy decisions to address the needs of the most vulnerable while improving population compliance with prevention and control guidelines. . strength of the health sector: health systems in sub-saharan africa do not possess the resources or resilience of those in the western world, that still struggle to control covid- outbreaks [ , ] . the health of populations, especially those with co-morbidities such as malnutrition, tuberculosis, or hiv, are expected to suffer as a result of the pandemic. for example, with interventions such as lockdowns, some patients are unable to access transportation to get medication or needed treatment; on top of limited transportation, systems may not be in place for televisits or home delivery of medications. further, weak health systems limit the capacity to care for critically ill patients with covid- while maintaining primary care services during an outbreak. unless implementation strategies are chosen and adapted to address weak health systems, there could be dramatic health repercussions, including increasing under-five and maternal mortality rates, decreasing vaccination rates, and limited access to health care [ ] . strategies to mitigate the weaknesses of the health sector include task shifting from clinicians to community health workers, community based education and engagement (especially where community health systems are strong) and leveraging existing systems for implementation. . cross-border economies: the need to transport goods and workers regionally is a major contextual factor for implementation of evidence-based interventions. preventive measures such as border closings between countries with different levels of covid- create a major barrier for a successful implementation measures. for example, despite strict lockdowns and limited spread, rwanda reported a jump in the number of cases since early april, due to truck drivers infected with covid- crossing the border from tanzania, a country without social distancing or lockdown policies [ , ] . strategies of international and multisectoral collaboration are key to addressing this issue. institutions such as the african union and east african community need to influence, develop, and sustain regional and national responses while encouraging dialogue and alignment of cross-national policies and regulations. while the east african community has brought together heads of states and cabinet members with varying level of success, more needs to be done to improve collaboration and supra-national coordination [ ] . collaboration as a strategy will be crucial to facilitate successful border openings and allow countries to quickly adapt based on changes to covid- spread. as the world begins to see subsequent waves of covid- , and before an affordable treatment or vaccine is available, an implementation research approach to understanding, responding to, and addressing contextual factors will be needed more than ever. african countries need to learn at the national and regional levels how to acknowledge contextual factors. as key challenges arise, they need to also develop the capacity to carefully identify and adapt relevant implementation strategies reflecting these factors, including a focus on equity, using and leveraging existing systems, international and multisectoral collaboration, and data gathering and interpretation to inform decisionmaking. this ongoing learning will be critical in determining the approach and timing of a phased re-opening or in responding to increases in cases and changes in local pandemic patterns of spread. in conclusion, implementation research offers policy makers, implementers, and public health professionals the tools to identify contextual factors, choose relevant strategies, measure successes and failures, and continue to adapt and learn. implementation research can also help generate broader knowledge useful to other countries facing similar challenges while sustaining stronger work from ongoing health systems. this knowledge is important in reducing needless mortality from covid- and future pandemics; at the same time, eliminating broader barriers to quality, equitable healthcare for all. africa coronavirus cases could hit million in six months: who coronavirus disease (covid- ) situation reports; world health organization. global health observatory data repository: population data by country (all years) unpacking the theories behind africa's low infection rate experts sound alarm over lack of covid- test kits in africa. the guardian nations-are-teaching-the-westabout-fighting-the-coronavirus?fbclid=iwar ys pghynlqbagikpu wt aw upbhnvx mtyzyvb ytvonpedvnqtlfazq the problem with predicting coronavirus apocalypse in africa address on the corona virus (covid ) implementation research: an efficient and effective tool to accelerate universal health coverage we need compassionate leadership management based on evidence to defeat covid- prevalence of asymptomatic sars-cov- infection: a narrative review implement binagwaho et al: changing the covid- narrative in africa: using an implementation research lens to understand successes and plan for challenges ahead art african science steps up to covid challenge. cornell alliance for science early estimates of the indirect effects of the covid- pandemic on maternal and child mortality in lowincome and middle-income countries: a modelling study. lancet glob health high risk of contracting coronavirus in tanzania heads of state consultative meeting of the east african community the authors have no competing interests to declare. this paper underwent peer review using the cross-publisher covid- rapid review initiative. key: cord- - h g authors: ogunkola, isaac olushola; adebisi, yusuff adebayo; imo, uchenna frank; odey, goodness ogeyi; esu, ekpereonne; lucero‐prisno, don eliseo title: rural communities in africa should not be forgotten in responses to covid‐ date: - - journal: int j health plann manage doi: . /hpm. sha: doc_id: cord_uid: h g rural areas in africa make up a large proportion of the continent. since the emergence of covid‐ on the continent, major attention and responses have been placed on urban areas. rural areas are typified by certain challenges which may serve as limitations to the provision of resources and tools for covid‐ responses in these areas. these major challenges include limited access to these areas due to poor road networks which may hamper the possibility of conveying resources and manpower. shortage of healthcare workforce in these areas, poor health facilities/structures and limited access to covid‐ diagnostics services may also make containment challenging. it is therefore important that investment should be made in these areas towards providing the necessary tools, resources, and manpower to ensure effective containment of covid‐ and to alleviate the plight caused by the pandemic in rural africa. rural communities in africa should not be left behind in covid‐ responses. rural areas in africa make up a large proportion of the continent. since the emergence of covid- on the continent, major attention and responses have been placed on urban areas. rural areas are typified by certain challenges which may serve as limitations to the provision of resources and tools for covid- responses in these areas. these major challenges include limited access to these areas due to poor road networks which may hamper the possibility of conveying resources and manpower. shortage of healthcare workforce in these areas, poor health facilities/structures and limited access to covid- diagnostics services may also make containment challenging. it is therefore important that investment should be made in these areas towards providing the necessary tools, resources, and manpower to ensure effective containment of covid- and to alleviate the plight caused by the pandemic in rural africa. rural communities in africa should not be left behind in covid- responses. africa, challenges, covid- , responses, rural areas | commentary since the emergence of coronavirus disease, also known as covid- , in africa, the continent appears like it could be the worst hit from the economic fallout of the covid- crisis including pushing million africans into extreme poverty if action is not taken. unfortunately, the threat of the disease continues to grow, and rural africa is not exempted. due to disruptions in food systems, there is a high prospect of more africans falling into hunger, especially rural dwellers. rural dwellers, many of whom work on small-scale farms, are particularly vulnerable to the impact of covid- pandemic. their produce will have no markets, as supply chain will be affected due to lockdowns and lack of transport. the loss of jobs in the urban areas will also push people to go back to their rural homes thus allowing the virus to spread. this paper seeks to highlight the challenges facing the covid- responses in rural areas of africa. although there has been a number of actions implemented to address the pandemic and its impact, the increasing number of covid- cases poses a major threat particularly with the various limitations and challenges that plague health services in rural areas of the continent. according to the world bank, about six out of every persons in sub-saharan africa lives in a rural area representing . this population comprises of various age groups which include the high-risk group of covid- such as the elderly and communities facing a double burden of communicable and non-communicable diseases. the challenges facing health services in rural areas have been mainly characterized by poor healthcare access and coverage, and health workforce shortages. considering the proportion of africa's population in rural areas, the impact, and the efforts of the containment activities should be examined. communities have limited basic amenities. the challenge of water supply, electricity, roads, schools, and health centres have always been pointed out as significant limitations affecting these regions. most diseases, including neglected tropical diseases, malaria, typhoid, tuberculosis and hiv/aids are not uncommon in rural africa. most communities do not have a functional and sufficient health centres that caters to the health needs of the people. poor health service delivery has remained a significant challenge in rural communities, and efforts are needed to improve healthcare delivery more than ever. other challenges, such as shortage of drugs, lack of equipment and limited diagnostic testing capacity, to very few primary healthcare centres, may also pose an additional threat to responses in rural africa. therefore, these problems contribute massively to the figures depicting problematic health service delivery in africa in entirety. most communities have been able to manage the available structures poorly. some have also made efforts to provide alternatives, which are not sustainable for the needed healthcare coverage. rural communities in africa are typically conservative and uphold culture to a greater extent. rural settlements are found in the form of clusters which means daily physical contact between individuals is inevitable. community clustering and family clustering have been shown to affect covid- responses in africa. amidst the rage of the pandemic, individuals in rural areas may seek to hold on to the cultural and norm practices as it would be challenging to have socio-cultural adjustments, posing an additional threat to stay-home orders, physical distancing and other precautionary measures. accessibility to rural communities is made difficult due to poor roads network and its settlements structures. poor information access, as well as infodemic and poor health literacy in rural areas of africa, have been a challenge. rural areas in africa have limited access to the media. just fewer persons have devices and gadgets that provide media content. it is no news that the media today is flooded by issues relating to covid- including mode of transmission, prevention, and control measures. rural dwellers have limited access to these contents. this can make them ill-informed about the pandemic resulting in reliance on anecdotal evidence about the pandemic which may be incorrect-making rural dweller more prone to incorrect information regarding the pandemic, which may further hamper containment. this also reiterates the need for telemedicine in africa and the rural areas should not be left out. the problem of accessing rural areas seem to create a barrier on reaching the people in these areas towards their health needs. the possibility of having good access point to these areas will encourage the distribution and dissemination of materials and other resources geared towards covid- response. special awareness programmes cannot effectively hold in these areas since the problem of access continues to exist. however, initiatives should be set up to solve this problem. additionally, trained community health workers should be leveraged to improve the reach of covid- related information in rural communities. such programmes would serve to educate and encourage the adoption of basic hygiene methods towards the prevention of the disease. the benefit of these practices will limit the community spread of the virus. ogunkola et al. poor hand hygiene and living conditions in some of the rural communities in africa may also make containment challenging. additionally, there are fewer doctors, nurses, community health workers and other health service workers in rural africa. the dearth of qualified health workers may affect access to healthcare services for rural dwellers. diagnostic services for covid- is also a challenge in africa , and rural dwellers will suffer disproportionately on the access. since most covid- testing centres, isolation centres, as well as treatment centres, are mainly situated in the urban areas. for these reasons, rural africa may be disproportionately disadvantaged in the fight against covid- . african rural communities should not be left out in covid- responses as we geared towards promoting health equity globally. there are chances that the spread of the diseases in rural africa is likely to be faster. the inability to meet the response needs of rural african communities may also contribute to the disease burden on the continent. resources and efforts towards the containment of the pandemic should be increased in rural areas. major response projects should be situated in rural areas as well as urban areas for equity in health. innovative approach towards information dissemination should be leveraged, for example, the use of town criers and other tailor-made strategies. this will increase the level of awareness and heed to precautionary measures towards effective covid- pandemic containment. current efforts and challenges facing responses to -ncov in africa covid- response must target african agriculture and the rural poor rural population-sub-saharan africa healthcare access in rural communities neglected tropical diseases in sub-saharan africa: review of their prevalence, distribution, and disease burden the impact of covid- pandemic on medicine security in africa: nigeria as a case study enhancing rural population health care access and outcomes through the telehealth ecosystem™ model increasing access to health workers in remote and rural areas through improved retention: global policy recommendations. geneva: world health organization rural communities in africa should not be forgotten in responses to covid- the authors appreciate the reviewers for their insightful comments. the authors have no competing interests. the concept for this commentary was developed by isaac olushola ogunkola and yusuff adebayo adebisi. uchenna frank imo, isaac olushola ogunkola, and yusuff adebayo adebisi developed the draft and prepared the manuscript.goodness ogeyi odey, ekpereonne esu, and don eliseo lucero-prisno iii assisted with data collection, article interpretation, and language edits. all the authors have read and agreed to the final manuscript. https://orcid.org/ - - - key: cord- -lbxmteyn authors: erokhin, vasilii; gao, tianming title: impacts of covid- on trade and economic aspects of food security: evidence from developing countries date: - - journal: int j environ res public health doi: . /ijerph sha: doc_id: cord_uid: lbxmteyn the stability of food supply chains is crucial to the food security of people around the world. since the beginning of , this stability has been undergoing one of the most vigorous pressure tests ever due to the covid- outbreak. from a mere health issue, the pandemic has turned into an economic threat to food security globally in the forms of lockdowns, economic decline, food trade restrictions, and rising food inflation. it is safe to assume that the novel health crisis has badly struck the least developed and developing economies, where people are particularly vulnerable to hunger and malnutrition. however, due to the recency of the covid- problem, the impacts of macroeconomic fluctuations on food insecurity have remained scantily explored. in this study, the authors attempted to bridge this gap by revealing interactions between the food security status of people and the dynamics of covid- cases, food trade, food inflation, and currency volatilities. the study was performed in the cases of developing economies distributed to three groups by the level of income. the consecutive application of the autoregressive distributed lag method, yamamoto’s causality test, and variance decomposition analysis allowed the authors to find the food insecurity effects of covid- to be more perceptible in upper-middle-income economies than in the least developed countries. in the latter, food security risks attributed to the emergence of the health crisis were mainly related to economic access to adequate food supply (food inflation), whereas in higher-income developing economies, availability-sided food security risks (food trade restrictions and currency depreciation) were more prevalent. the approach presented in this paper contributes to the establishment of a methodology framework that may equip decision-makers with up-to-date estimations of health crisis effects on economic parameters of food availability and access to staples in food-insecure communities. over the decades, food insecurity concerns have been emerging, along with the growth of the world population. among the united nations sustainable development goals [ ] to be achieved by , ending hunger and establishing food security hold an important place. however, despite the best efforts of the international community to combat food insecurity across the globe, the number of undernourished people has resumed growth in , after a steady decline during the - s. the food and agriculture organization (fao) reports that over million people in the world suffer from hunger, while about two billion people experience moderate or severe food insecurity [ ] . in view of the fact that an additional million people have become affected by hunger since , the number of undernourished people is projected to exceed million by [ ] . in the past, the main reasons for food shortages used to be droughts and other natural disasters. with the emergence of globalization, food security has become an economic rather than an agricultural issue. being a combination of the physical availability of food and economic access to adequate supply [ ] , food security at the national these countries are net importers of food and agricultural products. according to the fao [ ] , out of developing economies and ldcs where recent adverse impacts of the economic downturn due to the covid- pandemic on food security have been strongest, countries rely heavily on agricultural imports. in a situation of disrupting food supply, dependence on imports tremendously threatens the food security of those nations, especially when export restrictions are imposed by the world's leading suppliers like russia, vietnam, and ukraine. as the spread of covid- and strict quarantine measures trigger economic decline, even developed economies experience food price rises unless the governments take preventive actions or retailers absorb some of the costs. since february , the global average price for rice has increased by . %, for meat of cattle-by . %, for meat of chicken-by . %, for potatoes-by . % [ ] . due to a limited capacity to produce staple crops domestically, developing economies are more vulnerable to food inflation and supply shortages. in just the first three months of at the very onset of the covid- outbreak, over fifteen developing countries already experienced an increase in the cost of a basket of food staples (over %) [ ] . at many markets, food prices have been increasing because of local logistical problems [ ] . there is also a dependence of developing countries with their limited resources on a small range of food products exported to a few markets [ ] , many of which have been affected by the covid- outbreak [ ] . in one of the trade scenarios simulated by vos et al. [ ] , a % global economic slowdown due to the pandemic could cause a decline in developing-country agri-food exports by almost %. there is an array of studies that address trade aspects of food supply [ ] [ ] [ ] [ ] [ ] , but the majority of them focus on food self-sufficiency rather than food security. according to the fao [ ] , a self-sufficient country satisfies its needs in food by means of domestic production. although some developing countries of africa (mali and senegal) and latin america (bolivia, ecuador, and venezuela) have embraced the idea of food self-sufficiency in their national policies [ ] , progressing liberalization of food trade over the past few decades has refocused attention from self-sufficiency, a concept that is often related to protectionism and even autarky [ ] , to food security. the latter incorporates a wider range of parameters of food availability, economic access to adequate nutrition, utilization of nutrients, and stability of food supply [ ] . while wegren and elvestad [ ] , meskhia [ ] , clapp [ ] , and saidi and diouri [ ] , among others, argue that food security is about establishing a balance between domestic production and imports, many studies categorize food security as agricultural [ , ] , economic [ , ] , or health [ ] [ ] [ ] issues rather than as a trade one. however, at the height of the covid- crisis, both larger demand gaps and higher food price surges suggest that international trade policies play a more pervasive role in ensuring food security at the national level than previously thought. against the backdrop of the health crisis, an increase in the number of undernourished people is coupled with a global economic slowdown [ ] -a trilemma that has not been adequately explored in previous studies. lockdowns, export restrictions, and quarantine measures exacerbate these problems and call for the investigation of trade and economic impacts on food security in a new reality of food chain disruptions. so far, empirical assessments of the pandemic's effects on food and agriculture sectors have been grouped around international organizations, such as fao (food and agriculture organization of the united nations), who (world health organization), wfp (world food programme), unctad (united nations commission on trade and development), and ifpri (international food policy research institute). in a collective study compiled by the unctad's committee for the coordination of statistical activities [ ] , three dozen organizations and institutions identified the pandemic's primary channels of transmission to food and agriculture sectors, and quantified the potential impacts of covid- outbreak on agricultural input markets, food trade, and food consumption. since the report covered a wide range of topics, it thus was not particularly focused on the analysis of trade-related aspects of food security. in the regional section of the report, the economic and trade impacts of covid- on food security were not detailed for developing economies and ldcs. in the ifpri study that particularly focused on developing countries, vos et al. [ ] applied a general equilibrium model to assess possible impacts of the pandemic on prices, income, and poverty. the impacts of productivity declines on prices of some food products were forecasted, as well as on income of households, but the parameters of food availability and access to food and agricultural products were not addressed. similarly, trade impacts on food supply chains have remained scantily explored across the array of studies on covid- that have emerged in . most of these recent papers have particularly emphasized the aspects of food safety [ ] , agriculture productivity [ , ] , and healthy nutrition [ ] , rather than of food imports and trade balance as dimensions of food availability. the impacts of both international exchange fluctuations and food inflation on the access pillar of food security have also remained under investigated. the link between price increase and access to food has been primarily considered in terms of supply disruptions and shortages along the retail food supply chain [ , ] , not currency exchange rates. to the best of the authors' knowledge, there are no comprehensive studies that link the incidence rates of covid- with either the number of undernourished people or the degree of dependency on food imports. in this study, the authors attempt to bridge the said gaps in the "covid- -trade-food security" agenda by ( ) identifying interactions between the number of covid- cases on one side and availability and access pillars of food security on the other; ( ) assessing the cointegration between the pandemic-induced trade parameters of food availability and the number of undernourished people; ( ) revealing the impacts of food inflation and currency exchange volatilities amid the global health crisis on economic access to food in domestic markets; and ( ) detailing the analysis of above-mentioned health, food security, trade, and economic parameters across an array of developing economies and ldcs. the approach employed in this study is to assess the relationships between the food security parameter, on one side, and health and macroeconomic variables that affect availability and access pillars of food security, on the other. the number of people with insufficient food consumption (y) was used as a dependent variable (table ) . it is defined by the world food programme (wfp) [ ] as a total number of individuals with a poor or borderline level of food consumption. poor food consumption refers to households that are "not consuming staples and vegetables every day and never or very seldom consume protein-rich food such as meat and dairy" [ ] . households in borderline food consumption status are those "consuming staples and vegetables every day, accompanied by oil and pulses a few times a week" [ ] . the value of exports of food and agricultural products less imports of food and agricultural production. month-on-month percentage change in the price of a standard basket of food as calculated from the national consumer price index. the number of confirmed covid- cases (x ) was utilized to show the overall effect of the pandemic on food security. the selection of x ( ) ( ) ( ) variables is based on the wfp's hunger map patterns. balance of food trade (x ) reflected the dependency of a country on food imports and thus demonstrated the changes in the food supply. food inflation (x ) and currency exchange (x ) were used to reveal the influence of changes in access to food and agricultural products on food security. the choice well correlates with the recommendations of huseynov [ ] , who used exchange rate, inflation rate, and food trade as variables to identify short-term and long-term effects on food security. the period of analysis included six months from january (when first covid- cases were confirmed outside china) till the end of june (when many countries gradually lowered health alert levels). the data were obtained from the wfp's hunger map portal [ ] , trading economics [ ] , and the united nations conference on trade and development (unctad) [ , ] . among developing economies, the wfp [ ] reports countries that experience the prevalence of undernourishment (pou), a percentage of people in the total population that are in the condition in which an individual's habitual food consumption is insufficient to provide the amount of dietary energy required to maintain a normal, active, healthy life. the study proceeded with economies where the pou was the highest as of june (table ) . to reveal diverse effects on food security across a variety of macroeconomic environments, the selected countries were distributed into three groups. group included low-income economies defined by the world bank [ ] as those with a gross national income (gni) per capita of $ or less. group comprised lower-middle-income economies with a gni per capita between $ and $ . in group , we included countries with the upper-middle level of gni per capita between $ and $ , . note: * portion in the total population of countries included in the group; ** change in percentage points; "+" parameter increment; "-" parameter decrement. source: authors' development based on wfp's hunger map portal [ ] . to capture potential divergences in both economic and geographical specificities of food security, we selected the countries from six regions of africa, asia, latin america, and the middle east ( figure ). the classification by income group is based on the world bank atlas method [ ] , while that by geographic region-on the world bank country classification [ ] . to capture potential divergences in both economic and geographical specificities of food security, we selected the countries from six regions of africa, asia, latin america, and the middle east ( figure ). the classification by income group is based on the world bank atlas method [ ] , while that by geographic region-on the world bank country classification [ ] . the following hypotheses were established to reflect supposed variations in y-x( - ) interactions depending on the level of income: the covid- pandemic has hurt the entire international community ranging from the least developed countries of africa to the wealthiest economies of europe and america [ , ] . therefore, we hypothesize that: in low-income economies, food shortages and other disruptions of food availability are commonly considered to be the major factors of food insecurity [ ] [ ] [ ] [ ] [ ] . additionally, due to the world's highest portion of disposable income spent on food in low-income countries [ ] [ ] [ ] [ ] , even a slight deterioration in the economic access to staple foods harms the food security status of the households. as the spread of the covid- and lockdown measures trigger economic decline, we suggest that: hypothesis . in group countries, the strongest influence over y is exerted by food availability and food access parameters, x and x , respectively. the following hypotheses were established to reflect supposed variations in y-x ( - ) interactions depending on the level of income: the covid- pandemic has hurt the entire international community ranging from the least developed countries of africa to the wealthiest economies of europe and america [ , ] . therefore, we hypothesize that: hypothesis . x exert a direct strong effect on y across groups - countries without regard to income level. in low-income economies, food shortages and other disruptions of food availability are commonly considered to be the major factors of food insecurity [ ] [ ] [ ] [ ] [ ] . additionally, due to the world's highest portion of disposable income spent on food in low-income countries [ ] [ ] [ ] [ ] , even a slight deterioration in the economic access to staple foods harms the food security status of the households. as the spread of the covid- and lockdown measures trigger economic decline, we suggest that: hypothesis . in group countries, the strongest influence over y is exerted by food availability and food access parameters, x and x , respectively. with a rise in income level, a portion of imported food in consumption increases due to importing higher-quality and pricier products [ ] [ ] [ ] , whereas the fluctuations in world prices and import volumes exert stronger effects on the food security status of the households compared to those of domestic supply. in a situation when global food supply chains are disrupted by currency exchange volatilities and trade restrictions amid the covid- pandemic, we assume that: hypothesis . in group countries, the effects of x and x on y are the highest among the economies included in the study, while that of x is the lowest. across the array of six variables, the four-stage analysis was conducted individually for each of the forty-five countries ( table ) . at stage , a stationary test was conducted to check whether a co-integration existed between the selected variables. to illustrate short and long-run interactions between the variables, the autoregressive distributed lag (ardl) method was employed at stage . then, we applied yamamoto's causality test to reveal the causality directions of the variables. finally, by utilizing the variance decomposition approach, we attempted to predict the future relative strengths of causalities between the variables. table . study flow algorithm. stationary test by augmented dickey-fuller (adf) and phillips-perron (pp) methods. as certainty of cointegration between y and x ( - ) . autoregressive distributed lag (ardl), fully modified ordinary least squares (fmols) and dynamic ordinary least squares (dols). identification of short and long-run interactions between the variables individually in forty-five countries, generalization of the results across three groups of economies by income and seven groups by region. prior to the identification of the relationships between the variables, it is important to understand if the data is stationary [ , ] . the system behaves correctly in the case where static and dynamic properties of the variables remain unchanged and values of the system state belong to an acceptable interval [ ] . a variety of approaches have been developed to check the stationarity and to investigate further the cointegrating interactions between stationary variables. concerning macroeconomic parameters, the most commonly used techniques are the adf test by dickey and fuller [ ] and the pp test by phillips and perron [ ] . they were used by herwartz and reimer [ ] to reveal the relationship between interest rates and inflation across developing economies, by chang et al. [ , ] to investigate stationarity of gdp per capita in the oecd countries, by ranjbar et al. [ ] and su et al. [ ] to study income convergences in developing and least developed countries of africa, and by hoarau [ ] to test the purchasing power parities for real exchange rates in central america. in combination with the adf and the pp tests, aliyev et al. [ ] , humbatova et al. [ ] , and naseem et al. [ ] , among others, used the kpss (kwiatkowski-phillips-schmidt-shin) unit root method to enhance the robustness of the stationary test results. the kpss test has been widely used in macroeconomics and international finance (for instance, by kuo and mikkola [ ] , gunduz [ ] , and tsen [ ] ) to check long-run and functional time series for stationarity [ , ] . in short-run time series similar to those used in our study, the employment of the kpss test might be misleading due to the invariance of the technique to seasonal dummies [ ] and the duality of the level stationary and time trend stationary models used in the test [ ] . to ensure the correct interpretation of data in the short-run, we abandoned the kpss method and utilized the adf and the pp techniques to check the cointegration between y and x ( - ) . after the stationarity of the variables is confirmed, the interactions between the variables may be verified. to identify the relationships between the variables within the two established multitudes, we employed the autoregressive distributed lag (ardl) method elaborated by pesaran et al. [ ] (equation ( )). although the use of this technique in food security studies has been very rare, many scholars have employed the method to identify both short-and long-run relationships between various macroeconomic parameters in developing countries. for instance, Öztürk and Özdil [ ] used ardl to investigate the interplays between economic growth and unemployment in the oecd countries, elian et al. [ ] tested the relationship between foreign direct investment inflows and economic growth across the brics countries, and appiah et al. [ ] studied growth determinants in emerging economies. to the best of the authors' knowledge, we have not been able to track previous applications of the ardl method in studying availability or access-related parameters of food security. however, there are abundant examples of an effective utilization of the ardl in revealing the interplays between domestic supply and imports [ , ] , trade balances [ , , ] , inflation [ , ] , international currency exchange [ , ] , and health [ ] . where ∆ = first difference operator; δ = constant term; δ , δ , δ , δ , and δ = short-run elasticities of the variables; i = ardl model lag order; ect t− = error correction term; ε t = error disturbance; t = time. if f-statistics is larger than the upper critical bounds value [i( )], the series are cointegrated. if it is below the lower critical bounds [i( )], the variables are not cointegrated. as robustness tests for the ardl, we utilized fully-modified ordinary least squares (fmols) and dynamic ordinary least squares (dols). according to phillips and hansen [ ] , testing the ardl results by fmols allows one to correct the system for endogeneity and serial correlation effects. it is a non-parametric method to identify a correlation between the components of model error terms [ ] . the approach was used by narayan and narayan [ ] , abu [ ] , and adebayo [ ] to test the interactions between various macroeconomic variables, including trade volume, inflation, and currency depreciation. the rationale of using fmols in our study is that it allows receiving consistent parameters even in the small samples in the short-run. additionally, it helps to overcome the problems of endogeneity and serial correlation and thus allows for the heterogeneity in the parameters [ , ] . dols has been commonly utilized in combination with fmols as a computationally convenient alternative to fmols estimators. according to stock and watson [ ] , dols is employed to estimate the equilibria that is corrected for potential simultaneity bias among explanatory variables. similar to fmols, dols is applicable to small samples in the short term [ ] . its estimators obtained from least-squares estimates are unbiased and asymptotically efficient even in the presence of the endogenous problem [ ] . echoing the successful application of both fmols and dols in testing the robustness of the ardl results by yuzbashkandi and sadi [ ] , pasha and ramzan [ ] , priyankara [ ] , and adebayo [ ] we consider these two methods as efficient estimators to study serial interactions and examine potential correlations between y and x ( - ) . some scholars, for instance, aliyev et al. [ ] , guan et al. [ ] , yue et al. [ ] , and rahman et al. [ ] , further checked fmols and dols results by employing the canonical cointegration regression (ccr). the method is commonly implemented to remove the long-run dependencies between the cointegrating equation and stochastic regressors, which does not apply to small samples in the short-run used in our study. the utilization of the ardl method allows us to identify the interaction between the variables, but not the direction of causalities. to capture these directions, we employed a causality test elaborated by toda and yamamoto [ ] . this technique has been extensively used by many scholars, including pantamee et al. [ ] , adebayo [ ] , and bilgehan [ ] , to estimate causal relationships between domestic market parameters and exogenous factors across developing countries worldwide. among the drawbacks of the ty causality test is the inability to predict the relative strength of causalities between the variables beyond the period under study. sankaran et al. [ ] , rana and sharma [ , ] , and wang and ngene [ ] suggested to overcome this problem by using the wald or modified wald (mwald) tests, but hayashi et al. [ ] and lemonte [ ] demonstrated that, in small samples when used empirically to search for unimportant parameters, the wald test procedure could be misleading. in furtherance of zhang et al. [ ] , mao et al. [ ] , adebayo [ ] , and chan et al. [ ] , we used variance decomposition instead of the wald test to explore the strengths of inter-variables causal interactions and to reveal potential causality impacts. the method was applied for nine consecutive periods from july till march . the results of the adf and the pp tests across three groups of countries (see supplementary materials to this paper, tables s -s ) demonstrate that all five variables are stationary at a level of either i( ) or i( ). in all cases, the calculated f-statistics values exceed the upper bound (table ). it means that the precondition for co-integration between y and x ( - ) is established in all countries included in the study. the stationarity of the data series along with the revealed co-integration between the variables both confirm the appropriateness of the established data set for the ardl analysis. since the study includes six periods (months), it is mainly centered on explaining the short-run relationship between the number of people with insufficient food consumption and independent variables. the ardl short-run estimates for the three groups of countries are summarized in table , the detailed per-country calculations are provided in supplementary materials (tables s -s ). in group countries, the strongest effect on the growth of y is caused by an increase in food inflation x . this effect is statistically significant across the group. some variables also exert strong direct influence on y, for instance, x in sierra leone and yemen and x in haiti and niger. when other factors remain constant, an increase in the number of registered covid- cases by % results in the growth of y by . % in tajikistan and by . % in mozambique and sierra leone. in niger, a . % increase in the number of people with insufficient food consumption is caused by a % rise in x ( . % in guinea, . % in tanzania, and . % in afghanistan). in group countries, we see kaleidoscopic linkages between y and x . in pakistan and india, the countries of south asia which have been severely hit by the pandemic, an increase in covid- cases by % results in the growth of the number of people with insufficient food consumption by . % and . %, respectively. in east asia, on the contrary, we see that the food security status of the households improves when the number of registered covid- cases goes up (when other variables remain constant). in cambodia and vietnam, where the growth of ∆x in january-june was more moderate compared to some of their neighbors in south asia, we see a negative x -to-y relationship. the lower portion of imports in the balance of food trade has a positive and statistically significant impact on the number of people with insufficient food consumption in cameroon, kenya, tunisia, and india, whereas, in cambodia, the relationship between x and y is negative. the effects of x and x on y are positive in all countries, except cambodia, but not that significant compared to x and x . while the increase in the number of confirmed covid- cases is found to have a significant positive effect on y in the countries of latin america and the caribbean, in the case of many other group countries, there is a negative relationship between these variables (botswana, namibia, libya, jordan, and iran). the strongest impact of x on y is revealed for peru and ecuador, where an increase in covid- cases by % is associated with the growth of the number of people with insufficient food consumption by . % and . %, respectively. statistically strong interplays are reveled between y and x in algeria, botswana, and colombia, between y and x in sri lanka and turkey, and between y and x in ecuador and namibia. the negative influence of x on y is identified to be statistically significant in sri lanka and iran, of x on y-in algeria, dominican republic, iran, and iraq, of x on y-in sri lanka. error correction measure is statistically significant in the case of all three groups of countries. the results of the fully-modified ordinary least squares (fmols) and dynamic ordinary least squares (dols) tests are employed to check the robustness of the ardl estimates (table for a group-based summary, tables s -s for country-specific data). the number of registered covid- cases is confirmed to result in higher food insecurity across three types of economies included in the study, except some countries of sub-saharan africa (burkina faso, chad, ethiopia, zambia, botswana, and namibia), middle east and north africa (yemen, iran, jordan, and libya), and east asia and pacific (cambodia and vietnam). among these twelve countries, for which we see a reverse relationship between covid- cases and the number of people with insufficient food consumption, there are representatives of various income groups. reasoning from this fact, we can assume that in a particular country, the direction of the y-x link does not depend on gni per capita. however, when the relationship between these two parameters is positive, there is evidence of a stronger y-x correlation in group countries compared to that in group low-income economies. the toda-yamamoto test demonstrates the most significant causality flowing from the number of covid- cases to the number of people with insufficient food consumption in group countries of latin america (colombia, ecuador, and peru) and europe (turkey), whereas, in low-income economies, the x →y causality is weaker (table , tables s -s ). similarly to bidirectional interactions between covid- cases and food insecurity across all groups of countries, both the fmols and dols tests confirm divergent relationships between the number of people with insufficient food consumption and the balance of food trade. in group and group , y-x relations are positive (except for cambodia, iran, and sri lanka), while in group , they are negative for almost half of the countries. in sub-saharan africa (burkina faso, chad, mali, niger, and tanzania), an increase in the balance of food trade is identified to be effective at reducing the number of people with insufficient food consumption. from the estimation of the toda-yamamoto causality test (table ) , we see the unidirectional x →y causality in group countries, but the significance of the link is low. the strongest influence of food access on food security is revealed in low-income economies of sub-saharan africa (burkina faso, ethiopia, guinea, mali, mozambique, and sierra leone), as well as some countries of central asia (tajikistan) and middle east (yemen). in some group countries, robustness tests show a negative relationship between x and y when the number of people with insufficient food consumption goes up amid food deflation. we also see examples of such reversal links in upper-middle-income countries of the middle east (iran and iraq), where food prices are to a large extent under government control. confronting hypothesis , in lower-middle-income economies of southeast asia (cambodia, india, indonesia, pakistan), seasonal retreat in food prices does not immediately result in higher food security expectations among people. in these countries, the x →y causality link is weak due to the high portion of locally produced seasonal food in consumption. among group economies, more significant causality flowing from food inflation to food insecurity is revealed for the countries of sub-saharan africa (cote d'ivoire, nigeria, zambia, kenya), where diversity of locally-produced staples is narrower compared to asia. when a portion of marketed food in supply is higher, a deterioration in economic access to marketed products imposes a more significant impact on the aggravation of food insecurity. it is assumed that in the countries where a large portion of the food supply is ensured by imports, food inflation might correlate with currency exchange. however, we see that in low-income economies, where food access strongly correlates with food inflation, the number of people with insufficient food consumption is marginally affected by currency exchange fluctuations. the weaker link between y and x across group stems from the fact that low-income economies import a considerably lower amount of high-quality and expensive food products compared to lower-middle and upper-middle-income countries. as contrasted with low-income countries, group economies are deeper integrated into global supply chains of value-added food products. from this perspective, amid the covid- pandemic, the most significant causal relationships between volatilities in currency exchange and food supply are found in the countries with the highest gni per capita among those included in the study-turkey, colombia, and peru. with the current dynamics of registered covid- cases across three groups of countries, the extrapolation of the short-run ardl estimates to the future forecasts a gradual increase in the proportion of food insecurity variance explained by the effects of the pandemic. variance decomposition of y-x ( - ) interactions (table , tables s -s ) indicates a diversity of potential causality impacts of covid- cases, balance of food trade, food inflation, and currency exchange on the number of people with insufficient food consumption. for group countries, the decomposition analysis suggests a rather stable and weak y-x linkage over a three-quarters horizon (table s ) . only in nepal, yemen, and mali, the food security situation could be significantly predicted by the variations of x . but even in these countries, we see that the expected proportions of x and x in y nearly equal that of x in size. for most of the low-income economies, variance decomposition projects an increase in the proportion of y explained by food inflation ( . % in ethiopia, . % in chad, . % in the democratic republic of the congo) and currency exchange ( . % in burkina faso, . % in mali, . % in niger). in lower-middle-income economies, the number of people with insufficient food consumption seems to be increasingly affected by food availability. by march , in import-dependent kenya and kyrgyzstan, the proportion of y explained by the balance in food trade is forecasted to exceed % (table s ). the weight of food access in establishing food security will grow in the countries of east asia ( . % and . % of y explained by x in vietnam and cambodia, respectively) and sub-saharan africa ( . % in cote d'ivoire and . % in zambia). the projected causality between y and x is the strongest in the countries of south asia. in india, at the current rate of registered covid- cases, almost . % of the proportion of insufficient food consumption will be impacted by the pandemic. it is the highest expected impact of the pandemic on food security among forty-five countries included in the study. in bangladesh, the strength of the y-x linkage will exceed . % by the second quarter of . across sub-saharan africa and east asia, a relatively low number of registered covid- cases allows one to predict the moderate role of x in the explanation of y variations over a nine-month horizon. among upper-middle-income countries, the impact of the pandemic on the number of people with insufficient food consumption is not expected to vary significantly from region to region. the proportion of y explained by x is expected to peak in the countries, where the number of covid- cases per capita in january-june was the highest among group economies. over the entire time horizon considered in this study, the growth in x will most likely and consistently be converted into a higher percentage of the population in food insecurity status in peru, iran, and turkey (table s ) . variance decomposition also projects significant contributions of x to y in colombia ( . %), algeria ( . %), and ecuador ( . %). the revealed interplays between the variables across three groups of countries allowed us to test the hypotheses: hypothesis : not confirmed. the x -y relationship is uneven across group - countries, where the strength of causal interaction between the two variables increases with the growth of income level. the effect of the covid- outbreak on the number of people with insufficient food consumption is observed across the three groups of countries. this finding supports the expectations of the fao [ , ] , the wfp [ ] , and the wto [ ] , as well as the projections of many scholars [ , , ] , who say that the spread of covid- may bring damage to global food security, particularly painful in the least developed and developing economies. according to our results, the number of registered covid- cases is indeed associated with higher food insecurity in many countries included in the study. the y-x linkage is statistically significant in the countries (primarily, middle-income economies) where the number of registered covid- cases per capita is high (pakistan, india, peru, ecuador, turkey). across low-income economies; however, the impact of covid- on food insecurity is much weaker compared to that in upper-middle-income countries. this result well agrees with the fao's estimation that higher-income countries are more likely to face food supply disruptions during the novel health crisis, given their deeper integration in global supply chains and capital-intensive agricultural systems [ ] . in , the wfp [ ] reported yemen, the democratic republic of congo, afghanistan, venezuela, ethiopia, south sudan, syria, sudan, nigeria, and haiti to constitute the worst food crises. confronting the established hypothesis , we see that in most of these countries, the relationship between the number of people with insufficient food consumption and the number of covid- cases is not strong but moderate. for example, in afghanistan, where at least % of the population is in a state of food crisis [ ] , the increase in the number of covid- cases by % results in the growth in food insecurity by only . %. moreover, we see that in several low-income countries, the dynamics of covid- cases is related to y in a negative way. in some countries, where the number of covid- cases remained low during january-june , there is a reversal y-x relationship. in haiti, an increase in the number of covid- cases by % is associated with the improvement in the food security status of the population by . % (by . % in nepal and by . % in chad). such a relationship can be explained by a statistically insignificant correlation between x and y due to the low number of confirmed covid- cases per capita. still, the effects of the pandemic on food security in low-income countries should not be underestimated. even without considering the direct health-related influences of the spreading covid- virus, the fao projects low-income economies of africa to overtake both lower-middle-income and upper-middle-income countries of asia and latin america to become the region with the highest number of undernourished people in [ ] . covid- could exacerbate this trend, while the effects of the current health crisis on food security may be amplified by local outbreaks of other diseases that have been endemic in africa and asia. many scholars, including mouloudj et al. [ ] , bakalis et al. [ ] , poudel et al. [ ] , and siche [ ] , witnessed significant adverse effects of sars, mers, avian and swine flu, ebola, and other outbreaks on both agricultural production and food consumption behavior. on a smaller scale and in a more localized context, endemic diseases cause disruptions across local food supply chains similar to those the covid- pandemic does to the global food supply. according to ceylan and ozkan [ ] , both sars and mers had a downsizing effect on the production and supply of food, as well as on labor demand in agriculture. kodish et al. [ ] and wernery and woo [ ] found movement restriction policies and quarantines introduced during mers, ebola, and other more local outbreaks to have substantial effects on agricultural production, food industry, as well as on distribution and retailing of many staples. dounamou et al. [ ] revealed a significant shift in consumption patterns during ebola outbreaks in west africa. in an attempt to avoid the consumption of wild meat potentially associated with the ebola virus disease, many people tend to switch to domestic meat and fish. in a situation when affordability and availability of alternative protein sources are deteriorated by trade and economic factors (as we see it amid the covid- pandemic), local outbreaks of other diseases may substantially aggravate both health and food security status of broad segments of the population. transmissibility of covid- is estimated to be . compared with . for sars. other recent pandemics had lower basic reproductive rates- . for the influenza pandemic and only . for mers [ ] . despite comparable transmissibility rates, the trajectories of covid- and sars are different. while sars outbreak was contained within eight months with a global total of reported cases across countries [ ] and mers caused reported cases in countries [ ] , covid- is spreading rapidly with over million known cases as the end of june . but the unprecedented spread of covid- throughout the world compared with other pandemics of the past is caused by greater ease of global transportation [ ] and higher population density [ ] the world has achieved by , not exclusively by higher contagiousness or better transmissibility of the novel coronavirus. with the growing globalization, any local outbreak has its chance to emerge to the global pandemic, while climate change and environmental degradation may increase the appearance of zoonotic diseases in humans [ , ] . in ldcs and developing countries of africa, asia, and the middle east, the impact of outbreaks on the food security status of people is particularly severe in transitional food value chains, such as wet markets [ ] . they bring together large numbers of people in crowded spaces at considerable risk of contagion [ ] . according to hasöksüz et al. [ ] and silva-jaimes [ ] , in such traditional food markets where human-wildlife interactions and cross-species infections are frequent, novel coronaviruses are likely to emerge periodically. petersen et al. [ ] also expect a post-covid- pandemic of another coronavirus, an influenza virus, a paramyxovirus, or a completely new disease to be highly likely in the nearest future. due to rather high economic and social costs of bringing local outbreaks under a successful level of control at early stages [ ] , ldcs and developing countries of africa and south asia are particularly vulnerable to the frequency and intensity of disease cycles that may realize their "pandemic potential". on top of the health and economic effects of covid- , there are climatic pressures that often aggravate supply-side food shocks in africa and asia (droughts, heatwaves, locust swarms, etc.) [ ] . in , production declines due to dry weather conditions are expected in morocco and tunisia [ ] . in east africa and south asia, significant rainfall amounts resulted in floods and caused damages to farmland and livestock deaths. zurayk [ ] has recognized locust invasion in the countries of the middle east and east africa as a further destabilizer of the stability of food supply in the times of the pandemic. shilomboleni [ ] prognoses the covid- pandemic to put a further strain on africa's agricultural sector amid the recent desert locust outbreak in the horn of africa. in west africa, covid- lockdowns are limiting population movement and causing local labor supply shortages [ ] . according to fao's crop prospects [ ] , adverse weather resulted in a below-average output in north africa and central asia and near-average cereal harvests in central america and the caribbean. amid such climate-change driven disruptions of food systems, the pressure of both covid- and local outbreaks on food consumption may be intensified by lower harvests and higher food prices in group countries, as well as across a wider community of developing economies. mouloudj et al. [ ] and janssens et al. [ ] expect developing countries of africa and asia in which agriculture contributes significantly to gdp (sierra leone, chad, niger, mali, cambodia, and vietnam) to be affected by both climate and economic effects of the pandemic (suspension of agricultural activities, agricultural labor lockdowns, etc.). according to the fao estimates [ ] , over million people in africa in need urgent food assistance, including million in nigeria, . million in burkina faso, million in niger, . million in mali and sierra leone, and million in chad. with respect to food availability, domestic agricultural production in ldcs and developing countries of africa may be severely affected by the disruption of the supply of various inputs [ ] , including animal feed and ingredients for food product preparation, especially if they need to be imported [ ] . hypothesis : partly confirmed. in group economies, the influence of food inflation over access to food and agricultural products is stronger than that of food trade over food availability. in low-income economies, the food security status of people is significantly influenced by both the physical availability of and economic access to food products. according to fao's most recent food security report, a key reason of growing food insecurity in developing countries is that many people cannot afford the increasing cost of healthy diets, while the nutritional status of vulnerable population groups has been deteriorated due to the economic impacts of covid- [ ] . martin and anderson [ ] and freund and Özden [ ] assumed that protectionist trade policy could bring a risk of additional economic losses for developing countries by insulating domestic markets from global food price fluctuations. the fao's monitoring of food price changes [ ] since february demonstrates that amid the covid- crisis, trade restrictions are imposed against the backdrop of growing food prices. the fao food price index averaged . points in june (by . % higher than in may ) [ ]. zurayk [ ] reports a global price increase in the food basket of % to % with the prices of dairy products, vegetable oils, sugar, and other food and agricultural products rebounded to multi-month highs [ ] . our results indicate that rising food inflation deteriorates food access across group countries as it is tightly linked with the increasing number of people with insufficient food consumption. this correlates with fao's estimation that the cost of a healthy diet in has exceeded the international poverty line, making it unaffordable for the poor and thus fueling food insecurity in most developing countries, particularly in sub-saharan africa and southern asia [ ] . healthy diets have become % less affordable compared to the nutrient adequate diets and five times more expensive than diets that meet only dietary energy needs through a starchy staple [ ] . many scholars, including bakalis et al. [ ] , berkowitz et al. [ ] , gundersen and ziliak [ ] , and garcia et al. [ ] , associate undernourishment with adverse health outcomes, including chronic conditions, mental health challenges, and increased risk of mortality. niles et al. [ ] found that lower economic access to food forced many food-insecure households to disrupt eating, cut meals, eat less to stretch their food, or even go hungry. this link between the cost of a diet and food security status has an important impact on individual health. an increase in food inflation is confirmed to have a significant effect on food insecurity in group countries, thereby supporting hypothesis and confirming previous findings of smith et al. [ ] , power [ ] , sonnino et al. [ ] , esturk and Ören [ ] , and many other authors who linked food insecurity with the level of income rather than with food imports. in our study, the strongest influence of food inflation on the number of people with insufficient food consumption is revealed in low-income economies of sub-saharan africa (burkina faso, ethiopia, guinea, among others), as well as some countries of asia and the middle east. the unctad [ ] also acknowledged the countries of sub-saharan africa to be particularly exposed to demand-side risks of food access during the covid- crisis, including contracting incomes, downturns in economic growth, undernutrition, and micronutrient deficiencies in response to income shocks. food inflation affects demand, but inflation itself is often a product of changing demand patterns. during the economic crisis of - , reduced income made people spend less and resulted in shrinking demand for food [ ] . the novel health crisis is quite a different story. on the back of rising lockdown fears in february-march , food inflation was fueled by higher demand due to panic buying [ , ] . although yuen et al. [ ] , zurayk [ ] , and fawzi et al. [ ] did not account for the level of income as a factor that affected such consumer behavior, we may assume the contribution of panic buying to food inflation to be more significant in group countries. in low and lower-middle-income economies, people have less free money to stock up food, while most cases of panic buying have been evidenced in developed countries [ , ] . in ldcs and developing economies, no significant spikes in food demand have been registered in the first quarter of . on the contrary, the fao [ ] expects the crisis-induced economic downturn to alter dietary patterns in the developing world due to a disproportionately larger decline in consumption of higher-value products like meat, fish, fruits, and vegetables. many scholars [ ] [ ] [ ] have found the likelihood of food insecurity to increase with income inequality. according to the fao [ ] , the inequality-insecurity link is % stronger for low-income economies compared with middle-income ones. this well agrees with our finding of the disproportional effects of food inflation on food insecurity across the three groups of countries. for instance, in mozambique (group ), keeping other variables constant, a % increase in food inflation leads to a growth in the number of people in food insecurity status by . % (by . % in tajikistan, by . % in burkina faso, . % in guinea, and so on down the list of group economies). in group , the x -y link is weaker while that in group is the weakest among the countries included in the study. there are even negative relationships between x and y in some group countries of the middle east and southeast asia. with that said, our study demonstrates that in lower-middle and upper-middle-income developing countries, the causality link between food inflation and food security is weaker compared with that in ldcs. generally, in low-income countries, food supply is for the most part ensured by local staple foods, whereas extensive import is prohibitively expensive. according to the fao [ ] , low-income countries rely more on staple foods and less on fruits and vegetables and animal source foods than high-income countries. as previously found by thome et al. [ ] , ritchie et al. [ ] , and elbushra and ahmed [ ] , weak cointegration between food inflation and food security in low-income economies could be explained by the high portion of locally produced staples in consumption. amid the covid- outbreak, some countries have decreased food purchases from abroad, thus automatically increasing their foreign trade balances due to the lower portion of imports. as more households switched to locally produced staples, their food security status improved. however, as noticed by devereux et al. [ ] and farrell et al. [ ] , a closure of open-air markets and a ban on street vendors (the two most common food outlets in poorer countries) may disrupt food access even in a situation when consumption is reoriented on local products. prior to the current health crisis, many food-insecure households have reported such food coping strategies as, for example, seeking resources from the charitable food sector or relying on social networks for support [ , ] . amidst covid- lockdowns and restrictions, most of the nutrition assistance programs have been frozen. therefore, it is revealed that food availability seems to be strongly related to the food security status of households, but through local supply, not import. following deuss [ ] , martin and anderson [ ] , and hendrix [ ] , we assume that food trade restrictions were more pronounced in the countries with a higher import dependency. according to wood et al. [ ] , for import-dependent economies, both global food chain disruptions and protectionist trade policies on the part of key suppliers could have serious negative consequences for food security. this agrees with puma et al. [ ] , who found that ldcs suffer greater import losses due to disruption of food supply chains through their increased dependence on imports of staple foods. there is a unidirectional x →y causality across group , but the significance of the link is low even in the countries where food availability largely depends on imports (haiti, guinea, tajikistan). these findings do not support hypothesis . with an increase in the level of income, the link between food trade balance and food availability becomes tighter. the strongest effect of x on y is revealed for import-dependent upper-middle-income economies (jordan, lebanon, botswana, algeria, colombia). in most low-income countries, we see how a lower proportion of food imports in trade amid the covid- outbreak is associated with a reduction in the number of people with insufficient food consumption. hypothesis : confirmed. different from the low-income economies, in group countries, the food security status of people is affected by food trade and currency exchange rather than by food inflation. as recognized by wood et al. [ ] and hendrix [ ] , food import is particularly essential to ldcs for meeting the dietary needs of their population during the covid- outbreak. our results; however, suggest that group and group economies rely on less diversified imports compared to group countries which are deeper integrated into global supply chains. for the latter, higher dependence on imports results in a stronger influence of food trade balance and currency exchange on food supply and, consequently, on the food security status of people. while devereux et al. [ ] stated that covid- had not compromised food supply globally, mouloudj et al. [ ] and toffolutti et al. [ ] found food security status of developing countries that depended on imports of staples to be particularly threatened by disruptions of the food supply in the first half of . in import-dependent developing countries, currency depreciation drives up the cost of food imports [ ] . thus amid market uncertainties induced by the covid- crisis, currency exchange becomes a factor of both food availability (more expensive imports due to currency depreciation) and access to food (the higher price of imported food on the domestic market when expressed in national currency). the unctad [ ] revealed heightened risks to food security in those countries of north africa and the middle east that rely on food imports and thus are dependent on currency volatilities triggered by the pandemic. in support of this unctad's estimation, the strongest effects of x and x on y are found for algeria and turkey. in furtherance of hypothesis , we expect an increase in the proportion of y explained by both food trade and currency exchange, particularly, in upper-middle-income countries. in libya, where the dependency on food imports exceeds %, the impact of x on y is projected to be the highest among the three groups of countries ( . %). in namibia, another group country largely dependent on imports, the proportion of x in y will almost reach . % by march . the importance of currency exchange in securing food supply will go up in the countries deeply integrated into global food supply chains. for instance, in turkey, . % of y will be explained by x . the effect of food inflation on the number of people with insufficient food consumption is found to be weaker across upper-middle-income economies compared to that in low-income countries. this finding both supports hypothesis and agrees with frankenberg and thomas [ ] and smith and glauber [ ] , who revealed that higher prices for staple foods aggravated poverty traps for low-income households, but might not have much effect on the food security status of relatively well-off households. on the other hand, domestic price volatility may be exacerbated by trade restrictions that have been implemented by some group and group countries on the backdrop of the covid- outbreak. in the studies on the effects of export restrictions during the global crisis of - , deuss [ ] and djuric et al. [ ] demonstrated that protectionist policies did not achieve their objective of reducing price volatility in the country imposing the restriction. there are also studies that show how trade restrictions resulted in food price spikes during the food crises in - [ ] , - [ ] , - [ , - ] , and - [ ] . dawe and timmer [ ] and abbott [ ] found that, in the short-run, an export ban could be a successful decision to ensure the food security of a country by both establishing a reserve of staples and isolating domestic market from the global price volatility. for instance, in cambodia, that limited exports of certain agricultural products in march-april , we see how both negative balances of food trade and low food inflation resulted in the reduction in the number of people with insufficient food consumption. for vietnam and turkey, on the contrary, their decisions to restrict food export have not brought much success. the ardl analysis demonstrates that in vietnam, a % change in the food trade balance is associated with an increase in food insecurity by . %. in turkey, the x -y relationship is weaker but still positive. in both countries, we revealed substantial causal interaction between x and y ( %→ . % in turkey and %→ . % in vietnam). this result supports the estimations of anderson and nelgen [ ] , giordani et al. [ ] , and rude and an [ ] , who found that trade protectionism might trigger food inflation and thus aggravate food insecurity. irrespectively of any particular economic or food crisis, developing countries with their limited resources are more vulnerable to the deterioration of the macroeconomic environment. food price volatility, no less food trade bans, is particularly detrimental to low-income countries where either a disruption of a supply chain or a contraction of economic access to staples may raise food conflicts. before the covid- outbreak, over two billion of the most impoverished people in the world spent up to % of their disposable income on food. the economic downturn stemmed from the pandemic may result in substantial growth of this figure, since in poorer countries, food demand is particularly linked to income [ ] . in the past, both global (sars and mers) and local (ebola, avian and swine flu) outbreaks had significant adverse effects on not only the health of people but also agricultural production and food consumption patterns across the developing world. the fao expects hunger to increase in developing countries where the economy has slowed down or contracted due to the covid- crisis [ ] . there are threats to the access of the poor to food as a consequence of lost income from lockdowns, trade restrictions, food inflation, and currency depreciation. most ldcs as well as many developing countries also suffer from underinvestment in public health, which may amplify the pandemic's impacts [ ] . this study is the very first try to assess the preliminary effects of the covid- pandemic on the food security status of people across the developing world. in the cases of ldcs and developing countries most vulnerable to food insecurity, the authors attempted to contribute to the nascent array of studies on trade and economic influences of the global health crisis over food availability and access to food and agricultural products. as distinguished from those few studies on covid- effects on food supply chains that have been published so far, we revealed interactions between the number of covid- cases and food security status of people across three groups of ldcs and developing economies. the consecutive application of the ardl method, yamamoto's causality test, and variance decomposition allowed us to assess the impacts of foreign trade, inflation, and currency exchange on the number of people with insufficient food consumption during the global health crisis. three key findings have emerged from testing of the hypotheses in this study. first, the covid- pandemic affects both the food security status of people and the stability of food supply chains in developing countries across the world. the effects are more perceptible in upper-middle-income economies than in ldcs given the deeper integration of the former in global supply chains and capital-intensive agricultural systems. second, in lower-income developing countries, food security risks attributed to the emergence of the covid- health crisis are mainly related to economic access to adequate food supply (represented by food inflation parameter). third, in higher-income developing countries, availability-sided food security risks are more prevalent (represented by the parameters of food trade and currency exchange) (figure ). obviously, the estimations provided in this paper are rather rough. the study is built on a short array of data covering only six months that have passed from the start of the covid- spread. over time, seeding of new data on the number of new covid- cases, dynamics of food trade balances, food inflation rates, and currency exchange volatilities will allow one to use the established methodology framework to obtain more well-grounded quantitative assessments of the pandemic's impacts on food security. as more comprehensive data become available from the reports by wfp, fao, wto, and other organizations, the set of variables should be expanded to capture a multidimensional character of food security, including stability of food supply and utilization of food and agricultural products. we do not know whether the pandemic will decelerate by the fall of or whether the second wave will strike the world in . it is yet hard to predict how effective the containment measures will be in slowing the spread of the virus. that is why the three-quarter variance decomposition projections presented in this study must be tested and adjusted continually to monitor the strengths of inter-variables causal interactions in the long-run. this will equip decision-makers with reliable estimations that may help to design coherent and effective policies to mitigate the impact of covid- on food security across developing countries in various parts of the world. supplementary materials: the following are available online at www.mdpi.com/xxx/s . table s : adf and pp tests results, group , table s : adf and pp tests results, group , table s : adf and pp tests results, group , table s : ardl short-run estimates, group , table s : ardl short-run estimates, group , table s : ardl short-run estimates, group , table s : fmols and dols tests results and ardl long-run estimates, group , obviously, the estimations provided in this paper are rather rough. the study is built on a short array of data covering only six months that have passed from the start of the covid- spread. over time, seeding of new data on the number of new covid- cases, dynamics of food trade balances, food inflation rates, and currency exchange volatilities will allow one to use the established methodology framework to obtain more well-grounded quantitative assessments of the pandemic's impacts on food security. as more comprehensive data become available from the reports by wfp, fao, wto, and other organizations, the set of variables should be expanded to capture a multidimensional character of food security, including stability of food supply and utilization of food and agricultural products. we do not know whether the pandemic will decelerate by the fall of or whether the second wave will strike the world in . it is yet hard to predict how effective the containment measures will be in slowing the spread of the virus. that is why the three-quarter variance decomposition projections presented in this study must be tested and adjusted continually to monitor the strengths of inter-variables causal interactions in the long-run. this will equip decision-makers with reliable estimations that may help to design coherent and effective policies to mitigate the impact of covid- on food security across developing countries in various parts of the world. table s : adf and pp tests results, group , table s : ardl short-run estimates, group , table s : ardl short-run estimates, group , table s : ardl short-run estimates, group , table s : fmols and dols tests results and ardl long-run estimates, group , table s : fmols and dols tests results and ardl long-run estimates, group , table s : fmols and dols tests results and ardl long-run estimates, group , table s : ty causality test results, group , table s : ty causality test results, group , table s : ty causality test results, group , table s : variance decomposition of y over a nine periods (three quarters) horizon, group , table s : variance decomposition of y over a nine periods (three quarters) horizon, group , table s : variance decomposition of y over a nine periods (three quarters) horizon, group . author contributions: v.e. designed the research framework and wrote the paper; t.g. analyzed and interpreted the data. all authors have read and agreed to the published version of the manuscript. sustainable development goals food and agriculture organization of the united nations; international fund for agricultural development united nations children's fund; world food programme; world health organization. the state of food security and nutrition in the world . safeguarding 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no conflicts of interest. the funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. key: cord- -pne qolr authors: yassi, annalee; bryce, elizabeth a; breilh, jaime; lavoie, marie-claude; ndelu, lindiwe; lockhart, karen; spiegel, jerry title: collaboration between infection control and occupational health in three continents: a success story with international impact date: - - journal: bmc int health hum rights doi: . / - x- -s -s sha: doc_id: cord_uid: pne qolr globalization has been accompanied by the rapid spread of infectious diseases, and further strain on working conditions for health workers globally. post-sars, canadian occupational health and infection control researchers got together to study how to better protect health workers, and found that training was indeed perceived as key to a positive safety culture. this led to developing information and communication technology (ict) tools. the research conducted also showed the need for better workplace inspections, so a workplace audit tool was also developed to supplement worker questionnaires and the ict. when invited to join ecuadorean colleagues to promote occupational health and infection control, these tools were collectively adapted and improved, including face-to-face as well as on-line problem-based learning scenarios. the south african government then invited the team to work with local colleagues to improve occupational health and infection control, resulting in an improved web-based health information system to track incidents, exposures, and occupational injury and diseases. as the h n pandemic struck, the online infection control course was adapted and translated into spanish, as was a novel skill-building learning tool that permits health workers to practice selecting personal protective equipment. this tool was originally developed in collaboration with the countries from the caribbean region and the pan american health organization (paho). research from these experiences led to strengthened focus on building capacity of health and safety committees, and new modules are thus being created, informed by that work. the products developed have been widely heralded as innovative and interactive, leading to their inclusion into “toolkits” used internationally. the tools used in canada were substantially improved from the collaborative adaptation process for south and central america and south africa. this international collaboration between occupational health and infection control researchers led to the improvement of the research framework and development of tools, guidelines and information systems. furthermore, the research and knowledge-transfer experience highlighted the value of partnership amongst northern and southern researchers in terms of sharing resources, experiences and knowledge. working conditions for health workers are undergoing rapid change [ ] . new methods for diagnosis and treatment of diseases, combined with rapid communication technology, makes the world's ability to communicate and disseminate new knowledge remarkably effective; the speed with which the sars outbreak was controlled [ ] and pandemic h n information transmitted are clear illustrations [ ] . on the other hand, economic globalization is severely straining healthcare resources, preferentially benefiting richer countries [ , ] . the changes in labour flow [ ] and trends to deregulation [ , ] also impact the health and well-being of the labour force. international travel, representing million passengers in [ ] , adds complexity in preventing and reducing rapid transmission of infectious diseases across borders. rapid travel has intensified the global need for consistent application of infection control principles to ensure the safety of patients, hospital visitors and health workers. healthcare acquired infections (hais) are often linked to invasive devices, longer hospital stays and more time spent in intensive care [ ] . these infections make up a substantial proportion of the infectious disease burden in high income as well as in low and middle-income countries (lmics) [ ] . the risk of a hai is - times higher in lmics than in high income countries, and this may be an underestimate, due to differences in the intensity of surveillance [ , ] . an estimated % of patients could suffer from preventable hais [ ] . along with patients, healthcare workers are also at high risk of exposure to biological agents in healthcare settings [ , ] . almost half the cases of sars were in health workers [ ] , % of the hepatitis b and c that occurs in health workers is estimated to be due to occupational exposures [ , , ] , and health workers have a high risk of multiple drug-resistant tuberculosis [ ] . to protect the health and safety of patients and health workers in all countries, infection control and occupational health professionals must work closely together. our interdisciplinary international collaboration has contributed to produce practical tools such as guidelines, online and face-to-face training products, checklists, research materials, frameworks and a health information system. this innovative participatory paradigm that has been widely embraced by collaborators and front line health workers. post-sars epidemic, the canadian-based team (led by co-authors ay, an occupational health researcher, and eab, an infection control specialist) conducted research to ascertain the determinants of sustainable adherence to appropriate infection control practices, refining a framework on individual, organizational and environmental factors [ ] . in a survey of , workers across sixteen hospitals in british columbia the team found that health workers who rated the environmental protective measures highly at their institutions were times more likely to report a high level of compliance with appropriate personal protective practices compared to those who did not rate this factor highly at their institutions. similarly, those who perceived organizational factors in the workplace to be consistent with safe practices were times more likely to report good compliance. interestingly, though, there was no association with the individual factors previously thought to be pivotal in affecting compliance [ ] . next, a survey of infection control and occupational health resources and a questionnaire completed by healthcare workers were compared with on-site observational audits in facilities in british columbia and ontario. health workers believed that plans were available to protect against future sars-like events but audits revealed that these did not exist in many facilities. both occupational health and infection control were underresourced post-sars, with occupational health professionals particularly lacking in british columbia. there was a discrepancy between health workers' perception of what was available and what is actually accessible in facilities [ ] , highlighting the need for better communication. the findings from our initial research in canada led to our developing an evidence-based workplace assessment tool. our initial research in canada also showed that training health workers was significantly associated with health worker perception of a positive safety culture in their healthcare workplace [ , ] . one of the identified constraints was the limited quantity of information that could be presented at group sessions due to the time restrictions. these sessions were insufficient to build knowledge and good practices on the selection and use of personal protective equipment [ ] . these research observations were the impetus for our developing online infection control courses that were self-directed, flexible, interactive, and relevant to day-to-day work activities [ , ] . in the region of the americas, our team collaborated with the pan american health organization (paho) on a project related to the prevention of occupational transmission of infectious diseases among health workers. in collaboration with the ministry of health from ecuador, the team members collectively adapted the canadian workplace assessment tool and questionnaire to assess knowledge, attitudes and practices in three hospitals in ecuador (two in quito and one in the amazon) [ ] [ ] [ ] . the workplace assessment tool comprises a list of occupational hazards, including physical, chemical, biological, ergonomic, safety, and psychological hazards. under each hazard classification, the evaluator completes the workplace assessment form by indicating whether the environment and practices are satisfactory, require correction but are not an immediate hazard, or require immediate correction. using the results of the questionnaire and needs assessment, local colleagues identified strengths and challenges at each healthcare facility and initiated projects to address the issues unearthed. for example, campaigns were begun to improve hand hygiene and reduce needlestick injuries, as well as implement muchneeded renovations in the emergency department of one of the hospitals [ ] all priorities identified by using the tools developed. following the success of this initial work in canada and ecuador, the government of the republic of south africa (through co-author ln) invited our team to lead a healthy hospital initiative in that country. again, working closely with local colleagues, we revised the assessment tools, then invited participants to a three-day workshop on occupational health and infection control to complete the initial survey. invited participants included all the representatives elected from the workforce to serve as health and safety representatives as well as the occupational health and infection control staff members from pelonomi hospital, the health facility selected for our pilot study [ ] . the participants were then divided into ten groups to conduct workplace audits, covering five domains; physical environment, specific occupational health practices and hazards, specific infection control practices, equipment and procedures, and ergonomics. training sessions were also conducted specifically for medical practitioners, a usually hard-to-reach population, as the canadian-based research also confirmed [ , ] . having identified the need for better data collection instruments, we developed the occupational health and safety information system (ohasis), a web-based health information system, to track incidents, exposures, risk factors, immunizations and occupational injury and diseases. based on experience in canada [ ] , we ensured that this system particularly focused on preventing hais in health workers. we then began the process of implementation and evaluation [ , ] . meanwhile, paho invited our team to assist in preparing health workers for the global summit and the pan american games in trinidad and tobago. the workplace audit tool, developed originally in canada by the team (comprised of experts in program evaluation, infection control, occupational health, information technology, public health and medicine), and refined from use in ecuador and south africa, was again adapted and workshops held to train occupational health and infection control practitioners from countries across the caribbean. the audit tool is a structured form, which enables healthcare workers to evaluate their working environment in a systematic manner. health and safety professionals have noted that the tool has enabled them to set priorities and act upon identified needs. a novel animated skill-building tool that permits health workers to practice selecting and wearing personal protective equipment was also developed for the caribbean training (http://www.ghrpinnovation.com/protectpatti/eng/index. html). in collaboration with paho, the basic infection control course originally developed in canada post sars was then translated into spanish (http://www.ghrpinnovation.com/ infectioncontrol), with input from colleagues in ecuador (led by co-author jb). we collaborated with member countries to pilot the online course in several countries to ensure its relevance to the local context. during the pilot phase, the participants expressed high levels of satisfaction towards the training specifically the interactive format and comprehensive content. the online course and tools, such as the workplace assessment, have been presented at various regional and national trainings such as the paho train-the-trainer workshops which were held in venezuela, colombia, ecuador, trinidad and tobago and belize. the latin american and south african work also included development of evidence-based training programs to specifically build capacity of health and safety committees, as our previous research indicated was important [ ] . the tools developed have since been revised and are now being used to train health and safety committees in canada as well. advances in worker health and safety have been historically tied to workers' struggles, led usually by trade unions, to obtain better working conditions. the well-being of the workforce, particularly when the economy is strained, as is occurring ever more forcefully in this era of deregulated globalization [ , ] , is often treated as expendable by decision-makers. ironically, perhaps, worker health and safety has not received greater attention in the healthcare sector than in other economic sectors [ ] , despite the fact that health workers constitute the largest workforce in the world, with an estimated million worldwide [ ] . while the tools we produced are limited in conveying an indepth understanding of the complex global forces that weaken public health systems, hindering the allocation of resources to infection control and worker health, they do help mitigate the impact of resource strains in countries such as ecuador and south africa, where strong government commitment has been expressed towards health system improvement and worker well-being. our collaboration has produced a better understanding of the social, cultural, environmental, occupational and economic processes that determine the health of health workers locally [ , , , , [ ] [ ] [ ] and globally [ , , , ] . our conceptual framework has been since used by other research groups [ ] ; our findings were used by hospital decision-makers and government planners; and these research findings were taken into account by our own team in the development of the tools described above. as noted above, the research we conducted first confirmed that providing health workers with training to properly protect themselves from infectious diseases is significantly associated with better perception of a positive safety climate. after we created training tools to address the organizational, environmental and individual factors we identified as important determinants of infection control compliance, we conducted further research followingup on the use of these online tools. we then found that providing time to take the course on work time was significantly associated with higher intention to comply with safety precautions compared to promoting the course on a voluntary basis (logistic regression model showed a statistically significant difference between supervisor-required and voluntary groups with respect to perceived importance of infection control in the workplace, the extent to which the facility ensures patient safety, and the extent to which the facility ensures staff safety) [ ] . this led to the course becoming mandatory in british columbia [ ] . building on the findings of our research in canada, initial work in ecuador, and our pilot study in south africa (for example, poor staff knowledge on recapping of needles as well as the finding that more than half the respondents felt that they were not given guidance as to how to perform their jobs safely [ ] ), we collaborated with government officials in ecuador, south africa and the caribbean to develop guidelines, policies and programmes. we also worked with international agencies to develop new policy guidelines [ ] . acting on our own research findings, we created further training materials, addressing not only basic infection control and how to don and doff personal protective equipment, but how to establish health and safety committees, inspect workplaces, investigate incidents, and establish policies and health and safety programs based on solid evidence. our work has squarely addressed north-south power relations and the digital divide, always building on local capabilities to transfer knowledge south-south, north-south and vice versa in a respectful manner that benefits both northern as well as southern partners [ ] . the products developed have been widely heralded as innovative and important components of "toolkits" used internationally. the tools now used in canada have, in turn, been improved from the collaborative adaptation process for south and central america and south africa. thus this research has resulted in health service approaches, products and policies that are being embraced nationally (e.g. in ecuador, trinidad-tobago and south africa) and internationally (e.g. through international organizations including paho) as well as having canadian impact [ , , ] . the guidelines, research and needs assessment instruments, web-based health information system, and on-line learning modules will continue to have widespread impact well into the future. more importantly, by elucidating the links between worker health and the health of patients, we have begun to show that attending to the health of the healthcare workforce is not only the right thing to do to protect this vulnerable population, but also produces safer healthcare for all. this case thus illustrates the benefits of infection control and occupational health researchers working together and also how canadians and southern partners alike benefit from international collaboration. this case study is really about a partnership of partnerships. first, there was the partnership between canadian occupational health and infection control [ ] [ ] [ ] [ ] [ ] , ] researchers, and simultaneously, a partnership between an inter-disciplinary ecuadorean occupational and environmental health team and canadian counterparts who shared an appreciation of an ecosystem approach to human health [ ] , including its applicability to emerging infectious diseases [ ] . meanwhile, a new partnership was being forged between the combined canadian occupational health and infection control team and their south african counterparts [ ] , brought together by the world health organization (who). finally, with the assistance of paho and later also the who, the various partnerships were brought together, informing each other in what became an integrated international approach to promoting healthy healthcare. knowledge translation experts emphasize the importance of good quality evidence [ ] as well as involving users of the research findings at the earliest stage. thus it was essential that we involved the local healthcare leadership, already established occupational health services as well as health and safety committee members and governmental-based expertise at the outset. in ecuador, the project built on a strong partnership between the university of andina simon bolivar, the university of cuenca, and various other universities and healthcare facilities on one hand, and the various centres at the university of british columbia on the other. having a strong local champion is key to success, and ecuadorean co-author (jb) fulfilled that role. similarly, we chose pelonomi regional hospital in the free state as a research pilot site to support knowledge translation and capacity building, in large part due to the local champion. a major impact of our work to date has been the demonstration of the benefits of close collaboration between infection control and occupational health, which, in most jurisdictions, was weak. the director of the national institute for occupational health in south africa cited our collaboration as a model that should be embraced in south africa. linkages are now being fostered between infection control and occupational health personnel, modeled on the canadian-initiated collaboration; ohasis, or at least some modules from ohasis, is being used by occupational health and infection control professionals and by health and safety committee members in latin america, the caribbean and south africa, as are the interactive online training modules. the full benefits of these innovations will increasingly manifest over time, but the impact on knowledge, attitudes and practices has already begun to be demonstrated [ ] . collaboration requires mutual respect and trust, as well as a shared vision and sense of common mission. we were fortunate that the various partnerships within this partnership-of-partnerships all agreed to an open source, creative commons philosophy, in which none of the products of our work would be commercialized. this viewpoint also maintains that all derivatives must be approved by all members of the collective, which ensures on-going quality improvement and a flexible, yet standardized, and more easily communicated approach. with this sense of common mission, we are confident that the fruits of our collaboration will continue to provide high quality knowledge transfer of best available evidence. our first real challenge was in sustaining engagement of politically active workplace stakeholders, specifically the trade unions. we have had decades of successful experience in this regard [ , , ] , but may have taken for granted that labour union trust would be there. while this was not problematic in our latin american work, a communications breakdown occurred in the south african work, creating a setback. the lesson learned was that trust can never be assumed, and it is well worth taking the time to ensure that all key stakeholders are indeed engaged before the project moves ahead too far. getting process issues right is paramount to success. a second challenge, also stemming from politicallycharged labour relations, was the advent of a major strike in south africa just as we were beginning what was supposed to have been an intensive two-week capacitybuilding effort. the team therefore had to come up with training innovations (including role-play, drawn scenarios, and interactive on-line learning modules [ , , , ] ); with necessity being the mother of invention, the products created were very well-received and will serve the crosscontinental partnerships well for years to come. another important lesson to note is the importance of thinking about scale-up and sustainability from the start. while the ecuadorean pilots were successful, resources are not in place to continue the efforts at the desired intensity. learning from this, before launching the full pilot in south africa, decision-makers (including coauthor ln) started planning for scale-up early, should the pilot prove successful. this required thinking through complexities beyond the pilot, such as who will continue to implement and monitor the model after the pilot has ended, and how should the model be altered in the pilot with such questions in mind. by working closely with the who, the international labour office, the international commission on occupational health, and a world-expert on scaling up [ ] , we are now optimistic that the tools produced will be successfully used not only in local pockets, but on national and international scale. from a funding perspective, the increasingly embraced philosophy of open source [ ] and creative commons licensing [ ] assures that these tools are available without charge. key however, will be the extent to which local (and national) colleagues are indeed comfortable in using the tools and promoting their use locally. also, in the case of information technology that requires maintenance and periodic updating, commitment from authorities (either government or external funders/partners) is needed. the "business model" of using revenue from distribution in high-income countries to fund maintenance and updates globally, is one way that lmics can have their systems maintained and updated without strain on their resources, and assist high income countries to assume their global responsibilities [ ] . finally, it should be stressed that the success of this work has been, and will continue to be, based on frontline support and active engagement of the decisionmakers. this can never be taken for granted. severe acute respiratory syndrome (sars) and health care workers public health communication with frontline clinicians during the first wave of the influenza pandemic understanding "globalization" as a determinant of health determinants: a critical perspective taming 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creative commons licensing submit your next manuscript to biomed central and take full advantage of: • convenient online submission • thorough peer review • no space constraints or color figure charges • immediate publication on acceptance • inclusion in pubmed, cas, scopus and google scholar • research which is freely available for redistribution authors' contributions ay and eab conceived these projects and created the first draft of this manuscript. jb was responsible for the coordination of the projects in ecuador. nl was responsible for the projects in south africa. mcl aided in the coordination of the projects in venezuela and in trinidad and tobago. all authors (ay, eab, jb, nl, mcl, kl and js) helped to write and revise this manuscript. no competing interests to declare. key: cord- -q r g ue authors: williams, lloyd b.; prakalapakorn, s. grace; ansari, zubair; goldhardt, raquel title: impact and trends in global ophthalmology date: - - journal: curr ophthalmol rep doi: . /s - - -x sha: doc_id: cord_uid: q r g ue purpose of review: our goal is to provide a review of the impact, global estimates, and projection of vision impairment as well as ongoing systems for eye care delivery. recent findings: many of the blinding diseases in developing countries are preventable or curable, but the lack of ophthalmologists, the lack of education, and the lack of access to any eye care are some of the major obstacles encountered. summary: as our world becomes more interconnected through globalization, the interactions between different cultures and populations increase. global ophthalmology is a field dedicated to building sustainable eye care delivery systems to deliver high-quality care in minimal resource settings, with the aim of reducing blindness around the world. on october , , the world health organization (who) released a world report on vision that stated there are over . billion people with vision impairment or blindness worldwide, and over billion of those have conditions that could be treated or prevented [ ] . globally, the burden of vision impairment and blindness is greatest in low-and middle-income countries. despite effective and relatively low-cost interventions, refractive error and cataract remain the largest causes of vision impairment and blindness. there is expected to be an increasing demand for global eye care due to an aging population, changing lifestyles (leading to increased lifestyle-related blindness (e.g., diabetes)), and population growth. the global eye health report indicates several challenges in meeting this anticipated demand, including poor data to aid in planning and lack of integration of eye care into overall healthcare systems. the who global action plan emphasizes a delivery model relying on primary eye care as an approach to tackle visual impairment. one recently reported example of primary eye care enhancement is the global sight initiative [ ] . the global sight initiative is a strategic initiative of the seva foundation and supports a collection of non-governmental organizations and eye hospitals collaborating to reduce blindness and increase services. vision centers in this model aim to accomplish the following: ( ) provide primary eye care so referral hospitals can divert their resources to focus on sightsaving surgical interventions, ( ) identify patients that need surgical intervention or urgent referral for sight-saving treatment, ( ) help patients and families overcome barriers (fear, cost, transportation, lack of awareness of eye care needs) to receive advanced medical or surgical care, ( ) reduce cost to patients by decreasing geographic barriers, ( ) improve healthcare-seeking behavior and follow-up, ( ) improve gender equity of care, as vision centers have been shown to improve access for women by reducing cultural and transportation barriers, and ( ) improve community involvement, which provides economic development for the community and better compliance [ ] . the vision centers carry out three primary functions-recognize eye conditions, refract and provide spectacles, and refer patients to the sponsoring institution as needed. they also provide low vision and school and community eye services. progress in eye care can and is being made. a recent example is a collaboration between sightsavers and the government of nigeria. a vision right to sight strategy was implemented between and in sokoto state, nigeria. the zone chosen for the intervention had the lowest eye health indices in a baseline survey. over the decade, the number of ophthalmologists increased from zero to six and cataract surgery coverage from . to %, and among people over years old, visual impairment decreased from . to . % [ ] . lv prasad eye institute (based in hyderabad, india) created a system which is testing application of its eye care delivery system in liberia, west africa. the success of cross-cultural application of processes is of particular importance to developing eye care in countries that have the least resources. lv prasad uses a graded fee structure for the same clinical care, but provides the option of additional non-clinical services for a higher fee, i.e., air-conditioned waiting room, dedicated appointments, and more. lv prasad also uses a clinical urgency-based -tiered system ranging from the quaternary referral center to basic rural eye care and screening [ ] . this review presents details about the lv prasad system and we await the results of this endeavor in liberia. cataract is the most common cause of vision impairment or blindness, affecting million people worldwide [ ] . numerous ongoing public efforts have been devised to tackle the global cataract burden, but in recent years, these efforts have been focused on the often variable outcomes of surgery. in malaysia, a cumulative sum analysis metric was introduced in to assess the quality of cataract surgery outcomes. they evaluated trainees and surgeons who together perform - % of cataract surgeries nationwide. surgeons who fell below acceptable levels were mentored and monitored for improvement. over the implementation period from to , posterior capsule breakage rates fell from . to . % and post-operative best spectacle-corrected visual acuity (bscva) > / has increased from . to % [ , ] . implementation of quality control by monitoring outcome measurements and providing interventions as needed is important, but this should be implemented without requiring excessive manpower, which would divert resources from healthcare delivery. another utility in eye care planning is the onehealth tool, a program developed by the united nations (un) interagency working group on costing for use in national healthcare planning [ ] . it has been used in over countries to date. onehealth tool will be adding eye care to its healthcare planning interventions in and we look forward to seeing its effectiveness in assisting eye care planning particularly in the setting of detecting and intervening early in cataract blindness. far and away, the largest causes of vision impairment remain to be refractive error and presbyopia. the burden of myopia and presbyopia is increasing and unequally borne by lower socioeconomic status countries [ , • ]. an estimated . million people have vision impairment or blindness due to uncorrected refractive error and another million have unaddressed presbyopia [ ] . living in a rural area or underdeveloped region and increasing age are associated with decreased likelihood of adequate optical correction [ ] . globally, potential productivity lost due to visual impairment attributed to myopia (estimated $ billion) greatly exceeds the cost of correcting myopia [ ] . worldwide, east asia bears the greatest burden of myopia [ , • ]. although increased screen time and near vision work have been suggested to correlate with myopia [ , ] , a new systematic review demonstrated mixed results and did not establish a clear causal relationship between screen time and increased myopia [ ] . the -year results of a -year study of the low-concentration atropine for myopia progression study showed that atropine . % (compared with atropine . %, . %, and placebo) is the most effective dose for slowing myopia progression and axial elongation in children - years of age [ ] . public health efforts in the future need to address refractive error and reduce spectacle procurement to improve this large and growing cause of visual impairment. globally, vision impairment and blindness from diabetic retinopathy have increased over the decades from about . million visually impaired and , blind in to . million visually impaired and , blind in [ ] . as the global burden of diabetes grows, these numbers are expected to increase, as much of the growth in diabetes rates are occurring in middle-and low-income countries. by , an estimated million people worldwide are expected to have diabetes ( % in low-and middle-income countries) and about one-third of them are expected to have diabetic retinopathy [ ] . diabetic retinopathy is the leading cause of blindness in working age adults (age - years old). in africa, the prevalence of diabetic retinopathy is about % of diabetics [ ] . the presence and progression of diabetic retinopathy in african populations have been reported to be up to times higher than in european populations and there are few retina specialists to provide management [ ] . artificial intelligence (ai) and deep learning have been proposed as solutions to the growing problem of visual impairment and blindness due to diabetic retinopathy. while most studies on ai and diabetic retinopathy have been conducted in high-income countries, a promising new development in and is the publication of multiple studies addressing the use of ai in low-and middle-income countries. the first ai pilot programs in africa were published in , using retrospective kenyan patient images from the nakuru eye study cohort [ , ] . in , data from urban centers in the copperbelt province of zambia was published. this prospective study used ai to screen patients for diabetic retinopathy (i.e., referable diabetic retinopathy, visionthreatening diabetic retinopathy, and diabetic macular edema). their sensitivity of detecting vision-threatening diabetic retinopathy or macular edema was . % and . %, respectively. rarely were critical cases missed by their ai system. in all cases, grading by the ai system was similar to human graders [ ] . a key finding of this study was that the ai system was able to identify disease in an african cohort with high sensitivity and specificity even though the system was trained on patients of asian origin from the singapore integrated diabetic retinopathy program. a limitation of this study was the use of a high-complexity system (i.e., retina cameras and cloud-based telecommunications network). systems that incorporate ai into retinal cameras may have an advantage in the developing world by eliminating the need for internet access. another concern is that, once an image was identified as qualifying for a referral, there must be an eye care provider available who the patient can access. this can be difficult because a much lower ratio of ophthalmologists per diabetic retinopathy patients exists in sub-saharan africa compared with that in other regions of the world [ ] . in circumstances where cloud-based and high network resource-dependent systems may not be possible due to lack of consistent electrical power or internet access, simpler technology may be indicated for screening. a prospective study based in mumbai, india, used ai to examine remidio smartphone-based, nonmydriatic images for diabetic retinopathy screening. in this study of participants, this system detected referable diabetic retinopathy (i.e., diabetic retinopathy worse than mild, with or without macular edema) with a sensitivity of % and specificity of . %, and any form of diabetic retinopathy with a sensitivity of . % and specificity of . % [ ] . population-based screening programs like the uk program have reduced blindness due to diabetic retinopathy, but they require highly trained retinal graders and complex equipment. an advancement of the mumbai study was the use of an off-line automated analysis algorithm rather than a processor and internet-intensive deep learning and ai networks, which may be difficult to access in the developing world. two other data sets of patients have been published using the remidio system in bangalore and chennai. in bangalore, among patients screened, the sensitivity and specificity for detecting referable diabetic retinopathy were . % and . %, respectively [ ] . in chennai, among patients screened, the sensitivity and specificity for detecting any retinopathy was . % and . %, respectively [ ] . of note, when the ai system gave a false negative for diabetic retinopathy, the patient often did have other fundus lesions that were worthy of referral (e.g., central and branch retinal vein occlusions, drusen), thus would have been appropriately referred to an ophthalmologist. in thailand, using a google-based ai system, a retrospective clinical validation study of patients with diabetes demonstrated a sensitivity of . % and specificity of . % for detecting moderate or worse non-proliferative diabetic retinopathy. in the thailand study, the ai system was better or equal to regional graders for severe or worse non-proliferative diabetic retinopathy [ ] . an excellent review of ai and telemedicine describes the experiences in many countries that are just beginning to implement the use of ai in screening for diabetic retinopathy, which includes country-specific reviews of the application of ai for diabetic retinopathy screening in china, the usa, the uk, thailand, australia, singapore, and the african continent [ ] . in , a review discussed current ai systems (e.g., idx-dr (idx technologies inc., coralville, ia), retmarkerdr or retmarker screening (retmarker s.a., coimbra, portugal), singapore seri-nus (singapore eye research institute -national university of singapore, singapore), the bosch dr algorithm (robert bosch gmbh, bangalore, india), retinalyze® (retinalyze system a/s, hellerup, denmark)) [ ] . the united states food and drug administration has approved the idx-dr ai system for detecting diabetic retinopathy levels more severe than mild and without the requirement for further interpretation by a clinician [ , ] . proponents of ai screening programs report the potential benefits in reducing reliance on manual work and savings in healthcare costs and resources compared with in-person screenings performed by an eye care provider. in particular, the cost and time of producing retina-trained ophthalmologists are prohibitive. reduction of the need for specialists to screen diabetics may allow specialists to efficiently provide treatment to patients. globally, the number of people with vision impairment and blindness due to glaucoma is about . million persons [ ] . treatment and diagnosis of glaucoma are often marred in lowresource environments by failure of early diagnosis, medication procurement, limited minimally invasive surgical options, and access to glaucoma providers. artificial intelligence and deep learning algorithms have emerged as a potential powerful screening tool in the field of glaucoma. one study in the usa found that the detection of glaucoma from fundus images using ai was equivalent to or better than human graders [ ] . other studies are currently ongoing to apply deep learning algorithms in retinal nerve fiber layer octs in the diagnosis of glaucoma. to our knowledge, a prospective study of glaucoma detection via ai has yet to be published from the setting of the developing world, though it is foreseeable that a low-cost implantation of this technology may aid eye care professionals in the early diagnosis and treatment of glaucoma (fig. a) . chlamydia trachomatis is the leading infectious cause of blindness worldwide. children are the main reservoir of c. trachomatis, which is spread via ocular and nasal secretions. blindness is the result of corneal scarring due to trichiasis from repeated infections from c. trachomatis leading to conjunctival scarring of the eyelid (fig. b) . the who uses a "safe" (surgery, antibiotics, face cleanliness, environmental improvement) strategy for trachoma elimination from endemic areas. a who report states that, from to , the number of districts where the a, f, and e components of safe are lacking has decreased from million to million and the number of people with trachoma has fallen from . to . million [ ] . eight countries have been validated as having eliminated trachoma as a public health problem: cambodia, ghana, the islamic republic of iran, lao people's democratic republic, mexico, morocco, nepal, and oman. other countries have achieved elimination targets: china, the gambia, iraq, myanmar, and togo. a recent study out of southern ethiopia confirmed lack of face washing, soap, and access to latrines was associated with active trachoma and face washing and environmental cleanliness were factors in trachoma prevention [ ] . antibiotics, a key component of the safe strategy, has been a hot topic over the last couple of years as results of the mordor (macrolides oraux pour réduire les décès avec un oeil sur la résistance) trial have been published [ ] . in particular, they investigated mass azithromycin distribution mechanisms and its effects on trachoma and childhood mortality. the mordor trial, conducted in malawi, niger, and tanzania, showed for the first time in a randomizedcontrolled clinical trial that mass administration for azithromycin reduced child mortality in sub-saharan africa. the primary endpoint, mortality in children aged to months, was reduced in all locations, especially in niger ( % mortality reduction). in this study, , children were monitored, and azithromycin and placebo were given two times a year over years for a total of four doses. mortality was . % lower in the azithromycin group and this effect was greatest in niger and in children - months of age [ ] . this groundbreaking randomized-controlled clinical trial has led to more studies investigating the mechanism of mass azithromycin on both reducing trachoma and childhood mortality [ ] . the timing, frequency of administration, discontinuation strategies, and effects of mass azithromycin administration on trachoma were reported in several trials. in keenan et al. [ ] , the longitudinal effect of discontinuing a -year period of twice yearly mass distribution of azithromycin was that ocular chlamydia prevalence nearly doubled in communities where azithromycin was discontinued versus communities where it was continued. in the amhara region of ethiopia, an assessment of the progress of safe strategies was undertaken. the trachoma program began in amhara in and expanded to all districts between and . during this study, from to , this hyperendemic region was the first region in ethiopia to complete trachoma impact surveys (conducted to months after last mass drug administration) in every district. despite uptake of safe strategies and reductions in active trachoma (i.e., trachoma follicular (tf) infection and intense trachomatous inflammation (ti)), across the region, % of districts remained hyperendemic and only districts out of had prevalence of tf < % in children aged - years, the trachoma elimination threshold [ ] . these data suggest that - -year annual drug administration programs may not be enough to reach trachoma elimination levels and perhaps - -year programs in hyperendemic regions may be more appropriate [ ] . azithromycin administration in the gambia and in senegal led to decreased active trachoma (i.e., tf and ti), but did not decrease the prevalence of ocular c. trachomatis infection by amplicor testing year after a single round of treatment in children aged - years [ ] . this study was unable to determine why there was poor correlation between active trachoma as graded by an ophthalmic nurse and c. trachomatis infection. other studies have found a correlation between decreased clinical findings and decreased infection as determined by pcr testing at and months after a single administration of azithromycin; however, the decrease in inflammatory gene expression had returned to near pre-treatment levels at months [ ] . while current recommendations for communities to qualify for mass antibiotic treatment are based on the prevalence of tf in - -year-old children [ ] , one study introduced a new term, "trachomatous papillary inflammation (tp)," which is an expansion of ti (defined as p , severe papillary hypertrophy), including both p (moderate papillary hypertrophy) and p . based on their findings, they suggest that tp be added as a measure in trachoma control programs as an indication of the future risk of developing trichiasis [ ] . this -year longitudinal cohort study, carried out in northern tanzania to explore the relationship between c. trachomatis infection, clinical inflammation, and scarring development in children - year of age, found in multivariate analysis that scarring progression was strongly associated with increasing episodes of tp, and not associated with c. trachomatis infection or follicular trachomatous inflammation [ ] . currently, there are two major ongoing studies in treatments for trachoma. in , sie et al. published the study protocol for the community health with azithromycin trial (chat) which aims to assess child mortality in burkina faso with early azithromycin intervention in children between the th and th weeks of life and to study the efficacy of twice annual azithromycin distribution on children under years of age. the study began in august and plans to record macrolide resistance, serological markers of pathogen exposure, and child growth markers. completion is expected in [ ] . a second study, the maximizing trachoma surgery success (mtss) trial, began in april to study trachomatous trichiasis surgery techniques. enrollment is planned for a total of first-time trachoma surgery patients in ethiopia and will follow them for months after being randomized to one of the following surgical interventions: bilamellar tarsal rotation at mm or at mm from the lid margin, and posterior lamellar tarsal rotation (pltr or trabut procedure). study completion is expected in [ ] . at the time of this review, manuscripts are just starting to be published regarding the coronavirus (covid- ) pandemic. with regard to eye care, some trends are beginning to emerge, including ( ) the possibility of eye-related transmission of emerging infectious diseases [ ] ; ( ) the presence of eye findings and disease in novel infectious disease such as covid- [ , ] ; and ( ) the potential for patients, ophthalmologists, and other eye care providers to be infected with these diseases through clinical and surgical eye care [ ] [ ] [ ] . as the covid- pandemic continues to spread, patient and provider infection control strategies will need to be developed and refined. also, in the future, as new infectious diseases emerge, protocols planned and put in place now may help prevent future infection of patients and providers and the spread of disease through patient interactions. there is currently a "third epidemic" of blindness due to retinopathy of prematurity (rop). the first epidemic of rop occurred in the s- s in industrialized countries due to primarily unmonitored supplemental oxygen, the second epidemic began in the s in industrialized countries due to increased survival rates of extremely premature infants, and the third epidemic began in the mid- s in low-and middleincome countries (i.e., initially in eastern europe and latin america, spreading to east and south asia, and now in sub-saharan africa) due to both high rates of preterm birth and varying levels of neonatal care in these countries [ , ] . in , it was estimated that, of the approximately million premature births globally, % occur in south asia and sub-saharan africa [ ] . while appropriate screening and timely treatment have been shown to reduce the risk of blindness due to rop, there are many obstacles to achieving this, especially in low-and middle-income countries. in many parts of the world, at-risk infants are not being screened and treated for rop due to lack of country-or region-specific guidelines, not having enough ophthalmologists trained in how to screen and/ or treat rop, and limited resources (e.g., availability of laser for treatment, family's ability to follow-up following hospital discharge) [ ] . while rop screening guidelines have been suggested in some asian countries, many countries lack trained ophthalmologists to perform laser retinal ablation and pediatric retina surgery [ , ] . sub-saharan africa collaborative working groups comprised of ophthalmologists and neonatologists have resulted in the development of national screening guidelines in south africa and kenya, and in a national screening protocol in nigeria (serving as a precursor to developing national screening criteria) [ ] . these advancements in rop screening have been the result of committed local leaders, the aforementioned collaborative working groups, support from professional societies, and input from external experts [ ] . a review of the literature found that, as of may , , only of recognized sovereign african states had published data on rop and the authors felt that, based on the rate of these publications, rop seems to be emerging across the african continent [ •] . to increase rop screening standards and reduce rop-related blindness worldwide, countries need to establish realistic and countryspecific screening guidelines; to increase education, training, and collaboration between ophthalmologists and neonatologists; and to utilize other healthcare professionals in rop screening (e.g., explore cost-effective telemedicine approaches to rop screening) [ ] . it is known that the early diagnosis of retinoblastoma (rb) can be both vision-and life-saving. the global rb study group carried out a cross-sectional study of all new rb patients diagnosed in from rb treatment centers from countries, which was felt to have included > % of all new rb cases that year [ ••] . approximately % of new cases were from low-or middle-income countries [ ••] . this study found that lower national income was associated with older age at presentation, higher proportion of more advanced disease, and a smaller proportion of family history of rb, the latter theorized due to fewer children with familial history of rb to survive to childbearing age [ ••] . interestingly, this study found that both lower national income level and older age at presentation were independently associated with advanced disease [ ••] . overall, the most common indications for referral were leukocoria ( . %), strabismus ( . %), and proptosis ( . %) [ ••] . because rb is a curable disease, intervention at the national and international levels is merited and supported by the world health organization global initiative for childhood cancer in their efforts to raise survival for key childhood cancers. as our world becomes more interconnected through globalization, barriers that once existed between eye care professionals have been upended. this has allowed for greater opportunities to collaborate with eye professionals and systems around the world to work towards the common goal of characterizing and reducing preventable visual impairment. global ophthalmology is a branch of ophthalmology concerned with the influence of historical, environmental, cultural, political, and social conditions on eye health and disease epidemiology in all parts of the world. by learning and appreciating these factors, we can develop effective, data-driven methodologies to decrease visual impairment and blindness in any resource setting. this review describes the magnitude of the problems that global ophthalmology aims to address and outlines effective models that are currently being studied. to achieve our shared goal of eliminating preventable visual impairment in the near future, further studies and models need to be funded and constructed. primary eye care in india -the vision center model impact of a -year eye care program in sokoto, nigeria: changing pattern of prevalence and causes of blindness and visual impairment the l v prasad eye institute: a comprehensive case study of excellent and equitable eye care cusum: a dynamic tool for monitoring competency in cataract surgery performance potential lost productivity resulting from the global burden of myopia socio-economic disparity in global burden of near vision loss: an analysis for with time trends since the associations between near visual activity and incident myopia in children: a nationwide -year follow-up study the association between near work activities and myopia in children -a systematic review and meta-analysis the association between digital screen time and myopia: a systematic review two-year clinical trial of the low-concentration atropine for myopia progression (lamp) study: phase report global estimates on the number of people blind or visually impaired by diabetic retinopathy: a meta-analysis from management of type diabetes in developing countries: balancing optimal glycaemic control and outcomes with affordability and accessibility to treatment type diabetes complications and comorbidity in sub-saharan africans incidence and progression of diabetic retinopathy in sub-saharan africa: a five-year cohort study the nakuru eye disease cohort study: methodology and rationale results of automated retinal image analysis for detection of diabetic retinopathy from the nakuru study artificial intelligence using deep learning to screen for referable and vision-threatening diabetic retinopathy in africa: a clinical validation study do we have enough ophthalmologists to manage vision-threatening diabetic retinopathy? a global perspective [published online ahead of print diagnostic accuracy of community-based diabetic retinopathy screening with an offline artificial intelligence system on a smartphone medios -an offline, smartphone-based artificial intelligence algorithm for the diagnosis of diabetic retinopathy automated diabetic retinopathy detection in smartphone-based fundus photography using artificial intelligence deep learning versus human graders for classifying diabetic retinopathy severity in a nationwide screening program artificial intelligence screening for diabetic retinopathy: the real-world emerging application artificial intelligence for diabetic retinopathy screening: a review improved automated detection of diabetic retinopathy on a publicly available dataset through integration of deep learning strategies to tackle the global burden of diabetic retinopathy: from epidemiology to artificial intelligence human versus machine: comparing a deep learning algorithm to human gradings for detecting glaucoma on fundus photographs prevalence of active trachoma and associated factors among children aged to years in rural communities of lemo district, southern ethiopia: community based cross sectional study azithromycin to reduce childhood mortality in sub-saharan africa cause-specific mortality of children younger than years in communities receiving biannual mass azithromycin treatment in niger: verbal autopsy results from a clusterrandomized controlled trial mass azithromycin distribution for hyperendemic trachoma following a cluster-randomized trial: a continuation study of randomly reassigned subclusters (tana ii) trachoma control: a guide for programme managers. world health organization progress to eliminate trachoma as a public health problem in amhara national regional state, ethiopia: results of population based surveys impact of a single round of mass drug administration with azithromycin on active trachoma and ocular chlamydia trachomatis prevalence and circulating strains in the gambia and senegal ocular immune responses, chlamydia trachomatis infection and clinical signs of trachoma before and after azithromycin mass drug administration in a treatment naive trachoma-endemic tanzanian community progression of scarring trachoma in tanzanian children: a four-year cohort study a double-masked placebo-controlled trial of azithromycin to prevent child mortality in burkina faso, west africa: community health with azithromycin trial (chat) study protocol maximising trichiasis surgery success (mtss) trial: rationale and design of a randomized controlled trial to improve trachomatous trichiasis surgical outcomes the possibility of covid- transmission from eye to nose there may be virus in conjunctival secretion of patients with covid- characteristics of ocular findings of patients with coronavirus (covid- ) in hubei province coronavirus disease (covid- ) outbreak at the department of ophthalmology stepping up infection control measures in ophthalmology during the novel coronavirus outbreak: an experience from hong kong precautionary measures needed for ophthalmologists during pandemic of the coronavirus disease of (covid- ) retinopathy of prematurity: a global perspective of the epidemics, population of babies at risk and implications for control epidemiology of rop update -africa is the new frontier national, regional, and worldwide estimates of preterm birth rates in the year with time trends since for selected countries: a systematic analysis and implications retinopathy of prematurity treatment: asian perspectives anatomic outcomes of laser indirect ophthalmoscopy for retinopathy of prematurity in a tertiary referral center in the philippines this systematic review summarizes the published literature on rop from african nations. the results of this review can help future planning of rop efforts - ; this cross-sectional study of all new rb patients diagnosed across the world in , felt to include > % of new rb that year, allowed investigation of associations between clinical variables and national income level and risk factors for advanced disease at diagnosis. the results of this study can help efforts focused on improving rb diagnosis acknowledgments dr. raquel goldhardt and current ophthalmology key: cord- -id dn authors: carlitz, ruth d.; makhura, moraka n. title: life under lockdown: illustrating tradeoffs in south africa’s response to covid- date: - - journal: world dev doi: . /j.worlddev. . sha: doc_id: cord_uid: id dn this research note sheds light on the first three months of the covid- outbreak in south africa, where the virus has spread faster than anywhere else in the region. at the same time, south africa has been recognized globally for its swift and efficient early response. we consider the impact of this response on different segments of the population, looking at changes in mobility by province to highlight variation in the willingness and ability of different subsets of the population to comply with lockdown orders. using anonymized mobile phone data, we show that south africans in all provinces reduced their mobility substantially in response to the government’s lockdown orders. statistical regression analysis shows that such mobility reductions are significantly and negatively associated with covid- growth rates two weeks later. these findings add an important perspective to the emerging literature on the efficacy of shelter-in-place orders, which to date is dominated by studies of the united states. we show that people were particularly willing and able to act in the provinces hit hardest by the pandemic in its initial stages. at the same time, compliance with lockdown orders presented a greater challenge among rural populations and others with more precarious livelihoods. by reflecting on south africa’s inequality profile and results of a recent survey, we demonstrate how the country’s response may deepen preexisting divides. this cautionary tale is relevant beyond south africa, as much of the continent -- and the world -- grapples with similar tradeoffs. along with measures to contain the spread of disease, governments and other development focused organizations should seriously consider how to offset the costs faced by already marginalized populations. as covid- began its global spread, it still appeared that some world regions might be spared --in particular, sub-saharan africa (otu et al., ) . in short order, however, it became clear that such optimism was not merited. the virus quickly took a firm footing on the continent and as of august , the number of confirmed cases exceeded one million --likely a significant underestimate given limited testing capacity. the virus's impact has varied considerably across the continent, reflecting countries' varying degrees of global integration and capacity to respond . one country that stands out in both regards is south africa. as seen in figure , the virus has spread faster in south africa than in any of the continent's other large economies. [ figure here] at the same time, south africa has been recognized globally for its swift and efficient response (kavanagh & singh, ) . in this research note, we illustrate how the south african government's response affected the lives of ordinary people, focusing on the initial outbreak and subsequent lockdown. first, we look at the impact of the government's strict lockdown orders on population mobility, which may be understood as a proxy for compliance. we leverage anonymized mobile phone data from google's covid- community mobility reports, which chart trends over time, across different categories of places such as retail and recreation, transit stations, and workplaces. we look at changes in mobility by province to highlight variation in the willingness and ability of different subsets of the population to comply with lockdown orders. we then analyze how changes in population mobility relate to the spread of disease, and conduct statistical regression analysis to show that mobility reductions are significantly and negatively associated with covid- growth rates two weeks later. while this suggests the lockdown measures have been effective in achieving their goals, we also reflect on how the government's response and corresponding mobility reductions interact with existing inequalities, keeping in mind the country's status as the world's most unequal nation. this research note contributes to a rapidly expanding literature on covid- 's impact in the global south, and in particular to studies that demonstrate and explain variation within countries (okoi & bwawa, ; wenham & smith, ; brauer et al., ) . to our knowledge, ours is the first subnational analysis of population mobility in response to for south africa. we also contribute an important perspective to the emerging literature on the efficacy of shelter-in-place orders, which to date has been dominated by studies of the united states. finally, by discussing the tradeoffs inherent to stringent containment measures, we tell a story that resonates across the african continent and in other parts of the world where efforts to contain the spread of covid- may have as many or more negative consequences as the disease itself (coetzee & kagee, ) . this research note proceeds as follows. section details south africa's efforts to contain covid- , and compares the country's response to others on the continent. section then presents our analysis of mobility trends and their relation to the growth rate of new infections. section describes the nature of inequality in south africa in order to situate our results in context. section concludes. the first case of covid- in south africa was confirmed on march th, ; subsequent cases were confirmed in the days that followed among citizens who had traveled to italy on a ski trip. while the initial cases suggested the disease might be limited to the country's affluent, cosmopolitan population, president cyril ramaphosa announced broad measures to combat the spread of covid- on march th. as the timeline depicted in table shows, the response accelerated quickly from there. [ table here.] formal regulations were published on march th, promoting social distancing at one person per square meter of floor space (rsa government, a). the regulations also closed schools, called for isolation of sick people, quarantining of asymptomatic people, limited gatherings to people, and to people at the premises where alcohol is sold and consumed. these regulations were amended on march th, ushering in a strict lockdown phase (rsa government, b) . beginning march th, all businesses were to remain closed, except those involved in the production and provision of essential goods and services. every person was to be confined to a place of residence unless performing essential services, obtaining essential goods or services, collecting social grants, emergency care or chronic medication attention. all places of work were to be closed except those providing essential services. movements between provinces, metropolitan areas and districts were prohibited, including commuter transport services, except when rendering essential services. the lockdown was extended on april th to the end of the month (rsa government, c) to allow the government further time to prepare for management of the disease (karim, ) . revised regulations prohibited evictions from rental properties, permitted opening of refineries, and allowed mining to operate at reduced capacity. these were seen as laying the groundwork for re-opening the economy (rsa government, d). at the end of april, the lockdown was relaxed to allow transition into alert level beginning may st, (rsa government, e). the country transitioned to alert level on june st (rsa government, g), which provided for movements of school children across provinces and limited religious gathering to people. compared to many of its neighbors on the continent, south africa's response has been swift and extensive, as shown in figure . as of april st, , south africa scored an out of on the "stringency index," as coded by the oxford covid- government response tracker . only of other countries on the continent were coded as having more stringent responses as of that date. [ figure here.] as we show in the next section, the country's residents acted accordingly to reduce spread of the disease by dramatically reducing their mobility. this section examines how south african citizens responded to the government's strict containment measures, drawing on google's covid- community mobility reports. these reports are based on aggregated, anonymized data from users of google maps, and show how visits and length of stay at different places change compared to a baseline. , we examine four categories: . workplaces: mobility trends for places of work. mobility trends for places like restaurants, cafes, shopping centers, theme parks, museums, libraries, and movie theaters. . transit stations: mobility trends for places like public transport hubs such as subway, bus, and train stations. mobility trends for places like grocery markets, food warehouses, farmers markets, specialty food shops, drug stores, and pharmacies. figure shows that south africa consistently "outperforms" its peers in terms of reduced mobility relative to the stringency of government response with the exception of grocery and pharmacy visits reflecting the exemption of such businesses from the lockdown order. [ figure here.] the national average reduction in mobility masks considerable variation within the country. figure illustrates mobility trends by province in terms of retail and recreation from february -may , . although the provinces exhibit differences, in each case we can observe a substantial dip corresponding to the beginning of the strict lockdown period. table depicts the overall average percent change in mobility reductions during the most stringent lockdown period ( march- april ) by provinces for the different categories. [ table here.] western cape registers the largest average decrease in mobility for all categories. on the other side, limpopo registers the smallest decline in retail/recreation; mpumalanga the smallest declines in grocery/pharmacy and transit station visits; and northern cape the smallest declines in workplace visits and smallest increase in residential mobility. we also calculate the average mobility reduction for the three most highly correlated categories: retail/recreation, workplace mobility, and transit stations (see correlation matrix in appendix table a ). this is depicted graphically in figure . [ figure here.] in order to account for variation in mobility trends across provinces, we consider a number of economic and demographic factors. we also consider each province's caseload (number of confirmed cases) at the beginning of the lockdown period. these features are summarized in table . [ table here.] we use qualitative comparative analysis (qca) to identify the features shared by the provinces experiencing the greatest mobility reductions. our analysis suggests that the main factors associated with substantial mobility reductions are the number of confirmed cases prior to the lockdown period and the relative size of the provincial economy. the provinces containing south african's metropolitan hubs --gauteng (containing johannesburg) and western cape (containing cape town) also tended to experience larger mobility reductions. this may reflect the challenge of reducing mobility in rural areas among populations that are more likely to be food insecure (tibesigwa and visser, ) . emerging research on the determinants of compliance with social distancing and other measures suggests that concerns about income losses play an important role in determining compliance (wright et al., ; bodas and peleg, ) . in contrast to the united states, where partisanship has been shown to be a key determinant of mobility reductions and other efforts to contain the spread of disease (grossman et al., ; adolph et al., ) , party politics do not seem to feature prominently when it comes to explaining variation in mobility in south africa. both gauteng (controlled by the ruling african national congress party) and western cape (the only province held by the main opposition party, the democratic alliance) exhibit similar trends when it comes to mobility reductions. that said, such unity appears to be waning. for example, the democratic alliance filed a legal challenge against some coronavirus lockdown rules in mid-may (democratic alliance, ). the economic freedom fighters (the second largest opposition party) subsequently issued a statement calling for prolonged stringent lockdown (economic freedom fighters, ). south africa's strict lockdown policies --and corresponding reductions in mobility by the country's citizens --were put in place with the aim of reducing the spread of covid- . this leads us to ask: how effective have they been? before we attempt to answer this question, we first present the trajectory of disease by province in figure up until may th, . although the first cases were confirmed in kwazulu-natal, the figure indicates how the disease has taken hold primarily in western cape. [ figure here.] in order to determine how the spread of disease has changed as a consequence of the mobility reductions discussed above, we estimate a series of regression models with average weekly exponential growth in confirmed cases as the dependent variable. the independent variables are average weekly mobility reductions for each of the three main categories discussed above (workplace, retail/recreation, and transit stations) for the preceding two weeks. all models include province fixed effects and standard errors clustered by province. we also include a time trend to account for any other factors changing over time within each province. the results, depicted in table , suggest that people's mobility reductions have indeed helped to play an important role in reducing the rate of new infections. however, as we discuss in the next section, the benefits and costs of lockdown are unlikely to be distributed equally. [ table here.] as noted above, south africa bears the unflattering distinction of the world's most unequal nation in terms of income inequality. furthermore, the nature of inequality in south africa extends beyond economic well-being (leibbrandt et al., ; tibesigwa and visser, ) . we . inequality in the social domain: whereas access to basic education is high and fairly even across the country, access to health care is characterized by greater inequality. more than % of black africans use public health facilities and fewer than % use private health facilities. there are considerable differences in access to private medical care across provinces, with limpopo reporting private coverage at less than %, whereas gauteng and western cape reported rates of . % and . % in , respectively. . gender inequality: women were less likely to participate in the formal labor market as compared to men and also experienced higher unemployment ( . %) compared to men ( . %) in . gender inequality is also observable in food security (tibesigwa and visser, ) . this multidimensional view of inequality is important to keep in mind when it comes to identifying tradeoffs associated with the country's response to covid- . the dramatic reductions in population mobility documented above have come at a cost for many households, particularly those who are no longer able to work. income from the labor market has been the main source of household income in south africa, accounting for over % of overall income (statistics south africa, ). fears of losing such income can reduce compliance with measures to mitigate the spread of covid- , especially in low income areas (wright et al. ; coetzee and kagee, ) . a web-based survey conducted between april th -may th (statistics south africa, b) paints a picture of the pandemic's impact on employment, income, and hunger, highlighting the potential for deepening inequality. while . % of the respondents were employed on a permanent basis during the national lockdown, just under . % lost their jobs and . % had to close their businesses. further, while . % of those who were employed before the national lockdown remained employed during this period, . % lost their jobs or had to close their businesses, . % became unemployed and . % were out of the labor force. for those who stayed employed during the lockdown, . % indicated reduced income. given the voluntary, web-based nature of the survey, these and other estimates are likely significant underestimates. the survey also showed that while a majority ( . %) of respondents who had businesses before national lockdown were white, among black africans and the coloured population, the share among those who had to close businesses were larger than their share of business ownership ( . % vs. . % and . % vs. . % respectively). while social grants and remittances have played a crucial role in reducing income inequality over the years in south africa, the survey shows other coping strategies. for example, . % of respondents reduced their spending to compensate for the loss of income, while about half of respondents had to access their savings to close the income gap. some respondents ( . %) relied on extended family members, friends and/or their communities for support, while . % relied on claims from the unemployment insurance fund. disaggregated analysis of these claims is not yet possible but would shed further light on the extent to which lockdown has furthered pre-existing inequalities. as noted above, the more rural provinces and black africans on average have tended to lag further behind in access to basic services (statistics south africa, ). the covid- pandemic appears to have further deepened these inequalities. the survey shows that the majority of those able to work from home are in suburban areas ( %). in contrast, just . % of township residents reported being able to work from home, followed by just . % of those residing on farms and . % of respondents in rural areas. the survey also revealed considerable food insecurity and income losses. since the start of lockdown, the proportion of respondents who reported experiencing hunger increased from . % to . %. the percentage of respondents who reported no income increased from . % to . % by the sixth week of lockdown. again, these figures are likely significant underestimates. notably, the government of south africa has provided a number of relief measures, including the release of disaster relief funds, emergency procurement, wage support through the unemployment insurance fund, and funding to small businesses. on april , , the president announced a massive social relief and economic support package of r billion ($ , billion), amounting to around % of gdp (rsa government, h) . this was complemented by the south african reserve bank easing monetary policy with reduced interest rates (sarb, ) and subsequent loan of about $ . billion from imf (rsa government, i). these resources have been deployed to prepare health infrastructure, provide food and income support, and provide financial relief to businesses and individuals. the effectiveness and efficiency of such efforts are still yet to be determined. this research note paints a picture of life under lockdown in south africa, the world's most unequal nation. we present evidence of swift and effective action by the government -mirrored in substantial reductions in mobility among the population. people were particularly willing and able to act in the provinces hit hardest by the pandemic in its initial stages (gauteng and western cape). at the same time, compliance with lockdown orders presents a greater challenge among rural populations and others with more precarious livelihoods. by reflecting on south africa's inequality profile and results of a recent survey conducted during lockdown, we demonstrate how south africa's response may deepen preexisting divides. this cautionary tale is relevant beyond the country's borders, as much of the continent --and the world --contemplates similar tradeoffs. along with measures to contain the spread of disease, governments and other development focused organizations should seriously consider how to offset the costs faced by already marginalized populations. data from european centre for disease prevention and control (ecdc) in roser et al. ( ) . data from oxford covid- government response tracker . - . *** - . *** ( . ) ( . ) l .average weekly reduction in mobility (retail/recreation) - . *** - . *** we supplement our analysis of the google covid- community mobility reports with mobility trends reports published by apple maps (https://www.apple.com/covid /mobility). these reports present data on the relative volume of directions requests per country/region, subregion or city compared to a baseline volume on january th, . higher proportions indicate smaller mobility reductions. in addition to being available at the country and province level, these reports are available for the cities of johannesburg and cape town, allowing us to compare trends in these cities to the greater provinces. note that these reports are available for both driving and walking for the two cities and south africa as a whole; and for driving only at the greater province level. figure a depicts city/province comparisons for driving trends over the same period considered in the manuscript (february -may , ; see figure ). we see that the city-level trends appear to mirror the province-level trends. in order to confirm this and relate to the analysis presented in the paper, we also calculate average mobility reductions for the most stringent lockdown period ( march- april ). these are depicted in table a below. as with our analysis of the google mobility reports, western cape and gauteng exhibit the largest mobility reduction (fewer directions requests compared to baseline, suggesting people are moving around less), and limpopo and mpumalanga province the smallest (a higher proportion of directions requests in comparison to the baseline, indicating less of a change in mobility). we also see that the city-level mobility changes mirror the province level for cape town/western cape and johannesburg/gauteng, confirming the results suggested by the figures above. it is notable that in cape town, driving requests and walking requests are on par with each other whereas in johannesburg the lockdown appeared to have a greater impact on people's driving habits compared to walking. this may be due to the fact that cape town and western cape are mostly tourist areas and thus when the lockdown instructions and impact of the disease set in, both driving and walking habits were similarly affected. on the other hand, the driving and walking populations of johannesburg and gauteng tend to be distinct. most of the drivers are wealthier, while the walkers tend to be poorer. when the lockdown instructions set in, it was easier to enforce compliance with driving (using the existing traffic enforcement framework), while it was more difficult to enforce walking restrictions (due to the lack of a coherent enforcement framework and insufficient resources). all figures in this section depict mobility trends from february -may , , using data from google mobility reports in order to conduct crisp qualitative comparative analysis (qca) we begin by creating sets -dichotomizing the variables of interest to designate membership within a given set. the sets are defined as follows: • m = large average mobility decrease (defined alternatively as provinces in the top quintile of the distribution and provinces in the top two quintiles) • i = or more confirmed infections as at march , (start of lockdown) • d = densely populated provinces, i.e. those with an average of people or more per km sq. • g = provinces whose contribution to national gdp is greater than % • p = provinces with a multidimensional poverty rate greater than % • a = provinces with a proportion of agricultural households exceeding % we have reproduced a crisp set version of the relevant data in table a as a data matrix. we see that for either definition of m, the set also contains members of i and g --that is, provinces with at least confirmed cases pre-lockdown and those that contribute significantly to national gdp. the dependent variable is the average weekly reduction in mobility to workplaces, retail and recreation, and transit stations. all models include province fixed effects and robust standard errors clustered by province. * p < . , ** p < . , *** p < . figure a . confirmed cases by province, march -may , (excluding western cape) pandemic politics: timing state-level social distancing responses to covid- self-isolation compliance in the covid- era influenced by compensation: findings from a recent survey in israel: a cross sectional study of the adult population of israel to assess public attitudes toward the covid- outbreak and self-isolation global access to handwashing: implications for covid- control in low-income countries structural barriers to adhering to health behaviours in the context of the covid- crisis: considerations for low-and middle strong social distancing measures in the united states reduced the covid- growth rate: study evaluates the impact of social distancing measures on the growth rate of confirmed covid- 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the african continent play the long game coronavirus pandemic (covid- regulations issued in terms of section ( ) of the disaster management act disaster management act : amendment of regulations issues in terms of section ( ). (government gazette disaster management act : amendment of regulations issues in terms of section ( ). (government gazette disaster management act : amendment of regulations issues in terms of section ( ). (government gazette disaster management act : amendment of regulations issues in terms of section ( ). (government gazette disaster management act : amendment of regulations issues in terms of section ( ). (government gazette president cyril ramaphosa: additional coronavirus covid- economic and social relief measures social distancing to slow the us covid- epidemic: an interrupted time-series analysis south african reserve bank (sarb) inequality trends in south africa: a multidimensional diagnostic of inequality quarterly labor force survey results from wave survey on the impact of the covid- pandemic on employment and income in south africa assessing gender inequality in food security among smallholder farm households in urban and rural south africa discovery first case of covid- confirmed in kwazulu natal province second case of covid- confirmed in kwazulu natal province first case of covid- confirmed in western cape province first case of local transmission confirmed in free state province early response president announces measures to combat covid- government declares state of national disaster ports of entry closed (namibia testing capacity increased with new mobile lab units launched critical personal protective equipment secured for frontline healthcare workers lockdown extended until end of april (with days travel grace across provinces for relocation) government postpones may/june exam rewrites president announces interventions to address livelihoods of the vulnerable groups president outlines expanded covid- economic & social relief government recommends wearing of a cloth non-medical face-mask when in public president announces risk-adjusted strategy to respond to covid- pandemic oxford covid- government response tracker, blavatnik school of government census agricultural households key highlights mid-year population estimates estimate as of august , from the european centre for disease prevention and control (ecdc) cited in roser et al according to the world bank's world development indicators, south africa's gini index is / , the highest in the world according to available data the paper that bears the most similarity to ours is nyabadza et al. ( ), which models the impact of social distancing on the transmission dynamics of covid- in south africa these included travel restrictions, encouraging social distancing, limiting contact between persons who may be infected, and working to strengthen the public health response the prohibitions included the sale, dispensing, or transportation of alcohol the government has devised five coronavirus alert levels, in line with a risk-adjusted strategy that seeks to slow down the rate of infection and flatten the curve. level entails "drastic measures are required to contain the spread of the virus to save lives further details about these reports and other data sources analyzed in this research not can be found in table a in the appendix according to the world bank's world development indicators, the country had . mobile cellular subscriptions per people we are very grateful to clara tomé for excellent research assistance and to the organizers of the sustainability and development conference, which led to the authors' meeting and inspired our collaboration on this article. . we analyze subnational variation in population mobility as a response to covid- in south africa. . we leverage anonymized mobile phone data to capture mobility reductions across provinces. . people tend to reduce mobility substantially in response to government's initial lockdown orders. . mobility reductions are significantly and negatively associated with covid- growth rates. . we illustrate how the government's response and corresponding mobility reductions can exacerbate existing inequalities. south africa is labeled by its -letter country code, "zaf." the province is the lowest level at which comparable data on mobility trends is available. we supplemented our analysis with data from the mobility trends reports published by apple maps (https://www.apple.com/covid /mobility), which allow us to compare trends for cape town and johannesburg with the surrounding provinces. as shown in the appendix, this analysis depicts largely similar trends to those captured by the google reports. additional province-level comparison charts are shown in the appendix. this process is described in detail in the appendix. an alternative version of this figure, excluding western cape, is presented in the appendix for better visualization of the other provinces. we first calculate the daily exponential growth rate and then take the weekly average. daily exponential growth is calculated as the natural log of cumulative confirmed cases minus the log of cumulative confirmed cases on the prior day. as in other recent studies ), we use this functional form because epidemiological models predict exponential growth in the absence of intervention. in computing exponential growth, we follow recent studies and add one for province-dates with zero cases to avoid dropping observations. we take weekly averages given fluctuations in mobility, e.g. in workplace trends where the average reduction in mobility is considerably lower on weekends when people are typically less likely to go to their workplaces. this section draws heavily on a recent report profiling trends since conducted by the country's statistical agency (statistics south africa, ). the survey drew on a non-probability, convenience sample of , south african residents. the most recent afrobarometer survey, conducted between august-september , indicates that nearly % of all rural residents in south africa never use the internet compared to . % of urban residents (http://afrobarometer.org/online-data-analysis/analyse-online). key: cord- -h sxkqw authors: cheng, yang; cheng, feng title: china's unique role in the field of global health date: - - journal: global health journal doi: . /j.glohj. . . sha: doc_id: cord_uid: h sxkqw abstract china's participation in global governance, inspired by the united nations sustainable development goals, is driven by the guiding principle of “building a community of shared future for mankind”. china has been promoting the belt and road initiative and south-south cooperation and has made significant contributions to the prosperity of human beings. along with the opportunities that globalization brought about such as the world health organization and the boom in the economy, global health challenges also emerged. this resulted in certain obstacles for china when it sought to advocate the belt and road initiative and when it attempted to carry out its strategy to address global health issues. what are the emerging challenges for global health? what can china do for global health? why does global health need china? we tried to address these questions as china's global engagement continues to expand in the new era. this article makes the case for chinese approaches, including getting involved in public health, being consistent in addressing local conditions, sharing china's experience with handling health services, and strengthening government-led action while being guided by relative policies. china has a lot to offer in the promotion of global health and in overcoming the challenges and risks that this goal currently faces. thus, china should be considered an inseparable part of global health governance and bilateral health development cooperation. consistent with its emphasis on promoting global health, china follows the norm of "building a community of shared future for mankind", which operates as a guiding principle for china when it participates in global governance, as proposed by chinese president xi jinping, in keeping with the united nations (un) sustainable development goals (sdgs) to be achieved by . when the un millennium development goals (mdgs) were terminated in , un member states arrived at a consensus and adopted the sdgs and targets at the un general assembly in september . the third sdg aims to promote "good health and well-being". all targets under it are directly related to health. there are two concrete measures that have been proposed to build a community of shared future for mankind in the new era. the first is to advocate the belt and road initiative that seeks to share china's experience and wisdom with the world, to promote global peace and cooperation, and to engage in joint development endeavors. by the end of , china had signed intergovernmental cooperation documents with countries and international organizations, which widened the circle of friends for the belt and road initiative and included parts of asia, africa, europe, oceania, and latin america. the second initiative is to continue deepening south-south cooperation. china attaches great importance and is committed to its cooperation with other developing countries. in september , president xi announced the establishment of an assistance fund for south-south cooperation at the un sustainable development summit that he hosted at the un. he also stated that china would continue to increase its investments in least developed countries in the world and set up the center for international knowledge on development to provide new ideas, models, and impetus for south-south cooperation. during his visit to africa in december , president xi proposed the china-africa cooperation -"going forward hand in hand, cooperating with a win-win strategy, and developing with each other"-and pledged to provide usd billion to support major cooperation plans across africa. thus, china will continue to play its role as a responsible country and work with other countries to create a better future for mankind. globalization is a double-edged sword. when money is allowed to flow freely, the possibility of a global economic crisis becomes higher. the international health system is centered on each nation and state, and health global health journal j o u r n a l h o m e p a g e : h t t p : / / w w w . k e a i p u b l i s h i n g . c o m / e n / j o u r n a l s / g l o b a l -h e a l t h -j o u r n a l / problems encountered by each country are defined by its borders. the resolution of these health problems typically requires cooperation among multiple countries through measures that include customs quarantine and restrictions on the spread of colonial tropical diseases. the health sector in each country is primarily responsible for resolving these problems, and operates with "sharp divisions" among countries. the world health organization (who) is undisputedly the leading coordinator of its member countries. with globalization, health risks began to cross national boundaries. as the power of non-state actors rises and the participation of non-health sectors in the health sector expands its scope, diverse global forces cooperate to respond to national and global health problems. the who is one of these forces. the prevailing situation has precipitated existing global health initiatives. effective global health initiatives should: ( ) cross borders by promoting global health research aimed at breaking national territorial boundaries and focusing on the health of the global population; ( ) be interdisciplinary by solving these health problems using knowledge from many other disciplines and through interdisciplinary collaboration; and ( ) fully motivate various actors by identifying the global forces that need to be motivated to address health problems. global health emphasizes solutions that utilize a variety of cross-border cooperative actions. global health also poses security issues for countries. the rapid movement of people, goods, capital, technology, ideas, and cultures among different countries has resulted in unprecedented development opportunities and enormous public health challenges. emerging infectious diseases such as ebola, middle east respiratory syndrome (mers), and avian flu are on the rise and are changing constantly. traditional infectious diseases such as tuberculosis, malaria, and aids are resurfacing and spreading. as a result of the increasingly serious abuse of antibiotics, the types of multidrug-resistant pathogens have also increased. [ ] [ ] [ ] as people's behaviors and lifestyles have changed, the chronic non-communicable diseases have become more common in developing countries. the dual burden of infectious and non-communicable diseases is a pressing issue. in , million chinese citizens went abroad to travel, work, and/or study. tourist arrivals in china totaled million. the length of china's inland borderline is over , km and the border area accounts for about % of the country's total area. along this line, there are counties spread over provinces of china, and the outer boundary borders more than countries. along china's border, the northern border of china has a large population density, while the southern border has a small one. compared with the border areas outside china, there is greater population density in the northeast and northwest parts of chinese frontier regions, which is much less in southwest frontier regions. the population number in china's border areas is very low, and its density of the border areas outside china is even lower than that of inside china's frontier. population decline is a major feature of the border areas in recent decades. for example, in the northwestern border areas between china and russia and between china and mongolia, the concentration of population decreased. the population decreased significantly in china's northeastern frontier regions with north korea, and in the china's southwestern regions and its neighboring countries. the belt and road initiative requires the successful implementation of global health, although there are some challenges: ( ) the types of infectious diseases vary greatly in countries along the belt and road; ( ) health monitoring and management for hundreds of thousands of chinese engineers involved in the belt and road infrastructure will be difficult; and ( ) the main infrastructure projects are primarily implemented in major cities, ports, and transport hubs. to ensure the security and convenience of cooperation for global health and the influence and radiation effects of its relative projects, the layouts of funded hospitals, disease control and prevention centers, and medical laboratories should adopt some strategies. china's economic growth is closely tied to its role in the world. its health development is expected to have worldwide influence. the investment and scale of china's global strategy for health will affect the global stakeholders and their diplomatic policies. china has always been a strong supporter of and practitioner in the field of global health. since , china has been sending medical teams to more than developing countries in africa and other parts of the world. in recent years, china has created the association of southeast asian nations (asean) public health fund, actively participated in health cooperation efforts between the asia-pacific economic cooperation (apec) and the shanghai cooperation organization (sco), and hosted the first health ministers' meeting of the brics countries (brazil, russia, india, china, and south africa) in . china also contributed to the global fund to the extent of usd million by , hosted a fundraiser for avian influenza prevention and control in , and donated usd million to un agencies toward addressing global health issues. after becoming the sixth largest contributor to the un in , china continued to increase the extent of its voluntary contributions to the who and unaids. china is also a member of the decision-making body and expert advisory group at the who, unaids, and other major international organizations. with abundant experience in fundamental medical and healthcare systems, china can be a role model for other developing countries. china's new rural cooperative medical insurance has expanded significantly. in the past decade, china increased the coverage of basic medical insurance in rural areas from % to %. michel sidibé, the executive director of unaids, said that the un is learning from the experience of the barefoot doctors of china who are a part of the basic medical insurance initiative in china, and that the un is planning to train million community health workers in africa by . with a severe shortage of grassroots doctors and the difficulty in retaining talent, the tanzanian government has shown high interest in the barefoot doctors program. china has extensive experience in training barefoot doctors. many rural doctors are local villagers and serve the local area. this model may be useful for other countries that experience a shortage of talent. china's infant mortality rate (imr) dropped from . ‰ in to . ‰ in , and the maternal mortality rate dropped from . per , persons in to . per , persons in . by , china achieved the global tuberculosis (tb) control target set by who, with at least % detection rate and successfully treating more than % of those patients. china has eliminated lymphatic filariasis, malaria, and schistosomiasis, and implemented a national immunity program; it currently provides free vaccinations to prevent types of diseases that include vaccines for diseases and vaccines for hepatitis b. all great achievements in public health in china has been supported by solid technologies such as the development of vaccines and drugs, portable ultrasound detection equipment, fetal monitoring equipment, diagnostic reagents, the shang ring, artemisinine, and subepidermal contraceptive implants. concurrently, china is also a major producer of medicines and medical facilities. with reliable quality and reasonable pricing, medicaments developed and produced in china have drastically supported its public health services. using only % of the world's health resources, china successfully meets the health demands of % of the world's population. in march , during the first session of the th national people's congress of china, the proposal to reform the state council and establish the china international development cooperation agency (cidca) was passed, which officially opened on april , . the agency's primary responsibilities include: ( ) developing foreign aid strategies, plans, and policies; ( ) coordinating major foreign aid issues; ( ) offering suggestions, promoting reforms of foreign aid models, formulating foreign aid programs and plans; and ( ) supervising and evaluating the implementation of foreign aid projects. aiming to create a new type of public health aid team and build its capacity by setting up an expert-steering committee, it is very necessary to build a talent pool and offer specialized training. meanwhile, developing a guideline on international public health development and cooperation is also helpful. measures include writing official documents on public health in english, developing and managing international public health development cooperation projects, establishing relevant overseas project departments, and respecting the ethics, etiquette, and culture of international public health development and cooperation. in addition, it seeks to ensure the stability of overseas public health work and the implementation of public health projects, improving communication and negotiation skills used in international public health development cooperation, and understanding international public health strategies. to improve china-africa cooperation in public health, there could be a variety of ways, including regularly communicating and discussing relevant topics, short-term training ( days) and further study ( months) programs for the belt and road countries in africa, holding seminars, and sending experts to introduce the international public health development aid and enhance capacity to participate. china's public health aid capacity building projects are solidly supported by the chinese center for disease control and prevention (china cdc). first, with the expansion of globalization, world trade, migration, and international exchange activities, global health has become an increasingly important agenda worldwide and for individual countries, as it is closely related to national security, diplomacy, economy and trade, agriculture, and environment. given the outbreak of emerging and re-emerging communicable diseases in recent years and the public health measures included in many countries' national security strategies, the risk of transnational spread of diseases should also be considered in the course of strategy-and policy-making efforts, training talents, and developing projects. second, the world has increasingly high expectations for china, given its peaceful rise and growing power. president xi has shown a positive attitude and has promoted strong efforts to help african countries and to participate in global health initiatives. these include commitments announced at the un general assembly and the summit of the forum on china-africa cooperation to support public health policies and strategies of african countries, and to help them optimize their public health prevention systems. as the infrastructure and capacity of health systems in african countries are weak, especially in west africa which is still recovering from the ebola epidemic, the establishment of public health systems and the cultivation of talents become crucial. this provides an opportunity for china to make progress in public health assistance in terms of public health aid, the construction of talent teams, and the establishment of an external supporting environment. it is particularly urgent and necessary to train a team of competent experts and to design a reasonable top structure for cooperative public health projects such as the construction of the african center for disease control and prevention (africa cdc) and the establishment of the west african center for tropical disease research and control in sierra leone. third, among the chinese government's current practices in the field of foreign aid for health, public health aid is still in its early stages. medical assistance in response to the ebola outbreak in west africa in was the largest foreign public health assistance thus far and revealed numerous problems in policy, management, and fundraising. the process of designing and conducting this project improved drastically and stimulated the completion of china's foreign health aid policies and practices by improving and enriching the policies, mechanisms, teams, practices, and guidelines for public health aid. fourth, the china cdc is a leading public health institution in china, and an important technological force in foreign public health assistance. it is responsible for assisting in the ebola epidemic in west africa, the construction of the africa cdc, the technological cooperation with the p laboratory in sierra leone, and the control and prevention of malaria. it has accumulated vast expertise in medical aid. the design and implementation of this project is consistent with the chinese government's commitments to foreign health assistance and china's strategic development goals. however, to meet the needs of public health assistance in the new era, it is necessary to comprehensively and systematically develop and improve the construction of institutions, mechanisms, modes of cooperation, and the capacity of institutions and experts. these initiatives can help solve serious problems and urgent needs that challenge china's exploration of foreign public health assistance in the new era and can help meet the requirements for the construction of public health systems in african countries. global health governance and bilateral health development cooperation continue to face many challenges such as the lack of talent, knowledge, experience, and language (chinese personnel, institutions, and health officials in embassies abroad lack capacity and experience in handling foreign aid). therefore, the treatment of foreign aid workers and overseas workers should be heavily monitored to ensure that their children's education and their family's health are promoted, which would encourage more businesses and talents to work and live in africa. both state-owned enterprises and private enterprises seek assistance from governments to build hospitals and schools overseas for chinese citizens in africa. only when key issues concerning education and healthcare are addressed properly will overseas workers be able to work steadfastly and more talent can be attracted to africa. public health cooperation and exchanges are centered on people-topeople ties. this includes foreign health assistance from the government and the multi-level and multi-form cooperation and exchanges that take place between the authorities and the people. both should be equally emphasized. comprehensive long-term cooperation and exchanges are part of a grand project for at least the next years. however, people-topeople cooperation and exchanges have more potential and are more comprehensive and sustainable, and should thus be provided sufficient support and attention. for example, after the establishment of diplomatic ties between china and america, there were cooperation and communication between official authorities of the two countries at all levels. however, cooperation and communication between people, institutions, schools, enterprises, and organizations have become broader and deeper. although the driving power comes from many sources, the main power has come from enterprises as institutions and organizations are able to benefit monetarily. finding a sustainable motive for people-to-people health cooperation and exchanges is an issue that must be addressed. these types of health cooperation and exchanges should be led by universities, research institutes, academic organizations, national and provincial hospitals, centers for disease control and prevention, and local medical and healthcare organizations. they must include multi-level, multi-form actions that include hosting academic meetings and visits, developing exchange programs for scholars, undergraduates, and postgraduates, establishing scholarship, conducting joint research, and facilitating other kinds of research on communicable diseases. thus, policies and mechanisms to provide support and services for non-governmental health cooperation and exchanges are urgently needed, including overseas healthcare, accident aid, insurance, danger prevention, customs clearance of materials, tax exemption, and preferential treatment for investment in the medical and health industry. we must recognize the current global health situation and see it from the perspective of politics, diplomacy, and development to meet the challenges that lie ahead. china will, as always, follow its existing guidelines, work diligently, and promote development. work together to build a community of shared future for mankind from the millennium development goals (mdgs) to the sustainable development goals (sdgs): africa in the post- development agenda. a geographical perspective global health and the 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in china: a subnational analysis of the global burden of disease study did we reach the targets for tuberculosis control? regional and national incidence and death for hiv, tuberculosis and malaria during - : a systematic analysis for the global burden of disease study vaccination is essential-past, present and future the new face of china's foreign aid: where do we go from here? experiences and challenges in the health protection of medical teams in the chinese ebola treatment center we appreciate miss zihan si for her language editing support. we are also grateful to the two anonymous reviewers for their valuable comments in response to our submission. this study was funded by grants from the national natural science the authors declare that they have no competing interests. key: cord- -rozpps v authors: faye, c.; wade, c.; dione, i. d. title: a dissymmetry in the figures related to the covid- pandemic in the world: what factors explain the difference between africa and the rest of the world? date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: rozpps v humanity has experienced outbreaks for millennia, from epidemics limited to pandemics that have claimed many victims and changed the course of civilizations. the advent of vaccines has eradicated some of the serious pathogens and reduced many others. however, pandemics are still part of our modern world, as we continue to have pandemics as devastating as hiv and as alarming as severe acute respiratory syndrome, ebola and the middle east respiratory syndrome. the covid- epidemic with -exponential contamination curves reaching million confirmed cases should not have come as a surprise, nor should it have been the last pandemic in the world. in this article, we try to summarize the lost opportunities as well as the lessons learned, hoping that we can do better in the future. the objective of this study is to relate the situation of covid- in african countries with those of the countries most affected by the pandemic. it also allows us to verify how, according to the observed situation, the african ecosystem seems to be much more resilient compared to that of other continents where the number of deaths is in the thousands. to verify this, the diagnosed morbidity and mortality reported for different states of the world are compared to the ages of life and the average annual temperature of these states. the results show that the less dramatic balance of the african continent compared to other continents is partly linked to the relatively high temperatures on the continent but also to the relatively young character of its population. humanity has experienced outbreaks for millennia, from epidemics limited to universal pandemics that have claimed many victims and changed the course of civilizations. the advent of vaccines has eradicated some of the serious human pathogens and mitigated many others. however, pandemics are still part of our modern world, as we continue to have pandemics as devastating as hiv and as alarming as severe acute respiratory syndrome, ebola and middle east respiratory syndrome (saqr and wasson, ) . the covid- epidemic with exponential curves reaching million confirmed cases should not have come as a surprise. however, we seemed to ignore the past. (peeri et al., ; morse, ) . unfortunately, covid- is not the last pandemic in the world and we need to learn what we missed and how to avoid failures. today. while border closures and travel restrictions within countries may be helpful, this is much less effective than in the past. pandemics require a stronger who with sufficient resources (morse, ) . failure to manage a pandemic in one country can have repercussions for the entire planet; therefore, pandemics require more solidarity and coordination so that fragile countries can find the resources to treat, isolate and combat severe epidemics. there are good signs that such efforts are being implemented (for example, the european union has announced eur billion to combat the current pandemic in developing countries) and, hopefully, these efforts are being consolidated to become systemic, proactive and organized. in other words, pandemics require global efforts with a strong and resourceful world health organisation. having appeared in china in the city of wuhan, covid- , initially a zoonosis, has spread throughout most of the world to become a pandemic affecting all social strata and relatively all ages of life. today, more than million people are affected and the spread of covid- continues to grow beyond the world's best performing health systems. however, it is clear that the geography of covid- disease shows significant disparities between countries and age groups in terms of the level of disease and the extent of mortality. this differentiated prevalence prompts reflection on possible explanations by taking into account a set of endogenous and exogenous factors (geographical, environmental, biological, socio-cultural, political contexts, etc.) . new epidemiological trends on transmission and mortality in africa and the most affected regions of the world suggest that better studies of this infection in sub-saharan africa than in other regions of the world are needed. the covid- pandemic has lower rates of local transmission and mortality in africa, the region where the virus was the last to arrive (imaralu, ) . the daily statistics emanating from the high infectious property of the new strain of coronavirus covid- , particularly its rapid worldwide transmission and the nature of the resulting deaths sweeping across countries, call for concerted efforts to limit local transmission in already colonized territories. there is currently no known consensual cure for covid- infection and there is currently no evidence to recommend specific anti-covid- treatment for patients confirmed to have this disease (who, a). the news of very high mortality rates in industrialized countries with stronger health systems and sophisticated infrastructure is cause for concern (who, b). facilities and equipment in industrialized countries that have so far provided assistance to developing countries are overwhelmed and not even sufficient to meet the current challenges facing these countries. as of april , , , confirmed cases of covid- -positive persons and , deaths worldwide had been reported to who (who, c) . there was concern about the impact of this virus on african nations, given the weakness of prevailing health systems with suboptimal infrastructural support (who, c). the recent mass exodus of health workers to europe and the americas and the continuing security threats of terrorism and violent crime make this new deadly viral threat a source of concern for governments in this subregion (imaralu, ) . on the basis of the above, the social and health implications of intervention measures to limit the spread of covid- virus should be considered and interventions carefully planned . this study thus proposes a diachronic reading of the evolution of covid- with as inputs the diagnosed morbidity and mortality reported in different states of the world on the one hand, and on the other hand the life expectancy and the average annual temperature of these states for a comparative study in order to draw all the specificities generated. this contribution focuses on the factors explaining this disparity in a statistical, sociodemographic and geographical analysis. it is based on a statistical treatment of aggregated data with a plural input taking into account the specificities of the prevalence of covid- at the level of the countries of the world. the covid- statistics used in this study are from the world health organization database and are as of monday, april , (https://www.weather-atlas.com or http://data.un.org/data.aspx?d=clino=elementcode% a figure ). for this study, countries were selected, countries in africa (these are indeed the african countries that have counted the most cases of covid- as of monday april ) and countries generally located in other continents ( countries in europe, in america, in asia, in oceania). indeed, these are the countries in the world that have counted the most cases of covid- as of monday april . the objective of this study is to relate the situation of covid- in african countries with those of the countries most affected by the pandemic. it also allows us to verify in what way the african ecosystem seems, according to the observed situation, much more resistant compared to that of other continents where the number of deaths is counted in thousands. to verify this state of affairs, two key hypotheses are raised: one natural (this is the average annual temperature of the country) and the other anthropogenic (this is the structure of the population). according to several scientists, the less dramatic balance of the african continent compared to other continents would be linked to the relatively high temperatures on the continent but also to the relatively young character of its population. to carry out this correlation study, the data used are shown in the following table. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. . it reduces the number of variables to those that are the most significant among a set of variables and is used to find a link between variables and individuals in order to group them into homogeneous regions. one of the objectives of pca is to obtain useful information from a data matrix, and to provide a graphical representation of the data to facilitate analysis. the mathematical procedure of principal component analysis is actually a multivariate statistical method of data processing. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint we subjected all the variables studied for the different countries under study to a principal components analysis, in order to determine the affinities between these countries and to deduce the most characteristic parameters. to do this, a correlation matrix was used and the components were determined according to the type of rotation of the orthogonal axes. the first factorial axis (f ) of this representation is such that it determines the maximum inertia of the cloud and thus the variance. the second axis (f ) perpendicular to the first expresses the maximum remaining variance. the third axis, always perpendicular to the other two, is defined by the maximum remaining inertia; etc. principal component analysis, or pca, is a method of reducing the number of variables allowing the geometric representation of observations and variables. this reduction is only possible if the initial variables are not independent and have non-zero correlation coefficients (bouroche and saporta, ) . the method was applied to countries ( in africa and in other continents) and variables which are: the covid- situation on monday april (confirmed cases and reported deaths), the mean annual temperature and the structure of the proportion ( to years, to years and over years). the final reconstitution of the distribution of the countries allowed us to define the factor axes or factors responsible for this distribution and consequently, to highlight the affinities between the different countries and to deduce the variables linked to the covid- pandemic that best characterize them. analysis of tables and and the eigenvalue curve ( figure. ), shows that the first three factors represent the maximum amount of information. thus the first three factor axes express . % of the total variance, with . % for the first factor, . % for the second and . % for the third factor (table and figure ). this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint there is an inverse relationship between the covid- pandemic (confirmed cases and reported deaths) and temperature, suggesting that generally the warmer a country is, the less likely it is to be affected by the coronavirus pandemic, and vice versa. the opposing relationship between the covid- pandemic (confirmed cases and reported deaths) and the proportion of elderly (and/or young) is apparent, suggesting that generally the younger a country's population is (and therefore the fewer vulnerable people), the less likely it is to be affected by the coronavirus pandemic, and vice versa. the number of confirmed cases is well correlated with the number of deaths, weakly correlated with the ageing character of the population and negatively correlated with the average temperature of the country and the youthful character of the countries' population. the axes , and thus selected highlight their relations with the parameters studied (table ) . the correlation matrix of the covid- pandemic variables and variance weight factors (table ) and figure. show that axis (main axis of inertia) which represents more than . % variance is very well positively correlated with the mean annual temperature of the country and the proportion of young people in the total population of the country. it is also weakly but this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / negatively correlated with the number of confirmed covid- cases, the number of reported deaths and the proportion of elderly in the total population. axis , with . % variance, is positively related, strongly with the number of confirmed covid- cases, the number of reported deaths and the proportion of elderly in the total population, weakly with the average annual temperature of the country and the proportion of young people in the total population of the country. it is negatively correlated, albeit weakly, with the proportion of the elderly in the total population. as for axis , which represents almost . % of the variance, it shows only a positive but weak correlation with the number of confirmed covid- cases and the mean annual temperature of the country. its correlation with the number of reported deaths and the proportion of young and old in the total population remains negative. the correlation of the covid- pandemic variables studied with this axis, whether positive or negative, is weak. these different characteristics of the covid- pandemic-related variables and of the countries studied are represented in circles and planes, respectively (figures and ) , which illustrate the projection of the variables and the variables on factorial planes and . each variable related to the covid- pandemic is associated with a point whose coordinate on a factorial axis is a measure of the correlation between that variable and the factor (axis or axis or axis ). projected on a factorial plane, the variables studied fit into a side plane ( figure ). they are all the closer to the side of the plane the more the variable is well represented by the factorial plane, i.e. the variable is well correlated with the two factors making up this plane. .. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. in plans i-ii and i-iii ( . % of cumulative inertia), axis i is determined by variables related to the covid- pandemic such as the mean annual temperature of the country and the proportion of young people in the total population, which are opposed to the number of confirmed covid- cases, the number of reported deaths and the proportion of elderly people in the total population. the purpose of this representation is to provide approximate planar images of the cloud of the countries located in the plane. thus, the x-axis represents the thermal component (mean annual temperature of the country) and the anthropogenic component (proportion of young people in the total population) of the countries, while the y-axis represents their profile (in terms of number of confirmed covid- cases and number of reported deaths). indeed, a country represented on the positive part of axis generally has a high temperature and a young character of its population; this is the case, for example, of african countries. in the u.s. plan, plan i-ii highlights three groups. the first group is made up of the countries that have recorded the greatest number of cases of contamination and deaths (e.g. united states, spain, italy, germany, france, etc.). these are the countries with the highest form values (a, p, kg , l and l). in this group, the united states stands out clearly from the others due to its higher number of contamination and deaths. the second group is made up of european countries (belgium, netherlands, switzerland...), american countries (canada, brazil, peru...), asian countries (israel, south korea, japan...) and oceania (australia) which have recorded a lower number of cases of contamination and deaths than those in the first group, despite certain common characteristics (such as temperature and the ageing of the population). the last group is made up of african countries with the lowest number of cases and deaths related to covid- . these countries also benefit from a high temperature and a young population. for use under a cc license. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. what analysis can be made of this cpa figure , which distinguishes three categories of countries? • the first category (usually - ) and the second category (usually - ) are made up of the european, american and asian countries most affected by the covid- pandemic. these countries are generally located in the temperate zone (where temperatures are relatively mild and conducive to the easy spread of the pandemic). in addition, they are countries with an aging population, and therefore a high number of vulnerable people), hence the high number of deaths related to the pandemic. however, there are some exceptions because among these countries there are a few that are located in the tropical zone, such as brazil, and are in this group. some african countries, such as mauritius, are also located in the group, due to its low average annual temperature, which brings it closer to countries in the temperate zone. • the third category (generally - ) consists strictly of african countries selected for this study (those most affected by the covid- pandemic). these countries are generally located in the tropical zone (whose temperatures are relatively high and unfavourable to the spread of the pandemic). in the early stages of the epidemic, the speed of contagion decreases with the temperature of the country or region and high temperatures reduce the initial rates of contagion (demongeot et al. , ) . containment policies and other rules of expulsion should take into account climatic heterogeneities in order to adapt public health decisions to possible geographical or seasonal gradients. in addition, these are for use under a cc license. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / countries with young populations (i.e., with very few vulnerable people), hence the low number of pandemic-related deaths. ultimately, the principal component analysis (pca) synthesized the information contained in table by crossing countries (individuals) and variables (quantitative). it produced a summary of information (figures , , and ) by establishing similarity between the selected countries, searching for homogeneous groups of countries, identifying a typology of countries and variables related to the covid- pandemic studied, and also identifying linkage budgets between variables related to the covid- pandemic, using synthetic parameters or variables. the cpa has generally established the linkages between these two typologies (kouani et al., ) . in conclusion, we note that the cpa has the advantage, on the one hand, of summarizing the set of correlated initial parameters into a reduced number of uncorrelated factors. on the other hand, it has enabled us to highlight similarities or oppositions between parameters and subbasins (faye, ; baba-hamed and bouanan, ) what analysis can be made of this cpa figure , which distinguishes three categories of countries? • the first category (usually - ) and the second category (usually - ) are made up of the european, american and asian countries most affected by the covid- pandemic. these countries are generally located in the temperate zone (where temperatures are relatively mild and conducive to the easy spread of the pandemic). in addition, they are countries with an aging population, and therefore a high number of vulnerable people), hence the high number of deaths related to the pandemic. however, there are some exceptions because among these countries there are a few that are located in the tropical zone, such as brazil, and are in this group. some african countries, such as mauritius, are also located in the group, due to its low average annual temperature, which brings it closer to countries in the temperate zone. • the third category (generally - ) consists strictly of african countries selected for this study (those most affected by the covid- pandemic). these countries are generally located in the tropical zone (whose temperatures are relatively high and unfavourable to the spread of the pandemic). in the early stages of the epidemic, the speed of contagion decreases with the temperature of the country or region and high temperatures reduce the initial rates of contagion (demongeot et al. , ) . containment policies and other rules of expulsion should take into account climatic heterogeneities in order to adapt public health decisions to possible geographical or seasonal gradients. in addition, these are countries with young populations (i.e., with very few vulnerable people), hence the low number of pandemic-related deaths. ultimately, the principal component analysis (pca) synthesized the information contained in table by crossing countries (individuals) and variables (quantitative). it produced a summary of information (figures , , and ) by establishing similarity between the selected countries, searching for homogeneous groups of countries, identifying a typology of countries and variables related to the covid- pandemic studied, and also identifying linkage budgets between variables related to the covid- pandemic, using synthetic parameters or variables. the cpa has generally established the linkages between these two typologies (kouani et al., ) . in conclusion, we note that the cpa has the advantage, on the one hand, of summarizing the set of correlated initial parameters into a reduced number of uncorrelated factors. on the other hand, it has enabled us to highlight similarities or oppositions between parameters and subbasins (faye, ; baba-hamed and bouanan, ). for use under a cc license. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / two months after the first cases of covid- appeared in africa, the spread of the disease appears to be progressing more slowly than elsewhere. since the first cases of covid- infection detected in africa in mid-february, as of may , there have been just over , reported cases (including those already cured) and deaths in africa, compared with over , , cases of illness and , deaths worldwide (who, d) . statistically, many experts still point to the african anomaly and link it to climate, geography and, in the most extreme cases, even to a kind of biological resilience (savana, ) . africa, with per cent of the world's population, is home to only . per cent of the world's sick and . per cent of its dead. better still, with already more than , recoveries, it seems to be much more resistant than others to covid- . for the time being, in any case, no one denies that the spread of the virus seems to be singularly slow on the continent, and many reasons are cited to try to explain this (marbot, ) . climate: like influenza, coronavirus is believed to be a disease that thrives in the cold season and does not tolerate heat, drought, or even heavy sun exposure. the hypothesis seems to be supported by the fact that the countries most affected by the pandemic have a rather temperate climate and that most cases are concentrated either in the extreme north of the continent or in the extreme south, where heat and drought are less overwhelming. on the research side, a british study confirms that, on average, fewer respiratory illnesses are found in hot and dry countries, and an american report of april states that the half-life of the virus, i.e., the period required for its infectious power to be halved, may increase from to hours if heat and humidity increase (marbot, ) . researchers nevertheless remain very cautious, like the director of international affairs at the pasteur institute, pierre-marie girard, who stresses that during in vitro experiments it was found that the coronavirus "multiplied very well in heat". sun, heat and humidity could weaken the covid- virus. according to a study of the american government, presented thursday april in washington, the virus responsible for the pandemic of covid- weakens in a hot and humid atmosphere as well as under the rays of the sun. "our most striking observation to date is the powerful effect that sunlight seems to have in killing the virus, both on surfaces and in the air," said a senior department of homeland security official bill bryan ( ). despite this, health minister olivier véran was sceptical and the who believes that high temperatures do not prevent the virus from being contracted. the youth of the population: this is the other major explanation put forward. in englishspeaking countries, it has even become a slogan: "the virus isold and cold and africa is young and hot". doctors confirm that the majority of severe cases of covid- involve people over years of age, which would be fortunate for the continent, where the median age is . years and % of the population is under years of age. it is also pointed out that one of the hardest hit countries, italy, has . per cent of its population aged and over, compared to per cent in africa. there is almost unanimous agreement on this hypothesis, but scientists qualify it by pointing out that although the african population is young, it is unfortunately more affected than others by diseases such as hiv or malnutrition, which can make it vulnerable. finally, some researchers note that in europe and the united states the elderly often live among themselves in old people's homes, which encourages the spread, whereas in africa they more frequently live with their families. this could protect them. average, and that cities such as lagos or abuja have record population densities. today, this position must be put into perspective because in some countries, it can be observed that most cases of infection concern localities with dense populations, including cities. another rational explanation that is difficult to circumvent is that the african population moves less, on average, than that of many advanced countries, and the risks of contamination are therefore necessarily lower. as a reminder, there is only one african airport in the list of the world's sites with the highest concentration of air traffic: johannesburg. the experience of epidemics: as many point out, this is not the first epidemic in africa, and there have been far more deadly ones, including the recent ebola crises. healthcare workers and populations alike are therefore used to dealing with health crises, lessons have been learned and "good practices" have been put in place. certain methods of detection, isolation of patients, and precautions during care developed previously are duplicable in the face of the coronavirus. the authorities also took the measure of the danger more quickly than others and put in place very early on the control or closure of borders, distancing or containment. this led dr moumouni kinda, who has faced several crises with the non-governmental organization alima, to say, "epidemics like ebola have given us experience on communication and awareness, which are key points in breaking the chains of transmission of the virus. for some african scientists, the continent also has the advantage of practicing true solidarity. when one country lacks masks or test kits, neighbouring countries that are less affected are likely to provide them. lesotho, which does not yet have an operational laboratory, has its samples tested in south africa, and a network for detecting seasonal influenza, used against covid- , already brings together some countries on the continent. without being overly optimistic, it must be said that solidarity sometimes seems to work better in africa than in certain richer regions, where we see the major laboratories jealously watching over their discoveries in the hope of being able to market a treatment or a vaccine. not to mention a donald trump trying to get his hands on the patents of drugs under development for the sole (financial) benefit of the united states...on a much more local scale, it is also pointed out that the community-based functioning of many african populations makes it possible to better convey prevention messages, but also to detect patients more quickly, since few people are likely to be left to their own devices. this hypothesis is the subject of much controversy, and the who, in particular, is very cautious. however, some doctors have noted some disturbing coincidences: there are reportedly fewer coronavirus contaminations in the countries most affected by malaria" or tuberculosis. or in those that massively vaccinate their population with bcg. would contracting certain diseases be a barrier to covid- ? it will take time to prove it, but many doctors believe that antimalarial treatments such as chloroquine have some effectiveness. that's partly why french professor didier raoult and teams like the drug discovery and development centre (h d) at the university of cape town are giving priority to testing antimalarial drugs. the who is critical, noting that some countries such as burkina faso, nigeria and senegal, where malaria is devastating, are not spared by the virus. more recently ( april), the malagasy president announced that his country was in possession of a "vita malagasy" remedy (made in madagascar) with preventive and curative virtues against the coronavirus. covid-organics, the name given to this treatment, is an herbal tea made from dried artemisia leaves, produced by the malagasy institute for applied research (imra). despite who warnings, member countries of the economic community of west african states (ecowas) will now be able to treat their for use under a cc license. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / coronavirus patients with covid-organics, and test the effectiveness of this improved traditional remedy proposed by imra. faced with the fight against the covid- pandemic, africans have chosen to put forward the unity and solidarity of africa. madagascar was able to demonstrate to the world that we africans can cooperate and help each other not only in an economic situation but above all in a health and humanitarian situation. a "genetic" immunity: what if africans were protected by their dna, which, for some reason yet to be determined, would be more robust against the coronavirus? the hypothesis is far from unanimous -at the pasteur institute, pierre-marie girard "doesn't really see why" such a specificity would exist -and will take time to be explored. the cameroonian professor christian happi, specialist in genomics, who divides his time between harvard university and nigeria, does not completely rule out this possibility: "africans are exposed to many diseases, so it is possible that their bodies react better. you'll have to look for antibodies to find out, but it's possible. after ebola, we saw that many people in nigeria had been exposed to the disease but had not developed it. » another version of the virus: an idea that is similar to the previous one: since it now seems that several different strains of covid- are present on the planet (up to eight distinct forms), perhaps the one present in africa is less aggressive? this could also explain the fact that there seem to be more asymptomatic cases there than elsewhere. the hypothesis remains audacious insofar as the virus arrived through patients who contracted it elsewhere. could it have mutated afterwards? the who does not rule out the idea, but stresses that in order to validate it it will be necessary to sequence the genome of covid- , which is currently underway. better masks: when asked about the specificities that could work in favour of africa, matshidisomoeti, who africa director, points out that the continent "has a very active and competent textile industry", especially in brazzaville, where the organization's offices are located. this particularity perhaps allows the population to benefit from more and better quality cloth masks than in some rich countries, where scarcity is the rule. in conclusion, the scientists point out that what probably explains the low number of cases observed on the continent is, above all, the fact that most countries took drastic protection measures very early on. and perhaps also the fact that because the disease initially affected people who were travelling, rather better informed than average and living mostly in cities, it was easier to identify the first cases than in other epidemics. but the modesty of the figures continues to amaze, as congolese biologist francine ntoumi notes: "in some countries on the continent, people eat bats, people live on top of each other... in fact, everything is done to make it explode, but it doesn't. "it's up to african scientists to find out why. however, caution should be exercised in the face of the figures because even if africa is not the continent most affected by covid- , the damage could be considerable, according to virologist denis chopera. in addition, the contamination rate would be underestimated due to the lack of medical facilities. in the context of this sars-cov- virus, transmission can take place during the last days of viral incubation, before symptoms appear or at least are significant. this is a viral strategy that has certainly allowed the virus to spread so impressively. another risk of under-evaluating cases is the lack of diagnostic tests or one of the reagents that make them up. given the international demand, the whole world is struggling to obtain everything necessary to fight the pandemic and africa is not always in an ideal position to be able to negotiate prices compared to other regions of the world. at the moment, patient management is going relatively well in the hospitals that have been identified to play this role and the system is not overwhelmed, although some tools, such as respirators, are sorely lacking. at present (as of may , ), just under ( ) deaths for approximately times the number of identified confirmed cases, which would correspond to for use under a cc license. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint a lethality of . %. although the global case-fatality rate is generally higher ( %), severe cases are more easily identified than non-symptomatic or minimally symptomatic cases, and it is possible that several foci of the infection have not been identified. if this is the case and the virus is insidiously transmitted in the population, it is likely that hospital infrastructures will be rapidly overwhelmed when the weakest are affected. globally, deaths due to covid- are lower among young people, including women and children, but higher among the elderly and people with chronic diseases. the pandemic appears to have lower local transmission and mortality rates in africa, the region with the youngest median age of the population and where the virus arrived last. while special efforts should be made to protect the elderly and infirm from infection, preventive measures among women (especially pregnant women) must provide access to emergency care to prevent the maternal mortality caused by covid- . similar to the crisis of the late s, the current crisis will have an impact on international relations. the structural changes already seen in the globalisation process can be expected to accelerate. in general, the world needs serious investment in research and development to understand current epidemics and to prepare for possible future ones. we need to prepare our health care infrastructure, develop new diagnostic and therapeutic solutions, invest in broadspectrum vaccines and antivirals, and fund research infrastructure and pandemic predictability. we need more social science research to help understand the social aspects of the pandemic, to foster engagement and trust in our communities, to improve our education to be more adaptive and to target misinformation. we need each other more than ever with greater compassion, solidarity and collaboration. a global pandemic requires global efforts. there will be future severe pandemics. who, d : coronavirus disease (covid- ) situation report - data as received by who from national authorities by : cest, may this report has been reformatted to improve accessibility for persons with visual impairment. p. https://www.who.int/emergencies/diseases/novel-coronavirus- /situation-reports for use under a cc license. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / for use under a cc license. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / : caractérisation d'un bassin versant par l'analyse statistique des paramètres morphométriques : cas du bassin versant de la tafna temperature decreases spread parameters of the new covid- case dynamics a principal component regression method for estimating low flow index méthode d'analyse statistique de données morphométriques : corrélation de paramètres morphométriques et influence sur l'écoulement des sous-bassins du fleuve sénégal temporal evolution of groundwater composition in an alluvial aquifer (pisuerga river, spain) by principal component analysis clinical features of patients infected with novel coronavirus in wuhan : emerging statistics on the epidemiology of covid- : making prevention in pregnancy less grievous than the disease analyse en composantes principales une méthode factorielle pour traiter les données didactiques. radisma : coronavirus : décryptage des hypothèses qui expliqueraient la faible contamination en afrique du mai à h pandemic influenza: studying the lessons of history covid- ) epidemics, the newest and biggest global health threats: what lessons have we learned? application of principal components analyse to the study of co -rich thermaineral waters in the aqufère system of alto guadalentin (spain) covid- : lost opportunities and lessons for the future covid- : l'exception africaine à l'épreuve des statistiques exploration des séries chronologiques d'analyse de la qualité des eaux de surface dans le bassin de la tafna en algérie. revue des sciences de l'eau who, a : world health organization. clinical management of severe acute respiratory infection (sari) when covid- disease is suspected: interim guidance who, b : world health organization. health systems in africa: community perceptions and perspectives. the report of a multi-country study. who. geneva; situation report- . who. geneva; key: cord- - sldbte authors: nkengasong, john n; onyebujoh, philip title: response to the ebola virus disease outbreak in the democratic republic of the congo date: - - journal: lancet doi: . /s - ( ) - sha: doc_id: cord_uid: sldbte nan the unfolding outbreak of ebola virus disease in the democratic republic of the congo (drc) dominated discussions at last month's world health assembly (wha) in geneva, switzerland. several funding pledges were made and who estimated that us$ million will be required to control the outbreak. on may , , the drc government declared an outbreak of ebola virus disease, initially in a remote area of the equateur province (figure). as of june , , the government of drc reported cases of ebola virus disease and deaths (case fatality rate · %). of the cases, were laboratory confirmed, were probable where it was not possible to collect laboratory specimens for testing, and were suspected. of the confirmed and probable cases, ( %) are from iboko, ( %) from bikoro, and four ( %) from wangata health zones. a total of five health-care workers have been affected, with four confirmed cases and two deaths. although this is the ninth outbreak of ebola virus disease in drc since , certain features of the current epidemic have caused serious concerns in the international community. first, four cases have been identified in wangata, a district of mbandaka, the capital of the equateur province with an estimated population of · million inhabitants. thus, this is the first time the drc government and partners are response to the ebola virus disease outbreak in the democratic republic of the congo aaa screening. routine management includes a ct angiography of the whole aorta for large screeningdetected aaa and an ultrasound of the popliteal arteries for all screening-detected aaas to detect concomitant popliteal artery aneurysms. sometimes, another aneurysm in the thoracic aorta or a more complex aortic aneurysm can be detected, which needs more careful planning and advanced interventional techniques. according to a recent report of screening-detected aaa, % of individuals who had surgery did not have a straightforward and simple evar. instead, they had a complex procedure associated with increased operative morbidity and mortality. an increasing proportion of popliteal artery aneurysms are found and operated because of screening for aaa. these scenarios have not been taken into account in the debate about the benefits and harms of aaa screening. smoking is eight times more common in individuals with aaa than in healthy controls and is implicated in % of aaa cases. the decreasing prevalence of smoking in sweden (from % of the population in , to % of the population in ) should be viewed as the main cause of the decreasing incidence and mortality of aaa. every percentage drop in the prevalence of smoking will have a huge effect on smoking-related diseases such as cancer and aaa. primary prevention programmes to reduce the prevalence of tobacco smoking is a top priority, whereas screening for aaa is not. department of clinical sciences, lund university, malmö , sweden stefan.acosta@med.lu.se i declare no competing interests. tackling an outbreak of ebola virus disease in an urban city. second, the other epicentres of the ebola virus disease outbreak are in rural remote areas: bikoro and iboko are located close to the river congo, which serves the two neighbouring countries of the central africa republic and the republic of the congo, creating an increased risk of the disease spreading to these countries if the outbreak is not rapidly controlled in drc. the - outbreak of ebola virus disease in west africa, which resulted in deaths, showed how rapidly the disease could spread into neighbouring countries. although the outbreak of ebola virus disease in drc is ongoing, two features of the response are noteworthy: the swiftness of the response time and the introduction of ring vaccinations, an innovative, pre-emptive strategy to vaccinate those most at risk of infection. the global health community learned from the - west africa ebola virus disease outbreak that a speedy response was vital to control the outbreak. the response to the current outbreak in drc has been rapid at the national, continental, and international levels. the drc health minister, oly ilunga kalenga, has led his country's response with pragmatism and expediency, both in kinshasa and at the provincial levels, by developing a comprehensive response plan and establishing appropriate technical committees and mobilising the requisite political, financial, and technical support. at the continental level, within days of declaration of the outbreak the africa centres for disease control and prevention (africa cdc), which one of us (jnn) leads, had activated its emergency operation center in addis ababa, ethiopia; deployed an advance team of epidemiologists to kinshasa to assist the ministry of heath; and briefed an extraordinary session of the permanent representative committee of the african union member states. in addition, the director of the africa cdc (jnn) led a delegation to kinshasa, bikoro, and mbandaka for an assessment of the gaps in the responses requiring support from africa cdc. the africa cdc team worked with the staff from who to assist the ministry of health to develop three strategies: surveillance and contact tracing; focal health-care zones to ensure adequate control measures; and laboratory testing. africa cdc is also deploying more than health-care workers, including epidemiologists, infection control and laboratory experts, and anthropologists. globally, who has had a crucial role by rallying appropriate attention to the outbreak and mobilising essential international partners to action. who has augmented the drc health ministry's response plan by deploying many health-care workers in the field and is supporting a ring vaccination programme with a merck-produced ebola vaccine. the vaccination programme is led by drc's ministry of health and supported by who and partners. this is the first time such a vaccine has been used outside of the west africa - epidemic. importantly, the vaccine is being deployed as the outbreak unfolds as part of a new international approach for rapid mitigation of outbreaks through multiple interventions. anthropological and sociological determinants of the uptake of the vaccination programme will be crucial as the intervention is scaled up. moreover, issues of access, equity, and ethical considerations in deploying the vaccine will need to be considered. containment centres at the affected sites to minimise transmission and improve clinical outcomes for detected patients. several other partners are assisting with the response, including the us centers for disease control and prevention, the international federation of red cross and red crescent societies, and others. however, six important gaps in outbreak governance and logistics management must be addressed to ensure a more comprehensive response to the ebola virus disease outbreak in drc. the first is leadership of the response. much has been learned from dealing with past outbreaks of ebola virus disease in west africa but each new outbreak has unique challenges. it is the responsibility of each country to ensure the health security of its citizens. however, effective leadership of the government of drc may be challenged given the weak health system of the country due to its long history of conflict and resulting economic and political difficulties. all efforts should be made to strengthen their leadership. as such, financial, human, and material assistance from the global community to drc's leadership will be central to ensure an effective response. second, coordination-but not controlof contributing partners' effort is essential to create efficiencies to control the outbreak. third, translating global material and financial commitment into countrylevel disbursements must be accelerated. fourth, commitments made to support the response in drc must be fulfilled. there have been huge logistical challenges with airlifting supplies and health-care workers from kinshasa to mbandaka, iboko, and bikoro, because no commercial flights exist from kinshasa to mbandaka and motorable roads from mbandaka to the other affected areas are non-existent. although financial and material support was expressed at the wha, ensuring that these commitments reach drc in a timely way is not yet evident. fifth, there has been inadequate support of the focal health-care zones (bikoro, iboko, mbandaka, and equateur province) to establish appropriate control measures and minimise transmission. finally, laboratory testing has been challenged by insufficient supplies and a shortage of experienced staff. the outbreak of ebola virus disease in drc is far from over and may take several months to bring under control. the steps taken in the next few weeks will be crucial to the trajectory of the outbreak and it is vital that effective coordination of partners' efforts and rapid provision of requisite and well tested interventions are put in place. in this context, fiscal and infrastructural support to drc will be important for rapid containment of the outbreak. as more partners join the fight to control this outbreak, standard operating procedures for engaging with the government, coordinating with other partners, allocating financial resources, and deployment in the field should be established quickly to ensure effective coordination, but not control, of partners' efforts. such standard operating procedures for outbreak governance will ensure that aid is not a burden to drc but an asset in the response. any successful public health response is based on trust between practitioners, patients, government, and communities. trust is essential for effective outbreak control and must be underpinned by active case finding, contact tracing and follow-up, and engagement with communities. in addition, health-care infrastructure needs to be strengthened and supported to provide health care for non-ebola patients. strengthened health-care systems are needed to address existing endemic health challenges and respond to future ebola outbreaks and other emerging infections in drc. alongside the response to the outbreak, post-ebola recovery plans for drc must include supporting the country to develop a functional national public health institute. in future, the response to a potential tenth outbreak of ebola virus disease in drc must be led by the country's national public health institute. in november, , an outbreak of the severe acute respiratory syndrome caught china unprepared. in response to that outbreak, the government of china established the chinese center for disease control and prevention (china cdc). today, if faced with a similar disease threat, china cdc, and not the international community, would lead the response in china. this is what should be done in drc and all african countries. this is a vision africa cdc and the african union are promoting as a new public health order for africa's health and economic security. to ensure that this vision is achieved, the african union commission and africa cdc will be convening an international conference on ebola in drc: response in july, , to raise funding and advocate for sustained support for the drc's response efforts. cardiac troponin assays were introduced into clinical practice in for the diagnosis of acute myocardial infarction. originally, this assay could not help to reliably rule out myocardial infarction until about h after symptom onset. consequently, there has been a drive to develop more sensitive and reliable troponin assays that would facilitate an earlier exclusion of myocardial infarction, ideally in the emergency department. [ ] [ ] [ ] the new high-sensitivity cardiac troponin (hstrop) assays are able to detect troponin at much lower concentrations than those detected previously. this is in keeping with the universal definition of myocardial infarction, which recommends that a troponin assay used to diagnose myocardial infarction should have a coefficient of variation of % or less at the threshold concentration representing the th percentile upper limit of a so-called normal reference population. modern hstrop assays can detect troponin in more than % of the general population, with some assays able to detect some troponin in nearly everyone. however, there are important implications of this increased detection sensitivity on the interpretation of positive hstrop results by front-line clinicians, particularly in the context of the well established subclassification of myocardial infarction, the most clinically relevant being type and type myocardial infarction. type myocardial infarction is a classic heart attack, in which erosion or fissuring of the surface of an atherosclerotic plaque attracts a plateletmediated thrombus, thus reducing the coronary artery flow. by contrast, type myocardial infarction is due to a myocardial oxygen supply-demand mismatch, which occurs in conditions such as tachyarrhythmias, anaemia, and sepsis. evidence unequivocally supports the use of hstrop as a rule-out test for type myocardial infarction, allowing for early discharge of patients with a low subsequent clinical event rate. as a rule-in test for type myocardial infarction, however, the hstrop test is subject to considerable troponin cardiac protein molecule swedish national board of health and welfare. screening for abdominal aortic aneurysm-recommendation and assessment bases benefits and harms of screening men for abdominal aortic aneurysm in sweden: a registry-based cohort study outcome of the swedish nationwide abdominal aortic aneurysm screening program psychosocial consequences in men taking part in a national screening program for abdominal aortic aneurysm cost-effectiveness of screening for abdominal aortic aneurysm in combination with medical intervention in patients with small aneurysms population screening and intervention for vascular disease in danish men (viva): a randomised controlled trial clinical practice guidelines of the european society for vascular surgery on the complexity of screening detected abdominal aortic aneurysms: a retrospective observational multicenter cohort study increasing the elective endovascular to open repair ratio of popliteal artery aneurysm the aneurysm detection and management study screening program: validation cohort and final results tackling the tobacco epidemic in the nordic countries and lower cancer incidence by / in a -year periodthe effect of envisaged scenarios changing smoking prevalence as aid workers move to the heart of congo's ebola outbreak, "everything gets more complicated ebola outbreak in the dr congo: lessons learned la situation épidémiologique de la maladie à virus ebola ebola outbreak in west africa democratic republic of the congo. strategic response plan for the ebola virus disease outbreak democratic republic of efficacy and effectiveness of an rvsv-vectored vaccine in preventing ebola virus disease: final results from the guinea ring vaccination, open-label, cluster-randomised trial (ebola Ça suffit!) infectious disease trends in china since the sars outbreak africa centres for disease control and prevention, african union headquarters, po box , w k addis ababa, ethiopia nkengasongj@africa-union.org jnn is director of africa centres for disease control and prevention and po is senior adviser for policy and strategy in the office of the director at africa centres for disease control and prevention. we declare no other competing interests. key: cord- -m qe he authors: abbas, k. m.; procter, s. r.; van zandvoort, k.; clark, a.; funk, s.; lshtm cmmid covid- working group,; mengistu, t.; hogan, d.; dansereau, e.; jit, m.; flasche, s. title: benefit-risk analysis of health benefits of routine childhood immunisation against the excess risk of sars-cov- infections during the covid- pandemic in africa date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: m qe he background: national immunisation programmes globally are at risk of suspension due to the severe health system constraints and physical distancing measures in place to mitigate the ongoing covid- pandemic. our aim is to compare the health benefits of sustaining routine childhood immunisation in africa against the risk of acquiring sars-cov- infections through visiting routine vaccination service delivery points. methods: we used two scenarios to approximate the child deaths that may be caused by immunisation coverage reductions during covid- outbreaks. first, we used previously reported country-specific child mortality impact estimates of childhood immunisation for diphtheria, tetanus, pertussis, hepatitis b, haemophilus influenzae type b, pneumococcal, rotavirus, measles, meningitis a, rubella, and yellow fever (dtp , hepb , hib , pcv , rotac, mcv , mcv , mena, rcv, yfv) to approximate the future deaths averted before completing five years of age by routine childhood vaccination during a -month covid- risk period without catch-up campaigns. second, we analysed an alternative scenario that approximates the health benefits of sustaining routine childhood immunisation to only the child deaths averted from measles outbreaks during the covid- risk period. the excess number of infections due to additional sars-cov- exposure during immunisation visits assumes that contact reducing interventions flatten the outbreak curve during the covid- risk period, that % of the population will have been infected by the end of that period, that children can be infected by either vaccinators or during transport and that upon child infection the whole household would be infected. country specific household age structure estimates and age dependent infection fatality rates are then applied to calculate the number of deaths attributable to the vaccination clinic visits. we present benefit-risk ratios for routine childhood immunisation alongside % uncertainty range estimates from probabilistic sensitivity analysis. findings: for every one excess covid- death attributable to sars-cov- infections acquired during routine vaccination clinic visits, there could be ( - ) deaths in children prevented by sustaining routine childhood immunisation in africa. the benefit-risk ratio for the vaccinated children, siblings, parents or adult care-givers, and older adults in the households of vaccinated children are , ( , - , , ), , ( , - , , ), , ( - , ), and ( - ) respectively. in the alternative scenario that approximates the health benefits to only the child deaths averted from measles outbreaks, the benefit-risk ratio to the households of vaccinated children is ( - ) under these highly conservative assumptions and if the risk to only the vaccinated children is considered, the benefit-risk ratio is , ( - , ). interpretation: our analysis suggests that the health benefits of deaths prevented by sustaining routine childhood immunisation in africa far outweighs the excess risk of covid- deaths associated with vaccination clinic visits. however, there are other factors that must be considered for strategic decision making to sustain routine childhood immunisation in african countries during the covid- pandemic. these include logistical constraints of vaccine supply chain problems caused by the covid- pandemic, reallocation of immunisation providers to other prioritised health services, healthcare staff shortages caused by sars-cov- infections among the staff, decreased demand for vaccination arising from community reluctance to visit vaccination clinics for fear of contracting sars-cov- infections, and infection risk to healthcare staff providing immunisation services as well as to their households and onward sars-cov- transmission into the wider community. vaccines have substantially improved health and reduced mortality, particularly among children in low-income countries [ ] [ ] [ ] . access to vaccines in these countries accelerated after the formation of gavi, the vaccine alliance in [ ] . this access needs to be sustained to further advance the public health gains and maintain progress towards goals such as the elimination of polio, measles, rubella, and maternal tetanus [ ] . the world health organization has launched its immunization agenda strategy in order to accelerate progress towards equitable access and use of vaccines over the new decade [ ] . however, ensuring everyone has access to immunization services has proved challenging, with a quarter of children in the africa region not receiving three doses of diphtheria-tetanus-pertussis (dtp ) in [ ] . this is now further challenged by the coronavirus disease pandemic [ ] , which has necessitated physical distancing measures to mitigate or delay the coronavirus epidemic that threatens to overwhelm health care systems [ ] . the severe acute respiratory syndrome coronavirus (sars-cov- ) emerged in december causing cases of covid- in wuhan, china [ ] . as of may , , there were , , confirmed cases and , confirmed deaths affecting countries and territories [ ] . all african countries have reported cases with the majority reporting local transmission and rapidly rising case numbers [ ] . the prevention and control measures to suppress and mitigate the covid- outbreak in africa during the upcoming months will place immense pressures on the national health systems in their provision of essential health services, including the expanded programme on immunization (epi) and routine vaccination of infants [ ] . on march , , the world health organization and the pan american health organization issued guidance on the operation of immunisation programmes during the ] . the guidance advises for temporary suspension of mass vaccination campaigns and a risk-benefit assessment to decide on conducting outbreak response mass vaccination campaigns, while routine immunisation programmes should be sustained in places where essential health services have operational capacity of adequate human resources and vaccine supply while maintaining physical distancing and other infection control measures. our aim is to compare the health benefits of sustaining routine childhood immunisation in africa against the risk of acquiring sars-cov- infections through visiting routine vaccination service delivery points. specifically, we conducted a benefit-risk analysis of vaccine-preventable deaths averted by sustaining routine childhood immunisation in comparison to excess covid- deaths from sars-cov- infections acquired by visiting routine vaccination service delivery points. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org / . / . / we assess the benefit and risk of continued routine childhood immunisation during the pandemic in all african countries. we focus on the delivery of infant immunisation at: (i) , and weeks of age for diphtheria, tetanus and pertussis (dtp), polio, hepatitis b (hepb), haemophilus influenzae type b (hib), streptococcus pneumoniae , rotavirus (hereafter called epi- ); (ii) months for measles (mcv ), rubella (rcv ), neisseria meningitidis serogroup a (mena), yellow fever (yfv) (hereafter epi- ); and (iii) - months for the second dose of measles (mcv ; epi- ). the target age for mena routine immunization varies by country and is given along with the first or second dose of measles - months in central african republic, chad, côte d'ivoire, mali, niger, and sudan; months in burkina faso; and months in ghana [ ] . we did not consider bacillus calmette-guérin (bcg) or hepb birth dose because they are recommended for administration shortly after birth and thus were assumed not to require an additional vaccination visit, albeit home births or delayed administration may be common in some parts of africa. during the period of sars-cov- circulation, we assume that contact-reducing measures are in place and that while those measures fail to contain the outbreak, they will be able to substantially flatten the epidemic curve. in both other qualitatively different scenarios (uncontrolled epidemic or successful containment) sustaining vaccination as far as possible would be the largely obvious choice as doing so would not substantially affect the risk of sars-cov- infection. we assume that the risk from covid- , and hence the potential disruption to the health services including routine childhood vaccination lasts for months. the main analyses consider the impact of continuation of all five immunisation clinic visits in comparison with the risk for covid- disease in the vaccinees household as a result of attending the vaccine clinic, tracking the health benefits from immunisation among the vaccinated children until five years of age. we used the health impact estimates provided by li [ ] . polio is rarely fatal for children and hence we did not include polio vaccine preventable mortality into our estimates. antigen-specific estimates of per-capita deaths averted by vaccination were unavailable for countries, and were approximated to the mean estimates of other countries with available data. country and antigen-specific levels of routine vaccination coverage are assumed to be the same level as for . . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the child deaths averted by routine vaccination during a -month suspension period of immunisation are the product of country and antigen-specific estimates of per-capita deaths averted by vaccination from the time of vaccination until years of age [ , ] , country-specific population estimates of the vaccinated cohort [ ] , country and antigen-specific official country reported estimates of vaccination coverage [ ] , and the suspension period of immunisation. we considered two scenarios -high-impact and low-impact, for approximating the impact of sustained routine childhood immunisation. in the high-impact scenario, we approximate the impact of sustained routine childhood immunisation with the estimates for impact of vaccination of a -month cohort in . hence, this scenario assumes that the suspension of immunisation will result in a cohort of unvaccinated children who have the same risk of disease as children in a completely unvaccinated population, and their vulnerability persists until they are years old, i.e. no catch-up campaign will be conducted at the end of the sars-cov- outbreak. because of herd protection and likely catch-up activities at the end of a potential disruption of immunisation services, this high-impact scenario very likely overestimates the negative impact of suspending immunisation services for a short period of time. in contrast, the low-impact scenario attempts to estimate a lower bound on the expected number of deaths due to disruptions to routine childhood immunisation services. we assume that in the absence of immunisation, herd immunity would protect children missing out on vaccination from all diseases with the exception of measles, and that vaccination through catch-up campaigns would close measles immunity gaps immediately following the month covid disruption period. this scenario is implemented as illustrated by the following example. in a country with % routine measles vaccine coverage, the inter-epidemic period of measles outbreaks is about years [ ] . the suspension of the routine vaccination programme for months would correspond to an accumulation of susceptibles equivalent to months in normal times, thus shrinking the inter-epidemic period to years. in the absence of supplementary immunisation activities this would yield a % chance that an outbreak starts during the months of suspension. further, the physical distancing interventions in place to mitigate the covid- risk may decrease that outbreak probability by an additional %. thereby, there is a . % ( % * %) chance of a measles outbreak during the -month suspension period. we assume that in the coming months that african countries will experience sars-cov- spread similar to that observed in non-african countries affected earlier in the pandemic which were unable to contain the virus. particularly, we assume that climatic or other africa specific factors will not notably reduce the transmissibility of sars-cov- [ , ] . the risk of covid- depends on exposure probability to sars-cov- and progression to disease. for this analysis, we only consider the case-fatality risk for covid- and ignore other potentially severe health outcomes. we model the additional sars-cov- exposure risk for the vaccinated child, their . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . carer, and household members as a result of contact with the vaccinator and other community members during travel to the vaccine clinic. the covid- risk model is described in more detail in appendix a , and the simulation parameters for sars-cov- infection dynamics are shown in appendix a based on the reed-frost epidemic model [ ] . we use the country-specific household age composition to approximate the age distribution in households at risk of sars-cov- infection given that one of the household members is a child who has been vaccinated, and is further elaborated in appendix a [ ] . we apply age-stratified infection fatality risk for sars-cov- using estimates obtained from reported cases and their severity in china in combination with the proportion of asymptomatic infections estimated among international residents repatriated from china [ ] . for children, we used the reported risks for ages - years, for adults the risk for ages - years, and for older adults over the risk for ages - years. we conducted a probabilistic sensitivity analysis by conducting simulation runs to account for the uncertainty around the parameters governing the sars-cov- infection model, as well as the reported uncertainty ranges for the infection fatality rate estimates (modelled using a gamma distribution), and the vaccine preventable mortality estimates (modelled using a lognormal distribution), and assessed their impact on our findings. the program code and data for the benefit-risk analysis conducted in this study is accessible on github ( https://github.com/vaccine-impact/epi_covid ). all analyses were done using r . . [ ] . all data were from secondary sources in the public domain, and ethics approval was thereby not required. the funders were involved in the study design; collection, analysis, and interpretation of data; writing of the paper; and the decision to submit it for publication. all authors had full access to data in the study, and final responsibility for the decision to submit for publication. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org / . / . / in the high-impact scenario, we estimate that the current routine childhood immunisation programme (dtp, hepb, hib, pcv, rotac, mcv, rcv, mena, yfv) in africa during a months period in would prevent , ( , - , ) deaths in children from the time of vaccination until they are years old. about one third of averted deaths are attributable to measles and another third to pertussis. immunisation during the three epi- visits for dtp , hepb , hib , pcv , and rotac will prevent , ( , - , ) deaths, immunisation during epi- visit for mcv , rcv , mena, and yfv will prevent , ( , - , ) deaths, and immunisation during epi- for mcv will prevent , ( , - , ) deaths among children until they are years old (see table ). one-third of the deaths prevented by routine childhood vaccination are in nigeria, ethiopia, democratic republic of congo, and tanzania (see table ). we estimate that the three immunisation visits for epi- add . % ( . - . ) altogether and each immunisation visit of epi- and epi- add . % ( . - . ) to the probability of excess sars-cov- infection in the household. as a result, continuation of routine childhood immunisation in africa may lead to , ( , - , ) excess deaths attributable to additional sars-cov- infections associated with the immunisation visits of children. about ( - ) of these are expected to be among the vaccinated children, ( - ) among their siblings, ( - , ) among their parents or adult carers, and , ( , - , ) among older adults in the household. for every one excess covid- death attributable to additional household exposure to sars-cov- infections due to routine childhood immunisation visits, we estimate that the routine childhood immunisation programme would prevent ( - ) deaths in children until years of age in africa (see table ). the benefit of the three epi- immunisation visits in early infancy and the visit for epi- at months were ( - ) and ( - ) deaths averted among children per excess covid- death, respectively. the incremental benefit of the second dose of measles vaccination during epi- visit at - months was ( - ) deaths averted among children per excess covid- death. more than % of the excess covid- risk is due to the high fatality rate among older adults aged above years. if only the risk to vaccinated infants is considered, the benefit-risk ratio is substantially higher at , ( , - , , ) (see appendix a ). our findings were largely similar across countries (see figure , table , and appendix a ). country-specific benefit-risk ratios for epi- , epi- , and epi- are presented in the appendix (see a , a , a ). the overall benefit risk-ratio of sustaining routine childhood immunisation ranged from ( - ) in morocco to ( - , ) in angola, and the number of child deaths averted through vaccination substantially exceeded the number of excess covid- deaths for all the countries of africa. in the low-impact scenario that approximates the health benefits to only the child deaths averted from measles outbreaks, the benefit-risk ratio to the households of vaccinated children is ( - ) . when the risk to only the vaccinated children is considered, the benefit-risk ratio is , ( -. cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org / . / . / , ). even under these highly conservative assumptions, the benefit ratios for most countries in africa are larger than and indicates in favour of sustaining the routine childhood immunisation programme during the covid- pandemic (see figure ). tunisia, eswatini, and morocco have benefit-risk ratios lower than , since measles vaccination impact is relatively at the lower end in these three countries in comparison to other countries in africa. we evaluated the contribution of the uncertainty in the model parameters to the uncertainty in the benefit-risk ratio estimates ( figure ). the main factors influencing our estimates of the benefit-risk ratio were the average number of contacts of the child and their carer during a visit to the vaccine clinic, the average number of transmission relevant contacts of a community member per day and hence the risk for transmission given a potentially infectious contact, and the infection-fatality rate for sars-cov- infected older adults aged above years. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org / . / . / our analysis suggests that the benefit from sustaining routine childhood immunisation in africa far outweighs the excess risk of covid- deaths due to the additional risk for sars-cov- infections during the child's vaccination visit, particularly for the vaccinated children. this reinforces the guidance and statement issued by the world health organization and the measles & rubella initiative respectively to sustain routine childhood immunisation programmes where essential health services have operational capacity of adequate human resources and vaccine supply while maintaining physical distancing and other infection control measures to ensure the safety of communities and health workers [ , ] . we base our analyses on model-based country and antigen-specific vaccine impact estimates in low and middle income countries for [ , ] . there is considerable uncertainty in the impact suspending immunisation activities for a period of about months and whether a timely and high-coverage catch-up campaign can be conducted soon after. therefore, we presented two extreme scenarios -high-impact and low-impact, for the potential benefits from sustaining routine childhood vaccination. in the high-impact scenario, we approximate the impact of sustained routine childhood immunisation with the estimates of vaccination impact for a -month cohort in . while pathogen resurgence will happen gradually due to herd protection from the rest of the population, this could be counterbalanced by unvaccinated children of this and other cohorts continuing to be at risk of disease beyond the -month window. in the presence of social distancing measures, the exposure to non-coronavirus pathogens will also likely be reduced but those who may remain susceptible as a result of immunisation service suspension may get infected once distancing measures are relaxed. in the low-impact scenario, we approximate the impact of sustaining vaccination by the number of child deaths as a result of potential measles outbreaks during the covid- risk period while also accounting for catch-up campaigns to be delivered at the end of the covid- risk period. we show that in both scenarios that continuation of routine childhood immunisation is beneficial and outweighs the excess risk of covid- deaths due to the additional risk for sars-cov- infections during the immunisation visits. to calculate the number of covid- associated fatalities, we used infection fatality rates that were derived based on a combination of estimates from chinese surveillance for covid- cases and fatalities and the proportion of asymptomatic cases observed on repatriation flights from china. while the younger african age-demographic may mitigate some of the covid- disease burden, infection fatality rates in africa may be substantially higher because of the prevalence of likely risk factors including hiv, tuberculosis, and malnutrition as well as lack of access to antibiotics to limit the risk for bacterial coinfections in some parts of africa. however, our uncertainty analysis illustrates that while the uncertainty of the covid- infection fatality rate is a key factor in the overall uncertainty of our estimates, even at the upper mortality bounds, continuation of routine . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . childhood vaccination is beneficial. furthermore, the effects of a potentially higher covid- fatality ratio in africa may be balanced by a higher fatality ratio of measles and the other vaccine preventable diseases in times when the healthcare system is stretched and vitamin a supply is suspended. because of high transmissibility of measles, routine childhood immunisation coverage in many countries is insufficient to prevent outbreaks. to aid routine vaccination coverage, supplementary immunisation activities (sias) are conducted regularly, many of them scheduled for this year, at a point shortly before sufficient population immunity has built up to prevent measles outbreaks [ ] . supplementary immunisation activities have recently been postponed to reduce the risk for covid- infections during mass vaccination [ ] , further enhancing the likelihood and impact of measles outbreaks if routine childhood vaccination is suspended. because sias tend to be timed at the right interval to avoid outbreaks, our low-impact scenario is likely to underestimate the risk of an outbreak occurring due to sia suspension. we conducted a probabilistic sensitivity analysis to assess the impact of parameter uncertainty on the estimated benefit-risk ratios. we found that the biggest contribution to the uncertainty around the benefit of sustaining routine childhood immunisation during the covid- pandemic in africa are the transmission probability and the number of contacts during a vaccination visit. this highlights the need for personal protective equipment for vaccinators, the need to implement physical distancing measures including the avoidance of crowded waiting rooms for vaccination visits, and the importance of good hygiene practices to reduce the risk of sars-cov- acquisition and transmission at the vaccination clinics. it will be challenging to implement some of these infection prevention and control measures in many african countries due to resource constraints. we estimated the benefit-risk trade-off for sustaining routine childhood immunisation during the covid- pandemic in africa and found that the benefits substantially outweigh the risks. however, there are other factors that must be considered for strategic decision making to sustain routine childhood immunisation in african countries during the covid- pandemic. these include logistical constraints of vaccine supply and delivery cold chain problems caused by the covid- pandemic, reallocation of doctors and nurses to other prioritised health services, healthcare staff shortages caused by sars-cov- infections among the staff or staff shortages because of ill-health or underlying health conditions that put them at increased risk for severe covid- disease, and decreased demand for vaccination arising from community reluctance to visit vaccination clinics for fear of contracting sars-cov- infections. also, the opportunity risk of sars-cov- infection for the vaccinated children and healthcare staff involved in immunisation activities as well as to their households and onward sars-cov- transmission into the wider community should be considered (see appendix a ). . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org / . / . / in conclusion, routine childhood immunisation programmes should be safeguarded for continued service delivery and prioritised for the prevention of infectious diseases, as logistically possible, as part of delivering essential health services during the covid- pandemic in africa. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org / . / . . . doi: medrxiv preprint tables table : vaccine antigen specific benefits and risks of sustaining routine childhood vaccination. the benefit-risk ratio estimates (median estimates and % uncertainty intervals) show the child deaths averted by sustaining routine childhood immunisation in africa per covid- death attributable to excess sars-cov infections acquired through visiting routine vaccination service delivery points. note that the vaccine preventable deaths estimates are vaccine antigen specific, while the excess deaths are dependent on the number of required visits. as vaccination visits group delivery of several vaccines, these have a higher benefit-risk ratio than that for individual antigens. excess . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . the benefit-risk ratio estimates (median estimates and % uncertainty intervals) show the child deaths averted by sustaining routine childhood immunisation in the african countries per covid- death attributable to excess sars-cov infections acquired through visiting routine vaccination service delivery points. the combined impact of the routine childhood vaccination is shown for -dose dtp , hepb , hib , pcv for children at , and weeks, -dose rotac for children at and weeks, -dose mcv , rcv , mena, yfv for children at months, and -dose mcv for children at - months of age. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org / . / . . . doi: medrxiv preprint the number of vaccine preventable future deaths averted before completing five years of age by sustaining routine childhood vaccination of dtp, hepb, hib, pcv, rotac, mcv, rcv, mena and yfv per covid- death attributable to excess sars-cov infections acquired through visiting routine vaccination service delivery points. the routine childhood vaccines considered are -dose dtp , hepb , hib , pcv for children at , and weeks, -dose rotac for children at and weeks, -dose mcv , rcv , mena, yfv for children at months, and -dose mcv for children at - months of age. a benefit-risk ratio larger than indicates in favour of sustaining the routine childhood immunisation programme during the covid- pandemic. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . the number of vaccine preventable future deaths averted before completing five years of age by sustaining routine childhood vaccination of dtp, hepb, hib, pcv, rotac, mcv, rcv, mena and yfv per covid- death attributable to excess sars-cov infections acquired through visiting routine vaccination service delivery points. we consider a small chance ( . %) of measles outbreaks while no other vaccine preventable disease outbreaks take place due to herd immunity. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . sensitivity analysis shows the estimated contribution of different model parameters to the overall uncertainty in the benefit-risk ratio of continuing routine childhood immunisation during the covid- pandemic in africa. the tornado diagram was constructed using a multivariate poisson regression model to the estimated posterior distribution of the benefit-risk ratio using our model input parameters as predictors, and treating total deaths averted by childhood immunisation as a single variable. the main factors influencing the benefit-risk ratio estimates were the average number of transmission relevant contacts of a community member per day, the average number of contacts of the child and their carer during a visit to the vaccination clinic, and the infection-fatality rate of sars-cov- infected older adults aged above years. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://measlesrubellainitiative.org/measles-news/more-than- -million-children-at-risk-ofmissing-out-on-measles-vaccines-as-covid- -surges/ activities ( . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org / . / . / supplementary appendix a . covid- risk model a . simulation parameters for sars-cov- infection dynamics a . household structure and age composition a . age and antigen specific benefit-risk ratios for africa at the continental level a . country and age specific benefit-risk ratios for africa at the national level a . benefit-risk ratio of vaccines delivered in the first, second, and third vaccination-related clinical visits a . benefit-risk ratio of vaccines delivered in the fourth vaccination-related clinical visit a . benefit-risk ratio of vaccines delivered in the fifth vaccination-related clinical visit a . opportunity risk for vaccinated children and healthcare staff involved in immunisation activities a . age and antigen specific deaths averted by vaccination, excess deaths due to covid- , and benefit-risk ratios for africa at the continental level a . country, age, and antigen specific deaths averted by vaccination, excess deaths due to covid- , and benefit-risk ratios for africa at the national level a . age and antigen specific deaths averted by measles vaccination, excess deaths due to covid- , and benefit-risk ratios for africa at the continental level -scenario of measles-only vaccination impact a . country and age specific deaths averted by measles vaccination, excess deaths due to covid- , and benefit-risk ratios for africa at the national level -scenario of measles-only vaccination impact . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org / . / . / the risk of infection with sars-cov- depends on the stage of the epidemic. as a base case, we assume that through contact reducing interventions, community sars-cov- transmission will be spread over a period ( t ) of months and the exposure risk is constant during that time due to contact-reducing interventions successfully mitigating sharp peaks in disease (table a ) contacts per day during their infectious period of days (i.e., a community member) or potentially infectious contacts per day but who self isolates on symptom onset that occurred days into their infectious period (i.e., a vaccinator). both the vaccinated child and the parent or caregiver, will be at additional risk of exposure during travel to the vaccine clinic, while waiting at the vaccine clinic and during vaccination. in addition, we assume that if either of them gets infected they will infect all other household members, owing to the high secondary attack rates observed for family gatherings [ ] . we ignore any additional secondary infections outside the household, which are likely to be minimal due to physical distancing measures. based of the reed-frost epidemic model [ ] , the probability ( p ) for a sars-cov- infection for the whole household of a child who gets vaccinated is calculated as one minus the probability of either the infant or the mother not being infected by either the vaccinator or anyone else on any of the vaccination visits: , with v the number of vaccine clinic visits. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . hence, the probability for such infection to be in excess of sars-cov- infections that would have occurred otherwise is p e = p ( -Θ) . we assume that during the months of sars-cov- transmission, all children who get one dose of dtp will also get the other two doses. however, children receiving their measles containing vaccines will only get one dose during that time window because the two doses are given more than six months apart. the number of children who would normally get dtp during the considered time frame is approximated by half of the under one-year old population. similarly, the number of children who will get either the first or the second measles-containing vaccine dose is half of the under -year old children or half of the children aged - months respectively. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . t duration of period at risk for sars-cov- months u ( , ) [ ] Θ proportion of sars-cov- infected population at the end of the study period assuming neither (i) "overshooting" of the epidemic due to high rates of transmission or (ii) elimination of transmission prior to herd immunity being reached. we use the country-specific household age composition to approximate the age distribution in households at risk of sars-cov- infection given that one of the household members is a child who has been vaccinated [ ] . first, we estimate the number of siblings of an infant from the average number of household members aged less than in households with at least one member aged less than . the number of siblings is adjusted to account for the effect of birth order by assuming that on average the infant would be the mid-born child. secondly, we assume the average household will have two adults (parents or caregivers). thirdly we assume that a proportion of households with vaccinated children will also have older adults aged over years. we estimate this proportion using the percentage of households that have both members aged less than years and over years old. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org / . / . / . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org / . / . / ( -dose mcv , rcv , mena, yfv) for children at -months of age during the covid- pandemic in africa. the central estimates for benefit-risk ratio at the household level show the child deaths averted by continuing the routine childhood immunisation programmes ( -dose mcv , rcv , mena, yfv for -month-old children) per excess covid- death caused by sars-cov infections acquired in the vaccination service delivery points. benefit-risk ratio above indicates in favour of sustaining the routine childhood immunisation during the covid- pandemic. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org / . / . / . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org / . / . / the opportunity risk of sars-cov- infection for the vaccinated children and healthcare staff involved in immunisation activities as well as to their households and onward sars-cov- transmission into the wider community should be included in the decision-making process to sustain routine childhood immunisation. first, we need to know the opportunity risk of sars-cov- infection for the healthcare staff. similar to the concept of opportunity cost, what is the risk of sars-cov- infection to the healthcare staff engaged in alternative healthcare activities if not involved in immunisation activities? if the opportunity risk of alternative healthcare activities is lower than being involved in immunisation activities, then reallocation of healthcare staff from immunisation to alternative healthcare activities is a better risk-avoidance strategy. on the other hand, if the opportunity risk of alternative healthcare activities is higher than being involved in immunisation activities, then healthcare staff face relatively lower risk in continuing to provide the immunisation services, thereby posing relatively lower risk to their households and sars-cov- transmission into the wider community. second, we need to know the opportunity risk of sars-cov- infection to the vaccinated children. if the alternative activity that the children and their carers would be involved in had a higher risk of sars-cov- infection in comparison to the risk involved with the immunisation visits, then it is beneficial for the children and their carers to undertake the immunisation visits for the children to get vaccinated and thereby posing relatively lower risk to their households and sars-cov- transmission into the wider community. irrespective of the opportunity risk of sars-cov- infection for the healthcare staff providing immunisation services during the covid- pandemic, to ensure their safety, health care practices will need to be adapted to minimise the risk of sars-cov- acquisition and transmission at vaccination clinics. this includes physical distancing measures, personal protective equipment, and good hygiene practices for infection control at the vaccination clinics. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org / . / . / vaccination greatly reduces disease, disability, death and inequity worldwide cost-effectiveness and economic benefits of vaccines in low-and middle-income countries: a systematic review estimating the health impact of vaccination against pathogens in low and middle income countries from the power of vaccines and how gavi has helped make the world healthier: lasker-bloomberg public service award immunization: vital progress, unfinished agenda wuenic coverage estimates -vaccines monitoring system early estimates of the indirect effects of the covid- pandemic on maternal and child mortality in low-income and middle-income countries: a modelling study. the lancet global health clinical features of patients infected with novel coronavirus in wuhan covid- ) pandemic, world health organization who. coronavirus disease (covid- ) situation report - covid- disrupts vaccine delivery the immunization program in the context of the covid- pandemic. pan american health organization status of the rollout of the meningococcal serogroup a conjugate vaccine in african meningitis belt countries in vaccines for children in low-and middle-income countries united nations department of economic and social affairs population division official country reported vaccination coverage estimates time series, world health organization effective transmission across the globe: the role of climate in covid- mitigation strategies covid- pandemic in west africa an examination of the reed-frost theory of epidemics united nations, department of economic and social affairs, population division. database on household size and composition estimates of the severity of coronavirus disease : a model-based analysis mena ( - ) djibouti age and antigen specific deaths averted by vaccination, excess deaths due to covid- , and benefit-risk ratios for africa at the continental level age and antigen specific deaths averted by vaccination, excess deaths due to covid- , and benefit-risk ratios (central estimates and uncertainty intervals) for routine childhood vaccination are included in the dataset. the routine childhood vaccines considered are -dose dtp , hepb , hib , pcv for children at , and weeks, -dose rotac for children at and weeks, -dose we thank nicholas grassly, raymond hutubessy, and anthony scott for helpful discussions. kvz is supported by elrha's research for health in humanitarian crises programme, which is funded by the department for international development (uk) , the wellcome trust, and the national institute for health research (uk). sf is supported by the wellcome trust ( /z/ /z, /z/ /z ). pandemic. the health benefits are accrued by the vaccinated children while the excess covid- risk is disaggregated across the different age groups in the household. vaccinated children siblings (< years of age) adults ( - years of age) angola ( - , ) , ( , , ) , ( , , ) key: cord- - e akcjf authors: liu, peilong; guo, yan; qian, xu; tang, shenglan; li, zhihui; chen, lincoln title: china's distinctive engagement in global health date: - - journal: lancet doi: . /s - ( ) -x sha: doc_id: cord_uid: e akcjf china has made rapid progress in four key domains of global health. china's health aid deploys medical teams, constructs facilities, donates drugs and equipment, trains personnel, and supports malaria control mainly in africa and asia. prompted by the severe acute respiratory syndrome (sars) outbreak in , china has prioritised the control of cross-border transmission of infectious diseases and other health-related risks. in governance, china has joined un and related international bodies and has begun to contribute to pooled multilateral funds. china is both a knowledge producer and sharer, offering lessons based on its health accomplishments, traditional chinese medicine, and research and development investment in drug discovery. global health capacity is being developed in medical universities in china, which also train foreign medical students. china's approach to global health is distinctive; different from other countries; and based on its unique history, comparative strength, and policies driven by several governmental ministries. the scope and depth of china's global engagement are likely to grow and reshape the contours of global health. in only three decades, china's global engagement has accelerated from closed autarky to open engagement; from relative isolation to integration into the world system; from a low-income to a middle-income country; and from an aid recipient to an aid donor. as a global demographic and economic giant, china's prominence in global health should not be surprising. with % of the world's population, china weighs heavily in all global health metrics, such as life expectancy, disease burden, and health systems. as the world's largest trading nation, its movement of goods and services is associated with transfer of health technologies, diseases, and risk factors. in health knowledge and strategies, china has a rich history of traditional medicine and has pioneered many health-care innovations. china's ascendency has generated many questions and some concerns. a common assumption is that china uses foreign aid to secure energy and natural resources and to expand export markets. , china's claim of aid with "no strings attached", is considered by some to encourage corruption, weaken accountability, or ignore human rights. the international press has reported delayed and muddled notifi cation of infectious outbreaks, and much news of exported contaminated chinese manufactured products. china is sometimes perceived as working alone and insuffi ciently cooperating with other countries. in this review, we attempt to address the following questions: what is china's role in global health? is china's engagement distinctive or similar to other countries? what does the evidence illuminate of china's global health engagement? china, similar to most countries, has no single offi cial source of data for global health because of the multiplicity of governmental stakeholders, the absence of a national strategy on global health, and the unclear borderline between aid and trade investments. a study by nyu's wagner school has estimated china's foreign aid to africa, latin america, and southeast asia from to . strange and coauthors estimated all previous estimates of chinese development fi nance to africa. the state council of the chinese government, the highest body of state administration, published white papers summ arising china's overall foreign aid in and . none of the above estimations disaggregated or separately reported health aid. , we thus have resorted to an extensive search of data from multiple chinese sources-the state council, the ministries of health, commerce, education, foreign aff airs, and science and technology. reports from provincial governments, chinese embassies abroad, and the press were searched. altogether, we obtained data from sources- from various websites, from statistical yearbooks, from regular reports, and from newspapers. data sourced came from groups of organisations, including sources from the ministry of commerce, from the health ministry (national health and family planning commission), and from ministry of education. the overwhelming proportion of these data sources are in chinese ( %), with less than % in english. all data sources are shown in the appendix. interviews were done with dozens of former offi cials, medical team members, and key provincial authorities to collect fi rst-hand information. not surprisingly, the data quality is mixed, often incomplete, and the fragments need to be matched and fi tted together. the chinese government is essentially the only source of information, without other sources of independent verifi cation. reports of classifi cation and nomenclature often do not follow international standards. a common limitation is the mixing of stock data versus fl ow data. our compiled data, nevertheless, generate what we believe to be the most robust estimation possible. matching and piecing together the fragments allows inconsistencies to be double checked for consistency. most inconsistencies relate to exact numbers, but estimation of the general order of magnitude is believed to be reasonably robust. all data sources for this review are shown in the appendix in both original chinese and translated english. after introducing a framework, we present sections on china's work in health aid, health security, health governance, and knowledge exchange. china's participation in global health has deep historical roots, not only just in recent years. in the fi rst millennium, knowledge of medical cures were transmitted by the silk road that facilitated exchange between china, india, the middle east, and europe. in the th century, some chinese health crises such as the manchurian plague epidemic captured the attention of neighbouring countries of the international community. china has historically been the origin of many infectious epidemics and a source of key health innovations of breakthroughs such as the barefoot doctor (a term that emerged in the s and s, which refers to farmers who received minimal basic medical and paramedical training and worked in rural china to promote basic hygiene, preventive health care, family planning, and treat common illnesses. the name comes from southern farmers, who would often work barefoot in the rice paddies), and artemisinin, an eff ective antimalaria drug developed from plant-based chinese traditional medicine. , because there is no universal consensus for the defi nition of global health, some approaches focus on transnational health risks, which lie beyond the reach of national governments, whereas other approaches stress the global commitment and responsibility to address health inequities and to support health. we have adopted a framework of global health as characterised by health and related transnational fl ows of diseases, people, money, knowledge, technologies, and ethical values. [ ] [ ] [ ] four domains capture these globalisation processes (fi gure ). first, health aid aims to advance global health equity. it is the traditional area of offi cial development assistance (oda) coordinated by organisation for economic cooperation and development (oecd) countries. second, global health security should be ensured by management of interdependence in global health and mutual protection against shared and transferred risks, such as epidemic diseases. third, health governance is needed for global stewardship to set ground rules as mediated by health diplomacy. fourth, knowledge exchange is needed, which includes the sharing of lessons and knowledge production, ownership, and application worldwide. knowledge centrally aff ects all four pillars of global health, and global health governance is recognised to be central to all four domains (fi gure ). on the basis of this framework, china's modern timeline might be demarcated by fi ve landmarks. first, in , china sent its fi rst overseas medical team to algeria, followed years later by the donation of its fi rst hospital in tanzania. the explicitly articulated purpose of china's health aid was to further political solidarity as part of china's foreign policy. second was china's economic openings after , which launched the dramatic transformation of china from a low-income to a middle-income country, leading to china qualifying as an aid recipient followed by increasingly becoming an aid donor. third, starting from , china has hosted a series of forums on china-africa cooperation, with each forum announcing yet another major aid pledge-eg, hospital construction, malaria control, and high education scholarships ( - ); training of health workers and artemisinin drug donation ( - ); and brightness action (eye care) campaign ( - ). , fourth, global engagement greatly accelerated after when china entered the world trade organization (wto), an event that marked china's joining almost all international bodies. finally, and perhaps most dramatically, the severe acute repiratory syndrome (sars) epidemic underscored both china's neglect of its health sector and the reality that china's global trade cannot be done without mutual health protection. in recent years, the state council has published two white papers in april, , and july, , summarising china's foreign aid by volume and type. the white paper reports foreign aid of us$ · billion accumulated up to and including in three categories: grants of $ · billion; concessional loans of $ · billion; and interest-free loans of $ · billion. this amount is fairly close to another estimate of china's foreign aid at $ · billion cumulative from to , reaching $ · billion annually by . , the aid increased signifi cantly during the period of - , reaching an average of $ · billion per year, of which the grants accounted for · %. figure shows that african countries received % of all aid, with asia receiving about a third ( %) and latin america receiving around %, before the end of . the share for african countries increased to · % during the past years, whereas latin america received relatively less. another estimate computed china aid to africa in , at $ · billion in comparison with japan at $ · billion and usa at $ · billion. chinese aid in health is provided in fi ve categories: medical teams, construction of hospitals, donation of drugs and equipment, training of health personnel, and malaria control. the largest share of health aid is spent on medical teams and donated facilities. the fi nancial value of chinese in-kind health aid is diffi cult to estimate. crudely, from to , we estimated the value of chinese medical teams in africa to be about $ million annually, with donated facilities at a similar amount. total health aid to africa annually has been estimated at about $ million. understanding of the type of health support off ered rather than the precise volume of funding might be more important. diff erent from most oecd donors, china does not off er general sectoral support, albeit small cash grants given to several countries in recent years. its health aid uses a project approach. the in-kind provision in the fi ve categories is based on chinese competencies. health seems to constitute only a small proportion of the total chinese aid. health aid is mainly in donation form, whereas most of china's overall foreign aid is off ered as either concessional or interest-free loans. since , under the protocol on the dispatch of medical teams signed between the government of china and the recipient countries, about chinese medical workers have been sent to about countries to provide services to an estimated million people. at the end of , chinese medical workers were working in medical centres in countries. of the countries are in africa, and the remaining seven are mainly small countries-four in asia, one in europe, one in south america, and one in oceania. the table shows african countries in according to medical teams, aided facilities, and malaria control programmes, along with the chinese provinces twinned to each country. figure shows china health aid to africa with countries shaded according to density of medical team coverage and demarcated by aided facilities and malaria control. the distribution shows wide coverage of nearly all african countries with a higher density of medical teams in western and eastern africa regions. the largest and most powerful african countries such as south africa, nigeria, and kenya do not have chinese medical teams. chinese selection of hosting countries is based on country request and the joint decision by china's ministries of health, foreign aff airs, and fi nance. the medical teams are overseen by the chinese embassy economic and commercial counsellor's offi ces. medical teams are fi nanced by the health aid budget in the health ministry (except the basic salaries), which is responsible for dispatching medical teams. selected countries are twinned to specifi c chinese provinces with public hospitals and local medical schools responsible for staffi ng, supervising, and partially funding the medical teams. some practical criteria such as willingness and workload are used to match chinese provinces and recipient countries in the twinning arrangement. the number of members in medical teams ranges from a half dozen people to nearly , usually working out of chinese donated hospitals and clinics. most workers are clinicians, and most teams include a leader and a translator. public health skills are usually not included. medical teams mainly provide clinical services, especially for specialties in short supply-eg, surgery, gynaecology, and obstetrics. the average duration of an overseas assignment is years, with team members receiving housing and food plus enhanced salaries. over the period of - , these medical teams working in countries had provided about million medical consultations and treatments. panel describes some of these medical teams in southern sudan and the democratic republic of the congo. since , china has constructed more than a hundred health facilities overseas with its health aid. china accelerated its assistance in the construction of hospitals and clinics-from to , china has supported about construction projects of health facilities. most of these facilities are donated, and only a few are built as part of large infrastructure projects funded by chinese loans. african countries were the recipients of more than three-quarters of the donated facilities. although most countries have received at least one facility, some have received up to . these facilities are mostly so-called turnkey operations, for which chinese construction fi rms build the facility for transfer to local authorities. malaria control has recently been prioritised. control programmes are undertaken through anti-malaria centres, featuring artemisinin based on chinese traditional medicine. panel describes an ambitious chinese programme of malaria eradication with mass drug administration with artemisinin on the comoros islands. the question of whether health aid is mainly driven by china's commercial interest is not easy to investigate. much depends upon interpretation of underlying motivation. for example, chinese aid to africa might be viewed as either helping the world's poorest countries or building friendship with the origin of much of the world's energy and natural resources and potential export markets. a comprehensive analysis of this question would need access to data not currently available. as a preliminary fi rst step, we attempted to examine correlations between health aid and commercial economic indicators. regression analysis of african countries with variables of health aid (medical teams, donated facilities, malaria control) and economic interests (petroleum imports, china's foreign investment, and china's imports and exports) yielded no signifi cant pattern. figure shows four scatter-plots of china health aid and african trade. in the four diagrams, individual african countries are plotted according to health and commercial indicators. the scatter-plots did not show any association between medical aid and economic interests. spearman's rank correlation and t test analysis for the period of - showed no signifi cant fi ndings of correlations. these preliminary analyses should not be interpreted as conclusive. a core component of global health is mutual health protection against international transfer of health risks, which shows health interdependence. transborder movement of infectious diseases, contaminated goods and products, air pollution, and globally pooled co are prime examples. for china, the sars epidemic was a crisis with serious economic and political consequences. both disease control and international cooperation were delayed. chinese errors made in the early stage of sars have been acknowledged and have generated strong corrective measures, both domestically and internationally. domestic measures include major re-investment in the public health system via the chinese center for disease control and prevention (cdc), including development of the world's largest real-time electronic surveillance system. international eff orts include active participation and leadership in many international forums that foster cooperation in compliance of disease reporting and control, as shown by the initiation of the un resolution on enhancement of capacity-building in global public health in , and the joint international pledging conference on avian and human pandemic infl uenza with china, the european commission, and the world bank held in beijing in . [ ] [ ] [ ] subsequent management of infectious outbreaks such as avian infl uenza a h n virus shows that china recognises the importance of strict adherence to the international health regulations. in the sars outbreak, china needed days between fi rst case detection and report to who and another days for joint teams to investigate the outbreak. for h n one decade later, less than half the days lapsed between fi rst case and report to who and the initiation of joint investigations. [ ] [ ] [ ] infections can move in several directions. china has been the destination of cross-border infectious transmissions. in , a polio epidemic was imported from pakistan into china's xinjiang province. after making arduous eff orts and expending large resources. similarly, china has been threatened by the import of dengue fever, malaria, and several other transmissible diseases. , cross-border risks can also accompany the import and export of commodities. as the world's largest exporter of manufactured products, china, of course, transfers health risk overseas. news reports have been plentiful of contamination in chinese exports of toothpaste, lead paint, milk products, and heparin. [ ] [ ] [ ] [ ] these safety concerns are not limited to exporters. china has also been a destination in the dumping of contaminated chemicals from richer to poorer countries; these safety hazards are of equal concern to the chinese public. these concerns might be why china has upgraded its state food and drug administration (sfda) to the status of a ministry with larger budget, increased staff , and stronger regulatory powers. environmental pollution also moves across national boundaries. air pollutants in china have been cited as causing acid rain damage to forests in korea and japan. , china is today the world's largest emitter of carbon dioxide, contributing substantially to global climate change. to tackle air pollution, china's state council released an action plan setting a -year road map for air pollution control. its implementation deserves tracking for monitoring and evaluation of control eff ect. health governance sets ground rules for global stewardship of diverse activities. across the board, china has become an active member of the world system, opening with china's economic reform and accelerating after its entry into the wto in every aspect-eg, political (un), fi nancial (world bank, international monetary fund), economic (wto), and military (arm control and data underscore the participation of china in global governance. china's receipt of net offi cial development assistance and offi cial aid peaked at about $ million in , had steadily decreased to a third of that amount by , and is already disappearing as china increasingly becomes an aid donor rather than an aid recipient. from to , china's receipt and contribution to who were equal at about $ million. by - , china's assessed contribution to who had increased to $ million, while who funding to china had remained at baseline. in parallel with this increase in funding, the number of chinese staff members in who has expanded. whereas in , there were only chinese offi cials working in who, that number had tripled to by , although chinese staff in who are still under-represented. additionally, based on the newly released white paper, china allocated $ million to support the global fund and other international organisations in - . global health participation by china has been mainly governmental. in non-governmental stakeholders, growth in the international participation of some academic universities, business, and industry has occurred. china has very few non-governmental organisations (ngos) and thus the chinese are mostly absent from global civil society forums. a few international ngos work in china, but few have achieved offi cial registration from the chinese government. it will take substantial time, if ever, before china's civil society becomes active in global health. knowledge is both local and global, and its production, ownership, exchange, and application have global dimensions. china has much to share with and much to learn from the rest of the world. in medicine, strategy, and implementation, china has had some spectacular accomplishments, worthy contributions to the world's knowledge pool. chinese traditional medicine off ers many health-enhancing technologies-ranging from ephedrine to acu puncture. [ ] [ ] [ ] in the s, village health workers were fi eld tested, and later re-engineered as the barefoot doctor. china's three-tier rural health system was established soon after the founding of the people's republic. the alma ata movement for primary health care took great encouragement from china in showing what barefoot doctors could do at the community level. the three decades after the founding of the people's republic in witnessed some of the steepest advances of mortality control in human history. china's management of common infectious diseases, maternal-child health, tropical disease control, malaria and schistosomiasis containment, mass social hygiene campaigns, and recent achievement of near-universal health coverage are worthy of documentation as valuable lessons. physicians, two nurses, two chefs, two translators, and one medical engineer from shaanxi province constituted china's th medical team to sudan in - . the th chinese team from hebei province to the democratic republic of the congo arrived in , consisting of a team leader, physicians (including one in chinese traditional medicine), two nurses, one french translator, and one chef. for both teams, their primary role was to provide clinical care to patients. an ancillary function was to mentor, train, and improve the skill of local health workers. medical teams were self-suffi cient, bringing all their own supplies, equipment, and medicines. in response to questionnaires, team members commented positively on their experiences. higher salaries, fi nancial subsidies, and allowances from both central government and employers (about a six-fold increase) operated as important incentives. reported constraints included language barriers, unaccustomed disease profi les, poor facilities and equipment, unstable water and electricity supply, and homesickness. if the opportunity were off ered, nearly all would be willing to serve again. , panel : traditional chinese medicine to eradicate malaria? malaria eradication in some countries had been successful with dichlorodiphenyltrichloroethane, and hopes have focused on new vaccines. but a professor of chinese traditional medicine from guangzhou university of chinese medicine is leading an unprecedented eff ort to eradicate malaria on the comoros islands with traditional chinese medicine. starting in on moheli island where % of the residents were carriers of plasmodium falciparum, disease prevalence has dropped to · % in months with mass administration of artemisinin and piperaquine, donated by china's ministry of commerce. years later, the chinese team extended this programme to anjouan, an island of , reducing the prevalence of p falciparum carriers from % to · %. last year, the eff orts were expanded to the residents of grande comore, the country's largest island. the project goal is malaria eradication in the people of the comoros by . panel describes an innovative grant by uk government's department for international develop ment (dfid) to foster research by, and capacity building for chinese universities and other institutions to disseminate and share chinese lessons with other countries. for the future, china aspires to be a worldwide knowledge leader and it has fast growing research and development investments in biomedicine. chakma reported china's biomedical research and development at $ · billion in , in comparison with usa ($ billion), europe ($ billion), and japan ($ billion). the absolute size of these fi gures might undervalue chinese investments because the lower salaries, cost of infrastructure, and cost of operations in china might not be captured fully by purchasing power parity-adjusted values. strikingly, china's investments since have increased annually at % in comparison, for example, to − % for the usa. china, moreover, houses laboratories for most of the major pharmaceutical companies. it has advanced genetic research capacity as shown by its genetic sequencing of the h n virus within days of isolation and identifi cation. china is also a growing producer and exporter of generic products. china aspires to be a powerhouse in the discovery and production of new drugs and vaccines in global health. china's medical universities are increasingly undertaking research and education in global health. in the past year, several new multidisciplinary centres of china supports government offi cials, technical professionals, and young people from developing countries to participate in training and education programmes in china. in - , the government provided scholarships for such programmes, of which many were health related. china's medical universities also train foreign medical students. according to the data from the china education yearbook, in - , china trained foreign medical students, who constitute % of all foreign students in . for that year, the ministry of education reported almost foreign medical students studying modern medicine and studying traditional chinese medicine. , by , china had extended authorisation to medical schools to admit foreign students who will study medicine in english. figure shows the rapid increase of foreign medical students and scholarships in china in - . although foreign interest in traditional medicine is high, most foreign students register for modern medicine. about % of the foreign medical students receive chinese government scholarships that might be regarded as part of china's foreign health aid. chinese medical schools charge foreign students higher than chinese tuition fees, and the schools acknowledge foreign students as a source of school revenue. in , many of the students came from neighbouring asian countries, such as india, japan, pakistan, south korea, and southeast asia. our most salient fi nding is china's distinctive mode of engagement in global health. china's health aid volume is small, but the mode is distinctive, driven by china's health capabilities and national experiences. unlike many other traditional donors, china's in-kind aid focuses more on some important aspects of the health system. china's overall global engagement follows a very diff erent path from developed countries partly because it has no colonial experience nor did it participate in shaping the american-led post-world war world order. china was inward-looking until it expanded into the global economy in . over the ensuing three decades, china has had large shifts from a low-income to a middle-income country, and from aid recipient increasingly to aid donor. the spread of its foreign aid throughout the breadth of africa presumably refl ects both eff orts to solidify friendship politically, promote mutually benefi cial economic gains, and compete with taiwan for political friendship. china's health aid is embedded in the dynamic shifting of foreign and economic policies. the opening in marked a shift from economic development serving foreign policy to foreign policy serving economic development because china's association, for example, with africa, has developed from a political one in the s to a broader economic-based and trade-based engagement. , these are all defi ning characteristics of china's engagement in global health. china's global health work, unfortunately, does not seem to rank highly in government agencies. health has been assigned a lower position than political and commercial aff airs. taking advantage of both domestic and international resources and accessing both domestic and international markets is china's explicit national development strategy. these powerful economic motives drive much of china's global engagement, including its engagement in africa, to the point where the dividing line between trade and aid become blurred and hard to demarcate. health aid is only a very small adjunct to these much larger and more powerful forces. china's overseas forces include several government agencies. as a result, improved interministerial coordination is a necessary development for the evolution of a coherent overall engagement in global health. formulation of a china global health strategy could help bring coherent policy and harmonised action, because it would compel the articulation of specifi c health and humanitarian objectives in chinese governmental policies. an explicit china global health strategy would provide a stronger context for ngos and private sector overseas participation. china's bilateral approach diff ers substantially from its multilateral approach. although china's bilateralism takes an independent approach, china's multilateral strategy is full participation, joining as a regular member and complying with its responsibilities and privileges in un bodies such as who. the records show that china respects and complies with rules governing multilateral institutions in all aff airs-health, trade, migration, environment, and other aspects of global governance. china has increased its contribution to multilateral funding pools, such as the global fund from $ million per year in , to $ million per year in . how important china will become as a major donor to these pooled funds is uncertain. some see the early actions as symbolic gestures of cofunding, whereas others hope that the size of the chinese economy will propel it to become a fi nancial leader of multilateral funds. the new development bank being established by brics countries aims to compete with the world bank and international monetary fund, which is one example of how china has debatably played a leadership role. most important is the avoidance of over-simplifi cation. no country's international engagement is free from political or economic motives-eg, europe colonialism, us millennium development accounts, or sweden-vietnam partnership during the american war. and no single modality of foreign aid has proven to be more eff ective or more sustainable. , although china's health aid is generally appreciated by recipient offi cial statements, there are indeed complaints about the scale of china's intrusion, access to natural resources, and the trade market in africa. but energy resource-based trade structure with africa does not occur only in china; it occurs with all major african trading partners. the most fundamental improvement is to increase the capacity for independent development, to which all partners in africa should contribute. china's global health engagement is diffi cult to attribute to one motivation factor. chinese driving forces are undoubtedly several and complex-political, economic, social, and humanitarian. china's approach has been characterised as pragmatic that "combines the utilitarian logic of reaping material benefi t, the realist objective of expanding its global power and infl uence, the neo-liberalist interest in pursuing absolute gains from international cooperation, and the constructivist attempt to become a responsible stakeholder in the system". china's global health engagement will probably grow substantially with expanding budgets, more projects, and more staff sent abroad. china will pursue its own distinctive approach, not copying the developed world model; chinese government policy and indigenous professional capacity will be key. the fi rst generation of chinese professionals with experience and foreign language fl uency is emerging along with stronger global health institutions. given this trajectory, one should assume global health will likely be re-shaped by china's participation, with its structures and processes increasingly accommodating chinese characteristics. pl led and coordinated the authors' group. all authors participated in study design, data collection, analysis, interpretation, and paper writing and editing. lc and zl produced the fi rst draft. we declare no competing interests. emory global health institute. case study: can global sanitation contribute to china's prosperity? atlanta, e-mory global health institute china's global hunt for energy council on 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sars a watershed? shifting paradigm: how the brics are reshaping global health and development chinese development aid in africa: what, where, why, and how much? china to strengthen cooperation with africa on health key players in global health: how brazil, russia, india, china, and south africa are infl uencing the game characteristics of china-africa health collaboration: the case of democratic republic of congo the experience of chinese physicians in the national health diplomacy programme deployed to sudan fighting malaria china engages global health governance: processes and dilemmas china information system for disease control and prevention (cisdcp) permanent mission of the people's republic of china to the un. statement by chinese permanent representative wang guangya at the th session of the un introducing a draft resolution entitled "enhancing capacity building in global public health who. international pledging conference on avian and human pandemic infl uenza china's health diplomacy: sharing experience and expertise infl uenza a virus subtype h n joint mission on human infection with avian infl uenza a (h n ) virus timeline: sars virus controlling the polio outbreak in china xinjiang remains polio-free china tightens quarantine for malaria, dengue china regions on alert for malaria, dengue fever elements of a sustainable trade strategy for china made in china melamine in milk products in china: examining the factors that led to deliberate use of the contaminant contaminated heparin seized by fda toxic exports: the transfer of hazardous wastes from rich to poor countries china upgrades drug safety agency-people's congress: move aims to raise quality of food and drug supply trend of acid rain and neutralization by yellow sand in east asia-a numerical study air pollution from china reaches japan, other parts of asia world carbon dioxide emissions data by country: china speeds ahead of the rest ministry of environmental protection, the people's republic of china. the state council issues action plan on prevention and control of air pollution introducing ten measures to improve air quality data: net offi cial development assistance and offi cial aid received (current us$) who. financial and auditing reports from world health assembly, from wha to wha who. human resources: annual report chinese materia medica: chemistry, pharmacology and applications chinese acupuncture and moxibustion asian medicine. the new face of traditional chinese medicine health service delivery in china: a literature review mortality in china global health support programme supports shared international development objectives uk global health support programme (ghsp) asia's ascent-global trends in biomedical r&d expenditures duke kunshan university, and the leading chinese universities launch new global health consortium liberal education meets chinese tradition china consortium of universities for global health established in beijing ministry of education of people's republic of china. china education yearbook . beijing: people's education press ministry of education of people's republic of china. brief statistics of international students in china new list of chinese medical institutions admitting international students for academic year ministry of education of people's republic of china. interim provisions to control the quality of foreign students' undergraduate education (english class) in china beyond borders: potential gaps in the international system of public health surveillance china: foreign policy serves domestic development china's priorities in africa: enhancing engagements collection of important documents since third plenary session emerging economics to launch development five metaphors about global-health policy development assistance for health: critiques and proposals for change the great escape: health, wealth, and the origins of inequality china and global health governance we thank haomin yang, yang li, and jing bai for their work on data collection, data analysis, and research assistance. key: cord- -iu e jo authors: taboe, hémaho b.; salako, kolawolé v.; tison, james m.; ngonghala, calistus n.; kakaï, romain glèlè title: predicting covid- spread in the face of control measures in west-africa date: - - journal: math biosci doi: . /j.mbs. . sha: doc_id: cord_uid: iu e jo the novel coronavirus (covid- ) pandemic is causing devastating demographic, social, and economic damage globally. understanding current patterns of the pandemic spread and forecasting its long-term trajectory is essential in guiding policies aimed at curtailing the pandemic. this is particularly important in regions with weak economies and fragile health care systems such as west-africa. we formulate and use a deterministic compartmental model to (i) assess the current patterns of covid- spread in west-africa, (ii) evaluate the impact of currently implemented control measures, and (iii) predict the future course of the pandemic with and without currently implemented and additional control measures in west-africa. an analytical expression for the threshold level of control measures (involving a reduction in the effective contact rate) required to curtail the pandemic is computed. considering currently applied health control measures, numerical simulations of the model using baseline parameter values estimated from west-african covid- data project a % reduction in the daily number of cases when the epidemic attains its peak. more reduction in the number of cases will be achieved if additional public health control measures that result in a reduction in the effective contact rate are implemented. we found out that disease elimination is difficult when more asymptomatic individuals contribute in transmission or are not identified and isolated in a timely manner. however, maintaining a baseline level of asymptomatic isolation and a low transmission rate will lead to a significant reduction in the number of daily cases when the pandemic peaks. for example, at the baseline level of asymptomatic isolation, at least a % reduction in the transmission rate is required for disease elimination. additionally, disease elimination is possible if asymptomatic individuals are identified and isolated within days (after the incubation period). combining two or more measures is better for disease control, e.g., if asymptomatic cases are contact traced or identified and isolated in less than days, only about % reduction in the disease transmission rate is required for disease elimination. furthermore, we showed that the currently implemented measures triggered a % reduction in the time-dependent effective reproduction number between february and june , . we conclude that curtailing the covid- pandemic burden significantly in west-africa requires more control measures than those that have already been implemented, as well as more mass testing and contact tracing in order to identify and isolate asymptomatic individuals early. a new strain of coronavirus (sars-cov- ), that emerged from wuhan, china is the cause of the covid- pandemic that is currently ravaging the world [ - ] . as of june , , about , , confirmed cases of covid- infections and , deaths were reported worldwide [ ] [ ] [ ] [ ] . most of these reported covid- cases (approximately , , ) and deaths (approximately , deaths) were from the united states of america. the epicenter of the pandemic is expected to shift to sub-saharan africa, which as of june , had reported about , confirmed cases and , deaths. of these, about , confirmed cases and , deaths were from west-africa. the first confirmed west-african case was in nigeria on february , , i.e., approximately two months after the first case was officially announced in china [ ] . the highest burden of the disease in west-africa by june , was in nigeria (about , cases and deaths) [ ] . this is in line with a multilayered-risk assessment (based on nine risk factors) in [ ] that identified nigeria as the west-african country with the highest covid- risk. another study by martinez-alvarez et al. [ ] projected that some west-african countries, e.g., burkina faso and senegal might experience sharp increases in the number of covid- cases that are similar to those observed in european countries in march and april, . humans can acquire the novel coronavirus when they come into contact with contaminated surfaces or from droplets released by infectious symptomatic and asymptomatic individuals [ ] . mild to moderate infection symptoms of the disease include fever, cough, sore throat, nasal congestion, malaise, headache, muscle pain, and shortness of breath (or tachypnea in children). in severe cases, fever is associated with severe dyspnea, respiratory distress, and tachypnea [ ] . currently, there is no vaccine or widely accepted drug for covid- . therefore, governments and individuals are forced to rely on public health preventive measures such as basic hygiene, travel or movement restrictions, social-distancing, wearing masks, etc. current control measures being implemented in west-africa include regular hand washing with hydroalkolic solutions, quarantine of suspected cases, isolation of confirmed cases, social distancing (e.g., travel restrictions, school closures, and banning of gatherings involving more than people), contact tracing, and testing and treating identified cases. additionally, wearing of masks in public was recently recommended as another control measure in many countries in this region. unfortunately, it is difficult to implement these basic public health measures effectively in some west-african countries due to wide-spread poverty and poor investment in health care (staff, equipment, and infrastructure) [ ] . for example, in thirteen of the sixteen west-african countries, less than two medical doctors are allocated to every group of , inhabitants [ , ] . in particular, only nigeria, cote d'ivoire, and cape verde have or more medical doctors per , inhabitants [ ] . another possible explanation for this low doctor to population ratio is alternative medicine (especially traditional medicine) that is widely practiced in the west african region. the world health organization estimates that about % of the population of west-times below the average per capita health spending in countries like italy and spain-two european countries that experienced high covid- burden [ ] . as a result of poor investment in health care and health care systems, the region has been an epidemic hotspot for emerging and neglected tropical diseases including the ebola virus (ebov), lassa virus (lasv), and buruli ulcers in recent years [ , ] . with such inadequate healthcare systems and personnel in the region, the impact of covid- might be catastrophic. to compound matters, some countries in west-africa are still not well prepared to tackle this pandemic despite the observed devastating impacts and trend of the pandemic in the us, europe, and asia [ ] . there is, therefore, the need to exploit every existing tool and/or develop new tools that can be useful in guiding public health decision-making in the fight against the pandemic. this includes developing and using new qualitative and quantitative methods such as mathematical models. there has been an influx of mathematical models to assess the impact of covid- and to guide public health response in different cities, countries and regions of the world (see, for example, [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] ). few of these mathematical model frameworks have focused on the covid- pandemic situation in west-africa as a whole. among these few models, some have focused only on one or two countries, e.g. nigeria and ghana, while others have used basic regression or exponential growth models to analyze and predict disease trends [ , ] . martinez-alvarez et al. [ ] used a simple graph-plot based comparative analysis of observed covid- data for the first days of the pandemic to examine the future trajectory of the epidemic in six west-african countries (burkina faso, senegal, nigeria, côte d'ivoire, ghana, and the gambia). this far, only one study has considered the entire region of west-africa [ ] . in this study, a co-variate-based instrumental variable regression framework was used to predict the number of disease cases ( . million by june , ) and to assess the epidemiological, socio-economic and health system readiness of the region to the pandemic. in this study, we develop a new susceptible-exposed-infectious-recovered (seir)-type mathematical model for covid- in west-africa and use it to (i) study the current transmission pattern of covid- , (ii) evaluate the impact of currently implemented public health control measures such contact tracing, social distancing and use of face masks on covid- transmission, and (iii) predict the future course of the pandemic with and without currently implemented and additional control measures in west-africa. in addition to incorporating various basic public health control measures, our model accounts for asymptomatic infectious individuals -a class of individuals that render disease control more difficult since they do not exhibit clinical disease symptoms, although they contribute to disease transmission [ ] . to our knowledge, this is the first study that has used an explicit seir-type compartmental model together with data for the west-african pandemic period (from february , to june , ) to study the spread of the covid- pandemic in the region, assess the impact of current control measures, and discuss further control measures that might be required to better control the pandemic in the region. that lead to a reduction in the force of infection λ, such as social distancing and face mask use. following the approach in ngonghala et al. [ ] , we model the force of infection by the functional form ( − Ψ)(β a i a + β s i s )/(s + e + i a + i s + r), where β k (k ∈ {a, s}) is the disease transmission rate by individuals in the i k class and ≤ Ψ ≤ is the percentage reduction in disease transmission due to public health control measures such as social distancing and face masks use. note that Ψ = implies that no public health control measure leading to a reduction in disease transmission is applied and that Ψ = implies that implemented public health control measures are efficient enough to stop disease transmission. after the average incubation period /σ, a proportion π of the exposed population does not develop symptoms, i.e., joins the i a compartment, while the remaining proportion ( − π) join the i s class. identification and isolation of infectious asymptomatic individuals, e.g., through contact tracing occurs at rate ρ a , i.e., /ρ a is the average time it takes for an infectious asymptomatic individual to be identified and isolated. isolation or hospitalization of symptomatic cases occurs at rate ρ s , i.e., /ρ s is the average time it takes for an infectious symptomatic individual to be isolated. humans from the i a , i s , and i c classes recover at rates γ a , γ s , and γ c , respectively, while individuals in the i s and i c classes die due to covid- at respective rates δ s and δ c . the flow diagram for the model is given in fig. . fig. : flow-chart of covid- model showing the flow of humans between different compartments. the susceptible population is denoted by s, the exposed population is denoted by e, the infectious asymptomatic population is denoted by ia, the infectious symptomatic population is denoted by is, the isolated infectious population is denoted by ic, and the recovered population is denoted by r. the parameters of the model are described in the text. using the flow-chart and the preceding description, we obtain the following model system: where p is the actively mixing population, i.e., p = n − i c = s + e + i a + i s + r. since individuals in the i c class are in some form of confinement or isolation, we assume that they are not part of the actively mixing population and so they do not contribute in disease transmission. we denote the initial conditions of the model ( . ) by s( ) = s > , e( ) = e , i a ( ) = i a , i s ( ) = i s , i c ( ) = i c , r( ) = r , where for the pandemic to take off, at least one of the infected populations must be greater zero. west-africa comprises sixteen countries: benin, burkina-faso, cape verde, ghana, guinea, ivory coast, mali, mauritania, niger, nigeria, senegal, togo, sierra leone, liberia, guinea-bissau and gambia. based on the latest united nations estimates, the current population of west-africa is , , , i.e., about . % of the world population [ ] . the region includes nine of the poorest countries in the world [ ] . application of basic public health control measures against covid- spread in most west-african countries started on march , , i.e., about days after the outbreak in the region. the data considered for this analysis spans the period from february , , i.e., one day after the first case until june , . in west-africa, the reported confirmed cases are infectious symptomatic individuals who have been tested at a treatment center or infectious asymptomatic individuals who have been detected through contact-tracing or systematic testing on target groups and then tested at a treatment centre. hence, we assume that confirmed disease cases correspond to individuals isolated infectious individuals in isolation or at treatment centers (i c ). we use the cumulative number of cases in west-africa, downloaded from the global rise of education website [ ] to fit our model and estimate some of the key parameters presented in table . the fitting that was carried out using a nonlinear least squares method in matlab version (r a) involved finding the best set of parameter values that minimizes the root mean square differences between the observed cumulative covid- confirmed cases in west-africa and the predicted cumulative covid- cases from our model . . the minimization was achieved through the built-in constraint minimization algorithm "fmincon" in matlab. we repeated this procedure , times for each of the parameters and used the normal distribution to compute the mean values of the parameters together with a % confidence interval (ci). the goodness of fit of our model assessed using the root mean squared error (rmse) was . . the fitted and known parameter values are presented in table and the model fit is illustrated in fig. (a). it is worth noting that the choice of parameters to estimate from the data or to extract from the literature was motivated by its importance to the transmission dynamics of the disease. a plot of the observed confirmed daily cases and the predicted daily cases from system ( . ) using the fitted and known parameters is presented in fig. table . . in this section, we derive the basic reproduction number of the model, which is defined as the average number of new infections generated by a typical infectious individual introduced in a population where everybody is susceptible [ ] . it is denoted by r and provides a condition under which a disease can invade a population (when r > ), or can be contained (when r < ). using the next generation matrix approach in [ , ] , the basic reproduction number is: observe from eq. . that the reproduction number r , is the sum of two components, which represent the contribution of the infectious asymptomatic class r a and the infectious symptomatic class r s . for system ( . ) that already include some control efforts, the control reproduction number r c , is given by r c = ( − Ψ)r . the approach in [ , ] also assures us that the continuum of disease-free equilibrium (s , e , i a , i s , i c , r ) = (s( ), , , , , ) of system ( . ) is locally and asymptotically stable whenever the reproduction number r c is less than one. another useful quantity tht is associated with the reproduction number is the time-dependent effective reproduction number, which for model ( . ) is given by r e = r s/(s + e + i a + i s + r). it is worth mentioning that the epidemic grows when the effective reproduction number is greater than unity, peaks when the effective reproduction number equals unity and declines when the effective j o u r n a l p r e -p r o o f journal pre-proof reproduction number is below unity. to derive the threshold reduction in the disease transmission Ψ c , required to reduce the control reproduction number to one, we set r c = , i.e., ( − Ψ)r = in eq. . and solve for Ψ. this yields: note that the fraction in the right hand side of the threshold value Ψ c of Ψ is greater than zero and less than or equal to one since ≤ Ψ ≤ . note also that Ψ = Ψ c , which corresponds to the case in which r c = now serves as a threshold for an outbreak or the disease dying out. in particular, disease elimination is the epidemiological implication of this is that massive adherence to control measures that reduce covid- transmission, e.g., social distancing can lead to disease elimination, while low adherence to such measures will reduce disease burden, but might not lead to elimination. to compute the final size relation, we follow the method in [ ] . in addition to the final size relation calculation, this approach provides an alternative method for calculating the basic reproduction number of the model ( . ). to apply the method, we first identify the vector x of covid- infections, i.e., x = (e, i a , i s , i c ) ∈ r + . then, we identify the vectors y and z of the susceptible and recovered classes, respectively, i.e., y = s ∈ r + and z = r ∈ r + . with this notation, the system ( . ) can now be expressed in the compact form: by theorem . of [ ] , the basic reproduction number is [ ] , the basic reproduction number is given by this final size relation can be used to approximate the number of individuals who remain uninfected, and consequently the number of individuals who were infected during the pandemic. in this section, we use the parameters presented in table to simulate system ( . ) and to investigate the impact of control measures on key model outputs such as the control and effective reproduction numbers r c and r e , respectively. the basic reproduction number r , and the control reproduction number r c computed using this baseline parameter regime in table are to an approximately % reduction in the basic reproduction number due to implemented control measures. this calls for more effective control measures to limit the spread of the disease. all simulations were carried out using the computational software matlab (version r a). when it was necessary solve the system of ordinary differential equations ( . ) we used the inbuilt matlab function "ode ". the first analysis involves evaluating the impact of the percentage reduction in the effective contact rates due to the implementation of public health control measures such as lockdowns, social distancing, the use of masks in public, washing of hands, etc., denoted by Ψ on the control and effective reproduction numbers, as well as the pandemic peak and the time to peak. here, we fixed all the parameters at the baseline values provided in table and varied only the parameter Ψ. changes in the control reproduction number as a function of Ψ, depicted in fig. show that about % reduction in the disease transmission is required to reduce r c to one and possibly bring the pandemic under control. this value ( %) corresponds to the numerical value of Ψ c from eq. ( . ) computed using the baseline parameter values from table and a % increase from the baseline value of Ψ. furthermore, our results show that there will be a % reduction in the effective reproduction number by july , if no control measures are applied and a % reduction by the same date if there is a % reduction in disease transmission, i.e., an additional reduction of % in Ψ (fig. (b) ). we also simulated the system ( . ) to explore the impact of public health control measures on the timing and size of the pandemic peak in west-africa (fig. (c) . the results of our simulations show that in the absence of any control measure that results in a reduction in the effective transmission rates, i.e., if Ψ = , the covid- pandemic in west-africa will peak by july , with about , people infected on the day of the peak (red curve in fig. (c) ). it is worth noting that this is the worst case scenario. applying control measures at the baseline level, i.e., Ψ = % will bring about a % reduction in the number of cases (from , in the worst case scenario to , at the baseline control measures) when the pandemic j o u r n a l p r e -p r o o f journal pre-proof peaks and also delay the peak to october , (blue curve in fig. (c) ). improved control measures resulting in % and % reduction in disease transmission, will lead to reductions of % and %, respectively, in the number of daily confirmed cases when the epidemic attains its peak (black and magenta curves in fig. (c) ). thus, improved control measures that are related to reducing disease transmission have a significant effect in reducing the number of cases and flattening the epidemic curve-an outcome that will prevent the already weak and fragile health care systems in west-africa from being overwhelmed by a high covid- burden. table . other basic public health control measures include isolating symptomatic infectious humans and contact tracing and isolating asymptomatic humans. in our model we assume that isolating symptomatic infectious humans is at rate ρ s and contact tracing and systematic testing and isolating asymptomatic infectious humans is at rate ρ a . heat maps were plotted to investigate the individual and combined effects of pairs of control measures such as contact tracing, isolation, and using control measures that lead to a reduction in disease transmission, e.g., lockdowns, social and physical distancing, mask use, etc., on covid- in west-africa (fig. ) . our analyses show that the spread of the disease decreases with a higher reduction in the disease transmission rate and a decreasing proportion of exposed humans who do not develop clinical disease symptoms (i.e., become asymptomatic) after the incubation period, π ( fig. (a) ). thus, if a higher proportion of exposed humans do not develop clinical disease symptoms after the incubation period, a higher reduction in the disease transmission rate will be required to eliminate the disease. in particular, if half of the exposed individuals develop symptoms at the end of the incubation period, i.e., π = %, then only a % reduction in the disease transmission rate is required to eliminate the disease. but, if % of the exposed become asymptomatic after the incubation period, then a % reduction in the disease transmission rate is required to eliminate the disease (fig. (a) ). the combined impact of detection and isolation of asymptomatic humans (by contact tracing or mass testing) together with a reduction in the disease transmission rate is explored in fig. (b) . if journal pre-proof asymptomatic individuals are detected and isolated fast enough, e.g., within days, i.e., ρ a = . , then a % reduction in the disease transmission rate would suffice for elimination, while if it takes a long time to detect and isolate asymptomatic individuals, e.g., within days, a % reduction on the disease transmission rate is required to contain the pandemic in west-africa ( fig. (b) ). in particular, we found out that disease elimination is possible even if detection and isolation of asymptomatic humans is not complemented with any additional measure (maintaining Ψ = %). but such identification and isolation must occur in a timely manner, e.g., within days, i.e., ρ a = . (fig. (b) ). if only % of humans fail to develop symptoms at the end of the incubation period, then asymptomatic humans must be identified and isolated within days for disease elimination to be possible (fig. (e) ). thus, disease control is more difficult if it takes long to contact trace and isolate asymptomatic humans. our results also show that timely isolation of symptomatic cases is important in reducing the disease burden in west-africa but not enough as asymptomatic isolation do, although disease elimination is only possible if isolation of infectious symptomatic cases is complemented with another control measure (fig. (c) , (d)). in particular, if symptomatic humans are identified and isolated within days, i.e., ρ s = . , then a % reduction in the disease transmission rate is required for disease elimination, while if it takes a long time to isolate symptomatic infectious individuals, e.g., within days (i.e.,ρ s = . ), a % reduction on the disease transmission rate is required to contain the pandemic in west-africa (fig. (c) ). when isolation of symptomatic infectious disease cases is complemented with identification and isolation of asymptomatic infectious cases, disease elimination is only possible through timely identification and isolation of asymptomatic cases (fig. (d) ). thus, identifying and isolating asymptomatic individuals in a timely manner contributes more in curtailing the pandemic in west-africa than isolating symptomatic infectious individuals. furthermore, if more exposed humans develop disease symptoms at the end of the incubation period and more symptomatic infectious individuals are identified and isolated in a timely manner, disease elimination is possible (fig. (f) ). in particular, if % of exposed humans develop clinical disease symptoms at the end of the incubation period (i.e. π = %, then symptomatic infectious humans must be isolated within days in order to eliminate the disease. table . discussion mathematical models have been useful in understanding disease-outbreaks and in informing policy aimed at curtailing such diseases in a timely manner [ - , , , ] . in the context of the covid- pandemic that is currently spreading around the world, mathematical models have been very useful in predicting the course of the disease and in assessing the impacts of basic public health control measures [ - , , ] . in this study, we developed a mathematical model to inform the covid- trend and possible course of control measures in west-africa. the model is trained with covid- data from west-african countries for the period from february , to june , , and used to compute the reproduction number, as well as to assess the impact of basic public health control measures on the disease in the region. we obtained a basic reproduction number of r = [ ] . hence, although the disease is still spreading (r c > ) in west-africa, the spread is slow compared to other parts of world. this low transmission in the region can be attributed to the fact that there is limited movement of individuals within the region and between the region and the rest j o u r n a l p r e -p r o o f journal pre-proof of the world [ ] . furthermore, the low number of confirmed cases in west-africa might result from under-reporting of cases as was the case in peru [ ] . this is supported by the growing number of asymptomatic infectious individuals observed in our study. de leon et al. [ ] observed a similar trend in mexico, where over % of the infectious population was asymptomatic [ ] . in the absence of sufficient test kits in many west-african countries, and with the limitations in health care facilities and personnel, identifying cases is difficult [ ] . irrespective of the current trend, the covid- pandemic is still a more serious health problem in west-africa compared to previous outbreaks like the ebola outbreak ( . ≤ r c ≤ . ) [ , ] or the lassa fever outbreak in nigeria ( . ≤ r c ≤ . ) [ ] . although most countries in west-africa started implementing basic control measures since march , , our simulation results indicate that improvements are necessary to control the pandemic effectively in the region. because there is currently no safe and effective vaccine or drugs against the novel coronavirus, basic public health control measures have been used to curtail the pandemic in many parts of the world including west-africa. these measures include contact tracing, isolation, and measures that lead to a reduction in disease transmission, e.g., lockdowns, social or physical distancing, mask use, etc [ ] . in the absence of such measures, the worst case scenario prediction for west-africa from our model would have recorded around , confirmed covid- cases by july , when the epidemic peaks. this projection is lower than the , - , , confirmed cases predicted by achoki et al. [ ] for the same west-african region. the higher value in [ ] might be linked to the fact that the authors used linear models and considered the rate of infection between the first and second weeks of the epidemic in countries in which the number of cases might have been overestimated. however such prediction was not true since the control measures implemented in many west african countries back in march reduced the disease transmission. in fact, we found out that basic public health control measures, especially those associated with a reduction in the disease transmission rate such as lockdowns, social distancing, and mask use have a significant effect on reducing the burden of the disease, e.g, at baseline values, control measures reduce the number of cases when the epidemic peaks in october , by about %. also, improving control measures so that an estimated % reduction in the disease transmission is attained, will reduce the number of confirmed cases when the epidemic attains its peak by approximately % and shift the peak date to november , . such interventions are useful in reducing the disease spread and ensuring that the already limited and fragile health care systems are not overwhelmed by the covid- burden [ ] . studies have shown that asymptomatic, i.e., pre-symptomatic and asymptomatic infectious individuals and symptomatic individuals contribute in covid- transmission. asymptomatic cases might contribute more in disease spread since they are not even aware of the fact that they are infected with covid- . for example, on the diamond princess, % of all infections were due to asymptomatic individuals [ ] . similarly, the proportion of pre-symptomatic transmission varied between % and % in a study in singapore and in tianjin (china) [ ] . although, we do not have any documented information on covid- spread by pre-symptomatic and asymptomatic infectious individuals in west africa, we believe these groups contribute more in covid- transmission in west-africa. our parameter estimation confirms the fact that asymptomatic transmission in the region is higher than symptomatic transmission-a result that is consistent with recent findings in [ ] . it is also worth mentioning that many symptomatic cases might not be identified in the region, especially if they do not seek medical j o u r n a l p r e -p r o o f journal pre-proof attention [ ] or if they prefer alternative traditional medicine-a common practice in the region [ ] . our results suggest that early identification and isolation of both symptomatic and asymptomatic infectious individuals is an important step towards curtailing the burden of the pandemic. in particular, identifying and isolating asymptomatic individuals early enough, e.g., within - days after the end of the incubation period can result in a significant reduction in disease burden, even without any other control measure. the same is not true with identifying and isolating symptomatic individuals or when it takes a longer time to identify and isolate infectious asymptomatic individuals. in this case, the measure must be complemented with another measure that involves a reduction in the disease transmission rate in order to achieve a significant reduction in disease burden. asymptomatic infectious individuals can be identified through contact-tracing and diagnostic rt-pcr testing. however, since mass testing in most west-african countries only started during the last week of april, the primary way in which asymptomatic individuals were identified in west-africa before the start of mass testing was through contact tracing and then testing the contacts suspected to have the virus. one way in which contact tracing has been used successfully to identify and isolate both pre-symptomatic and asymptomatic infectious individuals is through mobile phone applications, see for example, ferretti et al. [ ] . we showed that a higher reduction in the disease transmission rate, e.g., through social distancing or using masks will be required to eliminate the disease if a higher proportion of exposed humans do not develop clinical disease symptoms after the incubation period. these results highlight the importance of early identification of disease tracing is already being implemented in west-africa, the measure is not very effective due to the lack of resources and high community transmission in the region. for example, as of june , , almost all the reported cases in the region resulted from community transmission [ ] . therefore increased compliance with measures like social distancing and mask use is very important for the region. since the disease can be transmitted from one human to the other through droplets from infected individuals that can travel though a few meters in air [ , ] , using masks and social distancing are very important in the fight against the pandemic. masks are useful in reducing the risk of both uninfected individuals wearing them from contracting the virus and infected individuals wearing masks from spreading the virus to others [ , ] . it is worth mentioning that the efficacy of n masks is about % ( − %), while the efficacy of surgical and cloth are % ( − %) and % ( − %), respectively [ ] . a study in us [ ] suggested that the higher the number of infected asymptomatic people in a population, the more beneficial the use of masks by the general public. both mask-use and social distancing are ongoing in many west-african countries. however, the effectiveness of these measures in reducing the spread of the virus is linked to the extent to which they are applied, the compliance level by the public, and how long they will last [ , ] . our analyses show that covid- can be reduced significantly in west-africa through social distancing and using masks if about % of the population complies with j o u r n a l p r e -p r o o f journal pre-proof these measures. this is consistent with recent results in [ , , ] , where strict compliance with social distancing and mask use can lead to a significant reduction disease burden. some west-african countries, e.g., benin have implemented measures involving isolating some densely populated portions of the country, especially overcrowded urban areas with dilapidated sanitary facilities and limited basic amenities like clean water [ ] . this has a positive effect on reducing the spread of the virus. finally, our study suggests that mass application of control measures coupled with appropriate testing and timely isolation of asymptomatic humans will go a long way in keeping disease numbers low, which is consistent with results in [ ] . however, with the fragile economic conditions and health care systems in the region, interventions like complete lock-down as was the in some european countries, most us states, and china for a couple of months is not feasible [ ] and can be more catastrophic than the disease itself. therefore, the choice of interventions by public policy makers in the region should aim at balancing the prevention of the epidemic with the need for maintaining livelihoods and social cohesion. our study confirms the fact that the novel coronavirus (covid- ) is highly contagious and that infectious humans who do not show clinical disease symptoms (asymptomatic or unreported cases) contribute significantly in disease transmission. this study also indicates that early identification of these unreported cases through contact tracing or systematic testing on target groups, and then isolating individuals who test positive plays a significant role in diminishing the burden of covid- in west-africa. furthermore, this study suggests that social distancing measures such as stay-at-home orders, closing educational institutions, limiting mass gatherings, etc., and using masks can reduce the spread of the disease significantly, with the possibility of disease-elimination if 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transmission-a modelbased analysis of the diamond princess outbreak. medrxiv estimating the generation interval for covid- based on symptom onset data quantifying sars-cov- transmission suggests epidemic control with digital contact tracing mathematical model for lassa fever transmission dynamics with variable human and reservoir population feasibility of controlling covid- outbreaks by isolation of cases and contacts airborne transmission of sars-cov- : the world should face the reality modelling transmission and control of the covid- pandemic in australia a final size relation for epidemic models hbt acknowledges the support of imu-cdc through graid program. kvs acknowledges the support of the wallonie-bruxelles international post-doctoral fellowship for excellence, belgium (fellowship # sub/ / ). cnn acknowl- the author declares no conflict of interest. key: cord- -ocfjj v authors: blumberg, lucille; regmi, jetri; endricks, tina; mccloskey, brian; petersen, eskild; zumla, alimuddin; barbeschi, maurizio title: hosting of mass gathering sporting events during the – ebola virus outbreak in west africa: experience from three african countries date: - - journal: int j infect dis doi: . /j.ijid. . . sha: doc_id: cord_uid: ocfjj v • mass gatherings at sporting events attract millions of international and national host-country travellers, who may put themselves at risk of acquiring local endemic infectious diseases. • the – ebola virus disease (evd) outbreak in west africa that resulted in over cases and deaths required that countries holding these events put in place public health programmes for enhanced surveillance and specific response plans for any suspected cases of evd. • three major sports events were held in africa during the evd outbreak, attended by athletes from numerous african countries including liberia, sierra leone, and guinea, the three countries most affected by evd: the african youth games (botswana), africa cup of nations (equatorial guinea), and all-africa games (republic of congo). • a large range of infectious diseases other than evd were considered with respect to the differential diagnosis of acute febrile illnesses and for the provision of laboratory diagnostics and treatment options. • the experience from these three mass gathering events during the ebola epidemic illustrates that these events can be held safely provided that countries put measures in place for enhanced surveillance and response systems for communicable diseases. mass gatherings at sporting events, , or religious pilgrimages, , attract millions of international and national hostcountry travellers, who put themselves at risk of acquiring local endemic infectious diseases. [ ] [ ] [ ] over the past five decades, the public health authorities of the host country have focused their attention on the transmission of infectious diseases and their impact on the attendees at the mass gathering, the local population, and the local health system. the appearance and reemergence of several new lethal pathogens of humans with epidemic potential have heightened awareness of the potential of rapid spread at mass gathering events. new zoonotic infectious diseases of humans include nipah virus, hantaviruses, west nile virus, ebola virus, severe acute respiratory syndrome coronavirus (sars-cov), middle east respiratory syndrome coronavirus (mers-cov), and avian viruses, among others. , the unprecedented ebola virus disease (evd) epidemic in west africa and the ongoing zika virus (zikv) outbreak in south america , were declared public health emergencies of international concern (pheic) by the world health organization (who) in august and february , respectively. yellow fever outbreaks in a number of african countries in / are cause for concern, with infections in unvaccinated travellers to angola posing a risk on return to their countries of residence. , there are a number of challenges for countries hosting major international sporting events during a pheic. , , the - evd outbreak in west africa, which resulted in over cases and deaths, required that countries holding these events put in place public health programmes for enhanced surveillance and specific response plans for any suspected cases of viral haemorrhagic fever (vhf). three major sports events were held in africa during different phases of the ebola virus outbreak, with participation by sportsmen and women and supporters from a broad range of african countries, including liberia, sierra leone, and guinea, the three most affected countries. at the invitation of the host countries, who missions were conducted to the three respective countries to support and advise on specific ebola prevention and response strategies. in this article, the three major sporting events are described, highlighting the activities undertaken to ensure public health security and the outcomes of these mass gatherings with specific reference to evd. the african youth games are held every years. the first games were hosted by morocco in rabat and athletes from countries participated. the second african youth games were held in gaborone, the capital city of botswana, from may to may , ; in retrospect, this was at a time when the ebola virus outbreak had expanded rapidly within the affected region. this event took place at a number of venues in gaborone and drew around athletes aged to years, who took part in a wide range of sporting events including football, swimming, fencing, boxing, cycling, and rugby, as well as their support teams; the participants came from african countries including liberia, sierra leone, and guinea. spectator attendance was mainly from botswana and countries in the region. at the beginning of may the ministry of health of botswana was on high alert and requested that the who provide rapid technical support in strengthening public health capacities under the framework of the international health regulations (ihr) , in the context of the expanding ebola virus outbreak. botswana had never previously managed cases of suspected or confirmed vhf. while no general travel restrictions were applied to athletes from the evd-affected countries, contacts of known cases of evd were not permitted to leave their respective countries. proof of yellow fever vaccination was required as a condition of entry for travellers from yellow fever endemic countries. at the international airport in gaborone, port health staff screened incoming travellers for fever; they were supported by a small team of medical personnel trained for the event. a small medical facility was established at the airport for the isolation of patients. while a strong national surveillance system supported by district outbreak response teams was already in place for epidemic-prone diseases, this was supplemented by a daily surveillance system for specific priority conditions pertinent to the event. both a syndromic approach and laboratory confirmation to identify participants with an acute febrile illness were used. a daily analysis attempted to establish trends. an emergency -h reporting system was established for persons with suspected meningitis or vhf, and for any outbreaks. an isolation facility was established in an existing health centre outside of the major hospitals. extensive staff training was conducted using videos and demonstrations in the use of personal protective equipment (ppe) and infection control practices, as well as simulation exercises. sourcing of adequate supplies of ppe was a challenge. since botswana did not have laboratory capacity for vhf and other specialized testing, arrangements were made for testing to be conducted in the biosafety level (bsl ) laboratory and reference laboratories at the national institute for communicable diseases in south africa, approximately h by road from gaborone. the requisite export permits and transport arrangements were facilitated. the public health and hospital laboratories in gaborone were able to test for malaria and meningitis and common pathogens. training sessions in the recognition and management of a range of communicable diseases were held for medical personnel. the africa cup of nations competition was organized by the confederation of african football and held in equatorial guinea between january and february , . initially scheduled to be hosted by morocco, this major football tournament was moved to equatorial guinea at a late stage after morocco requested postponement due to the ebola virus epidemic in west africa. south africa, egypt, ghana, and sudan all declined to take over as hosts. fifty-one countries competed and qualified for the tournament: south africa, equatorial guinea, congo, mali, algeria, gabon, burkina faso, cameroon, cote d'ivoire, guinea, ghana, zambia, tunisia, senegal, democratic republic of congo, and cape verde. four cities in equatorial guinea hosted the event: the capital city malabo, bata, mongomo, and ebebiyin. in addition to supporting the overall evd preparedness, the main objective of the joint who team was to strengthen the country's readiness to detect and manage evd during the africa cup of nations. equatorial guinea had never previously detected a human case of evd, neither associated with the most recent epidemic in west africa nor during any previous outbreak. nevertheless, the neighbouring country of gabon verified its first evd outbreak in and detected sporadic evd outbreaks in and / , with confirmed cases and deaths reported. with people coming to the country from many african countries, the risk of importing evd existed and required mitigation. a crisis committee to coordinate preparedness and response activities for evd, chaired by the prime minister, was established in december following the declaration of the pheic by the who. overall, no major communicable disease events were reported. the republic of congo hosted the xi edition of the all-africa games. the games were held in stadia throughout the city of brazzaville from september to september , , with participation of athletes from countries, including sierra leone, liberia, and guinea. the ministry of health and population of congo was responsible for the overall coordination and delivery of health services, and worked in close collaboration with other ministries, the organizing committee, and the who, to ensure rapid detection and containment of infectious diseases, especially evd. the republic of congo had previous experience of managing vhf with referral to the reference laboratory in kinshasa, democratic republic of congo, directly across the congo river from brazzaville. health risks to visitors and local communities during the all-africa games were assessed at an early stage, and planning for constant disease surveillance and risk assessment during the event was organized. enhanced surveillance for key notifiable diseases was implemented in all stadia and other important locations like the airport. during the games, the ministry of health participated in daily all-hazard assessment with the national organizing committee and developed and shared daily situation reports. the data gathered from the surveillance units at the sports village during the events showed that of the cases reported from the sports sites during the events, trauma accounted for %, followed by malaria at % and respiratory tract infections at %. no significant threat to public health was detected during the event, with a minimum effect on the surge capacity of the public health services. thus, early planning, risk assessment, and preparedness activities as well cross-sectoral collaboration resulted in successful organization of the event amidst the ongoing evd in west africa. no major public health incidents occurred during the three major sporting events. each of the countries enhanced their surveillance and reporting systems. only a few outbreaks of gastrointestinal and respiratory infections and malaria and a few traumatic injuries were recorded during the period, and importantly, no suspected cases of evd or other vhf occurred. while outbreaks of infectious diseases have been reported during events, mostly from faeco-oral, respiratory, and vectorborne transmission, to date there have been no published incidents of a case of vhf presenting at a mass gathering. [ ] [ ] [ ] even though the risk of introduction of a case of evd would in reality be quite low, the high profile of these sporting events and the major negative effect of even one suspected or confirmed case on the games, necessitated special preparations over and above those needed to monitor and manage the more usual communicable disease risks associated with mass gatherings. persons with early or acute evd are less likely to travel and unlikely to take part in a sporting event. exit screening was introduced after the declaration of evd as a pheic, and transmission requires direct contact with blood and body fluids of infected persons. however, evd was spread to a number of countries through travel, persons are asymptomatic during the incubation period, sexual transmission by survivors is now well documented, and certain contact sports may pose a risk, albeit small, for transmission. with specific reference to evd, the challenges are the nonspecific nature of early illness with its broad differential diagnosis, the infrequent finding of haemorrhage, which could raise the index of suspicion of a vhf, the many other infections presenting with bleeding, delays in laboratory exclusion of vhf in the settings of these three events or the confirmation of alternative diseases, the need to ensure that patients receive adequate treatment for common infectious diseases and importantly for a mass gathering scenario, the potential for panic amongst athletes and the local communities, and the risk of potential disruption to the games. there are many additional resources needed to respond to potential vhf cases, some of which are not readily available, and these require additional funding. given the countries of origin of the participants and spectators, a large range of infectious diseases other than evd needed to be considered with respect to the differential diagnosis of acute febrile illness and the provision of laboratory diagnostics and treatment options. training of health workers and resources needed to be provided, given that these were not necessarily common diseases in the host countries. these conditions included trypanosomiasis, meningococcal disease, crimean-congo haemorrhagic fever (cchf), lassa fever, dengue, arboviral infections, and leptospirosis, as well as the more familiar typhoid, malaria, hepatitis (a, b, and e), hiv, sexually transmitted infections, tuberculosis, and gastrointestinal (viral and bacterial) and respiratory infections, including influenza. the annual influenza season in temperate zones in southern africa typically occurs from late may to august. meningococcaemia or meningococcal meningitis was a particular concern, given the increased risks in young people, particularly those in close contact in hostel-type accommodation, the origin of some of the participants from countries within the african meningitis belt, and possible increased carriage rates. the typically very rapid progression to severe illness over a matter of hours, difficulty in recognition because of nonspecific signs and symptoms, particularly with meningococcaemia, high mortality rates, and occurrence of bleeding with confusion with vhf, was particularly concerning in the setting of a mass gathering. overall, for vaccine preventable diseases, such as measles, meningococcal meningitis, pneumococcal sepsis, influenza, mumps, and hepatitis a, pre-travel vaccination for participants is known to reduce disease incidence at mass gatherings. meningococcal disease at the hajj has rarely been recorded since pre-travel vaccination was enforced. for communicable diseases that do not have vaccines available, a high state of public health alert, with public health teams on standby coupled to educating the attendees and local population, can go a long way in improving their prevention and detection. brazil will be hosting the olympics in rio de janeiro in august , with many thousands of people from all over the world travelling to brazil. the unexplained rapid spread of the mosquito-borne zikv across south and central america adds another viral threat (in addition to dengue, japanese encephalitis, and yellow fever) for the attendees of the olympic games, further challenging preparedness and surveillance efforts. south africa successfully hosted two mass gatherings during the influenza a (h n )pdm virus pheic without any major communicable disease incidents. these were the confederation cup in and the fifa soccer world cup in . while epidemics due to vector-borne transmission pose different challenges to ebola virus and influenza, the same principles of enhancing surveillance and response efforts and reducing all possible risks would apply. the experience garnered during these three mass gathering events during the ebola epidemic illustrates that these events can be held safely even during a pheic provided that countries put measures in place for enhanced surveillance for communicable diseases and are well prepared to respond to any incidents. although additional resources and training will be required, the efforts are worthwhile and form part of the legacy of mass gatherings for the detection and response to future cases or outbreaks of formidable diseases. european football championship finals: planning for a health legacy olympic and paralympic games: public health surveillance and epidemiology hajj: infectious disease surveillance and control global perspectives for prevention of infectious diseases associated with mass gatherings communicable diseases as health risks at mass gatherings other than hajj: what is the evidence? emerging infectious diseases and pandemic potential: status quo and reducing risk of global spread emerging respiratory tract viral infections emerging and re-emerging infectious threats in the st century world health organization. ebola virus diseases outbreak rapid spread of zika virus in the americas-implications for public health preparedness for mass gatherings at the brazil olympic games yellow fever cases in asia: primed for an epidemic why is the yellow fever outbreak in angola a 'threat to the entire world'? public health for mass gatherings mass gatherings and public health: the experience of athens olympic games. who/euro ebola virus disease outbreak, end of ebola transmission in guinea and liberia morbidity and mortality of wild animals in relation to outbreaks of ebola haemorrhagic fever in gabon transmissibility and pathogenicity of ebola virus: a systematic review and meta-analysis of household secondary attack rate and asymptomatic infection assessing the impact of travel restrictions on international spread of the west african ebola epidemic potential impact of sexual transmission on ebola virus epidemiology: sierra leone as a case study we thank the public health authorities of botswana, equatorial guinea, and the republic of congo and their respective who representatives.conflict of interest: the authors have no conflict of interest to declare. key: cord- -eehb yny authors: haffejee, sadiyya; levine, diane thembekile title: ‘when will i be free’: lessons of covid- for child protection in south africa date: - - journal: child abuse negl doi: . /j.chiabu. . sha: doc_id: cord_uid: eehb yny background: covid- has highlighted and amplified structural inequalities; drawing attention to issues of racism, poverty, xenophobia as well as arguably ineffective government policies and procedures. in south africa, the pandemic and the resultant national lockdown has highlighted the shortcomings in the protection and care of children. children in alternative care are particularly at risk as a result of disrupted and uncoordinated service delivery. objective: the aim of this study was to explore the experiences and impact of the pandemic and the resulting social isolation on the wellbeing and protection of children living in a residential care facility. methods and participants: we used qualitative, participatory approaches – specifically draw-and-write methods – to engage with children (average age = . years) living in a residential care facility in gauteng. findings: children in care demonstrated an awareness of the socio-economic difficulties facing communities in south africa, and shared deep concerns about the safety, well-being and welfare of parents and siblings. although they expressed frustration at the lack of contact with family members, they acknowledged the resources they had access to in a residential care facility, which enabled them to cope and which ensured their safety. discussion and conclusion: we focus our discussion on the necessity of a systemic response to child welfare, including a coordinated approach by policy makers, government departments and child welfare systems to address the structural factors at the root of inequality and inadequate, unacceptable care. this is essential not only during covid- but also in pre- and post-pandemic context. with care facilities either shutting down and releasing children prematurely or keeping children in-care, without access to family and friends. emerging reports from south africa confirm this, showing that key government departments responsible for vulnerable children in residential care have been severely hampered by the crisis (wolfson-vorster, a). continuity of care as well as coordination of services between all essential service providers; key activities in ensuring the safety and protection of children, has been constrained (fallon et al, ) . in this exploratory study, we consider the impacts of covid- for children in one non-governmental organisation in johannesburg, south africa, which aimed to provide continuous and consistent care for children living in residential care. we ask 'what can the experiences and perspectives of south african children in care during lockdown tell us about the themes we should focus on to improve care moving forward? we focus on children's experience of the lockdown as well as covid- ; their concerns as well as the protective resources that enables them to cope. we frame the experiences of these children in care against a background of a crippled social system and reflect critically on what systemic changes are needed to support children. this study offers a way forward and contributes to an emerging body of research on the impact of pandemics on child well-being and protection. to address a global pandemic such as covid- requires inspired, informed leadership and co-ordination between all sectors of government and civil society. this has occurred to a limited extent in south africa. in comparison to the hesitancy that characterised some of the global responses to the pandemic, south africa's initial response was decisive. the complete national lockdown which began on the th march , saw trade, places of worship, and recreational activities shut down. a national curfew was mandated and movement between provinces prohibited. these stringent measures were considered necessary to flatten the curve and to ready the health system for a potential influx of cases. some rights groups and commentators however raised concerns about the impact and feasibility of such measures in a context with gross pre-existing and historic socio-economic inequalities (world bank, ) and a struggling economy (marais, ) . acknowledging these challenges and to mitigate against the worst impacts of the pandemic, the south african government introduced a number of temporary social and economic relief measures, which included increasing the health budget, economic support through the unemployment insurance fund, support for small business and tax relief measures. social relief support measures included the establishment of the special covid- social relief distress (srd) grant of r per month (£ /$ ) as well as increases to existing social welfare grants, for example, the basic child support grant was increased by an additional r per month (£ /$ ). the government, through the department of social development, also pledged to distribute food packages to communities most in need. as predicted however in a country with such disparate, intense needs these resources have simply not been enough, failing to buffer the majority of south africans from worsening j o u r n a l p r e -p r o o f social and economic conditions (van bruwaene, et al., ) . findings from the national income dynamics study-coronavirus rapid mobile survey (nids-cram), found that almost million people lost their jobs during the most intensive lockdown period and during this time in children reported that they had gone hungry in the week before they were interviewed during may or june (nids-cram, ) . compounding, what is rapidly being seen as a humanitarian crisis, is the constrained leadership at national and provincial level and lack of co-ordination between government departments (thebus, ) . the department of social development (dsd), a key department in the care and protection of children and its minister, have been severely criticised for providing little leadership during this period (weiner, ) . for example, dsd's delivery of the much needed and promised food parcels have been hampered by reports of corruption and theft, cumbersome processes, lack of capacity to distribute food packages, lack of data on who needs this assistance and insufficient funds to meet the needs of the population (wolfson-vorster, a). similarly, distribution of the covid srd grant has been challenged by complicated processes making it difficult to access. activists report that as at july , approximately four months into lockdown, % of individuals eligible to receive the grant have not received it (thebus, ) . the department of basic education (dbe), another crucial department, took a decision, at the beginning of the lockdown period to also stop the national school nutrition programme (nsnp), as a result, the . million children who are dependent on this one meal a day have had to go without food. a number of child's rights groups instituted legal action against the minister of basic education as well as the provincial mec's, arguing that the failure of government to recommence this nutrition programme was a regression of the rights to education and to basic nutrition (see www.centreforchildlaw.co.za). on the july , dbe was ordered to reopen the nsnp, with the judge asserting that in closing the programme, the j o u r n a l p r e -p r o o f minister, and her mecs were in breach of their constitutional and statutory duties (wolfson-vorster, b). to understand the impact that covid- has on the individual child we reference a multi-systemic framework; this framework situates the individual within broader systems and contextual factors, acknowledging the interconnectedness between physical, individual, relationships, community, and society. masten and motti-stefanidi ( ) note that risks to individuals span across all of these levels and as the pandemic unfolds, the challenges to these systems also change. similarly, factors that enable and support resilience are situated across levels. here we draw on a covid- specific explanation of systemic risks shared by the alliance for child protection in humanitarian action ( ) as well as that used by unicef ( ). from this perspective, individual level risks during a pandemic, include increased risks of child abuse, neglect, violence, exploitation as well as potential psychological distress and a negative impact on development. challenges also include adjusting to the changed circumstances, with school closures, disrupted routines, isolation from friends and peers and fear of the unknown and losing loved ones (ghosh, dubey, chatterjee & dubey, ; orgiles, morales, delvecchio, mazzeschi & espada, , zhou, . these changes may result in increased feelings of anxiety and distress or may exacerbate existing mental health issues and enhance the risk of developing psychological disorders (alliance for child protection in humanitarian action, ; wang, xiao, sun, wang & xu, ) . at the level of the family, risks may include family separation, reduced access to social supports, caregiver distress, heightened risk of violence/domestic abuse, disruption to family earnings as well as disrupted family connections and support and fear of the disease (spinelli, lionetti, pastore & fasolo, ) . community level risks may include distrust within communities, competition over j o u r n a l p r e -p r o o f limited resources, inadequate access to support services including educational resources and support (fischer et al., ; sekyere, bohler-muller, hongoro & makoae, ) . lastly societal level risks include corrosion of social capital and disrupted and inadequate access to basic services (fischer et al., ; scott, ; sekyere et al., ) . as discussed, within the south african context, these systemic risks are amplified by pre-existing challenges. present day south africa continues to be characterized by deeply embedded inequalities and structural violence, a legacy of colonialism and apartheid (loffell, ; tshishonga, ) . this inequality manifests in high levels of poverty, discrimination, poor access to education, health and social services, poor service delivery and exposure to high rates of communal and interpersonal violence (zizzami, schotte & leibbrandt al, ) . children in south africa are particularly vulnerable as a result of these structural challenges; for example, poverty creates food insecurity which impacts on a child's physical, mental and cognitive development (hall & sambu, ) . research suggests that prior to the pandemic a quarter of children in south africa were stunted, . million children were dependent on child support grants, % of children lived below the upper-bound poverty line, % of children were without access to water and % of children lived in overcrowded households (hall & sambu, , lake et al., ; van der berg & spaull, ) . poverty is recognized as a significant barrier to children's well-being, impacting on health and educational opportunities and increasing vulnerability to child maltreatment (fernandez, delfabbro, ramiac & kovacs, ; loffell, ; manyema & richter, ; meinck, cluver & boyes, ) . artz et al ( ) found that approximately % of young people in south africa have had direct experiences of abuse. fear and additional stressors caused by the pandemic provides an enabling environment that may exacerbate or trigger diverse forms of violence against children and women (peterman et al, ) . given the j o u r n a l p r e -p r o o f existing high levels of gender-based violence, sexual abuse and child abuse in south africa, of significant concern, during these exceptional times, is the safety of children, especially as many are in close, constant proximity to potential abusers. lack of income and employment opportunities and food insecurity are likely to increase conflict within families, thereby increasing risk to children (mathews, jamieson & makola, similarly, disruptions in education risks the wellbeing of children both in the short-term and may have significant long-term consequences. while some children have been able to access online learning, for the majority of children living in conditions of poverty, with no access to a phone, television or computer this has not been possible, further deepening the digital divide (fore, ) . van der berg and spaull ( ) report that by the beginning of august , at least million children will have missed more than half ( %) of the number of school days and they note that the education system in south africa is unlikely to make up this time. this has significant long-term consequences in a country with staggeringly high rates of illiteracy (howie et al., ) . j o u r n a l p r e -p r o o f (mamelani, ) . children identified as vulnerable includes a child who i) has been abandoned or orphaned and is without any visible means of support; ii) displays behaviour which cannot be controlled by the parent or care-giver; iii) lives or works on the streets or begs for a living; iv) is addicted to a dependence-producing substance and is without any support to obtain treatment for such dependency; v) has been or is at risk of serious physical or mental harm; or vi) has been abused, neglected, or exploited (mahery, jamieson & scott, ) . given the wide range of needs of children entering care, cyccs are mandated to not only provide for the basic needs of children in terms of food and shelter and access to education, but are required to make therapeutic programmes available. section of the children's act provides a comprehensive list of programmes that should be offered. jamieson ( ) schmid & patel, ). historically, poor coordination between social and health systems in south africa during periods of health crises has meant that services to child and youth care centres have been inadequate (allende & khota, ) . the lockdown has intensified these. many children living in residential care come from disadvantaged communities and have been exposed to one or multiple traumas within the home or the community and some have pre-existing health problems (meintjies et al, ) . in this context, children may be safer in care where they have access to regular meals, shelter, protection and access to educational resources. the aim of this rapid exploratory, qualitative study was to understand how children residing in a care facility in south africa understood and experienced the lockdown measures imposed as a result of covid- . we focus on the concerns that children in care experienced during this period as well as what helped them to cope. our decision to speak with children was informed by an acknowledgement that children are experts in their lives and capable of speaking on their own behalf. titi and jamieson ( ) found that only % of stories focus on children and less than half this number includes the voices of children, noting that such exclusion is in fact a violation of their rights. children residing at a child and youth care centre in gauteng, south africa (herewith referred to as cycc x) were invited to participate in the study. a cycc is defined as a facility that provides residential care for more than six children who are not living with their biological families (children's act, ) . cycc x is situated in gauteng (south africa) and was established by a social worker in , in response to a growing number of mainly black south african children living on the streets. during this period, south africa was slowly transitioning out of apartheid and the country was characterised by uncertainty and ongoing hostility between various racial groups. the needs of disadvantaged, black children were often not acknowledged and services for this group was lacking or non-existent (loffell, for over children and is an active member in the child and youth care sector (newsletter, august ). the majority of children at cycc x have been exposed to one or more risk factors, including poverty, neglect, physical, emotional and/or sexual abuse and streetism. reasons for admission noted in the cycc's most recent progress report show that; % of children were admitted because of familial poverty, % of children were exposed to domestic violence, % reported parental neglect, % reported some form of abuse, % were placed in care for substance use, % were not attending school, % were street connected and % displayed uncontrollable behaviour prompting parents to request placement (progress report, ). as mandated in the children's act (children's act, ) , cycc x offers extensive programs to meet the physical, psychosocial, and trauma needs of these vulnerable children. this is delivered to children primarily through the in-care, residential programme and through a pre-care, prevention and early intervention programme and an after-care, transitory support programme. children in therapy consulted therapists online. although many of the schools that the children attended did not have an online teaching programme, educational activities continued throughout the period at the centre, with lessons delivered by teaching staff and online learning forums. information regarding the study was shared with children, who were then invited to participate in the study. participation was voluntary. a total of children and youth chose to participate. the average age of participants was . years, children identified as girls and identified as boys. at the time of the study, all the participants were legally placed at the cycc. informed assent was obtained from the younger children and consent from the older children. to generate data, participants met in small groups, which were facilitated by a counsellor and a social worker, who both work at the centre. the decision to engage staff in j o u r n a l p r e -p r o o f facilitating groups was necessary during the initial, stricter levels of lockdown (when the data were generated) as non-essential staff were not allowed entry onto the premises. the first author has a working relationship with both the facilitators and provided information on the study aims and the methods. to guide the process, each participant was given a booklet with six open-ended questions related to covid- and the lockdown; each question had space allocated for participants to draw and/or write a response. the first question prompted participants to share something about themselves. the questions that followed included: - -what are some of the things that are helping me cope? participants were then invited to share verbally in the groups what they had written, and what the drawing meant to them (angell et al., ) . this qualitative method, referred to as the draw, write and tell method of data generation, foregrounds the voice of the participants and is flexible and sensitive to the context and of the content (mitchell et al., ) . this method is particularly useful for use with children as it fun and non-threatening; it also gives children time to think through and structure thoughts before sharing and may also address linguistic difficulties (backett-milburn & mckie, ) . the method is, however, not without criticism with suggestions that it may undermine children's ability to adequately communicate their experiences, may be superficial and assumes that drawing is a fun activity for all children (angell et al., ; backet-milburn et al., ) . in our research, we gave children the option data comprised of the textual information generated by participants and was analysed following the six steps to inductive, thematic analysis described by braun and clarke ( ) . this method of analysis is used to identify, analyse and report themes within data (braun & clarke, ) . author reviewed the data, becoming familiar with it and generated the initial codes and possible themes. these were then reviewed and refined by both authors and through a joint process, final themes were then defined and named. ethics approval for the study was granted by the university of leicester ( april ). the director at cycc x, acting as legal guardian, granted consent and as mentioned above, informed assent was obtained for children younger than and consent from those over . as well as delivering these fundamental ethical tasks, and aware of our positionality as researchers (both south africa, by birth, one indian and one white born during the apartheid era), our approach to ethics also accounted for four key dimensions accepted as important when delivering research in low resource settings experiencing chronic structural disadvantage j o u r n a l p r e -p r o o f association with cycc x and brought this experience to bear in ensuring a respectful approach was maintained throughout the data gathering process. author visited the cycc x in and spent time with the staff team, with the intention of beginning to build a trusted working relationship. -risk-benefit ratioour exploratory project aimed to surface the key worries experienced by the participants, and had existing mechanisms in place to ensure they had adequate counselling and other support should significant issues arise. to ensure trustworthiness of the data, author shared findings from the study with childcare staff and social workers based at cycc x; this group were in close contact with the children during the lockdown period and had engaged the children in similar conversations throughout the lockdown period. they were able to confirm the consistency of the findings. time constraints, for both children (including a demanding school schedule), staff (supporting online learning together with regular care duties) and ourselves, meant that, at the time of writing this, we were not able to share findings with the children. we used thick descriptions to describe the context and shared excerpts and images from the participants, ensuring we could begin to interpret the characteristics of each participant's contribution (schwandt, ) . findings from the study draws attention both to how the experiences and ways of coping for children in residential care are similar to that reported by children living in family contexts as well as how they differ. consistent with emerging literature on the impact of covid- on children's mental health, children in care reported experiencing a range of emotions ranging from frustration, anger and happiness and reported drawing on a host of resources to j o u r n a l p r e -p r o o f enable them to cope (ghosh et al, ) . children in care however differed with regards to their concerns, which centred primarily on worry for parents and siblings well-being. covid- as well as the variations in containment measures have raised concerns about the mental health and well-being of both adults and children (panchal et al., ) . for children in care, these feelings are exacerbated, as they are unable to have the normal contact visits with parents or extended family and tend to be under strict supervision, often grouped together with children with a variety of emotional and/or behavioural difficulties (lazzaro, ). children at cycc x similarly appeared to be experiencing a wide range of emotions in response to being under lockdown. fear, sadness and worry because of the virus, anger and frustration at having to be under lockdown away from family and school, as well as feelings of hopelessness and discomfort were mentioned. one of the participants aptly summarises the range of emotions she is experienced during this period, many of which were echoed by other the image (image ) below by child and her explanation reflects the complex relationship that children in care have with parents. for child , her concern for and attachment to her mum appears to override her mother's absence or potential parental neglect. speaking of her concern for her mum, [insert image : child articulates her concern about her mother] in their concern, children and youth in care demonstrated an awareness of the 'i also think about school, when i will go back to school also if i will repeat a grade because i don't want to repeat.' these concerns are not unfounded, with child protection agencies asserting that many of the . billion children currently out of school worldwide will never return to school and will have limited future prospects (wolfson-vorster, a). referring to the strict regulations that were of necessity imposed by the cycc, child and child both express frustration at not being able to leave the centre and go to school, in the image below (see image ), child draws attention to people that don't have homes. [insert image : child expresses concern about those without homes.] the majority of children drew on internal, self-regulatory mechanisms to help them cope, this included exercise, reading, listening to music and watching television. this was accompanied by engaging with others through play and group sports. some of these resources, like television and radio, were easily accessible for children while in residential care. engaging with others through play was especially important for the younger participants, while for some of the older children helping staff with chores and younger children with homework appeared to give them a sense of purpose and stopped them from feeling bored. complaining. going to home work class and helping the staff with whatever they need help with.' sense of purpose has previously been identified as a potential protective factor in psychological resilience during adolescence (e.g. wang et al, ) . in addition to these internal mechanisms, structural resources provided by the cycc enabled children to cope. the ability to access education, through access to the online learning programme, 'doing my homework online' (child ), alleviated some of the children's fears of falling behind and also kept them occupied, facilitating coping. it is important to note here that for the majority of children in south africa accessing education through online forums was not possible (van der berg and spaull, ). the awareness of being safe also helped children cope; 'we are very safe, we are in our homes and in our shelters because if we were outside we should have been dead or killed' (child ). child echoes this saying, 'by knowing i am safe.' as above, these statements suggest that participants in care are fully aware of the dangers present in communities; as mentioned above, approximately % have had exposure to some form of violence. the structure and support offered by the cycc enables them to feel safe. this sense of safety also enabled some children to focus 'on the positive side of life' (child ). the following images (images and ) from participants captures this range of protective, resilience-enabling resources. [insert: image and : participants share their protective, resilience-enabling factors] covid- has been referred to as an unprecedented event, unparalleled in its impact. in this global reach, it highlights more than any other event in recent times, our global inter-j o u r n a l p r e -p r o o f communities and societies are differentially impacted. in south africa, the social and economic disruptions caused by the pandemic and associated lockdown, combined with long-term structural social, economic and political inequality, and failures within government has impacted on service delivery, access to resources and availability of supportive networks, the absence of which increases vulnerability and heightens levels of anxiety and stress in children. in this exploratory study we aimed to address the research question 'what can the experiences and perspectives of south african children in care during lockdown tell us about the themes we should focus on to improve care moving forward?' as the findings emerged, we noted that there were a number of domains of concern that reflect the social ecologies in which our participants operated. in spite of being 'out' of community contexts, our findings show that children in care situate themselves firmly within their social-ecologies. they continue to express concern for families and for communities (some who may have rejected them). they acknowledged the resources that they have access to while at the cycc and through their concern for parents, siblings and wider society also acknowledged the prevalence of hunger, violence and food insecurity in south africa. for many south african children, pre-existing structural challenges heightens exposure to a multitude of risks. covid- has increased these risks factors. the majority of children admitted into care at cycc x have been exposed to poverty and child maltreatment. (jamieson, ) . cycc x, as many others, tries to provide an environment that is consistent, stable, and built on supportive relationships; studies show that access to this sort of environment provides a measure of protection in the face of multiple adversities (collishaw et al, ; mosavel et al, ) . many of the children acknowledged the protection and support offered to them and which helped them to cope. thus, even while in careoften thought of as the last possible resort for vulnerable children -in this protective context, they were also able to access their own internal resources and reach out to support others. research shows that child-level resources are most easily accessed within the context of a responsive, accessible ecology (ungar, ) , the absence of which may negatively impact on the child's well-being. the importance of self-regulation in mediating resilience pathways our findings showed that participants drew on a range of internal resources to help them cope, which was facilitated by caregivers that were available, access to therapeutic support as well as access to resources, like television, sports, books and online learning forums. of significant concern for the participants in our study, was the closure of schools. this experience is consistent with findings emerging from other studies, across diverse contexts. ghosh et al. ( ) note that being quarantined in homes and institutions presents a bigger psychological burden than that of the actual pandemic; adding that school closures, lack of physical activity and aberrant eating and sleeping habits may potentially promote monotony, distress, impatience, annoyance and varied neuropsychiatric manifestations. isolation and the absence of routines imposed by schools may also lead to psychological distress as schools provide stability and may be a coping mechanism for some children (lee, ). in the context of the residential care facility, the psychosocial support offered by schools, takes on further importance in that it represents an additional, external space away from the confines of the facility. in addition to the supportive role that schools play, for children at cycc x, absence from school was seen as a significant obstacle, potentially jeopardising future plans. south african research with youth exposed to structural adversity show that access to education and the presence of future oriented plans enable positive adaptation in contexts of risk and is regarded as a means to securing a better more economically stable future (lundgen & schekle, ; theron & van rensburg, ; walker & mkwanazi, ) . in the context of an emergency, such as this one, protecting the rights of children in residential care requires collaboration across multiple sectors, including government ministries (better care network, ). masten and motti-stefanidi ( ) suggest that every disaster brings with it lessons for future resilience planning at multiple levels. as such, learnings from this experience may be leveraged to repair and transform the child protection sector, strengthening system responses and building resilience. the findings of our study suggest that it is only through co-ordinated, holistic, and strategically sound collaboration that we will be able to protect children in care in south africa. some of the challenges experienced by children during lockdown particularly with regarding concern for family members, suggests a need for creative problem solving by care facilities to ensure that children have continued contact with families. digital technologies may j o u r n a l p r e -p r o o f offer new solutions using 'free at the point of use' services for families to stay in touch with cyccs, if not children themselves if access to technology is not universal. regional or national policy programmes facilitating solar chargers for communication devices in cyccs, and devices themselves in limited numbers, would overcome this barrier at a relatively low cost. beyond this emergency response planning, the pandemic has reinforced the need for broad scale systemic changes, necessary to protect and assist the most vulnerable communities in south africa. strengthening economic support for families is essential given the increasing levels of poverty, food insecurity and growing rates of unemployment. current calls for a universal, unemployment or basic income grant and general increase in child support grants are positive developments in the right direction. our findings on the significant role that parents play, even in their absence, suggest a need for positive parenting skills and family strengthening interventions that will ensure that children are cared for in family environments. combining social support grants that provides a measure of protection against the impacts of poverty with family strengthening interventions promotes greater child and youth development and well-being (cluver et al, ). families and communities should be safe spaces for children; the appallingly high prevalence of gender based violence and child abuse demands greater accountability from government and co-ordinated action from all departments, including justice, social development and health. the promotion of social norms that protect against adversity and violence through public education campaigns, legislative approaches that acknowledge and prioritise gender based violations and that develop and implement gender sensitive solutions is necessary (cdc, ). participants concerns regarding the interruption of their schooling highlighted the centrality of education in nurturing hope for children exposed to adversity. the importance of j o u r n a l p r e -p r o o f the schooling system has also been the subject of much discussion in the country throughout the pandemic. the role that education and educational systems have on youth development suggests a need for increased efforts in ensuring that these spaces are fully resourced and accessible. efforts must be to ensure that digital poverty is addressed, and that all children have equal access to adequate schooling. this study took place under unusual circumstances demanded by a global pandemic. as a result, there are limitations to the conclusions we can reasonably draw that could be mitigated by future research. our intention was to capture, in the most systematic way we could, the immediate experiences of our participants during the most intense period of south africa's lockdown, and our design reflects these priorities. the study has four key limitations to which we draw attention. . the size of the sample and length of the data-gathering period invite further investigation, in other alternative care settings in south africa and beyond. . qualitative research is dependent in part on the skill and experience of the person gathering the data. we mitigated the risk of poor data quality by ensuring the approach was closely structured and supported by author , and that a common prompt tool was used across the sample. . the qualitative nature of the study facilitates a rich and trustworthy understanding of the perspectives and experiences of our participants, but should not be read to imply causality. . in order to increase trustworthiness, our study relied on a well-tested method; arguably future research of this type should seek to take a more africa(n)-aligned approach to gathering data, which will bring with it additional strengths and some risks. our study with vulnerable children in care has provided a living example of the ways in which the covid- pandemic exposes and exacerbates the inherent structural inequalities that characterise south africa. this exacerbation of existing inequalities lies at the interface between public health, and societal and systemic structures. covid- , devastating in its impact, urges accountability and provides multiple opportunities to learn from and build the capacity and resilience of individual, family, community and societal systems. caring for children in uncertain times principle : strengthen children's resilience in humanitarian action draw, write and tell': a literature review and methodological development on the 'draw and write'research method relationship between resilience and selfregulation: a study of spanish youth at risk of social exclusion a critical appraisal of the draw and write technique social dimensions of covid- in south africa: a neglected element of the treatment plan spike in child abandonments and the physical abuse of youngsters during lockdown technical note on the protection of children during the covid- pandemic: children and alternative care. retrieved from: review, & yerkes. m. 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resilience among rural-to-urban migrant adolescents in china challenges in accessing higher education: a case study of marginalised young people in one south african informal settlement this study was made possible through seed funding from the leicester institute of advanced studies (lias), university of leicester. we wish thank our child and youth participants for sharing their knowledge with us as well the director at cycc x for granting us permission to conduct the study and staff cycc x for their assistance with data generation. key: cord- -sc fyqs authors: ogundiran, akin title: on covid- and matters arising date: - - journal: afr archaeol rev doi: . /s - - -x sha: doc_id: cord_uid: sc fyqs nan the final phase of the editorial process that culminated in this issue of african archaeological review (volume , ) took place in the atmosphere of panic and uncertainties unleashed by the coronavirus (covid- ) pandemic. i must first thank our authors, reviewers, editorial team, and the springer staff for keeping the clock of production moving despite the strains imposed by the pandemic on our working environment and mindset. five of the pervasive concepts in archaeology (and anthropology broadly) during the past years are vulnerability, collapse, resilience, regeneration, and sustainability (e.g., chase and scarborough ; lane ; logan et al. ; mcanany and yoffee ; redman ) . these concepts-for which i will use the acronym, vcrrs-are often invoked in discussions about how past societies have coped with (or failed to manage) climate change, natural disaster, conflict, ecological degradation, resource scarcity, and social inequality and the implications for the present and future. infectious diseases are always in the background of our archaeological thinking, but these are not usually given as prominent a space as these other sources of perturbations. unlike epidemical outbreaks, those other perturbations are easier to observe in the archaeological record. for example, natural disasters such as tsunami, earthquakes, hurricanes, and tornadoes are similar to contagions in terms of their sudden and unpredictable occurrences. however, natural disasters often leave much more detectable signs than epidemics, although the latter can last much longer. in some instances, we can receive forewarnings of impending natural disasters and therefore be proactive (e.g., through evacuation). it is not so with microbes. they do not give warnings of their arrival, and they cannot be seen with the naked eye. as a result, we are limited to a gradualist reactive approach to pathogens as they wreak havoc on our corporeal and social fabric. as it has been with covid- , past societies had to rely more on their political institutions and social systems than their medical know-how in breaking the chains of pathogenic spread. the coronavirus pandemic is relevant to the vcrrs concepts that have animated our scientific inquiry about social and cultural formation for several years. this ongoing pandemic is a stark reminder, on a grand scale, of human vulnerability. it is also a great test of societal resilience, and it presents us with the question of what to let go and what to keep. although, in some instances, the virus has not given us the choice. in the long run, the covid- crisis might force on us new ways of being, especially as we develop strategies of recovery and regeneration. but one thing is clear: epidemics will always be part of the human journey. exactly a hundred years ago, the world was just recovering from the influenza pandemic of - that took about million lives worldwide. as many as two million people in sub-saharan africa possibly died from the pandemic (patterson , p. ) . since then, we have developed the most connected, urbanized, and scientifically advanced global system in human history. alas, we may not have been as well-prepared and efficient as one would expect in dealing with the covid- outbreak. this first truly global pandemic in a century has not only halted business as usual but has also overwhelmed the resources of many countries around the world. according to the johns hopkins university coronavirus dashboard, the total confirmed number of infections globally is nearing six million, and over , people have died at the press time for this issue ( ). the african union's center for disease control and prevention has reported over , covid- cases and more than , deaths in africa. about , have recovered as of mid-may. overall, africa's covid- cases account for . % of the global number and less than % of the worldwide covid- -related deaths ( ) . several conjectures have been offered as to why africa's numbers are low, considering the poor state of its healthcare compared with the global north (moore ) . although this pattern may change as this situation evolves, we must also confront two realities. first, the advanced healthcare system of north america and europe does not translate into healthy living for some segments of their population and access to good healthcare is uneven. second, the aggressive efforts of most african governments helped to significantly slow the spread of covid- , as i witnessed in late february during my trip to the continent. the world health organization regional director for africa, dr. matshidiso moeti, has said that the covid- spread is unlikely to be as exponential in africa as it has been elsewhere. however, she also warned that without proactive testing, tracing, isolating, and treating, covid- could smolder in transmission hotspots across the continent for many years to come ( ) . coronavirus, like all zoonotics in history, is a product of ecological perturbations, an outcome of the interdependence between humans and fellow organisms (vidal ; vijaykrishna et al. ) . and epidemics are no respecter of the visible and invisible walls that people and societies build to separate themselves into classes, ethnicities, genders, races, tribes, and other hierarchies of power and social difference. hence, coronavirus has sneaked into spaces of power, from the white house to downing street, and it has penetrated the cramped working-class tenements from cape town to new york. covid- may defy social boundaries. however, social inequality-one of the staples of archaeological inquiry-has nevertheless mediated the brutal impacts of the virus. not surprisingly, the poor and the working class have higher chances to be exposed to and die from coronavirus because they have fewer opportunities for social distancing and must also work outside the home. not only do they have higher chances of contracting and spreading the virus to family members, but they often also have the underlying medical conditions and historically poor access to healthcare that make them more susceptible to death from covid- than the well-off. in the western world, where class and race tightly overlap, infected black people and other minorities in the usa are dying at a higher rate than their white counterparts (kendi ) . the class and age patterns of contraction and death from covid- are not yet clear in africa, but there is no doubt that the first wave of the infected were those who had recently visited europe, north america, and asia. as a result, according to a british broadcasting corporation report, covid- was initially perceived as the disease of the elite in many parts of africa ( ). these elite are still being blamed on the street for bringing the disease to their respective countries, a reflection of the sharp socioeconomic divides on the continent. it is noteworthy that as early as february , many african countries were at the forefront of proactive actions to stem the spread of the pandemic at the very time that many countries in the global north were in denial and foot-dragging about the disease. many scientists on the continent are also working to be part of the solution rather than waiting for what the global north can do for them. senegal, for example, is developing a $ covid- testing kit as part of the strategy to help flatten the curve of infection. amadou sall, the director of the pasteur institute in dakar where the test kit is being developed, reportedly said that his laboratory could analyze - tests a day and produce million test kits a year (yeung ) . currently, each coronavirus test costs hundreds of dollars, and analyzing one test would take several hours. in nigeria, a group of scientists at the university of ibadan is investigating the efficacy of a local herb, euphorbia hirta, for treating the respiratory conditions associated with covid- ( ) . many other examples abound in different parts of the continent. these efforts call attention to the need to support capacity building in africa rather than the usual benefactor gestures that merely reinforce the dependency syndrome in the continent. we are reminded that the most effective and lasting solutions to some of the contemporary medical problems in the world may originate in africa, as they did in the past. african herbal medicine and healing knowledge, for example, have made significant contributions to the advances in western science, from treating malaria to eradicating smallpox. the race by western scientists and drug companies to appropriate african knowledge of herbal plants for developing patented drugs has been ongoing for more than a century (e.g., osseo-asare ). all of these reinforce the need to expand the archaeological framework for heritage studies in africa beyond the valorization of places and monuments. of course, the agenda for archaeological heritage will always include the preservation of archaeological sites and landscapes, conservation of artifacts, and the use of these artifacts and sites for public education (volume , of the journal was devoted to this topic almost a decade ago; sulas et al. ) . but these cannot be the stopping point. heritage studies must take advantage of the interdisciplinary approaches of archaeology so that it can be relevant to the needs of african peoples, especially by supporting the quest to liberate africa from economic and intellectual dependency rather than perpetuating that dependency. therefore, one would hope that the documentation, analysis, and application of indigenous knowledge and epistemology will be an integral part of the burgeoning archaeological heritage studies on the continent (also see mire ). as i have advocated in a recent editorial, those archaeological programs invested in heritage studies need to collaborate with experts in other fields so that the body of heritage-related knowledge they are collecting can inform scientific and policy efforts to improve human conditions in africa and elsewhere (ogundiran ). this echoes david phillipson's much earlier observation of the purpose that african archaeology must serve in generating bodies of knowledge that would contribute to the appropriate "policies for. .. health, food, sustainable exploitation of natural resources, and. .. fostering a sense of pride and self-reliance" on the continent (phillipson ) . covid- is challenging us to rethink how we do business and engage in archaeological inquiry. if history is a useful guide in this instance, we know that epidemics never traveled alone. they were always accompanied by other ecological, economic, and sociopolitical upheavals that have altogether changed or shaped the course of human history (e.g., mcneill ; oldstone ). the shortand long-term impacts of coronavirus on global politics and power relations are still not clear. nevertheless, almost every economist is predicting recessions, and the unemployment rate has exponentially risen in many countries, while the trains of global supply chains have also been derailed significantly. drastic budget cuts by national and subcontinent governments in the next fiscal year are all certain. for most african countries, the reliance on single commodity export and importation of almost all essential infrastructure, including medical supplies, portend significant economic and social trouble. but these also present opportunities for african countries and regional blocs to think creatively about local production and innovations. how might these knowns and unknowns affect human lives, archaeology, and heritage issues in africa? a forum has been convened for future publication in the african archaeological review that will explore some aspects of this question while also providing a platform to discuss what we are learning in african archaeology and heritage studies from the social, political, economic, and ecological dimensions of the covid- pandemic. the forum participants have been tasked to explore how the pandemic is affecting the way they conceptualize and think about the african past with reference to their scholarly interests in social formations and social emergents. the participants will also reflect on the insights that archaeology can provide to inform the ways current pandemic is being managed on the continent. we hope to publish - short essays on these and related topics in the coming months. covid- has disrupted most archaeological plans for the summer and early fall of , especially fieldwork travels. most important, the much-anticipated biennial conference of the society of africanist archaeologists (safa) scheduled for september - , in oxford (uk), has been postponed till next year-august - , , and this will still take place in oxford university. one must commend the sagacity and consultative approach of the safa executive and the conference organizing committee, led by elisabeth hildebrand and peter mitchell respectively, in the way the decision to postpone the conference unfolded. it is a template for future crisis management by the association, and the sequence of events deserves to be summarized here ( ) . & april : the safa president, elisabeth hildebrand, announced the inauguration of a sixmember "covid matters committee" (cmc), in consultation with peter mitchell, "to gather perspectives and, in the next few weeks, decide whether or not we should postpone" the safa conference. the cmc members include two representatives from each of africa, europe, and north america: alemseged beldados, munyaradzi manyanga, timothy clack, paul lane, catherine d'andrea, and brian clark. & april : the safa members were given the opportunity to contact the cmc with ideas and suggestions on what should be done with the scheduled safa conference. hildebrand specifically charged cmc to determine the timing(s) and mechanism(s) for the th biennial conference and consider the maximum health, safety, and opportunities for participation across the safa membership. & april : events were moving very fast, and the alarming rate of new covid- cases and death in north america and europe, coupled with other factors, made it necessary for peter mitchell to announce, on behalf of the conference organizing committee, the postponement of the conference until mid-august . & may : the co-chairs of cmc, paul lane and catherine d'andrea, reported the committee's first meeting to safa members. the committee made two important decisions. first, the cmc did not recommend holding the conference in september in "an entirely online format" because of unequal access of safa members to the internet. second, the committee plans to explore the viability of holding limited and small-scale online sessions in september "as a 'test drive' for incorporating more online access to full safa meetings in the future." & may : the cmc co-chairs contacted safa members again to report the outcome of the committee's may meeting. they announced that the committee had reviewed and approved a google-based survey "to gather opinions from our membership on online options for september and future safa meetings" (the survey was released on may ). the cochairs also informed members that "a series of online events will be hosted by the safa oxford organizing committee in september , not as a replacement of the conference but to provide students and early career researchers with workshops on grant preparation and publications development. and, these junior scholars will also have the opportunity "to present aspects of their research in a poster format." the safa executive, the safa organizing committee, and the cmc members are to be commended for their hard work in leading the association through this uncharted path, although there are still several emerging questions yet to be answered. covid- no doubt challenges many of the ways in which we engage our sociality as scholars and professionals. the digital technology is playing a significant role in the ways we cope with these challenges. it is too early to understand the long-term effects of this technologyenhanced coping strategy on our future communication, interaction, knowledge sharing, and social networks, not to talk of global health, economics, and politics. covid- and its uncertain future notwithstanding, cameron gokee and i had the great pleasure of working with the authors whose articles appear in this issue of the journal. the lead article is the conversation that two senior african archaeologists, chap kusimba and innocent pikirayi, had with peter schmidt about his -year career (and still counting!). the interview covered a lot of ground, and we are pleased to feature peter schmidt's experience, accomplishments, and challenges in the following pages. his story is a significant part of the history of african archaeology. it offers many takeaways. also, this issue includes an article on new advances in archaeometallurgical study in senegal, with emphasis on the transformations in iron technology in the falémé river valley region between the fourth century bc and seventh century ad. the next article focuses on schroda, a tenth-to eleventh-century farming settlement in the middle limpopo valley (south africa), where a functional analysis of ceramic vessels was undertaken to answer questions of site use and social organization. two articles are based in tanzania. one is a synthesis of the archaeological profile of the iringa region, from the early stone age to the colonial period, a product of years of fieldwork. the other article explores the development of cognitive thoughts, planning depth, and cultural innovations by anatomically modern humans during the late msa and early lsa transitions in the famous mumba site. paul lane sent in a reflective commentary on the roles that the shanghai archaeological forum has been playing in world archaeology since and the implications of china's belt and road initiative for africa's archaeological heritage. this issue also features three book reviews. the reviewers noted the significant contributions of each book to africa's cultural history. the first book revisits the epistemology and methodology of sources in the study of west africa's history. the second provides the first booklength assessment of the state of middle stone age studies in nigeria. and the third examines mortuary culture, patterns of migration, and dynamics of identity in the ancient sahara region. on behalf of the editorial team of the african archaeological review, i wish you safety and well-being in this uncertain time. diversity, resiliency, and ihope-maya: using the past to inform the present what the racial data show: the pandemic seems to be hitting people of color the hardest developing landscape historical ecologies in eastern africa: an outline of current research and potential future directions usable pasts forum: critically engaging food security questioning collapse: human resilience, ecological vulnerability, and the aftermath of empire plagues and peoples the knowledge-centred approach to the somali cultural emergency and heritage development assistance in somaliland what african nations are teaching the west about fighting the coronavirus. the new yorker food security, food sovereignty, and indigenous knowledge viruses, plagues, and history: past, present and future bitter roots: the search for healing plants in africa the influenza epidemic of - in the gold coast archaeology in africa and its museums: an inaugural lecture given at the university of cambridge resilience theory in archaeology africa's fragile heritages: introduction destroyed habitat creates the perfect conditions for coronavirus to emerge evolutionary insights into the ecology of coronaviruses cheap and easy $ coronavirus test to undergo trials in senegal additional online sources for this essay african union's centres for disease control and prevention dashboard cause many deaths, says who. the new york times coronavirus: why some nigerians are gloating about covid- . bbc news covid- : ui scientists recommend euphorbia hirta linn. for relief key: cord- -rliv hms authors: naicker, saraladevi; jha, vivekanand title: nephrology in africa: forgotten no more date: - - journal: kidney int doi: . /j.kint. . . sha: doc_id: cord_uid: rliv hms nan d uring a time when the world is grappling with the coronavirus disease pandemic, african nephrology suffered a major setback, with the passing of of its stalwarts: oladipo akinkugke (nigeria), jacob plange-rhule (ghana)-whose obituaries are featured in this issue-and mohamed abdullah (kenya). these individuals bookend the period during which nephrology took roots in the continent. this editorial discusses the highlights of african nephrology during this development phase and recalls some of the individuals who made them possible. africa, home to . billion people distributed over countries, s has been called the cradle of humanity. despite being endowed with immense natural and human resources as well as great cultural, ecological, and economic diversity, africa remains the most underdeveloped of all continents. africa's share of global income has been dropping consistently, and african countries occupied of the lowest spots on the united nations human development index. s africa has the youngest (median age, years) and most rapidly growing (annual growth rate, . %) population in the world. s infectious diseases and neonatal and/or maternal deaths are the major causes of death and disability. an overwhelming majority of global deaths attributable to tuberculosis, malaria, and hiv infections occur in africa. at the same time, the burden of noncommunicable diseases, including kidney diseases, is also rising. according to the global burden of disease study, apart from a few countries in central america and southeast asia, african countries have the highest age-standardized rates of disability-adjusted life years attributable to chronic kidney disease. africa also has a large burden of acute kidney injury, caused by infections acquired in the community, diarrheal diseases, complications of pregnancy, and consumption of herbal remedies. lack of access to treatment leads to premature loss of a large number of lives. delivery of health care in africa presents major challenges, with a shortage of human resources, poor allocation of health care, and lack of infrastructure and political will coming out on top. ongoing civil wars, religious and ethnic conflicts, misrule, corruption, and military interventions have forced a large number of people to seek refugee status in neighboring countries. more than a quarter of world's refugees are in africa. the skilled and the educated often emigrate to western countries, further exacerbating the human resource shortage. africa's largest export has been said to be its health care expertise. as a result, specialty development, including that of nephrology, has been stunted. even today, the median nephrologist density in africa is less than per million population, compared with a global average of . per million population. several countries have no nephrologist. this is accompanied by shortages of allied health care professionals and lack of technical expertise. in this background we appreciate the remarkable and extraordinary contributions of individual leaders toward development of kidney care in africa. many of these leaders trained in the west, came back to their native lands, and set up renal services. africa has seen growth in kidney care services, ever since the first hemodialysis in johannesburg in and ain shams university hospital, cairo, in , and the first kidney transplants in johannesburg in , khartoum in , and cairo in . s ,s subsequently, services started in other countries, and today, hemodialysis is available in almost all countries. access is highly restricted, however, with just approximately % of all incident patients continuing hemodialysis year later in sub-saharan africa. peritoneal dialysis (pd) is gradually increasing, but only south africa, sudan, and tunisia have wellestablished pd programs. kidney transplantation is increasing in africa and is largely from living donors, with deceased donor saraladevi naicker the south african renal society and the egyptian society of nephrology and transplantation were founded in and , respectively. the african association of nephrology (afran) was born in cairo in february during the first international society of nephrology (isn)--sponsored "african kidney and electrolytes conference," which was attended by participants from african countries, and had a strong isn presence (donald seldin, klaus thurau, robert schrier). rashad barsoum was elected its first president. s afran holds biennial congresses, alternating between anglophone and francophone countries, has an established journal, and is developing a registry. oladipo akinkugke (nigeria), seminal research was conducted on the epidemiology and clinical aspects of hypertension by oladipo akinkugke, yackoob seedat (south africa), s and jacob plange-rhule (ghana). s the work of a lifetime by rashad barsoum has immensely contributed to the understanding of kidney disease caused by schistosomiasis. the unique pattern of glomerulonephritis in africa was described by yakoob seedat and rajendra bhimma s (south africa). the maladie rénale chronique au maroc (maremar) study, de broe (belgium), was conducted as a collaboration between the moroccan government, isn, the moroccan society of nephrology, and the world health organization. this is the largest population-based study that determined the prevalence of chronic kidney disease and its risk factors in morocco. a number of researchers studied kidney involvement in hiv infection, s ,s and dwomoa adu (accra, ghana) set up the h africa kidney disease research network s to study the genetics of kidney disease in africa. the international society of nephrology, through its capacity-building programs, has supported training of fellows and knowledge exchange for setting up renal services in africa. jean-pierre grunfeld (france) and rashad barsoum (egypt) were the first chairs of the africa committee of isn's commission for the global advancement of nephrology (com-gan), s later replaced by the global outreach (go) programs and the isn regional board. they were succeeded by saraladevi naicker the isn message of education and training in nephrology was enthusiastically received by the african medical community, and its programs were increasingly subscribed. in earlier years, isn fellows used to travel to western countries for training. this changed in , when yewondwossen tadesse from addis ababa, ethiopia, elected to train in durban, south africa, with saraladevi naicker. this started the new south-south initiative of isn. since then, african fellows have trained in south africa and india. of the isn fellows from africa, most have returned to their countries and set up independent services. they have created an isn fellow's network and stay connected through social media, discuss clinical problems, and develop collaborations. in , the isn started a reverse fellowship scheme, and fellows from e d i t o r i a l kidney international ( ) , - australia and united kingdom were selected to spend year in africa. the sister renal center and education ambassador programs have helped setting up new nephrology services. the first isn africa nephropathology workshop in was organized by mohamed abdullah, ahmed twahir, and saraladevi naicker in nairobi, kenya and supported by nephropathologists jan weeening (amsterdam), prabha naidoo (durban), and maureen duffield (cape town). the workshop was attended by clinicians and pathologists. the world congress of nephrology (wcn) in cape town in , the first time this event was held in africa, marked the coming of age of african nephrology and was a resounding scientific and social success. the congress was cohosted by the south african renal society, afran and isn, with pierre ronco (france) as the scientific committee chair and charles swanepoel as the local organizing committee chair. the collaboration ensured a unique african flavor, with archbishop emeritus desmond tutu giving an insightful and entertaining address at the opening ceremony. the wcn also marked the kicking off of intervention nephrology training in africa. the isn intervention nephrology working group-under the leadership of tushar vachharajani (united states)-has conducted a series of workshops in collaboration with afran, and the international society of haemodialysis. the isn allied health professionals working group spearheaded by marie richards (dubai) has made notable contributions toward training of nurses. recognizing the need to support service delivery, isn launched the saving young lives (syl) program in as a proof-of-principle to demonstrate that it was possible to set up sustainable pd programs to treat acute kidney injury in very low-resource settings. s the program was started in moshi, tanzania, in partnership with the international pediatric nephrology association, the international society for peritoneal dialysis, europd, and the sustainable kidney care foundation. it has a strong component of education; to date nurses and physicians have been trained in pd catheter insertion, pd fluid prescription, and clinical problem solving. learnings from africa prompted expansion of the syl program to other parts of the world. table provides a summary of the isn capacity-building programs supported in africa. the enthusiasm with which the isn fellows have established programs and emerged as leaders in nephrology and medicine in their respective countries augurs well for the growth of nephrology in africa. advocacy by nephrologists and patients is leading to an increase in access to dialysis and transplantation. there is increased focus on kidney disease prevention and in research in kidney conditions. there is still a long way to go, but the mood has changed from "nothing can be done" to "we can and will do." burden of noncommunicable diseases in sub-saharan africa, - : results from the global burden of disease study analysis of the global burden of disease study highlights the global, regional, and national trends of chronic kidney disease epidemiology from outcomes of acute kidney injury in children and adults in sub-saharan africa: a systematic review identifying key challenges facing healthcare systems in africa and potential solutions shortage of healthcare workers in sub-saharan africa: a nephrological perspective world epidemiology of hypertension in blacks chronic kidney disease, hypertension, diabetes, and obesity in the adult population of morocco: how to avoid "over"-and "under"-diagnosis of ckd a unique role in global nephrology key: cord- - vehcvhc authors: akintayo, richard o; kalla, asgar; adebajo, adewale title: covid- and african rheumatology: progress in adversity date: - - journal: lancet rheumatol doi: . /s - ( ) - sha: doc_id: cord_uid: vehcvhc nan the pandemic of covid- , the disease caused by the severe acute respiratory syndrome coronavirus (sars-cov- ), hit africa later than much of asia, europe, and north america. it has led to immense disruption of health-care services, economic hardship, and loss of life in africa. by sept , , more than million cases of sars-cov- infection and deaths from covid- had been confirmed across africa. however, the cataclysm of covid- has taught us major lessons and incited the potential for rapid growth in african rheumatology after the pandemic subsides. in response to the pandemic, an unprecedented number of research collaborations began in african rheumatology, mainly facilitated through the networks of the african league against rheumatism (aflar). the first collaborative effort was the pan-african survey of the experience of rheumatologists across all five regions of the continent, done between april and may , , which provided a far-reaching understanding of the structure of rheumatology services and the degree of service disruption as a result of the covid- pandemic. before the survey, no data were available on the number and distribution of rheumatologists across the continent. findings showed that there are far more rheumatologists in northern africa than in other regions, with the lowest number in central africa; that women represent % of rheumatologists; and that % of rheumatologists treat both adults and children. with ongoing lockdown in several countries, appreciation for the usefulness of virtual conferencing and telemedicine has increased. until now, telemedicine has not had substantial political support in many african countries, although the prospect of its use to supple ment service deficiencies in health care has been a lingering promise. videoconferencing has fostered and accelerated collaborations among rheumatologists across the continent. aflar also commissioned a task force to draft recommendations for management of rheumatic diseases in africa in the face of covid- . members of the task force assessed africa-specific challenges, in addition to the global crises of the pandemic, in the management of patients with rheumatic diseases. this process, which led to increased recognition of the diversity in the structures and resources of rheumatology services available in countries within the aflar network, culminated in the formation of statements of recom mendations for the management of rheumatic diseases in africa in the context of covid- . the task force also recognised the problem of limited resource availability, such as biological drugs, specialist doctors, and ventilators. the widespread suggestion of a role for various diseasemodifying antirheumatic drugs in the treatment of patients with covid- triggered an increase in demand that resulted in a shortage of hydroxy chloroquine in many rheumatology services. more than % of african rheumatologists reported shortages of this drug in their practice, leading some rheumatologists to reduce doses of the drug for their patients to prolong supply. hoarding of hydroxychloroquine, and hikes in prices of available supplies, have been seen across africa, while self-use by patients and toxic effects were reported after indiscriminate promotion of hydroxychloro quine as a covid- treatment, mostly via social media. , unfortunately, scant decisive governmental action has been taken to stem these ongoing shortages. other drugs commonly used in rheumatology have also gained prominence for treatment of patients with covid- . corticosteroids were initially shown to slow sars-cov- clearance in a small observational study, but pre liminary results from the large recovery trial later showed survival benefits with use of low-dose dexa meth asone in patients with severe disease. early in the pandemic, some patients with severe covid- were recognised to have cytokine storm. this find ing led researchers and clinicians to consider use of interleukin- inhib itors such as tocilizumab for the management of these patients. timing of administra tion, dosing, and efficacy of tocilizumab have not yet been determined; trials are ongoing across many countries, including centres in kenya and south africa, in which tocilizumab is being given at an average dose of - mg/kg bodyweight as a single infusion. however, there is yet insufficient evidence to recommend the wide use of tocilizumab for treating covid- outside of trials. due to its high cost, tocilizumab is available for treatment of rheumatoid arthritis in very few african countries, and it is uncertain whether this situation would change if tocilizumab proves to be effective for treating severe covid- . amid the upheaval caused by the covid- pandemic, aflar found renewed strength and brought together members from african countries by organising and launching virtual learning events, including national and regional sessions on the practice of rheumatology in the era of covid- , workshops on neuromuscular ultrasound, vasculitis, and connective tissue diseases, and monthly paediatric continuing medical education programmes. experts from different areas of rheumatology came together to a degree not previously experienced by the aflar membership, raising hope for a bright future with regards to educational and research growth for african rheumatology. for years, trainees have had to travel between african countries for rheumatology fellowship programmes. the new normal of increased virtual collaboration and real-time delivery of educational sessions offers aflar members a horizon of possibilities and the chance to learn from the models of the more vibrant rheumatology services, such as those in northern africa and south africa. the rise and sustenance of virtual academic offerings, service improvement, and research meetings will hopefully foster the growth of rheumatology services and promote effective continuing medical education in rheumatology across africa. following this trend, aflar is likely to grow in both its capacity and reach, as it uses the services of international volunteers and research collaborators to foster inclusiveness and develop afrocentric clinical guidelines for the management of the various rheumatic diseases in africa. optimistically, as rheumatology develops further on the african continent, patient advocacy will also increase, leading to greater attention by policy makers towards better funding of training, procurement of biologics and equipment, as well as investments into research. we declare no competing interests. *richard o akintayo, asgar kalla, adewale adebajo r.akintayo@nhs.net ); and faculty of medicine, dentistry and health coronavirus in africa tracker covid- and the practice of rheumatology in africa: big changes to services from the shockwave of a pandemic a meta-analysis of telemedicine success in africa african league against rheumatism (aflar) preliminary recommendations on the management of rheumatic diseases during the covid- pandemic chloroquine and hydroxychloroquine for the prevention or treatment of covid- in africa: caution for inappropriate off-label use in healthcare settings use of hydroxychloroquine and chloroquine during the covid- pandemic: what every clinician should know dexamethasone in hospitalized patients with covid- : preliminary report corticosteroid treatment of patients with coronavirus disease (covid- ) cytokine release syndrome in severe covid- : interleukin- receptor antagonist tocilizumab may be the key to reduce mortality covid- , immune system response, hyperinflammation and repurposing antirheumatic drugs key: cord- -vv zc gd authors: gutman, julie r.; lucchi, naomi w.; cantey, paul t.; steinhardt, laura c.; samuels, aaron m.; kamb, mary l.; kapella, bryan k.; mcelroy, peter d.; udhayakumar, venkatachalam; lindblade, kim a. title: malaria and parasitic neglected tropical diseases: potential syndemics with covid- ? date: - - journal: am j trop med hyg doi: . /ajtmh. - sha: doc_id: cord_uid: vv zc gd the covid- pandemic, caused by sars-cov- , have surpassed million cases globally. current models suggest that low- and middle-income countries (lmics) will have a similar incidence but substantially lower mortality rate than high-income countries. however, malaria and neglected tropical diseases (ntds) are prevalent in lmics, and coinfections are likely. both malaria and parasitic ntds can alter immunologic responses to other infectious agents. malaria can induce a cytokine storm and pro-coagulant state similar to that seen in severe covid- . consequently, coinfections with malaria parasites and sars-cov- could result in substantially worse outcomes than mono-infections with either pathogen, and could shift the age pattern of severe covid- to younger age-groups. enhancing surveillance platforms could provide signals that indicate whether malaria, ntds, and covid- are syndemics (synergistic epidemics). based on the prevalence of malaria and ntds in specific localities, efforts to characterize covid- in lmics could be expanded by adding testing for malaria and ntds. such additional testing would allow the determination of the rates of coinfection and comparison of severity of outcomes by infection status, greatly improving the understanding of the epidemiology of covid- in lmics and potentially helping to mitigate its impact. the covid- pandemic caused by sars-cov- , a novel coronavirus, has now reached all corners of the world, and cases have surpassed million. sars-cov- is currently spreading in low-and middle-income countries (lmics) that experience the highest rates of malaria and neglected tropical diseases (ntds). neglected tropical diseases refer to a diverse group of communicable diseases caused by parasites, fungi, bacteria, and viruses that occur primarily in tropical and subtropical climates; only parasitic ntds are considered here (table ) . with many lmics implementing movement restrictions or ordering their populations to stay at home to limit sars-cov- transmission, the threat to essential health services is likely to be immediate, causing delays to diagnosis and treatment for other diseases, including malaria and ntds. during the ebola epidemic in west africa, there were substantial reductions in all-cause outpatient visits and patients treated with antimalarial drugs ; modeling the potential for similar disruptions in malaria control due to covid- suggests that there could be up to an estimated , deaths due to malaria in (approximately double the number seen in ), mostly among children younger than years. countries working toward the elimination of malaria or ntds may face setbacks. less obvious, but potentially important, is the possibility of sars-cov- interacting with parasitic infections and changing the rate of severe outcomes, particularly among younger populations that have been relatively less affected by covid- to date. under the assumption that public health and social distancing measures are used to mitigate the epidemic, the modeled estimates for sars-cov- infection incidence rates for lmics, assuming comorbidity rates for all countries similar to what was seen in wuhan, china, are projected to be around infections per , population, similar to the rate anticipated for high-income countries. however, the mortality rate for lmics (∼ per , ) is projected to be about half that of the high-income countries (∼ per , ). the difference in predicted mortality rates between lmics and high-income countries is largely due to the younger age structure in lmics; in , the median age in sub-saharan africa is . years, compared with . years in china. syndemics, or synergistic epidemics, occur when two or more concurrent epidemics have a deleterious interaction, that is, when coinfections result in a worse overall outcome than for either individual infection. there are many examples of important interactions between malaria and ntds and other infectious diseases. for example, malaria plays a role in epstein-barr virus (ebv) infection, leading to burkitt's lymphoma by contributing to b-cell proliferation and increasing ebv loads ; hiv-infected individuals experience a greater frequency of severe malaria and increased hiv viral load following infection with plasmodium falciparum ; several parasite-hiv coinfections are associated with increased hiv viral load and worsened immunosuppression ; and schistosome infections are associated with increased transmission of hiv, whereas deworming is associated with decreased hiv viral load and improved cd counts among hiv-infected individuals. biological interactions between coinfecting pathogens could involve changes in host pathology related to indirect immune effects. the interplay of coinfections hinges on several host-pathogen factors and host immunodynamics. low-and middle-income countries in africa suffer the greatest burden of malaria; in , there were more than million cases per year, with an annual incidence of per , persons. despite substantial progress in reducing malaria mortality over the past two decades, more than , malaria deaths (> % in sub-saharan africa) were estimated to have occurred in . outside of africa, india has the greatest burden of malaria cases, accounting for % of the global burden. globally, ntds affect more than billion people, especially those living in poverty, who often lack access to clean water and adequate sanitation. africa has a disproportionate burden of ntds and malaria, with a significant geographical overlap. , with rapid transmission of sars-cov- , many people in lmics, particularly in africa, soon will be coinfected with sars-cov- and plasmodium spp. or one or more ntd pathogens; cases of covid- in the africa region will soon surpass , . preexisting infection with any of these parasitic infections may lead to changes in susceptibility and/or severity of covid- . it is unclear whether immunomodulation caused by malaria and ntds will be beneficial or harmful when hosts are coinfected with sars-cov- , but even small changes in the risk of severe outcomes due to coinfections could result in substantial changes in the impact and epidemiology of covid- in lmics. sars-cov- infection. common symptoms of infection with sars-cov- include fever, cough, shortness of breath, chills, myalgia, headache, sore throat, and new loss of taste or smell ; the onset of symptoms generally occurs - days after infection, although it can be as late as days, [ ] [ ] [ ] and not all infected people develop symptoms. [ ] [ ] [ ] approximately a week after the development of symptoms, some patients experience an acute worsening, with a pronounced systemic increase of inflammatory mediators and cytokines. the severe systemic inflammatory response, referred to as a "cytokine storm," is characterized by markedly increased levels of interleukins (il) and tumor necrosis factor (tnf)alpha, and is associated with the development of acute respiratory distress syndrome (ards). among , cases reported from china, % were rated as severe and % were critical (respiratory failure, septic shock, and multiple organ dysfunction or failure). case fatality ratios (cfrs) ranged from . % to . %, with higher cfrs among older adults ( . - . % among those aged - years and . - . % among those years and older, versus £ . % among those younger than years). , hypertension, diabetes, cardiovascular disease, preexisting respiratory disease, and obesity were common comorbidities , ; in a meta-analysis of , patients in china, all but diabetes and obesity were associated with increased risk of severe disease. potential plasmodium spp.-sars-cov- interactions. of the five parasitic species that cause malaria in humans (table ) , p. falciparum accounts for most morbidity and mortality, followed by plasmodium vivax. , clinical illness arises from asexual parasite replication within erythrocytes. infected erythrocytes lyse and release merozoites into the circulation, causing activation of the immune system and leading to the release of pro-inflammatory cytokines including tnf-alpha, interferon-gamma, il- , and il- . this cascade of cytokines leads to symptoms of uncomplicated malaria, including periodic fever, which, if left untreated, can progress to severe disease. severe disease manifests as severe anemia, respiratory failure, cerebral malaria, acidosis, and renal failure. children and infants are at greatest risk for severe malaria; % of malarial deaths are estimated to occur among african children younger than years. as with covid- , cellular immune responses in malaria involving the cytokine cascade must be carefully regulated to achieve a protective response without causing adverse impact on the host. studies in malaria-endemic regions have found that it is important to have a balance between a host pro-inflammatory, th response (e.g., tnf-alpha, il- , il- , and interferon-gamma) and anti-inflammatory, th response (il- , il- , and others) , ; severe manifestations of malaria are often due to excessive pro-inflammatory responses. the same appears to be true in at least some cases of covid- , suggesting that a coinfection that also leads to excess proinflammatory responses might result in more severe manifestations and poor prognosis. malaria-induced immunosuppression has also been observed in many coinfections, significantly inhibiting immune responses to the other infection (e.g., to salmonella spp.). , however, malaria-induced immunomodulation has been shown to be protective against severe manifestations of some respiratory viruses. in kenya, hospitalized children diagnosed with influenza and malaria were less likely to experience respiratory distress than those with influenza alone. coinfection with plasmodium spp. could suppress the production of pulmonary cytokines and decrease the recruitment of cellular inflammatory components to the lungs, leading to reduced clinical symptoms and inflammation, as was found during pneumovirus infections in a murine model. however, in the murine model, viral control was also impaired, leading to increased viral dissemination. similar dynamics could occur during plasmodium-sars-cov- coinfection; malaria-induced immunosuppression might lead to milder manifestations of covid- but simultaneously decrease viral control, potentially increasing or sustaining viral loads, which could increase the potential for viral transmission. age-related vulnerability to malaria and covid- . susceptibility to malaria in highly endemic areas differs by age: younger children are more vulnerable to malaria infections and at a higher risk for severe malaria. for covid- , children are less likely to develop severe disease, whereas older populations are disproportionately affected, with a higher risk of severe disease and death. this may be due to the fact that children are more likely to produce t-regulatory cytokines (il- , il- , and il- ) and have less inflammation (because of their immature immune systems) than older people who mount a more proinflammatory cytokine cascade, potentially contributing to pathogenesis. how age-related susceptibility to covid- will play out in africa, where many children are immunologically stimulated by several infections in addition to malaria, is not clear. importantly, malaria infections in endemic areas frequently result in chronic, afebrile disease in older children and adults. it remains unknown whether this underlying infection will alter susceptibility to or severity of covid- in these populations; it is important that surveillance systems be modified to collect data to inform our understanding of this issue. respiratory distress and ards. respiratory distress, observed in up to % of adults and % of children with severe p. falciparum malaria, has several causes, including severe anemia, metabolic acidosis, cytoadherence of infected erythrocytes in pulmonary vasculature, and coinfections with pneumonia-causing pathogens. the clinical spectrum varies from mild upper respiratory symptoms to acute lung injury and fatal ards. acute respiratory distress syndrome is rare in young children with malaria but occurs in - % of adults and % of pregnant women with severe p. falciparum infections, and less commonly with p. vivax malaria. in both malaria and covid- , ards is linked to inflammatory cytokine-mediated increased capillary permeability or endothelial damage, which results in major alveolar damage. [ ] [ ] [ ] given this situation, plasmodium spp.-sars-cov- coinfections may result in particularly rapid deterioration, with a poor prognosis. as the inflammatory-mediated alveolar damage in malaria-induced ards progresses even after treatment and parasite clearance, coinfected individuals may be prone to severe covid- . because both malaria and covid- can lead to similar clinical manifestations, including fever and respiratory symptoms, one or the other may be overlooked in a differential diagnosis of respiratory distress, leading to increased fatalities. as sars-cov- transmission increases in lmics, particularly in africa and india, clinicians should keep this in mind. in addition, documenting the frequency, distribution, and outcomes of these coinfections is important. anemia. anemia is highly prevalent in lmics and results from multiple causes. in cross-sectional household surveys in sub-saharan africa, %, %, and % of children younger than years had any anemia, moderate anemia, and severe anemia, respectively. more than one-fifth of children with malaria develop sma, with a cfr of . %. whereas the hematologic sequelae of covid- are still being elucidated, a meta-analysis describing , covid- patients from four studies found that hemoglobin values were . g/dl ( % ci: . - . g/dl) lower in individuals with severe disease versus milder disease. whether lower hemoglobin is a risk factor or a sequela of severe covid- disease is unknown. however, because of limited reserves, even small perturbations in oxygen-carrying capacity in individuals with preexisting malarial anemia may result in insufficient tissue oxygenation in the midst of covid- -induced respiratory failure. pro-coagulant state. numerous viral infections, including sars-cov- , induce a pro-coagulant state through the induction of tissue factor expression, endothelial dysfunction, von willebrand factor elevation, and toll-like receptor activation. , markers of a hypercoagulable state, including increased d-dimer and fibrin degradation product levels, and prolonged prothrombin time are associated with a poor prognosis. clinically, the hypercoagulable state manifests with a high rate of venous thromboembolism and arterial thrombotic complications (including pulmonary embolism and stroke). , covid- patients are at risk for developing disseminated intravascular coagulation (dic), , and autopsy findings have included both pulmonary hemorrhage and thrombosis. thrombocytopenia is another potential feature of covid- , thought to be due to excessive activation of the coagulation cascade, leading to platelet activation and subsequent consumption, and is associated with worse outcomes. malaria is also associated with a pro-coagulant state, with activation of the coagulation cascade, mediated by tnf-alpha and il- , proportional to disease severity. whereas microthrombotic complications are most commonly described, thrombosis of large vessels, including cerebral venous thrombosis, and pulmonary embolism have been described. , thrombocytopenia develops in - % of malaria cases. although bleeding and dic are rarely seen, occurring only in severe malarial cases accompanied by coagulopathy, they are associated with high mortality. lysis of activated platelets, along with tissue factor released from damaged vascular endothelial cells, promotes the pro-coagulant state, similar to the proposed mechanism in covid- . thus, plasmodium spp.-sars-cov- coinfection could lead to even greater degrees of coagulopathy and more severe disease than with either infection alone. potential interactions between ntds and covid- . helminths, including stool-transmitted helminths (sth), schistosomes, and filariae, typically push the immune system toward anti-inflammatory th pathways through a variety of regulatory mechanisms. , protozoal parasites, such as trypanosomes or leishmania spp., are more likely to induce a th , pro-inflammatory response. however, there are many deviations from this characterization. some helminths induce th responses in some stages of the life cycle (e.g., microfilariae of filarial parasites or schistosome eggs), resulting in symptomatic disease, but th responses in other stages (e.g., adults of both filarial parasites and schistosomes). the downregulation of the inflammatory response associated with helminths may reduce the development of immunity or response to vaccines, decrease inflammation associated with autoimmune diseases, reduce the ability to control mycobacterium tuberculosis and mycobacterium leprae coinfections, and reduce the severity of malarial coinfection. the pro-inflammatory effects of some protozoal infections may worsen the severity of some, but not all, viral infections. , in addition, polyparasitism is quite common, and the overall impact on inflammation depends on the sequence of infections and burden of each. thus, coinfection with parasitic ntds could result in altered risks and severity of clinical manifestations of sars-cov- infection, with the potential for decreased development of immunity with increased viral loads. the severity of covid- has been associated with underlying health conditions that usually occur with advancing age. several ntds, if left untreated, can result in chronic sequelae in much younger populations. for example, because acute trypanosoma cruzi infection is typically asymptomatic or results in a mild, self-limited illness, it is frequently undetected and left untreated. yet, in young or middle adulthood, - % of persons chronically infected with t. cruzi develop cardiac manifestations, commonly a complex, dilated cardiomyopathy. for these individuals, coinfection with sars-cov- could be lifethreatening. sth infections may result in anemia ; if, as described previously, anemia predisposes individuals to more severe outcomes, then coinfection of sths and sars-cov- in children and pregnant women could be problematic. malnutrition and covid- . chronic malnutrition is associated with both malaria and ntds, and is relatively common among children in sub-saharan africa as well as parts of latin america and asia. prealbumin, a marker for protein malnutrition, was found to be lower on admission in patients with covid- who developed ards than on those who did not. although lower prealbumin may be a marker for more severe disease, immunosuppression associated with undernutrition preceding infection with sars-cov- could exacerbate the severity of covid- . , undernutrition is thought to have led to excess mortality with both the and h n influenza pandemics. , given relatively high rates of undernutrition among children in lmics ( . %), an association between undernutrition and clinical severity of covid- could increase the proportion of severe illness above current predictions, particularly among children. although sars-cov- has spread globally, our understanding of the epidemiology and clinical course of covid- in countries with substantial burdens of malaria and ntds is just beginning, in part because community transmission generally started later in these countries and because testing for sars-cov- is limited in most lmics. although current predictive models suggest lower mortality rates in lmics than in high-income countries, if coinfections with malaria or parasitic ntds increase complications with sars-cov- infections and there is a shift in the age pattern of comorbidities to younger ages, then the burden of covid- in lmics may be substantially worse than predicted, and potentially higher than the burden in high-income countries. if a shift to a th response is more common, and if that shift provides some protection from severe disease while reducing long-term immunity or increasing the time frame of viral shedding, the epidemiology of covid- in lmics could be substantially different from what has been seen elsewhere. rapidly developing surveillance platforms to monitor signals of sars-cov- coinfection with malaria or other ntds will be critical. one early indication of a potential interaction would be a shift in the age pattern of severe covid- , with higher rates of clinical disease in children than has been observed in china, europe, or north america. however, more definitive information on coinfections and outcomes will be needed to interpret such shifts. efforts to characterize covid- cases in lmics, such as the who first few x cases protocol, and addition of sars-cov- testing to influenza sentinel surveillance could be expanded, based on local prevalence of malaria and ntds, to include testing for malaria and ntds. such additional testing could help determine rates of coinfection and compare severity of outcomes by infection status. additional efforts to more carefully describe the clinical impacts of coinfections can follow. these efforts are important to understanding the potential impact of covid- on lmics and for mitigating against the worst outcomes. who coronavirus situation report- effect of the 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goals: indicator . . -prevalence of undernourishment age-dependent effects in the transmission and control of covid- epidemics. supplementary information. london, united kingdom: london school of hygiene and tropical medicine world health organization, . the first few x cases and contacts (ffx) investigation protocol for coronavirus disease (covid- ) world health organization, . operational considerations for covid- surveillance using gisrs report of the committee on infectious diseases this is an open-access article distributed under the terms of the creative commons attribution (cc-by) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. key: cord- -h zpb authors: gautret, philippe; parola, philippe; wilson, mary elizabeth title: fever in returned travelers date: - - journal: travel medicine doi: . /b - - - - . - sha: doc_id: cord_uid: h zpb predominant causes of fever vary by different geographic areas of exposure. malaria is the most common overall cause of systemic febrile illness in travelers returning from tropical areas; dengue is the most common cause in travelers to some regions. the approach to a febrile patient must consider travel and exposure history, incubation period, mode of exposure, and impact of pretravel vaccination. initial symptoms of self-limited and life-threatening infections may be similar; focal signs and symptoms can help to limit the differential diagnosis. routine laboratory results can provide clues to the final diagnosis. while fever may be the manifestation of a self-limited infection, it can also presage an infection that could be rapidly progressive and lethal. international travel expands the list of infections that must be considered but does not eliminate common, cosmopolitan infections. initial attention should focus most urgently on infections that are treatable, transmissible, and that may cause serious sequelae or death. the characteristics of the places visited and the recency of travel will affect the urgency and extent of the initial workup. the recent emergence of the middle east respiratory syndrome coronavirus (mers-cov) in the arabian peninsula and of ebola in west africa and the recent epidemics of chikungunya and zika virus diseases underline the necessity of being aware of the possible implication of emerging pathogens in imported fever. this chapter will focus on identifying the cause of fever in a returned traveler. the reader should refer to other sources for the specifics of therapy. fever in the absence of other prominent findings has been reported in %- % of european and american travelers to developing countries. among american travelers who traveled for months or less to developing countries, % reported fever unassociated with other illness. these results are similar to those reported by steffen et al. in which of (almost %) of swiss travelers with short-term travel to developing countries reported "high fever over several days" on questionnaires completed several months after return. of those with fever, % reported fever only while abroad, % had fever while abroad and at home, and % had fever at home only. analysis of the geosentinel surveillance network database found that % of ill returned travelers seeking care at a geosentinel clinic had fever as a chief reason for seeking care. among patients with travel-related hospitalization, febrile illnesses predominated, accounting for % of admissions in a study from israel. findings from eight studies, each with at least cases, that examined causes of fever after tropical travel are shown in table . . [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] the geographic region of exposure helps to explain the marked differences in the relative likelihood of various diagnoses, as has been shown in a study by freedman et al. malaria was the most common diagnosis among those requiring hospitalization for fever in most recently published series. in a geosentinel study including cases of potentially life-threatening tropical diseases, % of which had fever as a symptom, % were caused by malaria ; in the study by bottieau and colleagues falciparum malaria was the only tropical disease that was fatal (n = ). in a geosentinel study % of febrile illnesses were caused by infections that are preventable with vaccines or specific chemoprophylaxis (e.g., falciparum malaria). common cosmopolitan infections were found in % of returned febrile travelers in the bottieau study. infections, such as respiratory tract infections, hepatitis, diarrheal illness, urinary tract infections, and pharyngitis, with a broad or worldwide distribution, account for more than half of fevers in some series, and the cause of fever remained undefined in about one-quarter of cases. , , while, overall, malaria is the most common specific infection causing systemic febrile illness, dengue fever, mononucleosis, rickettsial infections, and enteric fever are also important infections. their relative rank varies by geographic location, with top three diagnoses being falciparum malaria, rickettsial infections, and dengue after travel to sub-saharan africa; dengue, falciparum, and vivax malaria after travel to southeast asia; enteric fever, dengue, and vivax malaria after travel to south central asia; and dengue, vivax malaria, and enteric fever after travel to latin america and caribbean. leptospirosis is likely underrecognized because of difficulty in confirming the diagnosis in many laboratories. the major increase in chikungunya virus infections in indian ocean islands, asia, and now the americas has been reflected in an increase in cases in travelers to those regions (and even local spread of infection introduced by travelers in europe). incubation time is a valuable tool in evaluating a febrile patient. knowledge of the incubation periods can allow one to exclude infections that are not biologically plausible. for example, dengue fever typically has an incubation of - days. thus fever that begins > weeks after return from thailand is not likely to be related to dengue fever. remote travel is sometimes relevant, but most severe, acute life-threatening infections result from exposures that have occurred within the past months. important treatable infections that may occur > months after return include malaria, amebic liver abscess, and visceral leishmaniasis. in the study by o'brien et al. analyzing patients hospitalized with fever after travel, % were seen within months of return from travel; in the study by bottieau et al. of patients referred for fever after tropical travel, fever occurred during travel or within month of return home in %. although the initial focus should be on travel within the past - months, the history should extend to include exposures a year or more earlier, if the initial investigation is unrevealing. more than a third of malaria-infected travelers in a study from israel and the united states had illness that developed > months after return from endemic areas. onset of illness > months after return occurred in . % of malaria patients reported to the cdc in . table . lists many of the infections seen in travelers by time of onset of symptoms relative to the exposure and the initial clinical presentation. in assessing potential incubation period one must take into account the duration of the trip (and points of potential exposure during travel) and time since return. the fever pattern and clinical findings for many infections are similar. relevant exposures can also occur in transit (e.g., on an airplane flight or cruise ship). during the workup the clinician should keep in mind that fever after exotic travel may reflect infection with a common, cosmopolitan pathogen acquired during travel or after return home. at the same time it should be noted that unfamiliar infections can be acquired in industrialized countries (such as plague, rocky mountain spotted fever, tularemia, lyme disease, hantavirus pulmonary syndrome in north america, and visceral leishmaniasis, hemorrhagic fever with renal syndrome and other hantaviral infections, and tickborne encephalitis in europe). a detailed review of the clinical course, supplemented by the physical examination and laboratory data, will help to determine more likely causes and also to identify any infections that might require urgent interventions, hence expedited diagnostic studies. the process involved in the evaluation can be summarized in the following questions: the course of medical care, patients may become colonized or infected with bacteria that are extremely resistant to usual antibiotic therapy, as has recently been reported with the new delhi metallo-β-lactamase resistance mechanism, or they may have other hospital-acquired infections. the history should include a review of pretravel vaccines, including dates of vaccination, types of vaccines received, and number of doses for multidose vaccines. vaccines vary greatly in efficacy, and knowledge of vaccine status can influence the probability that certain infections will be present. for example, hepatitis a and yellow fever vaccines have high efficacy and only rare instances of infection have been reported in vaccinated travelers. in contrast, the typhoid fever vaccines (oral and parenteral) give incomplete protection. the protective efficacy with the available typhoid vaccines was estimated to be %- % in field trials in endemic regions. many febrile infections are associated with focal signs or symptoms, which may help to limit the differential diagnosis. undifferentiated fever can be more challenging. the following sections discuss common infections that can be acquired by a single bite of an infective arthropod, ingestion of contaminated food or beverages, swimming in contaminated water, or from direct contact with an infected person or animal are most often seen in short-term travelers. casual sexual contact with new partners is common in travelers ( %- % among short-term travelers) and inquiry about sexual exposures should be included as part of the history of an ill traveler. a canadian study found that % of travelers reported sex with a new partner, or potential exposure to blood and body fluids through injections, dental work, tattoos, or other skin-perforating procedures during international travel. thus history is important to review even in returned travelers who are not acutely ill. in many instances travelers will be unaware of exposures. for example, patients with mosquito-borne and tickborne infections may not recall any bites. in contrast, patients who have had freshwater exposure (such as swimming, wading, bathing, or rafting) that places them at risk for schistosomiasis will typically recall the exposure with focused questioning, though they may have been unaware that the exposure carried any risk for infection. the provider should also inquire about medical care during travel. travel for the purpose of seeking medical care (medical tourism) has expanded; travelers may undergo extensive surgery including cardiac surgery and organ transplantation overseas. in was . % in persons with prior dengue infection who became infected with a new serotype. diagnosis is usually confirmed by serologic tests; viral isolation or detection of viral ribonucleic acid (rna) by polymerase chain reaction (pcr) is available in some laboratories. because specific igm antibodies take several days to develop (usually present by day of illness), serologic diagnosis may not be possible in the early febrile period. igg antibody response can be difficult to interpret because of extensive cross reactions with other flaviviruses (e.g., yellow fever, japanese encephalitis, west nile, zika). in recent years, several diagnostic methods, including real-time pcr (rt-pcr) and ns antigen detection, have been proposed to optimize the early diagnosis of denv in travelers. however, it is likely that only a minority of cases that occur in travelers are documented. a recent prospective study of dutch travelers found that seroconversion to denv occurred in . % (incidence was . per person-months). in the geosentinel database, confirmed or probable dengue fever was the most common specific diagnosis in patients with febrile systemic illness who had traveled to tropical and subtropical areas in the caribbean, south america, south central and southeast asia. in , dengue was the second most frequent cause of fever among patients with travel-associated health complaints seen in geosentinel european sites (no dengue hemorrhagic fever/dengue shock syndrome), a significant increase over . chikungunya. chikungunya (chik) fever is a tropical arboviral disease responsible for acute polyarthralgia, which can last for weeks to months. after half a century of focal outbreaks in africa and asia, the disease has emerged or reemerged in many parts of the world in the past decade, and has unexpectedly spread, with large outbreaks in africa, around the indian ocean, in the americas, and rare autochthonous transmission in temperate areas. it has now become an important global public health problem, with several ongoing outbreaks occurring worldwide. since the beginning of this outbreak, several million cases of chikungunya virus disease have occurred in autochthonous populations and in travelers who were diagnosed after they returned home from epidemic areas. chik virus, usually transmitted by a. aegypti mosquitoes, has now been repeatedly associated with a new vector, a. albopictus (the "asian tiger mosquito"), which has spread into tropical and subtropical areas previously occupied predominantly by a. aegypti. introduction into europe and spread has been described. zika. zika viral infection is a tropical arboviral disease usually transmitted by a. aegypti and a. albopictus mosquitoes and responsible for acute fever. zika virus has spread rapidly throughout latin america and the caribbean since its initial identification in the americas in brazil in . although infections are asymptomatic or relatively mild in approximately % of persons, severe complications have been described, including guillain-barré syndrome, myelitis, and encephalitis; miscarriage, prematurity, and multiple fetal neurologic and developmental abnormalities. common symptoms in a recent series of travel-associated cases included exanthema ( %), fever ( %), and arthralgia ( %). given the clear evidence of different methods of sexual transmission of zika virus, infected travelers should be counseled on the need for and duration of barrier contraception to limit onward sexual transmission of the virus. rickettsial infections are widely distributed in developed and developing countries and often named for a geographic region where they are found, though names can mislead. rickettsial diseases are increasingly being recognized among international travelers. a recent study of ≈ returnees with fever as a chief reason to clinical presentations, with focus on more common diseases causing each. other chapters provide more detailed discussions of diarrhea, skin diseases, and respiratory diseases. always look for malaria. malaria remains the most important infection to consider in anyone with fever after visiting or living in a malarious area. in nonimmune travelers falciparum malaria can be fatal if not diagnosed and treated urgently. although most patients with malaria will report fever, as many as % or more may not have fever at the time of initial medical evaluation. risk of malaria varies greatly from one endemic region to another, but in general risk is highest in parts of sub-saharan africa; most severe and fatal cases in travelers follow exposure in this region. tests to look for malaria should be done urgently (same day) and repeated in - hours if the initial blood smears are negative. in recent years rapid diagnostic tests for malaria have become valuable tools for the diagnosis of malaria in both endemic and nonendemic areas. prompt evaluation is most critical in persons who have visited areas with falciparum malaria in recent weeks. in the united states in , % of reported patients with acute falciparum malaria had onset of symptoms within a month of return to the country; another % had onset of illness before arriving in the country. use of chemoprophylaxis may ameliorate symptoms or delay onset. no chemoprophylactic agent is % effective, so malaria tests should be done even in persons who report taking chemoprophylaxis. many antimicrobials (e.g., tmp-smx, azithromycin, doxycycline, clindamycin) have some activity against plasmodia. taking these drugs for reasons unrelated to malaria may delay the onset of symptoms of malaria or modify the clinical course. although fever and headache are commonly reported in malaria, gastrointestinal (gi) and pulmonary symptoms may be prominent and may misdirect the initial attention toward other infections. thrombocytopenia and absence of leukocytosis are common laboratory findings. a prospective study of travelers and migrants with suspected malaria found white blood cell (wbc) count < , cells/l, platelet count < , /µl, hemoglobin < g/dl, and eosinophils < % to be associated with malaria parasitemia. dengue. dengue, a mosquito-transmitted flavivirus that exists in four serotypes, is the most common arbovirus in the world. it is increasing in incidence in endemic areas and is an increasingly common cause of fever in returned travelers. , dengue is found in tropical and subtropical regions throughout the world. among travelers, dengue is seen most often in visitors to southeast asia and latin america (including the caribbean) and infrequently in travelers to africa, though infections may be underrecognized. because humans are the main reservoir for the dengue virus (denv), which is transmitted primarily by the aedes aegypti mosquito that inhabits urban areas and lives in close association with humans, travelers visiting only urban areas can become infected. symptoms of dengue, also known as breakbone fever, typically begin - days (range - days) after exposure. common findings are fever, frontal headache, and myalgia. approximately % of patients have skin findings, which can be a diffuse erythema or a maculopapular or petechial eruption. intense itching may be present toward the end of the febrile period. leukopenia, thrombocytopenia, and elevated transaminases are common laboratory findings. the most serious forms of infection-dengue hemorrhagic fever (dhf) and dengue shock syndrome (dss)-in many studies have been observed more often in persons who have a second dengue infection with a different serotype. in a well-characterized outbreak in cuba, . % of dhf/dss cases were in persons with a prior dengue infection. the attack rate of dhf/dss suspicion of intestinal perforation or other complication. diagnosis should be confirmed by recovery of salmonella typhi (or s. paratyphi) from blood or stool. culture of bone marrow aspirate may have a higher yield than blood or feces but is generally not favored by clinicians and patients. serologic tests lack sensitivity and specificity. increasing resistance of s. typhi to many antimicrobials makes it important to isolate the organism and to do sensitivity testing. the emergence of multidrug resistance and decreased ciprofloxacin susceptibility in salmonella enterica serovar typhi in south asia have rendered older drugs, including ampicillin, chloramphenicol, trimethoprim sulfamethoxazole, ciprofloxacin, and ofloxacin, ineffective or suboptimal for typhoid fever. multiple studies have identified the indian subcontinent as a destination with relatively high risk for enteric fever in travelers, especially those visiting friends and relatives (vfrs). the efficacy of typhoid vaccines in published studies varies widely depending on the type of vaccine, number of doses, and population studied. as noted, the efficacy of commonly used vaccines may be %- %. the important observation for clinicians evaluating returned travelers is that typhoid fever remains a concern (albeit lower) in persons who have received a typhoid vaccine. infections with s. paratyphi may be relatively more common as a cause of typhoid fever in vaccinated populations because vaccine protects mainly against s. typhi. notably, the course of s. paratyphi a was not found to be milder than that of s. typhi infection. leptospirosis. although leptospirosis has a broad geographic distribution, infections in humans are more common in tropical and subtropical regions. recreational activities of travelers, including whitewater rafting in costa rica and other sports involving water exposures, have been associated with sporadic cases and large outbreaks. among competitive swimmers in the eco-challenge in malaysia in , % met the case definition for acute leptospirosis. although clinical manifestations may be protean, common findings include fever, myalgia, and headache. among cases reported from hawaii, % had jaundice and % conjunctival suffusion. other findings such as meningitis, rash, uveitis, pulmonary hemorrhage, oliguric renal failure, and refractory shock may be present. a summary of sporadic leptospirosis cases in travelers from europe and israel shows that the majority were reported from southeast asia, were male ( %), the disease was associated with water activities in %, and % were hospitalized with no mortality. multiple different serovars exist, and clinical presentation and severity vary with infecting serovar. in israeli travelers % had severe leptospirosis, usually associated with ictero-hemorrhagic serogroup. owing to lack of sensitive and specific diagnostic tests to confirm infection early in the course in most institutions, early empiric therapy is recommended for suspected infection, especially if severe. agents used include doxycycline (and other tetracyclines), penicillins, and ceftriaxone. follows exposure to fresh water infested with cercariae that penetrate intact skin. the disease, seen primarily in nonimmunes, manifests - weeks after exposure. clinical manifestations include high fever, myalgia, lethargy, and intermittent urticaria. dry cough and dyspnea, sometimes with pulmonary infiltrates, are noted in the majority of patients. eosinophilia, often high grade, is usually present. in one outbreak involving travelers the median duration of fever was days (range - days) and of had eosinophilia during the first weeks of infection. in most cases the disease is acquired in africa (not only sub-saharan); however, in the last decade an seek medical care suggested that % of imported fevers are caused by rickettsioses and that % of these patients are hospitalized. most infections are acquired in sub-saharan africa, where spotted fever group (sfg) rickettsioses are second only to malaria as the most commonly diagnosed diseases in returnees with systemic febrile illness. rickettsia rickettsii, the cause of rocky mountain spotted fever in the united states, is found throughout the americas from canada to brazil. rickettsial infections such as african tick-bite fever (r. africae), mediterranean spotted fever (r. conorii), and murine or endemic typhus (r. typhi) are important treatable infections in travelers. many additional rickettsioses have emerged throughout the world. these are being increasingly recognized in travelers, probably reflecting increased travel to high-risk areas, such as southern africa, and increased awareness among clinicians. , diagnosis is usually confirmed with serologic tests or molecular tools such as pcr-based assay on skin biopsies or after eschar swabbing. clinical presentations of the rickettsial infections are varied, depending on the species. most rickettsial infections are transmitted by arthropods, such as ticks and mites, and an eschar may mark the inoculation site. eschars are often small (< cm in diameter), asymptomatic, and may be overlooked. in south african tick-bite fever eschars are often multiple (> % of cases). rashes may be present, but many rickettsial infections (even among the sfg) are spotless. r. australis, r. africae, and rickettsialpox can cause a vesicular rash that may be mistaken for varicella, monkeypox, or even smallpox. high fever, headache, and normal or low wbc cell count and thrombocytopenia are characteristic. lymphadenopathy may be present. infections may be confused with dengue fever. rickettsiae multiply in and damage endothelial cells and cause disseminated vascular lesions. without treatment, the illness may persist for - weeks. response to tetracyclines is generally prompt. patients with suspected rickettsial infections should be treated empirically while awaiting laboratory confirmation. other tickborne infections, human monocytic ehrlichiosis, and human granulocytic ehrlichiosis (granulocytotropic anaplasmosis), are most commonly diagnosed in the united states but are also found in europe, africa, and probably asia. clinical findings include prominent fever and headache. these infections may also be associated with leukopenia and thrombocytopenia, and respond to treatment with tetracyclines. when epidemiologic and clinical aspects of rickettsial diseases were investigated in international travelers reported to the geosentinel surveillance network during - , ( . %) had spotted fever (sfg) rickettsiosis, ( . %) scrub typhus, ( . %) q fever, ( . %) typhus group (tg) rickettsiosis, ( . %) bartonellosis, ( . %) indeterminable sfg/tg rickettsiosis, and ( . %) human granulocytic anaplasmosis; ( . %) of sfg rickettsiosis cases were acquired in sub-saharan africa and were associated with higher age, male gender, travel to southern africa, late summer season travel, and travel for tourism. enteric fever. enteric fever (typhoid and paratyphoid fever) is another infection that causes fever and headache and can be associated with an unremarkable physical examination, though a faint rash (rose spots) may appear at the end of the first week of illness. laboratory findings include a normal or low wbc count, thrombocytopenia, and elevation (usually modest) of liver enzymes. gi symptoms such as diarrhea, constipation, and vague abdominal discomfort may be present, as well as dry cough. in contrast to the abrupt onset of fevers in dengue and rickettsial infections, the onset of typhoid fever may be insidious. leukocytosis in a patient with typhoid fever should raise countries and was responsible for an outbreak of eosinophilic meningoencephalitis in travelers to jamaica in . african trypanosomiasis (sleeping sickness), transmitted by an infective tsetse fly, initially causes a nonspecific febrile illness. a chancre marks the site of the bite. if untreated, trypanosomes can infect the cns and cause lethargy. several cases have been seen in travelers after exposures, especially in tanzania and kenya. patients with malaria, typhoid fever, and rickettsial infections often have severe headache, but cerebrospinal fluid (csf) is typically unremarkable in these infections. cerebral malaria causes altered mental status and can progress to seizures and coma. mefloquine taken for malaria chemoprophylaxis has rarely been associated with seizures and other neuropsychiatric side effects, but fever typically is absent. neuroschistosomiasis can be seen in travelers, but fever usually is not present at the time of the focal neurologic changes, caused by tissue reaction to ectopic schistosome egg deposition in the nervous system. sexually transmitted infections such as hiv and syphilis, whether acquired at home or during travel, can involve the cns. lyme and ehrlichiosis are other treatable infections that can cause prominent neurologic findings. other treatable infections that are unfamiliar to clinicians in many geographic areas include q fever, relapsing fever, brucellosis, bartonellosis, anthrax, and plague. diagnoses to be considered in patients with persistent or relapsing fevers include nonfalciparum malaria, typhoid fever, tuberculosis, brucellosis, cytomegalovirus (cmv), toxoplasmosis, louseborne relapsing fever (borrelia recurrentis), melioidosis (burkholderia pseudomallei), q fever (coxiella burnetii), visceral leishmaniasis, histoplasmosis (and other fungal infections), african trypanosomiasis, and infections that may be unrelated to exposures during travel, such as endocarditis. for fever with prominent respiratory symptoms, please refer to references - and chapter . results of routine laboratory findings may provide clues to the diagnosis in the febrile traveler. an elevated wbc count may suggest a bacterial infection, but a number of bacterial infections, such as uncomplicated typhoid fever, brucellosis, and rickettsial infections, are associated with a normal or low wbc count. in the past hepatitis a virus was the most common cause of hepatitis after travel to developing regions. with the wide use of the hepatitis a vaccine, acute hepatitis a now is seen primarily in persons who failed to receive vaccine (or immunoglobulin) before travel. hepatitis b remains a risk for unvaccinated persons. hepatitis e, transmitted via fecally contaminated water or food, clinically resembles acute hepatitis a. cases have been reported in travelers. mortality may be % or higher in women infected during the third trimester of pregnancy. many common as well as unusual systemic infections cause fever and elevation of liver enzymes. among those that may be a concern, depending on geographic exposures, are yellow fever, dengue and other hemorrhagic fevers, typhoid fever, leptospirosis, rickettsial infections, toxoplasmosis, q fever, syphilis, psittacosis, and brucellosis. transaminases are often elevated in these infections. parasites that directly invade the liver and bile ducts (e.g., amebic liver abscess and liver flukes) often cause right upper quadrant pain, tender liver, and elevated alkaline phosphatase. drugs and toxins (sometimes found in herbal drugs or nutritional supplements) can damage the liver, so a careful review of these agents should be part of the history. important focus was documented in laos with infection due to s. mekongi. amebic liver abscess. an amebic abscess can cause fever and chills that develop over days to weeks. although focal findings may not be prominent, %- % of patients will report abdominal discomfort and about %- % will have right upper quadrant tenderness on examination. extension of infection to the diaphragmatic surface of the liver may lead to cough, pleuritic or shoulder pain, and right basilar abnormalities on chest x-ray, which may initially suggest a pulmonary process. the abscess can be seen on ultrasound and serology for entamoeba histolytica is usually positive. several infections in addition to exotic infections such as ebola and marburg can cause fever and hemorrhage in travelers and many are treatable. ebola and marburg are transmitted mostly through direct contact with patient body fluids and are rarely seen in international travelers. during the recent ebola epidemic in west africa, falciparum malaria was the most frequent cause of fever in travelers to the affected area. leptospirosis, meningococcemia, and other bacterial infections can cause hemorrhage. rickettsial infections can produce a petechial rash or purpura, and severe malaria may be associated with disseminated intravascular coagulation. many viral infections, in addition to dengue, can cause hemorrhage. most are arthropod-borne (especially mosquito or tick) or have rodent reservoir hosts. among those reported in travelers are dengue fever (dhf), yellow fever, lassa fever, crimean congo hemorrhagic fever, rift valley fever, hemorrhagic fever with renal syndrome (and other hantavirus-associated infections), kyasanur forest disease, omsk hemorrhagic fever, and several viruses in south america (junin, machupo, guanarito, sabia). lassa fever responds to ribavirin therapy if started early. several of the viruses can be transmitted during medical care, so it is important to institute barrier isolation in a private room pending a specific diagnosis. identification of viral agents causing hemorrhage may require the assistance of staff working in special laboratories, such as one available at cdc. (assistance is available through the special pathogens branch, division of viral and rickettsial diseases, cdc, atlanta, ga - - and other specialized laboratories.) even when specific treatment is not available, good supportive care can save lives. neurologic findings in the febrile patient indicate the need for prompt workup. high fever alone or in combination with metabolic alternations precipitated by systemic infections can cause changes in the mental status in the absence of cns invasion. one must consider common, cosmopolitan bacterial, viral, and fungal infections that cause fever and cns changes. additional considerations in travelers include japanese encephalitis, rabies, west nile, polio, tickborne encephalitis, and a number of other geographically focal viral infections, such as nipah virus. outbreaks of meningococcal infections (meningococcemia and meningitis) have been associated with the annual hajj pilgrimage to mecca in saudi arabia. beginning in , for the first time ever, infection with neisseria meningitidis serogroup w- caused outbreaks of meningococcal disease in pilgrims and subsequently in their contacts in multiple countries. pilgrims vaccinated with the quadrivalent meningococcal vaccine (serogroups a, c, w- , and y) can still carry n. meningitidis in the nasopharynx. dengue fever can cause neurologic findings that mimic japanese encephalitis. in a study in vietnam, dengue-associated encephalopathy was found in . % of children admitted with dhf. meningitis may be present in leptospirosis. the parasite angiostrongylus cantonensis causes sporadic infection in many prompt diagnosis and urgent treatment may be necessary to save the patient's life. fig. . provides an algorithm for the approach to a febrile patient following travel. useful algorithms based on expert opinion and review of published literature are also available. , during the evaluation and treatment, the clinician should also keep in mind the public health impact. familiar infections (e.g., salmonellosis, campylobacteriosis, gonorrhea) may be caused by multidrug-resistant organisms. it is especially important to recognize the potential for multidrug resistance in infections, such as typhoid fever, that can be lethal. absence of response to what should be appropriate treatment should lead the clinician to consider drug resistance, the possibility of the wrong diagnosis, or the presence of two infections. particularly in patients with acute undifferentiated fever, rickettsial diseases must be considered, and patients with severe disease may be treated empirically. use of empirical doxycycline treatment for patients with fever of unknown origin should be discussed, especially when empirical treatment with β-lactams has failed or, in severe cases, in association with β-lactams. a number of case reports document the simultaneous presence of malaria and typhoid fever, amebic liver abscess and hepatitis a, and other dual infections. , conclusion it should be reminded that some febrile illnesses in travelers are still associated with high mortality and should be rapidly suspected and treated. place of exposure and local epidemiology are key elements in the diagnosis process. knowledge of the epidemiology of infections in a given geographic area is valuable, but detailed, up-to-date information about a specific location may be unavailable. electronic databases are a useful source of current information about disease outbreaks and alerts about antimicrobial resistance patterns. eosinophilia is sometimes an incidental finding on laboratory testing. when it is found in a person who has visited or lived in tropical, developing countries, it is a clue that should suggest several specific parasitic infections. for further details see chapter . a careful, complete physical examination should be carried out, looking with special care for rashes or skin lesions, lymphadenopathy, retinal or conjunctival changes, enlargement of liver or spleen, genital lesions, and neurologic findings. the initial laboratory evaluation in a febrile patient with a history of tropical exposures should generally include all or most of the following: • complete blood count with a differential and estimate of platelets • liver enzymes • blood cultures • malaria and dengue rapid diagnostic tests • urinalysis and urine culture • chest radiograph if malaria is suspected, it is essential not only to request the appropriate tests for malaria but also to make certain that tests are done expeditiously and by knowledgeable persons. in patients with diarrhea or gi symptoms (or if enteric fever is suspected), stool culture should be requested. in a patient with persisting fever a repeat physical examination will sometimes identify new findings (e.g., new rash, splenomegaly) that can provide useful clues to the diagnosis. table . lists tests used to diagnose common infections in febrile returned travelers. the process of travel may lead to medical problems. the immobility associated with travel may predispose to deep vein thrombosis; sinusitis may flare up during or after air travel, related to changes in pressure during ascent and descent. noninfectious disease causes of fever, such as drug fever, and pulmonary emboli, should also be considered if initial studies do not confirm the presence of an infection. in the study by bottieau et al. noninfectious causes accounted for . % of the fevers. spectrum of disease and relation to place of exposure among ill returned travelers geosentinel surveillance network. acute and potentially life-threatening tropical diseases in western travelers-a geosentinel multicenter study geosentinel surveillance network. geosentinel surveillance of illness in returned travelers infection with chikungunya virus in italy: an outbreak in a temperate region transmission of the severe acute respiratory syndrome on aircraft delayed onset of malariaimplications for chemoprophylaxis in travelers malaria surveillance-united states blood and body fluid exposure as a health risk for international travelers emergence of a new antibiotic resistance mechanism in india, pakistan, and the uk: a molecular, biological, and epidemiological study the effect of oral and parenteral typhoid vaccination on the rate of infection with salmonella typhi and salmonella paratyphi a among foreigners in nepal comparison of enteric-coated capsules and liquid formulation of ty a typhoid vaccine in a randomised controlled field trial illness after international travel approach to fever in the returning traveler health problems in a large cohort of americans traveling to developing countries health problems after travel to developing countries fever in returned travelers: results from the geosentinel surveillance network epidemiology of travel-related hospitalization fever in travelers returning from malaria-endemic areas: don't look for malaria only fever in returned travelers: a prospective review of hospital admissions for a year period etiology and outcome of fever after a stay in the tropics fever as the presenting complaint of travelers returning from the tropics fever in returned travelers: review of hospital admissions for a -year period prospective observational study of fever in hospitalized returning travelers and migrants from tropical areas fever in travelers returning from tropical areas: prospective observational study of cases hospitalised in marseilles assessment of the clinical presentation and treatment of cases of laboratory-confirmed leptospirosis in hawaii travel-associated zoonotic bacterial diseases travel-related leptospirosis in israel: a nationwide study outbreak of schistosomiasis among travelers returning from mali, west africa pulmonary manifestations of early schistosome infection among nonimmune travelers travel-related schistosomiasis acquired in laos amebic liver abscess geosentinel surveillance network. differential diagnosis of illness in travelers arriving from sierra leone prospective case-control study of encephalopathy in children with dengue hemorrhagic fever an outbreak of eosinophilic meningitis caused by angiostrongylus cantonensis in travelers returning from the caribbean cruise ships: high-risk passengers and the global spread of new influenza viruses influenza virus infection in travelers to tropical and subtropical countries outbreak of coccidioidomycosis in washington state residents returning from mexico update: outbreak of acute febrile respiratory illness among college students fungal infections among returning travelers an outbreak of acute pulmonary histoplasmosis in members of a trekking trip in martinique, french west indies running like water-the omnipresence of hepatitis e diagnostic significance of blood eosinophilia in returning travelers practice guidelines for evaluation of fever in returning travelers and migrants approach to fever in the returning traveler rickettsioses as causes of cns infection in southeast asia concurrent falciparum malaria and salmonella in travelers: report of two cases simultaneous amoebic liver abscess and hepatitis a infection difficulties in the prevention, diagnosis, and treatment of imported malaria evaluation of rapid diagnostic tests for malaria in swedish travelers clinical and laboratory predictors of imported malaria in an outpatient setting: an aid to medical decision making in returning travelers with fever travel-related dengue virus infection dengue in travelers dengue virus infection in africa epidemiologic studies on dengue in santiago de cuba, early diagnosis of dengue in travelers: comparison of a novel real-time rt-pcr, ns antigen detection and serology travel-related imported infections in europe chikungunya: its history in africa and asia and its spread to new regions in - chikungunya virus infection chikungunya virus, southeastern france zika virus geosentinel surveillance network. travel-associated zika virus disease acquired in the americas through february : a geosentinel analysis tick-borne rickettsioses around the world: emerging diseases challenging old concepts african tick bite fever in travelers to rural sub-equatorial africa rickettsia africae, a tick-borne pathogen in travelers to sub-saharan africa human ehrlichioses multicenter geosentinel analysis of rickettsial diseases in international travelers clinical importance of salmonella paratyphi a infection to enteric fever in nepal treatment of typhoid fever in the st century: promises and shortcomings typhoid and paratyphoid fever in travelers outbreak of leptospirosis among white-water rafters-costa rica update: outbreak of acute febrile illness among athletes participating in eco key: cord- - xlmep authors: onovo, a. a.; atobatele, a.; kalaiwo, a.; obanubi, c.; james, e.; gado, p.; odezugo, g.; magaji, d.; ogundehin, d.; russell, m. title: using supervised machine learning and empirical bayesian kriging to reveal correlates and patterns of covid- disease outbreak in sub-saharan africa: exploratory data analysis date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: xlmep introduction: coronavirus disease (covid- ) is an emerging infectious disease that was first reported in wuhan, china, and has subsequently spread worldwide. knowledge of coronavirus-related risk factors can help countries build more systematic and successful responses to covid- disease outbreak. here we used supervised machine learning and empirical bayesian kriging (ebk) techniques to reveal correlates and patterns of covid- disease outbreak in sub-saharan africa (ssa). methods: we analyzed time series aggregate data compiled by johns hopkins university on the outbreak of covid- disease across ssa. covid- data was merged with additional data on socio-demographic and health indicator survey data for of ssa countries that reported confirmed cases and deaths from coronavirus between february , through march , . we used supervised machine learning algorithm, lasso for variable selection and statistical inference. ebk was used to also create a raster estimating the spatial distribution of covid- disease outbreak. results: the lasso cross-fit partialing out predictive model ascertained seven variables significantly associated with the risk of coronavirus infection (i.e. new hiv infections among pediatric, adolescent, and middle-aged adult plhiv, time (days), pneumococcal conjugate-based vaccine, incidence of malaria and diarrhea treatment). our study indicates, the doubling time in new coronavirus cases was days. the steady three-day decrease in coronavirus outbreak rate of change (roc) from % on march , to % on march , indicates the positive impact of countries' steps to stymie the outbreak. the interpolated maps show that coronavirus is rising every day and appears to be severely confined in south africa. in the west african region (i.e. burkina faso, ghana, senegal, cotediviore, cameroon, and nigeria), we predict that new cases and deaths from the virus are most likely to increase. interpretation: integrated and efficiently delivered interventions to reduce hiv, pneumonia, malaria and diarrhea, are essential to accelerating global health efforts. scaling up screening and increasing covid- testing capacity across ssa countries can help provide better understanding on how the pandemic is progressing and possibly ensure a sustained decline in the roc of coronavirus outbreak. funding: authors were wholly responsible for the costs of data collation and analysis. on jan , , who declared the current novel coronavirus disease epidemic a public health emergency of international concern . as of march , , the number of covid- cases surpassed , globally, and the epidemic registered a total of , cases and deaths in sub-saharan africa (ssa). at this time, of ssa's countries [excluding burundi, comoros, lesotho, sierra leone, south sudan and sao tome and principe] all reported confirmed cases of coronavirus and imported transmission as the major mode of spread. despite aggressive response by ssa countries to stymie the outbreak, the number of reported new cases and deaths continue to increase. as of march , , south africa is the only country with more than , cases, and eight countries: burkina faso, cameroon, cote d'ivoire, senegal, ghana, mauritius and nigeria including south africa account for % of ssa's covid- disease outbreak ( figure ). as reported by huang et al, patients with covid- present primarily with fever, myalgia or fatigue, and dry cough. although most patients are thought to have a favorable prognosis, older patients and those with chronic underlying conditions may have worse outcomes. certain epidemiological features and clinical characteristics of covid- have been previously reported , . however, these findings were based on prediction models or studies from america, asia and europe countries, and the use of these findings might be inappropriate for ssa context. the spatial distribution pattern of coronavirus disease outbreak and the risk factors leading to poor clinical outcomes have not been well understood and delineated. in this study, we employed the exploratory data analysis (eda) technique to maximize insights from our study data, uncover patterns and summarize risk factors associated with the coronavirus disease outbreak in ssa. eda is an approach for data analysis that employs a variety of technique for summarizing and visualizing important characteristics of a dataset. this will be the first study to use supervised machine learning algorithm, "least absolute selection shrinkage operator" (lasso) regression as the principle method for variable selection (predict important variables associated with covid- ) and for statistical inference (confirm or establish relationship of risk factors and covid- disease); and empirical bayesian kriging (ebk) used to create a raster estimating the temporal spatial distribution of covid- disease outbreak in ssa. we collected and analyzed time series aggregate data on the , confirmed cases and deaths of covid- disease outbreak across ssa between february , through march , . according to the united nations, ssa consists of all african countries that are fully or partially located south of the sahara. we focused on of africa's countries excluding algeria, djibouti, egypt, libya, morocco and tunisia, in accordance with the world bank lists of countries in ssa. we accessed the covid- data resource hub developed by the tableau community and utilized nearreal time data compiled by johns hopkins university (jhu) and includes data from world health organization (who) and the centers for disease control and prevention (cdc). additional data from socio-demographic and health indicator surveys was derived from resources of the world bank, unicef, who and unaids. this additional data was merged with the jhu covid- data to establish the dataset that was used for this study. the dataset included the most recent and available data across ssa, and period of the data spanned between and . for data on health systems performance index, these was derived from the who publication in entitled "measuring overall health systems performance for countries". the target variable included in the supervised machine learning model was confirmed cases of coronavirus disease. the target variable was log-transformed to control for skewness and ensure effective linear relationship with the independent variables. explanatory or independent variables in the model included total population, gdp per capita, percentage of population with access to electricity, percentage of population with access to basic drinking water, incidence of malaria (per , population at risk), percentage of men and women aged and over who currently smoke any tobacco product, diarrhea treatment (percent of children under receiving oral rehydration and continued feeding), percentage of infants who received third-dose of pneumococcal conjugate-based vaccine (pcv), incidence of tuberculosis (per , people), percent out-of-pocket expenditure, life expectancy at birth, health systems performance index, estimated incidence rate (new hiv infection per , uninfected population, children aged - years), estimated incidence rate (new hiv infection per , uninfected population, adolescents aged - years), hiv prevalence among people aged - years, transmission classification of covid- disease ( =imported, =local transmission), income group ( =high income, =low income, =lower middle income, =upper middle income), geocoordinates of ssa countries (latitude and longitude), and time (days) between the first and last reported coronavirus cases. these variables were included in the analyses because recent research on coronavirus has found that biological variables such as pneumonia, malaria, and diarrhea , socio-demographic variables like age , access to comprehensive health care system were associated with the transmission of coronavirus. consequently, other important variables particularly, cancer, diabetes or coronary heart disease (chd) were not available for analysis. we used lasso regression a supervised machine learning method for .) prediction and model selection, and .) inferential statistics. for prediction and model selection, we used three separate selection models available in statamp v. . these models were cross-validation (cv), adaptive lasso and minimum bayesian information criterion (bic). in running lasso, the dataset was split into two sample groups; group was training datasets we used to select our model, and group our testing datasets we used to test the prediction. we used lasso because of its greater prediction accuracy and increased model interpretability. for the inferential statistics, we used the cross-fit partialing out lasso technique to estimate the coefficients, robust standard errors, p-values and confidence intervals of the specified variables of interest while the other covariates were selected as controls in the model. we georeferenced all confirmed cases and deaths from coronavirus that was reported across countries and performed three analyses. first, we constructed maps of coronavirus infection across three different . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . timepoints; time (march , ), time (march , ) and time (march , ) and overlaid the coronavirus transmission classification type. second, we used spatial autocorrelation (global moran´s i) statistics to measure the degree, to which coronavirus infection is clustered, dispersed or randomly distributed. the expected value under the null hypothesis is that "there is no pattern of coronavirus infection in selected ssa countries". moran's i values range from - indicating perfect dispersion to + indicating perfect spatial clustering. a zero moran's i value indicates a random spatial distribution. third, we used ebk technique in the geostatistical analyst tool of arcgis . software to estimate the distribution of coronavirus across ssa. we analyzed of ssa countries that reported confirmed cases and deaths from coronavirus between february , through march , . we plotted a matrix graph to explore the strength and association between continuous variables and covid- . overall, in figure a, the matrix graph showed that a majority, % ( / ) of the continuous variables indicated strong to moderate positive linear relationships, while two variables, out-of-pocket expenditure and hiv incidence rate in children aged - years showed strong negative linear relationships. prevalence of smoking was weakly correlated with coronavirus. approximately % ( / ) of the ssa countries had missing information on smoking prevalence and this may have impacted on this variable as evident with the significant chi-square goodness of fit χ ( ) = . , p= . . all other variables included in the analysis had complete data for almost all countries, however, in few countries where data was missing, this was ≤ %. in figure b , spearman's rank-order correlation was run to determine the relationship between the two categorical variables and covid- . there was a moderate, positive correlation between transmission classification and covid- disease, (rs ( ) = . , p = . ), with transmission classification explaining % of the variance in covid- disease. we calculated time (days) between the first and last reported coronavirus cases by country and plotted a quadrant chart of confirmed covid- cases against time. in figure , majority, ( %) of the countries reported imported transmission as the main way coronavirus is spreading χ ( ) = . , p= . , while south africa, ghana, senegal, cameroon, kenya, rwanda and liberia indicated local transmission as the source of covid- transmission. there was a strong positive correlation between time (days) and covid- , (rs ( ) = . , p = . ), with time (days) explaining % of the variation in covid- . the result is suggestive that new cases of coronavirus tend to rise with rise in time (days). cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . clusters were identified and south africa the only country in cluster ( figure ) . overall, the result revealed an upward trend and similarities in the way coronavirus is presenting across certain countries in ssa. lasso for prediction and model selection all the explanatory variables, continuous and categorical were included as possible contributors to the lasso model evaluating association with coronavirus disease. the rows for all three models were sorted so that the variables with the highest standardized coefficients are listed on top, (table a. ). ten explanatory variables with the highest relative importance were simultaneously selected by all the three learning techniques. these were hiv incidence rate among adolescence aged - years, hiv incidence rate among children aged - years, time (days), hiv prevalence among persons aged - years, infants who received third-dose of pneumococcal conjugate-based vaccine, incidence of hiv among individuals aged - years, incidence of malaria (per , persons at risk), incidence of tb (per , people), smoking prevalence ( years and above) and diarrhea treatment (children under- years). we accessed the goodness-of-fit over our training sample and testing sample. (table b .) show that the adaptive lasso model has the smallest mean square error (mse), . * - and the largest r-squared ( %) in the testing datasets. the top ten important variables selected by adaptive lasso was included as variables of interest in the lasso for inference model using the cross-fit partialing out technique. the remaining variables included in the model were trained as controls. the lasso regression for inference established that hiv incidence rate among adolescence aged - years (p= . ), hiv incidence rate among children aged - years (p= . ), time (p= . ), infants who received third dose of pneumococcal conjugate-based vaccine (p= ), incidence of hiv among individuals aged - years, (p= . ), incidence of malaria (p= . ) and diarrhea treatment (p= . ) could statistically significantly predict coronavirus disease outbreak in ssa (table ) . for better interpretation of results, we exponentiated the coefficients, subtracted the output from and expressed the new coefficients as percentages. the exponentiated values are included in the lasso for inferential statistics table. all seven variables added statistically significantly to the prediction, p < . . the global spatial autocorrelation moran´s i statistics confirmed the random distribution pattern of coronavirus outbreak among ssa countries ( figure figure shows that coronavirus is increasing per day and spreading outwards. coronavirus appears to be severally confined in south africa and increasing in the west african region (i.e. burkina faso, ghana, senegal, cote d'iviore, cameroon, and nigeria). figure shows that coronavirus deaths tend to be concentrated in western african regions relative to central and southern african regions. . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . of the estimated , new hiv infections that occur globally each day, two out of three are in sub-saharan africa . currently in ssa region there is paucity of research on coronavirus and no documented evidence on how coronavirus disease is affecting or behaving in people living with hiv (plhiv). however, global and local hiv organizations and public health experts believe plhiv not on treatment, has cd count < copies/cell, a recent opportunistic infection and /or not virally suppressed may be at greater risk of coronavirus infection . our study indicated that hiv incident rate among pediatrics aged - years, adolescents aged - years and middle-aged adults - years were good predictors of coronavirus. our research shows that new hiv infections raise the risk of coronavirus infection by . percent (p= . ) in pediatrics - years, . percent (p= . ) in adolescents aged - years and percent (p= . ) in middle-aged adults - . this finding collaborates with a recent study by su l et al , which showed that children and youth are also infected and can spread coronavirus. a retrospective study by tang a et al revealed that there had been several and far more severe pediatric cases of covid- in wuhan hospitals than reported. pneumonia affects children and families everywhere but is most prevalent in south asia and sub-saharan africa . people who get pneumonia may also have a condition called acute respiratory distress syndrome (ards). it's a disease that comes on quickly after infection from coronavirus and causes breathing problems. the pneumonia vaccine protects against a kind of bacteria (streptococcus pneumoniae), not the coronavirus, but can support overall health, especially in older individuals or people who have a weak immune system . more than three-quarters, % ( % ci: . - . ) of surviving infants to months across ssa received the third dose of pneumococcal conjugate-containing vaccine (pcv). our study indicates that surviving infants who received pcv were good predictors of coronavirus disease. it is evident from our results that increased cases of pneumonia among infants increases risk of infection from coronavirus by . % (p= . ). malaria infection is common in sub-saharan africa, and it is often stated that the continent bears over percent of the global p. falciparum burden , and, generally, young children bear the brunt of the mortality burden. in , four ssa countries; nigeria, democratic republic of the congo, mozambique, and uganda accounted for nearly half of all malaria cases worldwide. according to our results, incidence of malaria was per , persons (iqr: - ) across ssa, and study results suggest that for every oneunit increase in the incidence of malaria, the risk of covid- disease increases by . % (p= . ). diarrheal disease is the second leading cause of death in children under five years old and is responsible for killing around , children every year. recent studies have demonstrated that there is an association between diarrhea and coronavirus transmission. a study among covid- patients at three hospitals in wuhan, china, indicated that among all patients who presented with digestive symptoms ( patients), about ( %) had diarrhea, and of these, ( %) experienced diarrhea as the first symptom of their illness . in our study, less than half % ( %ci: - ) of children under with diarrhea received oral rehydration salts (ort) or the recommended homemade fluids across ssa. study result suggests that for every one-unit increase in diarrhea cases among children under- , the risk of coronavirus increases by . % (p= . ). . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . in terms of growth rate, the trend cluster analysis from our study suggests a combination of linear and exponential growth trends across ssa. the trend in new coronavirus cases appears to be doubling in south africa at every time increment compared to the other countries demonstrating an exponential trend. for countries in cluster and in cluster the trend is linear suggesting increases by less than cases per day. countries in cluster and on the average indicated increases by cases or more at every time increment. spontaneous transitions from low (reporting cases on average) to high clusters (reporting more than cases on average) was evident among countries previously in cluster (i.e. cote d'iviore, cameron, nigeria and ghana). in the coming weeks, our study suggests, that countries in cluster ; burkina faso, ghana, senegal, cote d'iviore, mauritius, cameroon, nigeria, congo (kinshasa) and rwanda are the most likely to present an exponential trend growth similar to south africa in cluster . our study indicates, the doubling time in new coronavirus cases reported across ssa is days. covid- who surveillance reports indicate that the ssa countries have responded actively to the pandemic since the first case identified on february . many countries are requesting individuals to stay at home in self-quarantine, closing borders and imposing lockdowns and curfews. schools were ordered to close in the nigerian federal capital territory of abuja after only eight cases were confirmed nationwide in the month of february . south africa banned visitors from high-risk countries, closed schools and quickly opened drive-through testing centers in johannesburg. the steady decline in the roc of coronavirus as indicated in our study from % on march , to % on march , suggests that measures instituted by countries to stem the outbreak is showing signs of future success. this finding fits with a recent modeling study showing that a combination of multiple approaches (i.e. social distancing, home isolation of cases, augmented by school and university closures) has a substantial effect on slowing coronavirus transmission in a short term. on the other hand, the declining roc may be attributed to low testing capacity in ssa. marius gilbert et al, in a modelling study highlighted differences in african countries capacity to respond to the coronavirus outbreak. countries with the highest importation risk (ie, egypt, algeria, and south africa) have moderate to high capacity to respond to outbreaks. countries at moderate risk (ie, nigeria, ethiopia, sudan, angola, tanzania, ghana, and kenya) have variable capacity and high vulnerability . so far in ssa only a handful of countries (i.e. south africa, senegal, ghana and nigeria) have provided official figures on covid- testing data. spatial autocorrelation analysis using the global moran's i statistics indicated that coronavirus was spreading randomly across ssa. a major limitation in this study was that geocoordinate data used for this analysis represents locations of ssa countries not necessarily where covid- disease was detected, and this may have influenced results. at the time of this analysis, geocoordinates of counties, districts, and/or testing locations for coronavirus were not publicly available. the interpolated maps in our study show that coronavirus is increasing and spreading outwards per day to countries in central africa and the virus appears to be severely confined in south africa and in the west african region. the interpolated maps also suggest that countries in the west african region are most likely to repot increased number of deaths in the coming weeks compared to countries in central and southern africa. in conclusion, lasso was a good fit for variable selection and inference. the lasso regression model indicated that new hiv infections among pediatrics, adolescents and middle-aged adult plhiv, time, pneumococcal conjugate-based vaccine, incidence of malaria and diarrhea treatment could significantly predict coronavirus disease in ssa. this study can be repeated using more detailed patient-level granular data to provide more insight into the essential characteristics of patients diagnosed with covid- . our study suggests that experiences learned from the hiv epidemic can be applied to the fight against covid- . as in the aids response, governments should work with communities and civil society organizations to find local solutions, and health interventions delivered in an integrated manner. integrated and efficiently delivered interventions to reduce hiv, pneumonia, malaria, and diarrhea are essential to accelerating global health efforts. lessons learned from the hiv epidemics have shown that restrictive, stigmatizing and punitive measures can lead to significant human rights abuses, with disproportionate effects on already vulnerable communities. they can often undermine epidemic responses, sending people with symptoms underground and failing to address the underlying barriers that people face in attempting to protect their own health and that of their community. an approach that moves away from compulsory restrictions towards a focus on reaching and serving those who are most vulnerable, scaling up screening and testing for those most in need, empowering people with knowledge and tools to protect themselves and others (e.g. for covid- , increased social/spatial spacing) and the removal of barriers, mirrors the learnings from the hiv response. the consistent three days decline in the roc of coronavirus outbreak from % to % is suggestive of the positive effect of measures instituted by countries to stymie the outbreak. to gain better understanding on how the pandemic is progressing, and possibly ensure a sustained decline in the roc of coronavirus outbreak, all countries should scale screening and increase their testing capacity and provide detailed and reliable testing data. recent non-randomized control studies have confirmed that hydroxychloroquine and azithromycin have been found to be efficient on sars-cov- and reported to be efficient in chinese cov- patients. we propose a silver bullet approach to controlling the outbreak. this silver bullet approach here implies the use of presumptive malaria treatment, or the use of mass drug administration (mda)-which have proved useful in some previous emergencies. through mda, all individuals in a targeted population will be given hydroxychloroquine and azithromycinoften at regular intervalsregardless of whether they exhibit symptoms of the disease. aao conceived of the study including design and method. he was the principal in data management, analyzed the data and drafted the article. aa, co, ak, ej, pg, ge, do, dm and mr contributed to reviews of the draft and final version of the manuscript. we declare no competing interests. all data used are publicly available, and sources are cited throughout. . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint table a ): variables selected using three lasso selection techniques (the model displays an "x" if a variable was selected using any of the three methods, and most important variables are listed first.). . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint severe acute respiratory syndrome coronavirus (sars-cov- ) and coronavirus disease- (covid- ): the epidemic and the challenges a review of the novel coronavirus (covid- ) based on current evidence emergency committee regarding the outbreak of novel coronavirus (covid- ). geneva: who clinical features of patients infected with novel coronavirus in wuhan epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan, china report of the who-china joint mission on coronavirus disease (covid- ) -china zhongfa zhang & zhongtao gai ( ) the different clinical characteristics of corona virus disease cases between children and their families in china -the character of children with covid- : comparison of effects of strategies for mitigation and for suppression coronavirus (covid- ) and hiv the different clinical characteristics of corona virus disease cases between children and their families in china -the character of children with covid- hundreds of severe pediatric covid- infections in wuhan prior to the lockdown world health organization, world health organization pneumococcal infection in adults: burden of disease early origin and recent expansion of plasmodium falciparum diarrhea is first sign of illness for some covid- patients preparedness and vulnerability of african countries against importations of covid- : a modelling study data used for this analysis was obtained from the covid- data resource hub established by the tableau community and included near real-time data compiled by johns hopkins university. additional data from key: cord- -u xn m authors: mutala, timothy musila; onyambu, callen kwamboka; aywak, angeline anyona title: radiology practice in sub-saharan africa during the covid- outbreak: points to consider date: - - journal: pan afr med j doi: . /pamj. . . . sha: doc_id: cord_uid: u xn m covid- is a rapidly growing pandemic that has grown from a few cases in wuhan, china to millions of infections and hundreds of thousands of deaths worldwide within a few months. sub-saharan africa is not spared. radiology has a key role to play in the diagnosis and management of covid- as literature from wuhan and italy demonstrates. we therefore share some critical knowledge and practice areas for radiological suspicion and diagnosis. in addition, emphasis on how guarding against healthcare acquired infections (hais) by applying “red” and “green” principle is addressed. given that pandemics such as covid- can worsen the strain on the scantily available radiological resources in this region, we share some practical points that can be applied to manage these precious resources also needed for other essential services. we have noted that radiology does not feature in many main covid- guidelines, regionally and internationally. this paper therefore suggests areas of collaboration for radiology with other clinical and management teams. we note from our local experience that radiology can play a role in covid- surveillance. resources in this region, we share some practical points that can be applied to manage these precious resources also needed for other essential services. we have noted that radiology does not feature in many main covid- guidelines, regionally and internationally. this paper therefore suggests areas of collaboration for radiology with other clinical and management teams. we note from our local experience that radiology can play a role in covid- surveillance. epidemiology: covid- was first described in wuhan city, province of hubei, china in december with subsequent genetic sequencing that gave definition of the novel coronavirus known as n-cov or sars-cov- [ ] . within a short period of time it has spread across the world leading it to being declared a pandemic by word health organization (who) on march . on april , the numbers stood at , , and , for total number of cases and deaths respectively [ ] . though a seemingly late entrant in covid- reports, africa is also witnessing an upsurge with total cases almost tripling from , to , in a span of less than three weeks [ , ] . role of radiology in covid- : radiology plays a significant role in management of covid- patients, especially chest ct and chest x-ray [ ] [ ] [ ] . reports have also emerged on the utility of point of care ultrasound in management of this group of patients [ ] . there are certain chest radiological features being attributed to covid- from a sizeable database. these have been grouped into four categories namely: typical, indeterminate, atypical and negative for pneumonia emphasizing on the likelihood of covid- infection according to the radiological society of north america (rsna) [ ] . a more or less similar approach for reporting in suspicion of covid- lung disease is also emerging under co-rads, a standardized structured reporting tool developed by the dutch radiological society. radiologists in sub-saharan africa must be fully cognizant of the radiological features of covid- by referring to the aforementioned literature and the few cases they have from imaging patients with covid- disease in their local setting. these include ground glass opacification, mainly peripheral, basal and bilateral as well as multi-focal consolidations. these have been presented in major radiological and multidisciplinary forums and as such many radiologists are well versed with the imaging patterns of the disease. we highly encourage frequent refreshers at individual and larger group levels so as not to lose track of diagnosing complications in suspected cases or even pick clinically missed ones. indications for imaging in covid- need to be clear to the clinicians and radiology teams to optimize benefits and risks. imaging is not a screening tool for suspected covid- and rt-pcr still remains the gold standard diagnostic method [ , ] . again, not all diagnosed covid- cases will require imaging and the strongest case for doing it is in setting and assessment of severe ards [ , ] . utility of ct scan of the chest in probable cases as per the who case definition has been tried in some settings [ ] . this consists of negative rt-pcr but highly suspicious symptomatology and history of contact and in some cases positive ct findings have preceded positive rt-pcr test. however, all the cases in the series finally turned positive at a later test and also a negative ct scan in such patients cannot constitute covid- free status. from our country´s experience a few of the covid- positive patients for whose imaging was indicated had findings not different from the pattern widely published. "red" and "green" zones principle (minimize healthcare acquired infections): diagnosis of covid- starts at the public health and primary care realms with clear case definition as developed by who [ ] . patients are generally referred by clinicians for radiological examination. this means that imaging has to be clearly defined within national or regional covid- handling management protocols and/or guidelines. unfortunately, many national and international guidelines do not succinctly include radiology. radiology can be either a problem solver or multiplier in covid- management depending on how it is handled. the positive contributory factors are as highlighted in preceding section. the negative side is that general healthcare acquired infections (hais) have been associated with radiology units in some situations [ ] . general preparedness in tackling hais through radiology varies across different countries within sub-saharan africa [ ] . for that reason, national, regional and international infection prevention and control (ipc) guidelines should be made with input of radiology representatives. at the same time, in the main hospital setting, it is imperative that the radiology managers and their staff get actively involved in the development of their institutional standard operating protocols (sops) on handling covid- cases. that way they will "ring fence" their departments from being conduits of hais to their staff and other patients within the unit. patient traffic flow and handling in radiology during the covid- era must be guided by the principle of "red" and "green" zone principles. this is generally described in a publication by zhang et al. that captured the practice in wuhan, china during the peak period of the outbreak there [ ] . this is summarized in figure . the definition of the zoning starts at the health facility´s main entrance where screening and triaging is thorough to isolate confirmed or suspected cases at the earliest opportunity. "red zone" operations demand designation of facilities including imaging for the covid- diagnosed or suspected patients. a call for national planners and institutional managers is to make sure that every isolation facility has designated imaging units, preferably mobile ones stationed within it. radiological staff working within the "red" zone must be covered with adequate ppe as prescribed by authoritative health organizations [ ] . we have noted that supply of ppes continues to be a worldwide challenge, sub-saharan africa having its fair share of the same. therefore, it is prudent that designated imaging facilities be the ones that handle covid- patients to save on this scarce resource. this goes hand in hand with a primary triage that must be as watertight as possible to protect non-covid- units ("green zones") being inadvertently exposed. enhanced ipc protocols for imaging in covid- have been published including a video by dr pradeen srinivasan of fortis hospital, bangalore, india on their covid- patient radiography procedure [ ] . this has been adopted in our teaching facility, kenyatta national hospital and we highly recommend it. another good reference for the in-depth detailing of the covid- patient handling in the radiology department is also provided by mossa-basha et al. from their personal experience at university of washington [ ] . in short, "red" zone operations must be embraced by policy makers, health institution managers, radiology managers, radiologists and radiology technologists. "green" zone operations must also be emphasized so that no patient is denied essential diagnostic and interventional imaging services. of course, services will operate under general public health measures of hygiene, social distancing and wearing of face masks. spending the shortest time within the imaging facility should be a major goal of the managers and the entire team. patient preparation procedures that can be done before arriving to the department should be encouraged. examples include fluid intake before pelvic ultrasound and oral contrast for abdominal ct. further, patients should be encouraged to come with their own drinking cups for such procedures. also, it will be prudent to have patients not wait for the written reports within the facility as a way of managing queues. facility managers and their staff must be fully versed with the disinfection protocols guided by equipment manufacturers. at least three vendors, namely ge healthcare, philips and siemens healthineers have published their explicit cleaning guides in their websites. the authors do not endorse any vendor products or recommendations and equipment owners are advised to check with their local representatives for clear instructions. with these ipc practice it is also important to note that decontamination of ct scan machines has been documented to result in a downtime running into hours [ ] . this can lead to throughput issues for regular workflow if imaging is performed in non-designed facilities for covid- cases. challenges in radiology as part of the bigger healthcare system: radiological equipment and imaging centers are a scarce resource for the sub-saharan africa population. it is our estimation that there are about ct scans in kenya serving a population of about million people, giving a ratio of . units per million of the population [ , ] . ngoya et al. report that there are . and . ct scan units per million for tanzania and south africa, respectively [ ] . these are the confines within which imaging resources for covid- will be integrated to. hence more care in ensuring all the triage protocols are right. that sub-saharan africa is in dire need of radiologic human resource is not a new phenomenon [ , ] . from our experience as a training center of radiologists from several countries within sub-saharan africa since , we also have firsthand experience on the matter. our department has successfully trained about radiologists who serve in kenya, tanzania, malawi, zambia, zimbabwe, botswana and namibia among other countries. the radiologist to population ratio in sub-saharan africa is not flattering either. for example, nigeria the most populous country in the region has : , and kenya : , [ , ] . the ratio of other radiology workers, radiographers and physicists stands at : , in kenya [ ] . these are rare gems that must be handled with the greatest care during the covid- pandemic. in tandem with international practice, exposed persons to covid- in our country usually undergo mandatory quarantine for days. this can have great impact on essential imaging services even for the "green" zone. human resource managers should consider implementing noncontact rotational shifts for their staff to mitigate entire team grounding in the event of exposure. another area to invest in human resource is through education, lack of which has already been cited as a possible cause of mortality from covid- among health workers [ ] . covid- ipc education is available from many sources including the who website and many radiological society regular webinars. we encourage radiology to be given slots in local covid- multidisciplinary webinars as has been the case in our country. we envisage a challenge in sub-saharan africa arising from the ownership of the imaging facility. this is determined to a great extent on whether the department is part of a health institution like a hospital, mainly drawing its patients from within or a standalone facility which draws its patients from varied sources. in the former scenario, sops may be easily dovetailed within the system while in the latter this may not be realized. this is demonstrated in figure in which the inhouse referral is described as pathway i and external one pathway ii. further, we designate inpatients in both pathways as group "a" and outpatients as group "b". in addition, private imaging facilities, especially the standalone ones can easily be overlooked in support. they can also lag behind in catching up with the necessary linkages for the fight against covid- . thus, local authorities, professional societies and regulatory bodies must purposefully look for and support them so as to break any possible weak link. radiological units operate in linkages with the clinical departments, peers, community, national and local authorities and other stakeholders. collaborations must therefore be encouraged with all other stakeholders. collaboration with regulatory bodies will play a key role in enforcement, where such is required. professional societies must be very active in advocacy for best practice and at the same time in advising the policy makers in adjusting some approaches as far as covid- response management is concerned. the most important collaboration is between the radiology and other clinical teams or referring chains that they interact with on daily operation activities. radiological research and epidemiological surveillance in covid- : covid- is a field of research that will generate new knowledge to inform policy formulation and also help us become better radiology health workers in our service delivery. some areas that will require research include the individual follow-up of the recovered patients and emerging imaging methods like point of care ultrasound (pocus). the proportion of incidental diagnosis through radiological pathway in non-suspected cases will be of interest. not to forget the impact of the pandemic on radiological resources and operations will need to be quantified and qualified at the same time. research is best done through institutional and organizational collaborations and this is a good time for that. funders can strongly consider radiological research for covid- a priority given that many respiratory patients end up in imaging and also the radiology unit is a convergence zone for many other patients. in the same breath, utmost personal, patient and other players protection must be put into consideration when planning and implementing research related to covid- as it can be highly contagious. all in all, it will be for the benefit of current and future generations that effective covid- research is implemented in all spheres of diagnosis and care thus availability of ppes for such a venture should be considered an investment. epidemiological linkages will be key in informing radiology health workers in emerging cluster trends. at the same time radiology can be a good source for epidemiological teams to tap knowledge as far as suspicious imaging findings are reported. in fact, back in wuhan it is reported through mainstream media that dr zhang jixian raised the alarm of the covid- outbreak by describing a pattern of ct chest abnormalities within a cluster of family members [ ] . considerations can be made by the surveillance teams to have tools that can capture this information developed in conjunction with and shared between radiology practitioners and them. we could not trace a radiological surveillance tool but our faculty is looking forward to developing one in partnership with the ministry of health, kenya. four key areas will ensure that radiology serves its best purpose during the covid- outbreak in sub-saharan africa. these are good radiological knowledge of covid- manifestations, "red and green" patient handling principle, prudent resource utilization and integration of radiology in epidemiological surveillance. figure : simplified demonstration of how thorough separation of covid- and non-covid- case definition patients must be handled in a designated facility figure : radiology department patient catchment scheme that can have implications on adherence of covid- case handling sops. pathways ia and ib should have the lowest risk in that regard, while pathway iib would have the highest and iia in between. radiology managers need to incorporate referrals falling under ii to their inhouse triage sops before proceeding with the examination figure : radiology department patient catchment scheme that can have implications on adherence of covid- case handling sops. pathways ia and ib should have the lowest risk in that regard, while pathway iib would have the highest and iia in between. radiology managers need to incorporate referrals falling under ii to their inhouse triage sops before proceeding with the examination a novel coronavirus from patients with pneumonia in china -ncov) global cases (by johns hopkins csse). case dashboard coronavirus in africa tracker: how many covid- cases & where?accessed the role of chest imaging in patient management during the covid- pandemic: a multinational consensus statement from the fleischner society outbreak of novel coronavirus (covid- ): what is the role of radiologists? acr recommendations for the use of chest radiography and computed tomography (ct) for suspected covid- infection point-of-care lung ultrasound findings in novel coronavirus disease- pneumonia: a case report and potential applications during covid- outbreak radiological society of north america expert consensus statement on reporting chest ct findings related to covid- . endorsed by the society of thoracic radiology, the american college of radiology, and rsna the royal college of radiologists. the role of ct in patients suspected with covid- infection use of chest ct in combination with negative rt-pcr assay for the novel coronavirus but high clinical suspicion world health organization. coronavirus disease (covid- ) situation report- health care-associated infections and the radiology department infection control recommendations for radiology departments in malawi pubmed| google scholar . who operational considerations for case management of covid- in health facility and community. interim guidance covid patient x ray safe technique demonstration-fortis hospital bangalore policies and guidelines for covid- preparedness: experiences from the university of washington radiology department preparedness for covid- : radiologyscientific expert panel palladium, health policy plus national diagnostic reference level initiative for computed tomography examinations in kenya defining the diagnostic divide: an analysis of registered radiological equipment resources in a lowincome african country training for rural radiology and imaging in sub-saharan africa: addressing the mismatch between services and population diffusion of radiologic technology in sub-saharan africa: a jefferson college of health professions study the status of healthcare professionals in kenya, . accessed on radiation protection board, kenya. licensed radiation workers reasons for healthcare workers becoming infected with novel coronavirus disease (covid- ) in china the doctor who first reported -ncov infection. beijing review figure : simplified demonstration of how thorough separation of covid- and non-covid- case definition patients must be handled in a designated facility the authors declare no competing interests. all the authors have read and agreed to the final manuscript. key: cord- - xr ycm authors: bankole, taofik olatunji; omoyeni, olajide bamidele; oyebode, abiodun oluwaseun; akintunde, david olumide title: low incidence of covid- in the west african sub-region: mitigating healthcare delivery system or a matter of time? date: - - journal: z gesundh wiss doi: . /s - - -w sha: doc_id: cord_uid: xr ycm background: this study examines the growth trends in the covid- pandemic and fatalities arising from its complications among tested patients in west africa. countries around the world have employed several measures in order to control the spread of the disease. in spite of the poor state of the healthcare delivery system in west africa, the spread of the pandemic is relatively low compared to reported cases in other regions of the world. the study addresses this phenomenon by asking the question: is the low incidence of covid- in the west african sub-region a mitigating healthcare delivery system or just a matter of time? methods: the study adopted a cross-sectional time series method. data for ghana, nigeria, burkina faso, ivory coast, senegal, niger republic, and global data were extracted from the world health organization covid- databank. data were extracted in intervals of days from march through april , . data regarding the incidence growth rate and fatalities arising from covid- complications were generated from the total reported cases and fatalities over specified periods. descriptive and inferential statistical analyses were carried out using stata version . results: results showed that the trends in growth patterns of covid- for senegal, nigeria, ghana, republic of niger, and west africa generally followed the same fluctuating curves. the covid- pandemic accounted for . %, . %, . %, %, . %, . %, and % of complications that led to deaths of patients in burkina faso, nigeria, senegal, ghana, niger republic, ivory coast, and west africa, respectively. also, the results established that there was a significant positive association between increased incidence of covid- and percentage increase in fatalities arising from its complications in west africa (ß = . ; t = . ; p < . ). conclusion: the threat presently posed by covid- seems to be minimal in west africa despite the poor state of the healthcare delivery system in the region. it is unlikely, however, that the region is well prepared for the pandemic in the event that it escalates out of control with time. the recent covid- outbreak is the most devastating pandemic that mankind has experienced in the past ten decades. in fact, no other pandemic has claimed more human lives in the same amount of time. the severity and contagion is so high that no continent has been spared its threat. in fact, empirical reports show that over . million persons have been infected with the virus, while about , deaths have been reported across regions of the world, including about , , , , , and , deaths reported as of april , , in the united states, italy, spain, and france, respectively (who c) . across countries, several measures have been adopted to contain the spread of the pandemic. as noted in the world health organization interim guidance for infection prevention and control, it is imperative that member countries strictly adhere to standard precautions for all infected persons, while the establishment of an infection prevention and control focal centre was also recommended, supported by nationwide and facility senior management across countries (who a, b) . in fact, these recommended strategies and practices are considered vital for nations to attain the maximum level of effectiveness in response to the covid- plague. andrea and giuseppe ( ) posited that the covid- pandemic is manageable in the foreseeable future, but this is only achievable where and if all-inclusive and stringent control measures are taken. the spread of covid- across countries in the sub-saharan african region seems to have been relatively low compared to the reported cases originating from other regions of the world. in fact, as of april , , with the exception of south africa, no country in the sub-region has yet reached reported covid- cases since the outbreak in december . specifically, only cameroun has reported up to covid- cases, closely followed by cases reported in the ivory coast, in ghana, in niger, in burkina faso, and in nigeria (worldometer ) . in all, the total covid- cases across countries in africa was estimated at , , with countries in sub-saharan africa accounting for about . % ( , reported cases) of infected persons despite housing out of the countries (with the exclusion of egypt, algeria, tunisia, djibouti, libya, morocco, sudan, and somalia) on the african continent (worldometer ) . arguably, the spread of infection in the sub-region can be questioned. in fact, there are unclassified arguments among peoples of the sub-region that either the cases are overreported or the pandemic scarcely exists in the subcontinent. in contrast, it is also argued that covid- cases are being reported in many of the countries in the sub-region. specifically, melinda gates, in her wake-up call to african leaders, lamented that deaths from covid- in the region may escalate out of control unless drastic and immediate measures are taken (sahara reporters ). gates maintained that the logical reason for the present lower number of reported cases ( , ) and deaths ( ) is the lack of testing kits. she argued that it was often impossible to practice physical distancing in many african towns and slums (sahara reporters ). indeed, personal hygiene and physical distancing may be difficult to adhere to not only because of the widespread poverty in many of the sub-saharan african countries, but also due to the communal way of life in traditional african settings. indeed, the possibility of underreported cases of covid- is not likely restricted to countries of sub-saharan africa; the outcomes of data-driven modeling analysis in china showed a high likelihood that cases of infection were unreported . evidence from simulated reported cases revealed a significantly larger number of observed versus actual reported cases within a span of days . closely related to this, wu et al. ( ) noted that, in defiance of early expectations, the once-assumed epidemic is not only growing steadily and exponentially in many chinese communities, but has grown into a pandemic across the continents of the world. a retrospective study of the predicted outcomes of covid- infection from a simulated process revealed a significant likelihood of underreported cases of the virus . in agreement with the aforementioned, there is a clear indication that cases of covid- in the sub-saharan region are underreported, while many cases are surely not reported at all. the high possibility of unreported cases could be argued from the perspective of the ratio of tests carried out to reported cases of infections. the rate of tests per population is generally low across countries of the region-while the ratio was as low as per million population in the republic of niger, the ratios were estimated at , , , , and persons per million population in ethiopia, nigeria, mozambique, malawi, and burundi, respectively (worldometer ) . evidence from an empirical survey revealed that personal protective equipment, administrative control, and basic healthcare facilities are not only in short supply, but are also of poor quality in the region (who b). as noted by li et al. ( ) and zhou et al. ( ) , there is a need for stringent and timely epidemiological approaches in order to restrict the rate at which the virus is spread. could it be that these measures are being taken as part of daily routine by countries of this region? in fact, virtually all tests in healthcare facilities in the region were carried out on patients that met the suspected case definition as spelled out by the world health organization recommendations for covid- testing (who a). according to oleribe et al. ( ) and doctor et al. ( ) , practically all the sub-saharan african countries are faced with a shortage of quality human resources, lack of healthcare financing, poor governance, and management lapses. in fact, the healthcare insurance schemes are either not available or are non-functional in many countries of the region, thereby forcing healthcare workers to risk their lives with no assurance of better lives for their loved ones in the event that they die while working to save the lives of others (kiri and ojule ; lawumi ; gautier and ridde ; olugbenga ) . in spite of the weak state of healthcare facilities, shortage of well-trained medical professionals, and low level of adherence to physical distancing, the spread of covid- , as well as deaths arising from the viral infection, is still relatively low compared to other regions of the world with better healthcare service delivery systems and fewer slums or shanty communities. it is against this backdrop that the current study asks the question: is the low incidence of covid- in the west african sub-region the mitigating effects of the healthcare delivery system or just a matter of time? the study is restricted to the sub-region of west africa for three reasons. first, the population density of persons per square kilometre makes it the most congested region of africa (prb ). also, the life expectancy of years is the lowest across regions in africa (prb ; who ). lastly, the present state of healthcare service delivery is not only poor but is inadequate for the population of the region (kiri and ojule ; who ). the six countries with the highest reported cases of covid- infections as on april , , were purposefully and specifically selected for the study, although the aggregated trends for the sub-region (west africa) and the world at large were also investigated. hence, the specifically selected countries for the study include burkina faso, ivory coast, niger, ghana, nigeria, and senegal. according to mcleroy et al. ( ) , socio-ecological theory is a comprehensive approach to behavioural action, and such detailed action is typically influenced by factors on multiple levels. the proponents of the theory maintain that its adaptation must be built on the agreement between the benefactor and the beneficiaries of the proposed action. therefore, the fundamental aspects of the ecological approach, with the goal of reducing challenges of subjugation, and particularly repression, is the active involvement of the target population in problem classification, selection of targets for change and appropriate intervention, implementation, and appraisal. the sociological model according to mcleroy et al. ( ) is segmented into five classes, including intrapersonal factors, interpersonal processes, institutional or organizational factors, community factors, and public policy. our study is supported by the socio-ecological theory. the theory is found relevant since it explains the effect of environmental dynamics on human behaviour, with the primary aim of identifying environmental interference to addressing the phenomenon or subject matter. in the context of preventing and minimizing the spread of covid- in the sub-region of west africa, it is recommended that governments, stakeholders, and the entire population at large adopt measures that will enable then to become immersed in the immediate environment-while personal hygiene such as regular washing of hands and wearing of masks covering the nose and mouth are encouraged, social and physical distancing is also encouraged-with the governments expected to provide extra support for improving, expanding, and making healthcare facilities accessible for testing (who d) . also, the willingness and the extent to which the recommended measures were adhered to across the west african sub-region is strongly dependent on the ability of the governments to provide the needed covid- test kits across strategically well-equipped healthcare facilities, as well as the provision of palliatives in the form of food, energy, drugs, and other basic necessities, especially to those in dire need of them. also, the existence of functional or establishment of viable social and health insurance schemes is needed, as this will encourage healthcare workers and others who are directly involved in containing the spread of the virus to willingly perform their assigned duties. deductively, the extent to which the governments of nations in the west african sub-region are able to provide palliatives that will compel their nationals to totally comply with the pronounced lockdown in some communities, provide the population with a regular and accessible supply of face masks, equip healthcare facilities with covid- test kits and ventilators, and provide or implement social and healthcare insurance, will determine how well the region is prepared to contain the spread of the virus in case the unexpected arises. hence, there is no doubt that the socio-ecological model provides insight into a theoretical approach to tie the rate at which the infection is spread to the state of healthcare service delivery and socio-ecological factors preventing the population from totally complying with the recommended interim guideline issued by the world health organization. the study adopted a cross-sectional time series method. secondary data were sourced from the world health organization covid- databank. data including daily reports on the total reported cases of covid- infection and the number of related patient deaths were extracted for burkina faso, ivory coast, niger, ghana, nigeria, and senegal over the time span covered in this study. the extracted data were entered into an excel spreadsheet and later exported to stata analysis software. the incidence growth rate for the total number of reported cases was generated from two consecutive intervals (weekly), with the former retrieved data adopted as the base value (denominator) for the specified total reported cases of infection, while the latter was used as the numerator value. also, the death rate was generated by adopting the former retrieved total death data for each of the specified time intervals (weekly) for specified dates as the base value (denominator), and the latter retrieved data was adopted as the numerator value. descriptive (figures) and inferential (linear regression, correlation) analytic techniques were adopted to analyse the trend variations, cause-effect association, and strength of the relationship. stata version software was employed. figures , , , , , , , and show the trends in the percentage increase in the rate of reported cases of covid- in burkina faso, ivory coast, senegal, nigeria, ghana, republic of niger, west africa, and the world, respectively. the results show that the growth patterns for burkina faso and globally followed the same pattern of growth. although there are increases in reported cases, a decline in growth across intervals is found, as presented in figs. and , respectively. in contrast, the prevalence rates for ivory coast, senegal, nigeria, ghana, niger republic, and west africa as presented in figs. , , , , and generally follow the same patterns; fluctuations in growth patterns were recorded in these four countries, as well as in the west african sub-region. for instance, reported cases of covid- for burkina faso as captured in fig. showed a drop in the infection rate from the initial recorded growth of % in (tn+ ) to . % in (tn+ ) and a further decline to a growth rate of . % in (tn+ ). the infection rate subsequently dropped to % in (tn+ ), and further declined to % by the end of (tn+ ). for the ivory coast, as reported in fig. , the incidence growth rate of covid- indicated that the reported cases initially increased from % in (tn+ ) to . % in (tn+ ), and subsequently dropped to % in (tn+ ). also, the results indicated that the growth rate for the reported incidence of covid- in the country increased to . % in (tn+ ) and then dropped to . % in (tn+ ). the results as captured in fig. indicate that the prevalence of reported covid- for senegal dropped from an initial growth rate of . % recorded in (tn+ ) to . % in (tn+ ). a further drop to % was recorded in (tn+ ) and a subsequent decline to % in (tn+ ). however, the consistent declining growth rate pattern for the country over time was reversed in (tn+ ), which showed an increase of %. the results for nigeria as captured in fig. indicate that the country's reported cases of covid- grew by % in (tn+ ). although the growth rate dropped to . % in (tn+ ), an upward trend of . % was reported in (tn+ ), followed by a decline to . % in (tn+ ). this decline in (tn+ ) was followed by an upward trend to . % by the end of (tn+ ). the growth rate for reported cases of covid- for ghana is nearly the same as that for nigeria. the results as captured in fig. indicate a growth rate of % in (tn+ ), which subsequently dropped to . % in (tn+ ). the results indicate a sporadic decline-this was estimated at . % in (tn+ ). conversely, the country experienced a sharp increase in the rate of reported cases, which stood at % in (tn+ ). a further increase in reported cases in ghana, to . %, was then seen in (tn+ ). the growth rates for reported cases of covid- for niger republic, as captured in fig. , indicate a % growth rate in both (tn+ ) and (tn+ ). however, this was followed by an increase of % in (tn+ ), a subsequent drop to % in (tn+ ), and a further decline to % in (tn+ ). the cumulative results across countries of the west african region as captured in fig. indicate an increase of . % in cases of covid- in (tn+ ), followed by a decrease to . % growth of reported cases recorded in (tn+ ). the growth rate in reported cases of infection then increased to . % for the region in (tn+ ), and declined to . % in (tn+ ). the growth rate in reported cases of covid- in west africa was . % in (tn+ ). globally, the pattern of growth in the incidence of covid- as reported from (tn+ ) to (tn+ ) showed a downward slope. the results as captured in fig. indicate that the growth rate rose to . % in (tn+ ) and dropped to . % in (tn+ ). similarly, a growth rate of . % was reported in (tn+ ) and . % in (tn+ ). the global rate of growth for the pandemic was . % in (tn+ ). the trend in deaths arising from covid- infection was very similar for burkina faso, nigeria, ghana, niger republic, and west africa. this is captured in figs. , , , , and , respectively. the trend in reported deaths for the ivory coast and senegal followed the same pattern, as shown in figs. and , respectively. however, the global trend in deaths from covid- differed, and is shown in fig. . as indicated in fig. , the growth rate for deaths arising from covid- in burkina faso increased from % in (td+ ) to % in (td+ ). no deaths ( %) due to covid- infection were reported in (td+ ) or (td+ ) in burkina faso. the results also show that the growth in the country's death rate dropped to . % in (td+ ), but then increased to . % in (td+ ). the results for ivory coast as captured in fig. show that the death rate increased from % in (td+ ) to % in (td+ ); no deaths were reported in (td+ ), (td+ ), or (td+ ). an increase in deaths of % was reported in (td+ ) as a result of the spread of the pandemic in the ivory coast. figure shows that for senegal, there was a % growth rate in deaths arising from covid- infection in (td+ ), (td+ ), and (td+ ). recorded deaths due to covid- complications for the country increased from % in (td+ ) to % in (td+ ). the results for nigeria as captured in fig indicate that the death rate increased from % in (td+ ) to % in (td+ ). the earlier pattern showed % growth in deaths as a result of the infection in (td+ ) and (td+ ). however, the death rate was estimated at % in (td+ ). results for ghana as captured in fig. show that a % rate in deaths related to covid- infection was recorded in the country in (td+ ) and (td+ ). a % increase in the death rate was reported in (td+ .). the rate increased to % in (td+ ) and subsequently dropped to . % in (td+ .). as captured in fig. , the rate of deaths arising from the covid- pandemic in the republic of niger was % in (td+ ) and (td+ ). the rate increased to % in (td+ ) but subsequently dropped to . % in (td+ ). the rate rose to . % for the country in (td+ ). the pattern of deaths for west africa showed an initial upward movement from % in (td+ ) to . % in (td+ ), as captured in fig. . deaths arising from the covid- pandemic then dropped to % for the sub-region in (td+ ) and further declined to . % in (td+ ), but subsequently increased to . % in (td+ ). the global rate of deaths arising from the pandemic dropped from . % in (td+ ) to . % in (td+ ), as captured in fig. . this was followed by a further decline in reported covid- -related deaths to % and . % in (td+ ) and (td+ ), respectively. the rate then dropped from . % in (td+ ) to . % in (td+ ). table presents the results of the analysis of the association between the incidence of covid- infection and deaths arising from its complications across the studied countries and regions. the results show that complications of covid- infection accounted for . %, . %, . %, %, . %, and . % of patient deaths in burkina faso, nigeria, senegal, ghana, niger republic, and ivory coast, respectively. also, the pandemic accounted for % and . % of complications leading to the death of patients in the sub-region of west africa and the world at large. the results further reveal that the increase in deaths arising from covid- complications is positively and strongly associated. evidence from the study as presented in table showed a strong positive linear association between covid- incidence and deaths arising from its complications among patients in burkina faso (r = . ), nigeria (r = . ), senegal (r = . ), ghana (r = . ), niger (r = . ), and ivory coast (r = . ). likewise, a strong positive linear association was found between the spread of covid- and an increase in deaths related to its complications among patients in the west african sub-region (r = . ) and the world at large (r = . ). correspondingly, the results consistently showed a significant association between the spread of covid- and deaths arising from its complications among patients in the studied countries and regions, including burkina faso (ß = . ; t = . ; p < . ), nigeria (ß = . ; t = . ; p < . ), senegal (ß = . ; t = . ; p < . ), ghana (ß = . ; t = note: (td+ ) denotes percentage increase in deaths due to the covid- pandemic from march through march , ; (td+ ) denotes the percentage from march through march , ; (td+ ) denotes the percentage from march through april , ; (td+ ) denotes the percentage from april through april , ; and (td+ ) denotes the percentage from april through april , . this study comprehensively investigated the trends in the spread of the covid- pandemic in burkina faso, ghana, nigeria, ivory coast, senegal, and republic of niger. the study also describes the spread of covid- in the west african sub-region as a whole and the world at large. trends in deaths arising from covid- infection among patients are also described in the study. moreover, the study establishes a link between the spread of the covid- pandemic and the increase in deaths arising from the spread of the infection. our study shows that the spread of covid- in the subregion of west africa increased gradually. for instance, we observed that the rate of spread varied across the six countries encompassing west africa; nevertheless, all the countries recorded growth in reported cases within the time frame covered in the study. in burkina faso, the spread of the virus peaked in tn+ ( %), while the lowest growth rate of % was reported in tn+ . the growth trend in nigeria followed the same pattern. however, while the highest number of reported covid- cases was recorded in tn+ ( %), the lowest growth in the spread of the infection was reported in tn+ ( . %). our findings for the situation in senegal showed that the highest spread in the country was reported in tn+ ( . %), while the lowest reported case spread was recorded in tn+ ( %). we observed that the growth in the spread of covid- in the ivory coast peaked in tn+ ( . %) and was lowest in tn+ ( . %). our findings further showed that in ghana, the highest growth in covid- incidence was recorded in tn+ ( %), while the lowest growth rate was reported in tn+ ( . %). in contrast to ghana, in the republic of niger we observed that the lowest covid- pandemic growth rate was recorded in tn+ ( %), while the growth rate peaked in tn+ ( %). collectively, the growth rate in west africa was highest in tn+ ( . %), while the lowest growth in the sub-region was observed in tn+ ( . %). we found that the evidence from our study showed a continuous decline in the growth rate of the spread of the covid- pandemic globally, while the reverse was observed in the sub-region of west africa. thus, our findings showed a fluctuating trend in the spread of the infection in west africa. specifically, the trends of growth rates in the spread of covid- for ghana, nigeria, burkina faso, senegal, niger republic, and ivory coast vary over the period of the study. hence, it must be deduced from our findings that the lower cases of covid- infection reported in west africa as at april , , could not be attributed to the existence of a better, functional, and improved healthcare service delivery compared to that obtainable in the developed regions of the world. based on our findings, if the healthcare service had been the major factor for a lower number of deaths in the region compared to the alarming global figure, the growth rate should also be declining rather than the rise witnessed in ghana, nigeria, senegal, ivory coast, niger republic, burkina faso, and the subregion of west africa as a whole. in fact, the lower number of reported cases of covid- infection in west africa could also be attributable to the lower number of tests that have been carried out so far, which agrees with the prediction by melinda gates as reported by sahara reporters on april , . our assertion is supported by the fact that as of april , , a total of , , , and covid- tests per million population had been carried out in niger, nigeria, gambia, and togo, respectively (worldometer ) . moreover, evidence from contemporary studies indicates that the state of healthcare service delivery in the sub-saharan african region is characterised by poor funding, shortage of modern sophisticated healthcare equipment, poor or absent healthcare insurance schemes, shortage of well-trained healthcare personnel, and poor implementation of healthcare policies (azevedo ; doctor et al. ; kiri and ojule ; lawumi ; oleribe et al. ; who a) . we observed from our study that globally, the trends in deaths arising from the covid- pandemic has been steadily declining. growth in deaths among covid- patients peaked in td+ ( . %), while the lowest growth rate in deaths was reported in td+ ( . %). unlike the trend in deaths arising from the covid- pandemic in the world at large, we observed a rise and fall in covid- -related deaths among patients in ghana, nigeria, senegal, ivory coast, burkina faso, and niger republic, and in the region of west africa. for instance, we observed that the death rate growth in west africa peaked in td+ ( . %) and was lowest in td+ ( . %). specifically, we observed that the growth in deaths arising from covid- complications among patients in ghana peaked in td+ ( %), while the lowest growth in deaths was reported in td+ ( %). also, we discovered that growth rates in deaths arising from covid- infection among patients in niger peaked in td+ ( %), while the lowest growth rate in deaths was witnessed in td+ ( . %). our findings showed that deaths arising from covid- infection peaked among patients in burkina faso and ivory coast in td+ ( %) and td+ ( %), while the lowest growth in the rate of deaths arising from the pandemic was reported in td+ ( . %) and td+ ( %), respectively. in nigeria, the death rate peaked in td+ ( %), and the lowest rate was recorded in td+ ( %). likewise, the death rate in senegal peaked in td+ ( %). evidence from our study showed that the growth rate of deaths arising from covid- complications has been steadily declining globally. however, the reverse was the case for death growth rates for ghana, nigeria, ivory coast, burkina faso, senegal, niger republic, and west africa. our findings, therefore, suggest that if the relatively lower incidence of growth in the reported cases of covid- in west africa is as a result of the availability of an improved or functional healthcare delivery system, the number of deaths across covered countries and of the region as a whole should have declined gradually rather than the present gradually increasing rate of deaths that are being recorded. based on our findings, it is possible that cases of covid- are being significantly underreported or not reported at all. this could be due largely to the poor healthcare delivery system in many of the regional countries. in fact, our findings consistently showed the existence of a significant association between increased rates of reported cases of covid- and an increase in the rate of deaths associated with complications arising from the disease. our findings are supported by zhao et al. ( ) , who posited that cases of covid- were being underreported in china. also, our observation that it is possible that covid- cases in west africa have been significantly underreported as a result of the poor state of healthcare service delivery in the region was corroborated by wu et al. ( ) and chen et al. ( ) , who argued that the absence of substantial public health interventions could bring about an unanticipated spread of the virus outside china. the threat posed by the covid- pandemic seems to be low in many countries in west africa and sub-saharan africa in comparison to what is being witnessed in other regions of the world. this study demonstrated in detail that the present situation in the region may not be as a result of the availability and accessibility of functional or improved healthcare facilities for nationals in the region. therefore, the reason for the current slower trends in terms of growth rates of reported cases or deaths could be a result of lack of test kits, underreported cases, and the like. in fact, it is unlikely that many of the governments in this region could provide their nationals with adequate palliatives that are needed at this trying time. hence, the study concludes that time will eventually tell whether the region is prepared for the challenges that may arise from the pandemic should it spiral out of control. certainly, there is a need for the nations of the region to be fully prepared to execute measures to contain the spread of the covid- pandemic. based on the observed pattern of increased incidence of covid- and the increase in the proportion of recorded deaths over the time covered in this study, the authors recommend that the lockdown measures undertaken by governments in the region be fully implemented. also, in order to achieve total compliance with lockdown, regional governments should provide their nationals with palliatives in the form of food, drugs, preventive supplies (face masks, hand sanitizers), potable water, and other basic necessities of life. healthcare service delivery should be made available and at no cost to the public. in fact, the governments, and in collaboration with richer and developed countries, should work note: *significant at p < . , **significant at p < . , ***significant at p < . ; r = adjusted r ; r = correlation coefficients; ß = regression coefficient; t n _n = total cases reported for march , ( n ), march , ( n ), march , ( n ), april , ( n ), april , ( n ) and april , ( n ); t d _d = total deaths reported for march , ( d ), march , ( d ), march , ( d ), april , ( d ), april , ( d ) and april , respectively towards covering a wider range of the population. hence, there is a need to carry out more testing. there is a need to set up more quarantine centers, especially in high-risk areas. equally, additional intensive-care units should be established along with the required healthcare equipment such as ventilators, immunity-boosting drugs and the like. moreover, medical professional support should be sought from countries with a high covid- recovery rate. hence, there is an urgent need to seek medical support from germany, new zealand, australia, south korea, austria, iceland, iran, thailand, and china. finally, huge spending on healthcare service delivery and research, particularly in health science and technology, is critical, along with the establishment of functional and well-funded social and healthcare insurance schemes. covid- and italy: what next? the state of health system(s) in africa: challenges and opportunities in: historical perspectives on the state of health and health systems in africa a mathematical model for simulating the phase-based transmissibility of a novel coronavirus health facility delivery in sub-saharan africa: successes, challenges, and implications for the development agenda health financing policies in sub-saharan africa: government ownership or donors' influence? a scoping review of policymaking processes electronic medical record systems: a pathway to sustainable public health insurance schemes in sub-saharan africa health insurance: the theoretical basis predicting the epidemic trend of covid- in china and across the world using the machine learning approach an ecological perspective on health promotion programs identifying key challenges facing healthcare systems in africa and potential solutions workable social health insurance systems in sub-saharan africa: insights from four countries saharan report ( ) melinda gates predicts high coronavirus deaths in africa by sahara reporters booklet world health organization. ( a) infection prevention and control during health care when covid- is suspected: interim guidance infection prevention and control during healthcare when covid- is suspected world health organization ( c) covid- situations data world health organization ( d) laboratory testing for coronavirus disease (covid- ) in suspected human cases: interim guidance nowcasting and forecasting the potential domestic and international spread of the -ncov outbreak originating in wuhan, china: a modelling study estimating the unreported number of novel coronavirus ( -ncov) cases in china in the first half of january : a data-driven modelling analysis of the early outbreak a pneumonia outbreak associated with a new coronavirus of probable bat origin publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations acknowledgements the authors express their gratitude to the world health organization (who) for making the datasets available for use (granted permission number: ). also, the worldometer is acknowledged for usage of their data.authors' contributions tob developed the concept, analysed data and interpreted the results. obo, aoo and doa reviewed the literature. all the authors were involved in the discussion of findings. all authors read and approved the final manuscript. data authorisation please contact the corresponding author for the generated data request. the ethical issue of the study has already been met, since the datasets that were utilized in this study were extracted from the covid- world health organization databank. key: cord- -ycjzitlk authors: simons, robin r. l.; gale, paul; horigan, verity; snary, emma l.; breed, andrew c. title: potential for introduction of bat-borne zoonotic viruses into the eu: a review date: - - journal: viruses doi: . /v sha: doc_id: cord_uid: ycjzitlk bat-borne viruses can pose a serious threat to human health, with examples including nipah virus (niv) in bangladesh and malaysia, and marburg virus (marv) in africa. to date, significant human outbreaks of such viruses have not been reported in the european union (eu). however, eu countries have strong historical links with many of the countries where niv and marv are present and a corresponding high volume of commercial trade and human travel, which poses a potential risk of introduction of these viruses into the eu. in assessing the risks of introduction of these bat-borne zoonotic viruses to the eu, it is important to consider the location and range of bat species known to be susceptible to infection, together with the virus prevalence, seasonality of viral pulses, duration of infection and titre of virus in different bat tissues. in this paper, we review the current scientific knowledge of all these factors, in relation to the introduction of niv and marv into the eu. bat-borne viruses with pandemic potential have been identified as the origin of a number of recent human disease outbreaks. examples include the paramyxoviruses nipah virus (niv) in malaysia and [ ] and the filoviruses ebola (ebov) and marburg viruses (marv) in africa [ ] . bats have also been linked with the more recent middle east respiratory syndrome coronavirus (mers-cov) [ , ] . nipah virus, in particular, has been suggested to have pandemic potential as it is capable of limited human-human transmission and rna viruses in general have particularly high mutation rates. a human-adapted strain of niv, were it to emerge in asia, could spread rapidly due to high population densities and global interconnectedness [ ] . a large, and still increasing, number of different viruses have been isolated from bats, many of which are asymptomatic in the host and are closely related to human pathogens. these viruses have the potential for cross-species transmission (i.e., -spillover‖) to other mammalian species, for example, marv in monkeys [ ] and niv in pigs [ ] , and to directly or indirectly infect humans [ ] . a recent paper describes the infection of a wildlife biologist with a novel paramyxovirus during a field trip to south sudan and uganda [ ] . a recent study found that bats have, on average, significantly more zoonotic viruses per species than rodents, which are also known to host a large range of viruses [ ] . additionally, the authors estimated that viruses had a broader host range in bats, averaging . host species per virus. bat-borne paramyxoviruses have been identified in various bat species across africa, australia, south america and asia and recently the detection and characterization of paramyxoviruses in free-ranging european bats has also been reported [ ] . further to this, recent evidence places bats as tentative hosts at ancestral nodes to paramyxoviridae and pneumoviridae [ ] . bat species can have very broad geographic ranges [ , ] and multiple species can share the same habitats and even roost sites [ ] . studies of pteropus bats in australia and asia found they could travel hundreds of kilometers between roosting sites with their home ranges extending across national boundaries and over sea [ , ] . factors that affect the degree and rate of contact between animals and humans are important for spillover of any zoonotic emerging infectious disease. most human outbreaks of bat-borne zoonotic diseases have been suggested to be as a consequence of human activities. for example, outbreaks of marv in africa have been linked to human contact with bat caves, for reasons such as mining operations [ ] or tourism [ , ] . deforestation has also led to bat colonies moving closer to areas inhabited by humans in search of food and roosting sites [ ] . bats are known to have varying degrees of contact with domestic animals and commercial food crops [ , ] , in particular contact of pteropus giganteus bats with date palm sap producing trees in bangladesh is considered a risk factor for human niv infection [ ] . livestock can act as an intermediate host between bats and humans. the outbreak of niv in malaysia in was linked to infection of pigs via fruit bats and resulted in the culling of over one million pigs and the deaths of over people [ ] . similarly, in australia hendra virus is transmitted to humans via horses; to date horses and seven people have been infected (four people have died). bats themselves are a known food source for humans in some areas of africa [ ] and asia [ , ] . while bats in the european union (eu) are known to harbor zoonotic viruses that can be transmitted via close contact, such as the european bat lyssaviruses and (eblv and ), there is currently no confirmation of the presence of viruses with pandemic potential in bats in the eu (i.e., at least capable of sustained human-human transmission). however, it is important to note that this should not be taken as proof of absence of such viruses, but rather that they have not been detected during surveillance of bat populations in the eu to date. historically, the first reports of human marv cases were in laboratory workers in germany and yugoslavia in , through direct contact with blood from african green monkeys (cercopithecus aethiops) imported from uganda [ , ] . however, more recent cases of bat-borne viruses affecting humans in the eu have been isolated incidents, notably the case of a dutch tourist returning from uganda after visiting a bat cave in which marv-infected bats roost [ , ] . similarly, as of november , cases of mers-cov have been detected in europe [ ] , several clusters of which represent chains of transmission in which the primary case had been infected in the middle east. previous studies have demonstrated the presence of similar viruses in eu bat populations, suggesting there is a risk of spillover of related viruses in the future. the first filovirus discovered in europe that was not directly imported from an endemic area of africa was lloviu virus (llov), detected in dead insectivorous bats in massive bat die-offs in caves in spain in [ ] . simultaneous bat die-offs were observed in portugal and france, although a causal relationship between llov and mortality was not shown. countries in the eu have strong historical links with many of the countries where zoonotic bat-borne viruses such as niv and marv are present and, consequently, commercial trade and human travel pose a potential route of introduction of such viruses into the eu. many patients in the ebov outbreak in uganda presented with mild clinical symptoms raising concerns that travel is possible whilst infected, [ ] . other factors, such as the importation of bushmeat, including bats and body parts of primates [ ] , could be potential routes of virus introduction. a qualitative risk assessment for the introduction of henipaviruses to the uk concluded that there was a low level of risk from southern asia, south-east asia and australia, through import of fruit and bushmeat and a very low level of risk through import of bat meat, horses and companion animals and through human travel [ ] . however, the assessment highlighted the high levels of uncertainty, reflecting the limited data and specific details of the routes involved. a risk assessment for niv establishing in australia also identified a lack of relevant data in various areas, reflected in the high levels of uncertainty in the risk estimates [ ] . in this paper we review the scientific literature relating to the risk of introduction of niv and marv into the eu, but do not formally assess the risk. we begin by reviewing the current evidence for the geographical location of the viruses and thus where a potential risk of introduction to eu member states (mss) may exist. next, we review the evidence for factors which may affect the probability of an eu introduction via the various routes, such as prevalence and transmission dynamics in bat species and survival and transmission potential of the viruses. finally we review the evidence directly relating to potential routes for introduction into the eu. the main routes we consider in detail are human travel, trade of fruit and pig products and illegal importation of bushmeat. other routes such as bat migration, the unintentional introduction of living or dead bats by aircraft and the effect of climate change are also given consideration. identification of countries which have had human cases of niv or marv is important for assessing the risk of introduction to the eu, as it identifies the areas from which human travel may be a particular risk. knowledge of the risk factors regarding human infection in these countries is also of relevance as they may suggest other potential routes of introduction, highlight similar factors which are present in the eu and may facilitate spread of the viruses, or indicate potential control measures. niv: studies suggest that human outbreaks are linked to one of two distinct nipah virus strains; niv-malaysia or niv-bangladesh [ ] [ ] [ ] . the malaysian strain emerged in with an outbreak in commercially farmed pigs, resulting in > human cases reported in malaysia and singapore with a case-fatality rate approaching % [ ] . pteropus vampyrus and pteropus hypomelanus were subsequently identified as likely natural reservoir hosts for the virus [ , ] . in this instance, pigs were implicated as amplifier hosts with viral isolates from both sick pigs and humans showing identical nucleotide sequences [ ] . the presence of large commercial pig farms with fruit trees in the vicinity meant that foraging bats could drop partially eaten fruit contaminated with niv into pig farms. pigs could then have access to this fruit and become infected with niv [ ] . transmission was attributed to direct contact with infective excretions and secretions and viral spread among pig farms was due to movement of pigs [ ] . there were no reported incidences of human-human transmission and there have been no further acute human cases attributed to niv-malaysia since , although relapsed and late onset cases have been reported [ ] . laws in malaysia preventing fruit farming in pig farming areas may have prevented further niv outbreaks. in contrast, there have been regular seasonal outbreaks of niv-bangladesh since its apparent emergence in , predominantly in bangladesh, although two outbreaks have also been reported in west bengal, india, close to the border of bangladesh [ ] . up to january , there have been reported human cases linked to niv-bangladesh with deaths, giving a reported case fatality rate of % [ , ].this appears much higher than the case-fatality rate of niv-malaysia, although direct comparison may be complicated by various biases such as method of surveillance and reporting. while human-human transmission is considered a major pathway for human infection with this strain [ ] , studies in india and bangladesh suggest the main risk factor is consumption of raw date palm sap [ , , ] . date palm sap is harvested from december through to march by cutting into the tree trunk and allowing the sap to flow overnight into an open clay pot [ ] . infrared camera studies have demonstrated that p. giganteus bats frequently visit date palm sap trees and lick the sap during collection [ ] , potentially contaminating it with niv from saliva and/or urine. other reported risk factors for human infection include consumption of alcoholic beverages made from date palm sap [ , ] , climbing trees and contact with other niv infected patients [ ] or animals [ ] . a recent study investigating the role of landscape factors in niv spillover risk in bangladesh [ ] found a significant correlation between niv spillover and villages with higher human population density, more fragmented forest cover and p. giganteus roost sites containing the tree species polyalithia longifolia or bombax ceiba. the geographical distribution of cases within bangladesh is shown in figure . cases generally occur in areas near inland water, predominantly the ganges, which provides a suitable habitat for date palm trees. in , there were cases reported from districts, more than in any other year, but generally only a few cases per district; the largest number was five cases reported from manikganj [ ] . the pattern of cases suggests multiple small outbreaks in different regions, rather than large outbreaks caused by one source. [ , ] . initial laboratory investigations at the time of the niv outbreak in siliguri (india) in did not identify an infectious agent. retrospective analysis, however, identified the presence of niv antibodies in serum samples by enzyme-linked immunosorbent assay (elisa) and rna by real-time pcr (rt-pcr) in (stored) urine samples [ , ] . sequence analysis confirmed that the pcr products were more closely related to the bangladesh strain ( . % identity) than the malaysia strain. to date, there is no reported evidence of niv outbreaks in humans emerging in other parts of india or in any other countries. however, given the delay in identification of the siliguri outbreak and large distribution of bats that can carry niv, it is possible that more human cases have occurred where niv has not been detected or reported. additionally, surveillance for niv in bangladesh may be more sensitive due to the previous cases reported to the authorities each year. as such, wider geographical distribution of human cases of niv should not be ruled out. marv: since the outbreak of marv in laboratory workers in europe [ ] , outbreaks have been confined to sub-saharan africa, although there have been reported cases of individuals acquiring infection in uganda and then travelling to the netherlands [ ] and the usa [ ] . human cases of filovirus infection in africa have been associated with hunting fruit bats for meat and with entry to mines or caves where large populations of fruit bat species, such as rousettus aegyptiacus, are present [ , , ] . it has been suggested that human infection could be through exposure to the excretions from bats roosting in the caves [ ] , although an experimental study on r. aegyptiacus bats inoculated with the hogan marv strain (originally from the south africa outbreak [ ] ) did not detect virus in the faeces of infected bats [ ] . one study reported -working as a miner‖ as a significant risk factor for a positive antibody result to marv, with % of the population who tested positive for marburg antibodies working in the local gold mines [ ] . there has not been a direct food consumption transmission route reported for marv, although index cases of filovirus infection have often had suspected contact with dead primates found in the forest, with exposure thought to occur during the butchering process [ , ] and the hunting process, which may involve the use of shotguns, potentially causing spray of body tissue and fluids [ ] . identification of countries where niv and marv have been detected in bats is important to understand the potential for infected bats from these areas to directly enter the eu, contaminated trade products destined for the eu, or infected humans who may travel to the eu. knowledge of the species of bats that are susceptible to niv and marv is also a relevant factor for assessing the susceptibility of bat species present in the eu. there is a growing body of literature on the geographical distribution and range of niv and marv in animal species with particular reference to bats. a complicating factor in defining the range is that studies in bats typically report serological or rna detection results, rather than detection of infectious virus. while a seropositive result is strong evidence of historical exposure to a virus, there may be cross reactivity with related viruses, precluding exact identification of the virus to which exposure has occurred, as seen for niv and hev in australasia [ ] . detection of rna demonstrates the presence of genetic material, but does not prove current presence of infectious virus. additionally, there can be difficulties in using serological assays outside their original, validated scope, for example when an existing assay is used with samples from an alternative species [ ] . here, the absence of positive and negative control samples and -gold standard‖ diagnostic assays makes it hard to determine an appropriate cutoff point to distinguish between seropositive and seronegative individuals [ ] . as such, positive identifications do not confirm active virus infection at the current time and, in some cases, could only be an indication of historical exposure to a related virus. in the absence of virus isolation or full genomic characterization, it cannot, therefore, be definitely confirmed whether the virus is currently present. niv: table shows a summary of reported testing for niv in bat species. niv is predominately associated with asian fruit bats of the genus pteropus, which have been suggested as the natural reservoir for henipaviruses [ ] . only a few studies have successfully isolated niv virus from bats. isolation has been reported from the urine of p. vampyrus [ ] and p. hypomelanus [ ] in malaysia and p. lylei in cambodia [ ] , but at very low prevalence, with only / samples yielding a virus isolate in the cambodia study. such low prevalence could be a factor for the inability to isolate niv in test samples of bats in other studies. rna positive pcr results have been obtained for p. vampyrus in indonesia [ ] and p. lylei in thailand [ ] , which identified both niv-malaysia and niv-bangladesh rna sequences. niv rna has also been detected in p. giganteus in india [ ] and p. vampyrus and rousettus amplexicaudatus in east timor [ ] . of particular interest to the eu is the identification of henipavirus antibodies in myotis daubentonii in china [ ] , as this species is also found across much of europe, although it should be noted that niv specific rna was not detected in this study and virus isolation was not attempted. while niv is predominantly associated with asia there is increasing evidence for the presence of related viruses in africa. paramyxovirus rna related to hev and niv has been detected in eidolon helvum bushmeat in the republic of congo [ ] and in the faeces and urine from roosting e. helvum bats in ghana [ , ] . viral concentrations were estimated to be low using rt-pcr assays [ ] . other studies have identified henipavirus antibodies in eidolon dupreanum and pteropus rufus in madagascar [ ] . a recent study combined genetic and serological analyses to determine the extent of connectivity among e. helvum populations across central africa. antibodies to henipaviruses were present in bats from all locations with henipavirus seroprevalences reported to be between %- . %, with an overall average of . % [ ] . however, the presence of infection on isolated islands suggested that large population size and connectivity may not be responsible for viral persistence. these studies do not confirm the specific presence of infectious niv virus in bats in continental africa and madagascar, but they now constitute a reasonably substantial body of work, from a number of independent sources, which suggest increasingly strong evidence for the presence of henipaviruses in bats that have a geographical range outside of asia and oceania. marv: table shows a summary of reported testing for marv in bat species. there are several studies reporting the prevalence of marv in bats in caves in africa including the countries of gabon, uganda and the democratic republic of congo (drc) [ , [ ] [ ] [ ] [ ] [ ] . marv is now considered endemic in r. aegyptiacus bats in gabon [ ] and, in general, those bat species which serve as potential reservoirs for marv are endemic to regions of central africa. there is little evidence for the potential of marv to occur outside africa at this point, although there are few published reports of testing for this virus on other continents; a study in india showed that none of bats tested, including p. giganteus (n = ), cynopterus sphinx (n = ) and megaderma lyra (n = ), were positive by pcr for marv rna [ ] . within africa, there are also reports of antibody or rna evidence of marv infection in bat species other than r. aegyptiacus, such as rhinolophus eloquens, miniopterus inflatus [ ] and hypsignatus monstrosus [ ] , but reports are less frequent. this highlights the importance of knowledge on the exact species of bats for the purpose of risk assessment, suggesting the main zoonotic risk is likely from r. aegyptiacus. in an experimental study, marv was found to be present in the blood and saliva of viraemic r. aegyptiacus bats but not in their faeces or urine [ ] , suggesting that close contact between adjacent bats of the same species within the roost may be important for marv transmission. marv rna has also been reported in a pooled liver, spleen, lung extract from a female r. aegyptiacus fruit bat in kenya in , although tissues from other bats including r. aegyptiacus from two locations were negative [ ] . from an eu perspective, r. aegyptiacus are known to be present in cyprus [ ] and turkey [ ] and populations were found in the wild in tenerife in the early s, as a result of escaped captive animals [ ] , before being effectively eradicated by . there is no reported evidence to suggest presence (or absence) of marv in these populations. bat host heterogeneity of virus prevalence is important both in terms of further spread of infection within the roost and spill-over to humans, e.g., through being hunted for bushmeat. some fruit bat colonies in trees in ghana have up to million bats, so the prevalence may vary spatially within the colony [ ] . fruit bat colonies in caves with more than , r. aegyptiacus bats are structured with juveniles more likely to be exposed to bat droppings due to their peripheral positions within the colony [ ] . a study on active infection of marv in a bat cave in uganda found a higher prevalence in older juvenile bats ( . %) than younger juveniles ( . %) or adults ( . %), the older juveniles were six months old at the time of capture and younger juveniles three months old [ ] . thus, an important consideration is whether juveniles and adult bats have different behaviors that would affect the onward transmission of marv. for example, are older juvenile bats and non-breeding adult bats more likely to range further in migration (and hence spread disease to other hosts) than younger juveniles or the breeding adults, or to be caught by bushmeat hunters (as they are less experienced in survival)? based on data gathered in tables - , those countries of the world where there is evidence of recent niv or marv infection in humans or bats are highlighted in figure . we define that a country is positive for human infection only if it has had a reported human case in the last years (i.e., since ). such a period of time without a reported case suggests that while there may still be potential for a human case in the country itself, the risk of import to the eu is extremely low. thus, malaysia and singapore are not considered positive for niv and south africa and kenya are not considered positive for marv. given the issues regarding use of serological positive results as an indicator of current virus presence, we do not consider serological positive results alone to be an indication of current viral presence in bats for this analysis. information from the iucn red list website is used to determine the geographical range of those bat species known to have been naturally infected [ ] , as there is a potential for undetected viral presence in these countries. it can be seen that while recent human infections of both niv and marv appear to be limited in geographical range (the red areas in figure ), there are a number of countries where bats have been identified as having the virus, but no human infection has been reported. it is also noted that the full geographical range of these bat species is extensive and in the case of r. aegyptiacus encroaches on the south-east boundary of europe, although the range of pteropus bats is much further east. however, if species serologically positive for henipaviruses are considered then m. daubentonii would be included and the geographical range would be much wider, encompassing europe and australia. viral load is a measure of the number of viral particles present in an organism or bodily fluid, e.g., the mass/volume of bat faeces, urine, saliva or bushmeat. the virus may be quantified in a number of ways including plaque-forming units (pfu), tissue culture infectious dose % units (tcid ) or number of genome copies. currently there are no published dose-response curves that convert pfu or tcid units in to risk of infection in humans or livestock animals. furthermore, the genomic copies may not all be equally infectious (due to the mutant spectrum) and some may be defective. it is not clear whether dispersion of the virions lowers the risk of transmission. however, the viral load is an important factor in a release assessment for any virus because it directly affects the risk of transmission. niv: while the studies mentioned previously demonstrate the likelihood of a continual reservoir of niv in many countries, the actual prevalence of bats currently shedding virus may be very low. as such, data on viral load is limited. however, with the application of real-time pcr, henipavirus-related sequences ranging from to , genome copies per . cm and . × per ml of bat urine have been reported [ ] . experimental studies have also been conducted in other animals. titres of up to pfu/ml from brain and basal turbinates and pfu/ml from trachea swabs were obtained from niv infected piglets [ ] , with lower levels found in lung and spleen and shedding peaks during the first week post inoculation. titre data are also available for niv strains from bangladesh and malaysia in experimentally infected rodents [ , ] . marv: one study reported that no viraemia or presence of marv rna could be detected in various tissues collected from r. aegyptiacus bats experimentally inoculated through oral or nasal routes [ ] , but subcutaneous and intraperitoneal inoculation resulted in high levels detected in plasma ( to tcid /ml) for five to nine days post inoculation, with titres up to . and . tcid /g in the liver and spleen respectively. virus was also occasionally detected in lung, heart, kidney and salivary glands with loads up to . tcid /g. ranges for tcid /ml of marv in tissues of naturally-infected r. aegyptiacus in uganda have also been derived from a standard curve of diluted stock virus using q-rt-pcr [ ] . high values of , - , , tcid /ml were obtained from liver, spleen and lung whilst values of - tcid /ml were obtained from multiple tissues including blood and intestines. a potential factor affecting the prevalence of viruses, regarding the risk of zoonotic transmission, is seasonal pulsing, or oscillations of prevalence, with peaks in prevalence at specific times of the year. periods of higher risk are relevant to eu incursion as they will affect factors such as the probability of eu tourists contacting an infected bat and thus impact on routes such as human travel to and from niv and marv areas. indeed, seasonal pulses of marv circulation in juvenile r. aegyptiacus bats coincide with periods of increased risk of human infection [ ] . the influx of susceptible young is a crucial driver of infection dynamics and bat reproduction and survival are thought to be major drivers of bat disease dynamics [ ] . many bat species exhibit highly synchronised parturition which can dramatically alter population contact rates and susceptibilities. sex differences in behaviour and distribution of bats during times of the year when the potential for disease transmission is greatest may also have important implications for disease dynamics [ , ] . the role of bat torpor in infection dynamics is largely unstudied [ ] . torpor typically reduces pathogen replication rates and hence lengthens the incubation periods. a study found a clear indication for torpor being a key factor in allowing perpetuation of rabies virus through the hibernation period, through prolonged incubation period and reduced mortality [ ] . this enabled the virus to persist in the population until susceptible individuals from the annual birth pulse could become infected and continue the cycle. migration and coloniality may also be important drivers of disease dynamics [ ] , altered migration behaviour may result in declining immunity within specific colonies which could lead to more explosive hev epidemics [ ] . niv: there is evidence of a seasonal pattern for spillover of niv to humans; a review of all human outbreaks of niv between and found that, except for the initial event in malaysia, they all occurred in the first five months of the year [ ] . a longitudinal study in thailand found the bangladesh strain of niv was dominant in the urine of p. lylei bats, with highest recovery of rna in may [ ] . in two sites, the bangladesh strain was almost exclusively detected between april and june while the malaysian strain was found dispersed during december to june. breeding of the bats (including mating and birthing) occurs in december to april, and may not be the only factor involved in bat transmission. there is some evidence that pregnant and lactating pteropus scapulatus and p. conspicillatus females had a significantly higher risk of hev infection [ , ] resulting in a seasonal pattern due to seasonality of reproduction of these bats. a study on an orchard in new south wales investigated the legal shooting of pteropus poliocephalus [ ] , found that the majority of bats shot were female (ratio : . ) and that % of these females were lactating. this suggests that pregnant and/or lactating females are more likely to be foraging for food and coming into contact with crops/orchards, which could not only be eaten by horses, but also could contribute to seasonality of human spillover for viruses such as niv bangladesh, for which oral transmission to humans through date palm sap is a route. the wild date palm produces sap seasonally from mid-october to mid-march and winter (december to early february) is the traditional date palm sap gathering season in bangladesh. outbreaks of niv generally coincide with this season, appearing between december and may. marv: a study of marv in r. aegyptiacus in the python cave in uganda predicted an oscillating biannual pattern of bat prevalence in the cave, with peaks in february and march. these peaks in prevalence coincided with the birthing seasons of the bats in the cave and the temporal clustering of previous reported spillover events of marv into humans [ ] . pcr data showed distinct oscillating pulses of marv infection in older juvenile bats (~six months of age) peaking in february and august that temporarily coincided with the peak twice-yearly birthing seasons. the authors speculate that the marv pulses reflect the pulses of newly weaned bats which populate the -low-lying‖ roosting areas where they are infected and may pass infection amongst themselves [ ] . as they age, and are recruited into the adult population, their colony positions are taken by the next generation of juvenile bats. it is not clear whether the oscillation peaks in juvenile bats coincide with other environmental/ecological factors affecting the bats such as local shortage of fruit or migration. knowledge of survival of virus in different media and under different environmental conditions is important for assessing the concentrations of virus on contaminated fruit and infected bushmeat over time and ultimately the risk to humans. this can be used to predict the concentrations of virus on the surface of fruit after export by taking into account the duration of transport to the eu. duration of infection in both humans and bats is also important when considering the probability of shedding infectious virus on arrival in the eu. niv: the incubation period for niv in humans has been reported to be as much as days [ ] . surveillance in bangladesh in found that among secondary cases, who had a single exposure to niv, the delay between exposure to onset of illness ranged from - days, with a median incubation period of nine days [ ] . the incubation period following a single intake of raw date palm sap to onset of illness varied between - days, with a median of seven days. a laboratory study on persistence of henipaviruses under various environmental conditions found that they were sensitive to ph, temperature and desiccation [ ] . the study showed a - log inactivation of henipaviruses in fruit juice (lychee, pawpaw and mango) over three to four days, although titres were still detectable after three days. there were also large variations in the half-life of the virus at different temperatures and ph values; e.g., in mango flesh, the half-life of niv was . hours for ph . at °c but . hours for ph at °c. for the purpose of risk assessment it is the rate of inactivation which is important, rather than the limit of survival, which depends on the starting titre. marv: investigation of the outbreak of marv in germany suggested that the incubation period could be as much as nine days [ ] . an experimental study on the effects of marv on the common marmoset (callithrix jacchus) found that animals became febrile after - days [ ] . an experimental study looking at marv, zaire ebolavirus (zebov) and reston ebolavirus (rebov), demonstrated survival for long periods in liquid media at both room temperature and °c, with virus recoverable from glass and plastic surfaces over three weeks after the start of the experiment [ ] . similar decay rates were found for marv and zebov, while rebov had significantly better survival within an aerosol. although data for survival of filoviruses on fruit are not available, a study looking at survival of poliovirus, simian rotavirus and feline calicivirus in the uk found prolonged periods of survival on fresh fruit and vegetable produce at refrigeration temperatures ( - °c), extending beyond the shelf life of the product [ ] . survival at °c was poorer, but some viruses remained viable for over a week. removal of viruses using conventional chlorine washing could give more than log reduction, but was only < log for poliovirus. however, it should be noted that these are non-enveloped viruses, and may, therefore, have different survival properties to the enveloped filoviruses. human-human transmission has been identified for both niv and marv. this, combined with incubation periods that could be over a week [ , ] , suggest that human travel could be an important route for transmission of bat-borne zoonotic viruses into the eu. the recent mers-cov cases in the eu highlight the risk of virus introduction from human travel [ ] . there has been one high profile case of tourism leading to an introduction of marv into the eu [ , ] . a similar, but non-fatal, incident from a person who visited the same bat cave in uganda also occurred in the usa [ ] . neither incident resulted in identified infection in other individuals. data from eurostat show that there are large numbers of people travelling between the eu and areas where niv and marv have been reported, both by air and by sea [ ] . the number of immigrants from these areas settling in eu countries is generally increasing and they will naturally have strong ties to their homeland. for example, the uk censuses of and show an increase in both number and percentage of the population of england reporting to be of indian, pakistani, bangladeshi and african ethnicity [ ] . combined, the indian, pakistani and bangladeshi ethnicity groups make up . % of the england population and % of the population of london in and similar data show that there has been an increase in the number of people reporting to be born in these countries [ ] . one could generally expect the individuals and their friends and families to have frequent trips to and from their native countries. data from the uk in suggested that out of , trips to the uk made by individuals using a bangladeshi passport, , were made by people returning after a temporary leave of absence [ ] . figure shows the migration into the eu from the niv and marv countries identified in figure . it is apparent that, in terms of migration from niv countries, the uk has the highest influx of migrants of all eu countries, while from marv countries it is france. further analysis showed that the majority of bangladeshi migrants go to the uk. this might suggest that when considering the risk from humans entering the eu from bangladesh, the uk is more likely to be at risk (before considering the impact of border control measures). previous research suggests that historically the bangladeshis that travelled to the eu were predominantly from sylhet [ ] , an area in the north east with very few reports of human niv cases, although more recently this may no longer be the case. it should be noted that some airports, such as heathrow, london, act as hubs for passengers going on to other destinations, which may lead to an overestimate for individual mss. however, an infected individual may be a risk even if only passing through the airport, as they will still likely have contact with airport staff and other passengers. a study looking at the risk of human-human transmission of viral haemorrhagic fevers (vhf), including marv, on airplanes found only a few events of vhf cases in the literature and no documented infection in follow up contacts [ ] . the study suggested that contact trace back should be undertaken for passengers and crew with direct contact with an infected individual, passengers seated within one seat of the case and cleaning staff responsible for cleaning the section occupied by the case. however, trace back of passengers seated more than one seat away from the infected individual was not considered necessary. this suggests that close contact is thought necessary for human-human transmission and so not everyone on an aircraft with an infected individual is likely to be at risk. as such, this would mean that spread of the virus to multiple locations in an eu ms, due to the dispersion of multiple individuals infected during the flight, is unlikely. however, the lack of data regarding vhf on flights and subsequent reliance on expert opinion in this study suggests that there is fairly high uncertainty surrounding the conclusions and further evidence should be sought, particular with regard to other viruses; factors such as stronger capability for airborne transmission could lead to different conclusions. tourism may have specific risks independent of other human travel. people who travel to foreign countries on holiday are likely to be there for only short periods of time, e.g., - weeks and some, particularly ecotourists, may visit bat caves or colonies, returning home soon afterwards. entering such areas carries the potential risk of direct contact with infected bats and contamination of shoes and clothing with potentially contaminated bat guano/faeces. there is a documented incident, in the python cave in uganda, of this leading to marv infection [ , ] , but there are numerous unofficial reports of similar such events. tourists are perhaps also more likely to be unaware of the risks of virus transmission, and therefore unaware of the appropriate precautionary measures. an author of this paper recently returned from west africa where they witnessed tourists entering an occupied bat cave and having contact with fresh bat guano. the tourists were not aware of the potential risks of virus transmission. however, the recent case of infection of a wildlife biologist with a novel paramyxovirus highlights that there is still a risk for people who are aware of and carrying out appropriate safety precautions [ ] . the short duration that tourists generally spend away means that, if infected, it is likely that they will return to the eu before clinical symptoms have developed, and there is little time for decay of pathogens in guano or indeed loss of guano from the clothing or shoes. it is well established that foodborne zoonoses can pose a threat to human health. pathogens may be present in products destined for human consumption either through infection of the source product in the natural environment (e.g., contamination of growing crops by infected animals or infection of animal tissues to be consumed while the animal was alive) or cross contamination of the product during processing, typically with urine or faeces. for viruses such as niv and marv, while cross-contamination during transportation could result in the presence of virus in other products, the most likely products to be contaminated are those that are associated with outbreaks, i.e., fruit and pig meat. while pig meat has not been directly associated with human infection, live pigs were identified as the source of human infection in the niv-malaysia outbreak, although pigs in malaysia are now considered free of niv [ ] . marv has not been associated with infection in any livestock animals to our knowledge (marv is known to infect primates which have been found in bushmeat seizures [ ] , but in this section we only consider animal products that would be traded legally for food). drinking raw data palm sap, or alcoholic beverages made from it, have been identified as risk factors for human niv infection in bangladesh [ , , ] , primarily due to the risk of direct contamination of the sap by the local pteropus bats. we have found no evidence of official trade of either of these products to the eu, although it is possible that individuals may bring alcoholic beverages with them in their personal belongings (the raw date palm sap ferments very quickly so is less likely to be brought over to the eu). while there are a number of products that involve its use, such as palm sugar, there are no reports of human infection as a result of consumption of such products. this suggests that the processing that takes place during the preparation of such products, in the case of palm sugar the sap is generally boiled, mitigates the risk. fruit bats are known to feed on a wide range of crops and they are often considered pests due to feeding in commercial orchards, although their importance in pollination is recognized [ , ] . a study on a vineyard in india found the old world fruit bat c. sphinx was responsible for > % damage to crops at the periphery of the vineyard [ ] . as such, it is common practice to protect commercial crops through the use of measures such as netting or shooting; one study on a stone fruit orchard in sydney, australia, consisting of four hectares of nectarine trees, where shooting was known to occur in order to protect the orchard, found a total of dead or injured flying foxes over days at the time when the nectarine crop was ripening and being harvested [ ] . niv-malaysia was isolated from fruit on tioman island, and contamination of fruit by bats is thought to be a potential route for the infection of pigs during the malaysian niv outbreak [ ] . a number of outbreaks in bangladesh have been linked with consumption of date palm sap [ ] , with the sap likely being contaminated with bat urine or saliva. while the date palm sap is the only identified foodborne source of human niv infection in bangladesh, bats could potentially have contact with, and contaminate with saliva or urine, any unprotected fruit grown in the region. while unlikely, if these crops are exported, there could be a risk of virus introduction into the eu. transport times can be less than hours by air travel, not long enough to allow significant decay of the virus. this route is less likely for marv as, to date, it has not been detected in the faeces or urine of either experimentally or naturally infected r. aegyptiacus bats [ , ] . faostat databases contain details of volumes of trade between eu mss and extra eu countries [ ] . the eu has strong trade links with the niv and marv identified areas in figure . while these databases show that there is little trade of pig products from niv and marv regions to the eu there is trade of fruit products (e.g., dates, apples, fruit juice). figure shows the relative volume of trade of fruit products from these areas and eu mss. the biggest importers from these areas are the netherlands and the uk, with germany having a relatively high volume from niv areas and france from marv areas. as with the human travel, it should be noted that some countries may act as hubs for trade products, with subsequent further distribution to other destinations. figure . trade data from faostat [ ] . trade of infected animals for non-food purposes could also pose a risk of viral introduction. marv has been identified in the african green monkey (cercopithecus aethiops), which have historically been traded for research purposes. there is considerable movement of horses around the world, primarily for sporting events. horses are known to be susceptible to hev with infections in australia [ ] , but to date there have been no reported cases of niv in horses. pet travel could also be a risk as the pets could potentially be infected with bat-borne zoonotic viruses in endemic countries. recently a kitten, infected with rabies virus, entered france from morocco demonstrating that such events can occur, even though the accompanying certificate of good health did not meet the regulatory provisions for the import of domestic carnivores from morocco [ ] . data from traces suggests that movement of live animals such as pets between niv or marv countries (as defined in figure ) and the eu are primarily animals not considered a risk of carrying the viruses (e.g., tropical fish) [ ] . however, there are a number of movements of cats and dogs. an experimental infection study of two cats with the malaysian strain of niv found that they started to develop clinical symptoms after five days [ ] . one cat developed acute clinical disease while the other recovered. virus was recovered from the tonsils and urine up to eight days post inoculation. while a very small sample size, and being aware that the experimental challenge dose is likely much higher than would be received in nature, this demonstrates that there is a potential risk of pets bringing the virus back into the eu. there is currently no quarantine regulation for third country pets, although the risk of bringing in pets from niv and hev areas is recognized by at least some mss [ ] . bat guano is also a potential trade product; it is sold for use as a fertilizer in several countries including thailand, indonesia, mexico, cuba and jamaica [ ] , and in theory could be imported into the eu. one study reported four of bat guano samples from a bat cave in ratchaburi province, thailand, were positive for group c betacoronavirus rna, although none contained niv rna [ ] . the legal importation of bats could also be a risk. the emergence of wild r. aegyptiacus bats in tenerife was believed to be a result of the escape of captive bats [ ] . there are no instances of live bat imports into the eu from niv countries on traces, but there are many instances of bats used in scientific research and zoos. r. aegyptiacus bats, known to be susceptible to marv, have been kept in zoo's in the eu; in two such bats died of rabies after being imported from a dutch zoo to a danish zoo [ ] . additionally there are reports of r. aegyptiacus being kept as pets. however, given the low numbers and the likely increased testing/surveillance of animals destined for these purposes the risk of importation from this route is likely very low. bushmeat is a term used to capture a variety of raw, smoked or partially processed meat that originates from the hunting of a variety of wild animals, including bats. it is well documented that bushmeat is illegally imported into both europe and the usa [ , , ] and, as such, it could act as a conduit for pathogen spread. in a recent study, illegal bushmeat imported into the united states was found to contain retroviruses and/or herpesviruses [ ] and henipavirus-like rna has been detected in internal organs of bat bushmeat sampled in the republic of congo [ ] . the perception of bushmeat as having zoonotic potential is not well recognized among bushmeat hunters, traders and consumers; one study reported that only % of bushmeat hunters in sierra leone are aware of the zoonotic disease risk [ ] and in a survey on bushmeat in the usa, participants in a focus group considered bushmeat to be a wholesome healthy and safe alternative to commercially produced meat from a shop [ ] . in an experimental study of r. aegyptiacus bats, marv was not detected in muscle, brain or skin tissues collected after cardiac exsanguination [ ] . this suggests that these tissues (including muscle) are not heavily infected, and that positive results in liver, spleen and kidney were not due to the presence of blood. if confirmed to be the case in naturally occurring infections, it could mitigate the risk of marv infection from the consumption of bushmeat if internal organs are not eaten. hunting of wildlife for food is a widely distributed practice in many parts of the world and constitutes an important source of animal protein for some rural communities. one paper reported that . % of households in brazzaville, congo consumed bushmeat [ ] and a survey of municipal markets identified different animals species, nine of which it is prohibited to hunt [ ] . economic recession over the past years has driven the commercialisation of bushmeat as a trade item; bushmeat now reaches the international markets as part of the $ billion annual global wildlife trade. the commercial trade in bushmeat occurs across almost all of tropical africa, asia and the neotropics, notably in the densely forested regions of west africa [ ] . estimates of bush meat harvests in ghana are around , tons annually [ ] . the bushmeat markets across west africa are nowadays dominated by small bodied, fast reproducing species such as rodents like the grasscutter (thryonomys swinderianus) [ ] . there is little officially reported information on the use of bats as bushmeat, a review of survey papers on bushmeat did not report anything on bats [ ] , but unofficial reports and eye witness accounts suggest it is not uncommon to see bats for sale in african markets. it is possible that bats do not follow a typical bushmeat commodity chain and amounts are therefore underestimated in standard bushmeat surveys [ ] . bats are often hunted for pre-arranged orders and regular customers rather than sale through wholesalers who may prefer to concentrate on larger animals with a higher value-to-weight ratio. one study estimates that , e. helvum are sold each year in southern ghana [ ] . this involves a commodity chain stretching up to km and involving multiple vendors. no official data regarding the size of the bushmeat trade exist as much of the trade is informal or illegal. while much trade is intra-country, trans-border trade does occur through known trade routes throughout the region and there is a limited amount of inter-continental trade from africa to europe [ ] . recently a quantity of bushmeat thought to be from the central african republic was seized by french police, and was reported to include bats, although the species were not named [ ] . imports of bushmeat into the uk do occur and mostly take place from those parts of africa with which the uk has close historical connections, in particular west africa [ ] . residents of the uk who have their ethnic and cultural origins in central and west africa and who are returning from a visit there often bring bushmeat into the uk for their own consumption. in comparison with the domestic market in bushmeat in central and west africa the amount of bushmeat coming into the uk represents only a very tiny fraction of the total turnover [ ] . a wildlife policy briefing report, which sets out bushmeat preferences in urban liberia provides a good indication of the sort of bushmeat likely to be imported into the uk, since returnees and visitors to the uk are most likely to buy their bushmeat in urban markets and are likely to reflect current local preferences [ ] . the list comprises ungulates, rodents, primates and pangolins. bats do not feature in the most preferred animals for taste from urban communities in west africa or in the more generic list of animal involved in the bushmeat trade in west africa. chaber et al. sampled passengers from flights from central and west africa to france over days in june [ ] . fifty-five passengers were found to be carrying fish or domestic meat and nine were carrying bushmeat. average individual consignments of bushmeat were over kg, compared with and kg for livestock and fish. most illegal imports detected by uk border agency are small amounts and continue to be typically gifts by travellers visiting family (or returning from visiting family abroad), or seizures from tourists, business people and students travelling to the uk for the first time. most do not involve deliberately smuggled goods but are made from passengers who are not aware of the current rules and prohibitions in place for products of animal origin (poao) imports [ ] . as well as personal carriage, bushmeat may be imported either by postal carriage or commercial freight to the eu. hm revenue and customs found bushmeat to constitute % of poao customs seizures for the period - . some bushmeat samples entering eu states from africa do so from european transit flights, as under the single market goods can travel freely from one member state to another without checks. thus the situation in any specific member state depends on the effectiveness of border controls in other member states. the bushmeat from animals hunted in tropical forests destined to be carried to the eu is likely to be preserved in some form for the duration of the journey. the bushmeat consumed in the uk imported from west africa is most often either smoked, dried or salted [ ] . because of this processing the initial load of viable organisms on the bushmeat would be expected to be reduced significantly. the average duration of smoking of bushmeat was found to be about hours minutes per day at a maximum temperature of . °c [ ] . to preserve the bushmeat it may be frozen on arrival in the uk. freezing in general promotes virus survival and a laboratory study suggested long survival times of marv at °c [ ] . throughout africa and asia, bats have been used in zootherapy, which is the treatment of human ailments with remedies made from animals and their products. around % of the population in africa uses traditional medicine and there is also a growing interest in many developed nations [ ] . there is evidence of bats being used for specific ailments in zootherapy and it is possible that they may still be used by migrants in european countries. treatment of ailments with bats include disorientation in patients with mental illness [ ] , fertility medicines and post birthing remedies, [ ] , the use of bat droppings of p. giganteus to treat patients with alcohol and drug addiction, [ ] , and night blindness [ ] . in asia, asthma is the most frequently cited disease for which bats are used as a remedy [ ] [ ] [ ] . these therapies are frequently practiced in countries where there is evidence of niv infection in bats. kanda tribal healers in bangladesh use p. giganteus in formulations for the treatment of fever [ ] , one pharmaceutical company in vietnam reportedly imported tonnes of faeces of rhinolophus bats [ ] . in a survey of asthma patients in singapore primary care clinics on the use of complimentary therapies, patients ( . %) had used complimentary medicine out of which ( . %) used animal products, ( . %) of which had used fruit bats [ , ] . whilst there is evidence that bats, as bushmeat, are eaten extensively in africa and asia there is little evidence of them being internationally traded or brought to the eu in personal possessions; a number of studies have investigated illegal imports of bushmeat, but rarely have bats been among the samples seized. however, these are relatively small studies and do not confirm the extent to which bats are exported as bushmeat. additionally, other animals, such as monkeys, were identified in the seized samples and are known to be susceptible to viruses such as marv. a review of possible microbiological hazards associated with the illegal importation of bushmeat concluded that although there was a lack of quantitative data relating to the microbiological risks, the risk of foodborne illness from consumption of bushmeat appeared to be very low and the risk of foodborne illness from cross contamination was also minimal [ ] . normal cooking would probably destroy any viruses and bacteria present although there were no data presented to verify this. the risk from use of bats in zootherapy is not as well understood. however, while the risk of contaminated bushmeat may be low, the consequence could be very high. migration is a seasonal, usually two-way movement from one place or habitat to another, to avoid unfavourable climatic conditions and/or to seek more favourable energetic conditions [ ] . some bat species are known to migrate large distances and cross national borders [ ] . such behaviour will connect seemingly distant bat populations, and an infected individual could therefore act as a vector to introduce a new virus into a naï ve population. bat flights are generally short distances for the purpose of foraging, hunting, changing roost sites or social behaviour. indeed, the majority of bat species in the world are sedentary. some bats, however, particularly those in the temperate regions of the world, perform annual long distance flights [ ] . bat migration typically occurs along rivers, as shown for bats in poland and central slovakia [ , ] and tends to avoid mountainous areas [ ] . with regards to bat species and geographical areas relevant to niv and marv, in congo a massive annual fruit bat migration takes place up the lulua river with hunting of the bats by villagers. direct exposure to the fruit bats may have led to an outbreak of ebov in [ ] . regular mass long-distance migrations have not been reported for r. aegyptiacus [ ] and a sedentary life history for r. aegyptiacus is also supported by the morphological record [ ] . in contrast, some e. helvum individuals migrate more than km [ ] , in some cases following the seasonal fluctuation in fruit abundance [ ] . thus, one study reported that that out of ( %) e. helvum ( %) were migratory, although % ( of ) were non-migratory [ ] . the median travel distance of the non-migratory bats was km (compared to km for the migratory bats) and similar to the observed daily commuting distances of r. aegyptiacus [ ] . based on available data and their own capture information, it was assumed that e. helvum has a core distribution in equatorial africa, with migrations in the northern direction, e.g., mauritania and niger from may to september and towards the south e.g., tanzania, zimbabwe and zambia during the months of october and december [ ] . thus, e. helvum from regions of africa north of the equator will generally migrate south in the autumn, away from europe. there is no evidence to suggest that the return migration routes in the spring would take the bats north of the sahara desert or that bats that might accidentally fly north (instead of south) in the autumn and reach europe. a review of data collected over years from banding of some one million bats within europe, provides information on which bats cross national borders [ ] . these data suggest there are a number of european bat species which migrate seasonally in the range of a few hundred kilometers and four species that are considered long distance migrants (regularly to km in one return flight). the migration routes are generally limited to europe, with the general trend from north-east to south-west europe. however, there are data showing movements of nyctalus noctula from russia into bulgaria [ ] and it is reported that pipistrellus nathusii killed in summer and autumn at german wind turbines originated from estonia or russia [ ] . an occurrence of vespertilio murinus on a north sea drilling rig confirmed that bats can fly across large bodies of sea [ ] . this raises the question of whether migration of bats from africa to europe can occur, for example, across the strait of gibraltar. there have been studies in relation to the genetic diversity in ibero-moroccan bats, but this does not address the frequency of vagrant african bats flying from morocco into southern europe. colonies of r. aegyptiacus, known hosts of marv, occur in cyprus and southern turkey. no banding studies have been done and existing knowledge is based on field observations in europe [ ] . in cyprus, no long distance flights are known, but seasonal altitudinal shifts have been observed [ ] , which could alter contact rates with other bat species. thus, despite the growing evidence on migration of bat species within europe, there are no data to suggest whether migration of bats into europe from niv or marv endemic areas (as outlined in figure ) could occur. a longer term risk factor is the gradual spatial creep of viruses due to transmission to previously uninfected species whose habitat spatially overlaps that of known infected species. for example p. vampyrus are known hosts of niv. they are not found outside of asia, according to iucn red list (see figure ), but have been reported in the shaanxi region of china, close to where m. daubentonii have also been recorded [ ] . m. daubentonii are also known to be present across europe and there is a report of henipavirus antibodies in three of four myotis bat species at a location in yunnan province, southern china in and . this included nine of m. daubentonii bats [ ] . although pteropid bats are not widespread in china, henipaviruses could be introduced to china by other susceptible bat species whose habitats and ranges overlap those of pteropid bats in neighbouring countries. this raises the question of whether henipaviruses could eventually emerge in european bats. however, there are a number of additional factors that may delay and/or prevent this from occurring, such as mountainous areas providing geographical barriers to interaction of neighbouring bat populations. indeed according to the iucn redlist the populations of m. daubentonii in china and europe are not contiguous. it would be interesting to know if bats in south-east asia migrate in a north-westerly direction to the same regions as those migrant european bat species to give a -virus cross-roads‖. the risk of eu bat infection with marv due to overlapping species populations is potentially higher than niv, due to shorter geographical distances, r. aegyptiacus are already present in some european countries where their range may overlap with some migratory european bat species, and the fact that some african fruit bat species (e.g., e. helvum) migrate large distances, although generally within the sub-saharan african continent [ ] . however, marv has not been isolated from any bats in cyprus or indeed northern africa, although there have been few published reports of attempts to find marv outside its normal range. additionally, marv has not been isolated from as many different bat species as henipaviruses, so the risk of virus transfer between species may be more limited. this may reflect the ubiquity of molecular receptors for henipaviruses among mammal species. there are a number of less obvious routes by which bat carcasses or products could enter europe. for example a bat strike on a long haul aircraft may result in the carcass of the bat being carried long distances across international boundaries. the remains of a bat were found in the wing flap of a boeing that had flown from heathrow (uk) to ben-gurion airport in israel [ ] . the plane had previously flown from ghana to london and pcr was used to identify the bat as having highest similarity with e. helvum. flying foxes and other bats were the animal species most often involved in aircraft strikes in australia between and with the majority of air strikes occurring at locations on the east coast of australia [ ] . for the year period ( - ) , strikes were reported to the united states federal aviation authority of which bats were involved in . % [ ] . this raises the question of what happens to the bat carcass remains and in particular how it is disposed of. in theory it could drop off the plane on coming into land at the destination airport as the carcass thaws or the wing flaps change position. this raises the possibility of the carcass being eaten by scavenging animals or even pet dogs or cats. accidental translocations of bats between land masses by ships or aircraft have also been known to occur, almost certainly with a far greater frequency than is actually reported [ ] . as some viruses such as coronaviruses can survive for long periods in water [ ] , bat guano or even dead bats transported in bilge waters of ships could, in theory, serve as route of transport of bat viruses around the world. another route, again involving aircraft, is where the bat is a stowaway either in the aircraft hold, or even the cabin itself. for example, in , a bat flew through the cabin of a commercial airliner minutes after takeoff during an early morning flight from wisconsin to georgia [ ] . the emergence of new viruses typically reflect change and combinations of events [ , ] . in this respect, anthropogenic changes, and in particularly globalization, are drivers. other changes including farming practice, environmental and climate change not only affect land use but also influence zoological and ecological factors including habitat and food supply. thus, over time, there may be changes in both the range and distribution of species and intensity and nature of species' interactions. climate change is associated with extreme weather events such as drought and flood. it is most likely to be linked to the geographical distribution of fruit bats through availability of food sources; the species p. nathusii has been observed to be adapting its range in response to recent climate changes [ , ] . this raises the question of how the range and population of fruit bats will change; ultimately, warming could convert forests to grassland savannas which are unsuitable habitats. a shift in the range of pteropid bats due to climate change could have an impact on the circulation of henipaviruses, by putting bats under stress [ ] . pteropus spp. may excrete viruses more often than usual in stressful situations such as when their food is destroyed by climatic events and extreme stress can result in immune suppression which can facilitate increased shedding of the virus [ ] . bats may also spread the virus between regions if they search for food in areas unaffected by flooding. additionally one study found a significant association with the dry season for spillover events [ ] . in this paper we have discussed factors that should be considered when assessing the risk of introduction of two bat-borne viruses, nipah virus and marburg virus, into the eu. the routes considered to pose a significant risk of introduction into europe include human travel, legal trade and illegal importation of bushmeat. a number of other potential routes should also be considered, including, bat strikes on aircraft and bat migration, although migration may not be significant as currently there is little evidence of significant migration pathways into europe. however, it is unclear whether the absence of knowledge of migration routes into the eu from the countries identified as having infection in bats from figure is because they do not exist or because their existence has not been comprehensively investigated. additionally, if niv or marv were to spread to areas on a european migration route, such as russia, then bat migration could become a greater risk. another, more long term risk for introduction to the eu could be transmission between bat species with overlapping distributions; r. aegyptiacus are hosts of marv and present in cyprus (although marv is not known to be present in bats in cyprus), where the range of this species may overlap with some migratory european bat species. it should also be noted that migration could pose a risk for other bat viruses which may be present on these migration routes. the two viruses discussed in this paper were chosen as they are not known to be present in eu bat populations, but published literature indicates their potential for causing large scale human outbreaks. there are many other bat-borne viruses of similar potential that we do not cover in detail here, but also require in depth consideration, such as ebola virus, hendra virus and mers-cov. at the time of writing there was limited and not conclusive evidence that mers-cov was a bat-borne virus [ , ] . while the risks of introduction of other bat borne zoonotic viruses should be considered on a case by case basis, there will likely be a degree of commonality with the factors and routes discussed in this paper, especially for viruses within the same family as marv or niv, namely filoviruses such as ebov and paramyxoviruses such as hev. while there is serological evidence of henipaviruses and filoviruses on multiple continents, the isolation of infectious virus in either bats or humans is currently limited to more confined geographical areas; niv in asia and marv in central africa. human infection of niv in particular is currently limited to bangladesh and west bengal in india. given the more widespread identification of niv amongst bat species and countries in asia, it is not clear why human outbreaks appear to be confined to this region. this could reflect the route of transmission, sensitivity of surveillance and also perhaps the greater titre of niv-bangladesh in bat saliva or urine compared to niv-malaysia [ ] . further knowledge of why these viruses do not currently seem to be spreading further, could help in assessing the risk of further spread, including the risk of reaching the eu. while a number of studies report high serological prevalence, actual virus infection in bats is rarely detected. this could explain why human spillover events of niv-bangladesh are fairly localised. p. giganteus roosts have been identified within km of villages in bangladesh and can consist of around individual bats [ ] , so even a low prevalence of infection within the roost can mean that there are still sufficient numbers of infected individuals able to contaminate local food sources such as date palm sap. in this paper we have discussed risks posed by bats, regarding entry of zoonotic viruses to eu, but the ecological importance of bats should also be recognized. insectivorous bats are responsible for controlling populations of other species considered to be pests such as mosquitoes and other insects, while fruit bats feed on nectar and pollen and so provide an important function as pollinators and/or seed dispersers [ ] . while the mass culling of pigs in malaysia undoubtedly helped to control the niv outbreak there, culling, or relocation, of wild bats could potentially increase levels of infection [ ] . for example, research in peru found that culling campaigns failed to reduce the seroprevalence of rabies among the studied vampire bat colonies [ ] . additionally culling of bats is considered by many to be unethical and methods are unavailable that comply with current standards of animal welfare. there are many alternative methods to help control virus disease, such as the use of bamboo skirts to prevent niv contamination of data palm sap in bangladesh [ , ] , limiting potential for indirect contact between livestock and bats at a local level, use of personal protective equipment by investigators dealing with suspect cases and a vaccine against hev in horses in australia [ , ] . this review identifies those routes which could provide a potential for introduction of niv and marv into the eu, but does not formally assess the risk associated with each route. for niv we have shown that, of the eu mss, the uk has the highest volume of relevant human travel (figure ), but the netherlands has the highest volume of relevant trade (figure ) , suggesting that the most probable route for introduction may vary between eu mss. however, to formally assess this it will be important to also take into account virus specific factors such as prevalence, titre and survival and ms specific factors such as border inspections or controls. therefore, it would be preferential to develop a quantitative risk assessment (qra), which would require large amounts of data. this review suggests that while data may be lacking to fully assess the risk for routes such as bushmeat, or indeed any other illegal activity, there are sufficient data available to assess legal routes such as volume of trade and human travel. in general, we found no evidence to suggest that the risk of niv release to the uk has changed from that reported in a previous qualitative risk assessment [ ] . reported human cases of niv continue to be limited to bangladesh and an increase in the number of those cases may be due to enhanced awareness and surveillance. a number of human cases of marv have been reported in uganda recently, but again this could be attributed to better surveillance. while there is evidence to suggest henipavirus infection of m. daubentonii in china and the presence of r. aegyptiacus in the eu country of cyprus, these are not sufficient factors on their own to warrant undue concern. however, it should be noted that there is a lack of research and surveillance in this area and the evidence for absence of niv or marv in bats present in the eu is limited. human migration patterns continue to change across some areas of the eu, suggesting the frequency of human travel to niv or marv areas and corresponding illegal imports of products such as bushmeat may change. this could increase the probability of a -rare event‖ occurring, such as importation of a bushmeat sample contaminated with virus and, as has been observed in the past, a single introduction event can be enough to cause an outbreak of disease in humans. a better understanding of surveillance sensitivity and biases in reporting, and further investigations of the presence and prevalence of these viruses in both bats and humans should be carried out, as high uncertainty remains about the risks associated with these diseases and how best to prevent or limit the risk of an introduction event. this work was funded by the european union fp project antigone (anticipating global onset of novel epidemics ) and the uk department for environment, food and rural affairs (defra) project se . the authors would also like to thank trevor drew and 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disease emergence: the past, present, and future drivers of nipah virus emergence the effect of bat (rousettus aegyptiacus) dispersal on seed-germination in eastern mediterranean habitats flying foxes carrying hendra virus in queensland pose a potential problem for other states ecological and anthropogenic drivers of rabies exposure in vampire bats: implications for transmission and control piloting the use of indigenous methods to prevent nipah virus infection by interrupting bats' access to date palm sap in bangladesh guidelines for veterinarians handling potential hendra virus infection in horses the authors declare no conflict of interest. key: cord- -z x zkht authors: hailay, abrha; aberhe, woldu; zereabruk, kidane; mebrahtom, guesh; haile, teklehaimanot; bahrey, degena; mariye, teklewoini title: the burden, admission, and outcomes of covid- among asthmatic patients in africa: protocol for a systematic review and meta-analysis date: - - journal: asthma res pract doi: . /s - - -x sha: doc_id: cord_uid: z x zkht background: coronavirus disease outbreak is the first reported case in wuhan, china in december and suddenly became a major global health concern. according to the european centre for disease prevention and control, on august , the reported cases of coronavirus disease were , , cases worldwide, , , recovered with , deaths. evidence on burden, admission and outcome of coronavirus disease in among asthmatic patients has not been published in africa. this research protocol will, therefore, be driven to conduct systematic review and meta-analysis of the coronavirus disease in burden, admission and outcome among asthmatic patients in africa. methods: all observational studies among asthmatic patients in africa and written without language limitation will be included. a search technique was applied using databases (pubmed / medline, embase, hinari, cochrane library, world health organization covid- database, africa wide knowledge and web of science). two independent authors carried out data extraction and assess the risk of bias using a predetermined and structured method of data collection. we will use random-effects to estimate the overall pooled burden, admission and outcome of covid- asthmatic patients in africa. to assess possible publication bias, funnel plot test and egger’s test methods will be used. this systematic and meta-analysis review protocol will be reported based on the preferred reporting items for systematic reviews and meta-analysis protocol guidelines. discussion: the description will be used to show the covid- distribution data by interest variables such as residence, setting, and person-level characteristics. the findings of this review will notify health care professionals about the burden, admission and outcome of covid − in asthmatic patient, while providing evidence to bring about the requisite improvements in clinical practice for asthmatic patients. systematic review registration: this review is registered in the prospero international prospective register of systematic reviews with the registration number of crd . in december , a new virus (initially called 'novel coronavirus -ncov' and later renamed to sars-cov- ) causing severe acute respiratory syndrome (coronavirus disease covid- ) emerged in wuhan, hubei province, china, and rapidly spread to other parts of china and other countries around the world and it suddenly became a major global health concern [ ] . the world health organization (who) has called the outbreak of coronavirus disease (covid- ) a global emergency [ ] . covid- 's clinical symptoms vary from asymptomatic illness to flu-like disease, including high morbidity and mortality from multi-organ failures. the majority of patients diagnosed with covid- have developed mild symptoms including sore throat, dry cough, and fever. the majority of them have resolved spontaneously. some have developed multiple fatal complications, such as: septic shock, extreme pneumonia, and organ failure [ ] . according to the european centre for disease prevention and control, on august , , the reported cases of coronavirus disease were , , cases worldwide, , , recovered with , deaths. the united states has the largest number of confirmed cases , , cases, , , recovered with , deaths in the world and followed by brazil has , , cases, , , recovered and with , deaths. in africa, the total number of confirmed were , cases, , recovered and , deaths. south africa has the largest number of reported , cases with total deaths cases in africa [ , ] . according to different studies, clinical features of covid- infection is varied based on the groups and showed greater risks for the development of pneumonia as a serious type of infection among the elderly people and with chronic comorbidities, especially systemic arterial hypertension, diabetes mellitus and immunosuppression. additionally, official chinese information showed that % of pregnant women with covid- were serious cases and may also be especially susceptible to infection [ ] [ ] [ ] [ ] . patients with asthma have likely to develop severe covid- and other complications than patients without asthma [ ] . there have been different reports about covid- [ ] [ ] [ ] [ ] . forty-five percent ( %) patients with covid − receive non-invasive respiratory support via a nonrebreathing oxygen face mask [ ] . sputum cells among patients with asthma may give a risk for covid- morbidity [ ] . the prevalence of covid- among asthmatic patient was % [ ] . yet, there is no pooled result of the covid- burden, admission and outcome among asthmatic patients in africa. this research protocol will, therefore, be driven to conduct systematic review and meta-analysis of the covid- burden, admission and outcome among asthmatic patients in africa. this review is registered in the prospero international prospective registry of systematic reviews (crd ) and reported according to preferred reporting items for systematic reviews and meta-analysis protocol (prisma-p) guidelines [ ] (table ) . all observational studies; including cross-sectional studies, cohort, case-control, and baseline results from randomized controlled trials carried out in africa will be included. all asthmatic patients (all studies include all age groups) who are african residence and laboratory-confirmed and/or clinically diagnosed with having covid- . asthma with covid- infection. therefore, we want to assess disease burden, admission and outcome of covid- on asthmatic patients will be reviewed. morbidity, admission, mortality and other clinical outcomes of covid- among asthmatic patients (prevalence rate, infection rate clinical characteristics include symptoms (such as symptoms of upper respiratory tract infection, myalgia, fever, cough, dyspnea/shortness of breath, electrolyte imbalance and organ failure). laboratory/imaging (chest x-ray, ct, c-reactive protein and whole blood count), and outcomes of asthma (recovery, complications and death) and covid- outcomes. hospital-based studies. without the restriction of language all published and unpublished papers will be included in this review. no limitation on diagnostic methods but subgroup review will be carried out based on diagnostic instruments. interim guidance from the who and/or any diagnostic criteria proposed by the who shall be considered 'who interim guidance for laboratory biosafety related to -ncov' [ , ] (table ) . describe the mechanism(s) that will be used to manage records and data throughout the review selection process b state the process that will be used for selecting studies (e.g., two independent reviewers) through each phase of the review (i.e., screening, eligibility, and inclusion in metaanalysis) describe planned method of extracting data from reports (e.g., piloting forms, done independently, in duplicate), any processes for obtaining and confirming data from investigators data items list and define all variables for which data will be sought (e.g., pico items, funding sources), any pre-planned data assumptions and simplifications outcomes and prioritization list and define all outcomes for which data will be sought, including prioritization of main and additional outcomes, with rationale risk of bias in individual studies describe anticipated methods for assessing risk of bias of individual studies, including whether this will be done at the outcome or study level, or both; state how this information will be used in data synthesis describe criteria under which study data will be quantitatively synthesized b if data are appropriate for quantitative synthesis, describe planned summary measures, methods of handling data, and methods of combining data from studies, including any studies that have not clarified the requirements for the covid- outcome level; studies that have not been conducted in humans, qualitative studies, studies that lack valid data required to determine the outcome will not be included. studies such as experimental studies, commentaries, editorials, letters, case reports, or case series will be excluded from this review. a search technique was applied using online databases (pubmed / medline, embase, hinari, cochrane library, who covid- database, africa wide knowledge and web of science) from february to august ( table ). the quest was performed either individually or in combination using the following keywords: admission, asthma, burden, covid- , outcome and prevalence. search terms to be used: "wuhan coronavirus" or "covid- " or "novel coronavirus" or " -ncov" or "coronavirus outbreak" or "sars-cov- " or "sars " or "severe acute respiratory syndrome coronavirus " or "burden" or "outcome". other searching terms will be "mortality" or "prevalence" or "incidence" or "asthma complication of covid- ". data were extracted using a standardized method of data extraction. two assessors (ah and wa) will autonomously extract data using the predefined standardized extraction form from the included studies. for further consideration of whether to include in the study or not, full texts for the qualifying titles and/or abstracts, including those where there is ambiguity, will be collected. the agreement between the reviewers of the study will be calculated using cohen's λ statistics. disagreements will be resolved by mediation, and arbitration by a third reviewer (gm) will occur when necessary. reasons for excluding articles will be noted. where there is missing information, authors have been contacted for additional details to ensure study eligibility. where necessary, up to three emails have been sent to the corresponding author to request additional information before excluding the study. we will consider the most recent, detailed, and with the highest sample size for studies that appear in more than one published article. we shall treat each survey as a separate study for surveys that appear in one article with multiple surveys conducted at different time points. data extraction was including information: first author, publishing month, country and/or region, signs and symptoms, complications, diagnostic criteria, comorbidity, covid- , study upon introduction pick. maybe repeated sampling to clearance monitor. additional work is required to assess the repeated sampling is for efficient and accurate. serology and other blood and stool are also responsible for the coronaviruses (covid- ) paired samples are needed to confirm with the original sample obtained during disease of first week and the second one preferably obtained after - weeks (there has to be an ideal timing for convalescent samples undertaken). area, prevalence and/or incidence, characteristics of the study (study design, response rate). a tool developed by hoy et al. for prevalence studies will be used to evaluate the likelihood of bias and quality of studies included in this review [ ] . the tool contains items; items - assess the external validity, - assess the internal validity, and item offers a description of the overall risk by the reviewer based on the responses of the above items which are rated if yes and if no. studies are graded as low (< ), moderate risk ( ) ( ) ( ) or high ( - ) risk of bias. two reviewers did this exercise, and disputes will be resolved through discussion and, where possible, through arbitration involving a third author. besides, adequate sampling methods, consistent methods and procedures for collecting data, recorded methods of quality control and representative sample size will be considered as indicators of the study quality. studies of high quality will be studies that revealed all the points mentioned above. a framework was developed a priori to guide the screening and selection process, based on the inclusion and exclusion criteria. the tool will be piloted and revised before data extraction begins. first, to delete duplicates, the search results will be uploaded to endnote software. the remaining articles will be put on rayyan, a smartphone and a web-based software system that facilitates the collaboration between reviewers involved in the screening and selection of studies to be included in the review [ ] . data extraction was including: authors, month, country and/or region, sample size, type of publication, study area, characteristics of the study (study design, response rate). the primary outcome is the burden, admission and outcome of covid − among asthmatic patients in african. r software and r studio will be used during analyzing the data. all analyses will be carried out using a "metaprop" routine for windows using r version . . [ ] . results will be reported as proportions with corresponding % confidence intervals (cis). forest plots will be drawn to represent the combined outcome of covid- and the extent of statistical heterogeneity among studies. the statistical heterogeneity will be evaluated using the χ test and quantified using the calculation of the i statistics with values of , and % being representative of low, medium and high heterogeneity, respectively [ ] . if there will be heterogeneity between studies, we will use a meta-analysis of random-effects [ ] to estimate the aggregate pooled burden, admission and outcome of covid- among asthmatic patients in africa. to assess possible publication bias, funnel plot test and egger's test methods will be used [ ] . p-value < . on the egger's test is considered statistically significant for bias in writing. the study-specific outcome of covid- among asthmatic patients will be recalculated using crude numerators and denominators from individual studies. a metaanalysis will be performed on variables that are similar across the included studies. because there will be heterogeneity among the studies, the random effect model will be used to determine the pooled burden, admission and outcome of covid- in africa. african geographic regions, diagnostic methods, and based on their ethnic background where the study was conducted will be summarized by a subgroup analysis. this review will be done based on the prisma-p guidelines and the prisma flow diagram and also used to document the different phases of the review process [ ] ( fig. ) . the findings of this review will notify to health program planners, decision-makers and health care professionals about the burden, admission and outcome of covid − among asthmatic patients, while providing evidence to bring good quality health care, the good emphasis for the problem, improvements in clinical practice. conferences, peer-review articles, and social media sites will share conclusions from this study. this systematic review and meta-analysis will be expected to quantify the burden, admission and outcome of covid- among asthmatic patients in africa. geographical tracking and mapping of coronavirus disease covid- /severe acute respiratory syndrome coronavirus (sars-cov- ) epidemic and associated events around the world: how st century gis technologies are supporting the global fight against outbreaks and epidemics the epidemiological characteristics of an outbreak of novel coronavirus diseases (covid- ) in china epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study organization wh. novel coronavirus ( -ncov): situation report covid- and older adults: what we know clinical features of fatal cases of covid- from wuhan. a retrospective observational study clinical characteristics and intrauterine vertical transmission potential of covid- infection in nine pregnant women: a retrospective review of medical records what are the risks of covid- infection in pregnant women? distinct effects of asthma and copd comorbidity on disease expression and outcome in patients with covid- coronavirus disease (covid- ) in neonates and children from china: a review covid- in older people: a rapid clinical review covid- and cardiovascular disease: from basic mechanisms to clinical perspectives psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the covid- pandemic epidemiology, clinical course, and outcomes of critically ill adults with covid- in new york city: a prospective cohort study covid- related genes in sputum cells in asthma: relationship to demographic features and corticosteroids aria-eaaci statement on asthma and covid- preferred reporting items for systematic review and meta-analysis protocols (prisma-p) statement laboratory testing for coronavirus disease (covid- ) in suspected human cases: interim guidance assessing risk of bias in prevalence studies: modification of an existing tool and evidence of interrater agreement rayyan-a web and mobile app for systematic reviews metaprop: a stata command to perform metaanalysis of binomial data measuring inconsistency in meta-analyses meta-analysis in clinical trials bias in meta-analysis detected by a simple, graphical test publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations not applicable. authors' contributions ah, wa, db was conceived and designed the study. the conceptualization and design of the study were contributed by all authors. the initial protocol was drafted by gm, wa kz, and th. all authors contributed to the development of the selection criteria, the risk of a bias assessment strategy, and data extraction criteria. all authors read, provided feedback, and approved the final protocol. not applicable. this study has not been submitted and considered for publish in any journal. the datasets used and/or analyses during the study will be presented within the manuscript and available from the corresponding author on request.ethics approval and consent to participate not applicable. not applicable. the authors declare no competing interests. key: cord- - domp w authors: dramé, moustapha; godaert, lidvine; callixte, kuate tegueu; ecarnot, fiona; simo-tabue, nadine; tabue teguo, maturin title: coping with the covid- crisis in sub-saharan africa: let us not leave older people behind! date: - - journal: eur geriatr med doi: . /s - - -z sha: doc_id: cord_uid: domp w nan at present, certain colleagues affirm that africa is more prepared than ever to face the covid- pandemic, thanks to the lessons they have learned from epidemics such as ebola [ ] . while we are fully confident that this is the case, it is nonetheless clear that in previous epidemics, as well as in the ongoing covid- pandemic, older persons are, once again, paying the heaviest toll. indeed, in the case of the current covid- crisis, in sub-saharan africa, no specific measures have been taken to protect elders, as there have been in high-income countries. in african countries, the main measures taken to stem the spread of the disease include closing borders, grounding commercial flights from severely affected countries, and postponing or cancelling major cultural or sporting events. these measures, while necessary and effective (on condition that they are properly implemented and respected), actually barely affect older people, who travel less than their younger counterparts and less frequently participate in large cultural or sports-related gatherings. conversely, older people have a leading role in collective activities of daily life, which continue unimpeded, such as prayer groups, weddings, christenings and funerals. older people also continue to stand in for parents, minding children with whom they are naturally in very close contact. all these circumstances combine to put older people at risk of contracting a range of communicable diseases, not least covid- . if the epidemic continues along current trajectories, african countries are or will be among the last to be affected by the covid- pandemic. yet they are likely to draw but little benefit from the experience acquired in western countries, notably because the measures applied in high-income countries are not appropriate solutions for sub-saharan africa. at present, total lockdown is the only measure that is unanimously considered to be efficacious. it has been widely implemented in western countries. currently, the focal point of the epidemic, while we await, is either an efficacious treatment or a vaccine, either (or both) of which may take several months to emerge. the social, economic and cultural context in sub-saharan africa renders total confinement virtually impossible. we also must not ignore the deleterious effect that lockdown has on social terms, isolating frail individuals and leaving them without support or resources. in a context of poor medical infrastructures and weakened health systems, the governments of sub-saharan africa do not appear to be fully cognizant of the risk that the older population is incurring. we are aware that in today's world, where social intermingling and movement is highly prevalent, it is difficult to implement targeted measures. however, giving the issue sufficient thought is a prerequisite to finding acceptable and efficacious solutions. nkengasong and mankoula [ ] exhort us to act collectively and fast. we say hear, hear-but let us not leave the older population behind when we move forward! the covid- crisis is afflicting the whole world and so the search for solutions should also include the whole world, taking account of local context. similarly, provision of resources to fight the epidemic should also occur on a worldwide scale. indeed, the crisis will only come to an end when every country in the world has vanquished covid- . in this regard, and to avoid any ageism, we applaud and adhere to the suggestion of lloyd-sherlock et al. [ ] to take age explicitly into account in the development of national and global planning for covid- , and to convene a global expert group for older people to provide guidance and inform our response to this urgent global health threat. updated understanding of the outbreak of novel coronavirus ( -ncov) in wuhan novel coronavirus (covid- ) epidemic: what are the risks for older patients? bearing the brunt of covid- : older people in low and middle income countries is africa prepared for tackling the covid- (sars-cov- ) epidemic. lessons from past outbreaks, ongoing pan-african public health efforts, and implications for the future looming threat of covid- infection in africa: act collectively, and fast we would like to thank professor emeritus jean-pierre michel for his very pertinent and sound advice. author contributions md: literature search, study design, data collection, analysis and/or interpretation and manuscript writing; lg: study design, analysis and/or interpretation and manuscript revision; ktc: study design, analysis and/or interpretation and manuscript revision; fe: study design, analysis and/or interpretation and manuscript revision; nst: study design, analysis and/or interpretation and manuscript revision; mt: study design, analysis and/or interpretation and manuscript writing.funding there are no funding sources for this work. conflict of interest there are no conflicts of interest to declare. indeed, authors do not declare any financial interests or connections, direct or indirect, or other situations that might raise the question of bias in the work reported or the conclusions, implications, or opinions stated-including pertinent commercial or other sources of funding for the individual author(s) or for the associated department(s) or organization(s), personal relationships, or direct academic competition.ethical approval not applicable.informed consent not applicable. key: cord- - or vf authors: ayebare, rodgers; waitt, peter; okello, stephen; kayiira, mubaraka; atim ajok, maureen; nakatudde, irene; bhadelia, nahid; lamorde, mohammed title: leveraging investments in ebola preparedness for covid- in sub-saharan africa date: - - journal: aas open res doi: . /aasopenres. . sha: doc_id: cord_uid: or vf the emergence of sars-cov- in china and transmission to more than territories worldwide, including nine countries in africa, presents a delicate situation for low-resource settings. countries in eastern and central africa have been on high alert since mid- in anticipation of regional spread of the ebola virus from the democratic republic of congo. significant investment has been made to support enhanced surveillance at point of entry and hospitals, infection control practices, clinical case management, and clinical research. with a new threat on the horizon, african countries have an opportunity to leverage the existing capacities for ebola preparedness to brace for the imminent threat. a novel coronavirus (sars-cov- ) rapidly emerged in china and has spread internationally. on jan , , it was declared a public health emergency of international concern (pheic) by the world health organization (who) after exceeding , cases and deaths, with countries reporting cases. the declaration was in part justified by the need to strengthen preparedness in countries with weaker health systems . concerns exist about these countries' capacity to prevent, detect and respond to the covid- outbreak. as of the time of writing, more than african countries with in sub-saharan africa have each reported a case of covid- and other countries are at risk of importation of a covid- case from china. weaknesses in public health systems were a prominent driver of the - ebola virus disease (evd) outbreaks in west africa and similar challenges have fuelled the evd outbreak in the democratic republic of the congo (drc), which is ongoing. we, therefore, questioned whether capacities enhanced for evd could be leveraged to sars-cov- , a biologically distinct virus requiring a broader public health response. coordination structures are essential to ensure emergency and contingency plans are in place, operational structures exist with clear communication channels, and adequate resources are available for impending threats. during the west africa evd outbreak, nigeria, transitioned its emergency coordination centres and public health activities for polio eradication to respond to evd . in the current evd outbreak in drc, the who has provided dedicated preparedness support to enhance national capacities for evd in drc and its nine neighbouring countries. currently, seven out of the countries have met their minimum targets for evd coordination . the declaration of a pheic is a timely intervention to enable african countries to mobilize resources domestically and through international sources to operationalise preparedness plans. utilization of existing structures will be critical for the timely organization of preparedness and response efforts. yields from this resource have been key in establishing sars-cov- testing capacity in over countries on the continent within one month of declaration of a pheic through the africa cdc coordination body. risk communication entailing significant community outreach and education on infection prevention and control as part of the evd response has supported improvements in hand hygiene, social distancing, case identification and reporting. similarly, risk communication is needed for covid- ensure standard precautions are enhanced particularly in the context of respiratory hygiene. to date, the risk communication platforms are being utilized to disseminate infection control measures for covid- and to identify public myths about the novel disease condition, so that targeted communication to demystify public confusion and rumours is delivered. in healthcare settings, careful logistics planning is critical to ensure panic buying of face masks and respirators by the general public does not lead to scarcity in health units. stockpiles of personal protective equipment for evd could in the interim, support some needs for covid- but such decisions should only be made after careful assessment of ongoing risk of importation of evd. unfortunately, these same countries must also plan for scenarios with concurrent outbreaks for covid- and evd and test their systems to ensure resilience against resource limitations and workforce fatigue. surveillance efforts deployed for evd in eastern and central africa could be modified to incorporate current case definitions for covid- . consequently, surveillance in health facilities will be critical, including in private facilities frequented by international travellers and intensive care units that may not have been adequately addressed in evd preparedness efforts. already, expensive screening for evd at land borders neighbouring drc could require an extension to all national borders if covid- cases are reported in surrounding countries. in countries with laboratory detection capacity, testing is currently centralised in a few laboratories that meet the necessary biosecurity requirements. while domestic and international efforts are underway to acquire more testing capacity, sample collection and transportation systems enhanced for evd and international referral diagnostic testing could be utilized to inform public health and clinical management strategies. biological differences between ebola virus and sars-cov- in the mode of transmission and case presentation will limit some benefits of evd preparedness. country scenarios must include plans for exponentially larger patient numbers than for evd. while evd requires close contact, covid- is transmitted mainly through droplets, contact with contaminated hands and potentially through aerosol-forming procedures. facility-based isolation capacity is likely to be exceeded during a large outbreak and self-quarantine at home may be needed for milder cases. cohorting severe cases under investigation will be highly dependent on the availability of appropriate hospital beds, laboratory confirmation capacity and a skilled workforce. hospital-based clinical case management teams that have received training in care for critically ill patients are a resource to leverage to bridge the gap for covid- . in uganda, the existence five teams based at five different hospitals, two of which are in the capital, is an example of a scalable baseline human resource capacity. cardinal features of the training such teams have received include infection prevention and control , outbreak investigation, laboratory, clinical case management. optimised supportive clinical care for evd patients has been recently introduced but will be challenging to scale, even if adapted for covid- . respiratory support in dedicated facilities may rapidly become inadequate and consequently, efforts to detect early and contain imported cases are critical. african countries can engage in research for medical countermeasures (vaccines and experimental drugs). the successful conduct of the palm trial (pamoja tulinde maisha) in the ongoing evd outbreak in drc serves as an example that can be used for therapeutic research for covid- . sub-saharan africa also has vast experience working with some of the investigational products being studied in china; ritonavir-boosted lopinavir has been used in sub-saharan africa as antiretroviral therapy for treatment-experienced patients in sub-saharan africa and most recently, remdesivir was used in the palm trial for evd in drc. with results from the covid- trials set to be made available soon, africa has a unique opportunity to rapidly access life-saving investigational therapeutics that are familiar and potentially readily available. although challenges remain, african countries that have been supported for evd preparedness in ongoing and past evd outbreaks have capacities that can be enhanced for the covid- preparedness and response. no data are associated with this article. this concise, well-expressed open letter addresses the highly relevant topic of commonalities in emergency responses for immunization, evd and covid- and their importance to health system strength and resilience. this reviewer notes anecdotal reports of similar pivoting to covid- by coordination systems for emergency responses to polio in papua new guinea. this letter is timely and well presented. coordination: make specific mention of the under polio rapid response and contract tracing functions emergency responses, as applied first to evd and now to covid- ; consider whether new communication channels such as whatsapp group necessitated by travel restrictions, apply as examples in this analysis. consider whether the option of integrated surveillance for vaccine-preventable-disease syndromes (e.g. measles) and for other public health priorities apply to this analysis, noting the likely decline in essential health service coverage will increase vulnerability to other outbreaks. consider including mention of rapid diagnostics and low-cost sample transfer, which may become available and differ for covid- from evd. infection control: given the dynamic nature of covid- evidence, consider review and update of modes of spread. use of "cohorting..." as verb slightly confusing, consider revision -also seems to repeat idea in preceding sentence. minor grammatical error in sentence "in uganda, the existence ...". consider special mention of oxygen (by concentrator or cylinder supply) as an essential medicine, with or without assisted ventilation, as a distinctive need of covid- at all levels of clinical care (see open letter from stoppneumonia.org). overall, noting over views now, congratulate the authors on this submission. https://stoppneumonia.org/open-letter-to-leaders-of-the-global-coronavirus-response-on-access-to-medical-oxygen/ is the rationale for the open letter provided in sufficient detail? yes are all factual statements correct, and are statements and arguments made adequately supported by citations? yes where applicable, are recommendations and next steps explained clearly for others to follow? partly no competing interests were disclosed. reviewer expertise: global immunization, health services delivery in resource-constrained settings, global child public health. botswana institute for development policy analysis (bidpa), gaborone, botswana the letter is written in clear language and a format accessible for decision makers and clinical practitioners. a few comments to make: while the authors duly note the distinct biological characteristics of sars-cov- from evd, the article could benefit from the acknowledgement that researchers worldwide are still learning the effects of covid- on patients, such as organ failure, apart from respiratory problems. it would be interesting what the implications of that would be on the clinical capabilities of african states to emergency committee regarding the outbreak of novel coronavirus ( -ncov) usa many thanks for asking me to review this very valuable open letter that describes how ebola response and preparedness "assets i see that the letter has already been viewed over times, which i believe attests to its value. the letter is short, beautifully written, clear, and concise. there has been much discussion and debate about both the strengths and challenges that countries in sub-saharan africa (ssa) face in preparing for and responding to covid- . interesting what the implications of that would be on the clinical capabilities of african states to address the challenge.sub-saharan african countries often have financial challenges to effectively implement their health policies and other interventions. the authors could look into what fiscal lessons has africa learnt from evd that they could apply to covid- ?the evd, as the authors state, affects largely two blocks of countries -central and west africa. at that scale it would catch the attention of the african union and trigger their response. this could have been brought on to bear on the collective response of the african countries under the auspices of the au or sub-regional groups and the lessons this carries for their response to covid- . this is a must read for all actors in the health sector in sub-saharan africa. the piece is succinct and proposes pragmatic approaches african countries could explore. where applicable, are recommendations and next steps explained clearly for others to follow? yes no competing interests were disclosed. reviewer expertise: public policy, health governance, governance, decentralisation. the letter states that "african countries can engage in research for medical countermeasures (vaccines and experimental drugs)." i think diagnostics should also be included as a mcm. are all factual statements correct, and are statements and arguments made adequately supported by citations? yes yes where applicable, are recommendations and next steps explained clearly for others to follow? partlyno competing interests were disclosed. competing interests:reviewer expertise: global health and public policy i confirm that i have read this submission and believe that i have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. key: cord- -mzd c authors: huang, yanzhong title: china's response to the ebola outbreak in west africa date: - - journal: glob chall doi: . /gch . sha: doc_id: cord_uid: mzd c beginning in march , west africa has endured the largest outbreak of ebola viral disease (evd) in history. the crisis highlighted the role of china in addressing public health emergencies of international concern (pheic). through bilateral and multilateral channels, china kicked off its largest ever humanitarian mission in addressing a pheic. the unprecedented generosity served the domestic needs to prevent evd from spreading into china, but it was also consistent with china's foreign policy objective to pursue soft power in africa. while its total funding to evd control in west africa was no match of top donors like the united states, it becomes much more impressive when adjusted for gross domestic product (gdp) per capita. as beijing becomes more sensitive to disease outbreaks overseas and as the scope of its humanitarian engagement grows and diversifies, the space for china's cooperation with international actors over global health governance is expected to further expand. china been in addressing the outbreak? what factors have incentivized china to respond in the way that it did? did china contribute its fair share? and to what extent does this tell us about china's engagement in future global governance for public health emergencies? using both quantitative and qualitative data, this paper examines the patterns and performance of china's response to the ebola outbreak. the study finds that beijing has become increasingly sensitive to disease outbreaks that originate from abroad, and the expanding humanitarian engagement opens the space of international cooperation over the global governance for pheic. unlike its initial mishandling of the - severe acute respiratory syndrome (sars) outbreak, the chinese government's response to the ebola outbreak was swift and proactive. on march , , right after guinea health authorities confirmed the presence of an evd outbreak, the chinese embassy sent warnings to chinese nationals there. in early april, the chinese government provided guinea with $ in cash as emergency humanitarian aid. [ ] this was followed by emergency assistance to the two other western african countries most severely impacted by the outbreak, liberia and sierra leone. at that time, china claimed that it was the first country to provide sierra leone medical aid to fight ebola. [ ] almost at the same time, china began to undertake ebola prevention and control measures back home. emphasis was placed on monitoring passengers arriving from ebola-affected countries for fevers. in guangzhou, which has up to african residents, [ ] the local government authorities implemented de facto quarantine measures against passengers from west africa, who were asked to stay at designated hotels and report their body temperature at required intervals using global positioning system (gps)-enabled mobile phones. [ ] on august , d after the world health organization (who) declared the evd outbreak to be a pheic, china set up a joint prevention and control mechanism consisting of central ministries to address ebola prevention and control and to develop a contingency plan for the outbreak. [ ] by november, the mechanism had enabled the health and inspection departments to screen more than arrivals, identifying people with fevers, though no confirmed cases of ebola were found. [ ] the outbreak also prompted china to accelerate the development of ebola diagnostic kits and medical countermeasures. in beginning in march , west africa has endured the largest outbreak of ebola viral disease (evd) in history. as of june , the virus has infected over people and caused more than deaths. [ ] the catastrophe brought to light "massive failure of global health governance." [ , ] but the same crisis also seemed to highlight the role of china in addressing public health emergencies of international concern (pheic). [ ] while visiting west africa in august , chinese foreign minister wang yi noted that china in carrying out its largest ever health aid program in history created multiple "firsts": the chinese president was the first head of state to commit explicitly to answering the call for help by three western african countries; china used large chartered airplanes to ship the first batch of badly needed anti-epidemic supplies; china for the first time deployed a whole unit of epidemic prevention forces and military medical staff abroad; china built a biosafety level (bsl- ) lab overseas, and set up an infectious disease medical center in another country for the first time. [ ] while the accuracy of wang's remarks is debatable, they raise interesting questions regarding china's involvement in the global response to the evd outbreak. how responsive has august, the people's liberation army (pla) academy of military medical science announced that it had developed china's first drug (jk- ) for treating ebola. in november, the chinese food and drug administration approved the test reagent developed by three chinese firms, making china one of the few countries that could produce diagnostic kits. the same month, the national health and family planning commission (nhfpc) distributed clinical guidelines on ebola response to all local health administrations and hospitals in china. [ ] yet compared to its high-profile responses to the h n pandemic and the h n outbreak, china seemed to adopt a less aggressive domestic approach toward the evd outbreak. in sharp contrast to the zealous coverage of the previous two flu outbreaks, chinese media and society appeared nonchalant toward the possible spread of ebola in china. [ ] between august and december of , the author had three times visited china, but did not notice any apparent panic or fear among ordinary chinese over the potential spread of ebola in china. the relatively low-profile domestic response was not so much the result of growing confidence in the government response capacity as it was the result of a more realistic assessment of the risk that evd posed to china. a cross-sectional survey carried out in guangzhou in november found that more than half of the respondents lacked confidence in the government ability to control an evd outbreak. [ ] earlier, a study conducted by chinese scientists predicted a total of to imported cases in china. [ ] in view of the growing trade and travel links, some leading international public health experts were concerned that china was at serious risk of ebola. [ ] senior chinese health officials agreed that there was risk of the virus spreading into china or chinese citizens contracting the virus overseas, but they apparently had no intention to overestimate the risk and incite major worries at home. [ , ] after all, china did not have any direct flights to the three western african countries. according to a study published in the lancet, the top six destination countries of flights departing from west africa were all in other parts of africa followed by three european countries. china was ranked number ten in terms of passenger destinations, but the total passenger flow only accounts of % of that of uk and france combined. [ , ] that being said, and the perceived low risk of ebola spread did not lead china to write off the threat of the virus completely. the evd outbreak unfolded at a time when the youth olympic games was about to be held in nanjing and a large number of africans were anticipated to visit china in late august. [ ] noting, "a single ebola case during the games would become headlines overshadowing news on the games," an editorial of the official global times on august called for "doing a seamless job in preventing the virus from infiltrating china." [ ] there were also concerns that the ebola virus might ruin the annual world economic forum meeting in the city of tianjin, where hundreds of business and research leaders were to gather in september, and the asia-pacific economic cooperation economic leaders' meeting, which was to be held in beijing in november. the chinese center for disease control and prevention (china cdc) vowed to implement "olympiclevel preventative measures" to contain the virus. [ ] in mid-august, when the youth olympics began, the government kicked off new preventive measures, including banning athletes from affected countries from competing in certain events. [ ] the evd outbreak in west africa also threatened beijing's economic interests in the region. china is africa's largest trade partner and chinese firms currently engage in $ billion worth of work in west africa. it is a key trading partner for the three most affected countries, accounting for % of sierra leone's total trade volume, % of liberia's, and . % of guinea's. [ ] prior to the outbreak, china's growing economic activities with africa had raised the question of whether beijing was only interested in accessing the market in order to secure the supply of natural resources in africa and not in promoting inclusive economic development in the subcontinent. during the evd outbreak, there were reports suggesting that china's efforts to develop mineral deposits and build roads in western africa might have brought infected animals into closer contact with humans, thereby facilitating the rapid spread of ebola. [ ] for economic and reputational reasons, it was in beijing's interest to improve its image in the region. besides participating actively in peace building efforts, health aid had increasingly become an important foreign policy instrument for china to project in africa its soft power, defined by joseph nye as the ability to shape the preferences of others through appeal and attraction. [ ] [ ] [ ] as the second white paper on foreign aid indicated, china emphasized the delivery of emergency humanitarian aid as a major form of china's foreign aid. [ ] the ebola outbreak thus opened a window of opportunity for china to showcase its soft power in africa while foiling criticism about beijing's mercantilist behavior in the region. [ ] china made no secret its intention to use the humanitarian aid as a tool to compete with other countries for soft power in africa. according to a scholar at the government think tank: as a matter of fact, china's soft power building in africa is still at its preliminary stage. in particular, china suffers from the deficit of cultural soft power in africa. china's advantages in soft power building in africa lies more in the attractiveness of its african policy, that is, foreign policy, in which health diplomacy to africa as an important component of public diplomacy is the most effective and most influential. [ ] against this background, it came as no surprise that the front line of china's battle against ebola was moved beyond its borders. according to senior chinese health officials, providing aid to west africa was crucial in china's efforts to construct a "barrier" against the spread of the virus. [ ] minister li bin of nhfpc was candid when she explained why china supported western africa's fight against ebola: "infectious diseases know no boundaries … china by helping west african nations is also helping itself." [ ] overall, china responded to the ebola epidemic in west africa with unprecedented generosity. while it was not unusual for china to offer humanitarian aid to countries affected by natural disasters, this was the first time china extended massive humanitarian aid to countries fighting a public health emergency. by late november of , china had-throughout four consecutive phases in april, august, september, and october-offered $ million ( million yuan) worth of humanitarian aid to the global ebola control efforts, china's largest ever response to an international humanitarian crisis. the package included the provision of in-kind contributions comprising of ambulances, motorcycles, medical equipment as well as prevention care supplies. it also included food aid, deployment of medical teams, and public health experts, as well as labs and treatment centers. unlike other donors, china also provided aid to countries surrounding the three western african countries: it provided tons of equipment and supplies to countries in the region. [ ] in guinea, two-thirds of the anti-ebola supplies were reportedly from china. there were also reports that by mid-october china had sent enough of the experimental anti-ebola drug (jk- ) to west africa to treat people. [ ] while the effectiveness of the drug remains unknown, another chinese-developed experimental drug (mil ) successfully treated a british military nurse who contracted ebola while serving in sierra leone. [ ] chinese scientists also developed their own ebola vaccine that was found to be effective based on results of the first phase-one clinical trial. [ ] unlike the other two experimental vaccines in human trials developed by the u.s. and canadian scientists, the chinese vaccine is the only one that has used genetic material from the current outbreak strain. [ ] in may , the who also approved an ebola test reagent developed by a chinese firm, which was ten times more sensitive than the benchmark for existing ebola diagnostic. [ ] china dispatched a large number of health personnel to west africa. in august , it sent three teams of infectious disease experts (totaling people) to assist local medical professionals in the ebola-stricken countries. this occurred at a time when aid groups from the united states, europe, and japan were evacuating their own in droves. [ ] in mid-september, a member chinese laboratory team departed for sierra leone to help the country build its lab testing capacity, joining the chinese medical staff that had been on the ground virtually since the beginning. the who director-general margaret chan called china's commitment "a huge boost, morally and operationally." [ ] in november, china launched a treatment center in liberia. according to the chinese ambassador to liberia, china was the only country to provide the construction of an ebola treatment unit (etu) as well as the operation and staffing of the unit. [ ] this was followed by the announcement that china would send an additional personnel to help fight the outbreak, making china the largest contributor of medical staff to the crisis. [ ] in sierra leone, the mobile lab that china helped construct reportedly tested % of the samples in the country, with % accuracy. in the meantime, china started to build a permanent biosafety lab in sierra leone. launched in march , the lab was the first permanent bsl- lab in africa. by the end of the month, chinese health personnel had tested samples and treated patients in west africa. [ ] the number of chinese professionals would eventually reach . [ ] in addition, chinese health workers trained local medical and public health personnel. [ ] despite its preference for bilateral aid, some of china's aid to western africa was routed through international and regional organizations. in october , china pledged to provide $ million to the world food programme (wfp) for vital food supplies, as well as $ million funding for who and the african union respectively. through wfp, china provided tons of food aid to the three most affected western african countries. [ ] on december , china contributed an additional $ million to complement un emergency efforts through the un ebola response multi-partner trust fund. [ ] besides tangible assistance, chinese domestic experience in fighting major disease outbreaks offered a reference point for the three countries most affected by the ebola virus. since the virus is transmitted through contact with bodily fluids, quarantine measures-widely used in china's fight against avian flu-could help break the chain of infection. given that early symptoms of ebola infection are similar to those of h n , china's experience in handling the flu cases could also be useful to ebola treatment. in august , the official xinhua news agency quoted who officials saying that african countries could learn from china's experience in addressing the h n outbreak as well as from its successful investment in public health. [ ] a chinese scholar went as far as to claim that, "china's experience [in disease prevention and control] applies to the whole world." [ ] there were reports suggesting that liberia did learn from china in applying some of the public health measures such as quarantine to ebola control. [ ] the role of major non-state actors such as médecins sans frontières (msf) notwithstanding, china appeared to be more responsive to the evd outbreak in west africa than many the organization for economic cooperation and development (oecd) countries in the initial stage of the crisis. in april and august , it twice provided aid packages worth more than $ . million to the three ebola-hit countries and guinea-bissau. in comparison, large amounts of personnel and funding support from other countries did not arrive until after august and september, when evd cases mushroomed and the potential global impact became clearer. still, international pressures built with calls for china to play a more aggressive role in the global fight against ebola. president barack obama voiced his frustration that china lagged behind the united states in funding the anti-ebola effort, while a un agency criticized chinese billionaires for not contributing enough to fight the virus. [ ] did china contribute its fair share to the global fight against ebola? it is hard to dispute that china trailed major oecd countries in certain aspects of health aid to western africa, such as building labs and etus. china constructed a total of bsl labs, compared with by the united states, by canada, and by united kingdom. it had only organized etu with treatment beds, compared with by the united states with treatment beds. [ ] its share in global humanitarian funding against evd outbreak was not significant, either. according to the data compiled by office for the coordination of humanitarian affairs (ocha), in china contributed a total of $ million ( . % of the grand total), which was dwarfed by the $ . billion u.s. contribution ( % of grand total). to be sure, funding from china was higher than traditional donors such as norway and switzerland, as well as countries such as india and russia. but china also lagged behind united kingdom, germany, the world bank, the european commission, france, sweden, japan, canada, and the netherlands in terms of total funding ( table ) . total humanitarian funding as compiled by ocha nevertheless may not be an accurate indicator of china's actual contribution to the global campaign against the evd outbreak. china's contribution becomes much more impressive if adjusted according to gross domestic product (gdp) per capita. adjusting for gdp per capita takes into account the country's still daunting domestic development challenges and its large population as compared to other oecd countries. when adjusted by gdp per capita, china's contribution is still no match of that of united states, but is close to that of united kingdom, and higher than the contribution of other oecd countries. interestingly, china and india had similar aid amount/gdp per capita ratio, suggesting a similarity in the dilemma that the two countries face in balancing their domestic development needs and the growing demands for them to assume more international responsibilities (figure ) . furthermore, the ocha data does not include all in-kind support such as ambulances, pickup trucks, motorcycles, incinerators, and personal protective equipment. it also does not include the contribution of medical staff and public health experts for ebola containment efforts, which accounts for a significant share in china's humanitarian assistance. equally important, it does not do justice to the shifting modalities of china's health aid to africa. for a long time, the chinese medical teams (cmts) posted in africa on a rotation basis have been the main instruments of china's health-related development assistance in the region. while the cmts play an instrumental role in providing routine medical services to local residents-indeed, a cmt treated the first case of ebola in conakry (guinea's capital)-they are not adaptable and flexible enough to respond to large-scale disease outbreaks. this may explain why in addition to mobilizing cmts already on the ground, china also dispatched emergency medical teams whose members were recruited directly from domestic health institutions. in addition, while beijing continued to rely on more traditional humanitarian assistance instruments such as in-kind contributions and food aid, it also diversified the modalities global challenges , , www.global-challenges.com www.advancedsciencenews.com of aid to building labs and treatment centers and health personnel training. this points to "a much more comprehensive, demand-driven response" to affected countries' needs. [ ] in doing so beijing might still prefer bilateral aid, but a significant volume of its humanitarian aid has been channeled through multilateral international institutions, suggesting that beijing is becoming more flexible in backing coordinated international response mechanisms. [ ] a lot of ink has been spilled on the implications of the evd outbreak for international relations and global governance. [ , ] interestingly, very little has addressed china's role in the global fight against ebola. this paper argues that china's participation sheds lights on its future engagement in global governance for public health emergencies. first, china's rise in a globalized context has made it increasingly sensitive to exogenous shocks such as pheic. while china's growing interaction with the outside world makes it more susceptible to global health hazards, its reemergence as a global power with ever greater interests also means that it cannot fulfill its domestic needs without a more proactive global strategy. in the case of ebola outbreak, the risk of the virus infiltrating china, and evolving into a major outbreak was comparatively low. however, the sheer prospect of having imported cases wreak havoc on major international events china was to host, coupled with china's significant economic and political ties to africa, prompted beijing to support a swifter and more decisive approach to the evd outbreak. it also explains why china quickly scaled up its efforts after it came under fire for the level of its response to the ebola crisis. in responding to the criticism, china made it clear that its aid to western africa would not stop as long as the epidemic raged. [ ] second, beijing's prompt response to the ebola crisis opens space for further international cooperation over global health security. over the past two decades, the interconnection between global health and security has attracted attention from both policy makers and scholars alike. [ ] [ ] [ ] [ ] unlike the united states and other countries, beijing has not explicitly framed the ebola outbreak as an international security threat or deployed a large number of military personnel to the affected countries (as the u.s. did). its dispatch of elite pla units to the affected countries nevertheless suggests that it did view the outbreak as an existential security threat that required a response out of the normal political boundaries. indeed, beginning in the pla has been entrusted with "new historic missions" requiring it to increase its involvement in more straightforward humanitarian and relief operations. [ ] in a move that demonstrated its new power projection capabilities, it took the pla no. hospital just days to assemble a team of medical personnel and mobilize tons of material supplies for the mission to west africa in september . it took the pla medical support forces in sierra leone just one week to convert a small general hospital into one specializing in treating infectious diseases, and just one month to construct a state-of-the-art ebola treatment centers (etc) with treatment beds. while there is no indication that pla medical corps worked closely with their u.s. and u.k. counterparts in evd diagnosis, treatment and containment, in light of the combined international efforts in this regard chinese actions should be viewed as part of a larger effort by the richer countries to provide direct aid through personnel and materials. [ ] furthermore, beijing's willingness to implicitly securitize trans-border disease outbreaks has opened a new area for future collaboration between china and other countries (e.g., the u.s.) under the global health security agenda, a global partnership that seeks to elevate global health security as a national and global priority. indeed, during the crisis chinese military personnel trained a liberian engineering company so that the latter could play an instrumental role in helping the u. s. army to construct its treatment center in the country. similarly, the u.s. air force provided large forklifts to help unload the supplies that china brought to liberia. [ ] when a limited supply of zmapp (an experimental drug being tested against ebola) was quickly exhausted, a small private chinese company raced ahead in the fall of and within three months made more potentially lifesaving treatments available by producing about doses of mil based on information in zmapp's patent. [ ] meanwhile, the application of a security approach to the ebola outbreak also underscored the need to reexamine the appropriateness of quarantine measures in handling acute disease outbreaks in the future. like china, the liberian government sought to enforce strict quarantine measures and restrict the movement of people during the crisis. while it is still unknown whether this actually resulted in reduced ebola infections throughout the country, evidence did support the exacerbated conditions in the sealed districts. [ ] in that sense, beijing's contribution to the fight against evd in west africa fits with hedley bull's model of a 'society of states' coming together to deal with a global public bad. [ ] third, china's differentiated response toward the outbreak highlighted the challenges of reconciling the gap between domestic and foreign policy objectives. in view of the devastating power of the virus as well as the absence of core surveillance and response capacities in the three affected countries, the seemingly self-serving containment strategy contributed positively to the global efforts to stem the spread of the virus and mitigate its devastating impact in west africa. its unprecedented generosity and its decision not to evacuate its citizens from affected countries may also help china win hearts and minds in the region. but the emphasis on preventing the virus from entering china also led china to discriminate against travelers from affected countries, such as imposing restrictions from athletes who were about to compete in the youth olympics. unhappy about being stigmatized over fears of ebola in china, sierra leone and liberia decided against sending delegations to nanjing. nigeria did send its team, but it pulled out of the competition after its athletes were isolated and barred from training due to concerns over ebola. [ ] while china might consider its discriminatory move necessary to protect its own people and ensure success of the games, it also tarnished its reputation and undermined its foreign policy objective of projecting soft power in the region. [ ] china faced a similar dilemma when dealing with the h n pandemic, where government quarantine measures targeting mexican citizens caused a diplomatic row between the two countries. [ ] this gap between domestic politics and foreign policy objectives is also attested to by the general absence of chinese civil society organizations in international humanitarian efforts, even though a small number of chinese professional volunteers reportedly participated in the front-line fight against ebola by joining msf and other non-governmental organizations (ngos). [ ] finally, while the crisis called for a coherent and coordinated approach to an overseas disease outbreak, the bifurcation of foreign policy and business interests in a new, globalized context makes such coordination increasingly difficult. in order to maintain laboriously built goodwill and future business opportunities in the region, it was in beijing's foreign policy interest to distinguish itself from western countries (whose workers fled west africa when ebola struck) by not evacuating the thousands of imported chinese workers at sites. [ ] however, ebola's devastating impact simultaneously triggered panic among chinese nationals in the region. not surprisingly, even though beijing did not broadcast any evacuations, the number of chinese living in affected countries-which included both workers affiliated with state owned enterprises and those who came there entirely of their own initiative-dropped by nearly half in the region from a high of chinese nationals in the summer of . [ ] this forced the chinese ambassador to liberia to intervene and requested local chinese companies not to allow their workers to leave the work sites. [ ] moreover, as the state expanded its engagement in global anti-ebola efforts, china's private sector contribution remained negligible, especially in light of the fact that the number of billionaires in the country is second only to the united states. a un agency reportedly lashed at out china's billionaires for not contributing enough to fight ebola. in liberia, locals were disappointed with the lack of significant contributions made by a chinese mining company. [ ] during - , china demonstrated a strong commitment to evd prevention and control in west africa. through bilateral and multilateral channels, china kicked off its largest ever humanitarian mission in addressing a pheic. its health aid package included cash and in-kind contributions, the dispatch of a large number of health personnel, the construction of bsl labs and treatment centers, and the development and implementation of medical countermeasures. the unprecedented generosity served the domestic needs to prevent evd from spreading into china, but it was also consistent with china's foreign policy objective to pursue soft power in africa. while its total funding to evd control in west africa was no match of top donors like the united states, it becomes much more impressive when adjusted for gdp per capita. as beijing becomes more sensitive to disease outbreaks overseas and as the scope of its humanitarian engagement grows and diversifies, the space for china's cooperation with international actors over global health security issues will only expand. the depth and breadth of that cooperation though will continue to be constrained by the gap between its domestic and foreign policy objectives, and the bifurcation of foreign policy and business interests overseas. in short, china's response to the evd crisis in west africa has revealed both opportunities and limits for its participation in future global governance for pheic. ebola virus disease time for the reckoning the national interest embassy of the people's republic of china in the federal republic of nigeria embassy of the people's republic of china in the republic of guinea science insider [www document east china likely to handle ebola transfer cases, china daily (beijing) (accessed renmin zhengxie bao (cppcc news) the new york times xinjing bound to lead: the changing nature of american power soft power: the means to success in world politics information office of the state council, white paper on china's foreign aid china builds its soft power in africa during the ebola crisis ebola technical lunch meeting china sends thousands of doses of anti-ebola drug to africa the guardian reuters issue brief: china's role in the ebola crisis introduction at "the health sector meets the security sector" event, graduate institute the telegraph [www document the civilmilitary response to the ebola outbreak in west africa, the university of sydney disease and security: natural plagues and biological weapons in east asia living weapons: biological warfare and international security contagion and chaos: disease, ecology, and national security in the era of globalization routledge handbook of global health security the china challenge: shaping the choices of a rising power the new york times the anarchical society: a study of order in world politics the world post the people's network media interview with ministry of commerce spokesman the author would like to thank suerie moon and the harvard global health institute for their support in initiating this study. the author would also like to thank the council on foreign relations, where he is a senior fellow for global health, and ariella rotenberg, lauren greenwood, and gabriella meltzer for their research support. the author declares no conflict of interest. key: cord- - sgr xx authors: zhou, zibanai title: critical shifts in the global tourism industry: perspectives from africa date: - - journal: geojournal doi: . /s - - -y sha: doc_id: cord_uid: sgr xx the study investigates critical shifts impacting the international tourism space in contemporary times. furthermore, the current study examines tourism policies and product development challenges faced by tourist regions as a consequence of market dynamics. drawing upon a sample of thirty tourism experts in southern africa, the critical shifts were identified and key among them include brics, terrorism, ageing population, and trophy hunting, are increasingly framing a new narrative for the future growth trajectory of the international tourism industry’s value chain in the context of africa. a conclusion is reached that to attain long term sustainable development of the sunrise multi-trillion dollar industry, it is critical that tourism operators re-set and deploy sharpened strategies which are in synch with the realities obtaining in the broader operating environment. policy recommendations and managerial implications are proffered. globally, tourism contributes significantly to the national economies in terms of employment creation and revenue generation (musavengane et al. ; unwto a, b) . understanding travel motivations and shifts in the global tourism marketplace is critical for unpacking future travel patterns and consumption perspectives, and also for tourist destinations to leverage on tourism spin-offs. anton et al. ( ) observed that growing competition in the tourism landscape has resulted in destinations increasingly becoming concerned with balancing tourists with attracting new visitors. while it is true that tourism is sensitive to violent events, political instabilities, disasters and calamities as well as economic meltdown (alvarez and campos ; woyo ; dieke ), it could be argued that tourism is also highly responsive to dynamics in the tourism market place. hapairai et al. ( ) state that political crises often lead to a decline in visitorship and public and private tourism organisations should constantly adjust policies, and product offerings in tandem with market dynamics. however, research examining the fundamental shifts in the international tourism landscape is limited. primary source markets such as the united kingdom (uk); european union, (eu) and north america consider emerging tourist destinations like africa as offering alternative authentic touristic experiences as compared to over trodden traditional z. zhou (&) tourism and hospitality management department, midlands state university, p. bag , gweru, zimbabwe e-mail: zhouz@staff.msu.ac.zw destinations. based on this, understanding the implications of the global tourism market place fundamental shifts on emerging tourist regions such as africa is critical for the formulation of destination-specific management strategies. the current study is informed by dieke ( ) who opined that in africa while there is a general disappointment with the economic returns from the tourism sector, there is insufficient knowledge of the market mix of international tourism, the market-driven nature of the sector, and the inability of governments to react to market changes or market signals. this is the research gap addressed by the current study. the current study therefore seeks to update and respond to these three issues at regional level in relation to africa's tourism industry in view of tourism dynamics in the marketplace. in addition, this study seeks to also make a contribution to the disproportionate in extant literature on the burgeoning of literature on western and mature tourism markets at the expense of africa (rogerson and visser a, b) . the other major contribution of the current study is on the geographical ecology of tourism literature that largely remains dominated by western writers. the current study therefore ties well with mkono ( ) 's call for more african voices on tourism issues. ''a sizeable proportion of tourism research on africa has been conducted by outsiders.'' (mkono , p. ) . ''… locals' opinions are often not meaningfully represented in tourism studies.' ' mkono , p. ) . ''if tourism studies are to reflect a more balanced representation, then the lens for viewing needs to be adjusted and diversified by having more page space for africans in scholarly works (mkono ) . henceforth, the study would give a fresh african narrative in the current global tourism discourse. in addition, naude and saayman ( ) and kester ( ) observed that observed that the economic dimensions of tourism to africa, and specifically the determinants of the demand for africa as a tourist destination, are neglected in the economic research literature. it is on the strength of naude and saayman ( ) 's observed scholarly literature gap pertaining to africa's tourism industry that the current study seeks to address. furthermore, christie and crompton ( ) bemoaned the lack of appropriate empirical research on tourism to africa that undoubtedly contributes to the 'limited policy guidance to the sector in relation to tourism market dynamics. in this respect, rogerson and visser ( ) argued that the imperative exists for strengthening the tempo of critical research on geopolitical developments, development debates, and global economic crises. in the past decades, there is an expanding body of critical work on tourism in southern africa, though still, very little is known with regard to the critical shifts in the global tourism sector. another context underpinning this study is trophy hunting, a controversial phenomenon which has been the subject of extensive but inconclusive research from a variety of angles (batavia et al. ; batara et al. ; mkono ) . to add on, scott et al. ( ) noted that one of the limitation of the tourism literature in africa is that studies have tended to examine the travel and tourism industry only in terms of one element of the tourism system, usually at a nation state level, or tourism sub-sector level, rather than conducting the broader tourism system (see, donaldson and ferreira ; mbaiwa and stronza ; buscher ; kavita and saarinen ; tichaawa ; hoogendorn and fitchett ) . research investigating these shifts have done so from a developed country context (see, giraldi ; debyser ; maria-irina ; weston et al. a ) leaving a theoretical gap in the context of africa, as an emerging destination. understanding such global shifts is critical not only for destination managers, but also for institutional investors and public sector because it helps in terms of forecasting travel patterns, weighing investment opportunities, and budgeting. furthermore, the constructs of terrorism, brics, trophy hunting and an ageing population are yet to be measured and applied simultaneously with the interconnectedness of nation states in the context of an emerging tourist region like africa. though there is an emerging stream of literature focusing on factors shaping international tourism future trends at the global level (unwto a, b; oecd a), there is a general absence of literature regarding the specific lynchpin variables which pertains exclusively to emerging tourist regions like africa. furthermore, the tourism related challenges and opportunities spawned by such fundamental variables in emerging tourist destination contexts like africa remains mostly unknown. the international tourism landscape is not only dynamic, but fraught with an environment that is constantly changing in a very unpredictable manner (badulesani and rusu ; kyyra and rantala ; unctd ) . whilst the unwto and practitioners acknowledge the centrality of the market dynamics in the global tourism space, there has not been a corresponding sufficient academic gaze in the current literature discourse dedicated to interrogating and unpacking such issues within the frame of africa. the tourism industry is considered a key growth sector in southern africa economy. safety and security are regarded as primary ingredients for tourism growth and destination competitiveness (donalsdson and ferreira ; correia et al. ; langfield et al. ) ; however tourism demand and factors impacting on it remain under-researched areas (visser and rogerson ) . since this study deals with the global dynamics in the areas of terrorism, brics, trophy hunting, and ageing population; it differs conceptually and contextually from other previous tourism development studies in tourism. this paper is therefore theoretically situated in the international tourism futures literature. the research was inspired by the fact that the contemporary international tourism sector has matured since the s. it has grown from being an exclusive preserve of advanced societies to becoming a multi-party phenomenon in which the emerging markets are now actively participating (unwto a, b) . another motivating factor was that the industry has been traditionally dominated by the most advanced economies, especially the g countries, in the global north at the expense of intermediate economies, however emerging markets are encouragingly catching up (bhatia ; cooper et al. ) . document analysis, archival information and expert opinions were employed to solicit for information that enriched the international tourism discourse from africa's perspective. the study highlights the critical shifts that undergird tourism future development and growth trajectories. the aim of this study is to enhance and build on ( ) christie and crompton ( ) 's observation that there is lack of appropriate empirical research on tourism to africa, which undoubtedly contributes to the limited policy guidance to the sector; ( ) naude and saayman ( ) 's assertion that there is a neglect of the economic dimension of tourism to africa; and ( ) rogerson and visser ( ) in which they opined the existence of an imperative for strengthening the tempo of critical research on geopolitical developments, development debates and global economic crises; and ( ) dieke ( ) who stated that in africa there is not only insufficient knowledge of the market mix of international tourism, but also the market-driven nature of the sector as well as the inability of governments to react to market changes or market signals. the objective of this study is to understand the fundamental global shifts in the international tourism landscape with special focus on africa. to achieve this objective, data were collected from tourism experts drawn from southern africa region. specifically, this study seeks to answer the following research questions: ( ) why should emerging tourist regions like africa be concerned with dynamics on the broader international tourism landscape? of these factors, which ones significantly predict the future growth trajectories of the tourism industry in african context? which specific tourism market shifts have impacted on africa's tourism sector? ( ) what challenges and opportunities do emerging tourist destinations face in the advent of these global shifts? what challenges and implications do these shifts pose on africa's tourism product offering, marketing strategies and planning for her tourism sector. in addressing these research questions, this study advances the understanding of the long term consequences of the global shifts on africa's travel and tourism landscape. this study also adds to the debate focusing on travel motivations, trophy hunting (baker ) crises (steiner ; al-shorman et al. ) , and mitigation strategies from a context-specific emerging tourist destination. the results of the survey can meaningfully inform the formulation of marketing messages aimed at repositioning africa, thus making it even a more appealing tourist destination in spite of headwinds in the marketplace. in what way can africa better prepare and anticipate the impacts of these shifts on custom, turn over, sales, investment etc. the remaining sections are structured as follows: the next section briefly reviews key themes in relevant existing studies highlighting the sector's economic significance at global level. this is followed by a brief description of the data and the empirical methodology. the analyses section provides a discussion of the empirical results using the content analysis highlighting the multi-faceted nature of tourism market dynamics. the final section provides overall conclusion and recommendations. current state of tourism research in africa: a regional and international context several studies have examined variables impacting international tourism at global level in different regional contexts, for example, tourism senior market (naude and saayman ; alen et al. ) ; brics (pop ; abdou and adawy ) using a number of relationships including data panel analysis, time series, arrivals and receipts; direction flows and distribution. however, studies examining the constructs of brics, terrorism, senior tourism market (ageing population demography), and trophy hunting controversy, from the african region perspective are limited. for example, existing studies have only investigated international tourism trends from advanced societies' contexts; cases in point include maria-irina ( ) , debyser ( ) , weston et al. ( a) among others. likewise, rogerson and visser ( ) argued for the continued need to understand the market dynamics fuelling tourism development trajectories in different tourist destination contexts. additionally, previous studies that focused on tourism development in african tourist destinations have not only been restricted to a specific country or sub-region of continental africa, but also limited in scope as they largely focused on specific segments and certain clusters of the tourism sector such as mega events, wildlife (saarinen ) , tourism and poverty alleviation (spenceley and meyer ) , urban tourism (rogerson ) , ecotourism (mbaiwa ) among others. while these studies provide in-depth analyses and insight into africa's tourism, there has not been an attempt to engage in other evolving issues with the potential to change the complexion of the region's tourism sector. on the international scale, there has been a sustained research on issues influencing the unpredictable dynamics of the international tourism ecosystem that hogged the global limelight, ranging from the september , terrorist attacks on the us, tsunami; sars epidemic in asia (gaetano ; schuurman ; qui et al. ; zeng et al. ; bongkosh ; tang et al. ) ; asian financial crisis, the current covid- virus, ebola outbreak in western africa (song and lin ; wang ; gossling et al. ; al-tawfiqef et al. ; maphanga and henama ; kongoley ) ; political conflicts in the middle east; icelandic ashes, the disappearance of malaysian airplane (al-shorman et al. ; steiner ; benediktsson et al. ; heimisdottir et al. ; weng ; fan et al. ); cites's trophy hunting ban, as well as climate change induced extreme weather patterns like hurricanes, cyclones and heat waves njerekai and mabika ; baker ; pandy ; moore ) . whilst acknowledging the diverse and richness of the current international tourism body of literature, the current study argues that very little attempts have been made to explore the policy and product development implications of the constructs of brics, terrorism, ageing population and trophy hunting in the context of africa. perspectives on these evolving issues from emerging tourist destinations contexts seem neglected in the academic gaze, yet in contemporary times these are the issues increasingly influencing dynamics in the tourism space. none the less studies offering a regional perspective from emerging tourist destination context are limited; with existing studies only investigating specific segments of the tourism industry in africa, for example, township tourism (boyens ); conference tourism (donaldson ) ; communities and trans-frontier parks (ferreira ) , and green guest houses (hoogendorn et al. ) , with very little attempt to relate these to market shifts. though there is a substantial research on tourism, the tourism marketplace, remains dynamic. debyser ( ) analysed the challenges and policy responses to the tourism sector by the eu, whilst tolkach et al. ( ) explored current and emerging tourism trends in the asia pacific region through a content analysis. tolkach et al. ( ) study found that economic growth, favourable political environment and improved infrastructure were sustaining continual growth of the sector in the region. furthermore, maria-irina ( ) examined tourism in the new member states of the european union in which the focus was on the importance of tourism, factors and trends that affect the industry within the eu community. still, weston et al. ( b) provided an overview of the current state of affairs in european tourism, considering the latest developments, identifying future challenges and emerging opportunities. the study established that changes in tourist behaviour and generational issues were significant challenges. even though there is a burgeoning tourism studies in the african contexts for the past decades, for example, ferreira ( ) , donaldson and ferreira ( ) , ferreira et al. ( ) , booyens and visser ( ) , rogerson ( ), zhou ( , scholtz and slabbert ( ) and tichaawa ( ) ; still these researches apart from being disproportionately too low to tourism researches in europe and the americas, they have been consistently oblivious of the quartet of brics, trophy hunting, ageing population and terrorism as critical shifts in the tourism landscape, hence leaving a theoretical gap in emerging tourist regions like africa. to put the issue into perspective, studies examining dynamics in the international tourism industry since in the context of africa are limited. a case in point is the study by signe ( ) who examined africa's tourism potential, renewed trends, key drivers, opportunities and strategies. the study found that there was huge potential due to the continent's richness in natural resources and cultural heritage; and that west african countries had introduced a visa policy to enable free movement of people across member states. furthermore, the study established that tourism was important to africa as it was driving economic growth and job creation, infrastructure development, generating foreign exchange. globalisation was the key driver of tourism. challenges of poor infrastructure and weak institutions were cited, whilst opportunities were that africa was the best candidate for investment. similarly, diakite et al. ( )'s study was country-specific. they examined tourism trends, opportunities and challenges in guinea in which it was established that ebola was a major challenge. in addition, jaensson ( ) examined potential for tourism development in sub-saharan africa in cooperation with sweden. the study results showed that the sector is important in poverty reduction, foreign exchange earnings, employment and economic growth. still, zhou ( ) analysed recent trends and future prospects of tourism in southern africa sub-region. the study's focus was on tourism development and growth at sub-regional level, and the study found that the need for economic diversity, job creation, foreign currency generation were factors motivating southern africa countries to develop the tourism sector. hosting of mega events, establishment of nature parks and aggressive marketing campaigns were identified as key elements allowing for the resurgence of tourist arrivals in the sub-region. dieke ( ) examined a production-nexus of tourism in sub-saharan africa. dieke ( ) analysed tourism issues and prospects in africa. the study focused on the current state of tourism to and within africa, highlighting key themes and issues that confront the industry across the continent. the results of the study showed that human resources have had consequences for the sector, resulting in the further marginalisation of africa in the global pleasure periphery. taken together, these studies revealed that understanding the dynamics in the international tourism arena is critical for destination managers because it helps in terms of forecasting travel patterns, demand for tourism products, growth projections and investing in new product development, investment into new markets, trends among a host of others. furthermore, from the analysis of previous studies it seems researches making a direct application of these critical shifts to a particular or specific emerging tourism region like africa are lacking. though there is an emerging stream of literature focusing on various facets of africa's tourism industry, (see , there is a general paucity of literature regarding how the dynamics obtaining on the broader international tourism arena would mean for africa's tourism industry and how the continent should respond to such critical shifts at operational and policy making level, tactically and strategically. it is a compelling case to investigate how such dynamics inform tourism policy formulation, inform investment options into product development, inform investment into new markets, and inform re-calibration of marketing strategies; which in the context of africa remain mostly unknown. alvarez and campos ( ) and woyo ( ) posit that tourism is sensitive to political, economic, ecological, technological, legal and socio-economic environment. however, research examining such critical shifts in the broader global tourism environment and their attendant implications to emerging tourist regions like africa is limited. overview of international tourism and its socioeconomic significance the post world war two (wwii), boom factors chiefly the advent of jet engine, political peace and economic stability, dual family income, inclusive tours, coupled with icts and education, generally laid the ground work for the growth and development of the tourism industry (bhatia ; boniface and cooper ; lockwood and medlick ) . however, whilst these factors are still relevant, the tourism industry has mutated as new variables evolve, presenting a new set of opportunities and challenges for the tourism industry requiring a different approach from tourist destinations. international tourist arrivals world-wide grew over . billion in , . billion in and most likely the threshold of . billion travellers is now likely to be exceeded in advance of (oecd ). globally, international travel receipts reached $ . billion in , and globally expenditures on travel have more than tripled since the turn of the century, rising to . trillion in (unwto b (unwto , . tourism is crucial to the global economy, and is regarded as a trillion dollar industry, contributing immensely to gdp, as well as employing one in every people (unwto a, b) . tourism contributes to the world economy gdp directly and indirectly through provision of full time jobs, it has a multiplier effect on down and upstream economic sub-sectors (wttc ; zhou ; musavengane ; mbaiwa et al. ; saarinen et al. ; nyahunzvi ) . the recent developments in the broader global economic environment underpinned by the emergence of brics, an ageing population demographic, calls for cites reform cum ban on trophy hunting, and the scourge of terrorism are collectively recognised by the academia, tourism fraternity and policy makers as shaping the global tourism growth agenda and its development trajectory dynamics in the twenty-first century. despite the severity and weight of these evolving issues, the global tourism industry is poised to grow in stature. while this is the case, there seems to be limited academic rigour on such phenomena, given that the available scholarship on global tourism industry dimension has not adequately explored the extent to which individual factors like the brics, population demographics, trophy hunting debate are shaping and influencing the global tourism industry growth trajectory. the tourism industry is one of the fastest growing sectors of the global economy, and the sector is a benefactor of the globalisation process. in there were million international tourists arrivals, in there were billion tourists, in it is envisaged that . billion international tourists would engage in touristic activities, and further still in the figure is forecast to hit the . billion (unwto (unwto , a . however, despite these impressive aggregate arrivals figure, the sector has to grapple with a milieu of opportunities and threats born out of the ever evolving tourism market place. on the employment front, tourism is extremely labour intensive and a significant source of direct, indirect and induced employment. it is among the world's top creators of jobs requiring varying degrees of skills and allow for quick entry into the workforce for youths, women and migrant workers and the untwo indicated that the tourism sector provided million jobs in (wttc ; oecd b; unwto a, b) . with over . billion people world-wide crossing international borders each year, tourism is increasingly becoming a major source of growth, employment and income for many countries including many of the world's developing countries. tourism has the potential to contribute to all of the sustainable development goals (sdgs) found within the agenda for sustainable development, including sdg on inclusive and sustainable economic growth, sdg on cities and human settlements, sdg on sustainable consumption and production. this underlines the need to rightly place tourism as one of the key pillars of socio-economic development. the world bank ( ) and unwto ( a, b) posit that tourism will be one of the main drivers of economic growth in africa over the next decade. an increasing number of countries, for example, south africa, kenya and rwanda henceforth, have made tourism a central pillar of their economic development and reform program, and have made significant economic strides using tourism as a plank to boost their economies. page ( ) and coulibary ( ) concurred that tourism is an escalator of development. however, in order for africa to reap tourism benefits, the region has to align its tourism offerings to marketplace dynamics. despite africa's documented perennial challenges, curtailing the growth and expansion of the tourism industry, that encompasses infrastructure underdevelopment, access issues, lack of direct flights, little appropriate promotional marketing strategies and investment budgets, portrayal of africa as a land of war, disease, poverty, hunger, anguish and desperation by foreign mainstream media, million tourists visited the region in the region, generating $ . billion worth of revenue (diakite et al. ). henceforth, tourism is a powerful vehicle for economic growth and job creation all over the world. tourism's main comparative advantage over other sectors is that visitor expenditures have a ''flowthrough'' or catalytic effect across the economy in terms of product and employment creation (christie et al. ; schubert et al. ) . given the multisectoral nature of tourism, its success is dependent upon the external and internal dynamics on the environment. the potential for tourism growth in africa is significant, anchored not only on the region's abundant pristine wildlife coupled with expansive beaches, but also on its cultural heritage. continental africa is poised to realise $ billion in revenue from billion people travelling internationally. at first glance, it may appear that its smooth sailing for africa, however, on closer inspection, such a bright future projection is made without taking into account the critical shifts panning out in the tourism market place. africa's adaptive capacity in relation to the risks and opportunities posed by market dynamics will ensure the success of its tourism sector. the fact that the brics, ageing population, terrorism and trophy hunting issues are taking root in the marketplace it is about time that emerging tourist destinations tourism starts a serious conversation to establish the implications of these dynamics on the tourism system. it is no doubt that africa has had an impressive average growth rate of her travel and tourism, which trends have continued into the twenty-first century, bolstered by a period of impressive economic growth and improvements in political stability and opportunities across the continent. the african development bank (afdb) indicated that in , africa recorded . million visitors, contributed . million jobs directly and generated $ . billion international tourism receipts (afdb , p. ). looking into the future, there is substantial room for growth in africa's travel and tourism market, particularly in light of current sectoral growth patterns, as international tourists are increasingly interested in developing countries as travel destinations, provide the region properly align its tourism sector to dynamics obtaining in the marketplace. tourism is a major global economic sector that is undergoing tremendous growth in emerging economies and is often touted as salient for the development and poverty alleviation in developing countries (scott et al. ) . tourism has been embraced largely due to its employment and foreign currency generative capacity, as it continues to make a substantial contribution to the economies of many countries around the world (zhou ; mkono et al. ) . with the exception of , each year, the tourism industry has outrun projected international tourist arrivals riding on the back of liberalisation of the aerospace, globalisation, and rising income levels. it is forecast that if the current momentum is maintained, international tourist arrivals are expected to reach . billion by (unwto ). tourism is an important economic sector to many african economies in terms of its contribution to gross domestic product (gdp), employment and trade (unctd ). at a time when the region is building its productive capacities, consolidating regional integration and pursuing economic diversification, tourism in africa continues to grow. apart from stimulating employment creation and enticing investment, tourism also contributes towards the preservation of ecosystems and biodiversity. at continental level, the african union's agenda recognise tourism's importance in driving africa's socio-economic development and structural transformation through job creation. the economic development in africa report ( ) reported that tourism can be an engine for inclusive growth and economic development and that it can complement development strategies aimed at fostering economic diversification and structural transformation within the right policy context. however, conspicuously missing in the report is any reference to terrorism, ageing population, trophy hunting, and brics, and the extent to which they threaten the envisaged economic gains. to achieve this africa must be cognisant of changes taking place in the global tourism market place. tourism marketplace dynamics provide greater scope for the region to boost international travel into africa, leveraging on africa's comparative advantage of its renowned tourism resource base. market dynamics will inevitably alter the competitiveness of tourist destinations as well as the suitability of major tourism market segments. it is evident that all tourist destinations will need to adapt to market dynamics, whether to minimise risks or to capitalise on new opportunities associated with the constructs of brics, terrorism, trophy hunting and ageing population. data were gathered through document analysis, combing archival information and expert opinions canvassed from key informants drawn from the broad travel and tourism industry who were knowledgeable about the dynamics and trends of the international tourism industry from africa's perspective. regional market shares, and tourist arrivals from to , unwto forecasts and projections were employed. key interview informants were qualified as tourism experts on the basis of their extensive working experience directly in various sub-sectors of the tourism industry at regional and international level, that is, hotels, tour operations, conventions, nto as regional and international tourism markets, tourism attachés in charge of overseas tourism markets, tourism market development, planning and forecasting. informants' intimate knowledge on international tourism and market dynamics coupled with extensive working experience in the hospitality and tourism sector earned them the expert status. in order to participate in the study, respondents had to have over years working experience in the tourism sector at senior management level in the marketing department in charge of regional and overseas tourism markets. to widen the pool of informants, the study included responses of tourism experts including representatives from government, international organisations and other tourism industry related government departments selected through snowball technique. this was also supported by a review of recent literature and data. resultantly, a total of interviews were administered out of a total population of potential informants (krejciie and morgan ) . a pilot study was done before the actual data collection to ensure the comprehensiveness, readability and clarity. in-depth interviews were conducted with purposively sampled respondents. interview session lasted an average of min. interviews were discontinued after data saturation was reached. the study was based on predominantly a series of open-ended, semi-structured interviews conducted with ten female, and fifteen males purposively selected from tourism representative bodies. semi-structured interviews were chosen because they allowed the researcher to probe for additional information and to seek clarification. the above is in line with the assertion that semistructured interviews offer insights ''into respondents' memories and explanations of why things have come to be what they are, as well as descriptions of current problems and aspirations'' (stake and torrance , p. ) . the interviews that were conducted were restricted to people who gave their informed consent and each interview lasted on average min. items on the interview schedule were informed by literature and prior studies related to tourism growth in other touristic regions. the research participants were asked a broad range of questions in order to gain an understanding of the interplay between the global tourism industry and dynamics in the broader global operating environment in the context of africa. the line of questioning explored, key variables driving tourism at global and regional level, critical shifts in the tourism market place influencing tourism development, tourist regions' responsive strategies to market dynamics, implications of contemporary market dynamics to emerging tourist destinations among other aspects. data were recorded manually (saldana ) . the interpretation and analysis of the qualitative materials was an on-going process that proved inseparable from the field work. in the field, after each interview, the data was analysed to inform subsequent interviews and to capture preliminary emergent themes as recommended by mertens ( ) . after fieldwork, the interview material was later, thematically analysed to reveal emergent themes, following miles et al ( ) and veal's ( ) guidelines. in line with qualitative research, interviews were discontinued when theoretical saturation or data redundancy was reached (jennings ) ; in this case five out of the interviews held contained no new themes. the next section provides a detailed and concurrent presentation and discussion of the dominant themes that emerged during the interactions with the research participants. four themes were identified in the analysis of the qualitative materials that were obtained from the interviews. these were brics, senior tourism market, cites' trophy hunting debate, and the scourge of terrorism. each one of the five themes is discussed below. recurrent themes which emerged from respondents' narratives were grouped into five key themes, which were; brics, ageing tourism market, trophy hunting and terrorism. a number of respondents found that the brics economic grouping was indeed a game changer in the tourism marketplace. brics being a post phenomenon was set to establish a new economic world order, competing with the g countries which traditionally dominated the tourism sector. in particular, informants described brics as revolutionary in tilting the balance of economic prowess in favour of the developing countries. this is a critical milestone in the historical development of the tourism industry in the sense that for the first time the global south is playing a significant role in the global tourism affairs. in light of such market realities and as a way of going forward it implies africa should now improve its tourism infrastructure to match world class standards ahead of increased tourists from brics. africa's tourism product should also be now tailor made to accommodate new a new market with a new set of preferences, tastes and travel habits/behaviour different from the traditional western markets. this echoes the sentiments of unwto ( a, b) and znojek ( ) that going forward emerging economies will drive the key economic sectors at global level, including tourism. to illustrate, respondents pointed out that china, india, brazil, russia and south africa are increasingly emerging as key tourism source markets ahead of the traditional markets of western. in contemporary times, countries from the global south, buoyed by an uptick in per capita income are poised to become leading contenders for the first time in international tourism growth matrix despite being insignificant in the broader global tourism industry in the s. another insight revealed by respondents was that since wwii, the global financial sphere was been dominated by the bretton-woods institutions, however, this was changing with the rise of the asian tigers, coupled with rapid economic transformation in the emerging markets fronted by brics. tourism is driven by an economic boom, a characteristic feature punctuating the brics. brazil of south america, russia of eastern europe, india and china of asia pacific, and south africa from southern africa constitute the brics gamut. on the horizon, the five-nation state grouping is determined to set up a multilateral financial institution modelled alongside the century old international monetary fund (imf) and world bank (wb) as a way of disrupting the status quo in the global financial services market systems. the implications of the brics bank after its eventual full consummation would be the source of funding of tourism developmental projects for the emerging markets. such projects would be prioritised in terms of funding without the bureaucracy and exclusionary tendencies synonymous with the imf and wb. it also imply that nation states from the global south would easily access loans as seed capital to shore up and stimulate economic development which will later on spur economic prosperity and eventually boost tourism. the birth of brics is changing the face of the international tourism in much the same way as the boom factors of the s- s did through enhanced tourism access, free flow of international tourism traffic and capital without restrictions, enticing of fdi, and boosting of demand in favour of the emerging markets. favourable implications on africa are the characteristic features punctuating the brics which support tourism, that is, fastest growing economies, rapidly expanding middle classes and promising domestic markets, as well as the potential to overtake the g as the world's best performing economies by (pop ) . given the positive relationship between economic performance and tourism, this would mean that a huge boost for the brics nation state's respective tourism industries with a potential spill over to the rest of african region. the emerging markets of the brics countries have long been highlighted as the future power houses of the travel and tourism industry. abdou and adawy ( ) contend that brics countries are the leading economies in the world as they are expected to cause a global economic shift and have power more than europe economies and us in the near future. informants were excited by prospects of china and india morphing into citadels of commerce at global level. the brics premise is very significant to the tourism industry of emerging countries in several ways. china and india are set to mutate into hubs of manufactured goods and services globally, while brazil and russia will become leading suppliers of raw material. the brics is set to become the seat of influence on tourism affairs, from being the leading global tourism market, leading tourist destination, leading recipient of tourism related fdi unlike the period in the early s. this finding is in line with projections made by the imf and wb that in future china and india will become global centres of commerce and trade. one official had this to say: certainly, brics will upset the applecart, already there is a seismic shift in the tourism marketplace, where we see traditional tourist destinations becoming less and less popular, whilst emerging markets are shining currently, brics account for more than % of the world's population, over % of world economic growth, % of world foreign investment (zhao ; znojek ) , and has been deemed as a platform for the emerging economies to share a stronger voice on the international stage. to be specific, brazil occupies a prominent place in world affairs, and is one of the world's ten biggest economies, india is an emerging global power, south africa is equally a regional power with global aspirations and has taken a more assertive continental role. it is africa's largest economy and regarded as a doyen of democracy, whilst at the same time it is a key player in the region's stability (carothers and young ) . brics' long haul objective is to accelerate the shift towards a multi-polar international order and to gain an adequate presence for emerging economies in reformed global institutions. unlike before when the global tourism industry was dominated by the g countries, which are essentially proxies from advanced economies, the emerging markets of the brics have thus been regarded as the future powerhouses of the travel and tourism industry as evidenced by the increasing trend where upon the brics feature prominently in the world travel market industry report (world travel market ). on inbound tourism china is increasingly becoming a leading tourist destination at global level, brazil at second place challenging traditional leaders like france, spain, and the us. to its credit, brics is well endowed with natural and cultural tourism resources, massive infrastructural developments in the way of air and ground transport, protected land areas, and richest fauna in the world. this gives it comparative advantage over the traditional g countries. in essence, this is driving the global tourism trends to gravitate towards the emerging markets as opposed to the traditional western markets. africa should take a cue on how brics is also shaping a new narrative in the event tourism space. the increasing importance of mega events particularly sporting events such as the olympics and the fifa world cups provide a window of opportunity for highly significant upgrades in infrastructures, human resources, products and quality. south africa's fifa world cup was a resounding success, olympics winter games in russia federation and fifa world cup in russia, fifa world cup in in brazil and the olympics summer games of helped putting the brics on the global tourism map. there is no doubt that the growth of the global tourism industry is being driven by emerging economies, that is, brics. the present dynamics confirm that unlike in the twentieth century where economic growth was mainly driven by the developed world, in the twentyfirst century, the growth engine has relocated to the emerging and developing markets, particularly the brics. as per capita incomes increase, the services sector grows relative to the other sectors of the economy, and this dynamic is important as the brics countries are planning to go from middle to high income status. resultantly, many countries world-wide are now actively courting tourist arrivals from the brics in particular china. given its large population, and the fact that a growing percentage of people can now afford, both in terms of time and money to travel overseas has had a major impact on the global tourist market. globally, on the economic and tourism front, there is a scramble for the brics as they represent tomorrow's tourism sunrise economy. there is huge appetite world-wide to invest in the brics' tourism sector, which in itself is an endorsement in terms of the shift of balance of power in tourism demand generating markets. the brics have indeed become a force to reckon with in international tourism affairs in the period post wwii just like the g countries. china and india, for example, buoyed by the population demographic factor are set to tilt the balance of power towards the asia-pacific as both a generator and recipient of outbound and inbound international tourism traffic. as such, brics have emerged as an important player in the global economic sectors, tourism included, with its services export growing faster than the developed countries. at the same time brics are generating an increasing number of tourists as per capita income rise and a relatively big share of this increase would be spent on tourism. in this milieu, the over trodden global north tourist destinations have now matured hence the focus has turned on exotic tourist destinations which are far flung from the beaten track. the majority of the respondents suggested that the elderly population presents a market of particular relevance to a large number of industries for its high purchasing power, comparatively higher than younger groups, more so to the tourism industry. it was apparent from the response that the tourism sector was emerging as one of the biggest beneficiaries of the ageing process as a result of changes in the lifestyle of the population. this finding conforms to alen et al. ( ) and cooper et al. ( ) who similarly established that the ageing baby boom generation was slowly becoming one of the most important markets in the tourism context. indeed, the ageing of the baby boom generation marks an important milestone in the development history of the tourism sector in light of their purchasing power. schroder and widman ( ) deemed the senior tourism market demographic change as one of the biggest growth and most important markets in the tourism industry, turning it into the engine of growth for tourism. this is in consonance with the unwto ( a, b)'s prediction that by there will be more than billion international travellers aged and above compared to million in (patterson ) . such demographic shifts will affect the structure of tourism supply and demand at regional level. the implication on africa about the increasingly ageing population is that market tastes and vacation habits will change. the senior market clientele is experienced, more discerning and high spenders. this corroborates glover and prideaux ( )'s observation that population ageing affects the future choice of tourism activities and destinations, and ultimately future tourism growth projections like trends, patterns and traffic. as the global tourism market gravitates towards the senior market, so does its tastes, preferences and holiday patterns. this is in synch with weaver and oppermann ( ) and salt ( ) who support the view that demand for tourism products and experiences change with age. the senior tourism market is keen to travel to exotic tourist destinations like africa calling for an overhaul of africa's tourism product. individual factors such as family status, employment, education, health status, travel experience and generational values change with age, henceforth tourist destinations have to pay particular attention to these and adjust product offerings accordingly (glover and prideaux ) . an ageing population implies that the demand for authentic tourism products and experiences most in emerging regions like africa aimed at the senior tourism market or older population is likely to increase both in actual number and in proportion of all holidays as the number of older people grows. the senior tourism market, given its old age, takes more leisure trips more frequently courtesy of the availability of time and higher discretionary income. it is therefore instructive that if emerging tourist destinations are to remain competitive and successful they need to be aware of the differences that may be apparent in the demand profiles of specific generation gaps. from africa's perspective, the battle for the competitiveness and growth of the global tourism market share will be fought and won on the basis of them being capable to appeal to multi-generation markets. tourist destinations in the global tourism industry vigilant to tourism market shift on tourism demand based on population demographics are poised to reap the benefits. prideaux et al. ( ) posit that the inability of tourist destinations from recalibrating current range of tourism products and services to reflect the aspirations and consumption patterns of senior market may result in a slow decline in visitor numbers in the coming years. ideally, tourist destinations world-wide recognise that a change in demand is underway hence the need to start working on modifying the tourism product that resonates with an ageing population. in short, tourism demand would be a function of population demographics. an understanding of where the world and tourism market is heading is crucial for identifying opportunities that are brought about by that change. embedded in ageing are health issues such as hypertension, obesity, and heart diseases which increase in prevalence along with age. ageing population equally has a business and financial dimension, that is, the elderly are better educated and wealthier than previous generations (callister ) . the elderly tourism market is keen to give back to the community or cultures they visit, they therefore combine tourism with volunteer work, aptly labelled as voluntourism (furlong ; thornhill and martin ) . the tourism industry must ensure that appropriate facilities are available to meet the needs of these consumers. whilst developing countries are still comparatively characterised by young population, industrialised countries are confronted with an ageing population, and low birth rates (un ; goldin ) . informants were unanimous that the tourism industry experienced an unprecedented poaching and decimation of wildlife on an industrial scale in the period post wwii, which was a cause of concern as it sends shockwaves on the tourism marketplace. the situation is grim in emerging markets mostly africa. respondents were unanimous that the tide needed to be tamed as it was threatening the very foundation of tourism hence putting the future of the tourism sector at stake. the above sad state of affairs in emerging tourist regions fed into a post wwii tension increasingly mounting between the global south and global north on the emotive issue of trophy hunting, which falls under the auspices of cites. another respondent seemed to indicate that trophy hunting was more relevant to africa given that the region's tourism industry is anchored on wildlife. it was interesting to note that the draw card of emerging markets' tourism industry was now at the centre of the contemporary global stand-off pitting the global north against the global south. perspectives from africa show that the region is much concerned about the power play on over-regulation, embargoing trophy hunting, and preservation of such wildlife in light of limited budgets characterising most african countries. ironically the consumers of africa's trophy hunting products are tourists who come from the global north who are lobbying for a total ban. this creates an awkward position for africa. what this implies to africa is that the region has to adjust and endeavour to co-exist with the global tourism family in the sense that if the region pulls out of cites it risks a serious backlash from partakers of wildlife experiences. the current state of the tourism industry has been predicated on the huge wildlife resource base sprinkled across the breadth and length of tourist regions. however, post wwii upheavals in the wildlife sector characterised by increased poaching, alienation of local communities' rights to the utilisation of wildlife resources, blanket imposition of a moratorium on trophy hunting and a plethora of other issues are set to continue fuelling a bruising contestation regarding the sustainable use of wildlife in the broader context of tourism development (mkono ) . consensus on how the contentious and divisive trophy hunting issue should be handled to the full satisfaction of all cites members and secure the sustainable future development of the tourism industry is still a challenge. whilst emerging tourist regions like africa feel hard done by cites stance, with sentiments indicating that the issue seriously undermine wildlife conservation efforts, and ultimately the tourism experiences in nature parks and conservancies, it is critical to have a holistically approach on the issue. indeed, exotic tourism regions like africa are well known for their pristine wildlife sanctuaries where tourists encounter with nature. world-wide the tourism phenomenon has been driven by flora and fauna, however given the increasing rate at which poaching and depletion of wildlife resources are happening, cites justifiably came on the scene to regulate the use of wildlife within the tenets of sustainable tourism. to this effect cites outlawed trophy hunting which arguably used to generate funds for the conservation and management of wildlife resources especially in emerging markets like africa and asia-pacific. subsequently, there has been a raging debate on trophy hunting which has divided global opinion. the future of the global tourism hinges on the reform of cites's stance on trophy hunting. arguments proffered mostly by the emerging markets revolve around the urgent for a review of trophy hunting ban to avoid what they claim an impending wildlife catastrophe since the wildlife population has ballooned to unsustainable levels as a result of a moratorium imposed on trophy hunting. yet on the other side of the spectrum, the global north is advancing the argument that a ban on trophy hunting should remain in force into the foreseeable future. the stalemate would definitely impact on global tourism trends and patterns, more so on africa in a negative way. trophy hunting has thus become a delicate matter in the international tourism discourse since it can rally nation states towards the conservation of wildlife resources which are the bedrock of the tourism sector. trophy hunting is a topical issue in international tourism affairs, so much that a divided global family of nations on it foments disillusionment, smacks fragmented approaches in fighting the poaching scourge and eventually lead to the decimation or a complete loss of the wildlife resource which is a key driver of the sector. global consensus on trophy hunting and the way forward between the global south and north will define the new course of tourism growth in the foreseeable future. without wildlife resources there is no tourism sector to talk about hence this is critical at this juncture. poaching remains the greatest threat to the integrity of natural sites globally. results showed that in the contemporary globalised village, emerging tourist destinations like africa are no longer immune to the scourge of terrorism that traditionally was more pronounced in the western countries and north america. however, respondents indicated that africa is increasingly becoming a target of terrorist, citing an example of kenya in east africa; tunisia in north africa. what it therefore implies is that it can no longer be business as usual but in essence emerging markets should start investing in ports of entry screening technologies and reviewing visa regimes with a view of strengthening security protocols. safety of international tourists is of paramount importance, hence this should be guaranteed. future global tourism trends will be defined and influenced by the safety records of tourist regions, as well as their response systems to terrorist attacks. this finding corroborates paraskevasa and arendell ( ) , hoffman ( ) and chalk ( ) who established that tourists rank safety and security highly when choosing vacation holiday. given the ever increasing rate at which conflicts are erupting in emerging markets in particular and at global level in general as a result of the increasing chasm between the rich and poor, it is important that tourist regions reflect deeply on terrorism threats and the instability it poses to the development and growth of the international tourism industry. it is apparent that transnational tourism organisation like the unwto and wttc quickly issue out advisories dissuading potential tourists from visiting destinations prone to terrorist activities, as they value the safety and security of vacationers. while at face value this may sound akin to destination de-marketing, tourists' safety and security is of utmost priority. the burden lies with destinations to ensure the safety of visitors. peace and security at tourist destinations would remain the single most important factor to guide tourism development going into the future. globally, as revealed above, the security situation remains precarious, impacting negatively on tourism growth projections. with such a remarkable shift, it therefore calls for a coordinated global approach in the fight against terrorism, a serious threat to tourism, which has become a global menace embedded in a modern society characterised by extremes of rich and poor in both the developed and the underdeveloped countries. terrorism has been targeting popular tourism spaces, and given the lack lustre security systems in place in emerging markets there is need for collaborative efforts to tame the wave of terrorism in order to create a better world where tourism can thrive. africa should realise that the interconnectedness of nation states celebrated under the auspices of a global village has opened up countries to global risks and vulnerabilities like terrorism, contagious diseases, for example, covd- virus. this has huge implication on tourist regions' immigration and border control issues, visa regimes, health issues with far reaching consequences for africa's tourism sector. taken together, these issues are at the centre of curtailing the free flow of tourists. emerging tourist destinations are in a dilemma on whether they should opt for a protectionist-cautious stance in terms of the free flow of people or a more liberal approach. perspectives from africa hold that improving security is a challenge, especially creating a more seamless experience and staying ahead of evolving threats is a true test facing the sector in the period post ; balancing the traveller's safety with traveller experience will continue to define the challenge into the foreseeable future. respondents confirmed that as tourist spaces in exotic destinations become more popular with millions of tourists trouping, it becomes apparent that tourists are increasingly becoming easy targets of terrorism. the implication for emerging markets like africa is that terrorism is now ubiquitous, as illustrated by a spike in terrorist incidences. given the ever widening chasm between the political elites and the poor, fundamental different religious views and political opinions, these are fuelling terrorism irrespective of geographical location. since time immemorial, tourism has been known as a peace sector. another perspective is that whilst the end of wwii was generally interpreted as marking the dawn of political peace at global level and was hailed as a seed bed to nurture tourism development, it is increasingly being realised it was an illusion. to date global peace is becoming elusive because of indiscriminate acts of terrorism. given the global publicity and media attention attendant to terrorist attacks on tourist destinations, the scourge dents the tourism phenomenon, especially for emerging tourism destinations whose safety and security systems are regarded as weak or inadequate. indeed, the tourism phenomenon has been known to be resilient but the negative publicity associated with terrorist attacks adversely affect tourism trends and patterns. terrorism has the potential to destroy tourism overnight despite its gigantic size. the present day society is become heavily infested with terrorist groups who are increasingly targeting, attacking, kidnapping and killing international tourists (stafford et al. ) . adeloye and carr ( ) argue that terrorist attacks on tourists serve as unpleasant reminders of how fragile and vulnerable the tourism industry is to terrorism. the unwto ( a, b) advocates for tourist destinations to be proactive and institute quick response or rescue strategies in the aftermath of an attack. alongside this, tourist destinations should have in place destination recovery plans and marketing strategies to restore market confidence in the post attack period. terrorism influences tourists' perceptions of risk and their resultant travel decisions. in the twenty-first century the notorious terrorist groups threatening world peace and stability are the islamic state, hamas, hezbollah, boko haram, taliban, al-queda, and al-shabaab to mention a few. the tourism sector, economic growth and development of countries can be seriously threatened if tourist destinations increasingly become scenes of terrorist attacks. to this effect, tourist destinations need to invest in security protocols, which would put them in a stead to recover in a faster manner, provided the protocols are well created and implemented correctly (world economic forum ) . crisis protocols, recovery strategies, and strong emergency plans are indispensible for tourist destinations to recover fast and should become buzz words in future tourism development trajectories. despite the resilience of the tourism sector, recurrent incidents of violence and terrorism at global level, increased insecurity and safety of tourists, as well as ruined perceptions deter potential tourists from fully and freely partaking in tourism. the scourge of terrorism imposes restrictions to visiting tourist destinations prone to attacks, henceforth matters of tourist safety and security are very critical when it comes to the future of the tourism industry. terrorism makes the tourism sector vulnerable and fragile making its future growth prediction uncertain (abadie and gardeazabal ) . conventional literature show that terrorism disrupts the entire tourism value chain where upon key stakeholders like travel agents would not actively promote tourist destinations perceived as being unsafe. terrorist attacks have continually degraded and undermined the popularity of tourist destinations. in the aftermath of terrorist attacks, the tourism industry experiences significant down turn, the kidnapping of tourists by terrorist's network groups also frightens tourists away. from africa's viewpoint, terrorism's effects on tourism are multi-faceted: a decrease in the number of tourist arrivals, reduction in fdi, cost of reconstruction of tourist facilities, safety and security upgrades costs, and increased marketing costs to attract visitors. this is in line with what was established by barth et al. ( ) that there is a very strong connection between terrorism and tourism, tourist sites which are targeted by terrorists have their social order and economic stability greatly shaken. the tourism sector is increasingly becoming a target of terrorists; the resonance being that the tourism sector is the main source of income of many countries, so by damaging it the core function of the economic basis of the nation stops working, destroying tourism attractions is the best way for the terrorists to get their message delivered through-out media coverage, thus getting the attention they need, and the tourism sector has not focused on security matters (tarlow ) . tarlow ( ) emphasise that security plus service and value for money will become the basis for twenty-first century services. terrorism encompasses the murder of high profile journalists, and media personalities which are covered by the international media contributing to the negative image of tourist destinations. potential tourists see such cases as indicators of lack of safety; this also shows that the security system at global level is fragmented and not sufficient to ensure the security of citizens. threats on global peace will remain a major issue hampering tourism growth, and stifle tourist destinations to realise full potential for foreign visitors and under utilisation of tourist attractions. in the absence of safety and security, tourism will not flourish. the effects of terrorism have destroyed tourist destinations brands in the tourism market. in conclusion, the current study contributes to literature by investigating the global tourism industry dynamics and their implications to emerging tourist destinations. the study examined fundamental shifts characterising the global tourism landscape since the end of ww . these were identified as the formation of brics countries, ageing population, trophy hunting debate and terrorism. at the inception of tourism, boom factors influenced the growth of the industry, driven by the g member countries, however, as time went by, emerging markets increasingly became more significant, largely driven by the brics. contemporary tourism dynamics framed as the constructs of brics, trophy hunting, ageing population and terrorism have been applied simultaneously to establish the extent to which they are impacting tourism growth projections from the perspectives of emerging markets. these have impacted on the trends of international tourism in a profound way. it is apparent that emerging markets are now in the front foot dictating the pace of tourism development. in light of such fundamental shifts, it is recommended that tourist destinations recalibrate their tourism product offerings so that they reflect the contemporary market dynamics. on the investment front, the emerging markets represent the future of the tourism sector, and finally in light of the devastating effects of terrorism, emerging tourist destinations should refine their terror responsive strategies. apart from the above, another area in need of attention is policy reform, in which immigration regulations and visa regimes should be constantly revised to strike a balance between screening travellers, balancing liberalising and softening the border control formalities to allow free flow of traffic but without compromising on the security and safety matters of tourists. finally, marketing and promotion efforts need to be directed and focused on emerging markets and less on mature tourist regions since the former represent the future of the global tourism industry. this study therefore made a contribution in the specific areas of emerging markets, tourism senior market, convention on international trade in endangered species (cites), and terrorism as key aspects that can make or break the global tourism industry in the twenty-first century. this research responded to the need for continuous research on africa's tourism sector and situate it in the global tourism industry (naude and saayman ; christie and crompton ; rogerson and visser ; dieke ) . to the best of the writer's knowledge, this study presents new knowledge from an emerging tourist region context regarding the dynamics obtaining in the global tourism environment and their subsequent implications. the current study was done in the context of africa an emerging tourist region, with a less influential influence in the international tourism stage. therefore, this study provides a significant addition to literature currently dominated by insights and perspectives from advanced societies like western tourism markets. ethical approval this research was carried out on respondents after full disclosure of the purpose and objectives of the study. participants voluntarily consented to participate in the study. no minors nor vulnerable groups/individuals were involved as respondents during data collection. the study did not use unorthodox means of collecting data. there was no conflict of 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. india: world travel and tourism council zeng brics. the engine of global economic growth. china economic times southern africa tourism industry; recent trends and future prospects tourism progress in the sadc region. post colonial era milestones from bric to brics: developments in the cooperation of emerging economies. the polish institute of international affairs (pism) publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations key: cord- -gozt aur authors: tambo, ernest; xiao-nong, zhou title: acquired immunity and asymptomatic reservoir impact on frontline and airport ebola outbreak syndromic surveillance and response date: - - journal: infect dis poverty doi: . / - - - sha: doc_id: cord_uid: gozt aur the number of surveillance networks for infectious disease diagnosis and response has been growing. in , the world health organization (who) established the global outbreak alert and response network, which has been endorsed by each of the who african members since then. yet, taming the dynamics and plague of the vicious ebola virus disease (evd) in african countries has been patchy and erratic due to inadequate surveillance and contact tracing, community defiance and resistance, a lack of detection and response systems, meager/weak knowledge and information on the disease, inadequacies in protective materials protocols, contact tracing nightmare and differing priorities at various levels of the public health system. despite the widespread acceptance of syndromic surveillance (ss) systems, their ability to provide early warning alerts and notifications of outbreaks is still unverified. information is often too limited for any outbreak, or emerging or otherwise unexpected disease, to be recognized at either the community or the national level. indeed, little is known about the role and the interactions between the ebola infection and exposure to other syndemics and the development of acquired immunity, asymptomatic reservoir, and ebola seroconversion. can lessons be learnt from smallpox, polio, and influenza immunity, and can immunization against these serve as a guide? in most endemic countries, community health centers and disease control and prevention at airports solely relies on passive routine immunization control and reactive syndromic response. the frontline and airport ebola ss systems in west africa have shown deficiencies in terms of responding with an alarming number of case fatalities, and suggest that more detailed insights into ebola, and proactive actions, are needed. the quest for effective early indicators (eee) in shifting the public and global health paradigm requires the development and implementation of a comprehensive and effective community or regional integrated pandemic preparedness and surveillance response systems tailored to local contexts. these systems must have mechanisms for early identification, rapid contact tracing and tracking, confirmation, and communication with the local population and the global community, and must endeavor to respond in a timely manner. electronic supplementary material: the online version of this article (doi: . / - - - ) contains supplementary material, which is available to authorized users. please see additional file for translations of the abstract into the six official working languages of the united nations. the current widespread ebola epidemic is estimated to infect , people before it is contained by early . the total number of probable and confirmed cases of the ebola virus disease (evd) in the five affected countries as reported by the ministries of health of guinea, liberia, nigeria, senegal and sierra leone is cases and has claimed more than deaths so far. more than % of the total number of cases have occurred and are concentrated within a few localities. the average case fatality rate is %; this ranges from % in sierra leone to % in guinea. a separate outbreak of the evd, which is not related to the outbreak in west africa, was laboratory confirmed on august by the democratic republic of congo (drc). there have been cases and deaths so far [ ] . priority responses and actions are needed to tackle the ongoing ebola crisis in west africa and this requires improvements in access to diagnostic technologies and healthcare resources, as well as improved surveillance and communication. as it stands, there is little incentive for vulnerable communities to seek professional diagnosis of suspected ebola. most people with the flu and febrile illnesses self-medicate and are treated at home or by traditional healers/practitioners, making difficult to define the true extent and nature of the outbreak [ ] . syndromic surveillance (ss) has been advocated and used to monitor illness syndromes and events, and to detect epidemics and bioterrorist attacks early, thus increasing and ensuring that the response from public health departments is timelier. however, its effectiveness and usefulness in ebola outbreak surveillance remains unclear [ , ] . up until now, no unified definition for ss coupled with limited predictive abilities of emerging diseases and ebola seroconversion with no associated clinical signs has been determined. the source of high rate of health workers and volunteers infections and death is worrisome and urgently required further investigations, probably resulting from poor adherence and poor compliance to protective measures protocols and standard operating procedures, hard to implement standard clinical and laboratory operating procedures in such challenging environments, stress and anxiety poor incentives and lack of health insurance of those high risk health and humanitarian workers and quality assurance of the local and humanitarian protective products, the protocols. a number of remarkable similarities exist between the humoral responses to filoviruses, in particular the ebola virus, and the response to hiv- infections, and these have been invaluable in demonstrating that antibodies can indeed provide protection against a virus [ ] . therefore, the efficiency of frontline and airport ss is compromised by a number of confounders/factors, such as acquired immunity, human-animal host asymptomatic reservoirs, inadequacies in diagnostic tools, infrastructure of health and social support systems, and various biosocial, environmental and climatic factors. these are still poorly understood in ebola bottlenecks and thus hinder the establishment of adequate and reliable responses to prevent new cases, control further infections, and contain the ongoing geo-distribution trend and pattern in west and central africa. it is common in ss that what is to be detected is unknown, and with asymptomatic and acquired immunity ebola appears to present long incubation periods and prodromes. in order to test detection methods, a simple disease simulation model examination of a spectrum of ultraviolet biosensors of temperature (fever) sensitivity and specificity can provide advantages and limitations in frontline as well as airport syndromic surveillance and could be applied at all times in monitoring any early symptoms in the absence of disease outbreak. it is then sufficient to run the detection method on a subset of simulated disease scenarios or on the challenges present in predicting unbiased diseases that are sufficiently different in order to determine the strengths and weaknesses of different methods at the point of care [ , ] . specific definitions for ss are lacking, and the name itself is imprecise. certain programs monitor just surrogate data sources (e.g., over-the-counter prescription sales or school absenteeism) rather than specific disease syndromes. meanwhile, certain well-defined disease or clinical syndromes (e.g., hemolytic uremic syndrome or kawasaki's syndrome) are not included in syndrome definitions, often leading to confusion about what "syndromic" surveillance actually monitors. the different types of public health surveillance systems for early detection of outbreaks include: ( )early warning systems in the region, disease control policies to restrict border crossings, as well as sales and accustomed consumption of bush meats, which have been ineffective implemented and sustained in diseases or outbreak surveillance and response. in addition, the handling of information by politicians, who have a history of partisan gain and constantly manipulate the media for political agendas, has been worsened over the years, underscored by corruption and nepotism. these coupled with weak health programs-continues to jeopardize genuine efforts to convey timely, trustworthy, and reliable information in a language accessible to the most vulnerable and remote communities [ , ] . symptom-based surveillance relies on self-reporting, health-based or routine admission procedures with clinical examinations, specific diagnosis, and recognition and reporting by clinicians to public health authorities/departments. smart phones should play a greater role in these systems as well. laboratories and other bodies in the region have shown that routine ss systems can be designed to rely on mobile phones which have become ubiquitous in west africa. some researchers forecast that mobile internet use in africa will increase -fold in the next five years, and will consequently double the growth rate in rest of the world, and could be of potential use for individual or community-based surveillance. ( )prodromal surveillance of flu or febrile like diseases has low specificity and may have insidious uncertainty based on differential diagnosis and overlapping early clinical multiple syndrome syndemics that trigger false alarms compared to post exposure, which can cause severe or life threatening disability. the type of prodrome varied from one individual to the next based on previous illness trends, pre-immunity, early indicators for response, over counter or self-medications, and various genetic, ecological and environmental factors [ , , ] . in west africa, the poor evidence-oriented approaches and tools, principles, and guidelines for communication before or during an outbreak require pivotal redesigning based on local contexts and taking into account social media and web-based health information and communication. the usefulness of who tools, guidelines, and recommended practices in ebola outbreak prodrome surveillance in this context is underscored by local limitations, gaps in knowledge, and other challenges. prodromal surveillance tools could be very timely and vital in the realm of emergency communication, advice, behavior change, hygiene and sanitation, and provide an integrated grassroots-based participatory approach. this could lead to more effective prevention, thus curbing the spread and containing the outbreak at the different levels of the disease, and at different places in time and space [ , ] . ( )outbreak detection systems urgently require reliable, effective, and cost-effective tools and interventions which allow for constant access to diagnostic tools and personal protective equipment in healthcare centers across the region [ ] . ( )information system-based sentinel surveillance. ( )biosurveillance systems are used in practice to augment classical outbreak investigations. the major advantages of syndromic systems include sensitivity, timeliness, and flexibility, and being able to provide data for situational awareness. however, biosurveillance precincts lack in specificity, rely on chief complaint data, and lack formal training for users. linking syndromic data to triage notes and medical chart data would substantially increase the value of biosurveillance in outbreak investigations and thus reduce the health burden [ , ] . ( )laboratory-guided detection of disease outbreak surveillance systems relies on detection and monitoring of biothreats enabled by laboratory methods of diagnosis and identifies trends in biosurveillance research. it is based on three approaches, namely: ( ) laboratory-initiated infectious disease notifications, ( ) ss based on health indicators, and ( ) genotyping-based surveillance of biothreats. the insufficient and delayed support for biosurveillance alerts for public health users and the inadequate integration of surveillance signals into action plans remain the major barriers, and require coordination between syndromic and laboratorybased surveillance for efficient public health outbreak monitoring and response [ ] . ( )health indicator surveillance provides authorities with vital health indicators such birth rates, motility rates, and life expectancy. however, trustful and reliable information and communication, health education on preventable fatalities and cautious behavior are also required in order to prevent fear, panic and community resistance to stem out the spread of the disease outbreak. ( )digital or electronic bio-epidemiology surveillance systems, including social media networking and web-based systems, provide valuable channels for timely collection of public health data; give information on the early detection of, and response to, disease outbreaks; and enhance situational awareness to communities. the creation of blogs and user-generated content has turned social networking into a conversation space in which everyone can participate. however in west africa, the low level of literacy and high inequality indices compromised the usefulness of such tools to trace and map the ebola outbreak, as compared to their usefulness and effectiveness in a community with high literacy, for example during the sars and h n influenza outbreak in hong kong and mainland china. social media (e.g., twitter, facebook) and web-based communication provide epidemiological knowledge dissemination, and creates virtual communities based on shared values about critical outbreak perceptions, seriousness of the crisis, and population evidence-based guidance. however, it is not subject to experts or authorities' advice and assessment, and doesn't receive guidance from associated communication or information risk management and security. this requires further development and attention. the implications of social media and web-based information and communication in creating fear, anxiety and stigmatization about ebola in some communities in west africa are noteworthy. during this outbreak, web-based activities were also responsible for fuelling rumors that led to counter-productive behaviors. improved communication between reliable health officials and the media, community leaders, health professionals, and the general public is necessary to reduce misinformation and improve compliance with ebola prevention and control measures that have proven effective. these include population dynamics of emerging infections and the optimal design of monitoring and management strategies in prevention, control, and containment of ebola in other countries in africa [ ] . nonetheless, the term "syndromic surveillance" (ss) has persisted to describe this kind of surveillance as its fundamental goal is to identify signs and symptoms of illness clusters early before diagnoses are confirmed, report to public health authorities or agencies, and mobilize responses rapidly. syndromic surveillance targets the threshold number of early symptomatic cases allowing outbreaks to be detected earlier than conventional reporting of confirmed cases would allow [ , , ] . response protocols for investigating ss alerts present some limitations in most endemic countries with syndemics acquired/partial immunity, diagnosis and identification of co-infections clusters, and sources of exact human-animal reservoirs [ ] . contact tracing and epidemiological case investigation of the nature and severity of the outbreak could provide timely and scientifically reliable information to curb the risk of propagation. hence, more effective surveillance and response systems such as point-of-care ebola molecular typing and immune-detection assays and rapid diagnostic kits in frontline and airport detection are urgently needed. for ebola outbreaks, ss is able to provide the early symptom (prodrome) period before clinical or laboratory confirmation of the disease, as is explained below, although difficult in endemic areas in africa where many tropical diseases with similar and/or differential signs and symptoms co-exist. ebola will continue to be a global threat if prompt and effective commitment is not directed towards control and containment. surveillance and response systems are of interest in public health and veterinary epidemiology for the early detection of the emergence or re-emergence of infectious diseases. in relation to several confounders of ebola outbreaks such as flu-like signs and symptoms of unknown sources, ss, which consists of the routine monitoring of indicators to detect adverse health events, may allow for early detection depending on continuous indicator measurements and sensitivity and specificity (timeliness tools for the detection or diagnosis of diseases outbreak emergence). the limitations in detection and spot diagnosis of asymptomatic reservoirs and preexisting immune confounders have been the challenges since ebola broke out guinea in december , was detected in march , and finally spread to liberia, sierra leone, and nigeria. it is the most severe outbreak of ebola since the discovery of the virus in , with the number of cases from the current outbreak outnumbering the combined cases from all known previous outbreaks. the who has declared the ebola outbreak in west africa to be a public health emergency of international concern and called for action [ , ] . below, we outline the characteristics of the ss approach. ( )the concept and application of ss is doubly attractive because in addition to its potential to increase the speed and effectiveness of the public health response to natural or deliberate disease outbreaks with a certain degree of assurance, it costs far less to implement than traditional, labor-intensive approaches to disease surveillance (both should complement each other) [ ] . however, the ability of ss to reduce disease-related morbidity and mortality remains to be demonstrated, as does its cost-effectiveness and warning devices. it will be critical to assess its utility, sensitivity, and accuracy in outbreak or bioterrorism within the context of health systems that respond to both "true" and "false" alarms in infectious disease syndemic settings. this involves the collection of information and clinical data that might indicate if an infectious disease outbreak might be happening in the community and whether it warrants further public health response. before an outbreak occurs, little is documented in health centers and by airport active ss, except for passive checks of yellow card immunization for bcg, polio, and hepatitis vaccines programmes, in addition to medical referrals for passengers requiring medical or surgical interventions abroad. during the ongoing outbreak of ebola in west africa, ss, along with collaborative efforts between local health departments, has been used on patients, ground staff, health workers, passengers across community/national borders, and airports across africa and in some other major airport hubs worldwide. ( )this approach is confronted by a lack of effective and accurate spot invasive frontline and airport rapid diagnostics tools, district and provincial health laboratories being equipped with little or no advanced molecular technologies, lack of drugs and vaccines to treat ebola, inadequacy in coordinated ebola frontline planning efforts in the community, as well inefficient or nonexistent community and national active infectious disease surveillance systems. syndromic surveillance systems monitor existing descriptive data of these behaviors (e.g., school and work absenteeism, sales of over-the-counter medications, illness-related information, emergency room admissions for symptoms indicative of infectious diseases) for patterns or clusters of behaviors suggestive of an illness outbreak [ ] . hence, ss is not sufficiently equipped to control and contain ebola in africa due to its complex web of interactions and challenges. the usefulness of laser thermal detection of febrile state or other characteristic symptoms of individuals in frontline and airport surveillance systems could be very challenging in hyper-, holo-, and meso-endemic settings, and present several limitations with the rampantly increasing confounders of poverty-related diseases in africa and elsewhere. in addition, it should be noted that several factors such as travel syndrome, menopausal or post-menopausal syndrome in women and other lifestyle stressors associated with an increase in temperature-although normal-can trigger false alarms. moreover, syndemics and partial acquired immunity in the region poses concerns about the spread and the burden of the disease due to asymptomatic reservoirs and the long latency period of infection [ , ] . efforts should be devoted to enhancing research and developing innovative, more sensitive detection and diagnostic tools for early-stage epidemic warning and preparedness in frontline and airport spot surveillance mechanisms and response, rather than increasing the use of empirical broad-spectrum detectors. the bottlenecks to ebola outbreak frontline and airport syndromic surveillance and response systems diagnosis is "the cornerstone of effective outbreak and disease control and prevention efforts, including surveillance" [ ] . current challenges in diagnosis of ebola by frontline and airport surveillance systems underscored the existing detection and diagnostic tools, and highlighted the importance of combining diagnostic needs with appropriate technologies. the need for rapid, accurate, inexpensive, and robust diagnostic low-detection thresholds can be met by recent advances in genomics, proteomics, and material science; profitable public-private partnerships; and sustainable profits in low-resource settings. the continued development and deployment of efficient, low-cost diagnostic platforms is essential for containment. detection methods suitable to local/international standard laboratories or sentinel for imported cases epidemiology must be validated prior to transition from malaria sustained prevention and control programs and interventions. the importance of developing and implementing sensitive diagnostic approaches to accurately quantify and monitor ebola reservoirs is imperative in curbing the persistent transmission dynamics, and preventing, controlling, and containing the disease given africa's engagement in achieving the millennium development goals (mdgs), and in the london declaration international health regulations ( ), the universal human rights declaration, and the new partnership for african's development (nepad) in africa. however, a number of challenges remain to be overcome before deployment of rapid, low-cost, sensitive, and specific point-of-care disease diagnostics become a reality. spot frontline and airport surveillance using laser imaging of febrile conditions with a latency period of - days for clinical manifestations require rethinking, more research, and funding for the development of simple, rapid, field adaptable, and effective detection tools in asymptomatic, presymptomatic, and symptomatic cases, to be used in addition to spot airport passengers' diagnostic kit(s). immune variability across african countries with syndemics is poorly understood, although it is believed that populations develop varied degrees of acquired/partial to complete immunity resulting from repeated exposure to infectious diseases, and can carry a certain load of virus for months or years before it becomes a clinical manifestation of the ebola disease [ , ] . the concept of immunization or vaccination as described by edward jenner ( - ) observed that people with cowpox infection developed immunity to smallpox, with several lifelong survivors. hence, smallpox was declared eradicated in the wild in after a worldwide immunization campaign took place similar to the ongoing polio eradication with effective immunity response to outbreak depending on the age and level of individual antibodies (cell-mediated immunity) and protective threshold. consequently, large asymptomatic population-animal reservoirs in the case of the ebola infection in africa may not be surprising, and further screening of ebola exposed and non-exposed populations is required. what are the lessons and challenges learned in shaping future research priorities? this makes the need for in-depth knowledge on the exposure of viral infectious (e.g., measles, yellow fever, chickenpox, or hiv/aids) even more urgent as this can contribute to ebola resurgence and the quest for an ebola vaccine [ ] . genetic and clinical variability have shown that genetic make-up or traits vary from one ethnic group to another, and within and between populations with different clinical manifestations, but the relationship between population genetic changes and ebola seroconversion and progression over time and space is still poorly understood. the precise role and efficacy of biosurveillance in public health has yet to be determined, as well as the limitations of ss systems to detect ebola infection or other outbreaks. health professionals should continuously aspire to accurately diagnose and treat patients, as well as to identify public health outbreaks or emergencies, combined with adequate local integration of infrastructure, facilities, and capacity building. environment, ecological, and animal interface, and encroachment factors due to landscape use and misuse, mining, deforestation, forest degradation, wildfire, conflicts/wars, and man and animal interactions also require further research. . infrastructure and capacity of health and social systems challenges in ebola control and containment in west africa are obvious due to a lack of humanitarian response models for fragile and under resourced health systems, and the local government and affected community's inability to contain the wide spread of the disease. these challenges include: insufficient regional and international political commitment, insufficient resources and funding, lack of an ebola vaccine or drug, detection and diagnostic limitations, and a lack of resources or infrastructure to support such activities. additional challenges include inadequacies in programs and approaches, weak or nonexistent primary healthcare infrastructure, poor access to health facilities, and a lack of effective mental, traumatic or neurological assessment tools, as well as national and regional functioning early-warning alert and surveillance response systems. other associated factors include social media and web-based information and communication; an artificial country colonial landscape demarcation and barriers amongst african countries with cross-border families; marriage; employment and commercial/trading activities; sociocultural realities and practices; attitudes to care seeking and utilization; environmental and ecological risk factors; human-animal migration and movement dynamics; conflicts/wars and violence in the region; intense mining activities in the region with an associated impact on the political sphere; and the socioeconomic, ecological, and epidemiologic impact of ebola and others infectious and chronic diseases. . acquired or partial immunity of local populations due to the scarcity of data on immune parameters and exposure doses, the exact impact of the disease on humans is hard to quantify. evaluating 'acquired immunity' may improve outbreak estimates when evaluating the risk of microbial illness from food or environmental exposures. this suggests that some current approaches may significantly overestimate their role in causing such illnesses. immune status is a major factor in susceptibility to disease outbreak, and the impact of acquired immunity to a pathogen needs careful insight when assessing the potential health risks of outbreaks and other infectious diseases of different sources of exposure, including ( ) low-frequency, low-dose exposure (recreational water); ( ) low-frequency, high-dose exposure (consumption of raw chicken liver); ( ) high-frequency, low-dose exposure (direct contact with sheep and goats, i.e., farmers); and ( ) high-frequency, high-dose exposure (visiting petting zoos, wildlife hunters or bush meat sellers/consumers). the public health community should also take acquired immunity into account in order to improve estimates of the potential impacts of infectious diseases and to assist in preventing and managing outbreaks. further studies to better characterize and quantify the effects of acquired immunity on ebola outbreaks are also needed. in humans, there may be apparent ecological, ethnic susceptibility and geographical landscape variations, but it is always important to disentangle such factors-as well as climate, nutrition, environmental, and economics drivers-from those that might be genetically determined in both animal and human transmission dynamics. ongoing efforts to control and contain the ebola outbreak have been limited by the estimated mass asymptomatic population and animal-human reservoirs, which enhance the tenacious transmission dynamics between and within some communities, provinces, and across african countries and elsewhere. viral infectious diseases such as hiv/aids, hepatitis coupled with malaria, tuberculosis, and other neglected and emerging infectious diseases are rampant in africa [ ] . assessment of transmissibility requires tools that can accurately identify the various developmental stages of the animal-human and/or human-human interphases. moreover, in most epidemic areas, asymptomatic carriers are not uncommon and, as potential carriers, represent a significant reservoir for ebola transmission regardless of successful local interventions. these are the challenges to the current humanitarian and national prevention, control, and containment programs [ ] . many of these asymptomatic infections may be present at densities below the limit for microscopic and rapid diagnostic tests threshold detection and thus lead to underestimation persistence of the epidemic burden and probably resurgence. there is very limited, if no, accurate information or data available on submicromolar asymptomatic carriers or presymptomatic surveillance, the detection and diagnosis responsible for ebola virus survival, and persistent transmission on susceptible populations. paucity information pertaining to the current status of the effectiveness of microscopic and rapid diagnostic test tools necessary for ebola control and containment interventions, except for molecular confirmation of cases done in very few selected research centers in africa and across the country since the first ebola outbreak in is also lacking. the development and deployment of active surveillance at all levels coupled with monitoring and evaluation (m&e) of outbreak risk factors and transmission dynamics in early active detection asymptomatic and presymptomatic cases, as well as prompt management of either local or imported cases, is paramount to understanding the viral seroconversion dynamics in suspected communities and travellers in africa and worldwide. sensitive and effective serological, immunological, and biochemical ebola biomarkers that can be used in these remote communities with uncertain or low animal and population reservoirs alongside spot airport testing, mass deployment in mapping geographical distribution, evidence informed policy decision, and prompt interventions-are also essential. understanding the ebola epidemiological trend and patterns including reservoirs and transmission dynamics can provide valuable information for the success of ebola control and containment strategies. although ss response systems are able to detect ebola outbreaks earlier than traditional surveillance, it will be more efficient for these systems to prepare for the standard operational protocol to avoid unexpected occurrences of events. therefore, we recommended the strengthening of the following activities in order to improve the frontline and airport ss responses to ebola outbreaks: . improving case investigation, tracking of susceptible populations, and quarantine period most african countries are challenged by insufficient or nonexistent facilities, a lack of qualified personnel, and the vicious cycle of poverty. cultural practices and myths, challenges in african traditional and alternative medicine implementation in healthcare systems, and attitudes towards health seeking should also be noted. the poor landscape mapping, rural and urban town planning, and especially the poor or nonexistent accessible roads to these communities are other contributing factors. tracking can be very difficult in areas with poor documentation habits, lack of appropriate reporting or a contact tracing system, uncontrolled migration and population movement across borders, unlimited cross-border marriages and trade, as well as animal in-and out-flow of foreigners at the entrance or departure terminuses (airport) in africa and elsewhere. the porous nature of west african country borders stresses the need for automated robust, high-sense human and animal health and movement detectors, in partnership with communities and governments so appropriate data can be collected to answer essential ebola questions. public health surveillance and powerful analytical tools are needed to accurately interpret the findings. the strengthening of the epidemiological capacity through surveillance response systems at the local level needs to be advocated in order to inform the interpretation of syndromic findings in light of "local epidemiological peculiarities," as well as to ensure a rapid response to syndromic alerts. under enabling conditions, community-based mobilization and empowerment in recognizing, informing and active case investigation and contact tracing could build strong relationships between public health and healthcare providers in effective early alert, prevention, control of current and future outbreaks. these relationships are critical for reliable and effective emergency outbreak response and follow up epidemiological investigation, and for evidence policy-building regardless of the type of intervention [ , ] . . nurturing "one health and one world" surveillance and response systems infectious diseases primarily affecting animals can have direct and indirect impacts on humans including significant economic consequences. two important factors can contribute to the proliferation of zoonotic diseases: the explosive growth of human and domestic animal populations, and the increasingly close physical proximity within which humans and domestic and wild animals live [ , ] . timely identification of current and future emerging microbial threats (on the order of sars, the west nile virus, and h n avian influenza) will require an integrated international approach to disease surveillance. however, progress has been hampered by a variety of mining, environmental, climatic, socioeconomic, and political factors, in addition to a weak and fragile or nonexistent surveillance infrastructure and technology, and inadequate expertise in africa. success in ebola control and containment requires a comprehensive and integrated strategy in human disease surveillance among the underserved populations that live in close contact with bat fruits, gorillas, and other wildlife animals. this strategy should incorporate capacity building, training, and empowerment of the local community by integrating simple data collection with basic laboratory diagnosis to identify the link between human outbreaks of the ebola virus, and poaching, the consumption of bush meats, basic hygiene measures such as hand washing and cooking meat thoroughly, overall food safety in communities, and early warning of outbreaks in animals [ ] . in view of the recognized potential of ss systems, there are many practical concerns about sensitivity and false-positive rate trade-offs and the time required to accumulate enough evidence of an outbreak to trigger a detection algorithm, as well as on the available control strategies of the local, national, and regional public health practice and utilization of these systems. the broad and multifaceted practices of surveillance approaches are used to monitor the progress and outcome of interventions to mitigate or stop the progression of an outbreak, including of economically and ecologically important animal or plant species and the transmission of zoonotic diseases among animal and human populations over space and time, as well as to predict future transmission patterns [ , ] . currently, disease outbreak surveillance and detection relies heavily on the astute individual: the clinician, the veterinarian, the grower, and the livestock manager noticing both routine and suspicious symptoms and bringing them to the attention of the public health or veterinary community including academics and zoological parks. most developed countries have a surveillance system in place and the ability to detect and diagnose human and animal diseases. innovations and strategies for the surveillance and detection of human and animal diseases, and assessing the resource needs and opportunities for improving and coordinating infectious disease surveillance, early detection, tracing, case investigation, prompt reporting, and management are needed in upholding health systems strengthening and future sustainable development in most under resourced countries [ , ] . technological advances in disease surveillance and detection that have benefited public health surveillance such as rapid, automated, and sensitive biosensors; portable sampling and assay systems; and dna-based diagnostic tools remain to be adapted to track animal diseases. models and interventions incorporating m&e systems and true coordination and collaboration would enable optimal surveillance response, thereby driving policy and action, with a feedback process to facilitate continuous evolution and adaptation [ , ] . information would be drawn from a broad range of disciplines relevant to physical and mental health, as well as domestic and wild animal health and plant health, through the complementary processes of agent or disease surveillance and host and environmental monitoring with potential economic benefits of surveillance systems for all. nevertheless, the release of surveillance information should be evaluated on a case-by-case basis, as trust is not built by merely sharing data, but by helping people understand information that is context-specific. active engagement to discuss the perception of risk of outbreak and identifying priorities for action is also essential. community or regional active surveillance systems, new effective rapid diagnostic methods, and prompt reporting have the potential to advance infectious disease control and prevention efforts in africa and elsewhere. although, the electronic surveillance system for the early notification of community-based epidemics (essence), operated by the department of defense, allows epidemiologists to track-in real-timesyndromes reported in daily data feeds from regional hospitals and clinics, it is yet to be actively implemented in most africa countries. due to the persistent outbreaks of infectious diseases across africa, it is crucial to analyze the applicability of surveillance response systems in order to improve the ability of hospital/health center triage systems to identify and appropriately treat patients who show symptoms associated with an emerging infectious disease, a threat of an infectious disease (e.g., influenza, sars, and ebola, as well as potential bioterrorism agents such as anthrax and smallpox), or an emerging infectious disease. laboratory diagnosis may be possible by building a network of information about early warning alert and response systems that travels up or down the public health hierarchy, from the local to the international level and vice versa [ ] [ ] [ ] . . shifting towards an effective public and global health paradigm due to globalization, health for all under the "one health" initiate calls for immediate ebola and other outbreak actions plans. a future, in which outbreaks and bioterrorism agents are continually reengineered to evade standard detection and diagnostic methods, as well as therapeutics, is imagined. hence, africa and the global community has no choice but to move from postsymptomatic to presymptomatic detection and diagnosis, and to prompt effective surveillance response systems that seek to benefit the global community. ultimately, to reach the best-case scenario stage in which microbes are ubiquitous, constantly evolving, and adapting requires community and national surveillance policies to inform and guide action on the basis of importance, not for reaction and emergency to dictate priority [ , ] . there is no magic bullet for changing paradigms; steady progress, albeit being slow, can be made through small successes. this needs to be properly recognized as an effective engine for change to educate the next generation of leaders early in their careers and encourage greater global, inter-, and trans-disciplinary awareness in future public health professionals. the quest for eee in shifting the public and global health paradigm to achieve the mdgs post the - agenda, the "one health, one world" and other global health initiates requires: community outreach and advocacy, and local and international mobilization to combat outbreaks in africa and globally. multidisciplinary approach studies to understand the drivers, determinant dynamics, and risk factors of persistent ebola outbreaks. strengthening south-south and public-private partnerships to build local capacity, health education, and empowerment in health and environmental community health for sustainable development. more research in host-based early-warning alert models and understanding of the contribution of context, culture, and ecosystems on asymptomatic/ presymptomatic factors in ebola pre-exposure diagnosis prior to the appearance of symptoms. monitoring a person's blood serum chemistry for changes that suggest a compromised health status or non-invasive sampling of breath and saliva is attractive in theory. rapid molecular markers for mass population screening and diagnosis-based triage and increasing the effectiveness of quarantine or other social distancing measures including the development of synthetic antibody techniques for monitoring infection-related changes in protein levels. monitoring the biological signatures of infectious disease devices: easily accessible (e.g., in the home), robust, inexpensive, and capable of quickly measuring thousands of ebola outbreak spatiotemporal minimum effective data for mining variables in understanding the progression from asymptomatic to clinical ebola cases and forecasting future ebola trends and geo-distribution. more infrastructure and facilities in rural and remote areas, especially in mining african countries, as well as research and development (r&d) funding for ebola drug and vaccine development. development and implementation of country and cross/regional active and integrated communitybased surveillance response systems and m&e initiatives to formulate alternative and innovate community/national recovery and rehabilitation programs, measures, and interventions post-ebola outbreak surveillance and response systems. given the considerable interdependence of surveillance, detection, and diagnostic activities and infectious diseases, it is not surprising that the key challenges identified in this paper can be overcome by innovative surveillance strategies and future prospects as described above. early detection is essential to control and contain the spread of the ebola outbreak. a disease such as this-in a profoundly interconnected world-requires active vigilance for rapid recognition, and prompt diagnosis, case investigation, and tracking of its causes and sources, as well as the mitigation of reliable and robust strategies and resources for an appropriate and efficient response. this paper illuminates the major gaps in frontline and airport ebola control and containment, and provides structured opportunities for leaders, governments, academia, industry, and stakeholders to more robustly mobilize and combine resources. we examine issues of shared concern regarding research, prevention, detection, and management of the ebola outbreak and other emerging and re-emerging infectious diseases. additional file : multilingual abstracts in the six official working languages of the united nations. effective early indicators; evd: ebola virus disease; hiv/aids: human immunodeficiency virus infection and acquired immune deficiency syndrome; mdgs: millennium development goals; m&e: monitoring and evaluations; r&d: research and development; sars: severe acute respiratory syndrome; ss: syndromic surveillance; who: world health organization ebola virus disease in west africa -no early end to the outbreak world health organization: no early end to the ebola outbreak syndromic surveillance and bioterrorism-related epidemics pre-and postexposure prophylaxis of ebola virus infection in an animal model by passive transfer of a neutralizing human antibody veterinary syndromic surveillance: current initiatives and potential for development evaluation of animal and public health surveillance systems: a systematic review use of syndromic surveillance at local health departments: movement toward more effective systems biosurveillance in outbreak investigations syndromic surveillance: review and prospect of a promising concept laboratory-guided detection of disease outbreaks: three generations of surveillance systems developing open source, self-contained disease surveillance software applications for use in resource-limited settings ebola in sierra leone: a call for action disease outbreak news syndromic surveillance: is it a useful tool for local outbreak detection? scaling up impact of malaria control programmes: a tale of events in africa and people's republic of china from prioritizing research for "one health -one world global infectious disease surveillance and detection: assessing the challenges-finding solutions, workshop summary. institute of medicine persistent infection with ebola virus under conditions of partial immunity spatiotemporal environmental triggers of ebola and marburg virus transmission need of surveillance response systems to combat ebola outbreaks and other emerging infectious diseases in african countries elimination of tropical disease through surveillance and response surveillance-response systems: the key to elimination of tropical diseases submit your next manuscript to biomed central and take full advantage of: • convenient online submission • thorough peer review • no space constraints or color figure charges • immediate publication on acceptance • inclusion in pubmed, cas, scopus and google scholar • research which is freely available for redistribution we would like to thank all of our researchers, field workers, and stakeholders, including humanitarian organizations and volunteers on the frontline of ebola and other outbreaks prevention, control, and containment worldwide, for all their hard work. this paper is especially dedicated to all the health workers and volunteers that contracted ebola and lost their battle with the disease. no funding organization supported this work. the authors declare that they have no competing interests. this study was conceived and designed by et. zx provided guidance on the technical aspects of the study. et and zx provided additional detailed scientific and technical information and commentary on the manuscript. et assembled the final version and performed extensive revisions. all authors read and approved the final manuscript. key: cord- -v rnvpg authors: orunmuyi, akintunde t; lawal, ismaheel o; omofuma, omonefe o; taiwo, olalekan j; sathekge, mike m title: underutilisation of nuclear medicine scans at a regional hospital in nigeria: need for implementation research date: - - journal: ecancermedicalscience doi: . /ecancer. . sha: doc_id: cord_uid: v rnvpg background: nuclear medicine needs better integration into the nigerian health system. to understand the relevant public health initiatives that will be required, this study assessed the pattern of nuclear medicine imaging services at the first nuclear medicine centre in nigeria from january to december . methods: the data of consecutive nuclear medicine (nm) scans performed between st january and st december at the nm department in a tertiary hospital in nigeria were extracted from patient records and analysed using sas version . (sas institute, cary, nc). the national cancer institute’s joinpoint software and qcis (qgis project) were used to estimate imaging trends and geographical spread of patients. results: an average of scans per year was performed during the study period. patients travelled from of nigeria’s states, and the majority ( %) travelled more than km to obtain nm scans. bone scans accounted for . % of the studies. the remainder were renal scintigraphy ( . %), thyroid scans ( . %), whole-body iodine scans ( . %) and others ( . %). conclusions: nm in nigeria appears underutilised. furthermore, the studies to characterise the access gaps and implementation needs will contribute to the design of practical strategies to strengthen nm services in nigeria. the availability of nuclear medicine in sub-saharan africa has increased significantly in the past two decades [ ] . whilst south africa has the most advanced nuclear medicine (nm) practices on the continent, spanning over six decades, the growth of nm in most of the other sub-saharan african countries is a recent event [ , ] . nm diagnostic and treatment procedures are among the most powerful analytic tools for decision-making in the management of cancer, cardiovascular and neurological diseases. appropriate utilisation of nm tools has led to fewer patients undergoing invasive and costly tests and sometimes unnecessary treatments including invasive surgeries [ ] . the impact of nm on the management of cancer led to the strengthening of nm capacity by the international atomic energy agency (iaea) among member states in africa, as a part of international cancer control efforts [ ] [ ] [ ] [ ] [ ] . however, the growth of nm in sub-saharan africa continues to face many challenges. the known barriers include ageing equipment [ ] , culturally embedded dread of radiation [ ] , logistic challenges with radionuclide delivery [ , , ] , lack of health insurance [ ] , as well as other systemic barriers that limit health systems in developing countries [ , ] . the incidence of cancer is increasing in most of the african countries [ ] [ ] [ ] [ ] . the demographic and epidemiological changes are leading to a rise in the non-communicable disease burden on public healthcare in nigeria, africa's most populous country [ ] . as a part of the national strategic health plans, nm planners in nigeria projected that the country would require a minimum of nm centres to provide equitable access to nm services in the country. using their intuitive judgement, the sites of the ten nm centres were in tertiary hospitals that will provide radiation oncology services [ ] . having received a grant from the iaea, the centre under review was established in as the first nm centre in nigeria. it is geographically located in the southwest region of the country at nigeria's first tertiary hospital and oldest medical school [ ] . the second centre was opened in at the nation's capital city, which is geographically in the northern central region of the country. both centres have a similar complement of nm physicians, which are in tertiary hospitals and major regional referral centres for radiotherapy. however, the centre under review is more established with four radiopharmacists, a dedicated medical physicist and two gamma camerasincluding the only hybrid single-photon emission computer tomography/computer tomography (spect/ct) scanner in west africa [ ] . furthermore, it is purpose built to accommodate two positron emission tomography (pet) scanners and a cyclotron and recently expanded from two to ten isolation rooms for radionuclide therapy, making it the largest nm facility in the country. the second centre is equipped with a double-head spect camera and has two radiopharmacists and two nm physicians. for unknown reasons, nm services have been interrupted for prolonged periods in the past years. as a result, opportunities to scale up existing capacity, create a better understanding of the benefits of nm and invest in research and education to support its growth in nigeria are desired. to inform the relevant public health initiatives that will be required to promote nm in nigeria, this study assessed the pattern of nm imaging services at the first nm centre in nigeria from january to december . the medical records of consecutive patients who underwent nm scans at the department of nuclear medicine at the university college hospital, ibadan, between january and december were retrospectively reviewed. the data on approximately , studies from to had been lost due to damage to the external hard drive for image storage and several missing pages on the data entry book. we collected sociodemographic and clinical information including age, sex, residential address, referral details, type of scan each patient received and the indication for the scan. a paediatric patient was defined as any patient aged years or younger at the time of imaging. furthermore, categories were created for age (missing, ≤ years, - years, - years, - years, - years, - years or ≥ years ), sex (male or female), type of referral hospital (in-hospital and outside hospital), type of scan, indication for referral (cancer related or non-cancer related) and referral physician speciality (unknown, surgical speciality, medical speciality, radiation oncology, paediatrics or others). the human research ethics committee of the institution approved this study, ethics number ui/ec/ / , and waived the need for patients consent due to the retrospective design of this study. the national cancer institute's joinpoint software was used to estimate the annual percentage change (apc) in imaging/scans from to . referral patterns were characterised by the type of referral hospital and referring physician speciality. the residential address provided by patients was used to determine the state of residence in nigeria. subsequently, the geospatial data were generated from the centroid coordinate of each state in nigeria and was obtained from a digital map of nigeria. new columns (latitude and longitude) were created, and the corresponding centroid coordinate of each patient was added. the file was saved as a text file and imported into the open-source qgis software. the distance to the nearest hub algorithms was implemented based on the data. subsequently, the distance travelled to obtain nm scans was estimated. a km distance was empirically chosen to categorise the distance travelled to obtain scans into two groups (≤ km or > km). we performed all scans in accordance with the international guidelines as published by the european association of nuclear medicine and the society of nuclear medicine and molecular imaging. procedures were characterised according to the common single-photon emission computer tomography (spect) scan types (bone, renal, thyroid or whole-body iodine scans or others). less commonly requested spect scans include brain, cardiac, lung and gastrointestinal (gi) scans and were grouped under the category 'others'. indications for nm scans were further subclassified as follows: common oncologic (cancers of the breast, prostate, cervix and gi tract), less common oncologic (all other cancers) and non-oncologic indications. descriptive statistics were assessed for the means and standard deviations (sd) for continuous variables, whereas the percentages were assessed for categorical variables. all statistical analyses were conducted using sas version . (sas institute, cary, nc) and the national cancer institute's joinpoint software. a statistical significance was set at p < . . a review of the medical records showed that a total of , nuclear medicine scans were conducted between january and december at the university college hospital, ibadan. these scans were performed in , patients. a total of repeat/follow-up scans were performed in patients, ranging from to scans per patient. table shows the general characteristic of patients. the mean age was . ± . years (range: . - years), and % were done in females. the highest proportion of nuclear medicine scans was conducted in persons aged between and years ( . %). the paediatric age group accounted for . % of scans performed. patients travelled from all but four states in nigeria (figure ), and most ( %) travelled more than km to obtain scans ( figure ). figure shows the speciality of referring physicians during the study period. surgical specialities and radiation oncology accounted for % and . % of total referrals, respectively. bone scanning with technetium- m ( m tc)-labelled diphosphonates was the most common procedure ( . %), followed by renal scans ( . %), whereas pertechnetate thyroid scans and whole-body iodine (wbi) scans using radioactive iodine- ( i) accounted for . % and . % of scanning procedures, respectively (table ) . overall, . % of scans performed were for oncology indications. table shows the common and less common oncology indications for scans. female breast cancers ( . %), prostate cancers ( %), cervical cancers ( . %) and gi cancers ( . %) were the top four. among the less common oncologic indications, head and neck cancer was the most common, also accounting for . % of overall scans. only scans were carried out for non-oncologic indications and are shown in table . renal scans ( %) were the most common nononcologic scans, followed by bone ( . %) and thyroid ( %) scans. less commonly performed non-oncology scans during the study period included hepatobiliary scans using m tc-labelled iminodiacetic acid derivatives, parathyroid scans using the cardiac imaging agent mibi (hexakis methoxy-isobutyl-isonitrile), lymphoscintigraphy and gastric emptying scan. technetium-labelled mercapto-acetyl-triglycine ( m tc-mag ) and technetium labelled-diethylenetriaminepentaacetic acid ( m tc-dtpa) accounted for % of renograms, whereas the remainder were m tc-dmsa scans (technetium- m-labelled dimercaptosuccinic acid). furthermore, an evaluation of non-oncologic indications for scans showed that that scans for the evaluation of pain/inflammation were the most common non-oncologic bone scan followed by scans to evaluate for infection. notably, all requests for infection imaging were from in-hospital orthopaedic surgeons. the trends of scans performed from to showed a significant increase in the apc of renal and thyroid scans by . % and . %, respectively. conversely, bone scans decreased by . %, but this was not statistically significant. furthermore, the analysis of the trend for bone scans showed a significant decrease in the apc for breast cancer ( . %), whereas bone scans for prostate cancer increased by . %. overall, a significant decline in in-hospital requests (apc: . %) and an increase in outside hospital requests (apc: . ) were noted (p < . ). the trend data are shown in figures - . this is the first study reporting on nm utilisation and referral patterns in nigeria, the most populous african nation [ ] . the volume of scans averaging scans per annum is consistent with the other studies reporting similar low throughput of nuclear medicine departments in sub-saharan africa [ , ] . besides the specific barriers of nm in nigeria [ , [ ] [ ] [ ] [ ] , general challenges that affect oncology and healthcare delivery significantly impact on nm scans. since the majority of the referrals come from oncologists, radiotherapy equipment downtime and industrial strike actions by health professionals trade unions impact on nm services [ ] . external strikes (aviation and logistics) are not only less frequent but also halt nm service delivery. for instance, since the global covid- pandemic started, an import of radionuclides from overseas has been disrupted. the affordability of scans also plays a major role in the utilisation of nm procedures in nigeria [ ] . in our experience, camera downtime as a factor for under utility of nm is infrequent. its effects are minimised due to the availability of two gamma cameras. the low utility of nm scans could be partly explained by the accessibility of services. with only two centres nationwide, patients would have to travel long distances to obtain services [ ] . although patients travelled from all but four states in the country, the numbers of scans diminished with distance travelled (figure ). the four states without referrals are a part of six states in nigeria with remarkably high rates of severe malnutrition [ ] . therefore, it is likely that travel distance and socioeconomic factors play a role in the utility of nm services. this could be evaluated in the further studies. the results show that few nm scans were performed for non-oncologic indications. remarkably, no cardiac imaging was conducted during the period under review. the absence of nuclear cardiology imaging may have contributed to the low scan volumes in this study. nuclear cardiology, in general, notably stress myocardial perfusion using single-photon emission computed tomography (spect), is underutilised in many developing countries [ ] [ ] [ ] . myocardial ischaemia appears to be an infrequent cause of hospital deaths in nigeria despite population-level changes in cardiovascular disease mortality and morbidity [ ] [ ] [ ] . the ability to foster the adoption and expansion of nuclear cardiology in developing countries may be blunted by the marked decline of spect cardiology imaging globally [ ] . infectious diseases continue to be the leading cause of mortality in sub-saharan africa [ ] . this proposes that the need for infection imaging will be high. the utility of nm for infection imaging was low and limited to referrals from in-hospital orthopaedic surgeons. although in-house orthopaedic surgeons are renown experts in the country and more informed about nm services [ ] , we do not believe that they are utilising nm scans to the maximum possible. feedback of their dissatisfaction with bone scans for the evaluation of prosthetic joint inspired efforts to introduce technetium-labelled ubiquicidin peptide ( mtc-ubi). however, the local research studies to evaluate its impact are required. conducting research has been shown to facilitate the adoption of new techniques in small-scale initiatives [ ] . given the recent development of infection-specific radiopharmaceuticals such as mtc-ubi [ ] , advances in spect quantification and standardisation of imaging procedures [ ] , the approaches to raise awareness about nm infection imaging and its potential adoption are needed. overall, the low utility of nm for non-oncologic scans may not be unrelated to the promotion of nm at its founding as an important tool for cancer management [ , ] . furthermore, the studies to explore other unknown factors that play a role in the low throughput of nm services in nigeria and other sub-saharan african countries are warranted. implementation science has been proposed as a means to foster the adoption of evidence-based strategies for health in low-and middle-income countries [ , ] . investigating the challenges of implementation and adoption of nm in sub-sahara africa should not be overlooked. the predominant use of diuresis renography among adults in this study is noteworthy. it contrasts with the reports from developed countries, where diuresis renography is predominantly used in children for the early detection and management of congenital abnormalities of the kidneys and urinary tracts (cakut) [ ] [ ] [ ] [ ] . in nigeria, cakut is responsible for between . % and . % of paediatric admissions and a major cause of chronic kidney disease among children [ , [ ] [ ] [ ] . coordinated efforts to improve the diagnosis and treatment of renal diseases in childhood are needed and may impact on renal diseases observed in adulthood. opportunities for multidisciplinary research and coordination of public health paediatric care in proximity to nm centres should be explored further. the role of nm in thyroid disease continues to be of interest. the current role of thyroid scintigraphy for diagnosis is adjunctive [ ] . several radionuclides are used for thyroid imaging, where nm contributes to the treatment of both oncologic and non-oncologic conditions. radioactive iodine ( i) and pertechnetate ( mtco -) are the radionuclides used for imaging, whereas i is used for treatment. similar to the other reports, this study shows mtc-pertechnetate as the main isotope used for thyroid imaging in resource-poor settings. its major indication for use is to evaluate clinically confirmed graves' disease. other indications include evaluation of thyroid nodules and thyroiditis to locate ectopic thyroid tissue [ , ] . its low cost, ready availability, rapid imaging and lower absorbed dose are major advantages. for patients undergoing radioactive iodine therapy for benign and overactive goitres, it is routinely used to guide empirical dosing [ , ] . however, personalised radioiodine therapy is best achieved by a radioiodine uptake test [ ] . radioactive iodine i therapy (rait) is the first targeted theragnostic radionuclide in nm and plays an important role in thyroid carcinoma treatment [ ] . the reports of the use of rait in nigeria predate the establishment of the nm imaging facilities [ ] [ ] [ ] . the rising patterns of thyroid and whole-body scintigraphy with i (wbi) in this study provide recognition for the impact of nm in nigeria. wbi is recommended for staging of patients with suspected metastases from differentiated thyroid carcinomas. the use of the same radionuclide ( i) for diagnosis and treatment has its controversies [ ] . however, it remains useful for identifying patients who will benefit from i from the other forms of therapy in the case of poorly differentiated or dedifferentiated thyroid carcinoma [ , ] . wbi provides information on nodal and distant metastases for staging of the disease and gives a visual representation for monitoring treatment response and detection of recurrence during follow-up [ , ] . therefore, the routine administration of radioactive iodine i without radionuclide imaging is not recommended [ , , ] . opportunities to educate oncologists/endocrinologist on the role of imaging for radioactive iodine therapy must be sustained. challenges with radionuclide supply continue to impact on timely access to nm services and its growth in nigeria [ ] . this may contribute to the observed stable imaging trends despite population health evidence shows the need for nm. the decline in bone scan for breast cancer may indicate the impact of evidence-based research on clinical practice. in a prior study, we had shown that bone scan was frequently showed metastases in patients with stage iii and iv disease. hence, the routine use of bone scan for staging is only in these patients [ ] . consistent with global patterns, bone imaging with technetium-labelled diphosphonates was the most common procedure in the centre. it is well established for staging of patients with prostate, breast, small-cell lung tumours and other cancers which frequently metastasise to bone [ , ] . the top four oncologic indications for nm scans in this study were consistent with country figures [ , ] . general advances in imaging are increasingly revealing the limitations of bone scanning, particularly for modifying treatment outcomes and early detection of treatment response in cancers [ ] [ ] [ ] . recent pet tracers are promising for the application of pet in the initial evaluation of several oncologic diseases [ , ] . since automated synthesis systems have increased the reliability, reproducibility and safety of radiopharmaceutical productions [ ] [ ] [ ] , the absence of pet services in nigeria is largely due to the high cost of investment. in the southern hemisphere of africa, the availability of pet is limited to south africa and, recently, kenya. recent advances in spect technology are projected to advance spect closer to pet imaging [ ] . however, it will require matching advances in spect radiopharmacy and affordability within the reach of low-resource countries. furthermore, the feasibility analysis on the need and utilisation of technological advances in nm technologies (cyclotron, pet, spect) in africa are warranted in the future. nuclear medicine in nigeria has been sustained for years but appears underexplored and underutilised. however, the limited availability of nm services creates unequal access for patients who require these services. differential and 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bone scan in the initial staging of skeletal metastasis in prostate cancer: a fait accompli prostate-specific membrane antigen pet-ct in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (propsma): a prospective, randomised, multicentre study quantitative bone scan lesion area as an early surrogate outcome measure indicative of overall survival in metastatic prostate cancer ) ga-fapi pet/ct: tracer uptake in different kinds of cancer positive fapi-pet/ct in a metastatic castration-resistant prostate cancer patient with psma-negative/fdg-positive disease gallium- dotatate production with automated pet radiopharmaceutical synthesis system: a three year experience asia ocean futureproofing [ f]fludeoxyglucose manufacture at an automation of the radiosynthesis of six different f-labeled radiotracers on the spect/ct -standing on the shoulders of giants, it is time to reach for the sky! key: cord- -c qdmkw authors: weiss, robin a title: hiv and aids: looking ahead date: journal: nat med doi: . /nm - sha: doc_id: cord_uid: c qdmkw although the future of hiv science is uncertain, we need to reappraise hiv diversity, pathogenesis and immunity. the aids pandemic threatens the success of existing vaccine programs and may accelerate the emergence of new infectious diseases. a pollo conferred on cassandra the gift of clairvoyance but later added the caveat that no-one would listen to her prophesy; thus, her warnings of the fall of troy and the house of agamemnon went unheeded. doctors and scientists are less farsighted, and making predictions exposes us to ridicule in hindsight. not long after the us surgeon general declared that it was "time to close the book on infectious diseases", hiv began to 'cruise' the san francisco bath houses while severe acute respiratory syndrome (sars) lay further in the future. in margaret heckler, then us secretary for health and human services, declared on behalf of the national institutes of health that "we hope to have a [aids] vaccine ready for testing in about years." how foolhardy it was to accept an invitation from nature medicine to comment on the next years of hiv science! if we could foresee the future of research, then we would surely be doing it now. the other contributors to this issue have made the sensible prognostications, whereas anything i put forward here must be regarded as unsure prediction, idle speculation or even wild conjecture . the pace of hiv science, like all science, is driven by technology with unexpected breakthroughs. without pcr, we would not have accurate measurements of hiv viral load and turnover; without rapid dna sequencing and bioinformatics, we would not have such an exquisite database on hiv genetic variation; and if plant virologists had not been curious to investigate gene silencing, we would not have rna-mediated interference (rnai) as a medical research tool. thus, my message for future progress on hiv is that we ignore non-hiv research at our peril. no doubt this prophesy will fall on deaf ears at the funding agencies, especially those in the charitable sector: the late bernie fields' exhortation to "get back to basics" in hiv science is not part of their mission. our colleagues at the institut pasteur must have felt as frustrated as cassandra when so few heeded their first report in may on a previously unknown retrovirus that was possibly associated with aids. at that time, 'lymphadenopathy virus' (lav) was just one more candidate agent alongside other animal and human viruses, and alongside an idea that a fungal infection secretes a cyclosporin-like immunosuppressant. but none of us present at the cold spring harbor laboratory meeting on human retroviruses in the fall of should have failed to be impressed by how the french scientists hardened their evidence. by early , they had detected the virus in individuals with aids, including gay men, two brothers with hemophilia and a heterosexual couple from africa and their child, and had pointed out the similarity of lav to animal lentiviruses on account of its cytopathic effects and morphology . they were accurate in almost every finding, including the only correct interpretation of the open reading frames when the viral genome was cloned and sequenced . hard on the heels of the second french report came news of other hiv isolates from the united states , . apart from the overoptimistic claims of a vaccine, early hiv research was extraordinarily fruitful (see accompanying reviews in this issue [ ] [ ] [ ] . propagating hiv in t-cell lines provided ample antigen for diagnostic tests of infection that by had been translated into kits suitable for the mass screening of blood donors. cd was identified as the cellular binding receptor for hiv in . the importance of the regulatory and auxiliary genes began to be elucidated in . azidothymidine (zidovudine) became the first antiretroviral drug to enter clinical trials in . meanwhile, we began to grasp the scale of the aids pandemic unfolding before our eyes: 'slim' disease in africa was indeed aids . figure illustrates both the success of hiv science and the formidable challenges before us; it contrasts the control of mortality from aids in the united states with its exponential rise in sub-saharan africa. but fig. a belies the heterogeneity of the african epidemic. as the 'four-city' studies have shown , we still do not know why hiv spread explosively in some places and not in others. fifteen years ago, aids in south africa was seen in a handful of gay white men who had traveled to the united states, but now more than four million south african black men, women and children are infected with hiv. by contrast, it was estimated years ago that about % of adults in kinshasa were infected, but this proportion remained stable until recently, despite the imploding infrastructure and human conflict that the democratic republic of congo has suffered. predicting the future of the hiv epidemic will be no easier than interpreting the recent past. epidemiological evidence for the transmission of hiv by sexual and parenteral routes was clear before hiv was identified, and mother-to-child transmission soon after. the modes of transmission remain the same today and seem unlikely to change tomorrow. i previously questioned whether biting insects with large mouthparts might act as 'dirty needles' to transfer hiv passively, given that another lentivirusequine infectious anemia virusis transmitted in this way. but there is no evidence of transmission by insects, and if it were occurring then we would expect to see more children seroconverting before puberty. it was recently postulated that in africa, contaminated syringes and needles are responsible for more hiv transmission than is sexual contact. although the number of infections by unsterile injections may have been underestimated during the pandemic phase of hiv, as well as during the mid-twentieth century , sexual spread is driving the african pandemic , . if injection were the main route of hiv infection in africa, as it has been in eastern europe and china, then again we would expect to see more children of hiv-negative parents developing aids. as valdiserri et al. argue in this issue, much has been accomplished in reducing the transmission of hiv and, given politi-cal will, persuasive 'risk' education and sufficient resources, "the science exists to turn the pandemic around." certainly, the continuing spread of disease could be slowed significantly, as has been seen in senegal, thailand and uganda, but whether without an efficacious vaccine we can reduce r to less than onethat is, reduce the mean rate of transmission from one infected person to less than one other personremains speculative. india is currently estimated to have million people infected with hiv (second only to south africa), and this number could rise to million in the next years. perhaps we should not be too pessimistic. people do change their outlook and lifestyle in the face of devastating disease. for example, male circumcision has been identified as a factor that lessens the risk of female-to-male hiv infection in africa . who would have thought a few years ago that men imbued with their traditional social customs would readily come forward to take part in randomized controlled trials of adult circumcision? whereas the 'sexual synapse' is a frequent route of hiv transmission from one person to anotherone that may be blocked specifically by a condom and hopefully one day by vaginal viricidesthe 'immunologi-cal synapse' is a pathway for virus transmission from cell to cell (see accompanying review in this issue) and has been elegantly shown for human t-cell lymphotropic virus type i. we are only just beginning to understand the impact of the multiple delivery of virions from dendritic or other antigen-presenting cells to cd + t-helper-cells. i propose that the immunological synapse may account for the recent observation that although only a small proportion of cd + t-cells in a lymphoid organ are infected by hiv, these cells contain several proviruses . this type of 'multihit' infection at the cellular level may overcome the saturatable restriction factors of the host cell , . packaged rna genomes transcribed from more than one provirus in the same infected cell will assemble into heterozygous virions, which in turn will accelerate genetic recombination and the evolution of drug resistance and immune escape. in the future, we should pay more attention to the comparative pathology of lentiviruses, including hiv- (ref. ) . in this issue, stevenson points to the lessons to be learned from primates that are naturally infected with a high viral load but do not develop disease. he contrasts oncoviruses to hiv and the primate lentiviruses that can infect nondividing macrophages and dendritic cells. i argue further that all lentiviruses are macrophage-tropic, but only some infect lymphocytes (primate and feline immunodeficiency viruses). for example, let us consider maedi-visna virus, which is solely macrophage-tropic. maedi-visna in sheep is the prototypic disease from which lentiviruses derive their name . infected sheep develop a wasting disease and neurodegeneration similar to that seen in humans with aids, but they do not show t-helper-cell immune deficiency. as maedi-visna is remorselessly progressive, with a high rate of mortality, i have argued previously that the infection, activation and apoptosis of t-cells in hiv are epiphenomena alongside the underlying progression of macrophage disease. like the prophecies of cassandra, this view remains unheeded perhaps because it would necessitate a complete reappraisal of both hiv pathogenesis and the inability of the immune system to ultimately control lentivirus infection. such a question has been posed for the katie ris variation observed in rna viruses in general ; for hiv, the answer is probably a lot of each. hiv generates variants at a far greater rate than do other rna viruses such as measles, polio and even influenza (fig. ) . the rapid radiation of hiv- group m into the subtypes or clades that comprise today's pandemic strains and all of their variants could have arisen from a conjunction of two features of hiv: the extraordinarily high level of sustained replication and turnover in vivo , and the functional tolerance of amino acid substitutions. it is estimated that humans were first infected with hiv- group m about years ago and with hiv- about years ago , with the viruses crossing from chimpanzees and sooty mangabeys, respectively . in the early years, hiv- radiated out into the different clades that we know today, probably from small founder populations of virus. the regions in which hiv- has been present the longest have the most complex array of genotypes (fig. ) . in the next years the pattern will change, and an increasing number of circulating recombinant forms (crfs) of hiv- will become apparent. thus, the neat geographic delineation of subtypesb in the americas, e in thailand, a and d in east africa and c in southern africaare likely to be superseded by crf viruses. indeed, crfs between hiv- groups m and o have been described , even though the parental genomes derive from distinct zoonotic events . it is possible that natural recombinants could arise between hiv- and hiv- now that hiv- has spread across west africa, where hiv- was already endemic. although there are some constraints to the co-packaging of hiv- and hiv- rna , it is worth investigating the possibility of hybrids in dually infected persons. does hiv variation matter? although there is no evidence that hiv has evolved in terms of virulence or modes of transmission in the past years, evolution of drug resistance and of immune escape (see accompanying review in this issue and refs. , ) clearly occurs under selective pressure. thus, hiv mutation and recombination have a great impact on therapy and vaccine design. i remain to be convinced, however, that the emphasis of vaccine design on the basis of clades is hiv science. efficacious, broadly based vaccines require immunogens representing those regions of the virus that change the least. when these have been identified, clades can be addressed. for humoral immunity, the challenge is not only the immunogen itself but also the access of antibodies to the neutralization targets. given the effect of the n-linked sugars of gp on immune escape from hiv , the glycobiology of hiv is back in fashion. will the drop in aids mortality owing to antiretroviral therapy (fig. ) be maintained so that people on treatment can expect a normal life span? this will depend on the ability of the virus to develop multidrug resistance while remaining fit for transmission. we shall need new drug targets , but a big practical challenge in the future will be to marry good drug therapy to easy adherence, particularly in resourcepoor settings. this means that drug formulation must be designed to optimize appropriate use. even then, if drugs administered to one infected individual are shared among their family or community such that several persons are simultaneously taking suboptimal doses, this could be a recipe for the rapid evolution and spread of multidrug-resistant hiv strains. in the future, i expect that host genetic variation will also have a larger role in hiv science. in addition to identifying individual host factors , [ ] [ ] [ ] , whole-genome scanning for pharmacogenomics and for what i call 'infectogenomics' (host genes that affect the virulence of infection) will provide information on how to better manage hiv infection. hiv may have a severe impact on several of the immunization programs for children and adults. inactivated or subunit vaccines may simply be ineffective in people infected with hiv: this has been shown for the pneumococcal polysaccharide vaccine , although antiretroviral therapy may restore responsiveness . with viruses, hiv-positive individuals have the potential to become long-term shedders of what would otherwise be acute, short-lived infections, changing the dynamics of immunization and eradication. thus, the large numbers of children with aids in africa may impede campaigns to eradicate measles and polio and to protect against yellow fever. a recent detailed review on the safety, immunogenicity and effectiveness of vaccines in children with hiv concludes that the benefits currently far outweigh the risks. nevertheless, epidemiological modeling will be needed to see whether one can minimize the untoward effects of hiv on other infectious diseases. another concern is that an 'attenuated' vaccine may itself act as a virulent pathogen in the immunocompromized individual. case reports of severe complications of bacillus calmette-guérin (bcg), measles and polio have been reported, and world health organization (who) guidelines recommend withholding bcg and yellow fever vaccines from symptomatic children infected with hiv . hiv hiv yea yea % % c c j g d figure the scale of hiv variation. sequence divergence of envelope glycoproteins of hiv (gp , v -c ) compared with that of influenza a h (ha ). the length of the spokes indicates the degree of divergence with the scale indicated. hiv variation in a single person years after infection ( genomes analyzed) is similar to that of worldwide influenza a ( genomes analyzed) in a single year. the greatest degree of variation is in the democratic republic of congo, where hiv first developed and has diversified into subtypes a-k (except for subtype b, prevalent in the west, and subtype e, prevalent in thailand). adapted with permission from ref. . gulliver's travels in hivland aids: time to turn to basic science isolation of a t-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (aids) isolation of new lymphotropic retrovirus from two siblings with haemophilia b, one with aids isolation of human t-lymphotropic retrovirus (lav) from zairian married couple, one with aids, one with prodromes a new type of retrovirus isolated from patients presenting with lymphadenopathy and acquired immune deficiency syndrome: structural and antigenic relatedness with equine infectious anaemia virus nucleotide sequence of the aids virus frequent detection and isolation of cytopathic retroviruses (htlv-iii) from patients with aids and at risk for aids isolation of lymphocytopathic retroviruses from san francisco patients with aids hiv and aids: years of science hiv- pathogenesis years of therapy for hiv- infection slim disease: a new disease in uganda and its association with htlv-iii infection multicentre study on factors determining differences in rate of spread of hiv in sub-saharan africa: methods and prevalence of hiv infection let it be sexual: how health care transmission of aids in africa was ignored the injection century: massive unsterile injections and the emergence of human pathogens expert group stresses that unsafe sex is primary mode of hiv transmission in epidemiology: sexual transmission of hiv in africa accomplishments in hiv prevention science: implications for stemming the epidemic male circumcision and risk of hiv infection in sub-saharan africa: a systematic review and meta-analysis male circumcision: current epidemiological and field evidence hiv- transmission, acute infection, and the quest for strategies to prevent infection spread of htlv-i between lymphocytes by virus-induced polarization of the cytoskeleton multiply infected spleen cells in hiv patients cellular inhibitors with fv -like activity restrict human and simian immunodeficiency virus tropism restriction of multiple divergent retroviruses by lv and ref human immunodeficiency virus type cultivation of visna virus in tissue culture lentivirus tropism and pathogenesis are rna viruses adapting or merely changing? evolutionary and immunological implications of contemporary hiv- variation modelling viral and immune system dynamics timing the ancestor of the hiv- pandemic strains tracing the origin and history of the hiv- epidemic aids as a zoonosis: scientific and public health implications human immunodeficiency virus type intergroup (m/o) recombination in cameroon nonreciprocal packaging of human immunodeficiency virus type and type rna: a possible role for the p domain of gag in rna encapsidation antibody neutralization and escape by hiv- rapid evolution of the neutralizing antibody response to hiv type infection isolation of a human gene that inhibits hiv- infection and is suppressed by the viral vif protein the effect of genetic variation in chemokines and their receptors on hiv transmission and progression to aids global survey of genetic variation in ccr , rantes, and mip- α: impact on the epidemiology of the hiv- pandemic -valent pneumococcal polysaccharide vaccine in hiv- -infected ugandan adults: double-blind, randomised and placebo controlled trial smallpox vaccination and patients with human immunodeficiency virus infection or acquired immunodeficiency syndrome disseminated vaccinia in a military recruit with human immunodeficiency virus (hiv) disease aids-related malignancies risk of human immunodeficiency virus infection in herpes simplex virus type -seropositive persons: a meta-analysis interactions between herpes simplex virus type and human immunodeficiency virus type infection in african women: opportunities for intervention infection with gb virus c and reduced mortality among hiv-infected patients effect of coinfection with gb virus c on survival among patients with hiv infection hiv- suppression during acute scrub-typhus infection decrease in human immunodeficiency virus type load during acute dengue fever catastrophic ape decline in western equatorial africa vaccine for aids and ebola virus infection hiv and aids in relation to other pandemics there is much concern over the risk of reintroducing smallpox vaccination to people infected with hiv because disseminated vaccinosis may ensue, as has been reported in an hiv-positive military recruit . aids is characterized by opportunistic infections and by what we may call opportunistic neoplasms . some opportunistic infections in turn exacerbate hiv in a vicious cycle. thus, genital herpes simplex infection is a risk factor for hiv transmission , while hiv increases and prolongs herpes shedding . other concurrent infections may ameliorate the risk or severity of hiv infection, as has been reported for gb virus c , , scrub-typhus and dengue . elucidating the mechanisms of cross-protection may give us clues to controlling hiv.many opportunistic infections are either zoonoses or come from nonparasitic, freeliving microbes. although they are typically not transmitted between humans, this pattern might change in the future if the opportunistic infections were to hop from one immunocompromised host to another. high-density immunodeficient populations are arguably unique in the annals of host-parasite evolution .thus, viruses, bacteria, fungi and protozoa now have million hiv-infected people in whom to adapt to human parasitism. zoonoses occur naturally, but the prevalence of hiv infection could greatly increase the chances of an infection of animal origin, such as sars, influenza, ebola or nipah viruses, to adapt more rapidly to human transmission. individuals with aids would be the 'superspreaders', as they are for tuberculosis. it is perhaps reassuring that such a horrific situation has not yet occurred, but predictive modeling is required to determine whether it could occur in the future. the aids pandemic compounds the threat from the deliberate or accidental release of new infectious agents. like cassandra, i shall end with a true prophesy that is at the same time optimistic and grim: years from now, the risk of further lentivirus transfer from apes to humans will approach zero because feral chimpanzees will be extinct, thanks to the bushmeat trade and the ebola epidemic , unless the apes are protected by immunization. who would have predicted years ago that we would have a vaccine for ebola before one for hiv key: cord- -s gw k authors: capps, benjamin; lederman, zohar title: one health, vaccines and ebola: the opportunities for shared benefits date: - - journal: j agric environ ethics doi: . /s - - - sha: doc_id: cord_uid: s gw k the ebola virus outbreak in west africa, as of writing, is declining in reported human cases and mortalities. the resulting devastation caused highlights how health systems, in particular in west africa, and in terms of global pandemic planning, are ill prepared to react to zoonotic pathogens. in this paper we propose one health as a strategy to prevent zoonotic outbreaks as a shared goal: that human and great ape vaccine trials could benefit both species. only recently have two phase / ebola human vaccine trials been started in west africa. this paper argues for a conceptual change in pandemic preparedness. we first discuss the ethics of one health. next, we focus on the current ebola outbreak and defines its victims. third, we present the notion of a ‘shared benefit’ approach, grounded in one health, and argue for the vaccination of wild apes in order to protect both apes and humans. we believe that a creation of such inter-species immunity is an exemplar of one health, and that it is worth pursuing as a coextensive public health approach. ebola virus has devastated parts of west africa, and has caused alarm worldwide. it is one of a number of notable zoonotic emergent infectious diseases (zeid), also including influenza, coronaviruses like middle east respiratory syndrome (mers), and the now pandemic human immunodeficiency virus (hiv). the majority of all eids are caused by zoonoses ; and most of these are pathogens of wildlife origin that become endemic in localised non-human animal and human populations (jones ) . these pathogens are emerging at an alarming rate, reflecting changes in local topologies and the global climate, triggered by human and animal causative and adaptive activities (epstein ) . ebola is endemic to central africa, and is normally dormant in still unknown reservoirs. periodically however, it infects local human populations, causing extensive mortalities but then fading out before widespread contagion (hayden ; marzi and feldmann ; macneil and rollin ) . the ongoing outbreak in west africa surpasses all previous occasions, although at time of this writing, the endemic appears to be receded (who ebola response team ) . many have been dismayed by the global efforts to curtail the epidemic, questioning international resolve to respond timely and effectively (mitman ; spencer ) . in particular, many have been critical of the systematic neglect of public health infrastructure, and have identified strengthening health systems as the long term solution to the disease (dawson ; farmer ; gates ; rid and emanuel ) . the measures used during this outbreak are focused on human communities, and includes clinical case management (that to date lacks any curative treatment), quarantine and isolation, surveillance and contact tracing, a rapid and reliable laboratory service, safe and dignified burials, and social education (dawson ; macneil and rollin ; marzi and feldmann ) . critics have much to say about the importance of infrastructure and basic supplies needed, but less has been said about the limitations of ebola containment measures. although these previously worked well within geographically isolated communities where ebola periodically emerged, they were less likely to do so in a sustained and widespread outbreak. in light of the current catastrophe, it now compels us to consider also the limitations of traditional public health measures during an epidemic of this magnitude, which although they may bring an acute situation under control eventually, are challenging to enforce, strain medical and social networks, and provide limited prevention and no cure. indeed, although these measures have brought the emergency to its current abating state, it took a great deal of time and vast efforts, many still died, and infection resurgence is a possibility. the importance of biomedical countermeasures, such as vaccines, therefore cannot be understated. in this respect, it has been resolved that failures in advanced drug development and production must be tackled (who ) , especially the political and economic barriers that hamper development and deployment in places such as west africa, and which further emphasise the neglect of certain transmissible diseases in that region (marzi and feldmann ) . the current perspectives to zoonotic risks and pandemic planning have changed little despite the warnings from the 'swine flu' pandemic of that the opportunities for expedient vaccine production and sustainable clinical access still seem someway off (gates ) . our particular concern, however, is that while the ethical debate is being dominated by global human threats, other considerations about endemic zoonoses are being overlooked. using ebola as a case study, we apply one health (oh) as an ethical framework to make the case for strategic changes. in particular, the debate about vaccines plausibly could be extended to the concurrent need in primate populations. this paper therefore proposes the possibility of shared immunity between species that are equally affected by ebola. our proposal for a novel approach to vaccination that protects both human communities and the fauna they interact with and often depend upon is speculative, as technical issues are far from resolved. however, we have two further intentions: firstly, to highlight the oh in general, prevention and then containment of highly pathogenic eids is about slowing and limiting the contagion, while often treating patients to the degree possible and who are likely to die, thus allowing the existing infrastructure to operationalize and then keep up. traditional public health methods of infectious disease control are known to work up to a point, depending on various factors such as the pathogen, victim and context. in particular, these methods rely to a large degree on the trust of the populations effected to follow non-pharmaceutical precautions under conditions of immensurable suffering and burdens, and the dedication, training and supplies made available to health care and other workers who sustain the infrastructure (such as, in the ebola case, the highly risky and stressful job of digging and filling graves). confidence in these may have become complacent (putting aside the question of political negligence), as it was only a matter of time before ebola would befall upon a highly populated city for the first time. ''ebola emerged nearly four decades ago. why are clinicians still empty-handed, with no vaccines and no cure? because ebola has historically been confined to poor african nations. the r&d incentive is virtually non-existent. a profit-driven industry does not invest in products for markets that cannot pay'' (chan ) . these failings have become, for some, symbolic of the abject failures of a global system which does not allow new possibilities for pandemic planning, such as more effective and urgent vaccine production (capps and lysaght ) . that ebola is a neglected tropical disease cannot be disputed, meaning that it has failed to attract significant interest for deployment of pharmaceutical interventions (until its full pandemic potential came to light in the current outbreak) (macneil and rollin ). so far, local responses fall back on traditional public health measures; these measures do little to benefit non-human interests, as victims or by finding mutual solutions. we propose that a different approach to pandemic prevention should invest in such technologies as vaccines, but do so using a broad ecological scope. we use primate (clade haplorhini) to identify the non-human apes (hominidae) that are susceptible to the ebola virus; our analysis will proceed to discuss the great apes (genus gorilla and pan), as more is known about the effects of the virus on them as highly sentient and endangered species. initiative as a source of alternatives to pandemic planning, so that, secondly, in the spirit of oh collaboration, we can encourage further and broaden the ethical debate. the paper unpacks in the following way: first, we explain the ethics of oh as an approach that recognises an ecological perspective. second, we define and expand upon the victims of the ebola epidemic so as to consider a new oh-grounded agenda. third, we articulate a possible preventive measure to prevent ebola in both human and animal populations. we argue that, along with efforts to test ebola vaccines in humans, existing vaccines that have been proven safe and efficacious in primates should already be deployed in order to protect both species. our proposal supports the conjecture that focusing on broadly ecological factors, and understanding and reacting to the natural ecology of zoonoses, is central to future zeid planning . one health (oh) has come to signify the interdisciplinary effort to optimize the health of humans, non-human animals, and their ecosystems. as an approach to biomedical enquiry, it has been adopted as a broad heuristic for evidence-based policy involving the usual suspects from public health, as well as veterinarians, animal and plant biologists, ecologists, and environmental scientists (scoones ; leach and scoones ) ; and thereby, it has become a stimulus for collaborative research. thus, its trans-disciplinarily-across multiple disciplines, encouraging de-siloing of sectors, and engagement with partisan stakeholders-creates change by identifying and solving real-world ecological problems. it is thus an extensive ecological perspective to that of public health. however, there are those who have been critical of the oh agenda because, like some existing study or practice lenses, it excludes the humanities and social sciences (lapinski et al. ) , and that, in part, obstructs the development of an inclusive bioethics framework (thompson and list ) . while the first is largely an empirical point, and we can point to anthropologists, among others, expressing solutions, but perhaps being less heard, in respect to ebola (aaa ); the latter observation indicates oh's lack of a philosophical grounding. in fact, oh has no origins in any particular ethical theory. one explanation for this is that normative enquiries are outside of the purview of oh. the collaborative model, therefore, is not about a distinctive oh ethics per se, but an attempt to integrate ecological perspectives on the same terms as public health activism; to probe conventional wisdom to find innovative solutions. this is perhaps a practical consideration because oh otherwise would likely lose political traction under anything more concretely conceptual. the oh goal is to assemble a comprehensive set of data across a broad spectrum of expertise, and to thereby provide solutions that are of benefit to human wellbeing within ecological settings. most recently, this idea is being framed as effectiveness gains through dynamic cooperation in environmental contexts, and has the effect of raising environmental concerns on par with concurrent efforts in public health such as in disease surveillance and animal management. this might be enough to create a vision of oh ethics: van rensselaer potter, in his earliest definition of bioethics, talked about a system of human survival that included environmental, or ecological ethics (potter ). this could easily capture the idea of oh as broadening public health into diverse fields. potter, a pioneer in challenging parochial and non-secular ideas shaping the human condition, noted a schism between the medical-science domains and humanistic ethics, and that both were distanced from environmental ethics. the ethics of oh, therefore, may just be signalling the resurgence of bioethics as a unified endeavour (thompson and list ) , allowing for reflective and critical engagement with current pandemic measures, which up to now gave little credence to solutions outside the scope of public health ethics. a deeper appreciation of secular bioethics, however, also points to the intrinsic interests beyond those of human beings. in the developing oh literature, it is more commonly acknowledged that human beings are part of and dependent upon the biosphere. one way oh has developed is in a perspective that a 'healthy' environment entails healthy animals along with healthy people. it is not 'us versus them', then, but a problem of shared risk that is something concrete to act on, thus providing opportunities to maintain healthy or rescue unhealthy ecosystems (rabinowitz et al. ) . however, in practice, reactions to these risks, and solutions to pathogens, still prioritise human interests, because there is no fundamental sense in which non-human animals, or the environment, matter morally. sure, while oh in this sense creates the grounds for humans to express compassion towards animals and ecosystems and to engage in novel approaches to health problems, overall it often achieves the same goals of prevention and response so far already installed in public health; so oh, in this sense, adds nothing to the ethical debate except by broadening the factors considered in any human cost-benefit analysis. the difference oh makes is in engaging with alternatives: it questions public health ideas entrenched as the only way to solve such problems, and indicates the dangers of the unreflective or blinkered view (leach and scoones ) . its effectiveness in ethical discourse, much like the collaborative idea, is that it asks questions about ecological benefits without overstepping public health priorities. finally, there is the sense in which oh has an enabling effect in respect to grounding an ethical theory in environmental issues. what that theory is, however, is contested. in this paper, therefore, we will sketch the idea that oh ethics ought to contain two elements: ( ) a focus on the inclusive and shared determinants of health; and ( ) a unifying theory. by spelling out these elements better, one is able to assess those projects that profess to be oh; and this will be essential in judging our shared immunity proposal. health is often understood as being normative: implying something good or desirable. this might be applicable from an internal view (being healthy), or an external one, such as the view from public health that concerns community (that is, conditions for being healthy). an 'unhealthy' state can be explained by a pathogen or other kind of destabilising event that impacts or creeps into a biological system, resulting in an altered, often unwanted and endured state. this might be the presence of a virus in an individual, or even the conditions (opportunities and barriers) of healthy living. public health often takes a similar focus, aiming to create healthy circumstances and conditions for people by focussing on the determinants of health. in this respect, oh uses health as an inclusive determinant, such that it includes actions that are broad in orientation and scope, so that health activism ought not be limited to human agents. oh is therefore an investigation of the scientific, social, economic and ecological determinants of human, non-human and ecosystem health, but also a 'shared benefit' approach. our use of 'shared' points to ethical consistency; that actions that affect a broad spectrum of agents should be fairly applied. just as racism is paradoxical in human societies, some exclusionary actions between human beings and non-human animals might be similarly judged as speciesistic. this echoes ideas of equality, and the interests of minorities or the vulnerable being protected against parochial or vested interests. it also befits an examination of incongruity, need and fairness, and justice-these components of comprehensive doctrines are only knowable through ethical study, and in this respect, we are less confident in setting the oh agenda, for such a task requires far greater elucidation than is possible here. we can, however, offer a basic account of 'benefits' that will begin the conversation in earnest about oh as a unifying theory. human beings act in ways that affect non-human animals and the environment, and this raises the question as to how much we should either change such actions, or, indeed, make efforts to assist in the wellbeing of other species. the basic assumption in public health has been that we should interfere only to the extent that their collective welfare is at stake, because animals' interests are outweighed by human interests . thus, public heath applies welfare conditions for the health of animals, which only occasionally includes ethical considerations, such as the humane culling of disease vectors and hosts. however, without engaging in a lengthy debate about non-human moral status, there is also a condition of interspecies connectedness. in the case of preventing zoonotic pathogens, oh on this reading implores us to study the causes and roots of transmission, counting each being as an equal unit in this biological process. the wider study of biospheres, ecosystems, and social networks achieves this. what is ethically important is that this study is concerned with the health of the ecosystem in its entirety, not solely that of humans. oh, therefore, becomes a study of 'natural' environments, enriching public health with animal and ecological studies, and creates a whole new frame of evidence to better design effective responses. in turn, the emphasis turns to discovering and developing creative ways to recover and maintain healthy ecosystems. these hint at plausible strategies that draw on the humanities and social sciences, which can better comprehend the emergent contingencies beyond statistical confines (neyland ) . but what are the objects, goods, or benefits(and harms) that enable states of heath? one way we might extend ethical concerns to non-human interests is by securing universal goods (capps and lederman ) . these are the kinds of goods that reach beyond the needs of human communities, describing benefits as inclusive across species, and feature broadly in ecosystems and the environment. for example, ecosystems are necessary for life by providing the basic requirements (and even complex determinants of heath, in terms of social and cultural goods), and can therefore create 'unhealthy' lives by becoming unproductive and even toxic. these effects can be observed in stressed and challenged environments when they are misused, exploited and degraded. the ecosystem is, therefore, a foundation of universal goods-goods necessary for the health of multiple species, and these goods are likely shared through interspecies connectedness. primarily, then, universal goods extend terms of reference beyond the restrictions of public health purposes. one set of solutions would emanate from comparative medicine originating in human beings (this is the opposite of current comparative medicine studies where animal models are utilised for human health). human trials and treatments may well be useable in animal populations, benefiting them directly, and in some cases, where a pathogen is eliminated, it might reduce risks for human populations. a second possibility would be adapting biobanks, which, because of the terms of reference in providing public goods, are restricted to furthering human interests only (capps ). this does not make good scientific sense, because there is a welter of data being lost or overlooked simply because of intentional institutional design that arbitrarily excludes other contributions. for example, animal samples may well show up zoonotic risks sooner, or enable the natural history of a pathogen to be understood. a recent proposal to create an ebola biobank would do well to consider extending its remit to include the animals that are the essential links in zeids (hayden ) . these are intriguing possibilities because they also allow real environment information gathering and sharing, and not just the artificial data, for example, from de novo animal experiments (capps and lederman ) . there are, however, going to be more or less hard cases where conflict between public health goals and securing universal goods is more or less likely; and solutions are going to be less amicable between human interests and an ecological perspective. at this level of disagreement, a debate about animal or environmental interests or rights is to be had. but in our paper, we develop this idea of universal goods to give weight to the broadly inclusive and shared determinants that are affecting both humans and animals as victims of ebola. according to oh, it behooves us to consider the opportunities to improve the health of those directly affected by the virus, in the sense that operationalizing public health should be extended to other primates such as chimpanzees and gorillas; related not only in their level of evolutionary sentience, but also as victims of ebola. the current ebola outbreak, which started in a single index case in december , but was not reported as an outbreak until march , is the largest known in history (rio et al. ; yakubu et al. ) . both humans and great apes have been affected. at time of writing, there have been , reported confirmed, probable, and suspected cases in human infections, mainly in guinea, nigeria, liberia, and sierra leone. , confirmed patients have died. in great apes, the effect of ebola is likewise devastating. gorillas and chimpanzees are susceptible to the virus (bermejo et al. ; kaiser ) . ebola has killed roughly one third of the western lowland gorilla population in the past years, which, along with habitat loss and poaching, led the world conservation union to declare it a critically endangered species (walsh et al. ) . three interrelated enquiries interest us as advocates of oh. first, a significant question is 'why now?' (bausch and schwarz ; farmer ) . why only now has the ebola virus, which has previously emerged in isolated regions, become a regional endemic (olival and hayman ; olson et al. )? this question has been asked in the context of other zoonotic diseases, most prominently hiv and its analogous emergence from primates in africa. answers will likely become evident as our understanding of zoonoses encompasses the exponential amount of accumulated knowledge from across disciplines, including the study of the reservoir, host and effected animals, the ecologies they inhabit, and their natural responses to the virus. it is therefore not only a question of what humans might have done differently this time to create the tragedy, but also their ongoing interactions with the environment whence the virus came from. these insights will be significant in developing strategies for potential future ebola outbreaks, and paradigms for other zeids, including possible preventative measures. second, it has been debated as to whether medical interventions for eid should be deployed in animal species. according to one view, we should not interfere with natural systems at all; apes have lived with ebola for years without need for human intervention. yet the state of wild populations today is such that no environment is free from human effects, and therefore such groups must adapt to the 'anthropocene' (hockings et al. ) . in fact, the landscape has changed so significantly that human intervention is perhaps necessary for them to survive at all. although dissent has been voiced against interfering in 'natural systems' and the effectiveness of medical interventions relative to other conservation strategies (ryan and walsh ) , the magnitude and significance of the current ebola outbreak should at least question the premise of non-intervention. intervention, therefore, can be justified because the alternative is decimation across the biosphere, affecting human beings who rely on it, and the animals that live within it. if this can be considered as a universal good, then, we can start to envision medical strategies to protect both human and animal populations. the plausibility of vaccinating other species during significant endemics has been voiced before, often from the conservation angle (marzi and feldmann ; ryan and walsh ) , but never received any serious consideration, as far as we are aware. two reasons for this might be postulated: limited resources are to be used to address human needs, especially at times when endemics or potential pandemics are occurring; and vaccine safety in administering to potentially critically endangered species. recently, a vaccine trial for ebola was carried out on captive chimpanzees to inform future conservation (warfield et al. ) . third, what (at least partially) grounds the need to respond to the queries posed above in respect to the shared risk of zoonoses, is the fact that human beings and primates are equally affected by the virus. therefore, if an ethics of shared benefits is persuasive, then one can start to see how conceptual change is necessary in zeid planning. for example, standard public health policies prioritise human interests, and often, these interests are perceived to collide with and outweigh the conservation of the biosphere. examples would include devastating and often ineffective culling (johansen and penrith ; jenkins et al. ) , or ravaging biodiversity on the basis of 'at-risk-to-human' calculations. oh, however, starts to give rise to different opportunities: for example, developing data storage from veterinary and conservation studies that can benefit humans, and vica versa (capps and lederman ) ; or strategizing to create healthy ecologies that will concurrently present fewer risks to human beings. concomitantly, humans, who often receive better medical care, may serve as 'concurrent research participants' and adaptive public/veterinary health models. the scientific literature to support oh as an approach to coordinate pandemics of zoonotic origin is rapidly accumulating (rabinowitz et al. ), such that it should be gaining traction in pandemic planning. it has, however, yet to feature in the solutions to ebola. oh ought to have some quite significant implications for pandemic planning (against ebola and generally) in various chronological phases. . the natural ecology of the ebola virus. the animal origin of the current epidemic is perplexing. the virus tends to only occasionally emerge in isolated villages, rarely appearing in hospitals and other health facilities (garrett ) . in this regard, the current outbreak is unique. beyond human interference, the ecology of the virus itself undoubtedly plays a key part. there are a number of species that could be implicated as the host, such as bats, other large mammals, or primates; even insects and plant viruses have been implicated in its transmission to human beings (hayden ; monath ) . it is imperative to conduct studies to locate the reservoirs and the plausible transmission routes to human beings and primates (in terms of group-to-group interspecies and cross-species transmission) and other known and unknown species contagions, to explain risks and spillover events. wildlife conservation workers have been tracking ebola in gorilla and chimpanzee populations for some time; but these data rarely reach the attention of public health planners (walsh et al. ). . manage habitat disruption. there is a vast and largely uncharacterized pool of possible zoonotic pathogens, and increasing opportunities for infection caused by disruptive human activities and ecological encounters (morse ). the understanding ecologies of vector-borne pathogens reveals some intriguing events, such as how biodiversity and diverse species networks can buffer, dilute and 'soak up' pathogens (harris and dunn ; keesing et al. ). that is, comparative studies and the reverse data use of human trials to benefit animal populations, such as in veterinary application (yeates ) . an early report from the current outbreak hypothesized that the host was a bat colony living in a local hollowed out tree (saéz et al. ). development of industry, such as mining, can bring people into regular contact with zoonotic reservoirs and hosts (kangbai and koroma ). these industries employ local and international workers who then travel to and from wild territories (allouche ) . anthropocentric activity also disrupts normal animal behaviour, for example, changing fruit bat roosting and foraging ranges so that they move to proximate sites to human dwellings (looi and chua ) . further, evidence suggests that biodiversity is a key element in emergent zoonotic diseases, where, in some cases, there is a reversed correlation: less biodiversity, or even deprived ecologies, create more risks for human zeids spillover events (cardinale et al. ; jones ) . . prevention of zoonotic infections. non-pharmaceutical measures can work well in eid outbreaks, but are only practical considerations once the spillover event has occurred in humans (in other contexts, personal protection equipment might be used as biosafety measures). reactive pharmaceutical measures, such as vaccines, take time to develop to specific pathogens, and then are often hampered by politics and investment, biological limitations, errors, and logistics. prevention, as is central to public health, might therefore be considered key. currently, several types of ebola vaccines have been proven effective and safe in primates, but none has been approved in humans yet (see below). human trials however are ongoing; and several captive chimpanzee trials have been conducted warfield et al. ) . once an ebola vaccine is approved for use in humans, several strategies to increase coverage may be used, such as ensuring that eco-tourists are appropriately vaccinated before visiting at-risk primate populations, and introducing health programmes in mining and refining communities often located in remote areas and near to potential ebola hotspots, such as bat roosts. . monitoring of disease in animals. studies have identified stereotypic behaviours in animals when burdened with zoonotic disease. for example, gorillas faced with endemic ebola reacted in ways that point to a decrease in social cohesion and lower reproductive potential: females were significantly more likely to transfer from breeding groups to non-breeding groups and males were more likely to transfer from groups to solitary-living. in general, there was a decrease in formation of breeding groups. interestingly, during the post-epidemic period, immigration of breeders between groups returned to normal while immigration of non-breeders remained low. observable social dynamics, then, may be used as indicators to detect ebola outbreaks (genton et al. ). this is an example of how animals can act as sentinels for imminent human risk. . animal-to-human transmission. several routes of animal-human transmission of ebola exist, including ingestion of raw infected meat (bats, primates and other animals) , and exposure to hosts and reservoirs through daily life, professions and tourism (köndgen et al. ). these various routes are potentially causing more zeid spillover events. for example, 'bushmeat' is consumed in higher amounts due to population growth in some areas (wolfe et al. ) ; mining is a growing industry in many regions (see below); and local economies rely on the growth of ecotourism. presenting these as local and global issues is challenging: for example, the local population is unlikely to support the prohibition of eating specific species as part of infection control. moreover, to have ethical credence, it would be consistent to address concurrent risks in developed countries, such as reducing intensive farming that also drives zeids. as regional industrial growth is essential for creating sustainable development for all countries, a call to reduce anthropocentric activity in rich wildlife areas in order to meet expedient conservation efforts would likely be rejected because of the local economic losses (and the international desire to visit such areas). nonetheless, efforts should be aimed at education of locals and visitors about the modes of transmission of ebola (muyembe-tamfum et al. ). learning about the local ecology-animal behaviour, biology, anthropology-would point to innovative ways to adapt in order to reduce the risk of transmission. the accumulated knowledge, therefore, raises some intriguing possibilities for the study and feasibility of potential zoonotic control measures; and in particular, using and adapting the 'shared' biosphere as part of the solutions to endemic ebola. however, despite the obvious ecological links to human zeid outbreaks, the interest in devising such possibilities has, until now, had little traction in public health and extant pandemic planning. most pandemic plans mention little about the ecosystem beyond its risk potential and stipulate requirements to devastate the animal populations (culling and the like) as a means to limit future human-to-human transmission. the one health solution to endemic ebola: inter-species immunity vaccination is by far one of the most significant responses to eid in human beings, and in the context of ebola its importance is beyond doubt; since the outbreak was first detected, public health, clinical staff and allied workers struggled against quite immense odds to bring it to the current state. the case for human vaccination speaks for itself. however it should not be understated quite how important it is since the alternative is to fall back on the objective: ''not to dramatically increase the person's chance of survival, it's to contain the spread'' (fjeldsaeter ) . one can only imagine what advantages the early deployment of an effective vaccine would have been. putting aside questions of the economic inequality that provides little incentive for vaccines until worst case scenarios prevail (capps and lysaght ; dawson ; farmer ) , the current upscaling in research to find a vaccine for ebola illustrates the standard phased approach to innovation: invention, animal experiments, trials in humans before large scale production and delivery. as with human beings, the obvious advantage to animals affected by the disease, such as great apes, is immunity from the disease (and relationally, although not always the case, such as with endangered species, is exclusion from culling measures), and prevention of cross infection (walsh et al. ). the obvious benefit is also in terms of conservation. specifically the case of highly endangered gorillas (and other susceptible animals on wwf lists) is extremely significant (ryan and walsh ) . no ebola vaccine has yet to be approved for therapeutic use in human beings. however, ebola vaccine development has been an active field of research for several laboratories worldwide, and candidate vaccines were found some time ago to be safe and efficacious in mice (blaney et al. ) . several human-targeted vaccines have been proven safe and efficacious in trials in primates, including adenovirus type and , human parainfluenza virus type , and vesicular stomatitis virus geisbert and feldmann ; marzi and feldmann ; stanley et al. ). these prospective vaccines, however, raise different concerns, such as safety, price, effectiveness, delivery and side effects. in an attempt to aver safety in the use of replicating viruses (see below), warfield et al. ( ) tested the protective effects of a virus-like particle in captive chimpanzees using adenovirus as a vector. first, they demonstrated that the vaccine was safe for chimpanzees. second, they documented the development of a robust immune response in chimpanzees, evidenced by a detection of virus-specific glycoprotein and vp antibodies - weeks post-vaccination. third, they demonstrated that total igg fractions taken from the chimpanzees that were vaccinated had a protective effect in mice challenged with murine ebola: - % of mice in the study groups survived compared to none of mice in the control groups. similarly, blaney et al. ( ) developed a live-attenuated and inactivated rabies virus vaccine that expresses the ebola glycoprotein. the vaccine had no adverse effects in primate models, it induced humoral response to both rabies and ebola, and was shown to be protective against both viruses. while this is obviously an early-phase study, it has great potential in terms of resources and feasibility in conferring immunity in mammals against two lethal pathogens. so far, two vaccines have passed phase clinical testing: chimpanzee adenovirus -vectored vaccine encoding ebola surface glycoprotein (chad ) (rampling et al. ) , and vesicular stomatitis virus (vsv)-vectored vaccine also encoding for the outer protein of the zaire ebola strain (agnandji et al. ) . the prevail study is an ongoing phase / trial taking place in liberia that examines the safety and effectiveness of these two vaccines. concomitantly, the strive trial is taking place in sierra leone, where healthy volunteers will be given the vsv vaccine in order to test its safety and effectiveness. agricultural policy tends to follow vaccinating all of the exposed animals so that those not already infected will develop sufficient immunity. however, when time and resources permit, it is normal for all exposed animals to be slaughtered (kahn et al. ) . vp is a matrix protein that together with glycoprotein constitute the virus-like particle vaccine. occasionally, nucleoprotein is also present. vp is essential for cell expression of viral antigens to which the body responds by creating antibodies (escudero-perez et al. ; marzi and feldmann ) . see: http://www.niaid.nih.gov/news/qa/pages/ebolavaxresultsqa.aspx; accessed june . http://www.cdc.gov/media/releases/ /p -ebola-vaccine.html; accessed / ; accessed june . the vsv phase trial in geneva was halted due to safety concerns when several healthy participants developed different adverse effects such as arthritis. the trial was continued a month later, to understand contagion networks and possibilities for control, first we need to see the connections between vectors and victims, and by understanding these within shared ecologies we might be able to better safeguard communities-both animal and human. as these authors postulated: ''in addition to the protection of threatened nhps [nonhuman primates], vaccination of nhp populations in endemic areas might also offer an additional, critical benefit to humans. the interaction of humans and infected nhps has been associated with transmission of ebov to humans and initiation of subsequent outbreaks, so prevention of disease in nhps may also serve to limit ebov transmission into the human population'' (blaney et al. ) . concurrently with the race to develop and test vaccines on human beings, we argue that already now, we can and should (upon assuring the degree of safety) deploy vaccines in captive and wild primates with the aim of benefiting both primates and humans. the current strategies, we submit, are driven by a too narrow vision: we propose that oh espouses a 'shared benefit' approach that is complementary to the 'shared risk' approach (rabinowitz et al. ) . a 'shared benefit' approach seeks to actively maximize health in one species while in turn benefiting another species as well. specifically, we refer here to research and interventions in humans that benefit animals and vice versa. our proposal is to implement the notion of inter-species immunity. one of the identified risks for ebola, while not knowing for sure the reservoirs of the virus, is close proximity between human and primate populations (towner et al. ). our proposal is for direct action to administer vaccinations to humans through public health and research paradigms, and additionally to animals to stave off future outbreaks in both populations. such an approach, aimed at vaccinating animals in the first instance, would be preventative rather than reactive to an outbreak in human populations, by protecting across species and thereby creating a potential barrier to future occurrences of ebola in the fauna. our proposal is to co-develop vaccines for human and primate use in ebola endemic and at-risk sites in africa; and simultaneously, to deploy such vaccines to these sites in animal and (in due course) human populations. the delay in getting vaccines to the people in africa is in part due to the need to conduct proper clinical trials first and the troubling consequences of creating randomization (donovan ; shaw ) . however, captive primate populations could be enrolled in trials as benefiting vaccine development at a lower safety level (in comparison to the footnote continued upon approval by the review committee. the ongoing phase / vsv trials were modified according to the results in that study (agnandji et al. ) . one health, vaccines and ebola: the opportunities for… standard profiles for first in human trials, and additionally avoiding the later phased stages of human clinical trials). primates might be research subjects who can contribute to a longer-term ecologycentred strategy to vaccinate wild animal populations urgently. simply put, researchers are already injecting captive primate populations, and, if proven safe and efficacious in these trials (i.e. would not to our knowledge wipe out remaining primate populations), this approach provides a fast track to wild primate populations. an oh approach would potentially justify animal research on captive primates within parameters of participation of 'vulnerable' populations (i.e. the agents likely to be the first cases or most at risk in future outbreaks because of their situation and circumstances). the next stage would be vaccinating the same species in the wild for the protection both of the same species (primates) and other at-risk species (human beings). this is, firstly, an ethical enquiry involving the status of primates as sentient beings who possess moral value (fenton ) ; and secondly, a conceptualization of animals as vulnerable populations such that risky clinical trials, with conditions, can be ethical. in answering the first enquiry, we note that ebola and the recent chimpanzee trials happen at a time when the national institutes of health is planning to reduce significantly the use of chimpanzees in invasive research, and therefore raises the case of whether minimally invasive research on still captive or retired chimpanzees is ethical at all. we might see experimentation, however, as a parallel development to research and treatment in vulnerable human beings, such as children and other people who cannot consent (wendler ) . the idea here is that trials might benefit wild populations and therefore it might be possible to justify within human research ethics paradigms. in human clinical research, the acceptability of such study is a function of acceptable risk, and, when vulnerability is in question, so are the chances of direct benefit (the 'best interests' test) and the possibility of appreciating benefits for others of one's own kind (children suffering from the same condition, for example). in this sense, developing protocols with primates in captivity might be justified, including using those that have 'retired', to meet the conditions of expediency; but concurrently we must anticipate that there is a direct benefit-or a best interest in play. while potential 'secondary ecological risks' exist, such as accidental extinction of the animal species, there would be some important caveats scholars concerned with animal ethics will blame us here for putting the animals at increased risk compared to humans. however, given a vaccine that has been proven safe in the lab, and the significant risk ebola poses for apes, we believe that the risks posed by the vaccine are proportional to the benefit that might be accrued to the animals themselves. http://www.nih.gov/news/health/jun /od- .htm; news release; wednesday, june , ; accessed june . this perspective is different from the predominant study of exogenous factors such as habitat disturbance and climate change as drivers of ebola emergence, and links directly to the contribution of transmission between gorilla or chimpanzee social groups in the wild. if this equivalency were to remain within an oh approach: that the vaccine is safe enough to use in human phase trials concurrently (shared risk) and that wild apes would receive the treatment as part of the same strategy (shared benefit). if this shared benefit paradigm of securing universal goods is legitimate, then it goes some way in justifying our strategy as mutually benefiting from a single intervention. this raises feasibility problems, but some intriguing ecological repercussions warrant serious consideration of an oh vaccine approach. . one would have to possess extensive knowledge about the reservoirs, vectors and hosts, and hierarchical zoonotic bridges between species, to understand the impacts of vaccines in terms of safety, stability, and effectiveness. this will involve knowledge of human, human-animal, and animal-animal interactions (i.e. comprehensive studies of fauna and flora), and their linked activities within the biosphere. at present, pandemic planning is focussed on public health, and to a degree, anthropocentric studies of how we contract and spread the pathogens amongst our own kind. this focus, for instance, locates some major challenges of vaccine use, specifically high levels of distrust and ambivalence towards medical interventions in some african populations that would impede wide human community vaccination programmes (mark ; macneil and rollin ; mitman ) . one might therefore face resistance in deploying an effective vaccination programme. oh, therefore, helps planners look to other solutions that may complement communitybased interventions. firstly, vaccinating domestic animal populations, both companion animals and those in husbandry, could avoid collateral loss to families and livelihoods. these losses are substantial and as targets for public health intervention might gain widespread support. secondly, and which we focus on here, is developing a novel approach to research and deployment in the field as a protective measure that demands immediate attention. thus, following the approach we outlined above, the vaccine will increase the welfare of humans and wild apes, both as protection (eventually) and in conducting knowledge based trials. to address the expediency argument, we again note that both the chad vaccine and the vsv vaccine have proven to be safe and efficacious in non-human primates (stanley et al. ; geisbert and feldmann ) . the human trials will take time to conclude. clearly, with the primate trials already concluded, there is an while the context of animal vaccinations has been debated considerably in respect to farming practices (and risks to humans as pathogenic risks, food safety and economics), there has been little coverage of the benefits to the animals. the debate is now further sparked by the quarantine and killing of companion animals exposed to potential contagions by their owners, such as the spanish dog killed for the fear of ebola transmission (associated press ). we note that the ongoing debate is deliberate in its assessment to get vaccines into the field as soon as possible to protect health care workers and needed staffing (i.e. burial teams and cleaners). this is a separate, urgent debate which does not entirely equate to the stage wise proposal we make here. however, the design to get vaccines first to primates as a joint shared immunity strategy could expedite human benefits and use, with a focus on employing biologists, veterinarians and the like to target the animal populations. opportunity to deploy these vaccines right away to wild apes. in the short term, we might be seeing every primate that lives as a benefit of vaccine deployment. the long-term benefits are immunity, possibly extending across species and thus limiting the future scope for spillover events. furthermore, it will provide in situ data to be gathered from the wild populations. . achieving broad coverage to widely dispersed animals would be costly and logistically challenging but has been achieved in other settings using low interventional methods such as baiting in the case of rabies (morters et al. ) . one challenge is the difficulty in reaching entire ape populations. the dense tropical forests and the animals' nomadic tendencies would make effective immunization difficult. however, by use of local and interdisciplinary knowledge and expertise, and various vaccination methods such as hypodermic darts and synthetic baits, this obstacle may be overcome (ryan and walsh ) . one long-term strategy may be to create buffer zones around villages by vaccinating domestic and wild animals, that might be enough to minimise risks of future outbreaks, following the alreadyexisting use of designated zones in farmed animal populations elsewhere (kahn et al. ) . the approach would require an increased evidence base, of course, but effectiveness could be achieved by focusing on 'hot spots', localized risk maps (jones ) , and using targeted empirical data, such as weather patterns that are known to influence zoonotic spillover events (bausch and schwarz ) . ring vaccination is another strategy, where vaccines are delivered to animals found in the ryan and walsh ( ) counted different pathogens that are harmful for apes, of which have licensed vaccines. they claim that the major obstacle in dispensing these vaccines is the delivery to the animals (ryan and walsh ) . the authors point out that ''the high seroprevalence among children indicates the same source(s) of exposure [to eobla] as in adults, either inside or near villages''. moreover, because great ape infection is often lethal, and direct contact with humans is rare, some other animal, perhaps bat roosts near settlements, represent the most likely common animal source of exposure: ''these animals, previously identified as a potential reservoir, are abundant in the forest ecosystem and consume fruits on trees located in or around villages'' (nkoghe et al. ) . 'hotspot' maps highlight regions: ( ) where the risk of disease transfer between wild primates and from wild primates to humans is greatest; ( ) where there are cross-species transmission events between wild primates due to a high diversity of closely related primate species; and ( ) where it is most likely that human beings will come into frequent contact with their wild primate relatives. ''these areas also are likely to sustain a novel epidemic due to their rapidly growing human populations, close proximity to apes, and population centers with high density and contact rates among individuals'' (pedersen and davies ). this would have to be an ideal, managed area, additionally creating the rural populations in control of the solutions. there are two elements to achieving this: ( ) engagement, cf. ''far greater community engagement is the cornerstone of a more effective response. where communities take charge, especially in rural areas, and put in place their own solutions and protective measures, ebola transmission has slowed considerably'' (who ); and knowledgeable land use, cf. protecting ''threatened habitats by reminding nearby communities of all the benefits they derive from keeping these habitats intact. forests, meadows and marshes prevent floods, supply clean water, provide habitat for species that pollinate crops, put oxygen into the atmosphere and take carbon out, and otherwise make themselves useful. in some cases, conservation groups or other interested parties actually put down cash for these ecosystem services-paying countries, for instance, to maintain forests as a form of carbon sequestration'' (conniff ). proximity of a known outbreak. further, vaccination campaigns in animals are likely to be cheaper and possibly more temporally feasible than in humans (ryan and walsh ; macneil and rollin ) . . technical issues, including the use of live attenuated viruses as vectors. for example, live attenuated vaccines are more effective than killed vaccines in conferring long-term immunity, thus necessitating fewer vaccine shots and lower rates of compliance and coverage. moreover, using viruses that are replication-competent as vaccine vectors will increase the chances for herdimmunity and therefore the potential for inter-species immunity. however, one of the risks in using a live attenuated, replication-competent vaccine in wildlife is the activation of the attenuated virus and spread to other species, including humans. beyond using killed viruses or viral particles, one solution may be using as vector a species-specific virus. for example, a recombinant murine cytomegalovirus (cmv) that was genetically engineered to express ebola particles was found to be protective in mice. since cmv is highly species-specific, a cmv-based ebola vaccine will potentially spread rapidly in a wildlife population, such as gorillas, without any cross infection to other species (marzi and feldmann ) . the use of replication-competent vectors raises another problem: pre-existing immunity to the virus that is used as the vector will hinder spread of the ebola particles, thereby preventing immunity to be acquired. this challenge could be addressed by the development of vectors to which there is no pre-existing immunity among the specific population. for example, newcastle disease virus, to which there is no detectable pre-existing immunity in humans, was developed as a potential vector of ebola particles with some (limited) positive results. vsv was also used as a vector with little if any pre-existing immunity in humans, with even greater success (marzi and feldmann ; stanley et al. ). the existing challenge with vaccine development was captured by the ghana academy of arts and sciences technical committee. they enumerated that development of vaccine is notoriously tricky given pathogen diseases' drift and other factors that impact on their individual effectiveness with different strains; the possibilities of emergent side-effects and other unforeseen incidents; the distrust of trials originating from certain foreign organisations; and how all of this will affect uptake (both in terms of willingness and immunisation) in the target population. within a 'shared benefit' approach, however, one originating in a one health perspective, we coin the term inter-species immunity to conceptually re-think the notion of immunity within a community; specifically, to extend the goods of health, such as immunity strived for in human populations, to other species and vice versa. we suggest that ebola incidence may be prevented or reduced in one species population by inducing immunity against that pathogen in another species population. so far, the best example of the success of such an approach can be seen in the response to the hendra virus, where vaccination of horses prevented disease in both horses and humans (middleton et al. ). the key to success of inter-species immunity might be with other measures that look to adapt and benefit other ecologies, such as preparing protected ecological zones (removing food and perching areas for bats) based on planned and managed farming areas, and identifying timely and imminent risks to initiate human and animal vaccination in and around these zones. one could adopt already-used surveillance programmes in at-risks regions (these, as we noted earlier, should already be modified to include 'indicative' behaviour in animals of possible zoonoses infection): ''previous serosurveys, together with the geographic pattern of outbreaks, have highlighted the potential role of the ecosystem, and an increased risk among forest populations has previously been described. our study confirms that the forest, particularly the deep forest, is the environment most at risk. this is the area harboring animals susceptible to the virus, such as great apes and bats, the latter representing a viral reservoir'' (nkoghe et al. ). we could not say whether the remoteness and distances between villages could create conditions for regional immunity by lowering the chances that an affected host might infiltrate the buffered populations from long distances away. however, as mentioned, oh is about interdisciplinary collaboration, and solutions to extreme situations such as the current ebola outbreak require such an approach more than ever (middleton et al. ) . understanding the needs of the various stakeholders such as villagers and hunters, and the ecology of all the organisms involved, is without a doubt essential for the success of any viable long-term solution. at the moment, inter-species immunity is likely to involve a programme of trials in captive primate populations, early role out to wild populations (assuming they are safe), and then a concurrent programme to vaccinate human communities in at risk regions (this human challenge is already featured in the literature with respect to other pathogens). however, with the impending imh prohibition on some primate research in the united states, and paralleled restrictions in other countries, this is a window that is potentially closing. invasive great ape research rarely has scientific justification and primate research in general is falling out of favour, although it remains possible in many jurisdictions under strict conditions. invasive research on great apes-using chimpanzees in particular-is likely to be prohibited; but we suspect that monkey research will continue for some time. this might provide the necessary level to proceed to trials in human and great ape populations. so, one could also look at it through a shared vision-if human beings are willing to volunteer for phase one trials, which was highly evident in recent calls, then possibly retired chimpanzees could be coopted as well. at this stage, it will be envisioned that the vaccine is safe for human beings, so this might be an acceptable concurrent risk for primate populations. we surmise that this vaccination strategy, inspired by the ongoing ebola outbreak, might be replicated in future ones. we make the case for the vaccination of wild primates even prior to the completion of the ongoing human trials, with the conditions of optimizing their safety and welfare, and assuring mutual benefits to them and their future offspring, as well as to humans. phase trials of rvsv ebola vaccine in africa and europe-preliminary report ebola and extractive industry strengthening west african health care systems to stop ebola: anthropologists offer insights excalibur, spanish ebola patient's dog, is euthanised despite global outcry. the guardian outbreak of ebola virus disease in guinea: where ecology meets economy ebola outbreak killed gorillas inactivated or live-attenuated bivalent vaccines that confer protection against rabies and ebola 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the tale of an evolving epidemic consequences of non-intervention for infectious disease in african great apes investigating the zoonotic origin of the west african ebola epidemic towards a one world, one health approach randomisation is essential in ebola drug trials. the lancet having and fighting ebola-public health lessons from a clinician turned patient chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge ebola needs one bioethics isolation of genetically diverse marburg viruses from egyptian fruit bats catastrophic ape decline in western equatorial africa potential for ebola transmission between gorilla and chimpanzee social groups vaccinating captive chimpanzees to save wild chimpanzees should protections for research with humans who cannot consent apply to research with nonhuman primates? ebola situation in liberia: non-conventional interventions needed second who high-level meeting on ebola vaccines access and financing. summary report west african ebola epidemic after one year-slowing but not yet under control bushmeat hunting, deforestation, and prediction of zoonotic disease the ebola outbreak in western africa: ethical obligations for care animal welfare in veterinary practice acknowledgments capps conceived of the idea for this article and led its drafting. lederman was integral to developing the idea and contributed equally to the research for the paper. the authors would like to thank the following people for helpful comments: wang linfa, paul anantharajah tambyah, and sharon amit. key: cord- -p vvbi authors: tai, dar‐in; jeng, wen‐juei; lin, chun‐yen title: a global perspective on hepatitis b‐related single nucleotide polymorphisms and evolution during human migration date: - - journal: hepatol commun doi: . /hep . sha: doc_id: cord_uid: p vvbi genome‐wide association studies have indicated that human leukocyte antigen (hla)‐dp and hla‐dq play roles in persistent hepatitis b virus (hbv) infection in asia. to understand the evolution of hbv‐related single nucleotide polymorphisms (snps) and to correlate these snps with chronic hbv infection among different populations, we conducted a global perspective study on hepatitis‐related snps. we selected hbv‐related snps on the hla locus and two hbv and three hepatitis c virus immune‐related snps for analysis. five nasopharyngeal carcinoma‐related snps served as controls. all snp data worldwide from populations were downloaded from , genomes. we found a dramatic difference in the allele frequency in most of the hbv‐ and hla‐related snps in east asia compared to the other continents. a sharp change in allele frequency in of snps was found between bengali populations in bangladesh and chinese dai populations in xishuangbanna, china (p < . ); these areas represent the junction of south and east asia. for the immune‐related snps, significant changes were found after leaving africa. most of these genes shifted from higher expression genotypes in africa to lower expression genotypes in either europe or south asia (p < . ). during this two‐stage adaptation, immunity adjusted toward a weak immune response, which could have been a survival strategy during human migration to east asia. the prevalence of chronic hbv infection in africa is as high as in asia; however, the hbv‐related snp genotypes are not present in africa, and so the genetic mechanism of chronic hbv infection in africa needs further exploration. conclusion: two stages of genetic changes toward a weak immune response occurred when humans migrated out of africa. these changes could be a survival strategy for avoiding cytokine storms and surviving in new environments. (hepatology communications ; : – ) c hronic hepatitis b virus (hbv) is a global disease. the majority of carriers of hepatitis b surface antigen (hbsag) are inhabitants of africa and asia. ( , ) immune tolerance is a hallmark of persistent hbv infection. ( ) typically, patients with chronic hepatitis b are infected through their parents in the early stage of life. ( ) remarkably, the immune system of the host may respond to the hbv ( ) but does not produce the immune clearance of hbv. hbv may replicate in host cells peacefully until they enter immune clearance phases - decades later. ( ) if the hbv can be eradicated, hbv replication will be terminated, and ultimately % of hosts may clear hbsag by years of age. ( ) genome-wide association studies from asia have revealed that the human leukocyte antigen (hla)-dp and hla-dq loci play roles in persistent hbv infection. ( ) ( ) ( ) ( ) ( ) ( ) ( ) our objective is to understand the evolution of the single nucleotide polymorphisms (snps) that were responsible for hbv-related immune tolerance during human migration and to correlate the hbv-related snps with a prevalence of chronic hbv infection among global populations. based on the data from , genomes collected worldwide, we conducted a global perspective study on the allele frequency of hepatitis-related snps. based on a literature review, hbv-and hlarelated snps, ( ) ( ) ( ) ( ) ( ) ( ) ( ) five hepatitis-and immune-related snps in complement factor b (cfb), clusters of differentiation molecule (cd ), and interferon lambda (ifnl ) loci ( ) ( ) ( ) ( ) ( ) , and five nasopharyngeal carcinoma (npc)-related snps in hla regions ( ) ( ) ( ) were selected for this analysis (tables and ). these snp data from around the world were downloaded from the phase data of , genomes (http://www. genomes.org/). ( ) the subjects participating in the , genome project were older than years and had three out of four grandparents who identified themselves as members of the group. the location of the populations evaluated in the , genomes are shown by abbreviation on a global hbsag prevalence map reported by hou et al. ( ) (fig. ) . the allele frequencies of different geographic groups in viral hepatitis-related snps and npc-related snps are illustrated in fig. . the snp genotype differences between groups are listed in tables and . we used interactive chi-square tests to calculate the difference in genotypes between groups (http://quantpsy.org). among two hbv-and immune-related snps in the cfb and cd regions ( , ) and three hepatitis c virus-related snps in the ifnl regions, ( ) ( ) ( ) allele type differences can be found between africa and europe or between africa and south asia ( fig. a ). all these immune-related snp genotypes differed significantly between esan in nigeria and toscani in italy and between luhya in webuye, kenya (lwk) and gujarati in india (gih) ( table ; p < . ). among hbv-and hla-related snps, ( ) ( ) ( ) ( ) ( ) ( ) ( ) the allele frequency showed marked differences between south and east asian genome samples (fig. b) . eight of the snps differed significantly between bengali in bangladesh (beb) and chinese dai in xishuangbanna, china (cdx); these areas represent the junction of south and east asia ( table ; p < . ). three of the hbv-and hla-related snps (fig. b , dotted lines; rs , rs , and rs ) also showed significant differences between lwk in africa and gih in south asia ( table ; p < . ). in contrast, we found the allele frequency of npc-related snps ( ) ( ) ( ) to be relatively stable among different populations (fig. c ). based on the well-known human migration pathways ( , ) and the recent data from , genomes, ( ) our analysis of hepatitis-and immune-related snps demonstrate a significant change in allele frequency shortly after the migration out of africa ( fig. a) . all genotypes of five immune-related snps differed significantly between esan in nigeria in africa and toscani in italy in europe and between lwk in africa and gih in south asia (table ; p < . ). in addition, both cfb and cd shifted from a higher expression in african genotypes (rs :tt; rs :cc) to a lower expression in european and south asian genotypes (rs :cc; rs : tt). ( , ) these changes conferred a decrease in the strength of immune responses. the cc genotype of rs (ifnl ), which is more prevalent in east asia, is associated with a lower baseline ifnl (interleukin- b) expression. ( , ) the ifnl open reading frame is truncated by a polymorphic frame-shift insertion (rs ), which turns ifnl into a polymorphic pseudogene in east asian populations. ( ) because the prevalence of hbsag is higher in africa than in europe or south asia, these trends of decreased immune protein expression are not related to hbv-specific immune tolerance. although it is clear that europeans and south asians are two different races, they showed similar genetic adaptions when they migrated out of africa. these changes suggest that the decreased expression of immune-related genes might have been an important survival strategy when humans migrated into new territories and faced new pathogens. the contact between different races of humans may induce devastating diseases, for example, when the new world was discovered by christopher columbus in . ( ) a similar situation was well documented when japan sent troops to taiwan in and ; only . % to . % of soldiers died in battle, while around % died of diseases in a short period of time after arrival. ( ) our second principal result is that the allele frequency of hbv-and hla-related snps show marked differences between south and east asian genome samples (fig. b) . eight of the snps differed significantly between beb and cdx ( table ; p < . ). these two populations are located at the junction of south and east asia. the unique allele types of hbv-related snps in east asian populations are different from those of other geographic populations. these genotypic changes could be related to antigen presentation and could be associated with persistent hbv infection. ( ) ( ) ( ) ( ) ( ) ( ) ( ) our findings are in agreement with a higher prevalence of hbsag in east asia than in south asia (fig. ) . these genotypic populations are generally overlapped in the y chromosome haplogroup o -o distribution map (https:// en.wikipedia.org/wiki/human_y-chromosome_dna_ haplogroup) as they started in the indo-china peninsula and travelled to northern china and japan. given the results, we theorized on the reason behind the dramatic allele differences in hbv-related snps between beb in south asia and cdx in east asia. one possible explanation for this variation involves the consideration of environmental landscape factors. ( ) for example, bangladesh is a predominately rich, fertile, and flat land, with many areas situated less than m above sea level. on the other hand, xishuangbanna is situated in a mountainous and forested area that has the largest diversity of plants and animals in china. regions with higher plant and animal biodiversity are often accompanied by an increased range and abundance of vector-borne or nonvector-borne diseases. ( ) ( ) ( ) ( ) ( ) ( ) ( ) accordingly, the inhabitants of these areas should be able to tolerate an increased number of unfamiliar microorganisms. we speculated that the subjects who demonstrate direct and strong immune responses may die of a cytokine storm in fulminant hepatitis, severe acute respiratory syndrome, influenza, and other infections. ( ) ( ) ( ) ( ) ( ) this concept is supported by a lower mortality rate from influenza h n in asia than in australia, new zealand, and north america. ( ) cytokine storm was first described in graft-versushost disease and was soon also identified in many infectious diseases ( ) ; many cytokines, chemokines, and complements are involved. ( ) ( ) ( ) the immunerelated snps selected in this study that included ifn (ifnl ), tumor necrosis factor-receptor (cd ), and complements (cfb) are all participants in cytokine storms. hla class ii molecules are associated with antigen presentation and are also modulated by cytokines. ( ) a cytokine storm is considered to be a hyperreaction of the immune response to a pathogen that may cause fulminant disease and mortality. ( ) ( ) ( ) ( ) when humans migrate to a new territory, they face many unfamiliar pathogens. those subjects with a strong immune response will die of disease, but those subjects with a weak immune response to the pathogens may survive. chronic hbv infection with an immune tolerance stage is an example of a weak immune response. ( ) ( ) ( ) east asian populations carry similar allele types of hbv-related snps (fig. b) , although the environments of northern china and japan differ substantially from those of southern china and the indo-china peninsula. ( ) we therefore propose that there was a significant physical block to gene flow on the indo-china peninsula. most of the survivors in east asia exhibit delayed hbv-related immune clearance genotypes. this could have been a survival strategy to pass through the indo-china peninsula and southern china during human migration. such hla class ii genotypes are aimed toward an immune tolerance strategy. ( ) ( ) ( ) ( ) ( ) ( ) ( ) these changes were successful because this group of people spread to northern china and japan and have become the largest population in the world numerically. however, such a survival benefit may have been a trade-off with cold tolerance as these populations were unable to cross the bering strait in large numbers. indigenous americans do not show the same hbv-related allele pattern; they have a low prevalence of chronic hbv infection and high influenzarelated mortality rates. ( , , ) overall, we identified two genetic adaptations that occurred during human migration. the first was the decreased expression of immune-related genes after leaving africa; the second was the evolution of an hla system with migration into the indo-china peninsula. both events may have aimed to decrease the strength of the immune response and avoid cytokine storms when facing different types of pathogens. the high prevalence of chronic hbv infection in east asia could be a consequence of such a strategy. however, persistent hbv infection-related hla genotypes are not present in the african population (fig. b) and cannot be responsible for the high prevalence of hbsag in africa. different genetic and nongenetic mechanisms of chronic hbv infection are presented between east asian and african populations. ( , ( ) ( ) ( ) we summarize the differences on hbsag carriers between east asia and africa in table . these differences may provide a clue for the mechanism of the function of snps in the persistent hbv infection. the high prevalence of lowexpression-type immune-related snps and chronic hbv infection-related snps on the hla locus may be a reason for a longer hepatitis b e antigen (hbeag)-positive phase in east asia. ifn-alpha has been recommended for treatment of hbeag-positive chronic hepatitis b. in a larger series from pediatric patients, ifn-alpha was found to be an effective therapy in chronic hepatitis b with severe inflammation that facilitates hbeag seroconversion in earlier life. ( ) in addition, hbv-and hla-related snps are also associated with spontaneous hbeag seroconversion. ( ) ( ) ( ) these genetic polymorphisms could be a reason for an early hbeag seroconversion and a lower vertical transmission in africa compared to east asia. it is well known that hbv genotypes a, b, and d show an earlier hbeag seroconversion compared to genotype c. ( , ) this early hbeag seroconversion was suggested to be the reason of low vertical transmission in africa. ( ) however, hbv genotype b also had an early hbeag seroconversion but had a high vertical transmission rate in east asia. ( ) therefore, host factors rather than hbv genotypes alone should be considered for the high vertical transmission rate in east asia. most hbv-related genome-wide association studies were done in east asia. we need studies to understand the genetic roles in persistent hbv infection in african populations. our study found two stages of genetic changes toward a weak immune response when humans migrated out of africa. these changes could be a survival strategy for avoiding cytokine storms and surviving in new environments. estimations of worldwide prevalence of chronic hepatitis b virus infection: a systematic review of data published between epidemiology and prevention of hepatitis b virus infection natural history of chronic hepatitis b virus infection in taiwan: studies of hepatitis b virus dna in serum effects of sex and generation on hepatitis b viral load in families with hepatocellular carcinoma trained immunity in newborn infants of hbv-infected mothers relative roles of hbsag seroclearance and mortality in the decline of hbsag prevalence with increasing age a genome-wide association study identifies variants in the hla-dp locus associated with chronic hepatitis b in asians a genome-wide association study of chronic hepatitis b identified novel risk locus in a japanese population new loci associated with chronic hepatitis b virus infection in han chinese genome-wide association study confirming association of hla-dp with protection against chronic hepatitis b and viral clearance in japanese and korean a genome-wide association study identified new variants associated with the risk of chronic hepatitis b association between hla variations and chronic hepatitis b virus infection in saudi arabian patients a genome-wide association study on chronic hbv infection and its clinical progression in male han-taiwanese genetic variants in five novel loci including cfb and cd predispose to chronic hepatitis b association of cd - c/t polymorphism in the -untranslated region with chronic hbv infection genome-wide association of il b with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis c impaired induction of interleukin b and expression of interferon k associated with nonresponse to interferon-based therapy in chronic hepatitis c selection on a variant associated with improved viral clearance drives local, adaptive pseudogenization of interferon lambda (ifnl ) genome-wide association study reveals multiple nasopharyngeal carcinoma-associated loci within the hla region at chromosome p . evaluation of human leukocyte antigen-a (hla-a), other non-hla markers on chromosome p and risk of nasopharyngeal carcinoma the principal genetic determinants for nasopharyngeal carcinoma in china involve the hla class i antigen recognition groove genomes project consortium a global reference for human genetic variation timing the first human migration into eastern asia late pleistocene climate drivers of early human migration the role of epidemic infectious diseases in the discovery of america germs of disaster: the impact of epidemics on japanese military campaigns in taiwan, and evolution and dispersal of the genus homo: a landscape approach vectors vs. humans in australia--who is on top down under? an update on vector-borne disease and research on vectors in australia influence of vectors' risk-spreading strategies and environmental stochasticity on the epidemiology and evolution of vector-borne diseases: the example of chagas' disease interleukin- -producing cd ( ) t cells increase with severity of liver damage in patients with chronic hepatitis b serum interleukin (il)- and il- , but not t-helper (th ) cells, are associated with survival of patients with acute-on-chronic hepatitis b liver failure molecular pathology of emerging coronavirus infections a question of self-preservation: immunopathology in influenza virus infection cytokine storm plays a direct role in the morbidity and mortality from influenza virus infection and is chemically treatable with a single sphingosine- -phosphate agonist molecule hospitalization fatality risk of influenza a(h n )pdm : a systematic review and meta-analysis into the eye of the cytokine storm magnitude and quality of cytokine and chemokine storm during acute infection distinguish nonprogressive and progressive simian immunodeficiency virus infections of nonhuman primates influenza virus pathogenicity regulated by host cellular proteases, cytokines and metabolites, and its therapeutic options combined inhibition of complement and cd efficiently attenuated the inflammatory response induced by staphylococcus aureus in a human whole blood model antigen presentation and mhc class ii expression by human esophageal epithelial cells: role in eosinophilic esophagitis identification of spatial genetic boundaries using a multifractal model in human population genetics clearance of hepatitis b e antigen in patients with chronic hepatitis b and genotypes hepatitis b virus infection during pregnancy: transmission and prevention the risk of perinatal hepatitis b virus transmission: hepatitis b e antigen (hbeag) prevalence estimates for all world regions predictors of hepatitis b e antigen-negative hepatitis in chronic hepatitis b virus-infected patients from childhood to adulthood association between single-nucleotide polymorphisms and early spontaneous hepatitis b virus e antigen seroconversion in children effect of host and viral factors on hepatitis b e antigen-positive chronic hepatitis b patients receiving pegylated interferon-a- a therapy effect of hla-dp and il b gene polymorphisms on response to interferon treatment in hepatitis b e-antigen seropositive chronic hepatitis b patients epidemiology of hepatitis b virus and genotype author names in bold designate shared co-first authorship. key: cord- -vb hygtv authors: elder, laurent; clarke, michael title: past, present and future: experiences and lessons from telehealth projects date: - - journal: open med doi: nan sha: doc_id: cord_uid: vb hygtv information communications technology has been a focus of the work of the international development research centre (idrc) since , when this organization was formed in canada with the goal of helping to improve the health of people in developing countries (http://www.idrc.ca). in this article, we focus on the field of telemedicine in developing countries and its role in improving health, using examples from the experience of the idrc. been a focus of the work of the international development research centre (idrc) since , when this organization was formed in canada with the goal of helping to improve the health of people in developing countries (www.idrc.ca). in this article, we focus on the field of telemedicine in developing countries and its role in improving health, using examples from the experience of the idrc. one of the authors of this article (le) was involved in a pioneering project on telemedicine in uganda in . the aim of this project was to enhance access to health services using telemedicine, such that consultations with doctors who worked in larger hospitals in mulago and butabika could be obtained for patients who did not live near a hospital. the project focused on cholera, malaria and hiv/aids. further goals were to disseminate health information and build a continuing medical education program. finally, the project was meant to document lessons on these different activities. these efforts were quite typical of activities that focused on health and on information and communica-tions technology (ict) at the time: overly ambitious, lacking in adequate capacity and planning, but spurred by the drive and determination of project proponents, who went on to use their experiences to become champions of telehealth in their countries. what actually happened? as was typical of early telehealth projects in africa, the project was faced with challenges related to procuring appropriate equipment and setting up infrastructure, as well as difficulties in achieving connectivity. disappointingly, the project never actually made an online consultation between kampala and the rural health centres, and it would be remiss to say that it resulted in any direct beneficial health outcomes for the rural population. nevertheless, the project did offer some valuable lessons for future e-health projects. it was in many respects ahead of its time, and set the stage for more successful e-health projects in uganda, such as the uganda health information network and a subsequent telehealth project in mengo. indeed, with the support of memorial university in st. john's, nl, the project helped train and mentor numerous staff in telehealth activities; it further helped focus the attention of the government on rural health problems and potential solutions; and it developed educational materials that are in use today. the project provided significant insights and learning. first, it helped the organization better understand the challenges of supporting telehealth projects in africa and helped define some of the key questions it would try to answer. key among these was a better understanding of how appropriate local capacities, both technical and institutional, should be built, second was the need to focus on the "e-readiness" of the country, particularly with regard to the availability of equipment, cost of access and an enabling regulatory environment. (e-readiness refers to the state of a country's ict infrastructure and the ability of consumers, businesses and governments to use ict to their benefit.) finally, this experience prompted greater consideration about the key underlying question: is telehealth a viable means of solving health problems in developing countries? in this case, cost-benefit analyses had not been done and health outcomes had not been measured, in large part because these efforts had been lost in the challenges to implement the pilot project. all these lessons helped shape future thinking about supporting i the development of effective health applications. however, it is also of interest to examine some of the lessons from programming in asia on telehealth to demonstrate how lessons coalesced from one region to the other, despite having been implemented through separate programs. the objectives of the impact of remote telemedicine in improving rural health project in india, part of the pan asia networking (pan) project, were to study the impact of remote telemedicine in selected villages in india. the activity specifically aims to conduct, with the help of n-logue, an internet service company in india (www.n-logue.com), a low-cost medical kit called remedi, which the manufacturer describes as a "medical data acquisition unit that captures multiple parameters," i.e., temperature, ecg readings, blood pressure, pulse rate, heart and lung sounds and oxygen saturation (www.neurosynaptic.com/telemedicine.htm). the telemedicine program can work in conjunction with a rural kiosk and transmit medical information remotely to a doctor in an urban centre. once the service was launched, there was a spike in the number of visitors to the kiosk. after the initial interest, however, the number of visitors dropped precipitously to a few regular, repeat visitors. the drop was explained by the following factors: "kiosk operator's ability to administer the kit properly, acceptability by the villagers, identification of the kiosk in a place where medical care is already dispensed, lack of awareness of the service, distance of the doctor from the village, and availability of competing services such as registered indian medical practitioners primary health centres, local doctors, etc." although the project faced challenges with respect to sustainability, it was, contrary to the ugandan experience, able to function as a working telemedicine project. however, despite the activity's stated objective of understanding telemedicine's "impact," no findings were documented with regard to health outcomes. in indonesia, the development of ict-based telemedicine system for primary community health care in indonesia project used existing internet technology to enhance pc-based medical stations and pilot-tested a telemedicine application. the pilot network consists of six medical stations within community health centres and a station for each referral hospital, health office and test laboratory. the pilot found that human resource capacity-building -in particular, training to facilitate the adoption of computer and telemedicine technology -required significantly more time than expected. the project therefore demonstrated the important role that human resource development plays in the sustainable implementation of ict-based telemedicine systems. however, as before, no findings were documented on the actual effect the pilots had on people's health or on health systems. what parameters were to be used for evaluating programs? textbox lists those factors that were felt to be relevant and important according to a report, commissioned by idrc, that unfortunately ranked all projects "low" with respect to demonstrated health benefits. common deficiencies included a lack of planning and health needs assessment, a need for sustainability planning, difficulty in the management of change, and a need for better evaluation, dissemination of findings, and knowledge transfer to influence policy-making. a comparison of respondents from the two countries showed, as expected, that most received information on antiretroviral treatment (art) from traditional media. however, increased access to information technology in south africa resulted in % of respondents receiving information from cellphones (versus % of respondents in tanzania). hence the assumption is that, as access to mobile telephony and the internet rises in africa, so will the number of people accessing health information through these technologies. moreover, according to the survey, illiteracy was the most important barrier to the use of icts in both south africa and tanzania. the results echo previous research that showed that illiteracy and localization issues are among the most important factors challenging the more widespread use of ict solutions. according to the survey on the effectiveness of icts, it was perceived that radio, print and television, as well as face-to-face meetings, were "extremely effective" media. the majority of respondents "didn't know" whether computers, email and the internet could be effective. strangely, almost % saw the internet as "harmful" (the highest percentage in that category). although one can question the methodology of a perception questionnaire as well as the terms used -what do "harmful" or "extremely effective" actually mean? -one cannot deny that conventional communication methods are still perceived as the most widely used modes of information transmission. the authors of the afriafya (african network for health knowledge management and communication) study conclude that the best practices for using icts in the fight against hiv/aids were ( ) use of mobile phones and sms; ( ) icts for up-to-date hiv management information; ( ) icts for mobilization; ( ) combination of different icts; and ( ) telephone counselling. they also pointed out that the use of "modern" icts is still very limited, but that there is huge potential; that because institutions and health workers remain reliant on "conventional" icts there is a need to integrate both "modern" and "conventional" to get the best results; and, perhaps most important, that changing perceptions and behaviours requires careful planning and patience. similarly, acacia's - prospectus (www.idrc .ca/en/ev- - - -do_topic.html) finds that the impact of icts has been constrained by the fact that access to them at the front lines of health care in rural areas has been generally non-existent. however, the rapid expansion of mobile telephony into urban and rural areas in africa is seen as having brought about new opportunities for access and innovation in the use of icts to facilitate the delivery of health care. although most mobile infrastructure in africa is too slow and expensive for connecting computers to the internet, low bandwidth communication applications have emerged that use mobile phones or personal digital assistants (pdas) such as palm pilots to connect via mobile networks. indeed, "while information designed and formatted for the world wide web is generally too bandwidth intensive to be transmitted over mobile networks, the information itself, properly formatted for small devices, takes up very little bandwidth." pdas and smart phones are also seen as more advantageous because of their robustness (no moving parts), their relative affordability, and their ability to be maintained "in areas with little or no electricity infrastructure through the use of solar power rechargers" (www.idrc.ca/en/ev- - - -do_topic.html ). of particular interest, therefore, is the fact that the acacia program, given that mobile telephony and pdas are increasingly pervasive in africa and have the potential to play an important role there, has focused much of its current project support on that theme (www.itu.int/itu-d/ict/statistics/at_glance/af_ictindicators_ .html). examples of mobile-enabled health applications supported by acacia are listed in textbox . according to the pan asia networking prospectus, health is the area where icts are likely to have the most direct positive impact in improving the well-being of asian communities (www.idrc.ca/uploads/user-s/ prospectus_final.pdf). however, the prospectus also affirms that the first generation of largely donor-driven "telemedicine" projects has generally had only a marginal impact on people's health. indeed, many of the technologies previously developed and tested were too expensive to be widely adopted in resource-poor settings. much like acacia, pan sees the advent of more pervasive technologies, such as mobile phones and pdas, as a new generation of health applications that have actually made a demonstrable difference. as mobile telephony use in asia is more widespread than in africa, it is clear that the potential for these types of applications is significant in asia. pan's strategic document also emphasizes that more research is needed to gauge which applications and projects in the area of health have made a difference, to understand why they have or have not been successful and, when warranted, to scale them up. however, the fast pace of innovation in both icts and health research means that there is also a need to develop, implement and evaluate new applications, particularly in the area of demographic surveillance of disease incidence and medical compliance, using new technologies such as mobile phones. according to the prospectus, another area that has recently come to the forefront in asia is the issue of pandemics. first severe acute respiratory syndrome (sars) and now the potential for an avian flu pandemic are perceived as serious threats to the health of asian populations as well as the rest of the world. a key to mitigating the spread of these infectious diseases is to ensure that data on outbreaks are captured and communicated to the relevant experts in real time. icts can play a critical role in helping to prevent or control pandemics, although more research and experimentation need to be done to identify the most appropriate and cost-effective effective means of developing health communications processes in rural and remote areas, where many of these outbreaks start. as a means of meeting most of its prospectus objectives as well as the challenge of developing evidencebased research on e-health, pan has recently been developing its flagship project, panacea (pan asian collaborative evidence-based ehealth adoption and applications). this program will support collaborative research that promotes the evidence-based adoption and application of technologically and socioeconomically appropriate e-health solutions in asia. it includes projects, involving countries (bangladesh, india, indonesia, mongolia, pakistan, philippines, sri lanka and thailand), and is coordinated by the aga kahn university in pakistan with support from the university of calgary, primacare malaysia, the molave foundation and angeles university foundation in the philippines. the health sector in latin america and the caribbean (lac) faces a number of key challenges, such as equitable access to health care services, the reduction of costs, and the necessary increase of disease prevention measures among low-income and vulnerable populations, among others. as with acacia and pan, the lac prospectus affirms that digital technologies and ictbased solutions provide a powerful tool to change the ways in which health services are managed and delivered to the population at large, and to low-income and marginalized communities in particular. icts and the internet, for example, can bring to these communities (at low cost) contacts with larger health centres located in urban areas, opening access to health prevention measures, consultations, updated valuable medical information, coordination in the treatment of patients, adequate and timely distribution of medicines, collection and effective distribution of valuable data on profiles and patterns of threatening epidemics, contagious diseases and other ailments, among others. attention will also be paid to the relationship between environmental degradation and its impact on the health of the lac population (see www.crdi.ca/uploads/user-s/ public_ict d_americas-programdescription.pdf). we believe that telehealth and e-health solutions can have real, short-term benefits at many levels, including a direct benefit to patients. reductions in medical error, the realization of costs savings, real-time monitoring of public health incidents and the provision of validated data and information for health systems decision-and policy-making are just some of these benefits. however, there is an ongoing need to support research that demonstrates these benefits within the framework of a cost-benefit analysis in order to justify the often significant up-front costs associated with the implementation of comprehensive, system-wide telemedicine solutions. this, of course, is particularly significant in the context of developing countries with limited financial resources and telecommunications infrastructure. although these constraints are limiting in many ways, there are significant opportunities to develop innovative approaches to telemedicine that often do not have to contend with legacy systems and bloated bureaucracies in these environments. telemedicine and e-health solutions that are shown to be appropriate, affordable and effective in one region can be adopted in other regions provided they are localized and contextualized. because significant threats to human health -such as infectious pandemics and geophysical disasters -do not respect political boundaries, these global initiatives carry a sense of urgency. it should be noted that the failure rate for ict projects as an industry average is around % (www.itcortex.com/stat_failure_rate.htm). the fundamental issue that seems to pervade the case histories of failed health ict projects -a lack of focus on the patient -must be addressed. by putting the patient at the centre and continually verifying that the link between the targeted intervention and the well-being of patients is clear, the likelihood of success will be sub-stantially improved. we believe that what is now required is the development of a rigorous research methodology that is relevant and applicable to the context of developing nations. such a methodology must be based on an applied research modality in which the fundamentals of the work address real and significant issues of human health as they influence the development process. the needs of people living in developing countries are profound. their pursuit of equity and full participation in global society faces enormous hurdles but, ultimately, is firmly dependent on a healthy society with full access to effective health care. we are committed to finding a way that ict can achieve this. exploring new modalities: experiences with information and communications technology interventions in the asia-pacific region. a review and analysis of the pan-asia ict r&d grants programme project planning for regional health and ict research network pan-asia past, present and future: experiences and lessons from telehealth projects copyright: this article is licenced under the creative commons attibution-sharealike . canada license, which means that anyone is able to freely copy, download, reprint, reuse, distribute, display or perform this work and that the authors retain copyright of their work. any derivative use of this work must be distributed only under a license identical to this one and must be attributed to the authors. any of these conditions can be waived with permission from the copyright holder. these conditions do not negate or supersede fair use laws in any country. for further information see http://creativecommons.org/licenses/by-sa/ . /ca/. key: cord- - ypqow authors: tegally, h.; wilkinson, e.; lessells, r. j.; giandhari, j.; pillay, s.; msomi, n.; mlisana, k.; bhiman, j.; allam, m.; ismail, a.; engelbrecht, s.; van zyl, g.; preiser, w.; williamson, c.; pettruccione, f.; sigal, a.; gazy, i.; hardie, d.; hsiao, m.; martin, d.; york, d.; goedhals, d.; san, e. j.; giovanetti, m.; lourenco, j.; alcantara, l. c. j.; de oliveira, t. title: major new lineages of sars-cov- emerge and spread in south africa during lockdown. date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: ypqow in march , the first cases of covid- were reported in south africa. the epidemic spread very fast despite an early and extreme lockdown and infected over , people, by far the highest number of infections in an african country. to rapidly understand the spread of sars-cov- in south africa, we formed the network for genomics surveillance in south africa (ngs-sa). here, we analyze , high quality whole genomes and identify new lineages of sars-cov- . most of these unique lineages have mutations that are found hardly anywhere else in the world. we also show that three lineages spread widely in south africa and contributed to ~ % of all of the infections in the country. this included the first identified c lineage of sars-cov- , c. , which has mutations as compared with the original wuhan sequence. c. was the most geographically widespread lineage in south africa, causing infections in multiple provinces and in all of the eleven districts in kwazulu-natal (kzn), the most sampled province. interestingly, the first south-african specific lineage, b. . , which was identified in april , became extinct after nosocomial outbreaks were controlled. our findings show that genomic surveillance can be implemented on a large scale in africa to identify and control the spread of sars-cov- . in march , the first cases of covid- were reported in south africa. the epidemic spread very fast despite an early and extreme lockdown and infected over , people, by far the highest number of infections in an african country. to rapidly understand the spread of sars-cov- in south africa, we formed the network for genomics surveillance in south africa (ngs-sa). here, we analyze , high quality whole genomes and identify new lineages of sars-cov- . most of these unique lineages have mutations that are found hardly anywhere else in the world. we also show that three lineages spread widely in south africa and contributed to ~ % of all of the infections in the country. this included the first identified c lineage of sars-cov- , c. , which has mutations as compared with the original wuhan sequence. c. was the most geographically widespread lineage in south africa, causing infections in multiple provinces and in all of the eleven districts in kwazulu-natal (kzn), the most sampled province. interestingly, the first south-african specific lineage, b. . , which was identified in april , became extinct after nosocomial outbreaks were controlled. our findings show that genomic surveillance can be implemented on a large scale in africa to identify and control the spread of sars-cov- . severe acute respiratory syndrome coronavirus (sars-cov- ) is a novel betacoronavirus, first detected in china in december , . since then, the coronavirus disease (covid- ) has developed into a global pandemic, resulting in several waves of epidemics around the world, infecting nearly million people, and causing > thousand deaths by september . lockdown and travel restriction measures have varied from country to country, dictating the profile of local epidemic outbreaks. through the unprecedented sharing of sars-cov- sequences during this pandemic, including from one of the first cases in wuhan, china (mn . ) , genomic epidemiology investigations globally are playing a major role in characterizing and understanding this emerging virus [ ] [ ] [ ] [ ] [ ] [ ] . sars-cov- has typically been classified into two main phylogenetic lineages, lineage a and lineage b. while both lineages originated in china, lineage a spread from asia to the rest of the world, whereas lineage b predominantly spread from europe, both circulating widely around the world . the covid- epidemic in south africa is by far the biggest in africa, with > , individuals infected and > , deaths by mid-september . the first case of sars-cov- infection in south africa (sa) was recorded in kwazulu-natal (kzn) on march in a returning traveler from italy. around mid-march, cases of community transmission were reported across the country. the profile of sars-cov- epidemiological progression in south africa was largely influenced by the implementation of lockdown measures in the early phases of the epidemic and the subsequent easing of these measures. on march, the governmentimposed nation-wide lockdown included the prohibition of all gatherings, travel restrictions, and closure of non-essential businesses and schools . although the epidemic was growing, lockdown measures were progressively eased on may and on june to mitigate negative impacts on the country's economy. restrictions were further relaxed first on august, once the peak of new daily infections had passed, and again on october (fig a) . the epidemic in south africa can generally be characterized by two important phases, one dominated by travelrelated "early introductions", and the second being the period of "peak infections" (fig a) . we monitored the likelihood of sars-cov- transmission by estimating the effective reproduction number, r, which provides a measure of the average number of secondary infections caused by an infected person . typically, a growing epidemic is characterized by r > and r < indicates a slowed progression. at the start of the epidemic, we estimated the r value to be > , quickly falling after the start of lockdown to a value of < . a subsequent jump in the r value to > was found to be concurrent with the timing of a number of localized outbreaks in the country, including nosocomial outbreaks . the r value again dropped to < at the beginning of august, coinciding with a decrease in the daily number of positive cases recorded ( fig a) . genomic epidemiology is important to understand sars-cov- evolution and track the dynamics of transmission across the world - . by september , at the tail end of the epidemiological peak in the country, we had produced high-quality sars-cov- whole genomes (> % coverage; publicly shared on gisaid ) in our laboratories as part of the network for genomic surveillance (ngs-sa) consortium . these whole genomes were sampled in eight of the nine provinces of south africa and in all the districts of kwazulu-natal province, (supplementary fig s ) , and represented consistent sampling from the beginning of the epidemic and corresponding to important events of the epidemiological progression ( fig a) . we estimated maximum likelihood (ml) and molecular clock phylogenies for a dataset containing global genomes, including south african genomes, sampled from december to august ( fig c) . time-measured phylogeographic analyses estimated at least introductions into south africa. the bulk of important introductions happened before lockdown from europe, where the epidemic was most quickly progressing at that time ( figure b ). although at least introduction events are inferred to have occurred after lockdown, these represent only % of the genomes that were sampled following lockdown ( fig c) . in the early phases of the epidemic, before april, introductions were inferred from genomes sampled ( . %), which we call "early introductions" (fig b) . the small number of apparent introductions after lockdown can be explained by more intensive genomic sampling at later stages, which likely revealed introduction events linked to previously undetected transmission chains. the early introductions were mostly isolated cases with a few instances of small onward transmission clusters, in contrast with large transmission clusters during the peak infections phase ( fig c) . the time period between these two phases was inferred to be characterized by localized transmission events which saw the emergence and spread of new lineages, which were later amplified during the peak of the epidemic. the south african genomes in this study were assigned to different lineages based on the proposed dynamic nomenclature for sars-cov- lineages . this included south africa specific lineages, defined as being lineages that are presently predominant in south africa by cov-lineages.org as of september (supplementary fig s ) . one of these has been assigned a novel sars-cov- main lineage classification, lineage c, the parent of which is lineage b. . . . extensive sars-cov- genomic sampling, which spanned the whole duration of the epidemic and increased during its peak, allowed for such lineage emergence to be observed, similar to the uk's genomic investigation of sars-cov- . we focused on the three largest monophyletic lineage clusters (c. , b. . . , b. . . ,) that spread in south africa during lockdown and then grew into large transmission clusters during the peak infections phase of the epidemic (fig c) . dominance of the epidemic by novel sa-specific lineages likely happened due to lockdownimposed travel restrictions fueling a largely local epidemic. accordingly, these three main lineages account for % of all sampled south african sequences. in addition to the three most widespread lineages in south africa, our analysis also focused on an early lineage, b. . , that emerged during nosocomial outbreaks in kzn province. this lineage was responsible for % of the infections in kzn at the start of april, but its prevalence decreased as the outbreaks were controlled. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . ; is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . ; https://doi.org/ . / . . . doi: medrxiv preprint b. . . , b. . . , and c. represent the three largest monophyletic clusters associated with south africa-specific lineages that emerged and spread in the country following lockdown and into the peak of the epidemic. they contain , , and genomes, respectively, which represents . % of the total genomes in this study (supplementary table ), with a clear overrepresentation in later stages of the epidemic (fig d) . genomes belonging to these lineages were sampled in five adjacent provinces of south africa and in all districts of kzn province (fig b, c, supplementary figure s ) , and corresponded to timepoints spanning from april to august ( figure b, c) . we compared ct scores for genomes that we generated (n= ) and show that there is no significant difference between the ct scores of sequences belonging to these three lineages and the others (supplementary fig s ) . this suggests that the fast spread of the lineages of interest is likely a result of localized outbreaks and expected transmission dynamics, rather than caused by any fitness advantage. in order to better understand the spatiotemporal diffusion of south african specific lineages, we used a continuous phylogeographic model that maps the phylogenetic nodes to their inferred geographical origin locations (fig a) . bayesian mcmc analysis in beast suggests these lineages emerged during the early phase of the south african epidemic between february and may (supplementary fig s ) . our phylogeographic reconstruction suggests that lineage b. . . emerged in the city of durban (ethekwini, eth) around mid march ( % hpd jan -april ). it appears that from june onwards, this lineage quickly disseminated throughout kzn to all of the districts. this occurred when the country moved from lockdown level to , which allowed greater movement of people and goods between districts. lineage c. most likely emerged in early may ( % hpd - - - - - ) in the city of johannesburg, located in gauteng province, from where it quickly spread to the adjacent north-west province, where it caused a large nosocomial outbreak . furthermore, the lineage spread through two independent events to the northern province of limpopo and to northwestern kzn. from this location, the lineage further spread into all districts of kzn and to the adjacent free state province. unfortunately, lineage b. . . showed poor temporal signaling (supplementary fig s ) and therefore bayesian spatiotemporal analyses could not be performed for this cluster. a closer look at the cluster (from the ml timetree) is, however, shown in supplementary figure s and indicates that this lineage was first sampled in kzn and gauteng and later spread in large numbers in the provinces of kzn, north west and the free state. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . ; (fig a) . this is relatively higher than the number of acquired mutations in other sequences, which is consistent with these three lineages having emerged more . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . ; recently than the rest, hence accumulating more genomic changes. sequences are assigned lineages based on the presence of certain lineage-defining mutations (supplementary fig s ) (fig b, in black) , including the a>g (spike d g) mutation, with additional mutations that differentiate them (fig b, in red) . sequences in b. . . have the t>c (nsp : y h) and c>t mutations in > % frequency, similar to c>t for b. . . , and c>t (nsp : t i) , g>a ( c-like proteinase: g s), c>t, c>t and c>t for c. (fig b) . the early hospital-linked lineage b. . was defined by the c>t (helicase: p l) mutation. five of these mutations, t>c, c>t, c>t c>t and c>t, are predominantly present in south african genomes, with just a few occurrences in the rest of the world (fig c and supplementary fig s ) , whereas the rest of the lineage-defining mutations are also common in the rest of the world (supplementary fig s ) . there are two other high prevalent mutations on the spike protein in the b. . and c. . lineages, c>t and c>t, but these are both synonymous mutations. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . ; major contributor to linage amplifications in south africa were hospital outbreaks for example, as previously mentioned, lineage c was amplified in a nosocomial outbreak in the north west province in april before spreading to kzn and other provinces. another south african lineage, b. . , also emerged in a nosocomial outbreak in kzn in april . this was a large outbreak that infected heath care staff and patients, and dominated most of the early infections in durban, south africa ( figure b ). this nosocomial outbreak attracted national . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . ; attention as it was responsible for % of the infections in kzn and over % of the national deaths in early april . we used genetic sequencing, together with active outbreak investigation to understand how the virus entered and spread in this hospital . this lineage also spread to the population and caused a second nosocomial outbreak in a nearby hospital that infected health care workers ( figure a ). these two nosocomial outbreaks were identified within days of the first infection and were followed with very active infection and prevention control measures , . the b. . lineage largely subsided following the outbreak investigations and isolation of all infected individuals. the b . lineage's prevalence at the population level decreased quickly after june (figure ). we report an in-depth analysis of the spread of sars-cov- in south africa, showing that the bulk of introductions happened before lockdown and travel restrictions were implemented at the end of march . however, despite drastic lockdown measures, the pandemic spread quickly, cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . ; causing over , laboratory confirmed infections. in order to track the evolution of the virus, we formed the ngs-sa, a consortium of genomics and bioinformatics scientists that worked with national government laboratories to quickly generate and analyze data in the country. we produced , sars-cov- whole genomes and mapped the emergence of south african specific novel lineages. these lineages became established during the hard lockdown and spread widely in the country. we find that three main lineages were responsible for almost half of all the infections in south africa. despite a relative sequencing bias in kzn, we were able to detect these major lineages across multiple provinces. it is therefore likely that more extensive sampling throughout the country could pick up the spread of these lineages all over the country, especially as lockdown levels were eased and mobility increased. indeed, recent data from cape town also identified the c lineage, which is the most geographically widespread lineage in south africa. genomic data was also used in real-time to identify and control nosocomial outbreaks. for example, the b. . lineage, which was the first south african lineage to be identified, was used to understand how the virus spread inside a large hospital in the country. the lessons learned in this outbreak were used to quickly control a second nosocomial outbreak. the active outbreak investigation itself may have limited the spread of this lineage. our analysis therefore shows that a number of sars-cov- lineages, each with unique mutations, emerged within localized epidemics during lockdown even as the introduction of new lineages from outside south africa was being curbed. it is currently unknown if any of the mutations originating in south africa have a fitness advantage in terms of transmission, viral replication, or a reduced immunogenicity in the south african population. that many of the mutations are synonymous and that differences in ct values do not seem to be appreciably affected by the infecting viral strain argues against selection for fitter variants. it is important to note that the four main lineages in south africa contain the d g mutation on the spike gene. we are currently investigating limits to crossreactivity between strains. limited cross-reactivity may lead to effects such as antibody dependent enhancement (ade) in response to a vaccine with a non-native strain. ade occurs in infections such as dengue when a previously infected individual is infected with a second strain of virus, which antibodies from the first infection can bind to but not neutralize . in conclusion, this study further emphasizes the usefulness of integrating genomic surveillance methods to understand sars-cov- spread in local settings. furthermore, genomics data can also be used in real-time to inform and consolidate national outbreak investigation and response strategies in africa. the proximal origin of sars-cov- a new coronavirus associated with human respiratory disease in china covid- ) situation reports genomic surveillance reveals multiple introductions of sars-cov- into northern california. science ( -. ) introductions and early spread of sars-cov- in the new york city rapid sars-cov- whole genome sequencing for informed public health decision making in the netherlands an emergent clade of sars-cov- linked to returned travellers from iran spread of sars-cov- in the icelandic population a territory-wide study of early covid- outbreak in hong kong community: a clinical, epidemiological and phylogenomic investigation a dynamic nomenclature proposal for sars-cov- lineages to assist genomic epidemiology disaster management act: regulations to address, prevent and combat the spread of coronavirus covid- : amendment | south african government a method to monitor the effective reproductive number of sars-cov- study tells 'remarkable story' about covid- 's deadly rampage through a south african hospital gisaid global initiative on sharing all influenza data. phylogeny of sars-like betacoronaviruses including novel coronavirus (ncov) krisp severe acute respiratory syndrome coronavirus (sars-cov- ) vi sars-cov- lineages rapid implementation of sars-cov- sequencing to investigate cases of health-care associated covid- : a prospective genomic surveillance study cluster outbreak at north west hospital: patients and nurses infected with covid- report into a nosocomial outbreak of coronavirus disease (covid ) at netcare st. augustine's hospital acknowledgements: this research was funded by the south african medical research council (samrc), mrc ship and the department of science and innovation (dsi) of south africa. krisp is funded by a core award of the south african technology innovation agency (tia). we key: cord- -rrwy osd authors: neiderud, carl-johan title: how urbanization affects the epidemiology of emerging infectious diseases date: - - journal: infect ecol epidemiol doi: . /iee.v . sha: doc_id: cord_uid: rrwy osd the world is becoming more urban every day, and the process has been ongoing since the industrial revolution in the th century. the united nations now estimates that . billion people live in urban centres. the rapid influx of residents is however not universal and the developed countries are already urban, but the big rise in urban population in the next years is expected to be in asia and africa. urbanization leads to many challenges for global health and the epidemiology of infectious diseases. new megacities can be incubators for new epidemics, and zoonotic diseases can spread in a more rapid manner and become worldwide threats. adequate city planning and surveillance can be powerful tools to improve the global health and decrease the burden of communicable diseases. t he industrial revolution in the th century led to larger cities with greater potential for growth and development both for the individual and the community. living in a city can provide you with several advantages, such as the possibility for higher education, a new job with higher income, the security of better health care, and the safety of social services. in , the united nations estimated that % of the world's population, . billion, lived in urban centres ( ) . economic growth for countries has been linked to urbanization and countries with high per capita income are among the most urbanized, whereas countries with low per capita income are the least urbanized ( ) . the financial and political power is often concentrated in the cities, which leads to unique possibilities for action and quick response if needed. the process of urbanization refers to increased movement and settling of people in urban surroundings ( ) . however, the meaning of the word 'urban' does not have a universal definition. a wide variety of different interpretations can be found in various countries, and often they do not share the same understanding. different versions could be: living in the capital, economic activities in the region, population size, or even density. the lack of a universal definition makes it hard to compare different countries and cities in regard to public health and the burden and impact of infectious diseases ( ) . many of the studies conducted address the differences between urban and rural areas, and do not compare different urban settings. it can thus be difficult to get a global overview and get a better understanding of the burden of infectious diseases in these specific environments. cities from around the world can also be very heterogeneous and the local diseases and health challenges can greatly differ. the challenges for one city can be completely different for another location ( ) . about a century ago, only % of the world's population lived in cities, and in the least developed countries the percentage was only % ( ) . approximately half of the world's population now live in these urban centres. the two inhabited continents, which currently are the least urbanized, are asia and africa, with respectively and % of the population living in cities. these percentages are expected to rise dramatically by the year to and % respectively ( ) . in the last decade, the growth in the urban population has been the highest in asia, adding . million urban migrants per week. africa was the second highest contributor with . million. the total figure of new urban residents per week during the last decade was on average . million. it is in africa and asia where the current rapid growth is taking place. years are that almost all of the population growth will be in urban areas, but the growth in developed countries is expected to remain largely unchanged ( ) . chronic illnesses have been increasing in importance for the developing world. worldwide the leading causes of death in were ischaemic heart disease followed by stroke, lower respiratory infections, chronic obstructive lung disease, and diarrhoeal diseases. however, if you look at the list for low-income countries, infectious diseases still have a profound impact. the top three causes of death in these settings are all infectious diseases: lower respiratory infections, hiv/aids, and diarrhoeal diseases ( ) . many of the lower income countries are expected to have a major growth among the urban population, which leads to considerable challenges for the governments and health care to keep up to pace and develop their social services and health care as these regions grow. the rise of the new modern cities also creates potential risks and challenges in the aspect of emerging infectious diseases. different risk factors in the urban environment can, for example, be poor housing which can lead to proliferation of insect and rodent vector diseases and geohelminthiases. this is connected to inadequate water supplies as well as sanitation and waste management. all contribute to a favourable setting for both different rodents and insects which carry pathogens and soil-transmitted helminth infections. if buildings lack effective fuel and ventilation systems, respiratory tract infections can also be acquired. contaminated water can spread disease, as can poor food storage and preparation, due to microbial toxins and zoonoses ( ) . the density of inhabitants and the close contact between people in urban areas are potential hot spots for rapid spread of merging infectious diseases such as severe acute respiratory syndrome (sars) and the avian flu. criteria for a worldwide pandemic could be met in urban centres, which could develop into a worldwide health crisis ( ) . adequate city planning can be a key factor for better overall health, and such considerations must be in the mind of the governing bodies. today's megacities are very heterogeneous with large slum settlements, which lead to challenges for overall health and health care in the community. within one large urban setting, there can be huge differences in health conditions depending on where you live. in general, the urban health is better, but in some areas, it can actually be worse compared to certain rural environments ( ) . of the estimated billion people living in urban centres, about one-third live in slum areas ( ) . the ever-changing environment of cities has made certain infectious diseases both emerge and re-emerge. pathogens which adapt to urban environments from rural settings can spread in a more rapid manner, and be a greater burden to the health care services ( ) . this review article examines the urban world and how the current rapid urbanization around the world is affecting the epidemiology of emerging infectious diseases. currently the most rapid growth in urban population is taking place in the developing countries, and poses many different challenges compared to traditional highincome countries. this review focuses on these growing regions and their implications and how emerging infectious diseases affect the community. urban population Á a heterogeneous group with different living conditions cities around the world can look very different if you compare the living conditions for the residents. however, it is not only different cities that can have completely diverse standards of infrastructure and social security. the same city can provide very varying conditions for their residents. living in the slums compared to more wealthy neighbourhoods, will expose the inhabitants to different risks. traditionally cities can offer many advantages compared to rural settings, but under certain circumstances they can rather be a health hazard. the rapid migrations of people to cities can lead to overcrowding, which can generate slums or shanty towns. these slums are characterized by poor housing, lack of fresh water, and bad sanitation facilities ( ) . all of these shortages can be a threat to the residents' health and be a possible breeding ground for infectious diseases. the location of slums are often outside of the city centres, in more hazardous locations and the population feels a lack of social and economic opportunities compared with other residents. in sub-saharan africa, % of the urban population in lived in shanty towns ( ) . for example, in , % of the urban population in central african republic lived in these slums ( ) . in kenya's capital nairobi, % of the population lives in slums, and child mortality there is . times greater than other parts of the city ( ). the community and health care services have great challenges to provide the entire population with equal and adequate service. the collected parties need to be aware of the differences in threats with respect to infectious diseases, both at the local and governmental levels. certain infectious diseases have been shown to be more widespread in the slums. an example of this is the diarrhoeal disease cholera. infections have been linked to slums in dar es salaam, tanzania, with high population density and low income ( ) . in several other countries, cholera incidence is the highest in urban regions with high population density ( , ) . differences in prevalence of asymptomatic carriers of antimicrobial drug-resistant diarrhoeagenic escherichia coli have also been found in brazil between slum settlements and more wealthy parts of the community ). the poor infrastructure in the slum can be a barrier for improvement, but at the same time targeted interventions for safer water and better sanitation carl-johan neiderud facilities could potentially have a profound effect of the overall health. overcrowded housing in high-density populations in the slums can be a breeding ground for infectious diseases such as tuberculosis. the rate of tuberculosis has traditionally been higher in urban centres compared to rural ( , ) . studies in slum settlements in dhaka city, bangladesh, indicate a high prevalence of tuberculosis, which was almost twice as high compared to the overall national average and four times higher than the overall urban levels ( ) . however, different patterns can be seen in different countries; for example, in poland the rates of tuberculosis have shown only slightly lower incidence in rural population compared to urban, . per , versus . per , respectively ( ) . tuberculosis in the united states has declined in the twentieth century, and several factors such as improved nutrition status, socioeconomic status, overall public health, and new drug regimens have been thought to play a major role. however, in the mid- s a resurgence occurred which reached its peak in , especially in urban areas among the homeless and incarcerated population ( ) . the knowledge regarding symptoms, transmission, and prevention has been shown to be greater among the urban population in pakistan's punjab province compared to the rural population. health-seeking behaviour was also better among the urban population, in the aspect of when to seek medical advice for early diagnosis and potential treatment ( ) . information about infectious diseases and how they spread in the community can help the individuals to protect themselves, but knowledge about the slums and the infectious diseases panorama is also crucial for local physicians. they need to know how to look for the correct diagnosis, even if their diagnostic tools might be limited. the right hypothesis from the start in these cases is even more important. the rapid urbanization around the world leads to great challenges in city planning. the rapid influx of migrants can lead to overcrowding and local governments might not be able to provide safe housing, drinking water, and adequate sewage facilities, all of which are potential health hazards and must be taken into account for safe city planning. today more than half of the world's population, almost billion people, have access to piped water connected to their homes. since , well over billion people have gained improved drinking water facilities, and almost billion people have access to improved sanitation. however, more than million people still lack access to improved sources of safe drinking water, and in sub-saharan africa half of the population lack such facilities. globally the decline of open defecation between and went from to %. however, billion people in the world still practice open defecation. in this group, % live in rural areas, but the actual amount of residents from urban settings is gradually increasing. between and , the group in urban settings which lacked sanitation actually significantly increased from million to million, which could be explained by population growth ( ). much of the hard work to improve sanitation facilities has benefited large population groups, but the rapid influx of new urban residents shows that there is still much hard work to be done. residents who are subject to overcrowding and who lack access to safe drinking water or proper sanitation can be more susceptible to soil-transmitted helminths ( ) . these infections are among the most important causes of physical and intellectual growth retardation in the world and have a major impact on public health ( ) . good hygiene practices and good sanitary conditions have lowered the prevalent levels of contamination. in the brazilian city of salvador, with a population of . million, an improvement of sewerage coverage from to % of the households led to an estimated overall reduction of diarrhoeal diseases of % ( ) . neglected tropical diseases can cause substantial health problems in developing countries, and some of these diseases have a faecal-oral transmission pathway. examples of such diseases could be schistosomiasis, trachoma, and soiltransmitted helminthiases. improved sanitation could contribute to a significant improvement for the public health. in many countries, however, the focus is on treatment by medication and not improved sanitation. the reason could be that it would be much more expensive to carry out the necessary infrastructural improvements ( ) . safe drinking water and proper sanitary facilities must be taken into account in city planning. factors like this can potentially have a profound positive effect in lowering infectious diseases with a faecalÁoral route. however, the real challenge lies in the uncontrolled growth of slum settlements. poor housing and overcrowding can also contribute to vector proliferation. one example of this is for chagas disease, which is a parasitic infection caused by the protozoan trypanosoma cruzi. an important mode of transmission is vectorial infected bites of triatomine bugs. living in close contact to domestic animals and poor hygienic habits have also been identified as risk factors ( ) . chagas disease affects an estimated million people every year, and is an important health challenge in latin america. in recent decades, progress has been made to reduce the burden of disease, by vector control, screening blood donors, improved housing, and epidemiological surveillance. chagas disease is a growing health problem in non-endemic areas because of population movements ( ) . it is estimated that , individuals in the united states are infected ( ) and the most affected country in europe, spain, is thought to have , Á , cases ( ) . the example of chagas disease shows that physicians who practice in countries where the disease is not present must be aware of the travel history of the patient to connect the potential symptoms to the correct diagnosis. the environment in urban cities has proven to be favourable for the rat population (rattus spp.) and close encounters between rats and humans can lead to transmission of zoonotic infectious diseases. they can carry pathogens such as yersinia pestis, leptospira spp., rickettsia typhi, streptobacillus moniliformis, bartonella spp., seoul hantavirus, and angiostrogylus cantonensis ( ) . new york city has one of the largest populations of rats in the united states. it has been shown that encounters between rats and humans have been linked to proximity to open public spaces and subway lines, the presence of vacant housing units, and low education of the population ( ) . information like this can be useful for health officials when they launch specific control initiatives. the changes in human population with increased urbanization and urban poverty has also altered our perception of some zoonoses linked to the rat population. leptospirosis has traditionally been perceived as a primarily rural disease, but the incidence in urban centres is increasing ( , ) . in chinese cities, the incidence of seoul hantavirus haemorrhagic fever with renal syndrome has been linked to urban growth, growing rat population, and increase ratÁhuman contact ( ) . large megacities all over the world have large rat populations, but the surveillance and local knowledge seem to be inadequate. a better understanding of how to prevent uncontrolled growth in rat population can potentially lead to a decline of these zoonotic diseases. the growing trend of urbanization around the world has shifted some infectious diseases, which have traditionally been perceived as rural, to urban settings. the world health organization (who) has published a list of neglected tropical diseases. several of them have now become a reality in the urban environment, these diseases are something the practicing physicians in these areas have to be aware of ( ) . many of the diseases on the list are present in the developing world, which sometimes lack the opportunity to solve these problems by themselves. these countries need help from the global community. one of the neglected infectious diseases is lymphatic filariasis (lf) with billion people at risk, and . million in urban areas. one of the main reasons is the lack of proper sanitation facilities ( ) . lf still has its major impact in rural settings, but the increasing urbanization in the developing world has made lf an infectious disease that also has to be considered elsewhere. one of the parasite species wuchereria bancrofti has been located in many urban areas and has the potential for transmission in this environment. moreover, one of the vectors for the parasite is the mosquito culex quinquefasciatus, which thrives in these surroundings, especially in overcrowded areas with poor sanitary and draining facilities. however, within one city the transmission can vary substantially depending on the standard of the sanitary conditions. the mosquito vector culex spp. can be found in large parts of central and south america, east africa, and asia ( ) . another vector which has adapted to urban surroundings is the mosquito aedes aegypti, which is a key component for dengue transmission. dengue is on who's list of neglected tropical diseases, and is on the rise worldwide. the number of infections has drastically increased in the tropical regions of the world in the last years. recent studies have estimated million cases each year, and the burden is the highest in india with onethird of all the new infections ( ) . several factors have played a big role in the escalation, such as urbanization, globalization, and lack of mosquito control. aedes aegypti lay their eggs in artificial water containers made by humans, which is a key component in the urban transmission cycle. the adaption of dengue through its vector has made dengue an infectious disease on the clear rise ( ) . thailand is a country with all four serotypes of dengue virus, and the epidemics of dengue haemorrhagic fever have shown a possible correlation to originate from the urban capital of bangkok and then spread geographically in an outward manner to more rural settlements and provinces. a model to understand this mechanism could lead to more effective use of the health systems in the affected areas ( ) . dengue has become a global problem and is no longer restricted to the developing world. despite better knowledge, it seems tough to control the vector, which has adapted to the urban environment and living close to people. an efficient vaccine is not yet commercially available, but could be a powerful factor in the fight against the global dengue epidemic. often several different factors need to be favourable for a vector-borne disease to adapt to the conditions in an urban environment. for example, west nile virus (wnv) infection is an infectious disease which has become a reality in the urban environment. the primary vector is the mosquito culex pipens, which lay their eggs in water resources which are often man-made. however, for a successful transmission cycle wnv also need the american robin (turdus migratorius), which has several broods per season and hatchlings are more susceptible to wnv infection than adult birds ( ) . the county of dallas, texas, experienced an epidemic of wnv infections in . surveillance reports revealed % of the cases in the united states were found in dallas county ( ) . it shows for a vector-borne disease to have a successful transmission cycle several different factors need to be in place to affect the human population. leishmaniasis is a disease caused by the protozoa leishmania, which affects million and threatens million people in different countries. there can be different clinical presentations such as cutaneous and visceral ( ) . leishmaniasis is transmitted by the vector phebotomine sandflies. when rural migrants bring their domesticated animals to urban settings, often slums, they create favourable conditions for an urban transmission ( ) . it has been shown that it is a growing health problem and the ongoing urbanization has contributed to the increase ( ) . if the different vectors can adapt to the urban environment and man-made resources, the potential health implications can be of major concern. control programs and adequate surveillance is of importance, but in rapidly growing cities and slums it can be tough to implement such measures. emerging infectious diseases can also make the jump to stable transmission in the urban surroundings and surveillance of these can potentially prevent major health concerns and high cost for the health care services. who can play a major role in the fight for better control and knowledge. many of the countries in the developing world do not have the proper resources and the problem is not concentrated to one region, but is a global concern. numerous of the neglected tropical diseases play a major role in the developing world, which is currently experiencing a much faster pace of urbanization compared to the developed world. the who's call for help is important and, for example, dengue is now turning into a global crisis. safe and targeted assistance can be a huge factor for overall health; such assistance could be an effective vaccine or safe and easy vector control programs. urban centres can be catalysts for rapid spread of infectious diseases. the basis of large population groups in a restricted area can provide the perfect conditions for different epidemics. international travel has connected the world in the last century, and this mobility creates a potential threat of many emerging diseases. international tourist arrivals have shown an exceptional growth from million in to , million in . according to the latest forecast from the world tourism organization, international tourism arrivals will continue to increase, and in the figure is expected to be . billion ( ) . with the pace of modern travel, highly contagious infectious diseases can be a potential threat in a completely different setting compared to the original outbreak. urban population and the density of residents can meet the criteria for a new epidemic and create a public health disaster, if not taken seriously. international trade and travel can potentially also contribute to the occurrence of a worldwide pandemic. sars emerged as a global threat in . sars is thought to originate from the sars-like coronavirus (scov) of bats and reached the human host in china due to hunting and trading of bats for food ( ) . the disease was first recognized in wildlife markets in guandong, china. investigations have found this scov from the himalayan palm civets in live-animal markets in the region. the first cases of sars reportedly occurred in individuals who handled these animals to prepare exotic food, and the virus is thought to have crossed over to their human host ( ) . sars could then spread throughout the world by, for example, international travel. it spread in urban dwellings in large cities and in wellequipped city hospitals. public fear of travelling led to considerable economic losses that affected entire countries ( ) . the example of sars shows that food markets in southern china can be the origin of a worldwide health crisis. travel routes around the world have connected the urban world and large megacities like never before. accordingly it is important to take necessary preventive measures before the epidemic gets out of control, and here big organizations like who, but also governments, play an important role. early action is of utmost importance, and functional surveillance programs needs to be in place. the zoonotic disease dengue is endemic in most tropical and subtropical regions, which often are also popular tourist destinations. travellers to endemic countries can contribute to the spread of the disease. the burden of disease is on the rise, and estimations are that in returning travellers from southeast asia, dengue is now a more frequent cause of febrile illness compared to malaria ( ) . dengue is now an urban health problem, which is one of the major reasons why the rise is exceptional. the global rising problem of antibiotic resistance has also been linked to international travel. the worldwide spread of certain antibiotic resistant staphylococcus aureus has been linked to tourism, which shows the potential impact on international health ( , ) . faecal colonization with esbl-producing enterobacteriaceae has also been linked to international travellers in several studies ( Á ). the physician needs to take into account the recent travel activities of the patient to better evaluate the current condition and need for potential treatment and care. global travel shows no signs of decline and the interconnected megacities around the world make global surveillance even more important when it comes to contagious infectious diseases. measurements to stop the spread need to be taken at the original location, but knowledge about the specific disease needs to be passed on to the global community and local health workers in other parts of the world. this global surveillance and alert system needs to be fast and efficient to, if possible, reduce the impact. the expected rise of travel makes it critical for the future global health and the possibility to react in time for possible threats. zoonotic disease a challenge for the future rapid and sometimes uncontrolled urbanization can, in certain circumstances, lead to closer encounters with wildlife. human influence on the ecosystems creates meeting points for new and potential zoonotic diseases, which could have a profound impact for both local and global health. the global trends of urbanization push people to previously untouched ecosystems. new housing in the outskirts of big cities can potentially be meeting points for new and already known zoonotic diseases. of emerging infectious diseases, which have been recognized between and , more than % have been zoonotic diseases ( ) . living in close contact to domesticated animals and hunt for 'bush-meat' can also be risk factors for an infectious disease to make the jump from the animal host to humans. major deforestation creates closer contact between humans and bats and even primates, who can potentially be host for 'new' viruses. a better understanding, surveillance, and prevention of zoonotic diseases would be of great value, to both prevent and manage this upcoming threat for global health. hot spots for this transmission have been found and they often correlate where the process of urbanization is on the clear rise ( ) . even if it is not always the urban population who is at the front of new encounters with wildlife, it can still have an effect on urban health. the trend of people moving to cities are at the highest, where many of these new encounters with ecosystems take place, and infectious diseases can be introduced to these growing urban environments. the sometimes uncontrolled growth of cities pushes residents to untouched ecosystems when new housing expands. ebola virus disease (evd) has had a profound impact on the world in . since the spring of , the world has witnessed an unprecedented epidemic of this zoonotic disease. the hub of the epidemic has been the three countries in western africa: sierra leone, liberia, and guinea. it all began in december in guinea, in the providence of guéckédou, in the eastern rainforest region. the disease transmission in the capital of conakry is thought to be the first major urban setting for evd ( ) . who was first notified of the evd outbreak in march , and on august , the who declared the current situation as 'public health emergency of international concern' ( ). before, evd outbreaks in central africa had been limited in size and geographical spread to a few hundred persons, mostly in remote areas and not large urban settings ( ) . the centre of the epidemic (guinea, liberia, and sierra leone) has, as many of their neighbouring countries, a large population living in rural settings; only , , and % of their population live in urban centres ( Á ). the population is, however, highly interconnected in these countries with travel and crossborder traffic, with good road access between rural and urban settings. these communications have made the magnitude of the evd epidemic possible. despite cases of evd in nigeria and lagos, a megacity with million inhabitants, the transmission has been limited, which proves that implementation of control measures can limit the transmission ( ) . the mortality rate has been high in previous outbreaks, up to % ( ) . the fatality rate in the west africa epidemic has been estimated to around % for guinea, liberia, and sierra leone when data for patients with recorded definitive clinical outcomes ( ) . this unprecedented epidemic points out the importance of better surveillance, understanding, and preventions measures for this potentially deadly virus. ebola virus (ebov) is thought to be a zoonotic disease, and fruit bats are under investigation to be the natural reservoir. ebov sequences have been found in these animals near the human outbreaks which implies where the virus might originate from ( , ) . closer contact with humans and fruit bats are thus risks for a new global health crisis and the severity of an ebola epidemic has already been witnessed. the high costs, both from an economic and overall health perspective, have affected entire countries and have even cost lives on the other side of the earth. urban centres offer their residents greater possibility for health and social services. different factors, such as education, direct primary care services, and the governments' capacity for rapid response to upcoming health threats, can contribute to the opportunities in a city. however, in many cities the poor can find it difficult to access proper health care, due to the cost of such services. in more rural areas, the problem can instead be the distance to the nearest clinic, which in reality makes it impossible for prompt and efficient treatment ( ) . malaria has historically been and is still a major health concern in large parts of the world. who estimates million cases ( Á million) of malaria and , deaths ( , Á , ) in . the highest mortality rates have been shown to be closely linked to poor countries with a low gross national income (gni) per capita ( ) . estimations have been made that nearly % of the total african population, million, currently live in urban settings where malaria transmission is a reality. the annual incidence is estimated at . Á . million cases of clinical malaria among the urban population in africa ( ) . the relationship between the malaria mosquito vector and the human host determines the burden of morbidity and mortality. this interface is dependent on many different factors and the degree of urbanization is an important one. a significant reduction in malaria transmission has been observed over the last century. increased urbanization and decreased transmission have correlated in several different studies ( ) . however, whether it was the increased urbanization that led to a reduction in transmission or the malaria reduction that led to development that promoted urbanization of societies is a challenge to determine ( ) . a clear connection has been shown between reduced transmission of plasmodium falciparum and urbanization; however, for plasmodium vivax it is less obvious. for p. vivax, a connection has been found globally and in asia and africa; inconsistent results, however, were found in the americas. several possibilities could explain these incoherent results, such as more widespread transmission of p. vivax, lower transmission intensity, the wide distribution in asia, and high prevalence of duffy negativity in africa, which protects against p. vivax ( ). the overall decrease of the burden of malaria has been a positive effect of urbanization, but the exact mechanisms are not yet known. however, it seems that urbanization can have a favourable influence. immunization status between residents in urban centres and rural areas can differ. coverage of measles vaccination in indonesia have shown to be . % in rural areas, compared with . % in urban regions ( ) . studies in nigeria have shown that sometimes the coverage can actually be better in more rural areas, and it might be explained by better mobilization and participation in the delivery of immunization services ( ) . in a study in uganda, % of the urban group compared to % in the rural areas were fully immunized, but polio vaccine was given to % in the urban group and % in the rural group ( ) . immunization coverage can also vary considerably among different settings, not only between rural and urban surroundings, but also between urban, rural, and slum settlements. in changdigarh, a union territory of india, full immunization of children at the age of was % in slums, % in urban, and . % in rural settings ( ) . it shows that there can be a wide variety of reasons for immunization status among the population in different regions and countries of the world. effective immunization can be a cost-effective measure in poorer countries. high coverage can prevent epidemics in large cities and save many lives; however, immunization needs to be available both for the rural and urban population to achieve the greatest benefit. a study in tanzania has compared the knowledge about certain zoonotic diseases among general practitioners in urban and rural areas. the rural practitioners had poor knowledge of how sleeping sickness is transmitted and clinical features of anthrax and rabies. laboratories in rural areas are often poorly equipped and cannot always diagnose certain zoonotic diseases, which could limit the doctors' capability for correct diagnosis and treatment ( ) . public knowledge about certain infectious diseases can also vary depending on many different factors. the knowledge about sexually transmitted diseases (stis) among bangladeshi adolescents was higher among people in urban areas compared to rural, both in general and hiv and aids ( ) . the same results about hiv and aids have been found among a canadian population ( ) . studies in chengdu and shanghai, china, have shown risk perception about stis and hiv and aids is profoundly changed in rural-to-urban migrants ( , ) . the same result has been shown in a study among rural-to-urban migrants in ethiopia ). the rapid influx of migrants moving to cities makes it hard to get adequate information to all the different groups in the society. to educate the public is one of the many challenges for local governments and health officials. campaigns to improve the public knowledge are useful to fight the threat of infectious diseases. residents need to be aware of symptoms of infectious diseases to gain knowledge about when to seek health care and when it is safe to treat yourself. knowledge about food storage, waste management, vector control, and sanitary facilities are all aspects that can lower the burden of communicable diseases. these campaigns can sometimes be easier in the urban environment because of the density of the population. urbanization is an ongoing process in the world at the moment, but the pace of the process is not universal. the developed countries, which have traditionally been thought of as high-income countries, are already urbanized, and it is in the developing world that the rapid rise is taking place. infectious diseases still have a big impact on the global health, and urbanization is now altering the characteristics of these diseases. living conditions in cities are overall better in urban environments compared to rural settings; better housing, sanitation, ventilation, and social services all play an important role in this improvement. certain pathogens can, however, adapt to the different conditions and thus create a new challenge for both local governments and the global community. the capacity for surveillance, control programs, prevention, and public knowledge programs is far better in cities. it is here where the resources and political and financial power are gathered. but some countries do not have the resources and because these diseases can be of global concern, it is also the international community's responsibility to help and support with knowledge and resources. the rapid urbanization has also interfered in previously untouched ecosystems. these new settlements create new and closer encounters with wildlife, which can be a potential source of zoonotic 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west africa Á the first months of the epidemic and forward projections ebola haemorrhagic fever fruit bats as reservoirs of ebola virus recent common ancestry of ebola zaire virus found in a bat reservoir world malaria report urbanization in sub-saharan africa and implication for malaria control urbanization, malaria transmission and disease burden in africa urbanization and the global malaria recession the effects of urbanization on global plasmodium vivax malaria transmission determinants of apparent rural-urban differentials in measles vaccination uptake in indonesia community participation and childhood immunization coverage: a comparative study of rural and urban communities of bayelsa state, south-south nigeria factors influencing childhood immunization in uganda reproductive and child health inequities in chandigarh union territory of india knowledge of causes, clinical features and diagnosis of common zoonoses among medical practitioners in tanzania nyströ m l. urban-rural and socioeconomic variations in the knowledge of stis and aids among bangladeshi adolescents talking about, knowing about hiv/aids in canada: a rural-urban comparison vulnerable but feeling safe: hiv risk among male rural-to-urban migrant workers in chengdu sexual behavior among employed male rural migrants in hiv-related sexual behaviors among migrants and non-migrants in rural ethiopia: role of rural to urban migration in hiv transmission i would like to thank the two anonymous reviewers for their insightful opinions. the author have not received any funding or benefits from industry or elsewhere to conduct this study. key: cord- -o zyt vb authors: motayo, babatunde olarenwaju; oluwasemowo, olukunle oluwapamilerin; akinduti, paul akiniyi; olusola, babatunde adebiyi; aerege, olumide t; faneye, adedayo omotayo title: evolution and genetic diversity of sarscov- in africa using whole genome sequences date: - - journal: biorxiv doi: . / . . . sha: doc_id: cord_uid: o zyt vb the ongoing sarscov- pandemic was introduced into africa on th february and has rapidly spread across the continent causing severe public health crisis and mortality. we investigated the genetic diversity and evolution of this virus during the early outbreak months using whole genome sequences. we performed; recombination analysis against closely related cov, bayesian time scaled phylogeny and investigated spike protein amino acid mutations. results from our analysis showed recombination signals between the afrsarscov- sequences and reference sequences within the n and s genes. the evolutionary rate of the afrsarscov- was . × − high posterior density hpd ( . × − to . × − ) substitutions/site/year. the time to most recent common ancestor tmrca of the african strains was december th . the afrsarcov- sequences diversified into two lineages a and b with b being more diverse with multiple sub-lineages confirmed by both maximum clade credibility mcc tree and pangolin software. there was a high prevalence of the d -g spike protein amino acid mutation ( . %) among the african strains. our study has revealed a rapidly diversifying viral population with the g spike protein variant dominating, we advocate for up scaling ngs sequencing platforms across africa to enhance surveillance and aid control effort of sarscov- in africa. towards the end of december , chinese authorities through the world health organization office in china made known of a new pathogen responsible for a series of pneumonia associated infections in wuhan, hubei province (who ). the pathogen was later identified to be a novel coronavirus closely related to the severe acute respiratory syndrome virus (sars), with a possible bat origin (zhou et al, ) . the world health organization named the disease covid- (chan et al, ) , and later declared it a pandemic on th march prompting concerted efforts towards prevention and control worldwide (who ). on febuary th the international committee on the taxonomy of viruses (ictv) adopted the name sars-cov- following the report of their coronavirus working group (csg, ) . the virus has been placed in the subgenera sarbecovirus, genus betacoronavirus, subfamily coronavirinea, family coronaviridea (de groot et al, ; gorbalenya et al, ) . coronaviruses are enveloped viruses containing a single-stranded positive sense rna genome with a size of between kb to kb (masters and pearlman ) . they are responsible for a host of human and animal infections. the betacoronaviruses host the most medically important species contains several human coronaviruses such as hucovoc , hucovhku . the severe acute respiratory syndrome coronavirus sarscov and the middle east respiratory syndrome coronavirus mers are also members of this group, both have been shown to be pathogens of high consequence that caused large scale epidemics and have been shown to be of zoonotic origin (lau et al, ; zaki et al, ) . genomic and structural analyses have revealed that sarscov- contains four structural proteins and several non structural proteins (chen et al, ; lu et al, ) . the spike protein is the major antigenic protein responsible for initiating infection, via attachment of its receptor binding domain (rbd) to the sarscov/sarscov- receptor angiotensin converting enzyme ace (donelli et al, ; monteil et al, ) . globally, there have been , , confirmed sarscov- cases globally, with , deaths as at st of may (ecdc ). the coronavirus pandemic began in egypt africa on the th febuary with an italian who returned into the country (who b). as at st of may there have been , cases in africa, with , deaths and , recoveries covering fifty four countries in africa with south africa having the highest number of cases of , (who c). several reports have traced the evolutionary origins of sarscov- to sarsrcov from bats (zhou et al, ) and pangolins (lam et al ) . phlogenetic analysis has shown that the virus has diversified through the duration of the pandemic into three major lineages a and b with several sub-lineage diversifications (rambault et al ) . majority of the reports were generated using genome sequences of sarscov- from america, europe and asia (rambault et al, ) . there has been paucity of data on the genetic evolution of sarscov- sequences from africa, despite the increasing number of genome sequence submissions into the gisaid database from africa; there were whole genome sequences available in the gisaid database as at th april . this gap in knowledge prompted the conceptualization of this study. this study was designed to determine to the genetic diversity and evolutionary history of genome sequences of sarscov- isolated in africa. full genome sequences with high coverage were downloaded from the global initiative for sharing of avian influenza data gisaid database. as at th april there were full genome sequences from africa available in the gisaid database we downloaded all of them excluding genomes with low coverage. a total of high coverage genomes were eventually selected from the african sequences, along with these high quality full genome sequences were also downloaded from three continents america (usa), asia (china and south korea) and europe (england, italy and germany). three different datasets were then generated from these sequences, the first dataset consisted of high coverage full genome sequences from africa, along with the sarscov reference genome sequence from wuhan, china, bat and pangolin sars related reference sequences and sarscov reference sequence. the second dataset consisted of complete genome sequences from africa, america, asia and europe, while the third dataset consisted of complete spike protein (s) gene sequences from africa, bat and pangolin sars related reference s gene sequences. whole genome sequences downloaded from the gisaid database were aligned using mafftv . (ff-ns- algorithm) following default settings (katoh et al, ). maximum likelihood phylogenetic analysis was performed using the general time reversible nucleotide substitution model with gamma distributed rate variation gtr-Γ (yang et al, ) with bootstrap replicates using iq-tree software (nguyen et al ) . lineage assignments for the sarscov- sequences were conducted using the phylogenetic assignment of named global outbreak lineages tool (pangolin), available at http://github.com/hcov- /pangolin (o'toole and mccrone ). we analyzed potential recombination events using the recombination detection program rpd software (martin et al, ) . the analysis was conducted on whole genome sequences of identified lineages among the african isolates, using rdp, bootscan analysis, genecov, chimera, siscan, seq, and maximum chisquare methods. a putative recombination event was passed only if three of the above mentioned methods gave a positive recombination signal (liu et al, ) . temporal clock signal was analyzed among the aligned sequences using tempest version . (rambault et al, ) . the root-to-tip divergence and sampling dates supported the use of molecular clock analysis in this study. phylogenetic trees were generated by bayesian inference through markov chain monte carlo (mcmc), implemented in beast version . . (suchard et al, ) . we partitioned the coding genes into first+second and third codon positions and applied a separate hasegawa-kishino-yano (hky+g) substitution model with gammadistributed rate heterogeneity among sites to each partition (hasaegawa et al, ) . the relaxed clock with gausian markov random field skyride plot (gmrf) coalescent prior was selected for the final analysis, after running different models and comparing them using bayes factor with marginal likelihood estimated using the path sampling and stepping stone methods implemented in beast version . . (suchard et al, ) . one hundred million mcmc chains were run with % burn in. results were then visualized with tracer version . . (http://tree.bio.ed.ac.uk/software/tracer/), all effective sampling size ess values were > indicating sufficient sampling. bayesian skyride analysis was carried out to visualize the epidemic evolutionary history using tracer v . . complete s protein gene sequence of afrsarscov- was aligned along with ratg btcov and pangolin sarsrcov sequences using mafft (katoh et al, ) . the alignment was then edited and visualized using bioedit software. the current global sarscov- pandemic, otherwise known as covid- began on the african continent from a european returnee in egypt on february th (who ). it has since spread to virtually all the countries within the african region. this study was based on sequences generated during the early phase of the pandemic in africa precisely between, february and april . sixty nine high coverage full genome sequences from six african countries, namely algeria ( ), senegal ( ), democratic republic of congo drc ( ), nigeria ( ), ghana ( ) and south africa ( ) were analyzed. phylogenetic analysis of the african sequences showed clustering within the sarbecovirus sub-genus forming a sub-cluster with sarsr cov and pcov (figure ) as previously reported by several workers (zhao et al, ; lam et al, ; . the root to tip regression analysis showed a not so strong signal with a correlation of coefficient of . and r = . (supplementary figure ) . results of recombination analysis of the african sarscov- (afrsarscov- ) sequences against references whole genome sequences of sars, recombination signals were observed between the african sarscov- sequences and reference sequence (major recombinant hcov- pangolin/guangu p l/ ; minor parent hcov- b batyunan/ratg ) between the rdrp and s gene regions (figure ). this result is consistent with a previous report from saudi arabia which investigated the recombination between sarscov- and closely related viruses such as sarscov and mers (nour et al, ) . evolutionary rate for the afrsarscov- isolates during the period under study was . × - substitutions/site/year, high posterior density interval hpd ( . × - to . × - ). this is slightly higher than that of an earlier report from early outbreak strains from china with a rate of . × - (li et al, ) , it is however lower than the calculated global sarscov- evolutionary rate estimated to be . × - reported by nexstrain (www.nextstrain.org/ncov/global ). the mcc tree of the african sarscov- sequences shows that they have evolved into two major lineages a and b with lineage b being more diverse. majority of the african sarscov sequences clustered within lineage b, while three ghanaian, three congolese, and four senegalese strains clustered along with the reference chinese and south korean strains within lineage a (figure ). the mcc tree for the dataset containing global reference sequences also showed a similar topology with that of the african tree, the tree was distributed into two major lineages a and b, with lineage b further diversifying into about four sub-lineages, while lineage a seemed to evolve into only two sublineages ( figure ) . the afrsarscov- strains were intermixed with the global sequences within both lineages, lineage b consisted mainly of strains from germany, england, italy and usa, intermixed with african strains; while lineage a consisted mainly of strains from south korea and china with a few african strains from senegal, ghana and drc. the result of the genotype analysis using the genotyping tool pangolin was largely in conformity with observed phylogenetic analysis. figure shows a summary of the lineage distribution of the isolates by country of origin using the pangolin genotyping tool. the complete distribution of the strains according to lineage and country is shown in supplementary table . from the analysis with pangolin, lineage b. was the most commonly encountered and the most widely distributed, consisting of sequences from seven countries, followed by lineage b. and genotype b. lineage a had positive sequences from six countries. majority of the sequences recorded high bootstrap values with over % of the sequences recording a bootstrap value of above %. this shows that the pangolin is a reliable tool with a broad scope of functions including a user friendly and interactive representation of phylogenetic clustering of the identified sub-lineages and lineages by means of graphical images of the trees generated using virtually all available sarcov- sequences available on gisaid platform as reference. the genotyping tool was recently introduced several reports have utilized it in predicting lineage assignments accurately (xaiveir et al, ) . the time to most recent common ancestor tmrca of the african sarscov- strains was december th (november th -december th ), while the tmrca of all the sequences under analysis was th october (july th -december th ). our tmrca was lower than a similar study which reported a tmrca of th october among global isolates including chinese isolates (li et al, ), but was slightly higher than another recent study investigating the evolutionary dynamics of the ongoing sarscov- epidemic in brazil which reported a tmrca of th february (xaiveir et al, ) . the epidemic history of the ongoing outbreak was investigated using the bayesian skyline plot bsp. the bsp showed a steady increase in viral population as the outbreak progressed under the study period ( figure ). this observation is expected as viral sequence population is supposed to increase as the infection spreads. a major limitation was the rather small number of sequences analyzed and very short study duration; therefore our results may not reflect the exact viral population dynamic of the outbreak in africa. the afrsarscov- sequences were analyzed for the d -g mutation within the s subunit of the spike protein, which has been reported to contribute to increased transmissibility of sarscov- (korber et al, ) . figure shows a representative amino acid alignment of selected afr sarscov- sequences along with reference sequences of btcov ratg and pcov. our results revealed high prevalence of d -g mutation among afrsarscov- with / ( . %). the mutation was recorded in isolates from all african countries analyzed in this study, supplementary figure . prior to this report the d -g spike mutation was found predominantly in europe accompanied by high number of cases and significant mortality rate (pachetti et al, ; korber et al, b) . the introduction of this strain in africa is quite worrisome, considering the population densities of most african cities and the poor state of public health infrastructure to support medical intervention of symptomatic sarscov- cases. although more evidence is still required to determine the extent of the effect of the d -g mutation on the virulence properties of the virus, current evidence from in vitro studies seem to support the hypothesis of increased transmissibility of this variant of the virus (korber et al, ; hu et al, ) . in conclusion we have reported the genetic diversity and evolutionary history of sarscov- isolated in africa during the early outbreak period. our findings have identified diverse sublineages of sarscov- currently circulating among africans. we also identified high prevalence of the d -g spike protein variant of the virus capable of rapid transmission in all countries sampled. a major limitation was the relatively low amount of sequence submission available in gisaid database compared with those of other regions such as europe and asia. we advocate for upscale of next generation sequencing ngs capacity for whole genome sequencing of sarcov- samples across the african continent to support surveillance and control effort in africa. figure . amino acid alignment of the partial s gene sequences covering amino acid positions to , of selected afrsarscov isolates along with reference sequences of closely related pcov and bat ratg . the red shaded region represents the receptor binding domain; the blue shaded box represents the d -g motive, while the empty red box represents the polybasic cleavage site bordering the s /s sub-unit. figure . amino acid alignment of the partial s gene sequences covering amino acid positions to , of selected afrsarscov isolates along with reference sequences of closely related pcov and bat ratg . the red shaded region represents the receptor binding domain; the blue shaded box represents the d -g motive, while the empty red box represents the polybasic cleavage site bordering the s /s sub-unit. novel coronavirus ( -ncov ) situation report - , who africa/second case of ncov confirmed in africa coronavirus disease (covid- ) a pneumonia outbreak associated with a new coronavirus of probable bat origin covid- situation world wide as at th may a familial cluster of pneumonia associated with the novel coronavirus indicating person-to-person transmission: a study of a family cluster commentary: middle east respiratory syndrome coronavirus (mers-cov): announcement of the coronavirus study group isolation of a novel coronavirus from a man with pneumonia in saudi arabia severe acute respiratory syndrome coronavirus-like virus in chinese horseshoe bats genomic characterisation and epidemiology of novel coronavirus: implications for virus origins and receptor binding inhibition of sars-cov- infections in engineered human tissues using clinical-grade soluble human ace epidemiological and genetic analysis of severe acute respiratory syndrome chapter , coronaviridea emerging sars-cov- mutation hot spots include a novel rna-dependent-rna polymerase variant spike mutation pipeline reveals the emergence of a more transmissible form of sars-cov- a dynamic nomenclature proposal for sars-cov- to assist genomic epidemiology the d g mutation of sars-cov- spike protein enhances viral infectivity anddecreases neutralization sensitivity to individual convalescent sera tracking changes in sars-cov- spike: evidence that d g increases infectivity of the covid- virus probable pangolin origin of sars-cov- associated with the covid- identifying sars-cov- related coronaviruses in malayan pangolins rdp : detection and analysis of recombination patterns in virus genomes. virus evolution exploring the temporal structure of heterochronous sequences using tempest (formerly path-o-gen) bayesian phylogenetic and phylodynamic data integration using beast . . virus evolution dating of the human-ape splitting by a molecular clock of mitochondrial dna codon usage bias and recombination events for neuraminidase and hemagglutinin genes in chinese isolates of influenza a virus subtype h n . archives of virology evolutionary history, potential intermediate animal host, and cross species analysis of sarscov the species severe acute respiratory syndrome-related virus: classifying -ncov and naming it sarscov- the ongoing covid- epidemic in minas gerais, brazil: insights from epidemiological data and sars-cov- whole genome sequencing maximum likelihood phylogenetic estimation from dna sequences with variable rates over sites: approximate methods insights into evolution and recombination of pandemic sarscov- using saudi arabian sequences. biorxiv preprint figure . boot scan plot of complete genome sequences of afrsarscov- sequences analysed with the rdp recombination software. the legend shows the identity of the sequences scanned within the plot; the light blue bars indicate the portions of the genome with recombinant signals in reference to the major and minor recombinant parent sequences. key: cord- -z u d ec authors: shears, p. title: poverty and infection in the developing world: healthcare-related infections and infection control in the tropics date: - - journal: j hosp infect doi: . /j.jhin. . . sha: doc_id: cord_uid: z u d ec in many hospitals serving the poorest communities of africa and other parts of the developing world, infection control activities are limited by poor infrastructure, overcrowding, inadequate hygiene and water supply, poorly functioning laboratory services and a shortage of trained staff. hospital transmission of communicable diseases, a high prevalence of human immunodeficiency virus and multidrug-resistant tuberculosis, lack of resources for isolation and disinfection, and widespread antimicrobial resistance create major risks for healthcare-related infections. few data exist on the prevalence or impact of these infections in such environments. there is a need for interventions to reduce the burden of healthcare-related infections in the tropics and to set up effective surveillance programmes to determine their impact. both the global (g ) international development summit of and the united nations millennium development goals (mdgs) have committed major resources to alleviating poverty and poor health in the developing world over the next decade. targeting resources specifically to infection control in low-resource settings must be a part of this effort, if the wider aims of the mdgs to improve healthcare are to be achieved. summary in many hospitals serving the poorest communities of africa and other parts of the developing world, infection control activities are limited by poor infrastructure, overcrowding, inadequate hygiene and water supply, poorly functioning laboratory services and a shortage of trained staff. hospital transmission of communicable diseases, a high prevalence of human immunodeficiency virus and multidrug-resistant tuberculosis, lack of resources for isolation and disinfection, and widespread antimicrobial resistance create major risks for healthcare-related infections. few data exist on the prevalence or impact of these infections in such environments. there is a need for interventions to reduce the burden of healthcare-related infections in the tropics and to set up effective surveillance programmes to determine their impact. both the global (g ) international development summit of and the united nations millennium development goals (mdgs) have committed major resources to alleviating poverty and poor health in the developing world over the next decade. targeting resources specifically to infection control in lowresource settings must be a part of this effort, if the wider aims of the mdgs to improve healthcare are to be achieved. ª the hospital infection society. published by elsevier ltd. all rights reserved. 'the widening gap between the developed countries and the poorest communities of the developing world has become a central issue of our time.' this is not a quote from the global (g ) international development summit of , or from international awareness events such as the live aid and live concerts e it is the opening sentence of the pearson report of , a commission set up by the world bank to investigate why, after a decade of 'development', little impact had been achieved for the poorest communities of the tropics. , in , the alma ata conference of the world health organization (who) stated as its aim 'health for all by '. a visit to a village affected by human immunodeficiency virus (hiv) and malaria in tropical africa, to a shanty town in south asia with inadequate water and sanitation ( figure ), or to a displaced community in southern somalia suffering from cholera, dysentery and rift valley fever, suggest that these aims are yet to be fulfilled. many medical journals are currently devoting part of their current issues to the themes of poverty and infection in the developing world, in recognition of the commitments made by the g summit and the united nations (un) millenium development goals (mdgs) to improve maternal healthcare, reduce childhood mortality and the impact of human immunodeficiency virus (hiv)/ acquired immunodeficiency syndrome (aids), malaria and other communicable diseases. if g and the un mdgs are to be catalysts for change, it will be necessary to look beyond international conferences and mission statements and to concentrate on specific objectives that can be implemented in resource-poor settings. from the viewpoint of hospital infection control, the concern is how hospital and healthcarerelated infections affect poorer communities of the developing world, and what can be done to begin to make a contribution to reducing the associated morbidity and mortality. a visit to a sub-saharan african country, where i had been looking at laboratory services and hospital infection control, left two particular memories. the first is the overwhelming disadvantages faced by health workers surrounded by hiv/aids, multidrug-resistant tuberculosis, overcrowding and lack of resources for the most basic of hygiene activities. the second is the impossibility of knowing the magnitude of hospital-related infections and optimum treatment strategies without effective laboratory services. these comments would certainly have been equally appropriate or years ago. might be a turning point? with the current emphasis of governments and un agencies to focus again on poverty and health, there is an opportunity to move healthcare-related infections, and the support required in terms of laboratory development, education, hospital infrastructure, and appropriate professional training, into a focused agenda, rather than the 'cinderella' position that has until now been the case. the ebola virus outbreak in southern sudan in was a vivid reminder of the potential magnitude of hospital-acquired infection in tropical africa. on august , a student from nzara presented to the local district hospital at maridi in equatoria province, southern sudan, suffering from a severe febrile disease. he died a week later. over the next week, a nurse, a cleaner, and a hospital messenger became unwell, and then further medical and auxiliary staff. by the time a ministry of health/who team arrived in maridi approximately six weeks after the first case, one of the two doctors in the hospital had been infected and died, all six of the medical assistants had been infected and five had died, and twenty student nurses had died. further spread and deaths occurred until the impact of basic infection control strategies, involving gloves, gowns and masks for healthcare workers, and hygienic measures in dealing with body fluids and the deceased, brought the outbreak to an end. while the maridi ebola outbreak was an extreme case, it emphasised that the priorities for healthcare-associated infection control in the tropics, particularly away from tertiary or university hospitals in capital cities, cannot be a simple translation of expertise from the west. while limited systematic data exist on the overall patterns and prevalence of infection, experience from the field, and a review of available literature, indicate that the following are the major groups of infection control areas: since the outbreaks in sudan and zaire (now democratic republic of the congo, drc), nosocomial transmission of ebola virus has been reported in drc (kikwit), uganda, and probable cases in gabon and sudan. nosocomial transmission of other viral haemorrhagic fevers has included lassa fever in nigeria, and marburg haemorrhagic fever in angola. e prevention of transmission is difficult in resource-limited settings, with no total protective clothing or isolation facilities available. specific guidelines for control in district hospitals have been drawn up by who, and these cover issues including patient isolation, locally produced protective clothing, waste disposal, disinfectants, and community education. early diagnosis of the first cases, often in the community or peripheral health centres, is the mainstay of ensuring that preventive measures are initiated in a timely fashion and that transmission is kept to a minimum. if severe acute respiratory syndrome, pandemic influenza or h n avian flu were to become pathogens in these underresourced tropical areas, the pattern of the ebola outbreaks could be repeated. in any hospital infection control programme in much of africa, and large parts of asia and latin america, prevention of the spread of hiv, between patients, from patients to health workers, and from health workers to patients, is a priority. largely due to the un and who global aids programme, there is considerable literature and guidance available. at the level of the individual, poorly resourced hospital with limited reuseable equipment and disinfectants, hiv is a major concern for all health workers and local health education and support programmes have been shown to be effective. with the rise in hiv, there has been an increasing prevalence of tuberculosis, both in hiv-affected patients but also in the wider community, and in many areas an increasing prevalence of multidrug-resistant tuberculosis (mdrtb). this poses a risk for nosocomial transmission between patients, but particularly for health workers who will have direct contact, often with undiagnosed cases, and with less than adequate protective clothing. there are likely to be few rural hospitals in africa with a supply of pfr masks. the strict barrier precautions described by uk and centers for disease control and prevention (cdc) guidelines are unlikely to be practicable and workers dealing with these issues daily have developed more appropriate strategies. nosocomial spread of other communicable disease where hospital hygiene is limited, and wards are crowded, the risk of transmission of communicable disease is high. the source may be an inadequately isolated index case, relatives who are staying in the hospital to provide food and general care for patients, or contaminated food or water in the hospital. although from observation such transmission must occur, few such episodes have been recorded. nosocomial outbreaks of cholera have been published from tanzania and mozambique and these reports suggest that outbreaks of other faecal-oral infections, particularly shigellosis, typhoid and hepatitis a and e, must also occur. , other reported hospital communicable disease outbreaks have included measles and non-typhoidal salmonellae. , for communicable diseases in the tropics, the boundary between hospital and community infection is blurred. among relatives camping within the hospital compound, there may be a case of undiagnosed tuberculosis? is the infected person part of the community or part of the hospital? this distinction between public health and healthcare-related infection is particularly complex in the setting of refugee camps. , direct hospital acquired infections studies of surgical and other hospital-related infections have been published from several countries in africa, including kenya, nigeria, tanzania, ethiopia and burkina faso. e these studies show a similar pattern of pathogens that are seen globally; staphylococci, enterobacteriaceae and pseudomonas spp., with high levels of antimicrobial resistance and a high and somewhat arbitrary use of antimicrobials. the studies are necessarily selective e only those hospitals in which there is a functioning microbiology laboratory, and which have sufficient staff, can undertake such work. in addition, with limited laboratory facilities, only the more easily culturable bacteria may be isolated and the results may give only a partial picture of the true prevalence and antimicrobial resistance patterns of pathogens. in situations where more sophisticated microbiological studies have been undertaken in two particular non-western environments e the tsunami area of south east asia and repatriated combatants from afghanistan e unusual and multiply resistant isolates have been found. , occurrence of multi-resistant bacterial pathogens a common theme in all published studies of hospital infections in the tropics is the high prevalence of antimicrobial-resistant bacterial pathogens. this raises one of the major areas of concern. in terms of hygiene facilities, crowding and laboratory support, many hospitals in the tropics are like those of the 'pre-penicillin era', yet within them are the multi-resistant bacteria of the twenty-first century. data in many areas are limited or non-existent, but, where surveys have been done, meticillin-resistant staphylococcus aureus and extended-spectrum b-lactamase-producing and other multi-resistant gram-negative bacteria have been shown to be widely disseminated. e the problem is compounded as antimicrobials, including quinolones and third-generation cephalosporins, are available without prescription, many areas have no laboratory facilities to provide accurate susceptibility data, and, despite several past attempts, there are no functioning international resistance surveillance programmes. , hospital infrastructure and facilities the 'catalogue of disadvantage' for a rural district hospital in africa demonstrates the commitment of local staff in providing even the most basic services (figure ). the catalogue includes: poor building infrastructure, inadequate water supply, electricity for perhaps only a few hours a day, overcrowded wards with patients lying on the floor as well as on beds, lack of resources for cleaning the environment, beds or equipment, often an absence of soap, and remoteness from regional centres or the capital city. maridi, the hospital of the ebola outbreak in southern sudan, is km from khartoum, with a road link not possible for three months in the rainy season. this situation is compounded by civil strife in the democratic republic of congo, southern somalia or darfur, for example, where hospitals may have influxes of patients with both infected injuries and communicable diseases. , as patients with communicable diseases are admitted from crowded refugee camps, they may become the index cases for further spread within the hospital if infection control facilities are overstretched (figure ). there is no director of infection prevention and control in an african rural district hospital. nor is there usually a dedicated infection control nurse, almost certainly not a clinical microbiologist, and rarely clinicians with sufficient time to work with the laboratory staff. there have been developments in training personnel specifically to work in infection control in larger hospitals, those supported in some way by outside agencies, and in teaching hospitals in larger cities. most published work on training for infection control has been from south africa, with an understandable emphasis on hiv transmission, but many hospitals will have developed local, basic policies. the requirements to improve hospital infection control in the tropics have been considered in a number of valuable papers. e the key areas that have been identified include the following: e setting up national and regional infection control networks. many of these will only occur when there are the resources for major economic change and that is why it is necessary to consider poverty reduction, institutional as well as individual, rather than to focus on improving infection control as simply a 'health' or 'medical' problem. whether g or the mdgs for can achieve this poverty reduction remains to be seen. past experience of the pearson commission and health for all by suggests that targets alone, without addressing the fundamental causes of poverty or ill health, need to be handled with care. in the mean time, what can be done to assist the improvement of infection control in resource-poor settings? local health workers themselves are the most likely to achieve progress. the resources for hiv infection control that are part of the global aids programme represent one means for local improvement. the main who strategy to improve infection control internationally is the global patient safety challenge. this has involved many meetings and recommendations, but whether these will have a significant impact in resource-poor, tropical settings has yet to be seen. however, the initiative may give support to policy-makers in giving a priority to infection control. certainly, links that have been established between hospitals in the uk and individual hospitals in africa can provide muchneeded resources, can share expertise and provide training opportunities. the existence of the internet has in many ways revolutionised the ability of even remote hospitals to acquire information, to download who or cdc guidelines, to communicate with distant colleagues, and in some situations to be part of a telemedicine network. such initiatives include the raft network in francophone africa (réseau en afrique francophone pour la télémédicine) and the who health initiative for access to research information (hinari) programme. , if the aim of an internetlinked computer in every village in africa or asia or latin america, or at least in hospitals in those areas is to be achieved, there are practical issues of connectivity and band width that have to be faced. providing laptop computers without adequate connectivity and support will not be productive. efficient internet links will enable very real possibilities of support between hospitals in the uk and rural tropical hospitals. the absence of effective laboratory services at district hospital level is a major impediment to the long-term control of hospital-associated infections. unless the causative pathogens can be identified, and where appropriate the antimicrobial susceptibilities determined, there is a considerable risk that multiply resistant bacteria will become the dominant pathogens, with few antimicrobials available for treatment. within the mdgs, no specific mention is made of infection control or laboratories; without these, we cannot achieve the three specific health goals of: (i) improving maternal health, (ii) reducing child mortality and (iii) tackling aids, malaria and other communicable diseases. healthcare-associated infections have been near the top of the political agenda in the uk, resulting in increased funding and commitment for change. for the developing world the same priority is required if the aims of g and the mdgs are to be approached. the g and global health: what now? what next? partners in development: report of the commission on international development achieving the millennium development goals report of a who/international study team ebola outbreak in kikwit, democratic republic of the congo: discovery and control measures outbreak of ebola hemorrhagic fever uganda review of cases of lassa fever in nigeria: the high price of poor medical practice lessons from nosocomial haemorrhagic fever outbreaks centers for disease control and prevention and world health organisation. infection control for viral haemorrhagic fevers in the african health care setting the joint united nations programme on hiv/aids. project update self reported infection control practices and perceptions of hiv/aids risk amongst emergency department nurses in botswana tuberculosis infection among health care workers in kampala, uganda practical and affordable measures for the protection of health care workers from tuberculosis in low income countries hospital outbreaks of cholera transmitted through close person to person contact a hospital outbreak of cholera in maputo nosocomial outbreaks e a potential threat to the elimination of measles? nosocomial outbreak of neonatal salmonella enteritidis in a rural hospital in northern tanzania epidemiological assessment of health and nutrition of ethiopian refugees in emergency camps in sudan communicable diseases in complex emergencies: impact and challenges nosocomial infections at kenyatta national hospital intensive care unit in aerobic bacterial nosocomial infections in paediatric surgical patients at a tertiary health institution in lagos risk factors for surgical site infections in a tanzanian hospital: a challenge for the traditional national nosocomial infections surveillance system index wound infection in tikur anbessa hospital surgical department survey of nosocomial infection prevalence on the surgery department of the central national hospital of ouagadougou rare bacteria species found in wounds of tsunami patients. gram negative bacteria from patients seeking medical advice in stockholm after the tsunami catastrophe multidrug resistant acinetobacter extremity infections in soldiers first report of mrsa from hospitalised patients in sudan staphylococcus aureus bacteraemia in the dakar fann university hospital nasal carriage of meticillin resistant staphylococcus aureus among health care personnel in abidjan (cote d'ivoire) extended spectrum beta lactamases among gram negative bacteria of nosocomial origin from an intensive care unit of a tertiary health facility in tanzania occurrence of extended spectrum beta lactamase enzymes in clinical isolates of klebsiella species from harar region, eastern ethiopia surveillance of antimicrobial resistance at a tertiary hospital in tanzania surveillance of antimicrobial resistance: the whonet programme burden of injury during the complex emergency in northern uganda the disease profile of poverty: morbidity and mortality in northern uganda in the context of war, population displacement and hiv-aids south african health service must strengthen infection control measures infection control in africa south of the sahara nosocomial infections in developing countries: cost effective control and prevention risk of nosocomial infection in tropical africa countdown to : will the millenium development goal for child survival be met? clean care is safer care'; the global patient safety challenge the raft network: years of distance continuing medical education and teleconsultations over the internet in french speaking africa who's health internetwork access to research initiative (hinari) access to electronic health knowledge in five african countries: a descriptive study none declared. none. key: cord- - o hydg authors: odeyemi, festus ayotunde; adekunle, ibrahim ayoade; ogunbanjo, olakitan wahab; folorunso, jamiu bello; akinbolaji, thompson; olawoye, idowu bolade title: gauging the laboratory responses to coronavirus disease (covid‐ ) in africa date: - - journal: j public aff doi: . /pa. sha: doc_id: cord_uid: o hydg the rampaging effect of coronavirus disease (covid‐ ) in africa is huge and have impacted almost every area of life. across african states, there exist variations in the laboratory measures adopted, and these heterogeneous approaches, in turn, determines the successes or otherwise recorded. in this study, we assessed the various forms of laboratory responses to the containment, risk analyses, structures and features of covid‐ in high incidence african countries (nigeria, south africa, egypt, ghana, algeria, morocco, etc.) to aid better and efficient laboratory responses to the highly infectious diseases. the critical roles of laboratory testing cannot be overemphasised in the prevention and management of infectious diseases outbreak (bedford et al., ) . laboratory professionals play essential roles in diagnosis, epidemiologic surveillance and monitoring of patients with suspected and established cases of severe acute respiratory syndrome coronavirus (sars-cov- ) infection, which is the virus strain that causes coronavirus disease (covid- ; lippi & plebani, ) . the effort of the laboratory professionals and the country strategies in the containment, risk analysis, structures and features of the novel coronavirus deserves understudying for some reasons. for a disease condition that has been categorised as transmitting from human-tohuman, there is a greater need for quick detection and subsequent isolation in order to flatten the curve and reduce the strain on the medical facilities that are largely dilapidated in africa. in other climes, clustering analysis is an essential pre-requisite to epidemic management and care surveillance aimed at the efficacy of treatment procedures. by identifying the cluster or group of society that are most vulnerable and susceptible to viral loads induced by contagion with pathogens from the virus, further care and treatment procedure can be established. in recent findings, o, rhesus d positive (+) individuals are reported to have more excellent antibodies to resist infestation of coronavirus. by assessing the laboratory response to africa, this study aims to establish the depth of covid- growth and subsequent policy recommendations, particularly as it relates to easing lockdown directives in place in most africa countries. it informs the government and stakeholders restrictive measures and the desire to return to a healthy life. covid- is an infectious disease of the novel coronavirus. the covid- pandemic is the third eventful zoonotic coronavirus disease outbreak in years (mackenzie & smith, ) . (poon & peiris, ) . the current pandemic emerged in wuhan, china and has spread rapidly around the world (adnan, khan, kazmi, bashir, & siddique, ) with an estimated over million cases globally with , deaths, above . million cases in europe with around , deaths, over , cases in asia with around , deaths (who, a). we observed heterogeneous approaches in the laboratory responses across nations in africa. these variations in the laboratory responses of the containment of covid- were primarily to aid early detection of the virus for prompt isolation, management of the infected individuals, and prevention of community transmission or sporadic cases of the virus (loeffelholz & tang, ) . the laboratory response of this novel virus comprises of a collection of appropriate samples from patients who meet up with suspect case definitions (as contained in the who guidelines) and selection of accurate laboratory methods (who, b). the sars-cov- has been detected from a multifarious of upper and lower respiratory sources, including throat, nasopharyngeal, sputum, and so on (who, c) . a number of laboratory methods have been adopted in africa for covid- testing, and they include the molecular test method of nucleic acid amplification tests (naat), serological testing, and viral genome sequencing (abdullahi et al., ; loeffelholz & tang, ) . amid these global health challenges which have caused panorama of problems in global medical supply chains, african countries have no options than to result to indigenous (herbal solutions) ways of combatting the pandemic, although in line with international practices. in this study, an attempt is made to unravel the underlying testing procedures adopted by high incidence african nations (nigeria, south africa, egypt, ghana, morocco, algeria) with attendant efficacy relative to their population density. policy measures, particularly alternative approaches that could induce greater efficiency in the laboratory reactions to the growth curve of covid- , are discussed in the study. in figures and testing, which contained the laboratory techniques which are currently in use and the future ones they hope to adopt to increase access to testing (mlscn, ) . molecular method of reverse transcription polymerase chain reaction (rt-pcr) has been adopted as the gold standard for accurate testing of the pandemic in nigeria with minimum sensitivity and specificity of % each (mlscn, ) . in the rt-pcr method, a reverse transcriptase approach was employed to convert the rna template into a complementary dna (cdna) with subsequent use of the cdna as a template for exponential amplification using pcr (abdullahi et al., ; udugama et al., ) . in the rt-pcr procedure, we confirm the existence of sars-cov- in a patient when the assay is positive. it should be noted that a laboratory outcome showing negative findings does not entirely rule out the presence of coronavirus in a patient (mlscn, ) . by intuition, a negative laboratory finding premediated on a suspected patient implies that the viral density was well below the detection point. in other climes, an rt-pcr assay laboratory finding could show adverse outcomes if the infection has run its cause leading to viral clearance (mlscn, ). ncdc also developed a framework for incorporation of up to high throughput hiv molecular testing laboratories, which are capable of raising national capacity to a minimum of , tests per day (ncdc, a) . genexpert machines have also been slated for incorporation into the laboratory network with a capacity of further increasing national capacity to , tests per day (ncdc, b). serology testing helps to investigate the current pandemic and retrospective assessment of the extent of the outbreak. nigeria's ncdc plan to look into the relevance of this antigen and antibody tests in the future to understand the rate of infectivity of the virus in the country. however, this method is subject to validation by the medical laboratory science council of nigeria (mlscn) before it can be deployed for routine testing in nigeria (ncdc, ). mlscn specifies that the sensitivity and specificity of this method of the assay must not be less than % with rt-pcr as a standard before approval can be given for its complimentary usage with other molecular methods (mlscn, ). nigeria's laboratory capacity for covid- testing is being worked on to carry out million tests in the next months by the utilisation of the maximum capacity of various laboratories within its network to improve the nation's undesirable testing coverage among countries with over , cases across africa (ncdc, a). confirmed cases of covid- in south africa stand at , with mortalities as the time of writing ( th may ). a total of , tests has been done in all provinces of the country, but less than % of the south african population, which is over million (statistics south africa, ), has been covered in covid- testing (national department of health, ). testing coordination for the novel coronavirus in south africa is led by the national health laboratory service (nhls), which is the biggest diagnostic pathology service provider with roles of assisting the national and provincial health authorities in healthcare deliv- nhls has laboratories in nine provinces across south africa designated for coronavirus testing (nhls, ). nhls procured mobile sampling and testing units which were deployed f i g u r e african countries covid- cases nationwide to join testing sites and testing units already in place across the country. nhls is currently using the molecular method of rt-pcr for covid testing across its network of regional laboratories and mobile testing sites. south africa planned to deploy the mobile laboratories for rapid serological kits for population surveillance when they are available in the country (un, c) . national institute of communicable diseases (nicd) partnered with the south african national bioinformatics institute at the university of western cape to publish a complete genome sequence of sars-cov- isolated from a south african patient with coronavirus disease who had returned to south africa after travelling to italy (allam et al., ) . with this, south africa is on the verge of increasing her current , tests for covid- daily by six-folds (national department of health, ). egypt has recorded , covid- laboratory-confirmed cases and (hassany et al., ) . egypt's laboratory network includes laboratories with the plan to augment with another four and university hospital laboratories, which can increase national capacity to , in a total testing frame (who, d). algeria has recorded , confirmed cases of covid cases with deaths as of th may (who, a) having conducted tests on , samples, which constitute . % of the total population of over million (un, a) . laboratory response to covid- management in algeria is anchored by the institut pasteur algeria (ipa). the institut pasteur algeria (ipa) based out of capital algiers was testing samples from across the country (who, e). the institut pasteur algeria (ipa) also invited hospital laboratories with the equipment to get involved in screening for the virus to meet the demand for more tests (kezzal, ) . rt-pcr is the method of choice for testing for the sars cov virus in institut pasteur algeria (ipa) laboratory network (kezzal, ) . ipa laboratory network is being expanded to accommodate other annexes in oran, constantine and ouargla, which is capable of increasing the testing capacity to tests per day. testing with procurements of tens of thousands of reverse transcription-polymerase chain reaction (rt-pcr) kits (amuedo, ) . also, moroccan health authorities are planning to diversify its laboratory expertise by adopting a more straightforward diagnostic techniques for more comprehensive national coverage and expansion of the covid- laboratory network without the inclusion of private laboratories for the time being (kasraoui, ) . reverse transcriptionpolymerase chain reaction (rt-pcr) is the only method of analysis currently in use for covid- testing in the country. morocco is currently deploying all machinery to achieve , tests daily capacity to curb the spread of the virus in the arab peninsula (amuedo, ghana has also adopted the pooled testing algorithm for the rt- services, ). an effort is also in place to add regional and district tuberculosis gene expert laboratories, which will make each region have at least one testing centre for covid- screening (ghana news agency, ). despite the rampaging nature of coronavirus disease across the world, laboratory responses in africa's high incidence in figure , we reported the laboratory testing conducted in the six high incidence countries in africa based on indices in table following. the pictorial representation and the tabular information apparently reveals that in all high incidence countries in africa, less than % of the total population has been tested. the implications of this are many, and the consequences are immense (adekunle, onanuga, akinola & olakitan, ). a large number of the populace who could have been in contact with an infected person has not been detected. thus, scaling up the risk of community transmission that could eventually strain already dilapidated and inadequate health facilities in africa. it remains to be seen what the dimension of covid- spread could take in africa in the coming days and months. we reported test per population in all african countries in table . the authors give thanks to almighty. research universities multiple responses to covid- exploring the genetics, ecology of sars-cov- and climatic factors as possible control strategies against covid- modelling spatial variations of coronavirus disease covid- infection: origin, transmission, and characteristics of human coronaviruses whole genome sequence of the severe acute respiratory syndrome coronavirus sars-cov- obtained from a south african coronavirus disease covid patient morocco prepares to generalise covid- testing covid- : towards controlling of a pandemic covid- testing: tb gene experts labs being recalibrated estimation of covid- burden in egypt morocco to purchase , covid- rapid diagnostic test kits hospital laboratories must have adequate equipment to carry out tests the critical role of laboratory medicine during coronavirus disease (covid- ) and other viral outbreaks laboratory diagnosis of emerging human coronavirus infections -the state of the art covid- : a novel zoonotic disease caused by a coronavirus from china: what we know and what we don't. microbiology australia, ma national guidelines for the testing of sars-cov- infection national strategy to scale up access to coronavirus disease testing in nigeria covid- outbreak in nigeria situation report covid- outbreak in nigeria situation report emergence of a novel human coronavirus threatening human health efficient and practical sample pooling high throughput pcr diagnosis of covid- mid-year population estimates diagnosing covid- : the disease and tools for detection south africa's covid- testing capacity increased with new mobile lab units launched population total-nigeria. retrieved from https://data. worldbank.org/indicator/sp.pop.totl?locations=ng world health organisation. ( a). coronavirus disease (covid- ) situation report - coronavirus disease (covid- ) situation report - -technical-mission-to-egypt.html. world health organisation africa. ( e). algeria's main lab anchors covid- response covid- coronavirus pandemic the authors declare no potential conflict of interest. festus ayotunde odeyemi: conceived and designed the template for the study, wrote the paper. ibrahim a. adekunle: proofread and reworked the draft manuscript and vet the final paper, wrote the paper. olakitan wahab ogunbanjo: provided the spatial density distribution, interpretations, wrote the paper. jamiu bello folorunso, thompson akinbolaji and idowu b. olawoye: contributed materials, data, analysis tools, wrote the paper. the dataset(s) supporting the conclusions of this article is available in the key: cord- -wwabxlgr authors: venter, w d francois; nel, jeremy title: covid- : first data from africa date: - - journal: clin infect dis doi: . /cid/ciaa sha: doc_id: cord_uid: wwabxlgr nan m a n u s c r i p t africa is no stranger to infectious disease pandemics prior to sars-cov- , with recent major outbreaks spanning ebola to listeria and measles, and ongoing high background incidence of malaria, hiv and tb. most countries on the continent have severe health resource constraints, and the focus of many far richer countries hit by the sars-cov- epidemic -pcr-guided contact tracing to prevent spread, reliance on intensive-care and ventilation to deal with those who became severely ill -struck fear into african public health practitioners, health workers and the public, where sophisticated laboratory infrastructure and high-tech intensive care is often severely rationed ( ) . there was speculation that the continent may be relatively protected from the worst of covid by its younger population age structure (and fewer associated chronic comorbidities linked to covid- mortality), limited public transport, possibly greater circulating seasonal coronaviruses, and even antiretroviral therapy programs with anti-coronavirus activity. however, the possibility of hiv and tb being risk factors for covid severe events, both relatively unusual in the richer countries, could mean worse consequences in these populations ( ) . dr mary-anne davies presents important data from the western cape province, the epicenter for south africa's initial wave of infections, in this edition of cid ( ) . south africa as a major business and tourism hub was always likely to be one of the earliest african countries struck. initial severe lockdown measures were announced in march as the first internal cases in international travelers were reported. community seeding, especially in poorer and more densely populated communities, was delayed, but infections rapidly accelerated, and at the time of writing (late august ), the country has the fifth largest epidemic in the world ( ). this data is from an ongoing surveillance cohort that has previously generated rich data on disease patterns in the western cape, and currently continues to provide near real-time updates on the impact of pcr-confirmed sars-cov- on factors ranging from death to oxygen consumption within hospitals. data from electronic clinical information systems is synthesized with laboratory, pharmacy and administrative data, providing a powerful population level dataset. reported data from other national surveillance systems from across the country confirms much of davies' findings, although her dataset is remarkable in its detail. key strengths of the paper include a dataset covering over million healthcare users in the western cape province, and the use of both hospitalized and nonhospitalized cases and deaths davies' data shows similar mortality risk factors, including age, sex, diabetes (especially uncontrolled diabetes), hypertension and renal disease to other cohorts from richer countries. the data do provide vital information on south africa's other two continuing pandemics, with hiv and past or current tb all giving a roughly two-fold increased risk of death. earlier reports from europe and north america had not found a clear association with mortality, but they were limited by small sample sizes and selection biases. davies' cohort had about hiv positive patients with covid in it -about times more than all the other published case series combined to date ( ) . the dataset shows an association between hiv infection and increased mortality, with a hazard ratio after adjusting for age, sex and other comorbidities of . ( % ci . - . ). the possibility of residual confounding exists, but davies makes a plausible case for hiv being an independent risk factor for covid- -related death. interestingly, davies' dataset does suggest a higher mortality in hiv patients with virological failure and/or pre-covid cd counts under cells/µl compared with those who were virally suppressed, though there is substantial overlap in the confidence intervals, m a n u s c r i p t and may be confounded by social factors associated with non-adherence, as well as covid- mortality. whether antiretroviral therapy somehow mitigates covid outcomes has been widely speculated in the hiv scientific literature, with in-vitro data suggesting tenofovir has activity against coronaviruses ( ) . intriguingly, in the multivariate analysis davies found that patients receiving tenofovir disoproxil fumarate as part of their antiretroviral therapy saw a statistically significant reduction in mortality (ahr . , p= . ). this supports observational data from a spanish cohort that similarly suggested better outcomes for those on tenofovir-based antiretroviral therapy ( ) . however, extreme care should be taken interpreting the tenofovir data, as the association is at high risk of confounding and channeling bias. patients not on tenofovir in south africa are very likely to have underlying renal dysfunction, or be on second-line therapy, which is often again associated with coexisting social issues that may make them more vulnerable to covid- consequences. davies' data again makes a substantial addition to the covid- literature with respect to tuberculosis, a previously unreported topic. both active tuberculosis and past tuberculosis were associated with an elevated risk of mortality in the study, the latter presumably on the basis of residual lung damage and consequent poor respiratory reserve. what does this data mean for the rest of africa? we should be wary of extrapolating too far -africa has enormous diversity, and western cape demographics differ markedly even from the rest of south africa. however, the data is broadly similar to other regions in the world, and so the immediate priority for african health systems remains to rapidly and practically design systems to protect the elderly and those with chronic diseases or tb. for south africa, a sigh of relief at a relatively small increase in mortality in hiv and tb should be quickly tempered; diabetes was the second commonest cause of death in the country pre-covid- , and most patients in the country have poor glucose control, a major risk factor from davies' data ( ) . in addition, obesity is an independent risk factor for covid- mortality in other cohorts, and while this was not collected in this dataset (weight and height was not available for this cohort), the country's obesity epidemic, especially among women, is well documented. among hiv patients, again more among women, the large-scale introduction of dolutegravir in late may markedly aggravate obesity and covid mortality in the near- million south african patients on antiretrovirals ( ) . sadly, south africa has not learnt from other african countries and their epidemics ( ) . when ebola struck in west africa, the consequence of locking down the society and suspending vaccine programs extracted a mortality from measles alone estimated to be similar to that from ebola ( ) . initially lauded by the who for the speed and severity of covid- lockdown measures, the south african response became increasingly militarised (over people charged or incarcerated since the start), characterized by bizarre decisions on commerce, an incoherent pcr-based testing and tracing program, poor food support programs, corruption around procurement of personal protective equipment, and chaotic re-opening of schools, with a temporary decimation of vaccination and hiv and tb programs ( ) . the country will face years of continuing infectious and other diseases well beyond this sars-cov- era, that may well lead to a far greater mortality than covid- . low-and-middle income countries will need to ponder future pandemic responses that pit any current epidemic against hard-won public health interventions. m a n u s c r i p t finally, the value of having integrated surveillance systems such as the western cape's that can rapidly inform urgent public health responses in real time are demonstrated in this paper. african governments and donors should invest more in these systems, as a major adjunct to public health programs. fv reports research grants from bill and melinda gates foundation, unitaid, usaid, samrc, and viiv healthcare; drug donations from gilead sciences and viiv healthcare; and honoraria from gilead, viiv, mylan, merk, adcock-ingram, aspen, abbott, roche, and j&j, all outside the submitted work. j.n. has no potential conflicts to disclose. covid- : shining the light on africa tackling covid- : can the african continent play the long game? j glob health risk factors for covid- death in a population cohort study from the western cape province who coronavirus disease (covid- ) dashboard coinfection: case reports, retrospective cohorts and outcomes triphosphates of the two components in descovy and truvada are inhibitors of the sars-cov- polymerase (preprint) mortality and causes of death in south africa: findings from death notification weight gain and integrase inhibitors reduced vaccination and the risk of measles and other childhood infections post-ebola covid- lockdowns in low-and middle-income countries: success against covid- at the price of greater costs a c c e p t e d m a n u s c r i p t key: cord- - ibprszo authors: fitchett, jennifer m; swatton, deryn-anne title: exploring public awareness of the current and future malaria risk zones in south africa under climate change: a pilot study date: - - journal: int j biometeorol doi: . /s - - - sha: doc_id: cord_uid: ibprszo although only a small proportion of the landmass of south africa is classified as high risk for malaria, the country experiences on-going challenges relating to malaria outbreaks. climate change poses a growing threat to this already dire situation. while considerable effort has been placed in public health campaigns in the highest-risk regions, and national malaria maps are updated to account for changing climate, malaria cases have increased. this pilot study considers the sub-population of south africans who reside outside of the malaria area, yet have the means to travel into this high-risk region for vacation. through the lens of the governmental “abc of malaria prevention”, we explore this sub-population’s awareness of the current boundaries to the malaria area, perceptions of the future boundary under climate change, and their risk-taking behaviours relating to malaria transmission. findings reveal that although respondents self-report a high level of awareness regarding malaria, and their boundary maps reveal the broad pattern of risk distribution, their specifics on details are lacking. this includes over-estimating both the current and future boundaries, beyond the realms of climate-topographic possibility. despite over-estimating the region of malaria risk, the respondents reveal an alarming lack of caution when travelling to malaria areas. despite being indicated for high-risk malaria areas, the majority of respondents did not use chemoprophylaxis, and many relied on far less-effective measures. this may in part be due to respondents relying on information from friends and family, rather than medical or governmental advice. malaria is a dangerous and potentially fatal vector-borne disease caused by the plasmodium parasite, transmitted to humans through the bite of an infected female anopheles mosquito (cohuet et al. ; cella et al. ) . in , an estimated million cases of malaria were reported globally, similar to million cases for , with a death toll of , in and , in (alonso and noor ; who a,b) . the burden of malaria was disproportionately borne by developing nations, particularly in the african continent, which accounted for % and % of the malaria cases and deaths recorded in , respectively (alonso and noor ; who b) . in , in an effort to combat malaria, the world health organization launched the e- initiative in which it identified countries with the potential to eliminate malaria within their borders by the year (who ). south africa was one of those countries, with an additional local objective of elimination by (baker ) . however, in , south africa experienced a severe setback in achieving both objectives, reporting imported and , indigenous cases of malaria-the highest number of cases reported by any of the identified countries, and more than four times the number of indigenous cases reported in the country in (who ; maharaj et al. ; abiodun et al. ) . this increase in numbers was due to a range of factors, including an increase in rainfall, temperature, and humidity following an abnormally mild winter (baker ) . as a result, the world health organization has classed south africa as "off-track" and has made a number of recommendations as to how the country can steer itself back on course (who ) . among these are efforts to refine malaria risk maps, to improve public awareness, and to revisit malaria strategies (who ) . due to the unlikelihood of achieving malaria elimination within south africa by , the south african government has now adopted the self-mandated goal of zero malaria transmission by , which it announced in the malaria elimination strategic plan for south africa - (national department of health ). one of the primary objectives of the malaria elimination strategic plan is to "ensure that % of the population affected by malaria receives information and education communication messaging by " (national department of health : ). this objective speaks directly to the recommendations given by the world health organization (who ) . the national guidelines for the prevention of malaria in south africa comprise five key components which are summarized as the "abc" of malaria prevention, namely awareness and assessment of malaria risk, avoidance of mosquito bites, compliance with chemoprophylaxis when indicated, early detection of malaria disease, and effective treatment (ndoh a; baker ; schmidt a, b) . adding fuel to the fire, climate change is resulting in both an increase in the extent of the south african malaria risk area and the incidence of malaria transmission due to increases in temperature and changes in rainfall patterns (morris et al., ; abiodun et al., ) . the spatial distribution of malaria globally is strongly determined by climate (caminade et al. ; cella et al. ) . by , a % increase in the probability of malaria incidence is projected globally due to increases in temperature and changes in rainfall patterns (cella et al. ) . temperature has been found to affect both the extent of malaria areas and malaria transmission incidence across the african continent (eikenberry and gumel ) . for south africa, both temperature and rainfall have been found to affect the malaria rate, with a notable increase in cases following flood events induced by strong tropical storms (adeola et al. ; makinde and abiodun ) . a change in malaria area extent is documented in the frequent updating of the national department of health malaria risk maps for south africa (coetzee et al. ; morris et al. ) . mathematical models have been developed to explore the role of climate in malaria incidence and to aid in projecting future changes in malaria risk distribution, and the risk of transmission (cella et al. ; eikenberry and gumel ) . at a local scale, seasonal malaria forecast models are being developed for south africa (kim et al. ; landman et al. ) . the modelling of the climate impact on malaria distribution and incidence and projections for future incidence are valuable in developing public health policies, and in communication to the public. however, the increased incidence of malaria cases in south africa in recent years would suggest that effectiveness of the distribution of these maps, particularly with regular updates, remains limited. a range of studies relating to disparate diseases have revealed the importance of public awareness and understanding of disease risk in determining the precautionary measures that they will adopt (cf. erhardt and hobbs ; glik et al. ; goldman et al. ; young et al. seale et al. . the role of sources of information, and the level of frequency of communication regarding diseases, is key in the veracity of public awareness (young et al. ). this has been widely understood in south african malaria control efforts (blumberg et al. ) , with malaria risk maps for the public dating back to (coetzee et al. ) . however, the efforts in assessing communities' awareness and understanding of malaria risk have largely been limited to regions within the high-risk zone, due to resource scarcity (maartens et al. ; cox et al. ) . in line with the who ( ) recommendations, this pilot study seeks to expand on previous work to explore public understanding of the location of the contemporary high-risk malaria zone, the anticipated future expansion of the high-risk malaria zone under climate change, and public behaviour regarding malaria precaution and prophylaxis, among those who reside outside of the malaria risk area, but travel into the high-risk zone on vacation. the aim of this study is to develop a methodology to explore any disconnects between reported and demonstrated awareness and behaviour regarding malaria for gaps in understanding to be addressed more effectively through government intervention, and for targeted awareness campaigns to be developed. malaria can be found in each of south africa's neighbouring countries, barring lesotho, where the altitude and consequent colder temperatures make it inhospitable to the malariacarrying anopheles mosquito (blumberg et al. ) . within south africa itself, malaria is confined to the north-eastern reaches of the country, where it is endemic to three of south africa's nine provinces, namely limpopo, mpumalanga, and northern kwazulu-natal (maharaj et al. ; adeola et al. ; fig. ). according to the latest malaria risk map produced by the south african national department of health in december , areas of moderate risk (where chemoprophylaxis is indicated for all travellers from september to may) are concentrated along the border between south africa and mozambique and zimbabwe (fig. ) . these areas of moderate risk can be found in the mpumalanga municipality district of ehlanzeni and in limpopo in the mopani and vhembe municipality districts (fig. ). areas of low risk (where malaria is still present, but only non-drug preventative measures are indicated), however, extend as far west as limpopo's waterberg district and as far south as the umkhanyakude district in kwazulu-natal province ( fig. ). at present, the regions of highest malaria risk in south africa have relatively low population density, with no major cities and a large proportion of the high-risk area limited to the kruger national park. this does however pose a threat to both local and international tourists visiting the kruger national park and nearby game farms and nature reserves, who may be unaware of the risk levels within south africa. this research explores respondents' malaria awareness and self-reported behaviours. therefore, questionnaires were selected as the most appropriate instrument for data collection. types of questions ranged from multiple choice and likert scale questions to more open-ended, paragraphstyle questions (bird, ) . topics included respondents' demographics and travel histories, awareness and perception of malaria distribution and risk in southern africa, understanding of climate change, and attitudes towards malaria prophylaxis-both in terms of bite prevention and chemoprophylaxis. the closing question of the questionnaire required respondents to draw two lines, in different colours, on a map of southern africa: a blue line indicating where they understand the boundary of the present malaria risk zone to be located and a red line indicating where they think the boundary of the malaria risk zone will be located in years' time. the map was created using arcmap and displayed national and provincial borders, but contained no other information to avoid leading respondents. questionnaires were distributed in hard copy. respondents were identified through a combination of purposive and snowball sampling (bernard ) . to ensure a degree of standardization throughout the study sample for this initial pilot study, a target population was identified and a number of parameters were defined. in order to qualify for the study, respondents had to live within the gauteng province of south africa (currently not a malaria area), have at least an undergraduate university degree, and have travelled to a malaria risk area within southern africa within the last years for leisure purposes. this ensured that the data gathered were relevant and that all respondents were middle-to upper-class leisure tourists with financial means to access to a wide range of precautionary measures to avoid contracting malaria when travelling to malaria areas, and have a reasonable level of education and understanding of health risks. this sample is not intended to be representative of the population of south africa nor the gauteng province. rather, this subgroup is used to determine whether any issues in awareness, behaviour, or use of chemoprophylaxis may warrant further, more extensive investigation. ethics clearance was obtained from the university of the witwatersrand's human research ethics committee (non-medical) prior to entering the field (ethics clearance: gaes- - - ). given the target population and the minimum requirement of a completed undergraduate degree, no individuals under the age of were approached. finally, it is important to note that this research dealt exclusively with the data collected from the completed questionnaires and no medical records were accessed or used in this study. responses to closed-ended questions from the questionnaire were analyzed using descriptive statistics, while responses to open-ended questions underwent thematic coding and content analysis (bernard ) . the hand-drawn maps generated in the last question of the questionnaire were digitized and layered over one another to create composite maps showing areas of consensus/disagreement among respondents. this particular methodology was adapted from a study conducted by roffe et al. ( ) which mapped agreement among experts regarding rainfall seasonality in south africa. finally, the composite maps were compared to the official malaria risk map created by the south african national department of health in to assess their accuracy. a total of questionnaires were completed. of these, six questionnaires were excluded from analysis as the respondents did not fall within the defined parameters of the target population, in most instances as a result of not having visited a malaria area within the past years. four maps were deemed unusable as the lines drawn could not be digitized as a contiguous vector line and/or what was drawn could not be meaningfully interpreted. neither the excluded questionnaires nor the unusable maps were used in the creation of the composite maps. in the cases where maps were unusable, but respondents met the selection criteria, the questionnaire responses were captured and included in descriptive statistics and content analysis. while the intention was to obtain a relatively even distribution of respondents across age groups, due to difficulty accessing people within the older age brackets who met the selection criteria (specifically the criterion relating to tertiary education), a skewed age distribution resulted. of the respondents who submitted admissible questionnaires, the highest number (n = ) fell into the - age group. the remaining age groups were comparatively poorly represented, with the - and - age categories comprising five respondents each, and the older age groups ( - and +) each representing one-eighth (n = ) of the sample group. the majority (n = ) of respondents held only a bachelor's degree, while nine held honours degrees (a postgraduate qualification in south africa), one held a master's degree, and two held a phd. the remaining three respondents selected "other" qualifications, in two cases citing university qualifications in the medical or nursing field. this last group, however, cannot be read independently, as respondents with medical or similar degrees may equally have chosen the equivalent qualification to their degree-type from the list provided. the overall spread of tertiary qualifications indicates a well-educated subset of the population. it is worth noting that the various levels of education were spread across the age groups, and it was not simply a case of the older the respondent, the higher their qualification. for example, all respondents in the to year-old age group (n = ) reported only holding a bachelor's degree, whereas of the two respondents in possession of a phd, one fell into the - age group and the other into the + age group. this distribution is important, as it means that age and highest qualification are not collinear, but are rather independent factors each of which could be possible determinants of perception, risk assessment, and behaviour. we reiterate that the results of this small group cannot be read as representative of any sub-population, but rather the variety of results indicates a heterogeneity which reveals the importance of further, extensive, investigation. the questionnaire included a mapping exercise in which respondents were required to draw a line across a map of southern africa indicating where they understood the boundary of the present malaria risk zone to be located. in this question, respondents were instructed to include the entirety of the southern african region in the drawing of their malaria zone boundaries. however, eight of the respondents who created usable maps only drew lines across south africa. therefore, for the sake of consistency, only the portion of the drawn risk areas which fell within the borders of south africa was digitized. overall, the composite map created from all usable maps reveals a fairly high degree of awareness among respondents regarding the general location of malaria risk areas in south africa (fig. ) . darker blue areas, which show a higher degree of consensus among respondents, can be found in the north-east of the country, concentrated along the border between south africa and mozambique and zimbabwe (fig. ) . the majority of respondents have also included eswatini, northern kwazulu-natal, and more westerly parts of limpopo and mpumalanga in their assessment of malaria risk areas (fig. ) . this is consistent with the official south african malaria risk map produced by the national department of health in (fig. ) . however, the composite map also shows that many respondents believe that the malaria risk zone extends further west and south than is indicated on the governmental malaria risk map, with one respondent including the entirety of south africa in their rendering of the malaria risk zone. another respondent included the west coast of the northern cape, and many drew lines which either dissected or encompassed lesotho. this indicates a poor awareness of the government-communicated malaria risk maps of south africa, and moreover a limited understanding of the relationship between climate and malaria distribution, or at least limited awareness of the climate in these areas. in addition to instructing respondents to map their understanding of malaria risk areas in southern africa, the study also sought to assess the accuracy of respondents' selfreported awareness. respondents were asked whether, prior to taking the questionnaire, they were aware of malaria risk areas in the region. of the respondents, the vast majority (n = ) indicated that they were aware, while one respondent answered that they were not, and one did not respond. the remaining five respondents stated that they had limited awareness. with such a high degree of self-reported awareness, one would expect more accurate maps than were captured (fig. ) . respondents were aware of the general location of malaria risk areas, but could not reliably recount their extent. this indicates a general, and perhaps intuitive, awareness among respondents, but little true, informed awareness. interestingly, despite the majority of respondents indicating that they were aware of malaria risk zones, only six felt that there was enough information available to the general public regarding malaria distribution, precautions to take against contracting malaria, and how to identify and treat malaria. respondents who indicated that they were either aware of malaria risk areas prior to taking the questionnaire, or who indicated that they had some degree of awareness, were then asked to stipulate where they accessed this information. importantly, government or official publications/websites were the least consulted (n = ) source of information, while family, friends, or colleagues were the most frequently cited (n = ) sources (fig. ) . many of the respondents who selected "other" indicated that they had accessed their information at school, through the media/news, or had been advised by a medical professional (fig. ) . this could explain the lack of convergence between the government malaria map and those drawn by respondents. respondents were asked to rate the level of risk posed by malaria to south african citizens on a likert scale of to , with being low risk, being moderate risk, and being high risk. respondents most commonly (n = ) rated the level of risk as moderate (as can be seen by the single peak), with a slight bias towards higher risk (fig. ) . approximately three quarters (n = ) of respondents indicated that they had taken precautions against contracting malaria during their most recent trip to a malaria risk area in southern africa, while eight reported taking no precautions and one declined to answer the question. among the eight respondents who did not take precautions, the most commonly reported reasons were issues around risk assessment and lack of awareness. interestingly, two respondents indicated that their risk assessment was informed by the advice of locals, with respondent stating: i heard from people who live there that it was not a risk. similarly, respondent reported: been travelling to mozam[bique] for a few years and nothing happened. locals there also say they moved there and lived there for yearsnothing happened. a further two respondents stated that they were not aware that their destination was a malaria area before departing, and only found out once they returned. for one of these respondents, their destination was mozambique, a country classified as high risk in its totality. of the eight respondents who did not take precautions, only one quarter (n = ) indicated that they would change their behaviour and employ preventative measures on future trips. for the respondents who did take precautions, insect repellent was the most popular (n = ) preventative measure used (fig. ) . insect repellent, along with travelling outside of the rainy season, were the two most common precautions used in isolation, each with four respondents. only respondents used more than one method simultaneously. both respondents who selected the "other" option (fig. ) cited wearing long trousers and long-sleeved shirts in the evenings. while this would minimize the chances of mosquito bites to the arms and legs, and is effective in reducing the irritation of mosquito bites, the efficacy of clothing worn in the evenings as a method of significantly reducing the risk of contracting malaria remains uncertain (nakazawa et al. ; del prete et al. ) . long clothing worn throughout the day and night (baker, ) , and impregnated with insecticides (shellvarajah et al. ) , shows more promise, but this is not the approach indicated by the respondents. in this context, wearing long clothing only in the evenings is less effective than these alternatives, and their combined use with chemoprophylaxis (baker, ) . of the respondents who did take precautions against contracting malaria, five indicated that they would only do so again on their next trip to a malaria area if it was in the rainy season/summer. one respondent (respondent ) stated that they would not take any precautions, as they believed that: risk is not significantly high when travelling for short time periods this is a misconception, and studies of imported cases of malaria in europe and the middle east resulting from tourists' short trips to southern africa underscore this (see ben-ami et al. ; baranova et al. ) . these erroneous sentiments are particularly concerning given the large proportion of respondents who obtain information on malaria risk from family, friends, and colleagues instead of government publications (fig. ) . chemoprophylaxis is indicated for travel to all malaria areas considered moderate to high risk (schmidt, a, b) . these areas can be found in all of south africa's neighbouring countries, and within south africa in limpopo and mpumalanga (fig. ) . of the respondents who submitted usable questionnaires, almost all (n = ) indicated that they had travelled to malaria areas considered moderate or high risk. however, only one-third (n = ) of these respondents reported that they had taken antimalarial drugs on their most recent trip to one of the areas. even more alarmingly, of the respondents who had only travelled locally within south africa, to either limpopo or mpumalanga, only one-fifth (n = ) had taken chemoprophylaxis. this indicates a very low level of compliance with chemoprophylaxis in indicated settings, which is particularly concerning among a sample group who have the level of education and socio-economic status to enable compliance. climate change awareness and impact on future malaria risk zones all respondents indicated they understood what was meant by the term "climate change". respondents were then asked whether they thought climate change would impact malaria risk and distribution in southern africa, and if so, how. almost all respondents (n = ) indicated that they believed that climate change would increase malaria risk in southern africa, while the remaining four indicated that they did not know. no respondents answered that climate change would decrease malaria risk in southern africa or have no effect. respondents also drew a line across indicating where they thought the boundary of the malaria risk zone would be located in years' time. the composite map produced shows a far greater extent of malaria distribution than the composite map produced for current malaria risk (fig. ) . respondents indicated that they believed the malaria risk zone would extend further west and south into the country's interior, with the majority of respondents including large parts of limpopo and mpumalanga (fig. ) . this is consistent with the trend shown by the malaria risk maps produced by the government over the past century (coetzee et al. ; morris et al. ). the composite map indicates that respondents are cognizant of the increased risk of malaria projected for south africa in future decades, and significantly aware of the spatial patterns projected for the increase in the distribution of malaria risk. however, many respondents indicated an expansion of the malaria risk zone years from now which is geographically impossible, and exceeds the model outputs for malaria projection. notably, the expansion into the mountainous highlands of lesotho, the temperate climates of the southern coast of south africa, and the arid west coast of south africa are unlikely in the next years, if ever. these exaggerated perceptions of future risk, when not realized, may result in further complacency among respondents, particularly as relates to chemoprophylaxis. efficacy of the "abc" of malaria prevention in increasing public awareness the first tenet of the "abc" of malaria prevention relates to public awareness and the accurate assessment of malaria risk (ndoh a). this emphasis on awareness and perception is further echoed in the malaria elimination strategic plan for south africa - which aims to "ensure that % of the population affected by malaria receives information education communication messaging by " (national department of health : ). when respondents were surveyed, it was found that while there is a relatively high level of self-reported awareness regarding the general location of malaria risk areas in south africa, the majority of respondents were unable to reliably recount the extent of these areas. the behaviour of the population regarding malaria avoidance similarly was not in line with governmental advice and scientifically determined best practice. this indicates that at least a proportion of the south african population are unaware of the precise location of the malaria risk zone, and their perceived awareness is incongruous with the demonstrated awareness or reality. this is consistent with prior research in kwazulu-natal (maartens et al. ). further research is needed to determine whether this lack of awareness in a statistically representative population amounts to greater than %. within the existing medium to high-risk malaria zones (fig. ) , targeted governmental efforts at increasing awareness have been conducted actively at the community level, rather than solely passively through websites and risk maps in clinics which is the case for the respondent group from gauteng province (govere et al. ; cox et al. ) . for example, members of communities in the vhembe district in largely rural limpopo province who have been involved in the governmental malaria awareness programme (map) are found to have a . times greater knowledge on malaria transmission risk and . times higher awareness of prevention methods than those who had not been involved in these programmes (cox et al. ) . the perceptions of residents living in current malaria risk zones regarding the boundary of these zones would be a valuable avenue of future research. it is notable that among the respondents, government and official publications/websites were the least consulted sources of information, while family, friends, and/or colleagues were the most frequently consulted. as only six of the respondents believed that there was enough information available to the general public regarding malaria distribution, precautions to take against contracting malaria, and how to identify and treat malaria, this suggests a weakness in policy's strategies regarding modes of delivery of malaria education and highlights the possibility of the transmission of misinformation from person to person. while targeted initiatives in high-risk malaria regions are of course imperative in addressing the epicentre of the problem, the significant tourism sector in south africa, and the large proportion of people migrating back to their homes in malaria areas during holiday periods, does necessitate a broader geographic reach of these activities (blumberg et al. ; raman et al. ) . following discrete epidemics, this has been facilitated through tourism operators distributing information (maartens et al. ), but this would not address tourists staying in less formalized accommodation. the incorrect perceptions that malaria risk is not high when travelling for short periods (see ben-ami et al. ; baranova et al. ) , or can be mitigated through wearing long clothing only in the evenings, reveal the dangers of relying on non-official sources of information when planning precautionary measures to avoid malaria (raman et al. ). these respondents appear to have misunderstood that while the longer the visit to a malaria-prone region, the greater the risk, short stays do not carry no or low risk; likewise, while long clothing is advised at all times, wearing it for short periods is not sufficient in preventing the risk of bites or malaria (baker ) . this misconception appears relatively unique to this study; an investigation into foreign tourists' awareness of malaria while at or tambo international airport in gauteng indicated that medical practitioners and travel agents were by far the greatest source of information on malaria (waner et al. ) . the low rates of use of chemoprophylaxis among respondents warrant particular concern. for persons with no immunity to malaria, which includes our study sample group, but also much of south africa (fig. ) , chemoprophylaxis is indicated for the period of travel (freedman ; morris et al. ; schmidt, a, b) . doxycycline, atovaquone-proguanil, and mefloquine are currently recommended for use in south africa, with an efficacy of~ % when taken correctly (baker, ; schmidt, a, b) . the former two drugs have recently been downscheduled to s , allowing for pharmacists to dispense these without prescription (baker ) , thus increasing access and reducing costs slightly through eliminating the necessity for a consultation with a doctor . while there are medical uncertainties regarding the safety of certain antimalarials, particularly mefloquine, in terms of neuropsychiatric adverse effects fig. overlaid map of respondents' perceptions of future malaria risk boundaries in south africa in years' time (n = ) (freedman ; baker ) , these were not cited by the respondents as the reasons for non-compliance. more minor side effects, by contrast, were indicated as a reason for non-compliance, a theme which is echoed in studies of international tourists (waner et al. ) . a lack of awareness of the need for chemoprophylaxis, due to poor knowledge of the malaria areas, or to a lack of understanding of the severity of the risk may explain some of respondents not having used this precaution (leggat et al. ; maartens et al. ). however, as the majority of respondents over-estimated the expanse of the south african malaria risk area, this seems unlikely. a significant barrier to the use of chemoprophylaxis is the cost (leggat et al. ; ukpe et al. ) . even among more affluent travellers, the large cost of the antimalarial drugs serves as disincentive, particularly for trips of short duration or outside of the rainfall season (leggat et al. ) . greater medical aid coverage for antimalarials and a reduction in the cost of the drugs would be important in addressing this component. despite a relatively low sample size, this study reveals notable gaps in the awareness and risk-taking decision-making among persons who travel into malaria areas, who are resident in a country in which some but not all areas carry a high malaria risk (blumberg et al. ) . this is distinct to the majority of studies for south africa which either assess the awareness and behaviour of international tourists visiting malaria areas (cf. waner et al. ; freedman ) , or of local communities within high-risk malaria areas (cf. govere et al. ; morris et al. ; cox et al. ). this group is important because they do not receive the same level of travel advice as international tourists (waner et al. ), yet frequently travel into and through high-and medium-risk malaria areas (maartens et al. ), often through self-booking (de jager and ezeuduji ). the greatest awareness among local tourists has been found to directly follow major malaria epidemics, which is coupled with booking cancellations for accommodation establishments in malaria-prone regions (maartens et al. ) . the changes in the methods of malaria risk mapping, and the extent of the risk areas in these maps, particularly under climate change, further yield much of the information that regular travellers might have outdated (coetzee et al. ; morris et al. ) . policy improvements therefore need to be aware of both the limitations in knowledge and shortfalls in risk-aversion behaviour, and the potential for these factors to worsen under climate change. for effective policy adaptation, however, a much larger sample group with greater socioeconomic heterogeneity would be valuable. while the regularly shifting extent of the malaria risk zone is posited as one of the reasons for a poor awareness among respondents, it could be argued that under climate change, an even more frequent updating and reporting of risk may be beneficial. seasonal malaria forecasts are being produced for south africa by local researchers (kim et al. ; landman et al. ) , which could be presented to the public biannually to refine malaria prevention behaviour. frequent and standardized government publication of season-specific information would potentially result in a greater reliance on these resources over word-of-mouth based on travel which occurred less recently. the avenues of the dissemination are also an important consideration in effective communication of malaria information (blumberg et al. ). finally, this study was conducted during , prior to the covid- pandemic (gilbert et al. ) . this pandemic has, both globally and in south africa, revealed an unprecedented public engagement with disease epidemiology and risk-aversion, and the extensive use of social media in government communication (gao et al. ) . south africa has been ranked second in the world for the most reliable covid- information, due in part to the conditions of the national lockdown which prohibit the dissemination of fake news (ryklief ) . announcements directly from the national institute for communicable diseases and the minister of health, each of which distributed both to the press and via social media, have allowed the public to follow both case numbers and the state of knowledge on precautionary measures. this provides valuable insight into methods of effective communication with the national populace involving disease prevention (young et al. ). this pilot study explores the self-reported risk behaviour and awareness of malaria area boundaries among south africans who are resident outside of the high-risk malaria area. while respondents in this study claim to have a high level of awareness relating to malaria, the vast majority overestimate the spatial extent of both the current and future malaria areas and do not practice the indicated precautionary measures when visiting regions that they report to understand to be malaria-prone. part of this disjunct between their understanding of the malaria areas and their behaviour appears to relate to their sources of information, with a considerable reliance on friends and family, rather than official sources. while this pilot study involves a small target group who cannot be considered representative of any broader sub-population, we provide insight as to avenues for more comprehensive research, and a methodology which could be used. this more extensive research would provide valuable insight to improve policy and intervention. investigating the resurgence of malaria prevalence in south africa between and : a scoping review rainfall trends and malaria occurrences in limpopo province, south africa the global fight against malaria is at crossroads malaria prophylaxis -can we conquer the 'mighty' parasite? sa imported plasmodium vivax malaria in the russian federation from western sub-saharan africa malaria in travelers returning from short organized tours to 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prevention recommendations for risk groups visiting sub-saharan africa: a survey of european expert opinion and international recommendations malaria: the unwanted souvenir case management of malaria: treatment and chemoprophylaxis malaria protection measures used by in-flight travelers to south african game parks update on the e- initiative of malaria-eliminating countries: report and country briefs. world health organization, geneva who ( a) fact sheet about malaria medicine in the popular press: the influence of the media on perceptions of disease publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations key: cord- -om xc bs authors: berhan, yifru title: will africa be devastated by covid- as many predicted? perspective and prospective date: - - journal: ethiop j health sci doi: . /ejhs.v i . sha: doc_id: cord_uid: om xc bs nan since the novel coronavirus disease (covid- or sars cov- infection) has been declared as pandemic, several mathematicians and statisticians have developed different trajectory curves for africa, with the assumption that the virus can have an exponential pattern of transmission. according to economic commission for africa, k- . million covid- related deaths may occur in africa ( ) . a large body of literature and international media have also predicted that africa is going to be flooded, much higher than europe and the united states of america (usa). for ethiopia alone, some estimated - million with full mitigation and - million people without mitigation actions can get infected. when the author of this perspective sees such an easy to do, but hard to conceive figures, he likes to join the closed loop forum and express what his thought is. as of st april , close to k confirmed cases and + deaths are reported from african countries, while the global figure climbs to more than two and a half million and individual countries in the west are reporting the highest ever cases ( k- k+) and deaths ( k- k+) in less than three months ( ) . the hardest hit countries being the most capable to tackle such kind of infectious outbreak, and the extremely contagious nature of this virus is the puzzle and unprecedented phenomenon. virtually, countries of the globe do not look like they are ordered by the burden of this infection; the actual magnitude of case and death load in each looks as if they are ordered by their economic power and financial muscle. the bottom line is that this infection has been exponentially spreading, and becoming highly prevalent and fatal in the richest countries. that is not yet happening in countries within the tropical climate zone. will it be like that in the weeks or months to come is the core question of this perspective. some may argue that the developed countries testing capacity is what has inflated the case load, citing usa and germany as an example. yes, the high test uptake has helped the developed countries to identify as many cases as possible in a short period of time. rising in the last three months in the western countries of the temperate climate zone was not only case load, but also the staggering mortality figure and the severely morbid cases (hospitalization for pneumonia, icu care, dialysis, and blood transfusion), which are the two key measurements to show how severe the actual magnitude of the covid- is. a very important argument is; had the covid- transmission been as contagious as in europe and usa, by this time, every health facility in africa and other tropical countries could have been flooded with severely ill patients and deaths. but, that is not the case in any of african and tropical countries. the other side of the coin is; the overwhelming cases and deaths experienced in europe and usa is despite the fact that they started to report covid- confirmed cases almost same time or later than many of the countries in the tropical climate zone. up to now, the proportion of mortality in the majority of covid- reporting countries is in the lower range (< %) ( ) . the relatively high case fatality rates among countries with larger case load are reported from europe and one north african country (algeria). this observation may lead to pose questions on the predilection of the transmission and the survival of the virus particle outside the human body at different climate zone, as discussed below. on blanket view of the global distribution of the infection, relatively low case and death load is observed across africa, south middle east, south and southeast asia and latin america. since the beginning, the epicenter has moved from east to west along the temperate climate zone, and causes incomparably massive casualties. even in africa, the relatively hardest hit countries are still outside the tropical zone (algeria, egypt, morocco and south africa). countries in the tropical zone of asia and latin america, with relatively high case load, are not yet as hot spot as western countries in the temperate zone, despite the proportional duration of exposure; the cumulative number of deaths is incomparably low. the mathematical modeling result for the stated period using hypothetical numbers and the reported data from several tropical countries is far apart. brazil looks an exception, probably due to the rainy season or high tourist flow just around the outbreak. further, this is despite the fact that some african countries has started reporting covid- cases even earlier than some western countries with high case load. many authors have underscored the high mobility of the global population for the rapid spread of covid- in hot spot areas. but, the number of cases in many of the african countries is large enough to result in exponential transmission of the virus and be able to make hot spot. age and sex strata are some of the factors determining the prognosis, but not that much strong to justify the exponential transmission. hereunder, some more critical appraisal is presented. what can we learn from history to upkeep the above argument? with our limited knowledge, what history tells us may be in line with what we are observing the covid- pandemic at this juncture. as read from chronicles of influenza and other coronaviruses pandemics, the biology of sars cov- may have something to do with the climate to have exponential or restricted rate of transmission. it is not debatable that sars cov- is the seventh well known new coronavirus that infects humans (after sars-cov, mers-cov, hku , nl , oc and e) ( ). sars-cov and mers-cov are also new coronaviruses detected in humans in and , respectively, and are highly fatal ( ) . the mean global case fatality rates of sars cov- , sars cov and mers cov are %, % and %, respectively ( , ) . the last four coronaviruses usually cause mild upper respiratory tract infection, with the exception of oc , which once had caused an outbreak of severe pneumonia in france ( ) . like sars cov- , sars cov originated in china (guandong province), and was subsequently able to disseminate to europe and america, almost similar with the current trend. sars cov has become pandemic by reaching to countries in different continents, while the epicenter was in hong kong, with a total , infections and fatalities in a year period globally ( ). asian and european countries are the ones which are still sporadically reporting sars cov infection. the dissemination of sars cov to countries in the tropical zone along the globe, however, was minimal or none at all. another important milestone that consolidates the origin of the previous and current sars is the emergence of another new coronavirus in (named sads cov) from china near the origin of sars cov, which killed k piglets ( ) . the point is; the spread of mers cov and sars cov was predominantly in asia and europe. probing the history of influenza pandemics and the tropical epidemics can also give some clue on the likelihood distribution and proportion of cases and deaths of the current pandemic. since the time of hippocrates ( - bc), infectious disease pandemics had ravaged millions of human lives. some of the attributed etiologies for the outbreaks had international and regional propensity. yersinia pestis, which caused the 'black death' of - million people and the typhus fever which killed more than million in europe alone during the second world war are bacterial etiology, and were not having continental or national boundary. neisseria meningitides (the one causing meningitis outbreak along the meningitis belt), malaria, yellow fever, cholera, shigellosis, dengue fever are still common causes of outbreaks in the tropical climate zone. seasonal influenza outbreaks due to h n , h n and h n have been predominantly occurring in the northern hemisphere. the implication is that geographical and climate change may influence the microorganisms' survival outside the human body, and may determine the incubation period of the pathogen in the human body. influenza outbreaks occurred in europe and usa during cold and low humid weather (usually starting in winter and subsiding in spring), while meningitis and cholera outbreaks occurred in the tropics during hot weather and rainy season (usually preceding flood), respectively. although there is a long list of highly catastrophic influenza pandemics at different period of human history, it is worth mentioning those in the late th , early and second half of the th century and early in this century. among others, like the current pandemic, the 'russian flu'/h n ( - ) and 'hong kong flu' pandemics/h n ( ) ( ) ( ) which each killed one to four million people, and 'asian flu' pandemic/h n ( ) ( ) which killed million people originated from asia and massively spread to europe and america. 'spanish flu'/h n ( ) ( ) ( ) , which originated from spain, and killed - million people spread globally. another 'russian flu' pandemic/h n erupted in - and killed around k people worldwide ( ) . an important observation was that, like the currently observed covid- pandemic, the morbidity and mortality of the aforementioned influenza outbreaks were not that much spreading and killing outside the temperate zone, at least in africa. the first 'russian flu', for instance, reached in northern african countries, including egypt and algeria, but the case load and mortality were not as high as the european countries. in england alone, more than , people died of 'russian flu' in just one year. the 'asian flu' pandemic had also reached to many parts of africa, but was not highly catastrophic as it was in the northern hemisphere. the spanish flu was a bit exceptionally highly fatal in many parts of the world. it was estimated that about % of africans died. even then, in south africa (temperate zone) the estimated mortality ( k) was -fold higher than ethiopia ( k- k), which is somehow in line with the current pandemic ( ) . as a continuation of the old pandemics, the seasonal outbreaks and casualties of influenza in europe and usa are still devastating. according to the centers for disease control and prevention (cdc) of usa report, the - influenza outbreak killed k people in the usa alone, which was higher than the influenza related deaths ( k) in - season ( ) . the global estimate of deaths due to seasonal influenza was between k- k ( ). most of these deaths due to seasonal influenza occur in north asia, europe and north america. the swine flu pandemic that originated from mexico was the third h n influenza pandemic ( - ) that resulted in about k- k fatalities predominantly in north and south america, west europe, south and southeast asia, and australia ( ) . interestingly, among african countries, only egypt, algeria and south africa were part of the swine flu pandemic. the who annual estimate of mortality due to seasonal influenza is also a quarter to half a million. the bottom line is that, with the exception of the spanish flu, neither of the influenza pandemics seriously affected the african continent. the purpose of citing the above mortality figures is to show that there are infectious disease conditions which follow seasonal changes and are not proportionally distributed across the globe. the common causes of infectious outbreaks in the tropics and temperate zone are not same. otherwise, the influenza viruses and coronaviruses are biologically, pathogenically and epidemiologically completely different. what is probably in-common in the two groups is their potential to cause pneumonia and ability to expose to secondary bacterial infection. from previous coronavirus outbreaks (sars cov, mers cov) and influenza outbreaks as a proxy, one may extrapolate that the tropical zone may not be hit by covid- as hard as the temperate zone. the explosive nature of the covid- spread to every corner of the six continents, however, may make it incomparable in all parameters with the previous coronavirus and influenza outbreaks. notwithstanding this thought, the already observed rate of spread in the tropics is not as skyrocketing as the temperate zone, despite the virus lands almost two months back in many countries. in other words, the cases and deaths will likely increase, but not with flooding nature as seen in the temperate zone. as noted earlier, the number of confirmed cases may be underestimated due to lack of adequate testing. however, the seriously ill and death rates cannot be underestimated. let alone the covid- like outbreak, we know how many hospitals are overwhelmed when there is an outbreak of smaller scale. therefore, the severe morbidity and mortality indicators so far reported in the two zones have shown a remarkable disparity. overall, the cumulative cases and deaths will as well increase in africa, and it may even last longer than other types of pandemics, but the chance of exponential increment looks less likely. as sars cov, covid- is likely to be endemic in asia, europe and north america. among others, the very crowded day and night social life and the poor personal and environmental hygiene in this zone can be thought as creating a very conducive environment for the spread of covid- and any other communicable diseases. the high prevalence of malnutrition, malaria, tuberculosis, stress and non-communicable diseases (including diabetes and hypertension) may also make the majority of the people at higher risk for death. it is probably with this background why many are predicting the worst in africa. there is also a different assumption that the majority of african people and many more in the tropics are already exposed to several viral and bacterial infections (the justification for the planned bcg trial), which could help them to have a herd immunity to be protected from closely related pathogens. however, this theory may not be that much valid as the observed case fatality rate among covid- infected persons is not different from other parts of the world. if that is not the case, why the european or the american type of cases flooding into hospitals and overwhelming deaths are not yet observed in africa, in particular, and other countries in the tropics? one may argue that the carriers of this virus are still few in the respective countries. as the international travel of the people in the region is relatively limited, yes, that is partly true. however, it is also hard to accept that many of the first carriers of the virus in asia, europe and usa had a chance to travel to china/wuhan and around; quite significant number of community transmission was noted in europe and usa. it is also not wise to think that the number of the first carriers of this virus was too few to transmit the virus in africa as the transmission is presumed to have an exponential pattern ( for , then for , for and the like). nigeria (the first most densely populated african country with highly mobile urban population) reported the first case on february th , but its case load and deaths after nearly two months are and , respectively ( ). the second most densely populated african country and owner of the famous ethiopian airlines (ethiopia), which has been flying to international destinations till march th / at which time restriction was made to countries, has reported its first case about five weeks back; so far, has cases and deaths. egypt (the third most densely populated african country with large tourist flow before the outbreak and large number of its citizens working in europe) reported the first case one week earlier than italy, but the magnitude of cases and deaths are totally incomparable (italy's deaths are nearly times of egypt). the case load curves of many african countries are also waxing and waning type; a steady type of increment is not yet observed in the last - months, which is against with an exponential spread. this may not be solely explained by the preventive measures implemented, as there were several inconsistencies and breaches in many parts of africa. some also argue that the absence of community transmission is what has contributed to the low case load in africa and elsewhere with few cases. it is true that the majority of the transmissions occur in the community in europe and usa. however, it is still difficult to take it as a major reason for the low case load in several countries after reporting their respective first case nearly two months back, and with limited containing and mitigating actions. if we take ethiopia as an example, the wisdom of the author is that the covid- was imported probably several weeks before the quarantine was initiated for those who were coming from abroad. ethiopian airlines have been flying to more than countries in the world (including china at destinations). therefore, as the very recently confirmed case reports showed, the assumption is that the virus carriers are already within the community, and probably in many other african countries too. the recently reported eight cases in ethiopia came from the community with no contact history. the majority (> %) of the reported cases had an incubation period for more than two weeks, which is in contrast to the experience in the temperate zone. in literature, with few exceptions ( - days), the incubation period is less than two weeks. this is probably another research area on the impact of the climate on the multiplication of the virus in the human body and its survival outside the human body. although it is too early to deduce, the author's assumption is that africa and many of other countries in the tropical zone are less vulnerable to coronavirus and influenza virus infections, primarily because of the weather condition. until proved otherwise, this is probably because of the lower survival of the coronaviruses and influenza viruses in the external environment here in the tropics, whereby the humid weather condition is probably hostile to the virus to live outside the human body, thereby having a limited chance of proliferation and transmission from one person to another one unless it gets access as early as possible it is out. this hypothesis is going to be tested soon, at least for sars cov- . in , chan and colleagues reported that sars cov viability was rapidly lost (> log ) at higher temperatures and higher relative humidity ( ) . thus, in europe, usa and north asia, in particular, sars cov and sars cov- may live longer in the cold seasons outside the human body and be able to proliferate fast in the human body and infect as many people as possible. furthermore, in europe, sars cov- is reported as staying viable up to -day outside the human body. had this been the case here in africa and other places in the tropics, by this time, the covid- related admissions to hospital and deaths could have been overwhelming. with this regard, ethiopia and many african countries may as well benefit from ultraviolet radiation (uvr) b exposure. it is well proven fact that ozone depletion, prolonged sunlight exposure, higher altitude and latitude increase the uvr b exposure, of which ethiopia specifically has double advantage to be protected from covid- like epidemics (high altitude and prolonged sun light exposure). living organisms in general and microorganisms in particular are at higher risk for uvr b effect. uvr b is known to kill viruses by chemically modifying their genetic material (dna and rna viruses). during rainy or cloudy season, %- % of uvr b type is blocked, which may be one of the possible reasons for low incidence of covid- in the african region at this dry moment ( , ) . although it is unlikely to be the reason for all, one cannot ignore the timely actions of many of the african governments' role in implementing many of the preventive measures, including lockdown in a few countries. in many places, the public response to the call was also appreciable. here in the ethiopian capital, contact tracing, handwashing and preparations with available resource for the worst ahead are very impressive and commendable. streets are not that much crowded with pedestrians, and traffic jams have significantly decreased, which all have probably played some role in reducing the exposure. here and there handwashing service and practice was looking as the campaign is active, but could not be long-lasting in many places. what is likely to happen next? in the author's opinion, the case load is very likely to keep on increasing in all parts of africa with a bit higher than the current pace; particularly, if the complacence of the people grows along with the slow increment of the cases and the deaths, the risk of transmission of this virus may be a bit higher than the current trend. whatever the risk of transmission is, the cumulative figure is very unlikely to be in several millions as many predicted. the argument is that since the majority of the african population lives in scattered rural area, with the current awareness and the weather condition as described above, the risk of a large area spread in short a while is less likely. the expectation is that, before the spread of this virus reaches a larger scale, the two-three waves of the outbreak will be over. then after, sporadic cases will keep on emerging until the season is favorable for the virus's spread. similar spread and trend is expected in the majority of tropical countries as learnt from the previous pandemics. if that is not the case, this virus will not have a pattern similar to other infectious outbreaks (ascending, flattening and descending pattern). if the latter is true, africa will not be an exception; years long outbreak can occur elsewhere and the destiny will be unpredictable. the experience in the last three months, however, has shown that covid- outbreak is almost similar with previous pandemics; some countries like china and south korea are already entertaining the second wave after coming from apex to close to the baseline. therefore, the first scenario is; like many of other viral infections, those infected with covid- will develop humoral immunity and be protected from reinfection. as the majority of the population becomes immune (herd immunity) in due course, the chance of outbreak and the incidence rate will be less and less. the coming generation as well will be exposed in their earlier age and similarly develop the herd immunity. the possibility of developing a vaccine is within the domain of this assumption. the second scenario is reinfection. naturally, the majority of viral infections do not recur (with exception of those integrating their genome to the human genome, like hiv, human papilloma virus). covid- antigen, however, may not stimulate the human immune system to develop antibody against reinfection. this is much worrying as it may herald the difficulty to develop vaccine. researchers are soon to rule in or rule out whether the first or the second scenario is true. anecdotal evidence from china and south korea shows the possibility of reinfection, but that needs to be verified whether it is reinfection, reactivation or false positive result of the earlier test. african government and health stakeholders should not develop complacence with the slow rate of increment or reduction from recorded apex. apart from the seasonal nature, the character of infectious outbreaks is having two-three waves of mass infection; the latter waves are usually severe, for which complacence takes the major share. as the rainy and cold seasons are coming along the equator, second and third waves may be harder than before. seriously ill patients in hundreds to thousands are not manageable in an african setting. therefore, the already in action preventive interventions have to be maintained or strengthened till this outbreak is declared over (particularly contact tracing, avoiding or minimizing physical contact, hand washing, social distancing and universal mask use when exposure to other persons or patients is inevitable). the lockdown for africa, in particular, is a very controversial and challenging action. the author's opinion is that, as far as the social distancing and other preventive actions are in place, the lockdown action is not a wise decision for africa. the living style in the village and at the household level is already congested type; it is not uncommon to find dozens of people living and sleeping in a room. if lockdown is implemented, it should be complemented by mass testing, which is not economically and technically feasible for africa. therefore, phase by phase, the workforce has to resume the daily activities with stringent application of physical distancing and universal mask use. then after, students may be allowed to attend class on shift base (may be odd/even number on a day) with good advice and in-school close monitoring of the physical distancing. otherwise, the economic and social devastating effect of this virus to the african continent in general and poor countries in particular may not be tolerable and easily reversible. it may even result in social unrest and political crisis. therefore, we should not further delay the resumption of economically rate limiting sectors. if things go significantly in the wrong direction, preventive actions can be retightened as many countries are doing. in the author's opinion, whatever the consequence of this pandemic is in africa or elsewhere, it is another turning point in human history after the spanish flu and the second world war, by bringing about an extraordinary change in the political, economic and social landscape across the globe. from social interaction, international connectedness and travel perspective, i do not think that i am wrong if i say that covid- has dramatically changed the so called "world is a village" to 'world is an individual'. the economic crisis described by many, as the deep recession looming, may also hit hard africa and other low income countries with fragile economy. beyond controlling the outbreak, the big lesson for the world is to get ahead better prepared to manage such scale of outbreaks, and to make a significant paradigm shift in resourcing future researches to prevent and treat infectious outbreaks. for decades, communicable diseases are left to low income countries (particularly to sub saharan africa) with limited effort to develop vaccines and antimicrobials in resource rich countries. in short, the lesson acquired from covid- pandemic is expected to be the legacy for the generation to come. specific to africa, it is not arguable that covid- is a practical test that has clearly shown how much the health facilities are scarce and ill-equipped to handle such scale of public health emergency. when nations in africa are aware of that the expected covid- caseload is projected to be in several hundred thousand at a time, they also realized that available hospital beds in each big town are only a few hundred or less. similarly, the available health facilities and the health force to provide intensive care to critically ill patients are either non-existent or rudimentary. it is ahead a very disturbing experience for many of them. as an example of status indicator, the two countries with large population size (nigeria and ethiopia) are each able to test < , individuals in nearly two months. some african countries reported zero, , and the like number of ventilators at the national level while the demand is in thousands. this is in contrast to the first and second world where the testing and the basic life support capacity is extraordinary. in one of his briefings, his excellency andrew cuomo, the new york state governor requested the federal government to supply k ventilators while he has k at hand. the author is not sure whether the nations in africa in total have this number of ventilators. it is, therefore, covid- is a learning curve for african governments in the tropical zone to revise their health policy and get better prepared for similar or larger outbreaks in the years to come. covid- is not only a deep wake up click, but also a great 'opportunity' to mobilize the human force and financial resource to catch up in a short period of time with affordable cost. around two decades back ( ), african leaders signed the abuja declaration, which was stated as african countries should allocate % of their annual budget for health services ( ). in practice, however, the majority could not make it even %. that is why the health system and health facilities in africa remained crippled despite the staggering case load in every referral hospital. as a result, african countries are enforced to export the financially capable patients (including leaders) to middle east and asia with a yearly increasing number that has exploited the country's scarce resource. in the era of covid- , however, no way, nowhere to go. this is another reality, what makes covid- a breathtaking phenomenon. neither the economic nor the military power enables the abler to escape this invisible disease by traveling somewhere else. invariably, the covid- victim or susceptible individuals worldwide are getting help only from the nearby hospitals. luckily, the hospitals and treatment centers in these poor countries are not yet overwhelmed by covid- cases. if the worst comes (cases flooding like the europe and usa), there is an extremely low chance of getting medical care in africa. whether we like it or not, it will be a natural death and survival ('survival of the fittest'), like in the time of the old pandemics. african vips and well to do's will not be an exception. it is from this bad experience, what african leaders and every one of us need to take a big lesson to get prepared ahead for the worst to come (taking covid- as 'a blessing in disguise'). in general, covid- is another 'red flag' for humankind. in other words, the recent 'red flag' for humankind is the emergence of four highly fatal coronavirus strains (sars cov, mers cov, sads cov and now sars cov- ) in less than two decades with extremely fast global dissemination of sars cov- in three months and the lack of treatment or vaccine for either. related to this, the sporadically exploding highly fatal viral hemorrhagic fevers in the tropical zone (like ebola and marburg viruses) with on and off migration to other countries and again with no treatment or vaccine are a previously well noted 'red flag' for humankind. above all, the emergence of four new coronaviruses as a human pathogen in the first quarter of the st century is a 'red flag' for the emergence of another new coronavirus in the years to come, whose effect and destiny cannot be predicted. could the climate change have an influence in the mutation of these new coronaviruses and probably many more is not yet well substantiated. overall, the earlier appearance of the third generation of diseases implies that the human battle with the emerging viruses and bacteria will be tougher than before. covid- in africa: protecting lives and economies a novel coronavirus from patients with pneumonia in china clarivate analytics solution. diseases briefing: coronaviruses. . accessed on an outbreak of coronavirus oc respiratory infection in normandy, france fatal swine acute diarrhoea syndrome caused by an hku -related coronavirus of bat origin reviewing the history of pandemic influenza: understanding patterns of emergence and transmission. pathogens are we prepared for the next pandemic? estimated influenza illnesses, medical visits, hospitalizations, and deaths and estimated influenza illnesses, medical visits, hospitalizations, and deaths averted by vaccination in the united states influenza vaccines: ummet needs and recent developments the effects of temperature and relative humidity on the viability of the sars coronavirus ultraviolet radiation: how it affects life on earth abuja declaration on hiv/aids, tuberculosis and other related infectious diseases sars = severe acute respiratory syndrome mers = middle east respiratory syndrome sads = swine acute diarrhea syndrome key: cord- -xc jaw authors: lembo, tiziana; hampson, katie; kaare, magai t.; ernest, eblate; knobel, darryn; kazwala, rudovick r.; haydon, daniel t.; cleaveland, sarah title: the feasibility of canine rabies elimination in africa: dispelling doubts with data date: - - journal: plos negl trop dis doi: . /journal.pntd. sha: doc_id: cord_uid: xc jaw background: canine rabies causes many thousands of human deaths every year in africa, and continues to increase throughout much of the continent. methodology/principal findings: this paper identifies four common reasons given for the lack of effective canine rabies control in africa: (a) a low priority given for disease control as a result of lack of awareness of the rabies burden; (b) epidemiological constraints such as uncertainties about the required levels of vaccination coverage and the possibility of sustained cycles of infection in wildlife; (c) operational constraints including accessibility of dogs for vaccination and insufficient knowledge of dog population sizes for planning of vaccination campaigns; and (d) limited resources for implementation of rabies surveillance and control. we address each of these issues in turn, presenting data from field studies and modelling approaches used in tanzania, including burden of disease evaluations, detailed epidemiological studies, operational data from vaccination campaigns in different demographic and ecological settings, and economic analyses of the cost-effectiveness of dog vaccination for human rabies prevention. conclusions/significance: we conclude that there are no insurmountable problems to canine rabies control in most of africa; that elimination of canine rabies is epidemiologically and practically feasible through mass vaccination of domestic dogs; and that domestic dog vaccination provides a cost-effective approach to the prevention and elimination of human rabies deaths. rabies is a viral zoonosis caused by negative-stranded rna viruses from the lyssavirus genus. genetic variants of the genotype lyssavirus (the cause of classical rabies) are maintained in different parts of the world by different reservoir hosts within 'host-adaptive landscapes' [ ] . although rabies can infect and be transmitted by a wide range of mammals, reservoirs comprise only mammalian species within the orders carnivora (e.g. dogs, raccoons, skunks, foxes, jackals) and chiroptera (bats). from the perspective of human rabies, the vast majority of human cases (. %) result from the bites of rabid domestic dogs [ ] and occur in regions where domestic dogs are the principal maintenance host [ ] . over the past three decades, there have been marked differences in efforts to control canine rabies. recent successes have been demonstrated in many parts of central and south america, where canine rabies has been brought under control through large-scale, synchronized mass dog vaccination campaigns [ ] . as a result, not only has dog rabies declined, but human rabies deaths have also been eliminated, or cases remain highly localized [ ] . the contrast with the situation in africa and asia is striking; here, the incidence of dog rabies and human rabies deaths continue to escalate, and new outbreaks have been occurring in areas previously free of the disease (e.g. the islands of flores and bali in indonesia - [ ] ; http://wwwn.cdc.gov/travel/ contentrabiesbaliindonesia .aspx). in this paper, we identify four major reasons commonly given for the lack of effective domestic dog rabies control including ( ) low prioritisation, ( ) epidemiological constraints, ( ) operational constraints and ( ) lack of resources (table ) , focussing on the situation in africa. we address each of these issues in turn, using outputs from modelling approaches and data from field studies to demonstrate that there are no insurmountable logistic, practical, epidemiological, ecological or economic obstacles. as a result, we conclude that the elimination of canine rabies is a feasible objective for much of africa and there should be no reasons for further delay in preventing the unnecessary tragedy of human rabies deaths. this paper compiles previously published data (see references below) and additional analyses of those data, but we present a brief summary of the data collection methods below. hospital records of animal-bite injuries compiled from northwest tanzania were used as primary data sources. these data informed a probability decision tree model for a national disease burden evaluation [ ] , which has since been adapted for global estimates of human rabies deaths and disability-adjusted life years (dalys) lost due to rabies [ ] , a standardized measure for assessing disease burden [ , ] . hospital records were also used to initiate contact tracing studies [ ] [ ] [ ] , whereby bite-victims were interviewed to obtain more detail on the source and severity of exposure and actions taken, allowing subsequent interviews with other affected individuals (not documented in hospital records) including owners of implicated animals. statistical techniques applied to these data for estimating epidemiological parameters and inferring transmission links are described elsewhere [ , ] . rabies monitoring operations including passive and active surveillance involving veterinarians, village livestock field officers, paravets, rangers and scientists were used to collect samples from carcasses (domestic dogs and wildlife whenever found), which were subsequently tested and viral isolates were sequenced [ , [ ] [ ] [ ] [ ] , with results being used to inform estimates of rabies-recognition probabilities [ ] and for phylogenetic analyses [ , ] . operational research on domestic dog vaccination strategies was carried out in a variety of settings [ , ] . household interviews were also used for socio-economic surveys and to evaluate human:domestic elimination of canine rabies has been achieved in some parts of the world, but the disease still kills many thousands of people each year in africa. here we counter common arguments given for the lack of effective canine rabies control in africa presenting detailed data from a range of settings. we conclude that ( ) rabies substantially affects public and animal health sectors, hence regional and national priorities for control ought to be higher, ( ) for practical purposes domestic dogs are the sole maintenance hosts and main source of infection for humans throughout most of africa and asia and sufficient levels of vaccination coverage in domestic dog populations should lead to elimination of canine rabies in most areas, ( ) the vast majority of domestic dog populations across sub-saharan africa are accessible for vaccination with community sensitization being of paramount importance for the success of these programs, ( ) improved local capacity in rabies surveillance and diagnostics will help evaluate the impact of control and elimination efforts, and ( ) sustainable resources for effective dog vaccination campaigns are likely to be available through the development of intersectoral financing schemes involving both medical and veterinary sectors. dog ratios, levels of vaccination coverage achieved and reasons for not bringing animals to vaccination stations [ , ] . the study was approved by the tanzania commission for science and technology with ethical review from the national institute for medical research (nimr). this retrospective study involved collection of interview data only, without clinical intervention or sampling, therefore we considered that informed verbal consent was appropriate and this was approved by nimr. permission to conduct interviews was obtained from district officials, village and sub-village leaders in all study locations. at each household visited, the head of the household was informed about the purpose of the study and interviews were conducted with verbal consent from both the head of the household and the bite victim (documented in a spreadsheet). approval for animal work was obtained from the institutional animal care and use committee (iacuc permit # a ). (a) there is not enough evidence to define rabies control as a priority a principal factor contributing to a low prioritization of rabies control has been the lack of information about the burden and impact of the disease [ , ] . data on human rabies deaths, submitted from ministries of health to the world health organization (who), are published in the annual world surveys of rabies and through the who rabnet site (www.who.int/ rabies/rabnet/en). for the who african region (afro) comprising countries, these surveys report an average of human deaths per year between and . it is therefore unsurprising that for national and international policy-makers, rabies pails into insignificance in comparison with other major disease problems. this perceived lack of significance of human rabies is reflected in the absence of any mention of rabies in either of the two published global burden of disease surveys [ , ] , which assessed more than major diseases. these surveys adopted the metric of the daly which is widely used as the principal tool for providing consistent, comparative information on disease burden for policy-making. until recently no estimates of the daly burden were available for rabies. official data on human rabies deaths submitted to who from africa are widely recognized to greatly under-estimate the true incidence of disease. the reasons for this are manifold: ( ) rabies victims are often too ill to travel to hospital or die before arrival, ( ) families recognize the futility of medical treatment for rabies, ( ) patients are considered to be the victims of bewitchment rather than disease, ( ) clinically recognized cases at hospitals may go unreported to central authorities, and ( ) misdiagnosis is not uncommon. the problems of misdiagnosis were highlighted by a study of childhood encephalitis in malawi, in which / ( . %) cases initially diagnosed as cerebral malaria were confirmed as rabies through post-mortem tests [ ] . several recent studies have contributed information that consistently demonstrates that the burden of canine rabies is not insubstantial. human rabies deaths. estimates of human rabies cases from modeling approaches, using the incidence of dog-bite injuries and availability of rabies post-exposure prophylaxis (pep), indicate that incidence in africa is about times higher than officially reported, with , , deaths in africa each year [ , ] . consistent figures have subsequently been generated from detailed contact-tracing data: in rural tanzanian communities with sporadic availability of pep (a typical scenario in developing countries), human rabies deaths occur at an incidence of , - cases/ , /year (equivalent to - , deaths per year for tanzania) [ ] . similarly, a multi-centric study from india reported , human rabies deaths per year [ ] , consistent with model outputs of , deaths for india [ ] . a crude comparison of annual human deaths for a range of zoonotic diseases is shown in figure (top). while diseases such as severe acute respiratory syndrome (sars), rift valley fever and highly pathogenic avian influenza cause major concerns as a result of pandemic potential and economic losses, these figures provide a salutary reminder of the recurrent annual mortality of rabies and other neglected zoonoses, such as leishmaniasis and human african trypanosomiasis (hat). decision-tree models applied to data from east africa and globally indicate that the daly burden for rabies exceeds that of most other neglected zoonotic diseases (figure -bottom) [ , , ] . human animal-bite injuries and morbidity. most of the rabies daly burden is attributed to deaths, rather than morbidity because of the short duration of clinical disease. the daly burden for rabies is particularly high, because most deaths occur in children and therefore a greater number of years of life are lost [ , ] . daly estimates incorporate non-rabies mortality and morbidity in terms of adverse reactions to nerve-tissue vaccines (ntvs) [ ] , which are still widely used in some developing countries such as ethiopia, however rabies also causes substantial 'morbidity' as a direct result of injuries inflicted by rabid animals, and this is not included in daly estimates. contact-tracing studies suggest an incidence as high as / , bites by suspected rabid animals in rural communities of tanzania [ ] . thus, for every human rabies death there are typically more than ten other rabid animal-bite victims who do not develop signs of rabies, because they obtain pep (figure bottom) or are simply fortunate to remain healthy. the severity of wounds has not yet been quantified, but case-history interviews suggest that injuries often involve multiple, penetrating wounds that require medical treatment. economic burden. the major component of the economic burden of rabies relates to high costs of pep, which impacts both government and household budgets. with the phasing out of ntvs, many countries spend millions of dollars importing supplies of tissue-culture vaccine (,$ million usd pa [ ] ). at the household level, costs of pep arise directly from anti-rabies vaccines and from high indirect (patient-borne) costs associated with travel (particularly given the requirement of multiple hospital visits), medical fees and income loss [ , ] . indirect losses, represent . % of total costs ( figure ). total costs have been estimated conservatively at $ us per treatment in africa and $ us in asia accounting respectively for . % and . % of annual per capita gross national income [ ] . poor households face difficulties raising funds which results in considerable financial hardship and substantial delays in pep delivery [ , ] . shortages of pep, which are frequent in much of africa, further increase costs as bite victims are forced to travel to multiple centres to obtain treatment, also resulting in risky delays [ ] . additional economic losses relate to livestock losses derived from an incidence of deaths/ , cattle estimated to cost $ . million annually in africa and asia [ ] . however, substantially higher incidence has been recorded in tanzania, with - cases/ , cattle reported annually in rural communities (hampson, unpublished) . canine rabies introduced from sympatric domestic dog populations is also recognized as a major threat to endangered african wild dogs (lycaon pictus) and ethiopian wolves (canis simensis) [ ] [ ] [ ] [ ] . potential losses of tourism revenue may be substantial; african wild dogs are a major attraction in south africa national parks with the value of a single pack estimated at $ , per year [ ] and ethiopian wolves are a flagship species for the bale mountains national park. psychological impact. an important, but often underappreciated component of disease burden is the psychological impact on bite-victims and their families. in rural tanzania, . % of households with dog bite victims feared a bite from a suspected rabid animal more than malaria [ ] because malaria can be treated whereas clinical rabies is invariably fatal and malaria treatment is generally affordable and available locally in comparison to pep. when human rabies cases occur, the horrifying symptoms and invariably fatal outcome result in substantial trauma for families, communities and health care workers [ ] . increasing incidence of rabies in africa has prompted concerns that the epidemiology of the disease may be more complex, involving abundant wildlife carnivores that may sustain infection cycles [ , [ ] [ ] [ ] [ ] . there is also uncertainty about the level of vaccination coverage needed to control rabies particularly in rapidly growing domestic dog populations [ , ] . to eliminate infection, disease control efforts need to be targeted at the maintenance population [ ] . this is clearly demonstrated for fox rabies in western europe, whereby control of rabies in foxes (through mass oral vaccination) has led to the disappearance of rabies from all other 'spill-over' hosts [ ] . despite the predominance of domestic dog rabies in africa, the role of wildlife as independent maintenance hosts has been debated, and many perceive the abundance of wildlife as a barrier to elimination of canine rabies on the continent. it has also been argued that the predominance of dog rabies is an artefact of poor surveillance and under-reporting in wildlife populations [ ] . in the wildlife-rich serengeti ecosystem in tanzania, evidence suggests that domestic dogs are the only population essential for maintenance [ , , ] : ( ) phylogenetic data showed only a single southern africa canid-associated variant (africa b) circulating among different hosts [ ] ; ( ) transmission networks suggested that, for wildlife hosts, within-species transmission cannot be sustained [ ] ; and ( ) statistical inference indicated that cross-species transmission events from domestic dogs resulted in only relatively short-lived chains of transmission in wildlife with no evidence for persistence [ ] . the conclusion that domestic dogs are the only maintenance population in such a species-rich community suggests that elimination of canine rabies through domestic dog vaccination is a realistic possibility, and provides grounds for optimism for wider-scale elimination efforts in africa. in other parts of central and west africa, transmission of rabies appears to be driven by domestic dogs [ ] . an outstanding question relates to southern africa. earlier and recent evidence indicate that jackal species (canis mesomelas and c. adustus) and bat-eared foxes (otocyon megalotis) may maintain the canid variant in specific geographic loci in south africa and zimbabwe [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] , but it is still not clear whether these cycles can be sustained over large spatial and temporal scales in the absence of dog rabies [ , , ] . independent wildlife cycles may preclude continent-wide elimination of this variant through dog vaccination alone and wildlife rabies control strategies, in conjunction with dog vaccination, may need to be considered in specific locations [ ] . a critical proportion of the population must be protected (p crit ) to eliminate infection and this threshold can be calculated from the basic reproductive number (r , defined as the average number of secondary infections caused by an infected individual in a susceptible population) [ ] . vaccinating a large enough proportion of the population to exceed p crit will not only protect the vaccinated individuals but will reduce transmission such that, on average, less than one secondary infection will result from each primary case (effective reproductive number, r e , ), which can ultimately lead to elimination. vaccination has eliminated canine rabies in many countries demonstrating the success of this concept [ ] . however, theory suggests that r increases with population density [ ] and thus higher coverage will be needed in higher density populations. however, evaluation of historical outbreak data from around the world and recent data from tanzania indicate that r in domestic dog populations is consistently low (between . and . ) [ ] , confirming the feasibility of rabies elimination through vaccination in african domestic dog populations. an important conclusion of this study was that in populations with rapid turnover (such as those in many african countries) at least % of the population must be vaccinated during annual campaigns to prevent coverage falling below p crit between campaigns. data from africa clearly show that very few control efforts have reached these levels of coverage [ table ], which is why rabies remains a persistent problem [ ] . although emergence of new variants maintained in wildlife also remains a possibility, as shown in the usa, where wildlife rabies now dominates since elimination of canine rabies [ ] . for africa, these questions are likely only to be resolved with large-scale intervention involving mass vaccination of dogs. several arguments are given for why mass vaccination campaigns have failed to achieve the high levels of coverage that are necessary to interrupt rabies transmission. we counter these arguments below: a perception of many inaccessible stray/ownerless dogs. a common claim is that the majority of dogs in africa are unowned 'stray' animals, and therefore inaccessible for parenteral vaccination. it is not hard to see why this perception has arisen -unrestrained dogs, without any apparent evidence of ownership, are commonly observed. further investigation, however, usually reveals that the vast majority are owned, and at least one household claims some responsibility, including presentation for vaccination. published studies in africa, which quantify the proportion of unowned dogs, are admittedly sparse, but all support this observation [ ] [ ] [ ] . capture-mark-recapture methodologies and household questionnaires used in african settings have all found consistently low estimates (tunisia , % [ ] , %, % and % in three sites in n'djamena, chad [ ] , and % in a peri-urban site in tanzania [ ] ). notably, the tanzanian site was selected specifically on the basis of reports of many unowned dogs. while mark-recapture methods yield reliable estimates of unowned dog numbers, their implementation and analysis is not trivial and efforts are underway to develop simpler, yet robust methodologies [ ] . certainly in traditional africa, i.e. most of sub-saharan africa, the issue of roaming dogs seems not to be one of a lack of ownership, but rather an inability or unwillingness by owners to confine their dogs. unwillingness/inability to bring dogs for vaccination. published studies tend to refute the idea that owners are often unable or unwilling to restrain their dogs for parenteral vaccination. a multi-country who-commissioned study (tunisia, sri lanka and ecuador) concluded that ''dogs which are not catchable by at least one person are rare and represent generally less than % of the dog population'' [ ] . similarly a study from nepal found that - % of dogs were accessible to parenteral vaccination [ ] . although an early study in turkey concluded that % of all free-roaming owned dogs could not be captured by their owners [ ] , more recent surveys found that most unvaccinated dogs could be handled (only % could not) and that a much larger proportion ( %) resulted from a lack of information about the campaign -a much easier problem to remedy (unpublished data). in africa, very similar figures were obtained in a multi-site study in urban and rural tanzania, where only % of vaccination failures were due to a reported inability by the owner to handle the dog, while % of cases were due to poor information dissemination [ ] . however, there may be settings in transitional africa (e.g. parts of southern africa including kwazulu natal [ ] ) where handling of dogs is more difficult due to a break-down in traditional animal husbandry and other social factors, and more intensive efforts may be required for these special cases. given that most dogs are accessible for parenteral vaccination, high coverage can be achieved with well-planned vaccination campaigns. during pilot programmes in urban and rural africa which have not charged owners for vaccination, coverages obtained have exceeded % [ , , ] . pastoral communities pose particular challenges due to remote locations and seminomadic lifestyles, but . % coverages can still be achieved through house-to-house delivery strategies or community-based animal health workers [ ] . young pups usually make up a large proportion (. %) of african dog populations [ ] and there is a widespread perception among veterinary authorities and dog owners that they should not be vaccinated, which leads to insufficient coverage [ ] . however, rabies vaccines can safely be administered to pups , months of age [ ] , and in village campaigns in tanzania, vaccines consistently induced high levels (. . iu/ml) of rabies virus neutralizing antibody [ ] . the issue of inclusion of pups can effectively be addressed through appropriate advertising before campaigns. cost-recovery, through charging dog owners for rabies vaccination, is widely promoted for sustainable programmes and to encourage responsible dog ownership. however, charging for a vaccination that represents a public rather than a private good, can be counterproductive, resulting in low turnouts and coverage (, %) with little or no impact [ ] . charging for vaccination may indeed be the principal reason why owners are unwilling to bring dogs for vaccination. ineffective campaigns that achieve , % coverage are a waste of resources and can be highly demoralising for veterinary staff and communities. when resources are spread thinly, such that only low coverage is achieved or only small pockets are well vaccinated, then large-scale failure is inevitable. a more epidemiologically sensible strategy is to focus resources into a single (preferably well-bounded) area where high coverage can be consistently achieved. uncertainty about dog population sizes and ecology for effective design and planning of vaccination campaigns. official figures used for planning frequently underestimate true population sizes. for example, gsell [ ] found that the owned dog population in a municipality in tanzania was six times larger than official records. although standard survey methodologies for estimating dogs/household or dog:human ratios [ , [ ] [ ] [ ] are not without problems (for example, double ownership of dogs), a rough estimate of owned dog populations can be derived from national (human) population censuses, and can be corrected for different demographic and ecological settings [ , ] . more detailed studies can be conducted to identify key household determinants of dog ownership (for example, religion, age and sex of household heads, household size, socio-economic level, and livestock presence/absence [ , , , ] . such determinants have been used to generate a 'dog density' map of tanzania, for assistance in planning national rabies vaccination campaigns ( figure ). the above factors are all generally described as obstacles that ultimately lead to a lack of investment into rabies control and surveillance. we suggest that investment would actually reap multiple benefits including economic ones, if appropriate strategies are implemented overcoming the constraints described. a lack of surveillance and diagnostic capacity for rabies detection. poor surveillance and diagnosis capacity means that ( ) data is insufficient to demonstrate disease burden and motivate policy-makers, and ( ) impacts of control efforts cannot be evaluated. considerable progress has been made in the development of simple and inexpensive techniques for sample preservation and rapid post-mortem diagnosis suitable for laboratories with limited storage and/or diagnostic resources with potential to increase incountry capabilities for surveillance. a new direct rapid immunohistochemical test (drit) requires only light microscopes [ ] , which are widely available. the test is simple and can be performed by a range of operators if appropriate training is provided. field evaluation studies in africa demonstrated that this assay has characteristics equivalent to those of the direct fluorescent antibody (dfa) test, the global standard for rabies diagnosis, including excellent performance on glycerolated field brain material [ , ] , the preservative of choice under field conditions [ , ] . other simple field-diagnostics that allow rapid screening, including enzyme immunoassays [ ] , dot blot enzyme immunoassays [ ] and lateral-flow immunodiagnostic test kits [ , ] are being evaluated. these tools offer hope of extending diagnostic capacity in resource-limited settings. animal-bite injury data from hospitals are an easily accessible source of epidemiological information and have been verified as reliable indicators of animal rabies incidence and human exposures [ , ] . furthermore, increasing availability of communication infrastructure through mobile phone network access in remote areas could enhance surveillance by allowing real-time reporting. costs of effective dog vaccination campaigns are beyond the budget of veterinary services. veterinary services in africa usually report very limited budgets and often have to divert resources during outbreaks of other diseases [ , ] . this is clearly the most significant constraint to effective rabies control. however, with increasing human and dog populations, dog rabies incidence, human exposures to rabies and the costs required to prevent human rabies deaths through pep will invariably continue to rise unless rabies can be controlled at the source, i.e. in domestic dog populations [ ] . many countries in asia, such as thailand, vietnam and sri lanka have greatly reduced human rabies deaths through increased pep use, but at a very high cost [ ] . in vietnam, for example, deaths fell from in to in with administration of . , pep courses per year at an estimated cost of ,$ million/year [ ] . although domestic dog populations need to be targeted for the effective control of rabies, this is usually deemed to be the responsibility of veterinary services even though many of the benefits accrue to the medical sector. in rural tanzania, dog vaccination campaigns led to a rapid and dramatic decline in demand for costly human pep [ ] . in pastoral communities, vaccination not only reduced rabies incidence, but has now resulted in a complete absence of exposures reported in local hospitals for over two years (figure ) . large-scale campaigns can therefore translate into human lives and economic savings through reduced demand for pep. costs per dog vaccinated are generally estimated to be low (rural tanzania ,$ . [ ] , philippines ,$ . - . [ ] , tunisia ,$ . [ ] , thailand ,$ . [ ] and urban chad ,$ . [ ] ) and preliminary studies suggest that including dog vaccination in human rabies prevention strategies would be a highly cost-effective intervention at ,us $ /daly averted (s. cleaveland, unpublished data; see also ) . developing joint financing schemes for rabies prevention and control across medical and veterinary sectors would provide a mechanism to use savings in human pep to sustain rabies control programs in domestic dogs. although conceptually simple, the integration of budgets across different ministries is likely to pose political and administrative challenges. however, given sufficient political will and commitment, developing sustained programmes of dog vaccination that result in canine rabies elimination should be possible. in conclusion, here we show that a substantial body of epidemiological data have now been gathered through multiple studies demonstrating that: ( ) rabies is an important disease that exerts a substantial burden on human and animal health, local and national economies and wildlife conservation, ( ) domestic dogs are the sole population responsible for rabies maintenance and main source of infection for humans throughout most of africa and asia and therefore control of dog rabies should eliminate the disease, ( ) elimination of rabies through domestic dog vaccination is epidemiologically feasible, ( ) the vast majority of domestic dog populations across sub-saharan africa are accessible for vaccination and the few remaining factors compromising coverage can be addressed by engaging communities through education and awareness programs, ( ) new diagnostic and surveillance approaches will help evaluate the impact of interventions and focus efforts towards elimination, and ( ) dog rabies control is affordable, but is likely to require intersectoral approaches for sustainable programmes that will be needed to establish rabies-free areas. appendix s appendix with additional references. can rabies be eradicated? emerging epidemic dog 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and canine rabies eliminationguidelines for programme orientation costdescription of a pilot parenteral vaccination campaign against rabies in dogs in n'djaména, chad we are indebted to the ministries of livestock development and fisheries and of public health and social welfare, tanzania national parks, tanzania wildlife research institute, ngorongoro conservation area authority, tanzania commission for science and technology, and national institute for medical research for permission and collaboration; the frankfurt zoological society and the mwanza and arusha veterinary key: cord- -hayhbs u authors: gonzalez, jean-paul; souris, marc; valdivia-granda, willy title: global spread of hemorrhagic fever viruses: predicting pandemics date: - - journal: hemorrhagic fever viruses doi: . / - - - - _ sha: doc_id: cord_uid: hayhbs u as successive epidemics have swept the world, the scientific community has quickly learned from them about the emergence and transmission of communicable diseases. epidemics usually occur when health systems are unprepared. during an unexpected epidemic, health authorities engage in damage control, fear drives action, and the desire to understand the threat is greatest. as humanity recovers, policy-makers seek scientific expertise to improve their “preparedness” to face future events. global spread of disease is exemplified by the spread of yellow fever from africa to the americas, by the spread of dengue fever through transcontinental migration of mosquitos, by the relentless influenza virus pandemics, and, most recently, by the unexpected emergence of ebola virus, spread by motorbike and long haul carriers. other pathogens that are remarkable for their epidemic expansions include the arenavirus hemorrhagic fevers and hantavirus diseases carried by rodents over great geographic distances and the arthropod-borne viruses (west nile, chikungunya and zika) enabled by ecology and vector adaptations. did we learn from the past epidemics? are we prepared for the worst? the ultimate goal is to develop a resilient global health infrastructure. besides acquiring treatments, vaccines, and other preventive medicine, bio-surveillance is critical to preventing disease emergence and to counteracting its spread. so far, only the western hemisphere has a large and established monitoring system; however, diseases continue to emerge sporadically, in particular in southeast asia and south america, illuminating the imperfections of our surveillance. epidemics destabilize fragile governments, ravage the most vulnerable populations, and threaten the global community. pandemic risk calculations employ new technologies like computerized maintenance of geographical and historical datasets, geographic information systems (gis), next generation sequencing, and metagenomics to trace the molecular changes in pathogens during their emergence, and mathematical models to assess risk. predictions help to pinpoint the hot spots of emergence, the populations at risk, and the pathogens under genetic evolution. preparedness anticipates the risks, the needs of the population, the capacities of infrastructure, the sources of emergency funding, and finally, the international partnerships needed to manage a disaster before it occurs. at present, the world is in an intermediate phase of trying to reduce health disparities despite exponential population growth, political conflicts, migration, global trade, urbanization, and major environmental changes due to global warming. for the sake of humanity, we must focus on developing the necessary capacities for health surveillance, epidemic preparedness, and pandemic response. infectious diseases have swept the world, taking the lives of millions of people, causing considerable upheaval, and transforming the future of entire populations. every year pathogens cause nearly million deaths worldwide, mostly in developing countries. more than infectious diseases have emerged between the s and [ ] . also among the known arboviruses, only are known to be human pathogens, while the others only infect wild animals and/or arthropods. to anticipate an epidemic one must identify the risk, prepare an appropriate response, and control the disease spread by first identifying the vulnerabilities of the population and circumscribing the potential space into which a disease will extend. when the epidemic expansion risk is identified, adequate information must be communicated to decision makers. ultimately, an appropriate response will depend on biosurveillance, prevention, sustained data processing, communication, strategic immunization campaigns, resilience, and mitigation strategies. the viral hemorrhagic fevers (vhfs) are a diverse group of human illnesses caused by rna viruses including approximately species of the arenaviridae, filoviridae, bunyavirales, flavi viridae, and rhabdoviridae (table ) . despite the efforts placed on early detection, viruses like dengue, ebola, lassa, crimean-congo hemorrhagic fevers continue to threaten the health of millions of people, mostly in areas where demographic changes, and political and socio-economic instability interrupt vaccination campaigns [ ] . however, the threat of vhf to global health is increased by intercontinental travel and global trade. moreover, because of the high case fatality rate of some of these pathogens, such concerns extend to the potential use of these viruses by bio-terrorists [ ] . global expansion of several diseases is exemplified by the spread of yellow fever from africa to the americas, the spread of dengue fever across continents, and recently, the spread of ebola virus from the democratic republic of the congo to western africa. the concept of an epidemic, as a disease affecting many persons at the same time and spreading from person to person in a locality where the disease was not previously prevalent, was not enunciated until when john snow produced his admirable demonstration of the emergence of an infectious disease in an urban area: the emergence of a cholera epidemic in london. at that time, none could clearly comprehend the mechanisms of emergence and spread since the existence of microbes had just been demonstrated by louis pasteur in the late s and microbe transmission modes were more speculative than based on medical or scientific facts, until when robert koch demonstrated that bacteria can be transmitted and responsible for diseases. nowadays, it is extremely difficult to make a retrospective diagnosis of historical pandemics, there are currently species in the orthohantavirus genus. the pathogeny of most of them is unknown during times when clinical descriptions were rare or lacking accuracy, and the extent of an epidemic was extremely subjective. thus, it is common to note that the first outbreak described in the western world was that of the plague of athens for which thucydides rather precisely reported the symptoms; today this epidemic has often been attributed to typhus through its clinical picture and epidemic profile [ ] . the first historically recorded outbreaks due to viral agents date to antiquity when the roman armies were returning from distant countries bringing with them "exotic" diseases. indeed, the rise of a "new" virus is an extremely rare event. most often, in terms of pathogen emergence, a virus adapts through mutation and selection pressure to a human host causing disease. presumably, smallpox, measles, and influenza were among the plagues that struck the ancient latins in gusts of epidemics more or less severe. the antonin plague that extended from to ad in much of western europe, when the troops of emperor lucius verus returned from war against the parthians, is often attributed to a smallpox pandemic by historians. in the middle ages, it seems that smallpox made a return around ad to france, germany, belgium, and the british islands [ ] . the acute respiratory infections reported during the winter of - ad accompanying the return of the carolingian armies from italy have been attributed by historians to a flu epidemic. many soldiers of charlemagne died then. the disease returned regularly and fiercely in and ad to the western european peninsula [ , ] (table ) . from the plague (sensu lato, including all transmissible diseases) of antiquity, to the severe acute respiratory syndrome that emerged on the eve of the third millennium, pandemics have followed in the history of mankind. as noted by mirko grmek, a historian of medicine, it seems that one pandemic will drive in another. if several diseases circulate concomitantly, one of them will take precedence over the other, an epidemic over the previous, and it is more likely that a pandemic will prevail [ ] . plague temporarily replaced the leprosy that appeared in eurasia for over , years; during the first millennium, plague was manifested by successive pandemics that crossed continents. during the first half of the past millennium, syphilis started its expansions, crossed oceans, and became global. tuberculosis originated in europe more than , years ago, but it was only at the turn of the seventeenth century that it was considered a pandemic; smallpox was also manifest as epidemics and then was pandemic at its peak in the late nineteenth century, then smallpox persisted until the jenner area. although early medical records of smallpox are available (egypt, china, india), large and devastating epidemics were only identified in the late fifteenth century of the millennium. smallpox was introduced into the americas by spanish settlers in the caribbean island of hispaniola in and arrived in mexico in . on hispaniola island, one third of a million of the inhabitants died of smallpox in the following years. smallpox devastated the native amerindian population and was an important factor in the conquest of the aztecs and the incas by the spaniards [ ] . in , children died in goa, india, from a smallpox epidemic. in europe, smallpox was a leading cause of death in the eighteenth century, killing an estimated , europeans each year [ ] . during the twentieth century, it is estimated that smallpox was responsible for - million deaths. the last known natural case of smallpox occurred in somalia in [ ] . it is only at the end of the first millennium that all these pathologies were better understood and their infectious origins elucidated. the first pandemic of the twentieth century was attributed to the h n spanish flu that emerged in kansas in . however, this "flu pandemic" is now thought to have had subepidemic circulation earlier in france or germany or even prior emergence in china in or [ ] , and to be exascerbated by concurrent bacterial infections. although it burned out quickly by , it has been estimated that one third of the world's population was afflicted; million people died, half of them in the first weeks of the outbreak. since the s, the frequency and magnitude of dengue fever epidemics increased dramatically as the viruses and the mosquito vectors have both expanded geographically in pandemic proportions [ ] largely extending the pandemic to all the intertropical zone. in the early s, human immunodeficiency viruses (hiv- and hiv- ) spread as an acquired immunodeficiency syndrome (aids), a pandemic that continues to take its terrible toll at the global level. since the emergence of aids, organization updates, as of june only million people were accessing antiretroviral treatment and among them, seven of ten pregnant women received treatment. in , a severe acute respiratory syndrome, sars, inaugurated the twenty-first century as a first pandemic of the millennium, involving more than countries with secondary epidemic chains in asia, europe, north america, south america, and a total of cases [ ] . ultimately, one of the major characteristics that defines today's pandemics, apart from the introduction of the disease within several continents or the rapid expansion across the administrative borders of countries, is the initiation of locally active transmission of the pathogen. although, the first ebola virus disease outbreak of western africa was considered a pandemic and witnessed several exported cases with secondary epidemic chains in distant countries of the african continent (i.e., nigeria, mali), outside of africa, exported cases rarely sparked local transmission. emergence from a sporadic case to an outbreak, to an epidemic, and ultimately to a pandemic depends upon effective transmission among nonimmune hosts, host availability (density), characteristics of the vector (natural or human made) that would enable it to circumvent distances, and the pathogen infectiousness. all these dynamics are essential for an effective disease transmission and spread. an outbreak is a sudden increase in occurrences of a disease in a particular time and place, more localized than an epidemic. an epidemic occurs as the disease spreads to a large number of people in a given population within a short period of time. to spark an epidemic chain of transmission depends on factors like immune population density, virus infectiousness, promiscuity, vulnerability, etc., while the efficiency of such transmission depends on how many persons will be infected by one person (i.e., the reproductive ratio or r ). an epidemic event will therefore expand in space (beyond the first cluster of cases) and time (rapid spread). a pandemic is essentially spatial, and represents an epidemic of infectious disease that has spread through human populations across a large region, extensively across two or more continents, to worldwide. however, all these typologies harbor the same fundamentals: emergence from one index case, transmission from one host to another, and spatial expansion. altogether, an epidemic and a pandemic are respectively a local and a global network of inter connected infectious disease outbreaks (i.e., epidemic chains). ultimately, understanding how disease (i.e., pathogens) spread in the social system is fundamental in order to prevent and control outbreaks, with broad implications for a functioning health system and its associated costs [ ] . also, after the last case occurs at the end of an epidemic, the goal is to control the risk of transmission for a -day time period. this three-week period represents an incubation when the infected subject does not transmit the virus and remains asymptomatic. the " days" is based on experimental methods use in virology to detect virus replication: influenza virus infected eggs should hatch in days, there is a -day limit for an arbovirus to infect a living model (suckling mice, mice, rats, guinea pigs, cell lines). moreover, most viral infectious diseases have a maximal incubation period of days, with few exceptions (e.g., hiv, and rabies). ultimately, such -day periods multiplied by the potential of a carrier to travel will produce the risk area for the emergence of secondary cases (from a walking distance to the long distances covered by commercial jets). however, it is important to clarify that many vhf including ebola virus can be carried by an asymptomatic host for several months [ , ] . the mode of transmission profiles the epidemic pattern of a transmissible disease. it is extremely helpful when a disease emerges to rapidly surmise the mode of transmission and how to respond (e.g., water-borne disease, arthropod-borne disease, human-tohuman transmission). pathogen transmission can be interspecific or hetero-specific, direct or indirect. direct transmission occurs by close contact with infected biological products (e.g., blood, urine, saliva). indirect transmission occurs with intermediate hosts such as arthropod vectors (e.g., mosquito, tick) or mammalian vector/reservoir (e.g., rodent, chiropteran) or from infected environmental means (e.g., soil, water, etc.). mobility and transportation are the main factors for diseases dispersion, as an emblematic example, one can simply show how the - evd outbreak of western africa expanded due to the transportation of patients during their -day incubation periods, first by foot-paths, then by motorbike, then taxis and public transportation, finally becoming a global concern with patients traveling by boat or commercial airline [ , ] . host population density and promiscuity, crowded places (like schools, markets, mass transportation system) also play an important role in the efficiency of transmission as well as the level of herd immunity (e.g., annual pandemic flu), altogether this gives us the level of population susceptibility (i.e., vulnerability). environmental factors can also be major drivers of pathogen expansion, for example the emergence of nipah encephalitis. the nipah virus, when it emerged for the first time in malaysia in , was transported by its natural host, a frugivorous chiropteran. a year earlier, an immense forest fire affecting several indonesian islands had forced the escape of disease-carrying bats that took refuge in malaysian orchards, planted to nurture newly developed pig farms. both pigs and farmers became infected and nipah virus was discovered for the first time. another classical example, more associated with human environment and behavior, is the old story of the spread of dengue virus via the used tires carrying infected aedes aegypti eggs and transporting dengue across oceans and continents [ ] . understanding the mechanisms of transmission and expansion of disease vectors with respect to the typology (epidemic pattern) of a disease is the ultimate challenge for controlling and preventing disease. typologies from human-to-human transmission, zoonotic diseases, arboviruses, water-borne diseases, and others play different roles in the rate of disease spread and need to be clearly understood. finally, while an epidemic pattern is driven intrinsically by the virus and its vector, the host population, the mode of transmission, and even the human environment (e.g., population density, urbanization, agricultural practices, health system, public health policies) as well as physical environment (season, meteorology, climate changing, latitude, altitude) factor into the rate of disease spread. with respect to pandemic risk (the rapidity and area covered by disease), the main characteristics of a virus are found in its environmental persistence while remaining infectious. environmental persistence depends on: virus structure, enveloped viruses are more sensitive than the naked viruses; its mode of entry into the body of the susceptible subject (transdermal, oral, respiratory); its ability to diffuse out of the body for a sufficient period of time which will, in turn, enable transmission to a greater number of subjects (r ). altogether these intrinsic factors link to the infectivity of the virus, indeed, viruses transmitted by aerosol possess certainly the most efficient way to spark an epidemic that increases with population density and vulnerability as well as with the resistance of the virus to environmental factors outside the host cells. the cycle of transmission shapes the epidemic in time and spatial dispersion. for example, animal to human zoonoses are dictated by chance encounters between host (population density, animal farming, pets, hunting) and, eventually transmission such as that observed between human and nonhuman primates [ ] . vectortransmitted diseases (i.e., arthropod-borne diseases) depend on the vector ecology (ability to transmit, length of the intrinsic cycle of the virus, trophic preferences, vector density, seasonality, reproduction, breeding sites, food abundance for hematophagous arthropods). mobility of hosts/vectors that are part of the natural cycle will also play a role in the potential for disease expansion (e.g., mosquito-flying distance, cattle transhumance, human migration). also, other factors associated with the hosts will render a more efficient transmission: human behaviors like fear/social responses, nosocomial infections, super-spreaders); viruses having multiple natural hosts (vicariates) or vectors; vectors with multiple trophic preferences (e.g., biting cattle, birds, and primates); the incubation period in the vertebrate hosts as well as the intrinsic replication in the arthropod vectors will also intervene; ultimately subclinical infection is also an underestimated factor of virus dispersion and transmission that modifies the epidemiological pattern of disease. one can distinguish also a typology of communicable diseases that reflects the spatial and temporal mode of transmission including arthropod-borne transmission, human-to-human transmission, human-to-animal (and vice versa) transmitted diseases (i.e., zoo- predicting hfv pandemics noses) including vector and nonvector transmitted diseases, and some other types of environmentally transmitted diseases. all of them represent unique types of transmission and risk of spread with a variable path of time, and also dependent on multiple factors (environment, climate, behavior, etc.). we have to consider territories as spaces where disease can potentially expand and that can be characterized by the fundamental factors of emergence and spread: the vulnerability of the population, the level of favorable transmission factors, and the probability for the population to be exposed to the virus. vhf are exemplary for their epidemic patterns of expansion dependent on the above reviewed factors (i.e., fundamentals of emergence) and their epidemiological characteristics (i.e., virus, host, environments). for example, let us consider the control of arenavirus spread by their strong host-species association. on a geological time scale, arenaviruses such as the agent for argentinian hemorrhagic fever (ahf) coevolved with their natural rodent host and then spread according to the expansion of the rodent host. one host-one virus ultimately produces a localized endemic cycle, the distribution of the disease overlaps the distribution of the rodent host while enzootic patterns appear naturally limited to an ecosystem (e.g., local rodent populations, behaviors, and environmental factors). hantaviruses also appear as a global complex, resulting from the coevolution of virus and rodent hosts and a global dispersion of generally localized enzootic diseases [ ] [ ] [ ] . as for the pandemic risk associated with a natural virus reservoir, chiropterans are unique flying and migratory mammals that have been associated with filoviruses and other viruses of major public health importance [ ] , their potential as vectors will eventually favor the spread of these viruses into new territories. also because there is potential for a long coevolution, epidemiological patterns are also dependent on virus-host spillover, host vicariate, and other environmental factors (e.g., climate change and man-made changes in land use). other arboviruses such as yellow fever virus, dengue virus, as well as west nile, chikungunya, or zika viruses show a pandemic risk associated with the existing distribution of their respective arthropod vector, vector density, and ability to transmit virus. investigating the fundamental factors of transmission and favorable territories for disease emergence are necessary to evaluate the risk, respond to the epidemic, and control its expansion from an index case to a pandemic. ultimately, when the fundamentals are understood and epidemic/pandemic risk identified, suitable emergency funding needs to be identified and made available in endemic areas to insure political willingness and community participation. ultimately, a suitable response will improve biosurveillance, data processing, communication, strategic immunization campaigns, and research for future risk prevention. several emblematic vhf and their original "epidemiological engineering" are presented in herein. vhf such as ebola virus disease, lassa fever, rift valley fever, or marburg virus disease are highly contagious and deadly diseases, with potential to become pandemics. remarkably, vhf are essentially caused by viruses of eight families; arenaviridae, filoviridae, hantaviridae, nairoviridae, peribunyaviridae, phenuiviridae, flaviviridae, and more recently rhabdoviridae [ ] (table ) . hemorrhagic fever viruses (hfv) have been classified as "select agents" because they are considered to pose a severe threat to both human and animal health due to high mortality rate, human-to-human transmission, and, in some cases, the potential to be aerosolized and used as bioweapons [ ] . each of these hfv shares some common features that define the nosology of the vhf group, from virus structures to the clinical and epidemiological characteristics of their diseases. -hfv spread person-to-person through direct contact with symptomatic or asymptomatic patients, body fluids, or cadavers. -vhf can have a zoonotic origin, as when humans have contact with infected livestock via slaughter or consumption of raw meat, unpasteurized milk, bushmeat, inhalation or contact with materials contaminated with excreta from rodents or bats. -hfv can be vector-borne, i.e., transmitted via rodents, mosquitos, and ticks. -vhf are zoonotic diseases. accidental transmission from the natural host to humans can eventually lead to human-to-human transmission, human infection, and sporadic outbreaks. -with a few noteworthy exceptions (i.e., ribavirin), there is no cure or established drug treatment for vhf, while limited vaccines could be available, including yf, ahf, and rvf (the latter is for animals only). -vhf have common features: they affect many organs, they damage blood vessels, and they affect the body's ability to regulate itself. clinical case definitions describe vhf with at least two of the following clinical signs: hemorrhagic or purpuric rash; epistaxis, hematemesis, hemoptysis, melena, among other hemorrhagic symptoms without known predisposing host factors for hemorrhagic manifestations. in fact, during an epidemic, all infected patients do not show these signs and a specific case definition needs to be defined in accordance with the suspected or proven viral etiology of the disease [ ]. also, vhf pathogenesis encompasses a variety of mechanisms including: ( ) alteration of hepatic synthesis of coagulation factors, cytokine storm, increased vascular permeability, complement activation, disseminated intravascular coagulation. moreover, severe pathogenic syndrome is often supported by an ineffective immunity, high viral loads, and severe plasma leakage and co-infection with other pathogens [ ] . the present chapter will mainly focus on the factors that can specifically and eventually contribute to a pandemic risk and how did we learn from historical spread of the vhf. the yellow fever disease pandemic is thought to have originated in africa, where the virus emerged in east or central africa and spread to western africa. in the seventeenth century, it spread to south america through the "triangular" slave trade, after which several major outbreaks occurred in the americas, africa, and europe [ , ] . the yellow fever vaccine is a fantastic gift from pioneering vac- cinology; it is efficient, affordable for developing countries, and protects for at least a decade or even life-long. however, yf remains a particular concern at the global level and the number of cases has unexpectedly increased this past decade. nowadays, yfv causes , infections and , deaths every year, with nearly % occurring in africa. nearly a billion people live in an endemic area [ ] . although yfv is common in tropical areas of south america and africa, it has never been isolated in asia [ ] . ultimately, the pandemic risk is there, from the uncontrolled epidemic as for example in the inland remote area of the brazilian mato grosso state, to the recent burst of epidemics in west and central africa including angola, drc, as well as imported cases in kenya and china [ , ] . indeed, the risk of a pandemic exists if any imported case goes to an area where the fundamentals of emergence are present (i.e., aedes aegypti and a nonimmune human population). for years it has been stressed that yf coverage needs to be exhaustive in the endemic area, and the who international health regulations (ihr) need to be strictly respected when peoples are crossing frontiers to or from an endemic area [ ] . even though the virus was known to actively circulate in asia, north america, and africa years ago, a global pandemic of dengue fever began in southeast asia in the s [ , ] . dengue virus (denv) expansion was followed by the emergence of a dhf pandemic that occurred in the late twentieth century (see above, the "tire-mosquito larvae connection"). by the end of the century, dhf emerged in the pacific and the americas, and extended to all asian continents [ ] . lately, in the s, epidemic dengue fever occurs in africa, with a predominant activity in east africa, while sylvatic denv circulation was described in western africa [ ] . the different dengue virus serotypes spread also independently to all continents. while it is remarkable that infection with one serotype does not provide cross-protective immunity against the others, epidemics caused by multiple serotypes became more frequent, and highly pathogenic denv were identified [ ] . dengue fever to date has a global distribution with an estimated . billion people at risk. yearly, hundreds of thousands of dhf cases occur [ ] . altogether, the requirements for a dhf pandemic are globally present [ ] : the highly competent aedes aegypti and aedes albopictus denv vectors, the globally distributed denv serotypes and highly pathogenic strains, and finally, climate change that opens new breeding opportunities for these mosquitoes to expand and eventually transmit imported denv into new populations and territories [ ] . mankind will have to live with this pandemic until the new denv vaccines can be implemented. in , an unknown disease was reported by a group of laboratory workers in west germany and former yugoslavia [ ] . over the course of months, cases and seven deaths occurred. conclusions made by treating physicians at the time (and published shortly thereafter) highlighted the following: high fatality rate, risk of relapse; risk of sexual transmission [ ] . a connection was made to infected african primates, chlorocebus aethiops, when laboratory workers were exposed to their imported tissues. it took years to effectively connect marburg virus, marv, to a bat, rousettus aegyptiacus, as a natural marv reservoir in central africa [ ] . marv is considered to be extremely dangerous for humans, is classified as a risk group pathogen, and also is listed as a select agent; however, the pandemic risk cannot be assessed because only four epidemics have occurred. although marv expansion appears to be limited to a few countries in africa, the recent emergence (estimated at a few decades ago) of a second human pathogenic marburgvirus known as ravn virus, and the widely distributed old world rousette fruit bats (rousettus spp.) serving as reservoir for both viruses [ ] , are two factors that favor pandemic risk. although more than years after its emergence from a remote area on the ebola river in the central african rain forest, ebola virus (ebov) remained hidden in a cryptic natural cycle. then a series of outbreaks occurred in the large congolese rain forest of central africa [ ] . the epidemic risk was always considered to be localized and circumscribed [ ] . then, suddenly without warning, in the late months of , ebov emerged for the first time in a remote area of western africa and sparked an outbreak more massive than ever witnessed before. more than , people were infected, ten countries recorded cases (transmitted or imported), the pandemic risk raised fear, and who declared it as an inter national health emergency that requires a coordinated global approach [ ] . besides the lack of preparedness of national and international public health systems, the other major factor that played an immense role for the dispersion of evd in western africa was the extreme mobility of village populations. they followed the kissidougou forest foot-paths to the towns in guinea using motorbikes, cars, and other public transportation, then later evd traveled by plane to the global level. the evd epidemic went from outbreak to pandemic risk. like marburg virus, another member of the filoviridae, ebola virus, shares bats as a potential virus reservoir, human and nonhuman primates are highly sensitive to the virus, and inter-epidemic periods play an important role since the epidemic silences tend to diminish the attention of health services and increase epidemic risk. in this way, the first western african evd epidemic is exemplary for showing the hidden risks contained in the natural cycle of a virus, and the sudden emergence followed by an unprecedented velocity of spreading. in the absence of biosurveillance, a pandemic risk remains. hemorrhagic fever with renal syndrome, hfrs, appears first as a global concern of one virus family, several human pathogenic viruses of the genus orthohantavirus, multiple clinical presentations, and different epidemiological patterns [ ] . hantaviruses and hfrs were first described in asia [ ] ; nowadays, hantaviruses are the cause of zoonoses that are expanding worldwide. indeed, since when a previously unknown hantavirus was implicated in the first hantavirus pulmonary syndrome (hps) outbreak in the united states, several other hantavirus infections were reported in western europe, and then hantaviruses were described in south america. ultimately, after an early suspicion of the presence of the hanta viruses in africa [ ] , a novel hantavirus, sangassou virus, was isolated in in guinea [ ] . altogether we observed the emergence of the hantaviridae in the western hemisphere, from the old world to the new world, and recently discovered its first tentative steps on the african continent. with respect to the orthohantavirus genus, a real pandemic exists even when multiple viruses are involved. ultimately, as for the arenaviridae, hosts are specific and certainly the major vectors of virus dispersion. the arenaviridae includes different viral species grouped as old or new world arenaviruses [ ] , each is maintained by rodents of individual species as natural reservoir host and as vector for the viruses that are human pathogens. the rodent hosts are chronically infected without obvious illness and they pass virus vertically to their offspring. de facto, the distribution of the virus covers that of its natural hosts but is isolated in an ecosystem generally limited by natural barriers, e.g., mountains, river. a phenomenon in which rodent lineages are naturally infected by a virus and remain in such a limited environment is called "nidality" [ ] . this is what it is observed for argentinian hf, venezuelan hf, bolivian hf, and lassa hf. regarding the pandemic risk of any of these hf, arenaviruses because of their strict association with their natural hosts, like the hantaviruses, have their expansion potential limited by their natural hosts even though the latter are widely spread and could certainly be infected. such risk lies in an unexpected encounter between infected and noninfected populations under the pressures of (as yet unknown) factors that favor their migration from enzootic to non-enzootic areas. in that matter, lymphocytic choriomeningitis virus, another member of the arenaviridae, has a worldwide distribution through its domesticated natural host, the ubiquitous house mouse, mus musculus. although crimean-congo hemorrhagic fever, cchf, is a widespread disease endemic to africa, the balkans, western asia, and asian countries south of the th parallel north, it is generally transmitted by ticks to livestock or humans and therefore geographically limited to regions where tick vectors feed on humans. although the competent ixodid vector is limited, as is the abundance of their natural hosts, climate change modifies the distribution and abundance of tick hosts (i.e., tick abundance) [ ] . additionally the cchfv pandemic risk is limited by low mobility, geographical repartition, and seasonal activity, although its main natural hosts are widely dispersed from africa, to asia and europe [ ] . ultimately, human-to-human transmission occurs from close contact with the blood, secretions, or other biological fluids of infected persons but these remain rare events with a r < . altogether, a cchf pandemic risk remains hypothetical but underlined by the risk of human-to-human transmission [ ] . as for cchf, rift valley fever, rvf, is first a disease of cattle and illustrates a unique subcontinental zoonotic spread along the path of traditional herders. rvf became a transcontinental risk with trade and transportation when the virus spread from north east africa to western africa, and even to madagascar [ ] . if one considers its pandemic risk, with respect to rvf epidemiology as a mosquito-transmitted disease, two factors have to play concomitantly: the presence of infected cattle (i.e., nonimmune) and competent mosquito abundance, both considered hazards, while concretizing the risks from human vulnerability (nonimmune; mosquito bite; direct exposure to infected blood). in order to streamline the prevention and the actions to reduce epidemic risk, the various elements involved in an outbreak are here considered from a systemic point of view, considering the risk as the convergence of a hazard and vulnerability: -the presence of the threat (or "hazard" pathogen, i.e., vector, virus reservoir) is considered to be a necessary-but not sufficient-condition for the development of a disease. it is often known only in terms of probabilities, sometimes very low and therefore often subject to significant random variability in time and space. we often seek to evaluate the spatial and temporal differences of this probability, trying to measure its significance. sometimes, it only uses one character necessary to the presence of the pathogen or vector (e.g., the presence of water, a minimum temperature, a type of vegetation). -the susceptibility of the host (which is essentially linked to individual characters, genetic, biological, such as immune status or age) is individual, and often given by a probability. -direct exposure of the host to the hazard is an element of active vulnerability, depending on the behavior of the host that increases the likelihood of contact between host and hazard by exposing it to an environment conducive to his presence (e.g., travel and contacts, professional activities). it also includes all the known "risk" behaviors that increase the likelihood of direct exposure to the hazard. -passive vulnerability of the host, which is not directly dependent on the pathology, is not even necessary nor sufficient for pathology, but influences the exposure of the host to the hazard or to protection from the pathology. this protection consists of prophylaxis, access to care, availability of care. it is independent of the real presence of the hazard; the host can be vulnerable without being exposed to the threat. the vulnerability is often defined by several levels (individual, context). it is very often "spatial" as linked to phenomena of segregation or spatial concentration. this is an area primarily studied by geography. ultimately, this vision can differentiate what is active, often subject to high variability, random in time and space (the emergence or the presence of hazards is often difficult if not impossible to control) from what is passive, generally situated among more stable population levels (sensitivities, exhibitions, behaviors, and vulnerabilities). this allows for better public health preventive actions, and also to understand rationally crisis situations by preemptively targeting the most important elements of the system in terms of vulnerability, and secondly by optimizing risk reduction (elimination of vectors, vaccinations, quarantine, etc.). in all cases, these actions must be adapted to social contexts to have a real impact on risk behaviors and vulnerabilities that they generate, hence the increasing role of anthropology in the field of health. to prevent or reduce the epidemic risk, it is necessary to act on each component of this system: -reducing the susceptibility of the host (e.g., immunization, vaccination, prophylaxis). -reducing host exposure to the pathogen (e.g., vector control, quarantine, exclusion zone). -eliminating the pathogen directly (e.g., animal slaughter, disinfection, hygiene), or indirectly (e.g., suppress transmission). -reducing host vulnerability (e.g., socio-economic, behavioral, access to health care system). -reducing host exposure to emergency condition (e.g., realtime data collection, warning systems for emergency, crisis management, implementation of treatment). the rapid detection of emergence is the key to controlling the spread of an epidemic. it requires comprehensive monitoring to trigger alerts and all other risk-reducing actions, in particular, reducing the exposure of the host to the pathogen and, if possible, the elimination of the pathogen. in parallel to the monitoring and warning systems, protocols must always take into account local characteristics of political power and decision-making bodies that could otherwise render ineffective year-long action plans or warning systems (for example, the management of the chikungunya epidemic in reunion island was largely impacted by bottlenecks related to local political system) [ ] . biosurveillance and efficiency in data collection and management will be the technical keys for prevention (early detection of epidemic risk) and forecasting epidemic emergence and spread (i.e., analyzing the data in near real time taking into account the vulnerability of a given population). also, this can be achieved only by exhaustive capacity building (human and technical) mostly in the more vulnerable developing countries but also where the most advanced technology needs to be developed. networking biosurveillance systems are a major undertaking from regional to global, involving politics and diplomacy. taking in account the local characteristics of political structures and decision systems is fundamental. despite our current recognition of the risks posed by emerging and re-emerging infectious diseases to global public health and stability, reliable structured data remains a major gap in our ability to measure (and therefore manage) globally infectious diseases. who has long served as an information hub for infectious disease events worldwide; however, extracting quantitative data from who information bulletins (weekly epidemiological record and the more recent disease outbreak news alerts) proves to be a time-consuming effort with limited results in terms of operability, and exists more for the record and future analysis. the current proliferation of geospatial information tools (i.e., geographical information system, gis) and stepwise advances in data extraction capabilities have made it possible to develop robust, systematic databases facilitating anomaly detection (like clusters), infectious disease models (and model evaluation), and apples-to-apples comparisons of historic infectious disease events worldwide. however, biosurveillance capabilities-the key to global prevention and health securityremain inadequate to support true early detection and response. increased access to technology, rapidly developing communications infrastructures, smartphone usage for suspected-case reporting, and global networks of (formal and informal) disease surveillance practitioners provide an explosive opportunity to patch and improve surveillance networks. the challenge is to leverage all these developments, implement technical and capacity building where needed, before the next epidemic with global impact emerges. several organizations have developed systems to collect epidemic information and facilitate rapid response: who has the department of pandemic and epidemic diseases (ped) that develops mechanisms to address epidemic diseases, thereby reducing their impact on affected populations and limiting their international spread. among them some have self-explanatory titles: the battle against respiratory viruses (brave); early warning and response systems for epidemics in emergency (eware); emerging and dangerous pathogens laboratory network (edpln); international coordinating group for access to vaccines for epidemics (icg); global infection prevention and control network; (gipcn ); global influenza surveillance and response system (gisrs); global leptospirosis environmental action network (glean); meningitis environmental risk information technologies (merit); weekly epidemiological record (wer); emerging diseases clinical assessment and response network (edcarn). global commitment to these efforts will insure their readiness in times of need. most certainly and most importantly, any preparedness and response requires emergency funding [ ] . it has been estimated that if the ebola virus disease response started months earlier, it could have reduced the total number of deaths by % in liberia and sierra leone [ ] . we learned from this last evd epidemic that in march , the african union's minister of finance requested the african risk capacity (arc) agency to help member states to better plan, prepare, and respond to devastating outbreaks by developing new applications for financial tools, like insurance, that can significantly improve the speed of funds to affected countries and shorten the time between event and response. the agency is now developing an outbreak and epidemic insurance product primarily based on responsibly and timely budget reallocation; however, viruses do not wait. moreover, the world bank's pandemic emergency facility is designed to finance surge capacity and support international government partners to actively participate to the response. ultimately, epidemics are not one-off events, but rather demonstrate financial patterns similar to other natural catastrophes. as natural catastrophes, large epidemics can be insured by creating financial mechanisms to facilitate the movement of critical resources within affected countries and ultimately manage the spread of disease and minimizing macroeconomic impact [ ] . classical tools and strategies for predicting epidemics encompass human disease surveillance (e.g., public health and hospital statistics) and, sometimes, environmental surveys (e.g., climate, el niño, earthquake, tsunami); also more recently complying with one health concept, human and veterinary health as well environmental risk factors have been reunited in a comprehensive approach of public health risk (i.e., outbreak, epidemic risks). however, this heuristic approach of health remains limited to specific diseases and territories and does not apply as a global predictor of pandemics. first, historical data is the only available objective view of past epidemics and pandemics, needs to be collected, formatted, corrected, and analyzed. this will be the foundation of the different tools and strategies described below. in that matter, with respect to the depth of the past data available, time series of disease observation, modern tools such as internet search data have actually led to the development of several specific sites (e.g., google flu and dengue) [ ], whose search-term reports have correlated strongly with incidence estimates in several public health reports in europe, asia, and the u.s. however, even though such tools can complement classical disease surveillance, most of these sites are geographically limited and cannot be used for live monitoring of epidemic risk and for neglected tropical disease surveillance [ , ] . however, from such historical and live-collected data, health alert systems can be implemented, and prediction models can be developed. moreover, thanks to the spatial analyses, combining multiple data sources will provide the ultimate tools for livemapping an outbreak, which will lead to an efficient response when tools and strategy have been specifically identified (i.e., sufficient and available in-country heath system resources and funding; identifying variations in pathogen sequences that contribute to ro and pathogenicity; monitoring population movement; etc.). the amount of data being digitally collected and stored is exponentially accumulating. it is estimated that, as of september of , the world wide web reached . billion pages containing eight zettabytes of accessible data, and the accumulation of information is growing around % every year [ ] . this situation has generated much discussion about how to use the unprecedented availability of information and computational resources and the sophistication of new analytic and visualization algorithms for decision-making to reduce the impact of infectious diseases. in fact, it is argued that the paradigm of "big data" will change not only the way business and research is done, but significantly improve the understanding of factors leading to the emergence of infectious diseases. big data could lead to the implementation of a decentralized biosurveillance enterprise allowing organizations and individuals to take full advantage of a large collection of disparate, unstructured qualitative, and quantitative datasets. with the proper integration and the right analytics, big data could find unusual data trends leading to better pathogen detection systems, as well as therapeutic and prophylactic countermeasures. however, the impact of these analyses and forecasts depends not only on how the data is collected, ingested, disambiguated and processed, but also on how it is relayed in different operational contexts to users with different backgrounds and understandings of technology. while impressive in data mining capabilities, real-time content analysis of social media data misses much of the factual complexity. quality issues within freeform user-provided hashtags and biased referencing can significantly undermine our confidence in the information obtained to make critical decisions about the natural versus intentional emergence of a pathogen. risk factors associated with a health event in a population are often linked to environmental factors (fig. ) . they are also linked to spatial relationships between individuals, especially for infectious diseases. the geographical distribution of these phenomena reflects spatial relationships. beyond "classic" epidemiology mainly based on statistical analysis, using the location and spatial distribution is essential in the understanding of health events and analysis of their mechanisms. spatial analysis in epidemiology is a method to help determine the location (georeferenced) of risk factors. it allows one to identify the spatial and temporal differentiation in the distribution of events, using their location in time and space. when the location is available, with precision for each studied object (i.e., individuals or geographical units), it is possible to: -characterize the overall spatial distribution, using synthetic indices on the absolute position of an object, on the average spatial arrangement of objects or their values (grouping/ fig. mapping environmental factors that have a major impact on insect vector population (i.e., mosquitoes and ticks). this map of laos constitutes the basis of a risk map showing part of the hazards contributing to virus vector density that could be matched with human density and pathogen prevalence leading to a risk map (spatial risk) and eventually extended through seasonality (temporal risk). mean temperature and mean rainfalls are interpolated as climatic conditions, as environmental factors influencing the presence of mosquitoes dispersion, spatial dependence, variogram measure of autocorrelation space). -look for characteristics of the overall shape of the phenomenon (tendency, shape), and search for a theoretical spatial distribution, or for a process to model the observed spatial distribution. -look for unusual places (geographical centers and source sites; aggregates; exclusions; hot spots, cold spots), and to study the spatial relationships at the individual level. -conduct spatiotemporal analysis: search index cases, reconstruction of paths, diffusion models, models of extinction, etc. -spatial analysis allows the development of applications for modeling epidemics, preparing warning systems, as well as crisis management systems, risk prevention and analysis systems, and vaccination campaigns. many tools for biomonitoring and prevention of epidemic risk have been developed (fig. ) , as well as software tools to: (a) visualize spatial distributions. (b) synthesize and analyze position and spatial relationships between events (continuity, consolidation, attractionrepulsion, shape, centrality, displacement, diffusion processes). (c) to analyze the relationship between spatial distribution of attributed values and environmental characteristics of the phenomenon (environmental correlations). (d) to model the phenomena of emergence, dissemination, extinguishment of an epidemic. cluster detection, space-time analysis, and spatial integration with environmental and demographic data are widely used in such warning systems. multiple and complex factors are associated with the emergence and impact of pathogens in a given geographical area. therefore, public health analysts are confronted with the task to identify the likely, and unlikely, consequences and alternative critical outcomes of a given vhf outbreak. this requires the ability to monitor in near real time the dynamics of the geographical dissemination of these viruses in villages, cities, countries, continents, or the globe using new analytical techniques within the emerging field of genomicbased biosurveillance. this concept integrates microbial genotyping, next generation sequencing, metagenomics, big data and database analytics, and contextualized visualization to identify, characterize, and attribute known and unknown pathogens and generate estimates of how different contingencies will affect their impact [ ] . a genomic-based biosurveillance system includes powerful microbial genomic characterization to rapidly identify a pathogen [ ] . this characteristic makes a genomic-based biosurveillance a useful approach not only for public health but serves as a deterrence tool for intentional biological weapon development and deployment. the initial step consists of integration of signals generated by molecular-based assays and next generation dna sequencing and unbiased microbial characterization for pathogen source tracing, attribution and forensics. while each of these techniques has been discussed in the literature in detail [ ] , the integration of this information can yield a more extended view of the scale of a pathogen outbreak. the development of high-throughput the exemplary case of the highly pathogenic avian influenza virus h n in thailand. from the emergence of one imported case (red-filled circle), the pathway direction (arrowed green lines) of h n infection in farms (yellow points) is reconstituted, using dates of infection and distance between farms. results show local spread with time-to-time medium distance jumps dna sequencing technologies (i.e., dna and cdna forms of rna viral genomes) is allowing the genomic characterization of previously unknown pathogens without relying on prior reference molecular information [ , ] . this information is available within days, and even hours, of sample collection, and well before the development of animal infection models. because of their portability, this technology will become widely used in the next years in routine clinical settings. however, to be clinically and epidemiologically relevant, dna sequences must be rapidly and effectively translated into actionable information defining pathogen characteristics (i.e., virulence or drug resistance), it must point to a source of origin, and discriminate a natural event from a manmade release [ ] . while some government agencies are considering use of genomic information to develop next generation level- and level- detection/surveillance devices [ , ] , there is no reference database where researchers can retrieve standardized genomic signatures and motif fingerprints to develop primer-, probe-, and antibody-based detection technology using reference moieties. the impact of genomic-based biosurveillance in public health and biodefense will not be fully realized until addressing the current impracticality of transferring the terabytes of genomic data generated by dna sequencing devices to a centralized architecture performing analysis operations, as that might take hours or even days. therefore, a new paradigm could emerge from encouraging the development of decentralized algorithms that first determine in situ the presence of pathogen-specific genomic signatures or motif fingerprints, summarize and relay the results into an operational biosurveillance metadata format for contextualized decision support. the localized data management, time, and space required for spatial analysis is performed by geographic information systems (gis). these are computer systems that manage large volumes of data and easily use the location to perform spatial analysis. most gis are not limited to data management functions, but also integrate multiple analysis tools, data transformation, and cartographic representation. these are for the most part complex applications with enormous features. the "gis" designation covers a wide variety of software projects built according to different technical options, functionality, and diverse performances. a gis is essentially a management tool (structure, organization, entry, storage), an analytical tool (statistical and geographical treatment, spatial analysis), and a communication tool (data visualization, descriptive mapping, thematic mapping, atlas). it is also a tool that allows the use of a spatial model for the simulation of a process, such as the development of an epidemic. gis facilitates the interface between modeling and simulation program, and the geographic database, and can ultimately take over the whole of access to spatial information needed by the modeling program. the gis should thus be at the heart of organizing the collection and processing of monitoring data. to ensure the management of this system, it is important to set up a body specifying all the collection, validation, processing and dissemination of information and results (alerts, risk modeling, near real-time dissemination of results). this body must be proposed and validated by political authorities, preemptively, to avoid further blockage and to ensure effectiveness in situations of epidemic crisis. mathematical modeling is a mathematical formulation of a parameter or risk; it depends on identified or hypothesized risk factors whose coefficients are determined by a statistical or heuristic analysis from historical or observed data with the use of r , as a basic reproduction rate, to timely and spatially predict the spread-speed of an emerging outbreak. spatial-temporal modeling of health events can be seen as the final stage of the analysis. it is different from statistical modeling. despite using risk factors, it considers the epidemic phenomenon as a whole, taking into account the spatial relationships between agents (hosts, vectors, reservoirs, and pathogens), between individuals, and relationships between individuals and their environment. this model is thus useful for understanding and anticipating the epidemics, and can be generally used to classify individuals in different states (susceptible, infected, sick healed, immune) and to model the major phenomena that can change the state of an individual. however, when a model takes into account many phenomena, it can quickly become very complex. the vast majority of models are simplifications of assumed reality. two broad categories of methods are usually developed in modeling: -a deterministic approach, based on differential equations whose coefficients are adjusted from observed data, or monitoring data from epidemics. in this model, one can introduce stochastic types of components in the coefficients, studying the variability of observed data. taking no account of spatial relationships is difficult in these models, which deal in general populations, not individuals. -a nondeterministic approach, which is based on agents whose behavior is described by expertly determined rules (multiagent models). the status of each agent is calculated at each time step, from its behavior, environment, and relations between the agent and all other agents. these models take into account a more realistic description of the phenomenon, near the complex system finely describing reality. they allow us to consider spatial relationships in each time step. these models require intensive calculation, and their use is made possible by development of the power of computer calculations. let us first honestly address the fundamental questions about epdimeics and preparedness: what did we learn from all the past epidemics, what will we remember in times of need? are we prepared for the worst of these hypothetic pandemics abundantly illustrated in the cinema and unfortunately sometimes overwhelmed when reality goes beyond fiction? certainly, we are not "globally" prepared, unfortunately, at that scale, the immense natural and human disparities do not permit it, but we do our best in our own societies. the concept of disease emergence, born only at the end of the twentieth century, is a societal marker, our desire to be on alert, understand and predict epidemics. ultimately, there are a few, but necessary and difficult goals to reach for the prevention and control of any epidemic, also these goals are part of the development of our societies, as well as for education, they become part of the wellbeing for all: first, beyond understanding transmission, is needed a clear understanding of the epidemiological pattern and the spread of a given disease, before it is too late; then, which is certainly one of the more complex and costly things to achieve, is having an efficient health system to respond to an epidemic and an operational network to respond at the regional and global levels; and last but certainly not a least, having identified funding for any public health emergency will be crucial to changing our world. perhaps, in a shrinking global community, after too many ebola virus disease outbreaks, we will learn and be prepared for future epidemic challenges? the progress made, mostly by computer sciences in the overall analysis of health data, should serve as a tool in the prevention of major epidemics. let us ultimately use our predictions of pandemic risk to meet and unite beyond the current frontiers of political and social wills. epidemic predictions in an imperfect world: modelling 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observations on biowatch generation- and other federal efforts: testimony before the subcommittees on emergency preparedness, response, and communications and cybersecurity, infrastructure protection, and security technologies, committee on house homeland security, house of representatives congress. house ( ) committee on homeland security. subcommittee on emergency preparedness response and communications., united states. congress. house. committee on homeland security. subcommittee on cybersecurity infrastructure protection and security technologies., united states. government accountability office: biosurveillance observations on biowatch generation- and other federal efforts: testimony before the subcommittees on emergency preparedness, response, and communications and cybersecurity, infra structure protection, and security technologies, committee on house homeland security, house of representatives acknowledgments w.a. valdivia-granda has been funded by the department of homeland security and the department of defense. we are greatfull to sarah cheeseman barthel, director, data acquisition & management metabiota, inc., for her review and input of the section on "global surveillance and data collection." key: cord- -f k authors: walsh, geraldine m.; shih, andrew w.; solh, ziad; golder, mia; schubert, peter; fearon, margaret; sheffield, william p. title: blood-borne pathogens: a canadian blood services centre for innovation symposium date: - - journal: transfus med rev doi: . /j.tmrv. . . sha: doc_id: cord_uid: f k testing donations for pathogens and deferring selected blood donors have reduced the risk of transmission of known pathogens by transfusion to extremely low levels in most developed countries. protecting the blood supply from emerging infectious threats remains a serious concern in the transfusion medicine community. transfusion services can employ indirect measures such as surveillance, hemovigilance, and donor questioning (defense), protein-, or nucleic acid based direct testing (detection), or pathogen inactivation of blood products (destruction) as strategies to mitigate the risk of transmission-transmitted infection. in the north american context, emerging threats currently include dengue, chikungunya, and hepatitis e viruses, and babesia protozoan parasites. the sars and ebola outbreaks illustrate the potential of epidemics unlikely to be transmitted by blood transfusion but disruptive to blood systems. donor-free blood products such as ex vivo generated red blood cells offer a theoretical way to avoid transmission-transmitted infection risk, although biological, engineering, and manufacturing challenges must be overcome before this approach becomes practical. similarly, next generation sequencing of all nucleic acid in a blood sample is currently possible but impractical for generalized screening. pathogen inactivation systems are in use in different jurisdictions around the world, and are starting to gain regulatory approval in north america. cost concerns make it likely that pathogen inactivation will be contemplated by blood operators through the lens of health economics and risk-based decision making, rather than in zero-risk paradigms previously embraced for transfusable products. defense of the blood supply from infectious disease risk will continue to require innovative combinations of surveillance, detection, and pathogen avoidance or inactivation. • through improvements in screening, testing, and real time surveillance, the residual risk of transmissible diseases in the canadian blood supply remains very low. • we continue to deal with infectious diseases which emerge or reemerge, such as chikungunya, babesiosis, and hepatitis e, as well as infectious diseases such as influenza, that threaten the security of the blood supply despite not being transfusion-transmissible. • new paradigms for transmissible disease prevention must become more cost effective in their scope, using targeted surveillance, donor screening, and risk-based decision making. dr margaret fearon, cbs medical director, medical microbiology, and assistant professor, university of toronto, discussed the current prevalence of classical transfusion-transmissible infections (ttis) in cbs blood donors, new and emerging infectious diseases, how cbs prepares for and manages new risks, and also addressed new paradigms for risk management. dr fearon began by emphasizing that several layers of protection in the canadian blood supply have likely reduced the risk of the classical ttis, (hepatitis b virus [hbv] , hepatitis c virus [hcv] , human immunodeficiency viruses [hiv] and , human t-lymphotropic viruses [htlv] i and ii, and syphilis). the success can be largely attributed to intensive donor testing for ttis, supplemented by donor education and deferral of donors with risk factors. the two latter approaches have reduced the number of donors with window-period infections and contributed to a decrease in confirmed transmissible disease-positive allogeneic donors over the last decade in canada, most notably for hbv and hcv [ ] . thus, the residual risk of ttis is low by any standard. the estimated residual risk in canada calculated in , using incidence rates from observed donor seroconversions to , is per million donations for hiv, per . million donations for hcv, and is per . million donations for hbv [ ] . dr fearon noted that updated residual risks are currently being calculated, but that compared to the report, the risks are not expected to change dramatically. dr fearon next turned her attention to newer and emerging infectious diseases that threaten the blood supply. some of these diseases have led to the introduction of new tti testing paradigms at cbs (ie, seasonal and selective testing for west nile virus [wnv] and chagas disease). other emerging infections are being monitored (eg, babesiosis, hepatitis e, chikv) while others such as influenza feature in contingency planning, in spite of not being transfusion-transmitted, due to their potential to disrupt blood donation and the health care system. she emphasized her opinion that transmissible disease testing must be context-specific, and account for local disease prevalence, environmental factors, and resource allocation. wnv is a mosquito-borne zoonotic arbovirus that emerged in north america in and was found to be transfusion-transmissible in [ ] . in humans, febrile illness occurs in % to % of wnv cases and % of patients have serious neurologic symptoms. since most cases are asymptomatic, tti testing is the primary means of preventing transmission [ ] . universal donor testing was adopted in using nucleic acid testing (nat). however, given the seasonal nature of wnv outbreaks, a more nuanced testing methodology was introduced by cbs in june that recognizes the lack of local transmission during the winter months. now, all donors are tested from june to november and only donors who travel outside of canada are tested during the rest of the calendar year. selective testing is also conducted for chagas disease. chagas is caused by the protozoan parasite trypanosoma cruzi and is endemic to central and south america and mexico, where it is estimated that - million people have been infected [ ] . with increasing northward immigration of people from these regions, it is estimated that n , people are infected in the united states, and most american blood services have implemented universal donor testing [ , ] . the rates of immigration from endemic countries are lower in canada and thus cbs tests donors who are identified to be at risk based on the donor questionnaire. those considered at high risk include those who were born or lived in an endemic country, or had a mother or maternal grandmother that was born or lived in an endemic country. the safety of this approach was demonstrated in a recent study that identified no evidence of infection amongst donors without risk factors identified on the questionnaire (with the exception of one very unusual transfusion transmissionvertical transmission case) [ ] . interestingly, the selective testing approaches used for wnv and chagas disease at cbs represent a change from the universal testing approach of the last three decades, which can be summed up as "test everyone for everything". the newer approach to certain ttis takes into account geographic location, seasonal effects, and other risk factors in setting the optimal testing strategy. dr fearon called attention to other infectious outbreaks that can impact the security of the blood supply despite not being transfusiontransmissible, and cited severe acute respiratory syndrome (sars) and pandemic influenza as examples. outbreaks of these diseases can lead to shortages of staff and donors due to illness and shortages of critical supplies. contingency planning is necessary to guard against these risks. staff and donor education, infection control procedures in the clinic, and reassessment of donor deferral criteria are key steps that must be taken to protect the blood supply in this context. other transfusion-transmissible diseases are currently being monitored as potential emerging threats to the safety of the blood supply, including babesiosis, hepatitis e, chikv, and dengue virus. babesiosis is caused by the protozoan parasites b microti, b duncani, and others in this genus, and spread by infected ticks. most infections are asymptomatic or unrecognized, but the spectrum of clinical severity also includes flu-like symptoms, ranging to more severe illness and death in the immunocompromised [ ] . babesia microti is the most frequently transfusion-transmitted microbial pathogen in the united states, especially in the northeast and upper midwest states [ ] . there were transfusion-transmitted cases reported from to in the united states with one case reported in canada [ ] . hepatitis e is clinically similar to hepatitis a and it causes water-borne outbreaks in developing countries. in canada, where it was previously thought to be primarily a disease of travelers, the actual prevalence of endemic hepatitis e is unknown. no cases of transmission by transfusion have been reported in north america, but transfusion transmission has been reported in endemic countries and recently in the united kingdom [ ] . chikv and dengue are two viruses common in the tropics that are spread by mosquitos. both lead to similar acute illnesses with fever, rash, and muscle/joint pain. transfusion-transmitted cases of dengue have been reported. chikv arrived in the caribbean in and was thus identified as a threat to north america [ ] . however, no transfusion transmitted cases of chikv have been reported to date. current malaria travel deferral provides some protection with respect to many but not all of the affected areas, particularly in the caribbean. how can blood operators best prepare for emerging threats? surveillance is conducted by multiple health agencies, including the world health organization (who), centers for disease control and prevention, and the international society for infectious diseases, which operates the promed (program for monitoring emerging diseases). available to any subscriber, promed is an internet-based reporting system dedicated to rapid global dissemination of information on transmissible diseases. the public health agency of canada is the federal agency responsible for transmissible disease surveillance in canada. public health agency of canada encompasses the national microbiology laboratory and in collaboration with the provincial public health laboratories, provides diagnostic testing and surveillance data that is useful in guiding cbs decision-making. testing data provided by the national microbiology laboratory on travel-acquired chikungunya was used by cbs to calculate an estimated risk of a case of transfusion transmitted chikv in canada of less than in million. collaboration with veterinarians, etymologists, and ornithologists may provide additional information to inform preparative and reactive strategies for emerging agents. for example, active tick surveillance reports provide risk data for lyme disease, but are also relevant to other tick-borne, transfusion-transmissible diseases such as babesiosis [ ] . a recent babesia seroprevalence study for b microti in canadian blood donors demonstrated that donor testing is not warranted in canada at this time [ ] . dr fearon presented as-yet-unpublished data on a collaborative cbs and héma-quebec (the transfusion service for quebec province) hepatitis e seroprevalence study that indicated that age is the only significant factor for increasing seroprevalence of hepatitis e. the absence of polymerase chain reaction (pcr)-positive results suggests that the risk of transfusion-transmission of hepatitis e in canada is extremely low; however, further prevalence data needs to be collected. a cbs donor travel survey from also provided data that is used to inform risk assessment. while the united states remains the most popular travel destination for cbs blood donors, nearly % of respondents reported travel to the caribbean. such donor travel survey data allows cbs to estimate potential donor loss when assessing the risk/benefit of deferring donors who have travelled to countries with outbreaks. the challenge facing all blood operators is to synthesize all of the available information on existing and emerging threats in order to rapidly make decisions that balance risks, costs, and safety. to meet this challenge, dr fearon suggested utilization of the alliance of blood operators' risk-based decision making framework for blood safety (fig : risk-based decision making framework) [ ] [ ] [ ] . this framework has a health sector focus, can aid evidence-based decisions using risk assessment tools, and accounts for multiple sectors included in the decision making process [ , ] . the use of this approach also represents a paradigm shift for blood operators, away from "zero-risk" to one that uses a decision-making process that integrates evidence, ethics, social values, economics, public expectations, and historical context with broader health care priorities [ ] . • the emergence of infectious diseases is unpredictable. • emerging infectious diseases (eids) is a global issue that demands international surveillance efforts. horizon scanning is important. • the eid tool-kit provides a useful framework for managing infectious threats to the blood supply. dr roger dodd, secretary general of the international society of blood transfusion, presented his perspectives on past and current pathogens affecting the safety of the blood supply. the objectives of his presentation were -fold: ( ) to define what eids are and why they occur; ( ) to discuss why some eids impact blood safety; ( ) to review how the impact on the blood supply is managed; and ) to examine some current examples of emerging infections and how they are being managed. dr dodd began with the institute of medicine's definition of an emerging infectious disease as one "whose incidence in humans has increased within the past two decades or threatens to increase in the near future". the institute of medicine further elaborates that "emergence may be due to the spread of a new agent, to the recognition of an infection that has been present in the population but has gone undetected, or to the realization that an established disease has an infectious origin. emergence may also be used to describe the reappearance (or reemergence) of a known infection after a decline in incidence" [ ] . eids often originate from animal-human interactions. a prime example is variant creutzfeldt-jakob disease (vcjd) which probably results from human consumption of meat from animals infected with bovine spongiform encephalopathy (also called mad cow disease) [ ] . it is estimated that approximately % to % of current eids are zoonoses, and they can be caused by any class of pathogenic agent (viruses, bacteria, parasites, and prions) and spread through several modes of transmission (fecal-oral, sexual contact, etc). infections emerge for a variety of reasons. pathogens may undergo a "species jump" as was the case in hiv [ ] and sars [ ] . environmental change, such as global warming, may increase the incidence and range of eids such as dengue, malaria, and babesiosis. drug resistance and mutations may lead to challenges in controlling malaria and hbv and subsequent spread. human migration and travel contributes to the dissemination of t cruzi (the chagas disease pathogen) and chikv. the migration patterns of birds, reservoirs for wnv, are also associated with the spread of this disease. certain parts of the world are considered to be "hot spots" for the emergence of infectious disease for a variety of reasons. for example, china is considered a prime site for the emergence of new strains of viruses (influenza and sars) due to the close proximity of human-human interactions and human-animal interactions, which can lead to the evolution of animal viral strains into novel strains that can infect humans. in a general sense, this evolution can be potentiated by the consumption of wild meat (meat from non-domesticated mammals, reptiles, amphibians, and birds). through careful phylogenetic analysis of simian and human viruses, africa has been recognized as the "hot spot" for hiv emergence, probably due to consumption of primate bush-meat by humans, [ ] . urbanization, poor sanitation, and crowding in the developing world have also been linked to hepatitis e emergence [ ] . although our understanding of the factors contributing to specific eid transmission has improved, these transmissions are likely multifactorial in nature. dr dodd emphasized that eids are both a local and a global issue. some infections may emerge explosively in new areas if appropriate conditions (eg, the vector or environment) are met, as is the case with wnv, dengue, and chikv. other eids, such as chagas disease, may expand slowly as a result of population movements, but can become constrained in their new environment. tick-borne infections, such as those caused by babesia in the united states, may be constrained regionally. infections that are characterized by direct human to human transmission may spread worldwide but at differing rates, depending on the mode of transmission such as the rapid respiratory spread of influenza and sars and slower sexual transmission of hiv. despite our understanding of infectious disease transmission, the emergence of these diseases remains largely unpredictable. understanding that eids may be spread by human travel and through animal contact allows us to understand the probability of acquiring an infection if specific conditions are met, but it does not allow us to predict which infectious disease will emerge and when. such unpredictability requires regular surveillance and hemovigilance efforts to be in place around the world. disease surveillance has many challenges, but warning signals may help focus efforts to better monitor disease spread. these warning signals may include disease outbreaks in particularly susceptible populations (such as the immunocompromised), and/or the blood-borne nature of a disease. why do some emerging infections impact blood safety? dr dodd noted that when an epidemic occurs, only a minute proportion is attributable to transfusion. for example, only % of hiv cases were transfusion-transmitted during the hiv epidemic [ ] . similarly, only of , wnv cases ( . %) were established as ttis [ ] . in other words, outbreaks are not likely to start from a transfusion, and transfused patients are not necessarily more likely to acquire an infection than the general population. for an infectious disease to be considered a transfusion-transmissible disease, certain pathogen-related and recipient-related characteristics have to be present. first, the pathogen must have an asymptomatic blood-borne phase (such as hepatitis b), which may either be acute or chronic. second, the pathogen must be able to survive the donated blood processing and storage procedures, including temperature changes, leukoreduction, and centrifugation. third, the disease must be transmissible by the intravenous route. fourth, the recipient has to be susceptible to infection. fifth, the disease must be a recognizable entity in the recipient once symptoms appear. next, dr dodd turned his attention to how the impact of eids on the blood supply is managed. in , the aabb published a list of eids of interest. each eid was categorized based on the threat it poses to transfusion safety, the level of regulatory concern, the lack of effective intervention, and the amount of public concern. the top priority was assigned to pathogens towards which intellectual and future resources should be focused: dengue viruses; babesia species; and prions causing human vcjd [ ] . the list also included chikv, plasmodium species, t cruzi, human parvovirus b , hiv, and hepatitis e. an eid tool-kit (fig ) was subsequently developed as a framework to guide health professionals and public health officials in triaging and managing infectious threats to the blood supply [ ] . the eid tool-kit presents: a variety of methods for eid surveillance; key questions to be asked when a threat is suspected; and potential courses of action based on the situation. the risk-based decision-making framework. the risk-based decision-making framework was designed by the alliance of blood operator to help blood operators identify, assess, act on, and communicate risk in decisions related to blood safety. it is a flexible tool, and its objectives are to optimize the safety of the blood supply while recognizing that elimination of all risk is not possible; allocate resources in proportion to the magnitude and seriousness of the risk and the effectiveness of the interventions to reduce risk; and assess and incorporate the social, economic, and ethical factors that may affect decisions about risk [ ] [ ] [ ] . included among the pathogens identified in the aabb report, several agents are being actively monitored both on a regional and global level. due to increasing reports of transfusion-transmitted cases, their poor prognosis in immunocompromised transfusion recipients, and the lack of effective prevention strategies, babesia species have been classified as a top priority for future blood supply safety efforts in the united states. prions such as vcjd are being monitored closely and donor screening has been successful in preventing their spread into the donor pool [ ] . prions are currently being investigated for their potential relationship with other protein-folding diseases such as alzheimer's disease [ ] . although respiratory infections (eg, middle east respiratory syndrome coronavirus) are not transfusiontransmissible, they do disrupt donor availability and organizational aspects of the blood collection and donation system. dr dodd expanded upon wnv, adding american insights into those earlier provided in the canadian context by dr fearon. west nile fever is caused by a flavivirus transmitted by culicine mosquitoes. the virus spread from southern europe, africa, and the middle east to india, and arrived in the united states in . by wnv was endemic in most of the continental us and canada [ ] . the experience of wnv in the us demonstrated that imported infections can be overwhelming and unpredictable. while wnv was considered a stable disease elsewhere in the world, in north america it was experienced as an explosive outbreak in and infecting over , individuals. public concern was high as wnv, previously unknown in north america, spread rapidly across the continent via infected birds, and then to humans via mosquitoes. although human to human transmission is not possible, there is potential for transfusion-associated transmission if the donation occurs during periods of pre-symptomatic viremia. nat of pooled donor samples offered a rapid route to testing. like other north american blood operators, cbs tests donors in pools. if a pool tests positive, individual donor testing is initiated. after nat was initiated in the us in , cases of transfusion-transmitted wnv have only rarely been encountered [ ] . horizon scanning efforts are actively monitoring other potential eids. dr dodd described several emerging agents for which there is some evidence that that have or an assumption that they may be transfusion-transmitted including severe fever with thrombocytopenia syndrome virus (no reported transfusion transmission [tt]), q fever (one report of tt, but no definitive evidence), hepatitis e virus (good evidence of occasional tt), vcjd, and other prions (evidence for tt) [ ] . dr dodd focused on two viruses that are current causes for concern. dengue virus is an important arbovirus. like wnv, it is a flavivirus and is spread by mosquitos (aedes genus). humans are the amplifying host, and while a vaccine is under investigation there is currently no vaccine or specific treatment. vector control is the only effective intervention. there are an estimated million infections per annum worldwide [ ] . in % to % of cases infection is asymptomatic. dengue viruses have been found to be transfusion-transmitted in separate geographic clusters in hong kong, singapore, puerto rico, and brazil. currently, there is no fda-licensed test for dengue rna [ , ] . chikv, which has caused recent massive outbreaks in the caribbean and co-exists with dengue virus, is a potential threat to the north american blood supply due to its geographic proximity and donor travel emerging infectious disease toolkit. the emerging infectious disease toolkit is a framework developed by the aabb transfusion-transmitted diseases, emerging infectious diseases subgroup to guide health professionals and public health officials in triaging and managing infectious threats to the blood supply. the eid tool-kit presents: a variety of methods for eid surveillance; key questions to be asked when a threat is suspected; and potential courses of action based on the situation [ ] . patterns [ ] . chikv recently appeared in the caribbean. should it arrive in north america, donors could be deferred for exposure or symptoms, nat testing for chikv rna could be initiated, and red cell and plasma collections could even be stopped. dr dodd stated that pathogen inactivation will likely become increasingly important in preventing transfusion-transmission of emerging agents. the american red cross in puerto rico is currently involved in a trial to investigate and monitor the safety of intercept pathogen inactivation technology (cerus corporation). intercept was recently approved by the fda for use with apheresis platelets. use of intercept to make available pathogenreduced apheresis platelets could prevent interruptions in the local platelet supply in areas where viruses like chikv emerge [ ] . • the ebola outbreak in west africa was the largest in history. • the difficulties in identifying the virus in west africa and in containing its spread were related to poverty, growing populations and deforestation, lack of healthcare infrastructure and resources. these fundamental issues must be addressed in order to prevent and/or contain future outbreaks. dr allison mcgeer, director of infection control at toronto's mount sinai hospital, used the recent ebola outbreak in west africa to provide a thought-provoking global perspective regarding pathogens and their spread. as a consultant on a who-initiated mission to liberia, dr mcgeer obtained first-hand information and impressions of the situation on the ground in west africa, where she navigated issues related to policy and healthcare set-up. ebola virus is difficult to study because of its high mortality rates, and because it often occurs in areas that are difficult to access due to poor infrastructure or because of conflict or political turmoil. ebola infections seem to emerge due to the interconnection of enzootic and epizootic cycles [ ] . the first sequence involves bats as the most likely reservoir host for the virus, which is spread by enzootic transmission within the bat population. from this pool of virus carriers, transmission to other non-human species is thought to happen in an epizootic cycle. initial transmission to humans involves contact with infected bats or other species through hunting or accidental contact with ill wild animals. humanto-human spread via direct close contact is then very efficient. once humans are infected, the ebola virus first appears to target the immune system and subsequently destroys the vascular system, leading to blood leakage. initial attacks on dendritic cells lead to decreased interferon production and macrophage and endothelial cell degradation [ ] . this pattern results in clinical presentations of hemorrhage, hypotension, drop in blood pressure, followed by shock and death [ ] . the ebola outbreak, which primarily affected guinea, sierra leone, and liberia in west africa, is the most recent in the history of ebola epidemics [ ] . since , more than outbreaks have been recorded in sub-saharan africa leading to hundreds of cases and deaths [ ] . historically, infection has been controlled by local communities with the isolation of any patient showing symptoms. however, in in west africa, the outbreak was on an unprecedented scale. dr mcgeer provided an eye-opening overview of health infrastructure in the affected west african countries. guinea, liberia, and sierra leone have populations of . , . , and million, respectively (vs million in canada). spending on health (total expenditure per capita) is us$ , us$ , us$ , and us$ in guinea, liberia, sierra leone, and canada, respectively [ ] . this imbalance is mirrored in the number of doctors per , population: , . , . for guinea, liberia, sierra leone, respectively, compared to . in the united states of america [ ] . under-resourcing of public health and healthcare delivery was an important contributor to the unprecedented scale of the epidemic. the first step in this epidemic was the spread of the virus from a reservoir in west africa, but the outbreak was aided by many economic, political, and geographic factors. being now relatively stable after periods of civil war, these countries have increasing birth rates and increasing populations. the median age in guinea, liberia, and sierra leone is . , . , and , respectively (vs in canada). the ever-growing population and deforestation is believed to have accelerated the frequency of the epizootic cycle. once rich in forests, west africa has been intensively logged over the last decade. guinea's rainforests have been reduced by %, while liberia has sold logging rights to over half its forests. some analysts have predicted the complete deforestation of sierra leone within the next few years [ ] . the forests are the habitat for fruit bats, ebola's probable reservoir host. with the loss of their habitat, the bats escape to urban environments to hunt for food, coming in contact with humans and triggering more frequent transmissions of the virus. dr mcgeer personally witnessed the huge barriers to effective control of the epidemic in hospitals in liberia. she pointed to the rudimentary nature of facilities and equipment, poor hygiene, and a lack of infrastructure for disposing of hospital waste. dr mcgeer commented that due to the lack not only of resources but also of any form of emergency plan, the base from which to fight the epidemic was completely lacking. the lack of resources for infection control and personal protective equipment are the main reasons for nosocomial transmission [ ] , and affected healthcare workers can act as amplifiers spreading the virus into the community. in the epidemic, in healthcare workers were infected, and of those, in are believed to have died [ ] . this devastated the ability of front-line healthcare workers to control the epidemic, and led to hospital closures. poor general infrastructure hindered transportation of medical supplies and expertise, isolating rural areas and limiting access. dr mcgeer highlighted the absence of public health and health care infrastructure as a fundamental issue in being able to fight this disease, not just on the ground in west africa, but globally. this issue is illustrated by a fragmented global health system is which the institutions, laws, and strategies are not interconnected. experience of this outbreak has led to calls to reform the worldwide health systems architecture and the who [ ] . some media reports led to widespread misunderstanding of the ebola outbreak as an "african problem," and unhelpfully perpetuated prejudicial colonial-era stereotypes. dr mcgeer took the audience through the evolution of the epidemic in liberia which peaked in august/september . during july and august the number of confirmed cases per day increased from about to about , and ebola treatment units and burial systems were overwhelmed. in monrovia, the liberian capital city, about % of patients with ebola virus disease were being managed at home. despite this, hospitals were overwhelmed with ebola patients, filling to % of its capacity. many health care workers were infected, which ultimately led to the decision to close hospitals. at the peak of the outbreak, the president of liberia quarantined west point, a township particularly badly affected. this decision led to riots in that area. similar actions took place in other parts of liberia [ ] . as a consequence of the deteriorating situation in west africa, international responses were initiated [ ] . by september , more than non-governmental organizations were on the ground in liberia to contribute to the fight against ebola. their work spanned a wide range of activities including: setting up medical care; contact tracing; opening orphanages; providing food for people in quarantine; building roads for improved access to cemeteries; identifying how to de-sludge septic tanks from ebola treatment units; and sourcing and supplying personal protection equipment for ebola treatment units. the crisis response also involved a coordinated international response of unprecedented scale to accelerate vaccine development. no vaccine had ever been tested in humans prior to , but several were fast-tracked through phases i and ii, and in june of , an international group of scientists published the interim results of an open-label, cluster-randomized ring vaccination trial of an engineered vesicular stomatitis virus-based ebola vaccine developed at canada's national microbiology laboratory [ ] . ring vaccination seeks to create a buffer of protection around each case, so that the virus cannot continue to spread. this initial trial found that % of recipients were protected from the virus; further study of this vaccine and trials of other vaccines are on-going. with improvements in the coordination of the overall emergency response, more than a year later, the outbreak is under control. occasional cases were still appearing in liberia in november , but on november , , who declared the end of ebola virus transmission in sierra leone, as days had passed since the second negative test of the last confirmed patient with ebola in the country [ ] . control of the outbreak was only achieved through the institution of effective control and quarantine measures and an understanding of local practices and challenges that impacted the spread of the virus. dr mcgeer added her voice to the chorus of experts recommending coordinated national and international efforts to prevent future outbreaks. early warning systems should be developed in connection with local communities in high-risk areas, and provision of clearly defined response recommendations specific to the needs of each community [ ] . recent advances in diagnostics, risk mapping, mathematical modeling, and pathogen genome sequencing have the potential to improve substantially the quantity and quality of information available to guide the public health response to outbreaks [ ] . however, prevention remains extremely difficult [ ] . the world bank estimated that an~$ m investment in public health in west africa would have prevented more than % of cases in west africa. this missed opportunity eventually led to a costly emergency response estimated by the un mission for ebola emergency response at about $ . billion. future epidemic control measures in poverty-stricken areas, including worldwide response teams and pre-approved emergency funds may improve outbreak response, but addressing the fundamental issues of poverty, infrastructure, education, healthcare, workforce development, and communications will be needed if outbreaks are to be prevented [ ] . • several approaches for the production of red blood cells (rbcs) ex vivo exist and have demonstrated feasibility; however, none can yet be conducted on a scale that would allow replacement of donor-derived rbcs • to improve the chances of success in bringing ex vivo rbcs to the clinic, a multidisciplinary approach and an integrated plan are required to navigate the long path from concept to commercial product. an alternative means to keep the blood system safe from pathogens is to move away from the current paradigm of donor-derived products. this topic was addressed by dr marc turner, medical director at the scottish national blood transfusion service and professor of cellular therapy at the university of edinburgh. dr turner began by mentioning some milestones in the history of blood transfusion, highlighting a number of events that took place in his adopted home city of edinburgh, scotland. for example, in the first systematic experiments in intra-species transfusion were carried out by john henry leacock, who was studying in edinburgh at the time. james blundell, a university of edinburgh medical school graduate, is credited with conducting the first successful human transfusions several years later. since early in the last century, transfusion has become a mainstay of clinical practice with around million rbc transfusions conducted annually worldwide [ ] . for the most part, and particularly in developed countries, blood transfusion is safe. however, limitations remain, including sufficiency of supply, immunological compatibility of the donor and recipient, the risk of ttis, and the risk of other complications such as iron overload. many of these limitations could potentially be overcome by the production of rbcs for transfusion in the laboratory. dr turner's talk focused on human stem cells and their potential use for the ex vivo generation of rbcs for transfusion. dr turner discussed the biological and engineering limitations that must be overcome in order for ex vivo generated cells to become viable alternatives to donor-derived rbcs. the first conclusive observation of stem cells was in by mcculloch and till in the host city of this symposium -toronto [ ] . stem cells have the capability for self-renewal and can differentiate into multiple lineages, ultimately resulting in the generation of differentiated cells or tissues. there are various types of stem cells, including those derived from embryos (eg, human embryonic stem cells [hescs]) and from adults. not all stem cells are the same. for example, hescs are pluripotent and have unlimited ability to replicate, whereas adultderived hematopoietic stem and progenitor cells (hspcs) can differentiate into cells of the hematopoietic and immune systems and have limited ability to replicate. found in the bone marrow, hspcs are morphologically indistinct from other bone marrow cells, and are distinguished as cd + cells using flow cytometry. in vivo, hspcs are found in a hypoxic environment at the edges of the bone marrow. as they differentiate, they move more centrally in the marrow into an environment with a higher o tension. it has long been known that when placed into agar/semisolid medium and provided with the right cytokine support, hspcs can differentiate along different hematopoietic lineages, forming granulocyte/monocyte, and erythroid colonies with to days [ ] . culturing hspcs in suspension using a two-phase culture system has several advantages over solid-phase culture [ ] , the in vitro environment can be more precisely controlled and can be separated more easily [ , ] . dr turner provided an overview of a two stage culture system which uses combinations of cytokines to control cell differentiation and proliferation and can be used to produce erythroid cells from cd + adult peripheral blood cells. during the enucleation process, which moves the cells into the early reticulocyte stage, the nucleus is extruded from the cell, and engulfed by macrophages. by days to of the two-stage culture, the population consists of approximately % normoblasts and % early (r ) reticulocytes. other -stage systems have had demonstrated success expanding cd + hspc from peripheral blood, bone marrow, or cord blood into functional rbcs [ ] . these proofs-of-principle demonstrated that rbc generation ex vivo is possible, but processes described to date have limited scalability and do not yet constitute a workable approach to generate rbcs for transfusion. dr turner spent the remainder of his talk discussing the two major types of challenges facing the ex vivo generation of rbcs for transfusion: biological challenges and engineering/logistical challenges. from the biological point of view, one major challenge is to determine the best source from which to derive the cells. adult hematopoietic stem cells (hscs), one potential source of ex vivo rbcs, have a limited replication capacity; they could generate a small number of units of rbc but the reliance on donors remains. unlike hscs, hescs have indefinite expansion capabilities and can self-renew, and were a source of much excitement when their derivation was first described [ ] . hescs are pluripotentthey can be cultured indefinitely as cell lines and are able to differentiate into all the cells of the body including hematopoietic cells [ ] . in , a considerably less ethically-controversial source of pluripotent stem cells was discovered-induced pluripotent stem cells (ipscs) [ , ] earning the discoverer the nobel prize for medicine in . initially generated by takahashi and yamanaka from human somatic skin fibroblasts by the use of four genes (oct /sox /klf /myc), ipscs are very similar to hescs, can be differentiated into all three germ layers and have huge potential for regenerative medicine applications and disease modeling. like hescs, human ipscs can be differentiated into hematopoietic cells in vitro [ ] [ ] [ ] [ ] , and this is an area of intensive research [ ] . dr turner provided an overview of a system by which rbcs can be derived from human pluripotent stem cells (hpsc) in vitro using a feeder/serum free approach and cytokine mixes that drive the hpsc to hspcs, then erythroblasts, normoblasts, and eventually reticulocytes over an approximately -day time frame. the differentiation process is complex and uses mixes of multiple cytokines and small molecules. several issues remain including the long differentiation time, and the fact that while hpsc-derived rbcs can enucleate, the resulting cells are fragile and difficult to maintain in culture. the hpsc-derived rbcs express α/γ globin chains, the same combination of hemoglobin polypeptides expressed in fetal rbcs (as opposed to α/β globin chains in adult rbcs); however, the oxygen-delivering characteristics of the hpscderived rbcs are acceptable and therefore this would not preclude their use. efforts are underway to optimize erythrocyte differentiation and enucleation and modify the hemoglobin to a more adult form [ , ] . another approach that holds promise is to immortalize multipotent stem cells using well-understood and established methods. conditional immortalization from hpscs or adult hspc can be achieved using human papilloma virus e /e or combinations of transcription factors. this approach can establish immortalized human erythroid progenitor cell lines [ ] . switching off the immortalization allows the production of enucleate rbcs ex vivo. this approach has several benefits over psc-as a starting material: the process is less complex and the differentiation time is shorter; there are reduced costs related to cytokines, growth factors, and media; and the final rbc phenotype is closer to an adult phenotype. the feasibility of this approach to produce enucleated rbcs has been shown [ ] . potential drawbacks of this approach include concerns regarding: the introduction of oncogenes into the cells; cell line stability; and the likelihood of being able to meet good manufacturing practice standards and produce clinical grade products. notwithstanding the difficulties involved, the potential now clearly exists to allow culturing of rbc with rare phenotypes or modification of the rbcs [ ] to help meet the needs of hard-to-match transfusion recipients. the first proof-of-principle human transfusion with ex vivo generated rbcs cultured from peripheral cd + hsc was conducted in , and showed that post-transfusion survival of ex vivo generated rbcs in a single, healthy subject was comparable to that of donorderived rbcs [ ] . dr turner then turned his attention to the engineering technology needed to make ex vivo generated rbcs a viable alternative to donorderived products. the key issues here are scale-up, process control, and intensification. dr turner described the use of the ambr bioreactor technology (from tap biosystems, part of the sartorius stedim biotech group) as an approach to optimising the in vitro culture environment. stirred tank bioreactors are a mature technology that is scalable and well-established for production of biotherapeutics. they allow for precise control of several physico-chemical parameters and economic/ rapid development screening at a variety of scales ( ml, ml, multi-liter). there are two gross limits to system efficiency. the first is the absolute density limit, which is calculated from specific oxygen uptake rate of cells and the mass transfer coefficient of the system. in this regard, the bioreactor system performs well; high density can be achieved, and the potential is certainly there to succeed in scaling it up to the needs of producing erythroid cells. the second limit is media volumetric productivity (liters of media/units of blood). volumetric productivity is precisely determined by cell growth rate and specific support capacity of the media-consumption and supplementation. specific rates are unstable and supplementation with glucose and glutamine does not improve growth, suggesting these are not limiting factors. in order for potential scale-up of this system, the limiting factors need to be identified. currently, dr turner estimates that the costs of ex vivo-derived rbcs stand at many times the cost of donor-derived rbcs. at this stage this technology is therefore only likely to be considered for "boutique" applications in patients for whom a donor-derived matched product is difficult or impossible to source. for more generalized application, many challenges remain, including control over the genetic and epigenetic stability of cell lines; optimization of the differentiation pathway to allow stable enucleation; efficiency of the differentiation pathway; process control over multiple physical and biochemical factors; scale up and intensification to control the cost of goods; detailed characterization of the product; demonstration of preclinical safety and efficacy; quality control and regulatory compliance; and the design and execution of pivotal clinical trials [ ] . many of the challenges dr turner mentioned are common to all cellbased therapeutics. regarding quality control and product characterization, one advantage in this field is that there is more than years of rbc product characteristic information, knowledge, and experience on which to draw. dr turner ended by noting that a sea change in the level of process control would be required to make the production of the ex vivo rbcs a reality. dr turner outlined the environment, resources, and approaches he believes are necessary in order for this type of innovation to take place and achieve commercial success [ ] . this includes multidisciplinarity, integrated planning, and lengthy time lines and in these regards dr turner acknowledged the commitment of the research teams and funders working in this space. • pathogen testing in canada is centralized, automated, and closely regulated by the federal government. ms. nancy angus, director of testing at cbs, provided an overview of the current state of testing at this organization, with an emphasis on donor testing. focusing on tests in use in canada, ms. angus described laboratory tests for the detection of blood-borne pathogens and summarized the differences in sensitivity among the tests currently in use. cbs testing sites include donor testing, diagnostic services, the national testing laboratory, national reference laboratories, quality control product laboratories, and the human leukocyte antigen laboratory. donor testing, which includes transmissible disease testing, is performed at two sites: calgary, alberta, where all blood collected west of ontario is tested; and toronto, where all blood collected in ontario and east of ontario is tested. each site is a mirror-image of the other in terms of equipment, and can act as a back-up for the other site for business continuity reasons should the need arise. all blood collected by cbs is tested for a number of blood-borne pathogens: syphilis; hiv- and − ; hbv; hcv; and htlv i and ii (table ). since implementation in , wnv testing has been performed on all collected blood; however, as of , that testing is now performed seasonally. in addition to mandatory testing performed on all collected blood, there are tests that are performed based on risk. approximately % of collected blood is tested for cytomegalovirus (cmv) in order to supply hospital demand and based on an algorithm identifying which donors are most likely to be cmvfree. testing for chagas is performed selectively, based on risk; donations from donors indicating on their questionnaires that they or their mothers or maternal grandmothers originate in a chagasendemic country or that they have had extended stays in endemic areas for greater than six months. chemiluminescent assays are performed using the abbott prism platform to detect the surface antigen of the hepatitis b virus (hbsag), total antibody to hepatitis b core antigen, antibodies to hepatitis c virus, antibodies to hiv- groups m and o and/or antibodies to hiv- , antibodies to human t-lymphotropic virus type i and/or human tlymphotropic virus type ii, and antibodies to t cruzi. agglutination assays are performed on the beckman coulter pk platform: syphilis infection is identified using a micro-hemagglutination assay to detect treponema pallidum antibodies, and cmv infection is detected using a passive particle agglutination assay to detect total cytomegalovirus antibodies. nat is performed using the roche cobas platform to detect hiv- rna (groups m and o), hiv- rna, hcv rna, hbv dna, and wnv rna. samples are screened in pools of , and single unit testing is performed on selected donations from the same geographic region when a positive donation for wnv is identified. in canada, all testing platforms require approval by health canada. other platforms currently available include the immucor neo platform, which is a solid phase system that allows for the serological detection of syphilis and cmv, and the grifols tigris platform, in use at hema-quebec, which performs nat to detect hiv rna, hcv rna, hbv dna, and wnv rna. if a blood donation is found to be serologically reactive, confirmatory testing is performed to determine if the donor is a "true" positive. confirmatory testing is either performed at cbs or at an external agency. within cbs, confirmatory tests include hbsag neutralization assay, immunoblots for hiv- , htlv i, htlv ii, and hcv, and enzyme immunoassay to detect hiv- . syphilis confirmatory testing is performed at either the alberta public health laboratory or the ontario public health laboratory and chagas confirmatory testing is performed at the national reference centre for parasitology in montreal. the medical services and innovation division at cbs performs surveillance to identify blood-borne pathogens that may pose a threat to the blood supply. if it is decided that a new test needs to be implemented to identify a new pathogen or new equipment is required to replace equipment at the end of its life, health canada licensure is required, unless there is an emerging threat. currently on the horizon, cbs is considering the possibility of introducing hepatitis e virus nat, and testing for babesia next generation sequencing: the future of pathogen testing? • next generation sequencing (ngs) is an advanced technology approach that involves sequencing all dna found in a clinical sample. • innovative bioinformatic approaches are required to minimize the computational time required to find pathogen dna in the sample and to maximize accuracy. • ngs is being increasingly used for otherwise indeterminate clinical diagnoses, for tracking of infectious disease outbreaks, and to detect novel pathogens. • ngs is unlikely to play a role in screening the blood supply for infectious disease markers in the near to medium term. dr samia naccache, associate specialist, department of laboratory medicine, university of california san francisco (ucsf) school of medicine, introduced attendees to the use of next generation sequencing, metagenomics, and bioinformatics for the detection and identification of infectious agents. dr naccache first pointed out that she was a member of the laboratory of dr charles chiu, which is home to the ucsf/abbott viral diagnostics and discovery center (ucsf/avddc), and that the center works closely with the ucsf clinical microbiology laboratory to provide advanced technology assistance with the most challenging problems in infectious disease diagnosis and tracking. dr naccache commenced her presentation by contrasting "classical" dna sequencing methods with next generation sequencing (ngs). anti-hiv and , antibodies to hiv- groups m and o and antibodies to hiv- ; nat, nucleic acid testing; anti-hbc, total antibodies to hepatitis b core antigen; anti-hcv, antibodies to hepatitis c virus; anti-htlv i/ii, antibodies to human t-lymphotropic virus i and human t-lymphotropic virus type ii. ⁎ only selected units are tested. § single unit limit of detection; theoretical sensitivity is calculated by multiplying single unit limit of detection by . frederick sanger and colleagues invented a method of dna sequence determination in the s [ ] that was intensively used by scientists for the next years [ ] . sanger sequencing was based on the selective and partial incorporation of chain-terminating dideoxyribonucleotides into copies of the dna strand being sequenced, and their separation by denaturing electrophoresis into a readable sequence "ladder". dr naccache stressed that sanger sequencing, even in later, high throughput versions, was employed on one limited piece of dna (typically a small dna sector amplified using pcr) at a time to yield a single output sequence. although this method was sufficiently advanced to be used to sequence first the human mitochondrial genome [ ] and then the entire human genome [ , ] , its robustness pales in comparison to ngs approaches. ngs yields huge amounts of dna sequence in parallel; in other words, many sequences in a sample can be analyzed simultaneously [ ] . for this reason, ngs is also called deep or massively parallel or high throughput sequencing. its information output is such that thousands or millions of sequences can be provided concurrently, in a matter of hours. ngs has made possible metagenomic approaches, in which all dna sequences from all genomes present in a clinical sample can be identified. this approach can now be used to determine if a blood sample contains only human dna, or human dna plus the dna of an infectious pathogen, as well as to identify that pathogen if its sequence is known. a brief technical overview of ngs methodology was provided by dr naccache. all dna/rna present in a sample is first rapidly extracted (or copied using pcr) and fragmented into pieces of uniform length, providing a library. short artificial dna sequences are then bonded onto either end of all library dna fragments. these adaptors allow hybridization of one strand of the modified dna to complementary, tethered pieces of dna in a flow cell. they are then "sequenced by synthesis" using fluorescent deoxyribonucleotide triphosphate building blocks. as each base is added to the growing chain, its position is noted via imaging and the positional information is captured in parallel. ngs can therefore provide to gigabytes of data-much of it "redundant" in that the same sequence has been detected and read multiple times-to ensure sufficient coverage of all dna sequence present in a sample. this huge amount of data is first processed using algorithms that detect and remove low quality reads, and then the "host" or human genome sequence information is subtracted. the remaining dna is assembled into contiguous arrays by alignment of overlapping sequences, and compared to reference genomes of known pathogens. if an identified pathogen differs slightly from reference genomes, taxonomic classification can then be done to determine how recently the variant has diverged from known sequences. dr naccache stressed that this approach will work on bacterial, viral, fungal, and parasitic pathogens, all encoded by rna-or dna-based genomes, but not on prions, which are protein-based pathogens that infect by causing host proteins to take on pathological conformations. ngs is an advanced technology approach fully dependent on the characteristics of the instrumentation employed. dr naccache surveyed the rapid development of commercial deep sequencing machines [ ] . first to market in was roche, with its sequencer, capable of reads of to bp. illumina and ion torent produced instruments that generated millions to billions of reads of slightly shorter sizes of to bp, with similar overall run times, between and . these products all worked on the paradigm of sequencing by synthesis. the most recent entries into this instrumentation field work on a different principle, called nanopore sequencing: pac bio's rs apparatus ( ); and oxford nanopore technology's minion ( ). both instruments are capable of a smaller number of reads than earlier machines (up to , ) but the reads are much longer, up to , bp. the technology works on the principle of detecting a growing dna chain electrically when the chain is extruded through an engineered protein pore of nanometer diameter. the minion instrument is amazingly small to essentially the size of a large memory stick [ ] . effective exploitation of the "mountain" of dna information produced by ngs from a clinical or blood bank sample requires minimizing computation time and maximizing the accuracy of the diagnostic output. dr naccache and co-workers developed a bioinformatics platform for these tasks called surpi, sequence-based ultra-rapid pathogen identification [ ] . such platforms are necessary given the size of the ngs output dna sequence, the size of pathogen reference sequence databases, and the fact that pathogen sequences typically constitute no more than . % to % of reads in the ngs output. this presents a needle in a haystack-type problem. to achieve rapid and robust detection, surpi employs two analyzer programs that work on both dna and translated protein alignments, using bacterial and viral databases. the platform can be employed in either fast or comprehensive mode; in fast mode pathogenic sequences can be identified in a clinical sample in minutes to hours, while comprehensive mode is more appropriate for detection of a novel pathogen's entire genome or to rule out infection in a clinically complex case. dr naccache noted that % to % of clinically significant respiratory infections are currently of unknown etiology. dr naccache presented data comparing the time of completion of analysis of ngs data using either surpi mode on a variety of clinical sample types. serum took less time to analyze than biological materials open to the environment (eg, stool samples); hiv spiked into plasma could be detected in minutes in either mode, down to viral copies per milliliter, with successful identification of strain specificity. surpi was extensively tested and optimized using such clinical samples prior to its employment in a prospective clinical case series carried out at the ucsf between april and december . this was a single-site study with respect to analysis, but included cases referred from across the united states and also from europe. the study included acutely or chronically ill, hospitalized patients with clinical features suggestive of an infectious disease but who tested negative for all candidate agents. dr naccache highlighted two of the diagnoses achieved by ngs in the clinical series. the first involved an adolescent boy whose fever and headaches evolved over the course of four months to hydroencephalopathy that forced his physicians to induce a coma to stabilize him [ ] . following over a hundred inconclusive laboratory tests, ngs revealed the presence of leptospira santarosai, a pathogenic bacterium, in cerebrospinal fluid samples. in view of the patient's poor status and the safety of the specific treatment for leptospira had the ngs-based diagnosis been incorrect, intravenous penicillin treatment was commenced before confirmation of leptospira infection was received from the center for disease control. following weeks' treatment followed by rehabilitation, the patient made a full recovery. in the second case highlighted by the speaker, a -year-old man underwent a bone marrow transplant, with immunosuppression, for treatment of chronic lymphocytic leukemia [ ] . a month later he developed tinnitus and partial deafness, which progressed rapidly and was accompanied by increasing mental deterioration. brain biopsy tissue was assessed by ngs, which detected neuroinvasive astrovirus infection, for which there is no known efficacious therapy; the patient died months post-ngs diagnosis and . months after the onset of symptoms. ngs sample to answer turnaround times were reported to be hours in the first case [ ] and hours in the second [ ] . a substantial list of the different pathogens detected by the ucsf/ avddc group using ngs in different biological fluids such as csf, respiratory secretions, and blood, was next presented by the speaker. in the latter category, the agents included pathogens familiar to the transfusion medicine-oriented audience such as the viruses epstein-barr virus, cytomegalovirus, hiv- and - , west nile virus, hepatitis viruses a through e, and chikv virus (chikv), the bacterium pseudomonas aeruginosa (which can be transferred from donor skin into blood products by venipuncture) and the parasite plasmodium falciparum (one of the causative agents of malaria). also included on the ngs detection list were less familiar agents, such as rna viruses enterovirus d , hantavirus, pegivirus, and rhinovirus c, double-stranded dna viruses such as four variants of human herpesviruses, and the bk and jc viruses, and various single-stranded dna viruses of the cycloviridae and anelloviridae families, the bacterium salmonella typhi, and the parasite leishmania infantum. the sensitivity of ngs is underlined by the detection of viruses that are not usually associated with disease (anelloviridae) or are only associated with disease in immunosuppressed individuals (the bk and jc viruses) that may be part of the "background flora and fauna" in humans that must be discounted in arriving at a bona fide ngs diagnosis. dr naccache continued with a consideration of recent results from the ucsf/avddc group employing nanopore sequencing. the ucsf/ avddc participated in a research program sponsored by oxford nanopore technologies designed to probe and optimize the capabilities of the minion instrument. dr naccache reported that, using minion and a surpi-like bioinformatics platform called metapore, plasma samples from individuals separately infected with chikv, ebola virus, and hepatitis c were rapidly identified in real time [ ] . for chikv and ebola virus, samples contained to copies/ml and were detected within to minutes of data acquisition; lower-titer hepatitis c virus ( copies/ml) was detected within minutes. the analyzer algorithms successfully identified these viruses despite the relatively error-prone nature of the sequence data. the total sample to answer time was less than hours, a feat apparently unprecedented in the ngs area. dr naccache then provided a cautionary tale illustrating the extreme sensitivity of ngs which involved parvovirus-like hybrid virus, a previously undescribed novel virus related to both circoviridae and parvoviridae families, initially detected in chinese patients with chronic seronegative hepatitis of unknown etiology [ ] . the ucsf/avddc group also found parvovirus-like hybrid virus by ngs in their hepatitis cohorts, but eventually realized that the virus was present in commercial silica-type spin columns used for dna purification/concentration, but not in any original patient sample [ ] . the silicates are typically sourced from cell walls of diatoms and a % concordant pvh sequence was found in environmental metagenomics databases of samples taken from north american coastal waters. this instance of laboratory contamination illustrates the extreme sensitivity of ngs and the methodological stringency that must be brought to its application. in wrapping up her presentation, dr naccache discussed the likelihood that ngs would contribute directly to blood donation screening. she assessed this outcome as somewhat improbable over the near term, in part because blood donation screening is currently highly effective. ngs is currently quite expensive in its most accurate form, leading dr naccache to estimate the cost of a well-covered ngs study of around samples using a total of million sequences on the hiseq platform at us$ , and a more shallow study, of the kind described above for rapid detection of ebola and chikv, of around samples using a total of million sequences on the miseq platform, at us$ . however, these estimates do not truly take into account the substantial infrastructure in place at ucsf/avvdc, which comprises specialized equipment for sample extraction, library generation, and validation, ngs sequencing, and extensive computational analysis, not to mention the skills of medical technologists, researchers, and bioinformatics specialists. the relevance of ngs with respect to keeping the blood system safe from emerging pathogens will more likely lie in determining patterns of disease transmission and providing the confidence necessary to re-qualify a previously deferred blood donor. suspected transmission by transfusion can be identified rapidly with great sensitivity and specificity using ngs of all implicated donors and recipients. it can also be used in a general, epidemiological sense, to trace patterns of infection and adaptation and speciation of infectious agents. while the contributions of ngs to clinical diagnosis of intractable cases and to public health, with respect to tracking and understanding disease outbreaks are already substantial, and will likely continue to accumulate exponentially, the prospects of using ngs for routine blood donation screening remain remote due to cost and throughput considerations. the biological impact of pathogen inactivation on blood product quality • pathogen inactivation (pi) of blood products may be advantageous as they overcome some of the limitations of current strategies (eg, assay sensitivity and threats of emerging pathogens). • pi techniques bring two sides of a coin into blood banking: improved safety versus a negative effect on blood component quality (damage to~ %- % of platelets). • in order to improve the quality of pathogen-inactivated blood products, molecular mechanisms triggered by these technologies need to be identified. • pi-treatment of whole blood might be the emerging method of choice in this field. dr peter schubert, research associate at the canadian blood services' centre for innovation and a clinical associate professor in the department of pathology and laboratory medicine at the university of british columbia, focused his talk on the need for pi to ensure the safety of the blood supply. he compared the currently available pi technologies and their mechanisms of action, and discussed the potential impact of this technology on product quality. dr schubert noted that blood safety has historically been achieved by mitigating known risks with interventions such as donor screening and universal donor testing for specific pathogens. however, risks remain, as all tests have a detection limit and current testing does not account for unknown or unexpected pathogens. thus, pi has the potential to improve the safety of blood products by preventing ttis, especially in platelet products, where bacterial contamination is a particular risk [ ] . in the united states, the intercept blood system from cerus corporation is currently licensed for platelet products, and both intercept and the octaplas product from octapharma are licensed for plasma (table , [ ] ). in canada, the only currently licensed pi product is octaplas plasma. three different pi systems for platelet concentrates are currently on the market ( table ) . these exploit the fact that pathogen proliferation occurs by replicating dna or rna, a mandatory step for all pathogens except prions. all use uv light, with or without a photosensitizer, to damage nucleic acids and subsequently prevent proliferation of pathogens. many of these systems are in routine use, mostly in europe and the middle east [ ] , and in many other jurisdictions regulatory approval is initiated and under investigation. worldwide, the cerus intercept blood system is the most adopted system, and has been in routine use for over years. hemovigilance data from jurisdictions that use these products are highly favorable and support their safety and efficacy [ ] . several clinical trials of pi technologies have taken place or are underway, including eurosprite (looking at intercept-treated platelet concentrates [ ] ), sprint (looking at intercept-treated apheresis platelets [ ] ), and miracle (looking at mirasol-treated apheresis platelets [ ] ). although safety and levels of adverse transfusion reactions were favorable with pi-treated platelets, one observation was that approximately % to % of the platelets appear to be damaged by the pi treatment. the sprint and miracle trials demonstrated a lower mean -hour post-transfusion count increment, increased number of platelet transfusions, and lower -hour corrected count increment, respectively, for patients treated with pi platelets [ , ] . the prepares (pathogen reduction evaluation and predictive analytical rating score) trial is a recently completed prospective, randomized, single-blinded, multicenter non-inferiority trial comparing mirasol-treated and standard of care pooled platelet products in hemato-oncological patients [ ] . initiated in the netherlands in november , prepares is sponsored by the sanquin blood supply foundation, the national blood operator in the netherlands, and financially supported by terumobct. the canadian arm of the trial involved cbs producing mirasol-treated pooled platelets at its ottawa manufacturing site and several hospitals in ontario. to account for the observed damage seen in pi techniques in other trials and to be consistent with the preparation of platelet pools in the netherlands, mirasoltreated platelets contain the donation of five donors, rather than four, which is the standard buffy coat platelet product prepared by cbs. although simply increasing the platelet dose in this setting is a straightforward solution to the issue of platelet damage seen with pi, dr schubert noted that the mechanisms of this pi-associated damage are unknown. currently in the literature, there is debate regarding the clinical efficacy of pi platelets. a meta-analysis of bleeding complications in randomized controlled trials using the intercept system suggests an increased risk of clinically significant bleeding [ ] while a meta-analysis from the cochrane collaboration suggests no difference in bleeding with pi platelets, although this conclusion is limited by significant heterogeneity between studies [ ] . thus, elucidating potential mechanisms is important to further finetune these systems and dr schubert provided an overview of the effect on quality parameters of platelet products by the three different pi systems. the common trend is a negative impact on routine quality measures as well as newer tools introduced to further characterize platelet quality and functionality; however, the magnitude of the effect can be different dependent on the pi technology. amongst other effects, pi treatment increases metabolism, apoptosis development, and platelet activation. these features lead to decreased platelet responsiveness and in vitro clot formation [ ] . furthermore, the effect of pi treatment on novel aspects of platelet function has also been extensively investigated. these studies show pi-dependent effects on cytokine [ ] , mitochondrial dna and microparticle release [ ] [ ] [ ] , generation of reactive oxygen species and initiation of signaling cascades [ ] , and expression profiles of mrna and mirna [ , ] . these "novel" platelet features might assist with explaining pi-effects associated with increased inflammation, cell damage, and apoptosis, transfusion-related acute lung injury, and modulation of endothelial cell functions. in addition, studies of the effects of pi on the proteome of platelets could provide further insights into mechanisms, although the overall impact on the protein expression profile is relatively small [ ] , suggesting pi-triggered modulations of protein activities. finally, some of dr schubert's own work on elucidating signaling cascades in mirasoltreated platelets revealed a central role of p mapk in regulating platelet activation and apoptosis development [ , ] . besides platelet concentrates, pi-treatment of plasma is used routinely in some jurisdictions [ ] ; however, pi of rbc concentrates has been challenging due to their high optical density, requiring a large amount of uv light, accordingly leading to significant rbc damage. the cerus s- system for pi of rbcs demonstrated similar -hour recovery to standard rbcs, but these products would not meet canadian standards due to their decreased shelf life [ ] . dr schubert then discussed how pi of whole blood may be a more efficient approach compared to pi of individual components. potential benefits of whole blood pi include early removal of pathogens, protection against transfusionassociated graft versus host disease due to wbc inactivation, and increased safety of all blood product components. the application of the mirasol technology on whole blood has demonstrated efficacy against hiv [ ] , trypansoma cruzi [ ] , and b microti [ ] . most recently, a study using mirasol for malaria inactivation in whole blood has been performed in ghana [ ] . however, reduction of ttis must be balanced against the effect that whole blood pi has on blood component quality. a study of in vivo viability of stored rbcs derived from mirasol-treated whole blood suggests decreased viability that correlates with quality variables such as hemolysis and atp concentration [ ] . this approach was complemented by a study by schubert and colleagues further demonstrating that platelet product quality seems to be less affected when produced from whole blood illumination compared to platelet component treatment [ ] . dr schubert concluded by acknowledging that there are two sides to the pi coin, and that a balance must be achieved between safety and quality. further research is needed to understand molecular mechanisms that lead to changes in quality with pi and to balance potential reductions in component effectiveness against reduction in ttis. ultimately, clinical trials are essential when it comes to making decisions regarding the implementation of pathogen inactivation into blood banking. economic and health outcome implications of introducing new pathogen testing and inactivation technologies • in order to be cost-effective, implementation of broad spectrum interventions such as pi are likely to require discontinuation of some current interventions. • the risk-based decision-making framework is a useful set of guiding principles for health economic assessments of blood safety interventions. to end the day, dr brian custer, a senior investigator with blood systems research institute in san francisco and an adjunct professor at the department of laboratory medicine at ucsf, gave an informative lecture on the economic and health outcome implications of introducing new blood safety interventions with a focus on pathogen testing and inactivation technologies. dr custer began his presentation by introducing the audience to the three main concepts that are the basis of economics in general, and of health economics in particular. the first concept, scarcity, stresses the current reality of limited resources and budgets, which may restrict the scope of services health care systems and practitioners are able to provide. the second concept, choice, has to do with choosing how to allocate the limited resources available. the third basic economic concept is opportunity cost, which relates to the next best alternative use of resources. in other words, opportunity cost is the benefit willingly forgone when we do not choose the next best alternative. these three notions summarize the challenge of the decision making process when it comes to economic information. in most jurisdictions, system-level health care decisions are made using a different decision-making framework. district health authorities resolve problems based on the determinants of health priorities such as: national and regional targets; clinical and research data; health experts' opinions and views; and the public's participation. for example, the fda annually tracks data on fatalities related to blood collection, transfusion reactions, and transmissible diseases (http://www.fda.gov). microbial fatalities from transfusion are tracked using variables that experts deem important for focusing future pathogen testing and inactivation efforts such as by the type organism and blood product. these fatality reports help determine the relative burden of fatalities from different causes. as a result, it was shown that in the united states, plateletrelated deaths are mainly caused by bacteria and red cell-related deaths are mainly attributable to babesia. data sources, such as the fda fatality data, help health authorities to understand the most important infection risks blood recipients face. with respect to health economics of the blood supply, dr custer suggested that the blood supply aims to serve the public good. achieving this aim necessitates that scarce resources be allocated in ways that maximize social welfare. the objective enumeration of costs, benefits, and consequences of alternate health programs must be weighed in comparison to society's ethical beliefs and expectations. if resource allocation does not align well with the values that society allocates to certain health outcomes, this may lead to friction between the determinants of health priorities, and ultimately to difficulties in decision making [ ] . the risk-based decision-making framework developed by the alliance of blood operators is intended as a guide for the assessment of blood safety interventions. as an integral part of any blood system's risk-management program, the risk-based decision-making framework has two components as shown in figure : policy foundations; and the decision making process. adherence to the framework increases consistency in methods and results, and it integrates contextual issues (social concern, legal considerations) into the decision making process. the concept of quality adjusted life years (qaly) has been developed to facilitate decision making by establishing a balance between public good (subjective qualitative outcome) and resource allocation (objective quantitative outcome). qaly is a tool that measures disease burden, including both the quality and the quantity of years lived. it is a measure of a medical intervention's "value for money". scientists may make various assumptions when measuring health resource outcomes, from choosing the wrong outcome to choosing an inappropriate test to measure it. these limitations, as well as an incomplete knowledge base, lead to uncertainty in data used for health economic analyses. when measuring health costs, one assumes that some expenditures are more important than others for the health care system; when measuring consequences from an intervention, one assumes that there is a sufficient understanding of the risks and benefits associated with that intervention. cost per qaly provides a common denominator for comparing interventions, but cannot reduce uncertainty introduced by unavoidable assumptions. established thresholds for what is considered "cost-effective" in health care interventions are in the range of $ , to $ , / qaly (all values in us dollars). blood safety interventions, however, consistently fall well above these thresholds. good examples are nat for hiv, hcv, and hbv ($ , , - , , /qaly; broad range reflects uncertainty and testing strategy used) serology and pcr for babesia species ($ , - , , /qaly) and wnv nat testing ($ , - , /qaly), and t cruzi antibody testing for chagas disease ($ , - , , /qaly). when it comes to considering pathogen testing and pi, some outcomes of interest may not be available to aid in decision making. for example, qaly data on the utility of testing for chikv, dengue viruses, and hepatitis e virus in the blood safety context are not available to inform an economic analysis. hence, understanding the budget impact of such tests becomes difficult. on the other hand, data regarding babesia testing are available. babesia screening in endemic american states was compared to universal screening using qaly and taking into account the number of deaths prevented and the testing methodology used [ ] . there are also qaly data available to support the practice of bacterial testing of platelets, and pathogen inactivation of plasma [ ] . the data estimate that platelet bacterial testing is more cost-effective ($ , /qaly) than pathogen inactivation ($ , /qaly) [ ] . when implementation of a cost-effective blood donor test is needed, qaly has been applied to several patient populations and several interventions. bell et al compared platelet pi using intercept in leukemia, lymphoma, orthopedic, and cardiac patients [ ] . the authors found that the new method's cost effectiveness ($/qaly) is similar to other accepted blood safety interventions. this means the method can be considered cost-effective in the blood safety context while preserving patient quality of life. dr custer and colleagues have modeled the costeffectiveness of pi as an addition to current pathogen testing based on canadian data. comparing mirasol treatment of whole blood, and of platelet and plasma, costs per qaly of $ , , and $ , , , respectively (cdn, in this instance), were shown [ ] . a more recent cost-utility analysis of implementing pi in poland suggest high costs, but better cost-effectiveness than found in previous analyses of pi and nucleic acid testing in north america [ ] . pi may replace other interventions that currently incur large costs to the health care system such as blood irradiation, bacterial culture, and maintenance of cmv negative inventory [ ] . if pi is implemented, removing costs associated with bacterial culture and irradiation could result in a reduction in the cost/qaly of pi by about % [ , ] . other operational gains may further offset investment costs, including reduction in product wastage [ ] . these analyses are based on assumptions, and while there is a high degree of uncertainty in the results, their potential usefulness, as blood operators move into the era of pi, is substantial. health economic analysis allows quantification of alternatives and comparison of interventions in different areas of medicine. broad implementation of pi for blood safety may thus prove unpalatable to funders without compensatory cost reductions in other aspect of component production. either a more focused application of pi or lack of implementation until lowercost alternatives are developed may ensue. decision making based on health economics and on risk assessments is likely to become the new norm in blood transfusion. this would comprise a strikingly different approach to blood safety implementation and decision making than in the past, when novel interventions were added to older ones, sequentially increasing costs and overall blood safety budgets. this shift represents a move towards effectively and transparently managing process change, rather than the traditional approach of reactive change in response to an emerging situation or disaster. defending the blood supply from the threat of transfusiontransmissible infections remains a high priority for transfusion services in canada and around the world. the residual risk from established pathogens is exceptionally small. the emerging agents of greatest concern in the north american setting are arboviruses and babesia. the west african ebola virus epidemic reinforced concerns about environmental change fueling the rapid emergence of pathogens not previously thought to have potential global significance. pathogen inactivation of blood products may further reduce residual risk from established agents and provide protection from new agents in the medium term; however, the most likely driver for a paradigm shift to the use of pathogen inactivation is to reduce the ever-present risk of bacterial contamination of platelet products. longer term, the possibility of donor-free cellular products and rapid next generation sequencing could drive down transfusion-transmission rates even further than the impressive safety margins now in place in canada and other developed countries. health economic analysis and risk-based decision making will be required to determine if anticipated benefits outweigh the considerable costs of these potential steps. the th annual international symposium received funding from the canadian blood services centre for innovation. among the authors of this report, dr geraldine walsh, dr mia golder, dr margaret fearon (author and speaker), and dr william sheffield have no actual or potential conflict of interest in the context of the subject of this program over the past five years. dr peter schubert, author and speaker, discloses grant/research support from terumobct and macopharma. among the speakers, dr allison mcgeer, nancy angus, and dr samia naccache have no actual or potential conflict of interest in the context of the subject of this program over the past five years. the following relationships that could be perceived as a related or apparent conflict of interest in the context of the subject of this program over the past five years are disclosed by dr roger dodd: grant/research support grifols and cerus; consultant with mosaiq and roche; dr marc turner: grant/research support from the wellcome trust; dr brian custer: grant/research support from grifols (formerly novartis), hologic (formerly gen-probe) and macopharma, and member of the speakers' bureau with terumobct. among members of the planning committee who were not speakers at the event, dr kathryn webert, dr robert skeate, dr sophie chargé, ahmed coovadia, and sue gregoire have no actual or potential conflict of interest in relation to this program over the past five years. dr ed pryzdial discloses grant/research support from biogen. blood group antigens and normal red blood cell physiology: a canadian blood services research 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title: the impact of covid- pandemic on malaria elimination date: - - journal: parasite epidemiol control doi: . /j.parepi. .e sha: doc_id: cord_uid: cpzp b sars-cov- has spread throughout the world and become the cause of the infectious coronavirus disease (covid- ). as low- and middle-income countries shift increasingly to focus on identifying and treating covid- , questions are emerging about the impact this shift in focus will have on ongoing efforts to control other infectious diseases, such as malaria. this review discusses how the spread of sars-cov- in low- and middle-income countries might impact these efforts, focusing in particular on the effects of co-infection and the use of antimalarial drugs used to treat malaria as therapeutic interventions for covid- . at the end of , a novel severe acute respiratory syndrome, coronavirus (sars-cov- ), was found in patients with severe pneumonia in wuhan, china [ , ] . coronaviruses are enveloped viruses, - nm in diameter, with a crown-like appearance and are classified into four main genera: alpha-cov, beta-cov, gamma-cov and delta-cov [ ] . there have been three previous zoonotic outbreaks of beta-cov. first, severe acute respiratory syndrome coronavirus (sars-cov), a lineage b beta-cov, emerged in - from the bat and palm civet, infecting more than , people and causing approximately deaths [ ] . the second, middle east respiratory syndrome coronavirus (mers-cov), a lineage c beta-cov, was discovered in to be the causative agent of a severe respiratory syndrome in saudi arabia. at present, there have been , confirmed cases of mers-cov and deaths [ , ] . now, sars-cov- has spread throughout the world and is the cause of the infectious coronavirus disease . the virus is transmitted by inhaling or coming into contact with infected j o u r n a l p r e -p r o o f droplets, with the incubation period ranging from to days [ ] [ ] [ ] . in most infected people, the disease is usually mild, with common symptoms such as fever, cough, sore throat, breathlessness and fatigue. the elderly and those with comorbidities may develop pneumonia, acute respiratory distress syndrome and organ dysfunction [ ] . in january , the world health organization (who) officially declared the covid- pandemic to be a public health emergency of international concern [ ] . thus, the covid- pandemic is likely to severely interrupt health systems all over the world and especially in the low-and middle-income countries over the coming months and years. to date, there have been more than million and nine hundred thousand confirmed cases worldwide [ ] . despite the extensive trade and travel links between china and low-income countries such as africa; african countries have appeared to be the least affected by this viral pandemic in terms of both the number of cases and the incidence of serious illnesses [ ] . as of rd may , there have been seventy one hundred thousand confirmed covid- cases reported to the who with around three thousand deaths reported from african countries. in comparison, the who covid- report indicates that there were around two million cases and one hundred twenty four thousand deaths in europe [ ] . reports show that most of the cases in africa were imported from the european union and the united states rather than china [ ] . also, the majority of reported cases are from middle-aged adults (median age . ), which may contribute to the low death rate in the african continent [ ] . however, it is not yet clear why this phenomenon did not yet spread widely in africa. it can be that africa has managed an effective shut down which limited the spread and this placed them ahead of time compared with other countries or perhaps that they are simply behind in the timeline as a result of poor reporting due to lack of molecular testing capacity [ ] [ ] [ ] . moreover, data regarding environmental conditions, genetic factors and differing immune responses to covid- are limited and still emerging [ ] [ ] [ ] [ ] [ ] [ ] [ ] . in contrast, many scientists believe that covid- is expected to hit the african region drastically, especially that covid- cases and deaths are beginning to rise in africa [ , , ] . the african countries are already fighting against the greatest infectious disease burden and chronic noncommunicable diseases with the weakest public health infrastructure. most of these countries have limited health budgets, limited supply of medicines, personal protective equipments and resources of personnel trained in critical care [ , ] . moreover, african healthcare systems rely predominantly on external funding provided for disease-specific programs [ ] . thus, efforts to control covid- would impact efforts to control other existing health problems that are endemic, such as malaria, human j o u r n a l p r e -p r o o f immunodeficiency virus (hiv), hepatitis b virus and tuberculosis [ ] [ ] [ ] . it is therefore reasonably hypothesized that the african region will be the most vulnerable against covid- . as a result, many countries are implementing societal measures to mitigate the transmission of covid- [ , ] . ( ) disruption of medical supplies and stockpiles [ ] . however, such an approach raises concerns that tracing, treatment and control of other diseases, such as malaria, is much harder during the crisis especially that the number of covid- cases is rising in sub-saharan african regions [ , ] where more than % of malaria deaths take place followed by south-east asia and central as well as south america [ ] . zimbabwe's matabeleland south province has also reported a significant spike in the number of malaria cases during the covid- crisis [ ] . west africa [ , ] . it was suggested that the decrease in antimalarial drug administration, reduced healthcare capacity and cessation of rapid diagnostic tests (rdts) contributed substantially to the increased morbidity caused by the ebola outbreak [ ] [ ] [ ] . it was also estimated that malaria cases in parts of africa, including liberia, guinea and sierra leona, increased by up to million in as a result of running out of stock of long-lasting insecticide-treated nets (llins) [ ] . there is now a similar concern that the malaria-endemic regions are facing a real danger when facing the threat of a novel covid- pandemic. this review addresses this gap in the literature by discussing how the spread of sars-cov- in low-and middle-income countries might impact efforts to control malaria. since most low-and middle-income countries will not be able to afford large-scale diagnostic tools, clinical case definition or presumptive diagnosis of covid- will be prioritized [ ] . this might affect j o u r n a l p r e -p r o o f malaria control efforts because of the overlap symptoms for covid- and malaria, such as fever, difficulty in breathing, headaches, and body pain [ ] . symptoms of malaria usually arise - days after the bite of female anopheles. severe malaria infection is usually associated with multi-organ failure in adults and respiratory distress in children, presenting what is commonly seen in covid- infected patients [ ] . as a result, patients with fever may get tested for malaria and sent home due to a negative result when they may, in fact, have covid- infection and vice versa. there are also laboratory-confirmed cases of both asymptomatic malaria and covid- infected individuals. this increases the possibility that both asymptomatic patients can transmit the infection through their respective modes [ , ] . a single case of covid- has the potential to transmit up to . susceptible individuals [ , ] . in contrast, malaria has the potential to cause further community infections which in turn continues to be a significant source of illness and deaths globally. consequently, undetected malaria and covid- cases may pose an immediate health challenge to the individual and public health consequences for the community. laboratory investigation is the definitive way to diagnose infectious diseases. thus, it is highly recommended to include malaria rdt in routine diagnosis for covid- in malaria-endemic areas to eliminate the misdiagnosis between malaria and covid- and subsequently mistreatment of co-infections. patients' travel and medical history should also be considered when screening for covid- in low-income malaria-endemic areas were large scale diagnostic tools are limited. it is also vital to rightly diagnose both diseases given that the same patient might suffer from malaria and covid- co-infection and as a result, diagnosis and treatment of one of them may lead to missing the other. there is limited data addressing whether co-infection with covid- affects the immune response and susceptibility to malaria and vice versa [ ] . previous studies, for example, have addressed the effects of virus co-infection on malaria pathogenesis in endemic areas. they showed that the presence of viral infections such as influenza, parainfluenza, adenovirus, coronavirus, rhinovirus repressed the p. falciparum burden in peripheral blood and elevated patients' haemoglobin levels, thus improved their anaemia [ ] . moreover, the presence of viral respiratory tract infection was highest in children not infected with malaria, and as the parasite levels increased during plasmodium infection, the viral infection decreased [ ] . others showed that chikungunya virus (chikv) infections prevented plasmodium-induced neuropathology in mice [ ] . conversely, prior exposure to plasmodium suppressed chikv tissue viral load and suppressed chikv-induced joint pathology in mice [ ] . overall, j o u r n a l p r e -p r o o f the impact of malaria and respiratory viruses co-infection on host susceptibility and pathogenicity remains unclear. however, it was suggested that the immunomodulatory and immune-evasion capabilities of plasmodium [ ] [ ] [ ] might play critical roles in altering virus clearance and virusesinduced pathology. these findings could be applied to improve covid- management in regions with malaria co-endemicity, leaving a gap for future studies. in contrast, there are concerns that malaria co-infection may compromise the pre-existing vaccine response. previous studies, for example, showed that p. chaubaudi [ ] and p. yoelii [ ] infections reduced pre-existing influenza-specific antibodies and increased susceptibility to influenza in mice. p. yoelii infection also led to an accelerated loss of pre-existing vaccine-specific igg (tetanus, measles and hepatitis b) in malian children [ ] . given the urgent need for developing a vaccine for covid- , these studies and others highlight the importance of addressing the impact of malaria on the upcoming covid- -vaccine-specific antibodies. to date, there are no specific treatments available for covid- . however, the anti-malaria drug, chloroquine (cq) and its derivative hydroxychloroquine (hcq), have been reported as potential drugs for the treatment of covid- [ , ] . both drugs have shown some efficiency in reducing viral replication in sars-cov and mers-cov, both in vitro and in pre-clinical studies [ , ] , with hcq found to be more effective than cq in hindering sars-cov- in vitro [ ] . although in vivo, the evidence is still needed for the drugs to be approved as covid- treatments or prophylactics [ ] . both drugs are being tested in ongoing clinical trials, which have been reviewed elsewhere [ ] . for example, the who developed the 'solidarity trial', which allows research contributions from any country with few bureaucratic barriers. the four drugs that will be evaluated individually or combined are chloroquine, remdesivir, lopinavir and ritonavir. there is also an open-label, non-randomized clinical trial in france to observe the effects of hcq and azithromycin on patients infected with covid- [ ] . moreover, cq and hcq are subjected to extensive off-label use in many countries, including italy, china and saudi arabia [ ] . both cq and hcq drugs were proven effective for malaria and helped malaria control and eliminating programs [ ] . subsequently, and due to the extensive use of cq, chloroquine resistance emerged, first in cambodia-thailand border in - s, after which, chloroquine resistance was reported around the globe [ ] . despite this issue, both drugs are still used as treatment and prophylactic agents in the majority of p. vivax endemic regions [ ] . the who has advocated a policy of artemisinin-based j o u r n a l p r e -p r o o f journal pre-proof combination therapies (acts) for treating p. falciparum. since then, act therapy has been implemented in malaria-endemic countries, with in africa, as the first-line therapy for p. falciparum infection [ , , ] . however, the widespread implementation of acts over the years has also led to the poor surveillance of malaria and the emergence of drug resistance to acts, including artemisinin derivatives and their partner drugs [ ] . thus, the widespread and unmanaged use of cq and hcq as prophylactic and therapeutic interventions for covid- may further influence plasmodium resistance in malariaendemic areas. india, for example, the country with highest infection rate with p. vivax [ ] might face many obstacles, especially that the indian council of medical research, under the ministry of health and family welfare, has recommended chemoprophylaxis with hcq for covid- [ ] . the overuse of cq in india might lead to a shortage of cq and thus might increase the number of morbidity and mortality due to malaria infection during covid- crisis. while after the crisis, this might massively increase the p. vivax resistance to cq and subsequently affect p. vivax treatment and elimination. while for p. falciparum, the widespread use of cq/hcq will have a minimal impact on the treatment outcome, as cq was also considered in malaria combined therapy for p. falciparum [ ] . thus, the extensive use of cq during covid- pandemic may further increase the selective pressure for p. falciparum resistance to cq, leading to delay cq sensitivity re-emergence. with that said, developing a multiplex polymerase chain reaction (pcr) that can identify both sars-cov- and chloroquine-resistant plasmodium might be essential in malaria-endemic areas. other than developing plasmodium resistance, it is interesting to know whether the genetic makeup of sars-cov- may become less susceptible to cq, the same way influenza a virus acquired resistance against both adamantanes and neuraminidase inhibitors [ ] . therefore, a combination of therapy involving different classes of drugs could be more effective and beneficial in reducing the emergence of antiviral and antiparasitic resistance. it is also worth outlining the research directions towards developing alternative effective anti-covid- therapies. despite the cq and hcq treatment potential for covid- , the use of these two drugs could pose many challenges in low-and middle-income countries and not just in malaria-endemic areas. cq and hcq are not limited to malaria; they have broad-spectrum activity against a range of bacterial, fungal and viral infections in addition to the control of inflammatory disorders. thus, the widespread demand on cq and hcq may lead to a prolonged shortage that will affect people with malaria and other critical diseases such as rheumatoid arthritis, erythema nodosum, systemic lupus erythematosus and carcinogenic j o u r n a l p r e -p r o o f tumours [ , ] . therefore, treatment should only be dispensed with a restriction to people who need it to help us navigate these challenging times [ ] . finally, we must remain vigilant when using cq and hcq as prophylactic agents for covid- to prevent low-and middle-income countries lacking access to health services left most vulnerable during the crisis. malaria control largely depends on the mass distribution of long-lasting insecticide-treated nets (llins), seasonal malaria chemoprevention (smc) and indoor residual spraying of insecticide (irs) across communities and households. together with slide-based diagnosis, rdts, case management delivered through trained health staff and increasing awareness have led to significant success in reducing malaria burden over the years [ , ] . understanding the effect of the concentrated campaigns against malaria is vital to inform future control planning during the covid- crisis. therefore, the who has stressed that all routine malaria prevention and control activities should not be hampered and be continued to the extent possible as they tackle the covid- pandemic. however, implementing these preventive activities house-to-house is harder during the current health and economic crisis. it substantially could be scaled back due to a shortage of budget and the requirement of different intervention delivery [ ] . for example, a recent modelling analysis by the who predicted a > % rise in malaria morbidity and > % mortality in sub-saharan africa during the covid- pandemic as a result of % reduction in routine malaria control measures including itn distribution and shortage of anti-malarial drugs [ ] . a recent study also suggested that in nigeria alone, interrupting malaria control management such as delaying llin campaigns for months could result in , additional deaths. other indirect effects of the covid- pandemic, particularly those that impacted people's lives and well-being, such as increased malnutrition, poverty, and social instability, may further influence malaria burden. thus, it is debatable whether the who strategy, in close alignment with the roll back malaria partnership's action and investment to defeat malaria - , can reach their goal of eliminating and eradicating malaria in at least ten countries by and countries by [ , ] . therefore, the who released guidelines for malaria control in areas affected by covid- [ ] . the guidelines include the continuation of all the routine malaria control measures while adhering to covid- local personal and physical distancing guidelines established by the authorities. these measures will require an arrangement with all relevant national covid- stakeholders and partners to minimize the risk of substantial additional mortality [ ] . j o u r n a l p r e -p r o o f conclusion malaria has been controlled by highly effective interventions across the world over the past decade. however, covid- pandemic can stress and disturb these health delivery systems. therefore, malariaendemic countries should consider diagnosing both malaria and covid- for all suspected cases. it is also recommended to follow all the who guidelines against both the covid- threat and malariaendemic as nations cannot afford to have malaria control programmes compromised at this time. this raises the need for global cooperative efforts in national programmes, health system, community measures, and donor investments to prevent reintroduction and reestablishment of existing endemics to avoid the increase of morbidity and mortality. ☒ the authors declare that they have no known competing financial interests or personal relationships that could have appeared to 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authors: kobia, francis; gitaka, jesse title: covid- : are africa’s diagnostic challenges blunting response effectiveness? date: - - journal: aas open res doi: . /aasopenres. . sha: doc_id: cord_uid: i ndb n since its emergence in wuhan, china in december , novel coronavirus disease - (covid- ) has rapidly spread worldwide, achieving pandemic status on (th) march, . as of (st) april , covid- , which is caused by severe acute respiratory syndrome coronavirus (sars-cov- ), had infected over , people and caused over , deaths in countries and territories. covid- has had its heaviest toll on europe, united states and china. as of (st) of april , the number of confirmed covid- cases in africa was relatively low, with the highest number registered by south africa, which had reported , confirmed cases. on the same date (also the date of this review), africa had reported , confirmed cases, of which , (almost %) occurred in south africa, algeria, egypt, morocco and tunisia, with the remaining , cases distributed unevenly across the other african countries. we speculate that while african nations are currently experiencing much lower rates of covid- relative to other continents, their significantly lower testing rates may grossly underestimate incidence rates. failure to grasp the true picture may mean crucial windows of opportunity shut unutilized, while limited resources are not deployed to maximum effect. in the absence of extensive testing data, an overestimation of spread may lead to disproportionate measures being taken, causing avoidable strain on livelihoods and economies. here, based on the african situation, we discuss covid- diagnostic challenges and how they may blunt responses. in december , a spate of pneumonia cases of unknown cause was observed in wuhan, hubei province, china (he et al., ). soon after, the causative agent for the novel illness was found to be a novel coronavirus ( -ncov) (lu et al., ; zhou et al., ; zhu et al., ) . coronaviruses (covs), are a large group of viruses that frequently cause mild respiratory disease in humans, including common cold (saif, ; niaid, ) . hundreds of coronaviruses exist in wild and domestic animals. in the last years, highly infectious covs have crossed from animals into humans through spillover events and spread globally, causing severe respiratory illnesses ( covid- then rapidly spread within china, where it infected over , people and caused more than , fatalities, mainly in hubei province (who, b). the disease's spread accelerated globally, prompting the who to declare it a global pandemic on th march (bedford et al., ). as of st april , over , covid- cases and more than , covid- -associated deaths had been confirmed in countries and territories. europe and north america are currently the continents most affected by covid- . so far, africa has reported the lowest number of confirmed covid- cases (who, b). as of writing, , covid- cases have been reported in africa with south africa reporting the highest number. countries (south africa, tunisia, morocco, egypt, and algeria) account for close to % ( , cases) of the confirmed cases, with the remainder being unevenly distributed in the rest of the continent. within the east african community, there have been a total of confirmed cases (african arguments, ; who, b). sars-cov , is an enveloped single stranded positive sense rna virus belonging to the family coronaviridae and genus betacoronavirus (lai et al., ). the sars-cov- virion ranges between - nm in diameter and houses a , bp genome (chen et al., a; chen et al., b). among other genes, the sars-cov- genome encodes structural proteins named spike (s), envelope (e), membrane (m) and nucleocapsid (n). the n protein holds the viral genome while s, m and e construct the viral envelope, where s mediates viral entry into the host cell (wu et al., ). sars-cov- is easily transmissible. according to the who, the main mode of covid- transmission is direct/indirect human-human contact, where the virus is transmitted in respiratory droplets or via contact routes. droplet transmissions happen when one gets into close proximity, (typically within a meter) with an individual exhibiting respiratory symptoms, such as sneezing or coughing. indirect transmission may occur when one touches objects handled by an infected individual and then touches their mouth, nose or eyes. transmission has also been reported to occur via airborne droplet transmission. in such cases, the virus is contained in droplet nuclei, which are typically < µm in diameter and can remain airborne for extended periods. airborne transmission can occur over distances beyond meter but such nuclei are typically generated by processes that generate aerosols, usually patient care procedures (who, d). as such, social distancing, rigorous hand washing, and avoiding touching the face have been recommended as means of minimizing transmission risk (who, a). once sars-cov- has gained access to the host's respiratory mucosa, it enters the host cells through an interaction between its s protein and the host cell's ace (angiotensin-converting enzyme ) receptors (hoffmann et al., ). unlike other coronaviruses that cause upper respiratory tract disease only, sars-cov- is capable of colonizing the lower respiratory tract as well (heymann & shindo, ). after infection, the virus incubates for a median period of about days before the onset of symptoms and almost all infections become symptomatic by day (lauer et al., ; rothan & byrareddy, ). symptoms include fever, fatigue, headache, dry cough, diarrhea and lymphopenia. while most patients experience mild symptoms that they overcome without need for hospital care, some experience serious complications including severe pneumonia, acute respiratory distress syndrome (ards), acute cardiac injury and acute ground glass opacity (ggo) that may necessitate life support (heymann & shindo, ; rothan & byrareddy, ). covid- diagnostic testing is recommended for individuals that satisfy the suspect case definition (leitmeyer et al., ). according to the who organization, the decision to test should be based on clinical signs, epidemiological factors and the possibility of infection (leitmeyer et al., ), such as contact with an infected individual. the who (who, c) defines a suspect case as one that: a) shows symptoms of acute respiratory illness i.e. fever and at least one respiratory disease symptom e.g. coughing and shortness of breath, and has travelled or resided in an area with community covid- transmission in the days prior to symptoms onset; or, b) shows acute symptoms of any respiratory illness and has been in contact with a confirmed or suspected case in the days prior to the onset of symptoms; or, c) shows symptoms of acute respiratory illness i.e. fever and at least one respiratory disease symptom e.g. coughing and shortness of breath and requires hospitalization in the absence of alternative diagnosis that fully accounts for the symptoms. suspected cases should then be validated by laboratory tests. this is routinely done by carrying out nucleic acid amplification tests (naat). currently, rt-pcr detection of unique sequences of the viral genome is the gold standard for covid- testing where the n, e, s and rdrp (rna-dependent rna polymerase) genes are targeted. sample handling should be carried out in a bsl- biosafety cabinet under strict adherence to personal protective equipment (ppe) guidelines. however, rt-pcr is labor intensive, severely constraining the capacity for quick turnaround times from sample collection to results transmission. in many contexts, getting results takes days (npr, ). as a consequence, laboratory testing of suspect cases is characterized by long wait periods and an exponential increase in demand for tests. to address this bottleneck, rapid diagnostic tests with turnaround times ranging between and minutes have been developed, even though most of these are currently undergoing clinical validation and therefore not in routine use (ecdc, ). in addition to suspect case diagnosis, widespread covid- testing is critical for disease monitoring and surveillance. such testing is recommended so as to meet the following objectives (who, c): (day, ) . mass testing has been suggested as a means to quickly stop the covid- epidemic in the uk (peto, ) and delayed roll out of large-scale testing is considered to have blinded the us to its worsening covid- situation (cohen, ; new york times, ). in germany, large-scale testing has been credited for limiting disease spread and the low fatality rate reported by germany relative to its neighbors (financial times, a). while many countries are ramping up surveillance testing, there are no guidelines for large-scale testing and decisions are based on individual countries' assessments. covid- diagnostic challenges are not unique to african countries and lmics. consequently, numerous private and public institutions have developed rapid diagnostic tests (rdts) aimed at speeding and expanding testing, crucial factors in the struggle to slow covid- spread. rdts, which are largely based on immunoassays, may be direct, through detection of sars-cov- antigens or indirect, through detection of anti-sars-cov- antibodies (ecdc, ). advantages of rdts include ease of use as they do not require special equipment or highly trained personnel and stability at room temperature, removing the need for constant refrigeration/freezing. rdts are therefore highly suited for point of care diagnosis (pocd) and are highly amenable to deployment in low resource settings, removing the need for sample transportation. several covid- rdts, capable of giving results in - minutes are now commercially available or in development (ecdc, ). in many african contexts, rdts would reduce the time needed to get test results from days to minutes. therefore, rdts offer a means to aggressively deploy mass testing across africa. however, the cost of rdts for mass testing may still be prohibitively high, calling for homegrown solutions. the covid- diagnostic challenges faced by african nations highlight long-running diagnostic challenges for a wide range of diseases. part of our group's research has been the development of rdts and pocds for various diseases, including placental malaria and bacterial infections. we contend that an effective means of achieving mass testing at the required scale, is to fund the development covid- rdts locally, to meet local demand -bearing in mind that the knowledge and relevant local and international collaborations are already in place. such solutions should then be aggressively deployed for points of care and home use, particularly in rural settings. in fact, this strategy is being used by senegal, which together with uk collaborators, is developing an affordable covid- rdt (expected to cost $ per test) for home use in african countries (financial times, b). similar approaches by other african countries would provide local solutions to the continent's test needs while supporting africa's research and innovation. evidently, covid- testing by rt-pcr is not applicable in most parts of africa considering that vast populations live in rural settings with poor transport and communication infrastructure. rt-pcr requires expensive equipment, skilled personnel, reagents and reliable power supplies. additionally, the long turnaround time of - hours (and days in some contexts) (npr, ), may discourage many from seeking tests. different strategies exist for point of care testing, all with inherent merits and demerits: ) use of antibody testing. as the body mounts an immune response, antibodies against sars-cov- antigens are generated. these antibodies may serve as indicators of infection. however, since detectable antibodies may lag behind the appearance of clinical symptoms, most infections will be missed, causing a high rate of false negatives. conversely, persistence of antibodies after virus elimination from the body may result in a high rate of false positives. moreover, a high cross reactivity of sars-cov- and sars-cov s protein against plasma samples from patients has been observed, which may impact test interpretation (lv et al., ) . however, in spite of these drawbacks, antibody tests will still be useful in community surveillance of exposed populations and this information will be useful in determining the extent of 'herd' immunity and guide tailored public health interventions. other near point of care tests include radiological imaging with chest ct-scan. this approach has been shown to be highly sensitive (at %) but poorly specific (at %) in a chinese study (ai et al., ) . ct-scan, unlike rt-pcr enables shorter result times especially when coupled with artificial intelligence (ai) enabled image analysis and interpretation. but this technology is highly limited to higher level hospitals in most african countries, with very low numbers of radiologists and poor adoption of ai. this technology may not be sufficient in addressing the covid- diagnosis challenges in africa. given these considerations, it is clear that the current gold standard tools, rt-pcr and radiological imaging, cannot adequately meet africa's covid- diagnosis challenges in the low resource settings that characterize most hospitals in sub-saharan africa. indeed, as the pandemic situation evolves with control goals focusing on both containment and mitigation (parodi & liu, ; who, f), capacity for large-scale diagnosis at most if not all levels of health care systems will be vital for sustainable control. crucially, as treatment solutions for the disease become available, prompt diagnosis will be essential in ensuring prompt treatment and determining isolation/quarantine decisions. covid- has severely tested the adequacy of global diagnostic preparedness and ability to rapidly develop point of care tests for emerging infections. the prompt release of sars-cov- whole genomic sequence data by chinese scientists helped with development of rt-pcr protocols that have been used worldwide. however, as the pandemic evolves, it is increasingly important to develop point of care tests that will facilitate proper last mile epidemiology, inform treatment and public health interventions. these poc tests will leverage available molecular platforms such as crispr, or be based on antigen or antibody detection. critically, it should be understood that these strategies have inherent merits and demerits and synergy will only be achieved where all are used appropriately. additionally, the covid- pandemic has highlighted the need for development and growth of in-continent poc diagnostics development capacity ranging from assay development, device fabrication, prototyping, validation, implementation research and entrepreneurial ecosystems including venture capitalization and regulation. underlying data no data are associated with this article. covid- and traces its spread to africa, details the mechanisms of transmission and pathogenesis of the disease in a concise and easy-to-understand style, and provides an in-depth examination of the diagnostic challenges africa faces in assessing the full scale of the pandemic in the continent. the authors contend that most african countries lack the capacity to administer mass screening to ascertain the extent of the disease spread, and call for support toward the development of homegrown rdts and pocts as a strategy to achieve mass screening of covid- in africa the authors provide a concise and thorough review covering covid- emergence, pathogenicity, transmission and diagnostic methods, as well as challenges faced by african countries. the authors indicate that current gold standard testing methods such as rt-pcr and chest ct scans are not accessible options given the long turnaround time (rt-pcr) and limited available personnel and implementation for these technologies. the authors describe the need for funding local development and production of rdts to detect covid- in order to achieve widespread availability and testing. the present form of the manuscript should be published given its valuable contributions for scientific review and policy but could be further improved with minor changes described below:in section "sars-cov- transmission and pathogenesis", the authors indicate that "…almost all infections become symptomatic by day (lauer , ; rothan & byrareddy, )." however, current et al. research (after this review was submitted, e.g. arons , ) indicates that many cases are et al. asymptomatic. it would be better to qualify the statement so as not to imply that asymptomatic infection is rare.in the covid- point of care testing strategies, it is possible that a confirmatory testing protocol for rdts could be implemented if specificity is insufficient. this could be done with with a second rdt against different antibody reactivities the way that hiv test protocols are commonly performed. even in the case of imperfect tests, extensive testing is better than none at all.the conclusion should definitively answer the title question: are africa's diagnostic challenges blunting response effectiveness? the authors have described diagnostic challenges and how they have limited effectiveness in other situations, but have not answered whether the diagnostic challenges specifically are currently limiting response effectiveness in africa.the conclusion indicates need for increased capacity for "assay development, device fabrication, prototyping, validation, implementation research and entrepreneurial ecosystems" (which i agree with) but the review does not highlight how this might be done and could benefit from examples of success overcoming these challenges in the diagnostics or other fields. the present review by the authors provides important information on diagnostic challenges facing african countries in their combat against the ongoing covid- pandemic. the paper reviews the history of the covid- and traces its spread to africa, details the mechanisms of transmission and pathogenesis of the disease in a concise and easy-to-understand style, and provides an in-depth examination of the overall, the paper succeeds in presenting a concise review of covid- situation in africa, identifies diagnostic challenges and suggests pocts as a widely deployable testing approach which, if implemented for mass screening, can be effective for monitoring the spread of the ongoing pandemic.hence, i find the paper to be of reasonable priority in view of the current situation, and recommend its publication even in the present form. i believe that paper contains scientifically valuable information and would be an important resource for scientists as well as policy makers in the battle against the ongoing scourge not only in africa but worldwide.however, in revising the article for publication, the authors may wish to consider the following minor comments/corrections:the authors ought to mention the impact of mass screening/diagnostics on the existing weak health infrastructure in africa. the success story from south korea arose out of a highly coordinated system of diagnosis, isolation and treatment, but this may not be possible with the underdeveloped healthcare infrastructure in africa. one concern would be that identifying positives without appropriate follow up measures can lead to public fear and stigmatization, which might undermine the intended purpose of mass screening.poor research funding has always been cited as a major hindrance to the development of homegrown scientific solutions in africa. the authors ought to comment on the challenges facing the suggested development of rdt/poc in africa, most notably, lack of financial support and political goodwill. specific to the present covid- case, would it be faster and cheaper importing the diagnostic tools, as is already being done by some countries?the authors may wish to put " " section before " covid- point of care testing strategies " section, for consistency with the conclusion. the authors ought to provide a clear-cut answer to the question "are africa's diagnostic which appears in the title. it would be nice to challenges blunting response effectiveness?" reassess and address the question by providing an answer to it in the conclusion part.it would be informative to provide a list of some of the rdts/pocts available for rapid deployment or, alternatively, cite this paper (access via the url below) which provides an updated list of pocts. https://aasopenresearch.org/articles/ - /v the link for the reference below is not correct. please check. key: cord- -ddwawfv authors: mendelsohn, andrea s.; ritchwood, tiarney title: covid- and antiretroviral therapies: south africa’s charge towards – – in the midst of a second pandemic date: - - journal: aids behav doi: . /s - - -y sha: doc_id: cord_uid: ddwawfv nan the covid- pandemic has spurred panic in south africa, a country with the highest number of hiv patients in the world and a persistent tb epidemic. south africa had its first covid- case on march , . fearful that a significant segment of the population was particularly vulnerable- . million south africans have hiv and even more live in crowded conditions-the president declared a national state of disaster on march th when the caseload rose to [ ] . the country initially implemented a -week lockdown to contain covid- 's spread, which was later extended to weeks. in preparation for a future swell of covid- patients, the western cape department of health (wc doh) implemented a plan to "de-escalate" healthcare services to reduce the spread of infection and increase capacity to accommodate covid- patients [ ] . all non-urgent elective surgeries and outpatient appointments were postponed. stable chronic patients were given -months supplies of medication with up to months of refills. only emergency life-saving care, contraception, antenatal care, and immunizations have continued as normal. telemedicine is not a viable alternative in the south african public health system. consequently, all patients are screened at the hospital gate for acute respiratory symptoms before entering. those with possible covid- symptoms are given surgical masks and isolated for clinical assessment, treatment and testing. inside the hospital, social distancing is adhered to as strictly as possible. in one clinic, rather than sitting in a crowded waiting area, patients are asked to wait . m apart from each other outside and brought into the building for their visit or pharmacy collection patients at a time. as much as possible, chronic medications are packaged and delivered by community health workers to community-based locations. the same de-escalation plan makes provision for the distribution of anti-retroviral medication (arvs) to the million south africans currently on arvs [ ] . while there is no evidence that people living with hiv (plhiv) who are virally suppressed on arvs are at increased risk of severe covid- disease, there is genuine concern that plhiv with advanced immunocompromise or unsuppressed hiv may suffer worse covid- outcomes [ ] . therefore, there is extra pressure in south africa to decrease the exposure of plhiv to covid- infection and rapidly increase viral suppression rates. further complicating the pandemic is south africa's rollout of a new first-line arv, a fixed-dose combination pill containing tenofovir disoproxil fumarate, lamivudine, and dolutegravir (tld). south africa has changed to a first line dolutegravir-based regimen because of its higher barrier to resistance and reduction in associated side effects compared to efavirenz. in the change to tld was delayed over concerns of increased neural tube defects when women conceive on tld. however, reassured by improved botswana data and persuaded that arv programs must respect a woman's right to make her own healthcare decisions, the south african national department of health launched tld on december , [ ] [ ] [ ] . providers began prescribing tld nationwide in january . prior to the covid- outbreak, the plan in south africa was to phase out the old first-line fixed dose combination pill of tenofovir disoproxil fumarate, emtricitabine, and efavirenz (tee) slowly over - years. since tee stocks in the western cape are limited and tld is plentiful, it is essential to roll-out tld as planned [ ] . what's more, tld is a more effective arv [ , ] . during a highly infectious respiratory pandemic, plhiv should be on the best arv regimen available to minimize their risk of virologic failure, immunocompromise, and severe covid- infection. to facilitate the rollout of tld with de-escalated hiv services, the wc doh and the southern african hiv clinicians society (sahcs) issued specific recommendations [ , ] . the sahcs strongly advocated that -month supplies of arvs be issued to stable patients, reducing the risk of covid- exposure inherent in seeking in-person treatment at healthcare facilities as well as to minimize patient flow in a clinic [ ] . ideally, to change from tee to tld a patient should have a vl < copies/ml within months, as stipulated by national guidelines. however, the sahcs and wc doh advocated switching a patient to tld, even without a recent vl, if the patient has been on arvs for > year, the past vls were < copies/ml, and they have regularly collected arvs over the past year [ , ] . patients fulfilling these criteria are very likely to be suppressed and can be switched to tld without delay [ ] . additionally, the wc doh urged same day initiation of arvs when not medically contraindicated, arv initiation for all co-infected tb patients weeks after starting tb treatment, and urgently changing all patients failing st line tee to a nd line arv regimen, preferably with dolutegravir [ ] . patients unsuppressed on arvs will need additional clinical contact and adherence support. the sahcs and wc doh recommendations seek to fast-track plhiv onto a robust arv regimen during the pandemic to maximize their possibility of viral suppression and minimize their exposure to the healthcare system and, potentially, covid- . the uncertainty is what impact this de-escalated hiv program will have on hiv outcomes in south africa. unsuppressed patients in need of additional adherence support are likely to suffer the most without the help of auxiliary services such as social work, treatment support groups, addiction rehabilitation, and psychotherapy. likewise, many of south africa's lay hiv-counselors have been re-deployed to community covid- screening. although hiv testing is ongoing, anecdotally testing numbers and new diagnoses of hiv are lower since the wc doh began discouraging nonessential healthcare visits. hiv self-testing at home or hiv testing in coordination with community covid- screens could potentially fill that gap. it is well documented that differentiated models of care, such as south africa's adherence clubs, for stable arv patients have improved long-term virologic suppression and retention in care in comparison to usual care [ ] [ ] [ ] . plhiv are more likely to continue treatment if it is convenient and they can keep working without sitting all day in un-friendly, stigmatizing clinics to collect medication. in fact, the who recommends that clinically stable patients receive arv refills every - months to decrease the burden of care [ ] . forced by the pandemic, the wc doh has advised clinicians to give stable patients up to months of refills of a highly efficacious arv-tld-with minimal clinic contact. we have effectively turned most of the hiv service into one giant alternative model of care. it is possible that without the burden of frequent visits, there might be improved retention in care during the pandemic because patients are given the medication and empowered to manage their own health. the roll-out of tld will confound outcomes, because it will be impossible to tease out if viral suppression rates are due to the better arv, less burdensome healthcare system, or both. crisis is often the catalyst for ingenuity. depending on outcomes, we suspect that south africa will ultimately return to a combination of the old and the new model of care. stable arv patients will be empowered to live their lives with - month supplies of medication and minimal clinic interaction. those struggling with arv adherence should be reabsorbed into multi-disciplinary teams to meet their medical, psychological, and social needs. universal hiv testing should be implemented and tld should be offered to all eligible plhiv given its limited side effects and greater accessibility. south africa country data health services response to covid- . . western cape department of health staff correspondence q&a on covid- , hiv and antiretrovirals neural-tube defects and antiretroviral treatment regimens in botswana consolidated guidelines on sexual and reproductive health and rights of women living with hiv press release: south africa to introduce state-of-theart hiv treatment circular h / . management of patients with hiv, tb and non-communicable chronic diseases during outbreak of covid- ; multi-month dispensing of chronic medicines, including art. western cape department of health dolutegravir plus abacavir-lamivudine for the treatment of hiv- infection dolutegravir plus two different prodrugs of tenofovir to treat hiv provision of months of antiretroviral treatment-position statement from the southern african hiv clinician society effectiveness of patient adherence groups as a model of care for sta high rates of retention and viral suppression in the scale-up of antiretroviral therapy adherence clubs in cape town, south africa art adherence clubs: a long-term retention strategy for clinically stable patients on antiretroviral therapy world health organization publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations key: cord- -f qh fva authors: adekunle, ibrahim ayoade; onanuga, abayomi toyin; akinola, olanrewaju olugbenga; ogunbanjo, olakitan wahab title: modelling spatial variations of coronavirus disease (covid- ) in africa date: - - journal: sci total environ doi: . /j.scitotenv. . sha: doc_id: cord_uid: f qh fva clinical and epidemiological evidence has been advanced for human-to-human transmission of the novel coronavirus rampaging the world since late . outliers in the human-to-human transmission are yet to be explored. in this study, we examined the spatial density and leaned statistical credence to the global debate. we constructed spatial variations of clusters that examined the nexus between covid- attributable deaths and confirmed cases. we rely on publicly available data on confirmed cases and death across africa to unravel the unobserved factors, that could be responsible for the spread of covid- . we relied on the dynamic system generalised method of moment estimation procedure and found a ~ . covid deaths as a result of confirmed cases in africa. we accounted for cross-sectional dependence and found a basis for the strict orthogonal relationship. policy measures were discussed. clinical and epidemiological evidence has been advanced for human-to-human transmission of the novel coronavirus rampaging the world since late (see kamph, ; shereen et al., ; yeo et al., for an extensive review). the contemporary disease is spreading exponentially around the world, and the pandemic has science of the total environment j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / s c i t o t e n v been felt in at least countries reporting , , confirmed cases with , deaths as at th april (who, a (who, , b . in this time of the global pandemic, fifty-two ( ) african countries have reported one or more confirmed cases of covid with only comoros and lesotho presently with no single confirmed case. as a result of changing medical data, africa at the time of writing has recorded , confirmed cases, with deaths. algeria is the most hardly hit nation with confirmed cases and deaths, although lesser confirmed cases compared to south africa ( ) with deaths (who, a (who, , b . in other regions of the world, the united states of america (usa) with , confirmed cases and , deaths remain the hardest-hit nation in america (north and south) and around the world. china, with , confirmed cases and deaths, is the hardest hit asian country. in europe, italy, with , confirmed cases and , deaths although relatively less compared to confirmed cases in spain with , with , deaths remains the hardest hit because of their superior coronavirus reported death cases. in the middle east region, iran, with , confirmed cases and deaths is the worst-hit nation. in ascertaining the structures, features, risk factors and severity of the novel coronavirus, clinical and epidemiological evidence has been leaned to human-to-human transmissions (community transmission). however, outliers in the human-to-human transmission could be as a result of clusters that are yet to be explored. by advancing arguments for clusters of the novel coronavirus in africa, we provided a social dimension to abating the spread of coronavirus diseases. africa is predominantly famous for overcrowding their megacities like pretoria, lagos, johannesburg, cairo and nairobi. clustering by people either in public gatherings or residential facilities makes them endangered species. even if social distancing is enforced in the public domain to prevent human-to-human transmission, it may be difficult if not impossible to enforce in an already overcrowded shared resident. by advancing arguments for inevitable human clustering at various residential or sub-groups in africa, the study provides an econometric analysis of the social dimensions of the spread of coronavirus diseases in africa. apparently, this study leads the debate on spatial density and statistical credence of how confirmed cases is statistically related to attributable deaths from coronavirus diseases in africa. we build upon the work of sarkodie and owusu ( ) to examine the phenomenological influence of outliers in the human-human transmission in africa. the intricacies of these unobserved factors in abating human-to-human transmission of coronavirus disease in africa underpin this study. we rely on publicly available data for africa countries confirmed and death cases. we use a novel estimation method capable of accounting for crosssectional dependence. we found a basis for the strict orthogonal relationship among the variable and accounted for unobserved heterogeneity of the human-to-human transmission. we rely on data obtained from the world health organisation (who) situation reports through to situation reports (a time plot of -time invariant observations). we transformed the daily observations in conformity with conventional panel data estimation procedure (wide to long) as in sarkodie and owusu ( ) . we relied on health indicators (number of covid- attributable deaths and number of confirmed cases) across africa states. in fig. i , we presented the spatial density of the number of confirmed cases and the number of deaths from covid across african states. our empirical strategy in gauging the statistical relationship between the number of attributable covid- deaths and confirmed cases was to estimate a series of baseline fixed effect estimator by assuming that all explanatory variables are strictly exogenous. we proceed to estimate the dynamic panel data system generalised method of moment (gmm) (arellano and bover, ) and impose (and test) the common factor restrictions to account for the potential endogeneity of the number of covid- attributable deaths and number of confirmed cases across africa states. the functional relationship is expressed as: where coviddeaths i, t is the total number of attributable covid- deaths in country i over period t; confrmd cases i, t represent the number of confirmed cases in country i over period t, t defines the time parameters, and i give the cross-sectional domain of the covid- attributable deaths model. we begin by imposing the assumption of strict exogeneity on the regressors, leading to violations and inconsistency in our fixed-effect model. we proceed to obtain asymptotically consistent parameter estimates in a single equation dynamic gmm estimators by using a common factor representation (blundell and bond, ) . our dynamic panel covid- attributable deaths model is specified as: all other variables remain as earlier defined except ρ, which gives the constant parameter. ω and θ are the output elasticities. with an attendant, country-specific fixed effect idiosyncratic errors (outliers) predicted upon the model in eq. ( ); we adjusted for violation of strict orthogonal assumptions by introducing the change parameter and by taking the semi-derivatives of the variables to account for variances in units and measurements to specify eq. ( ) ε i, t contains e i (the country-specific fixed effect that is timeinvariant) while μ it is assumed to be independent and normally distributed with zero ( ) mean and constant variance σ μ both over time and across cross-sections, i.e., u it ≈ n( , σ μ ). we also accounted for strict orthogonal violations that could be due to first differenced estimation of ordinary least squares since the transformed error term Δμ it still correlates with coviddeaths i, t− (a condition exacerbated when both contains μ it− ). the possibility of the e (coviddeaths i, t− Δμ it ) = ∀ h ≥ , t = , ……t justify the introduction of lagged variables as instruments in the strict orthogonal assumption relationship (anderson and hsiao, ; blundell and bond, ) . we estimated the dynamic system generalised method of moment (gmm) model for some reasons. the real-time reporting informed the observations of coronavirus disease in africa. we established a linear relationship between the variables of interest which informs our construct along such tangent. the number of cross-sections (countries) is higher than the numbers of time series (time plot of -time invariant reports) chosen. we estimated an unbalanced panel data model (predicted on non-occurrences of cases in some situation reports in some african countries). system gmm, renowned for glowing outcomes with persistent data under trifling assumptions (arellano and bover, ; blundell and bond, ) , was used to estimate the model of attributable covid- deaths as induced by confirmed cases. the result of the robust twostep estimates of the dynamic system generalised method of moment (gmm) is presented in table i . following pesaran ( ) , we estimated cross-sectional dependence. we rejected the null of no-cross-sectional dependence at a % level of significance. we also rejected the null of slope homogeneity at a % level of significance using the delta tilde and adjusted delta tilde estimates. we estimated the system gmm to account for cross-sectional dependence among heterogeneous observations. the one-period lag value of attributable covid- deaths is positive and statistically significant at %, implying its percentage increase will result in . percentage increase in covid- attributable deaths. the intuition point to the relatively less covid- attributable deaths as induced by previously confirmed cases. although the lagged factors control for simultaneity bias, we cannot completely rule out the devastating influence of historical information leading to covid- deaths. types of shared residents, proximity to health care facilities, choice of healthcare utilisation in the time of illness and most importantly during this global pandemic, existing health conditions, as well as the devastating influence of covid- attributable deaths to friends and family in terms of depression, frontline health workers who are saddled with the care and post-death management of patients, are magnanimous in this global pandemic era. in other climes, the number of confirmed cases is positive and statistically significant at %, implying . percentage increase in covid- attributable deaths in africa. by way of intuition, a proportionate rise in confirmed cases is attributable to potential deaths by~ . . principally, the cluster of residents and sub-group around regions with high confirmed cases should be dispersed to reduce the wave at which the virus transmits from human to human. in table ii , we validated the instrumental variable choice in the covid- attributable deaths in africa. dynamic panel data estimates are known to suffer from problems of unobserved heterogeneity, dynamic endogeneity and simultaneity bias (baltagi et al., ) . system gmm, known explicitly for heteroscedasticity and non-normality assumptions unlike the least squares estimates, assumes linearity and uncorrelated error terms. our first-order and second-order difference results in favour of the rejection of the null hypothesis in the firstorder serial correlation examination and acceptance of the null hypothesis for the second-order serial correlation test. blundell and bond ( ) argued that the system gmm estimators requires the presence of first-order serial correlation and not the second-order serial correlation in the residual term. the result of table ii confirms that we obtained appropriate diagnostics. z = − . ; p b . at % level of significance in the first order serial coreelation analysis and then no second order serial correlation based on calculated z that is not statistically significant at % (z = − . ;p n . ). the hansen ( ) j-statistics test result confirmed the model has valid instruments since we fail to reject the null of overidentifying restriction at a % level of significance (p n . ;i. e p = . ). the f-statistics value . indicates the model is jointly significant at % level of significance. this study examined the spatial density of the novel coronavirus disease (covid- ) across african states and leaned empirical credence to the relationship between confirmed cases and attributable deaths. we presented spatial and statistical evidence based on the situation reports from the world health organisation (who). we advise the public on the cautious interpretations of our statistical model, which rely on phenomenological models as in most social sciences research and not a clinical procedure that has a confidence interval of %. we found algeria to be the most hardly hit african nation (at the time of writing) by the rampaging virus (estimated in terms of the number of deaths recorded), and also we establish a linear relationship between the number of confirmed cases and the number of attributable deaths. our findings corroborate the finding of sarkodie and owusu ( ) in one of their strings of findings. the study is limited to facts obtainable at the present time of this global pandemic. note: * p b . , * * p b . respectively formulation and estimation of dynamic models using panel data another look at the instrumental variable estimation of error-components models dynamic panel data models. the oxford handbook of panel data initial conditions and moment restrictions in dynamic panel data models gmm estimation with persistent panel data: an application to production functions large sample properties of generalized method of moments estimators potential role of inanimate surfaces for the spread of coronaviruses and their inactivation with disinfectant agents general diagnostic tests for cross-section dependence in panels. cambridge working papers in economics investigating the cases of novel coronavirus disease (covid- ) in china using dynamic statistical techniques covid- infection: origin, transmission, and characteristics of human coronaviruses covid- ) situation report- . world health organization available at covid- ) situation report- . world health organization available at enteric involvement of coronaviruses: is faecal-oral transmission of sars-cov- possible? the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. key: cord- -e r s ee authors: katsidzira, leolin; gwaunza, lenon; hakim, james g title: the sars-cov- epidemic in zimbabwe: quo vadis? date: - - journal: clin infect dis doi: . /cid/ciaa sha: doc_id: cord_uid: e r s ee the trajectory, and impact of the sars-cov- pandemic in sub-saharan africa is unclear, but it is seemingly varied between different countries, with most reporting low numbers. we use the situation in zimbabwe to build an argument that the epidemic is likely to be attenuated in some countries with similar socio-economic and cultural structures. however, even an attenuated epidemic may overwhelm weak health systems, emphasising the importance of prevention. these prevention strategies should be tailored to the unique social and cultural networks of individual countries which may facilitate the spread of sars-cov . it is also equally important to maintain services for the major infectious diseases in the region such as tuberculosis and malaria. a breakdown of treatment and prevention services for these conditions may even overshadow the projected morbidity and mortality from covid- . m a n u s c r i p t the emergence of sars-cov- has shaken the globe in fundamental ways, and sub-saharan africa has been no exception. however, the magnitude and trajectory of the epidemic in the region is unclear, and the reflex response has ranged from nonchalant to assuming the worst-case scenario. the region was spared from the first two coronavirus epidemics of the st century, sars and mers, initially raising expectations of a similar scenario unfolding with sars-cov- [ ] . however, emerging information about the increased vulnerability of underprivileged groups to covid- disease in the united states has heightened fears that africa will be disproportionately affected by this pandemic [ ] . using zimbabwe as an example, we argue that the magnitude, and impact of the epidemic in most of sub-saharan africa is likely to be smaller than anticipated, with a reduced morbidity and mortality. however, the nature, and impact of such an attenuated epidemic remains unclear, and may still overwhelm weak health systems. in zimbabwe, the threat of covid- burst into national consciousness after the death of the second case to be diagnosed in the country. he was a young prominent media personality, and the son of a well-known politician and businessman, and had recently returned from new york. his demise gained intense media coverage, and highlighted the structural deficiencies in the zimbabwean health system in dealing with a highly contagious disease, particularly one which may require critical care [ , ] . this case strongly influenced the subsequent response to covid- by both the government, and the private healthcare industry in zimbabwe, and played a pivotal role in raising public awareness. subsequently, government reserved hospital beds and ventilators for covid- at one of the tertiary care hospitals in the capital, harare, and is upgrading and refurbishing infectious diseases hospitals around the country. another set of, five this highlights the need to balance the response to covid- with on-going public health needs [ ] . it is not inconceivable that we may see an increase in mortality from non-covid- related conditions, and this increase may even dwarf covid- related deaths, as was previously observed after the ebola outbreak in west africa [ ] . thus, it is essential to maintain a sense of proportion, particularly in sub-saharan africa, where access to healthcare is a challenge even during normal times. third, zimbabwe has been relatively isolated from global air travel. in , only foreign airlines were flying into the country, mostly from regional destinations [ ] . there is a link between the volume of international flights, and the magnitude of the sars-cov- epidemic in sub-saharan africa [ , ] . it is no coincidence that south africa, with the most advanced economy in the region, and multiple international flights daily, has the highest number of sars-cov- cases in the region [ , ] . countries such as zimbabwe, which are less integrated with the global economy, may have been inadvertently less exposed to the sars-cov- pandemic. even after arrival in zimbabwe, travellers are often ferried to their homes or hotels in private vehicles, limiting exposure to the public that may occur with efficient mass transport systems. this situation has an inherent social distancing, and may simplify contact tracing. finally, zimbabwe and most of sub-saharan africa have a predominantly young population. according to the census, % of the zimbabwean population was a c c e p t e d m a n u s c r i p t younger than years and only . % were older than years [ ] . older age has been consistently associated with heightened mortality from covid- [ ] [ ] [ ] [ ] . consequently, differences in the population age structure can lead to dramatic differences in mortality for covid- disease [ ] thus, it is reasonable to anticipate a much lower mortality from covid- in sub-saharan africa, compared to europe and north america, where there is a much larger proportion of older people. nonetheless, it is important to protect the small, elderly population in sub-saharan africa, and this may be easier to implement. there is limited use of institutional care for the elderly such as nursing homes, or retirement villages [ ] . this may reduce the risk of nosocomial sars-cov- outbreaks in a vulnerable, captive population since the majority of elderly people live in the rural areas, their risk of infection can be reduced by restricting movement between urban and rural areas. a potential source of higher than anticipated mortality from covid- disease in sub-saharan africa is the high burden of hiv infection [ ] . it is also possible that individuals with hiv infection may have increased susceptibility to sars-cov- infection. however, there is no robust data on the interaction between hiv and covid- , although initial evidence from a small case series suggests that the impact could be less than initially feared [ ] . moreover, considerable progress has it remains unclear whether complete lockdowns are the most ideal method to limit the spread of sars-cov- in sub-saharan africa [ ] . a complete lockdown has its m a n u s c r i p t own economic ramifications, and the sars-cov- pandemic in itself has led to the first recession in a quarter of a century in the region [ ] . however, the degree of the adverse impact of lockdowns on the economy will differ between different countries. in zimbabwe, there is likely to be disproportionate effect at household level, as most people now depend on the informal sector, in a country with limited formal social safety nets [ ] . moreover, enforcement of lockdowns is potentially unequal, and may take a punitive form in the poor neighbourhoods, that paradoxically, are less likely to have the initial imported, and imported-associated sars-cov- infections. flattening the curve may not have a significant impact if the epidemic is small, and the existing healthcare infrastructure is already overwhelmed by the large burden of communicable and non-communicable diseases. however, the net effect of lockdowns will only become clearer retrospectively, and data from countries such south africa becomes available. south africa has the largest epidemic in the region, and has implemented a strict lockdown, and is generating high quality epidemiological data. for now, policymakers have to make decisions based on imperfect information, which is continuously changing as our understanding of the virus incrementally increases. in the meantime, incorporating other approaches into the on-going measures may also help in limiting the spread on sars-cov- . one such approach that can be undertaken in sub-saharan africa is to restrict the movement of people between different suburbs, and between urban and rural areas, while allowing some level of economic activity. active surveillance, and testing for both imported and community cases with stringent contact tracing and isolation should continue. it is instructive that this approach has identified most of the reported cases in zimbabwe. localised lockdowns may also be considered for specific foci of infections. international travel a c c e p t e d m a n u s c r i p t should continue to be curtailed, and more effective screening strategies at the ports of entry must be developed and implemented when it resumes. in zimbabwe there is a dichotomous health system, one public, catering for the majority, and the other private sector, catering for the minority who are on medical insurance or can afford to pay. given the aforementioned profile of the typical case in the country, it is important to ensure that prevention strategies are also implemented stringently at the private health facilities, which should be capacitated where necessary. the protection of healthcare workers should be a key priority, and some of them serve both the public and private sectors, and are a potential bridge of infection. all the cases seen in zimbabwe so far have either been identified at private hospitals, or from screening returning travellers, or from contact tracing. as of may , there has not been a case, presenting initially to a public healthcare facility. in conclusion, it is conceivable that the impact of covid- in zimbabwe could be attenuated in comparison to what has happened in economies with mass transport systems, high volume air travel and over-crowded social gatherings. this however, is on the proviso that there is adequate insulation of the community from returning travellers and a robust implementation of hygienic practices and social distancing. finally, the covid- epidemic is an opportunity for countries in sub-saharan africa to invest and innovate in the delivery of better health care including critical care infrastructure and to redirect dollars being lost in medical tourism inwardly [ ] . strategy and technology to prevent hospitalacquired infections: lessons from sars, ebola, and mers in asia and west africa covid- and african americans zimbabwean broadcaster zororo makamba died 'alone and scared makamba family fumes over zororo's death the late arrival of covid- in africa -mitigating pan-continental spread effects of response to - ebola outbreak on deaths from malaria, hiv/aids, and tuberculosis passengers' destinations from china: low risk of novel coronavirus ( -ncov) transmission into africa and south america income inequality trends in sub-saharan africa: divergence, determinants and consequences zimbabwe national statistical agency and icf international zim's airline industry needs serious attention covid- pandemic in west africa preparedness and vulnerability of african countries against importations of covid- : a modelling study clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study prevalence of comorbidities in the novel wuhan coronavirus (covid- ) infection: a systematic review and meta-analysis risk factors for severity and mortality in adult covid- inpatients in wuhan clinical characteristics and outcomes of older patients with coronavirus disease (covid- ) in wuhan, china ( ): a single-centered, retrospective study demographic science aids in understanding the spread and fatality rates of covid- the key actors maintaining elders in functional autonomy in bobo-dioulasso (burkina faso) covid- in patients with hiv: clinical case series. the lancet hiv. . unaids. country factsheet: zimbabwe covid- : africa records over cases as lockdowns take hold covid- (coronavirus) drives sub-saharan africa toward first recession in years shadow economies around the world: what did we learn over the last years? essential care of critical illness must not be forgotten in the covid- pandemic a c c e p t e d m a n u s c r i p t funding: no funding was required for this work. a c c e p t e d m a n u s c r i p t key: cord- - en yey authors: nkengasong, john n; mankoula, wessam title: looming threat of covid- infection in africa: act collectively, and fast date: - - journal: lancet doi: . /s - ( ) - sha: doc_id: cord_uid: en yey nan because of the high volume of air traffic and trade between china and africa, africa is at a high risk for the introduction and spread of the novel coronavirus disease (covid- ); although only egypt has reported the first case, from a non-national. the greatest concern for public health experts is whether covid- will become a pandemic, with sustained year-round transmission, similar to influenza, as is now being observed in several countries. what might happen to africa-where most countries have weak health-care systems, including inadequate surveillance and laboratory capacity, scarcity of public health human resources, and limited financial means-if a pandemic occurs? with neither treatment nor vaccines, and without pre-existing immunity, the effect might be devastating because of the multiple health challenges the continent already faces: rapid population growth and increased movement of people; existing endemic diseases, such as human immunodeficiency virus, tuberculosis, and malaria; remerging and emerging infectious pathogens such as ebola virus disease, lassa haemorrhagic fever, and others; and increasing incidence of non-communicable diseases. models that enable the continent to better allocate scarce resources to better prepare and respond to the covid- epidemic are crucial. the modelling study by marius gilbert and colleagues in the lancet identifies each african country's risk of importation of covid- from china, using data on the volume of air travel from three airports in provinces in china to african countries. gilbert and colleagues use two indicators to determine the capacity of countries to detect and respond to cases: preparedness, using the who international health regulations moni toring and evaluation framework; and vulnerability, using the infectious disease vulnerability index. based on their analysis, egypt, algeria, and south africa had the highest importation risk, and a moderate to high capacity to respond to outbreaks. nigeria, ethiopia, sudan, angola, tanzania, ghana, and kenya had moderate risk with variable capacity and high vulnerability. in the model, the risk mainly originates from guangdong, fujian, and beijing. the study provides a valuable tool that can help countries in africa prioritise and allocate resources as they prepare to respond to the potential introduction and spread of covid- . the study should also be interpreted in light of the fast-evolving nature of the covid- outbreak. first, with the exception of ethiopian airlines, all african airlines have suspended flights to china. although these measures might delay, but not stop, the importation risk of covid- into africa, their implementation is still worthwhile. second, although beijing, shanghai, and fujian do not report the highest number of cases of covid- in china, the volume of travel from these cities to africa is high, which might increase the risk of exporting cases to africa. lastly, almost half of the flights from africa to china are operated by ethiopian airlines, so it is possible that cases might pass through ethiopia and affect destination countries. the report by gilbert and colleagues provides an important tool to map out the continental risk for the spread of covid- in africa, which should be used to inform a framework of action to prepare the continent for any potential importation and spread of covid- . first, collectively, africa needs a unified continent-wide strategy for preparedness and response. the strategy must be comprehensive, and member states, donors, and partners should immediately commit to releasing financial resources to support country-customised implementation plans derived from the strategy. to help develop a common strategy that will allow for effective coordination, collaboration, and communication, the african union commission, africa centres for disease control and prevention (africa cdc), and who, in partnership with african countries, have established the africa taskforce for coronavirus preparedness and response (aftcor). the partnership has six work streams: laboratory diagnosis and subtyping; surveillance, including screening at points of entry and cross-border activities; infection prevention and control in healthcare facilities; clinical management of people with severe covid- ; risk communication; and supply-chain management and stockpiles. because mitigating the potential spread of covid- in africa will require rapid detection and containment, the laboratory work streams of aftcor, africa cdc, and who are working closely to expeditiously scale up diagnostic testing capacity linked to enhanced surveillance and monitoring-eg, at the beginning of february, only two countries in africa had the diagnostic capacity to test for covid- . however, as of feb , , more than countries would have been capacitated to accurately diagnose covid- infection, thanks to the coordination efforts of aftcor. as testing becomes more available, it is possible that more cases might be detected. second, any effective preparedness and response strategy for covid- requires a committed political will; as such, the african union commission, africa cdc, and who convened, on feb , , in addis ababa, ethiopia, an emergency meeting of all ministers of health of member states to commit to acting fast and collectively to develop and implement a coordinated continent-wide strategy. aftcor taskforce was formed, and a continent-wide strategy was endorsed at the end of the emergency meeting, with a call for strong coordination of efforts. to prevent the occurrence of a social, health security, and economic tragedy, actions agreed at the emergency ministerial meeting will need to be acted on quickly, before any additional covid- cases are introduced to the continent, and result in sustained human-tohuman transmission. the potential social, economic, and security devastation that covid- could cause in africa should be enough of an incentive for african governments to invest immediately in preparedness for the worst-case scenario. third, commitment and release of financial resources from partners and donors before a crisis hits africa will help anticipate demand and address supply chain management, mapping, and stockpiling of covid- response needs, such as large quantities of personal protective equipment, gloves, surgical masks, coveralls, and hoods, and medical countermeasures like antiviral agents. supplies of these items will be limited in africa because of reduced manufacturing capacity. fourth, national, regional, and international organisations need to cooperate and collaborate to optimise limited supplies, using a whole of government approach. fifth, all member states will need to urgently develop and put in place proper quarantine and infection control protocols, including procedures for implementing social distancing (mass gathering and potential closure of public facilities). lastly, the capacity-building training efforts that africa cdc and who are conducting must be implemented and cascaded immediately down the health system pyramid in each country. medical staff at major hospitals must be trained in the proper protocols of quarantining individuals who are at-risk of covid- infection, as well as isolation and safe treatment of patients who test positive. as the director general of who has stated several times, the window of opportunity to act is narrowing. africa needs to be supported to act now, and needs to act fast. jnn is the director of the africa cdc and a who special envoy on covid- . wm is an epidemiology analyst at africa cdc. we declare no other competing interests. china's response to a novel coronavirus stands in stark contrast to the sars outbreak response update on covid- in the eastern mediterranean region italy covid- case count now , government introduces urgent measures preparedness and vulnerability of african countries against importations of covid- : a modelling study the effect of travel restrictions on the spread of the novel coronavirus (covid- ) outbreak countries rush to build diagnostic capacity as coronavirus spreads. reuters key: cord- -pnmycagi authors: tola, monday; ajibola, olumide; idowu, emmanuel taiwo; omidiji, olusesan; awolola, samson taiwo; amambua-ngwa, alfred title: molecular detection of drug resistant polymorphisms in plasmodium falciparum isolates from southwest, nigeria date: - - journal: bmc res notes doi: . /s - - - sha: doc_id: cord_uid: pnmycagi objective: nigeria bears % of global malaria burden despite concerted efforts towards its control and elimination. the emergence of drug resistance to first line drugs, artemisinin combination therapies (acts), indicates an urgent need for continuous molecular surveillance of drug resistance especially in high burden countries where drug interventions are heavily relied on. this study describes mutations in plasmodium falciparum genes associated with drug resistance in malaria; pfk , pfmdr , pfatpase and pfcrt in isolates obtained from symptomatic malaria patients collected in august , aged – years old from south-west nigeria. results: two pfmdr , n and y variants were present at a prevalence of % and . % of isolates respectively. there was one synonymous (s s) and two non-synonymous (m v, s m) mutations in the patpase gene, while pfcrt genotype (cviet), had a prevalence of %. the pfk c y mutant allele was suspected by allelic discrimination in two samples with mixed genotypes although this could not be validated with independent isolation or additional methods. our findings call for robust molecular surveillance of antimalarial drug resistance markers in west africa especially with increased use of antimalarial drugs as prophylaxis for covid- . malaria infects over million people with at least , deaths annually, % of those deaths occur in children under the age of five, and % of deaths according to world health organization data occurred in africa [ ] . drug resistance of malaria parasites to previously efficacious first line chemotherapies, chloroquine (cq) and sulfadoxine-pyrimethamine (sp), in sub-saharan africa (ssa), led to replacement with artemisinin combination therapies (act), and complete removal of cq [ , ] . a single point mutation k t, in codons - of the chloroquine resistance transporter gene (pfcrt) has been the main cause of resistance to cq [ , ] , while mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) were responsible for sp resistance in parasites [ , ] . p. falciparum has also developed resistance to acts, which combines a fast-acting artemisinin (art) derivative with a long-lasting partner such as lumefantrine, mefloquine or amodiaquine. act resistance is widespread in the greater mekong subregion (gms) in southeast asia [ , ] . resistance to art and its derivatives have been confirmed to be associated with mutations in kelch- gene (pfk ). mutations in pfk have been reported in gms, guyana, rwanda, and tanzania [ ] . in ssa, pfk mutations are yet to be associated with partial or complete art-resistant parasite isolates, and [ , ] . mutations in pfmdr on codons , , and copy number amplifications have also been linked to susceptibility to drugs including acts. p. falciparum sarcoendoplasmic reticulum calcium-atpase (serca) type protein encoded by a gene pfatpase has been described to modulate the susceptibility of parasites to art. pfat-pase protein of p. falciparum has therefore been suggested to be a target of arts [ ] [ ] [ ] . molecular surveillance of drug resistance associated mutations, especially to acts is particularly relevant in africa which bears > % of the deaths globally. this study describes the molecular prevalence of mutations in the drug resistant genes pfk , pfmdr , pfatpase and pfcrt from p. falciparum clinical samples in southwest nigeria, where arthemeter lumefantrine has been the main first line act for malaria treatment over the last years. this study was carried out in august in two communities-badagry (lagos state) and alajue (ede, osun state). badagry ( ° ′ n ° ′ e), is a coastal town with an area of m and a human population of , (npc, ) that borders the republic of benin. alajue village ( ° ′ n ° ′ e), is an ancient yoruba town with a total area of m and a human population of , (npc, ) . both towns are located in the south western part of nigeria, with similar environmental conditions, occupation and lifestyle of the people. a total of symptomatic malaria patients were recruited for this study. following informed consent of the participants, parent or guardian, they were tested with malaria rapid diagnostic test (rdt) kit and ml blood samples were collected into rnalater. dried blood spots (dbs) of each sample was made on mm whatman filter paper. dna from dbs was extracted using the qiagen mini kit (qiagen) according to manufacturer's instructions and stored at minus °c until needed. total rna was isolated from whole blood stored in rnalater using purelink ™ rna mini kit (invitrogen) following the manufacturer's instructions. dna from dbs of each sample was used for molecular speciation of p. falciparum by nested pcr through amplification of the s rrna following established protocols [ ] . nest amplified a large part of the s rrna common to the plasmodium genus, while the nest amplified a region in the genus specific for that species of plasmodia. differentiation of the species was based on amplicon band size with p. falciparum having a size of bp. pcr fragments were detected and sized on the qiaxcel automated electrophoresis system. to determine the gene expression levels of pfk and pfatpase, total rna was treated to remove genomic dna by digesting with µl of dnasei (fermentas) and µl of reaction buffer, incubated at °c for min and inactivated with µl, mm edta, °c for min. rna purity and concentration were determined using a nanodrop tm (thermo scientific). cdna was synthesised using the rna reverse transcriptase kit (invitrogen). synthesized cdna was quantified by qpcr on a cfx (bio-rad) with the following cyclic conditions: °c, min, cycles of °c, s and °c for s. relative fold increase of specific mrna transcripts in samples was compared to p. falciparum ( d ) wildtype control, normalised using the s rrna housekeeping gene. expression levels were calculated using −ΔΔct method. data was analysed using at least independent experiments. alleles of pfk propeller domain polymorphisms (y h, r t, i t, c y), and pfatpase (s s, m v, s m) associated with delayed clearance were determined by taqman allelic discrimination and sequencing and list of primers used provided in additional file : (tables s , ). for each sample a working master mix was prepared to include × of taqman universal pcr master mix (life technologies), nm of the forward and reverse primers, nm of each allele specific probe (additional file : table s ) and at least ng of dna from dbs in µl reaction volume. amplification was done on the bio-rad cfx realtime thermocycler set to detect fluorescent emissions for -carboxyfluorescein ( -fam) (mutant) and hexachloro- -carboxyfluorescein (hex) (wild type). each snp was amplified in a thermocycle of °c for min, min of initial template denaturation and enzyme activation at °c followed by cycles of °c for s and °c for min. allelic discrimination analysis was performed with the bio-rad cfx manager with parameters set to subtract background and correct for fluorescent drift prior to clustering of wild or mutant amplicons. all pcrs included dna from p. falciparum d as wildtype control. pfk , pfatpase , pfcrt and pfmdr amplicons were purified from a . % agarose gel and subjected to cycle sequencing using bigdye v . (details in supplementary methods section). sequencing was done on abi xl dna analyser. descriptive statistics was carried out in microsoft excel . sequence alignment was done on clc main workbench version . . and translation of nucleotide sequence to amino acid sequences and editing were done using mega . . software. a p-value of ≤ . was considered statistically significant. transcript level determination and allelic discrimination analyses were done with the bio-rad cfx manager software (additional file ). in this study, patients, ( . %) male and ( . %) females presenting with symptoms of malaria were recruited for the study (additional file : table s ). the age distribution was as follows; ( - years), ( - years) ( - years) and were > years. following confirmation of all rdt positive samples as p. falciparum positive by pcr, we carried out gene expression, detecting only wild type pfk transcript in samples. relatively low levels of pfatpase transcript was also detected with both wild and mutant strains identified in the population (fig. ) . probe-specific allelic discrimination, detected both wild type and mutant pfatpase alleles at known drug resistance snps (fig. ) . for pfk c y locus, mixed alleles (both c and y) were suspected in isolates but the mutant type variant was not confirmed by sanger sequencing of amplicons against the reference strain p. falciparum d . k sequence identified eight non-synonymous snps in pfk , but all in single isolates. a deletion variant a was identified in . % of isolates sequenced (additional file : table s ). sequence analysis of pfatpase revealed snps, one synonymous and two non-synonymous mutations (additional file : table s ). the act resistance related snp (s ) was present in . % of samples. pfmdr wildtype n allele was present in % of isolates sequenced. pfmdr y was at much lower prevalence of . % (additional file : table s ). pfcrt - variants were translated, and haplotypes inferred. the cviet haplotype associated with cq resistance had a prevalence of %, while the wildtype cvmnk was found in % of isolates from the population (fig. ). chemotherapy is one of the main malaria control strategies implemented by the national malaria control program in nigeria. today, it is mostly based on first line artemisinin based combination therapy that was introduced into nigeria in following the withdrawal of cq and sp due to widespread resistance. hence, there is samples fig. messenger rna transcript levels for pfk and pfatpase using −ΔΔct . total rna was isolated from whole blood preserved in rnalater, reverse transcribed to cdna in order to measure gene expression profiles need to continuously monitor drug resistance and genetic markers that are associated with reduced drug efficacy. this study characterized drug resistance associated polymorphism in four different p. falciparum drug resistance genes; pfcrt, pfmdr , pfatpase and pfk that have been implicated in reduced act efficacy [ , , , ] . as expression of mutated genes is needed for generating the resistance phenotype, the allele specific mrna transcript levels of pfk and pfatpase were also determined. most isolates expressed the wild type pfk while both the wild and mutant pfatpase variants were expressed by different strains. though pfk c y mutant allele was suspected in two mixed infections, only wildtype mrna was detected. these mutant variants might have been from a minority strain whose mrna expression might have been masked by predominant pfk wildtype parasites in the infections. in the absence of repeated detection and confirmation by sequencing, the possibility of the detected pfk c y mutants being as a result of contamination cannot be ruled out. acts have been in use for years in nigeria, and the classical south east asian pfk artemisinin resistance markers are rare in africa. however, the possibility of the pfk y resistance mutations is a call for concern, requiring further sampling and analysis of this population. the pfk c y mutant is the most prevalent snp associated with reduction in parasite susceptibility to acts. only few cases of delayed clearance of malaria after act treatment have been reported in africa and the c y is almost completely absent. a recent act therapeutic efficacy study with patients from the same populations detected persistent parasites days post treatment but no pfk artemisinin resistance associated mutants [ ] . future enlarged studies including in vivo and in vitro assessments, genetically characterising local parasite isolates may throw light on any possible emergence of tolerance to act components. though genetic epidemiology and in vitro forward genetic approaches have clearly implicated c y and other pfk mutations in delayed parasite clearance [ , ] , the artemisinin resistance phenotype and associated molecular mechanisms may be different in african parasites lacking these pfk variants. however, a recent report from rwanda confirmed de novo local emergence and spread of the pfk r h artemisinin resistance associated variant, though clinical cure rate remained > % [ ] . other pfk haplotypes containing mutations at positions a s and v f, close to the c y mutation, are known to circulate in africa and could have emerged prior to the introduction of acts [ ] . overall, any molecular indicators of resistance to artemisinins should be taken seriously and carefully monitored to prevent selection and spread of fit resistant parasites across africa, which heavily relies on drugs against high levels of infection and morbidity. we also detected polymorphisms of pfatpase , the r k, a s, i i found in brazil, double mutation e k, a e in senegal, and h y in central africa. the pfatpase s snp we detected has been widely reported as a potential molecular marker for p. falciparum resistance to artemether [ ] . this snp is found within the cytoplasmic n (nucleotide binding) domain close to the conserved hinge, which in many species is important for structural transitions in the pfatpase cycle, calcium binding and release [ ] . other well-known characterized mutations in drug resistant genes such as pfmdr -n y and y f, and pfcrt-cviet haplotype were also detected. polymorphisms of pfmdr (n y, y f, s c, n d, and d y) and copy number amplifications modulate resistance to quinolones and other act partner drugs. they have been associated with reduced efficacy of artemether-lumefantrine/mefloquine combinations [ ] . artemether-lumefantrine is the most common act combination in africa and nigeria. it selects for wildtype n and mutant y , as shown for other populations in west africa [ ] . surprisingly a high prevalence of the cviet haplotype was recorded despite the withdrawal of cq from the population almost years prior to this study. the high prevalence ( %) observed for pfcrt- t resistance marker in southwest nigeria is however lower than those reported from the south-eastern part of the country, where prevalence was as high as % [ ] . lumefantrine selects for wildtype pfcrt k , reversing cq resistance that is strongly linked to the cviet haplotype [ ] . this reversal to the cq susceptible cvmnk wild type haplotype following cq withdrawal has been reported across many malaria endemic regions; in china [ ] , tanzania [ ] , kenya [ ] and malawi [ ] , or following malaria decline as observed in ghana [ ] . exception are only seen in countries like ethiopia ( ) were cq is still being administered to treat p. vivax, maintaining cq pressure on the parasite to retain the resistant haplotypes. in nigeria, cq remains accessible through private drug suppliers together with amodiaquine, both of which could be slowing the reversal of the resistant haplotype in the population. this study provides a molecular profile of the drug resistance genes in malaria parasites from south western nigeria, highlighting the need for continuous and broader surveillance for antimalarial resistance of this high malaria prevalent population. our limited study locations and sample size is not sufficient to detect emerging resistance loci that may be at low frequencies in the populations. due to limited availability of sampled dna and rna, we were unable to repeat the detection of the suspected c y mutant or validate its presence using sequencing approaches. supplementary information accompanies this paper at https ://doi. org/ . /s - - - . additional file : table s . list of primers and cycling conditions for amplification. table s . taqman primers and probes. table s . demographics of respondents. table s . description of pfk , pfatpase and pfmdr polymorphisms. figure s . allelic discrimination of k single nucleotide polymorphisms (snps). art : artemisinin; act : artemisinin combination therapy; cq: chloroquine; ssa: sub saharan africa; pcr: polymerase chain reaction; npc: national population commission; snp: single nucleotide polymorphisms. world health organisation. malaria spread of artemisinin resistance in plasmodium falciparum malaria a 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malaria in hainan, people's republic of china trends in chloroquine resistance marker, pfcrt-k t mutation ten years after chloroquine withdrawal in tanzania chloroquine resistance before and after its withdrawal in kenya reemergence of chloroquine-sensitive plasmodium falciparum malaria after cessation of chloroquine use in malawi convenient online submission • thorough peer review by experienced researchers in your field • rapid publication on acceptance • support for research data, including large and complex data types • gold open access which fosters wider collaboration and increased citations maximum visibility for your research: over m website views per year • at bmc selective sweeps and genetic lineages of plasmodium falciparum drug -resistant alleles in ghana high prevalence of pfcrt-cviet haplotype in isolates from asymptomatic and symptomatic patients in south-central oromia, ethiopia springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations we wish to acknowledge all the parents and participants of this study including the management and staff of the hospitals where samples were collected (especially the laboratory scientist) and the support of laboratory staff at the public health division of the nigerian institute of medical research and mrcg at lshtm the gambia. key: cord- -w jqmpww authors: muzemil, abdulazeez; fasanmi, olubunmi gabriel; fasina, folorunso oludayo title: african perspectives: modern complexities of emerging, re-emerging, and endemic zoonoses date: - - journal: journal of global health doi: . /johg. . sha: doc_id: cord_uid: w jqmpww nan r ecent events have shown that public health, animal health and national economies have been threatened, globally, by the increased occurrence of emerging and re-emerging infectious diseases (ereids) [ ] . specifically, land use change cum agricultural practices, surging human demographic, pathogen evolution (antimicrobial resistance), failure of public health systems, global travel and more global interconnectedness in spatial and temporal dimensions have driven these threats [ ] . other aggravating factors include: ecological changes, incursion into previously uninhabited areas, changes in human behavior, environmental degradation, international trade, technology and industry, antimicrobial misuse, and deficiencies in public health infrastructure and decision-making [ ] [ ] [ ] . major ereids − including zoonoses − have been reported in the last two decades including: bovine spongiform encephalopathy, hendra, nipah, severe acute respiratory syndrome (sars), highly pathogenic avian influenza (hpai) h n , h n and h n subtypes, west nile fever, pandemic h n influenza, ebola virus disease (evd) and middle east respiratory syndrome coronavirus (mers-cov). many of these diseases have been documented in africa. in africa, of the countries ( %) have reported ereids to the who since ( table ) . while several initiatives have been implemented globally to accelerate progress toward a safer world [ ] , it is yet not clear whether african countries are ready and capable of handling the magnitude and threats associated with ereids [ ] . here, we reviewed plausible reasons and drivers for the upsurge of ereids in africa and proffer some mitigating measures. human populations in african countries have rapidly increased in the last few decades (figure ). population growth has occurred together with a substantial modification of human and pathogen behaviours [ , ] . for example, hoosegood has identified that societal behaviours eg, union formation and cohabitation, re-marriage and partnering, union instability-widowhood, divorce and separation, fertility and fecundity, and fertility-related decisions significantly impact on and are impacted by hiv and aids in sub-saharan regions particularly, in southern africa [ ] . second, urban growth has disrupted wildlife and pathogen ecology [ , ] . as human-pathogen contacts increase, so does the probability for more outbreaks. pathogens affected include cowpox, lyme disease, nipah, hendra and ebola viruses as well as the group named eskape -which includes enterococci, s. aureus, k. pneumoniae, a. baumannii, p. aeruginosa and en-terobacteria-which explains between and % of all african human mortalities [ , ] . as human-pathogen contacts increase, so does the probability of more outbreaks. to prevent epidemics, it is needed to markedly improve public infrastructures, sanitation, and the health systems. for instance, the public and animal health surveillance systems must transform, so interventions occur within acceptable response times [ , , ] . third, in the th century, the average temperature has increased approximately . °c in the african continent. climate change has predisposed africa to highly vulnerable situations, particularly around internationally shared water resources. consequently, new challenges have emerged, including: border-related conflicts, food security risk due to declines agricultural production, vectorand water-borne diseases, (especially in areas with inadequate health infrastructure), flooding and exacerbation of desertification by changes in rainfall and intensified land use [ ] . predictions related to water resources include: (a) decreased rainfalls in portions of the sahel, (b) increased rainfalls in east central africa, (c) increased temperature ranging from . °c to > . °c per decade, especially in the semi-arid margins of the sahara and central southern africa [ ] . some studies have also suggested that major climate change will influence water resource use, natural resources management and biodiversity, human health, food security, resettlement and infrastructure re-allocation, and desertification [ , ] . variance in climatic conditions will impact significantly on disease ecology and epidemiology with upsurge in human-animal disease conditions due decreased salinity of the soil which can increase the number of toxic bacteria and breeding sites for mosquitoes and rodents. these challenges can have consequences on international trade and commerce. since the liberalization of trade policies between countries over the past two decades, national economies have grown in leaps and bounds. while such policies have fast-tracked growth forecast for african countries, they also have augmented the risks of emergent and trans-boundary animal and human diseases especially associated with long flights, such zoonotic tuberculosis, influenza viruses, hiv/aids and cholera. because trans-border movements of livestock and/or some commercial practices may bring together disease vectors and humans, human and animal health should be addressed together [ ] [ ] [ ] . fourthly, the rapid expansion in human populations (and consequently, the need to meet the food security needs) has warranted the intensification of animal and crop agriculture. these changes have converted previously fallow lands and forest into arable, agricultural and/or grazing lands. associated with these changes are increased (a) rodents populations, (b) dispersal and redistributions of wild ruminants populations and their ectoparasites, (c) wildlife-livestock-human interactions, and (d) occurrence of diseases like rift valley fever. bodies of evidence have suggested that the rate of future zoonotic diseases will be closely linked to the evolution of the agriculture-environment nexus [ , ] . it is suggested that, as long as africa (or any other continent) does not address complex interactions -such as those that involve agriculture, the environment, economics, sociology, as well as zoonotic pathogens, disease outbreaks may follow human-driven disruptions, as those observed after major changes in land use, eg, those related with the construction of dams, mines, and intensive agriculture. the fact that pathogens have evolved and keep evolving should be emphasized. microbes such as mycobacterium tuberculosis, enterococcus faecium, enterobacter cloacae, klebsiella pneumoniae, s. aureus, acinetobacter baumanii and pseudomonas aeruginosa have developed multiple resistance mechanisms due to excessive and long-term use of antimicrobials, genetic transfers of resistance genes and selective pressures [ , ] . endemic antimicrobial-resistant africa will need to prioritize rapid detection, prompt response to ereids, optimize the benefit of geospatial epidemiology in policy decisions and utilize interdisciplinary educational programs. ) . intense human-animal interactions, and consumption of non-certified pathogen-free animal products facilitate the spread of zoonoses pathogens come with heavy clinical and economic burdens, especially in the developing countries. recent review had indicated that endemic infections associated with antimicrobial resistance requires a particular attention because such diseases are linked with approximately to % of all annual human deaths in africa [ ] . it has been estimated that, by , more lives will be lost due to antimicrobial resistance (amr) than cancer [ ] . one major component of antimicrobial resistance is the overuse of antimicrobials in the production of livestock, which are then passed to humans [ ] . because vaccines reduce the incidence of infectious diseases (and, therefore, antibiotic use), immunisations might reduce amr [ , , ] . prevention and mitigations: given the numerous and serious issues here identified, african governments need to prioritize efforts aimed at rapid detection and prompt response to emerging or re-emerging pathogens. for example, the critical response time (crt or time available to implement effective epidemic control measures) should be considered in decision-making [ , ] . that is so because for any intervention to be very effective (≈ %), it must be deployed under a realist timeframe; if it requires a longer period of time, it will necessarily be (i) less effective (if not ineffective), and (ii) more expensive [ ] . crt may or may not include geo-referenced data. when it lacks geographical data, it becomes much shorter, making useless almost any intervention. thus, the real significance of crt is that it should be expanded (giving decision-makers more time to complete interventions) − which can only be achieved when high-resolution geo-referenced epidemiologic data are analyzed in time and space. thus, to achieve improved epidemic control measures, geographically explicit data should be collected from epidemics, analysed and lessons learnt made available for future interventions. only such (local or regional) data can support scientifically valid decision-making. yet, even recent epidemics have been addressed with ad hoc policies, such as the classic ' -km radius control rings' -which assume all epidemics (ie, all pathogens, all host species, and all local geographies) are identical [ ] [ ] [ ] . failure to consider local bio-geo-epidemiological information has led to widespread dissemination of major epidemics, such as ebola in guinea, liberia, and sierra leone [ ] . infectious diseases and zoonoses are extremely expensive to nations both clinically and economically, for example a recent valuation had estimated such costs to include: sars in asia and canada (us$ - billion), hpai h n globally (us$ billion), worldwide influenza h n (us$ - billion), ebola in west africa (us$ billion) and zika in latin america and the caribbean (us$ - billion) [ ] , promptly delivered pre-emptive actions and control measures, as well as targeted interventions can significantly reduce burdens associated with these diseases. the creation of interdisciplinary educational programs aimed at local and regional decision-makers involved in disease diagnosis, dissemination, and control, is recommended. such programs could develop and integrate: (i) local data on antimicrobial resistance, (ii) high-resolution, local geo-referenced data, and (iii) site-specific control measures that can be implemented within biologically valid critical response times. one health contributions towards more effective and equitable approaches to health in low-and middle-income countries urbanization and disease emergence: dynamics at the wildlife-livestock-human interface clinical and economic impact of antibiotic resistance in developing countries: a systematic review and meta-analysis the world health report -a safer future: global public health security in the st century the demographic impact of hiv and aids across the family and household life-cycle: implications for efforts to strengthen families in sub-saharan africa working group ii). impacts, adaptation and vulnerability. the third assessment report of the intergovernmental panel on climate change working group ii the role of vaccines in preventing bacterial antimicrobial resistance ebola virus disease in west africa -the first months of the epidemic and forward projections investing in one health: a concerted approach to address shared risks to humans, animals, and the environment acknowledgments: population data from the united nations was utilized in this work. authorship contributions: am initiated the study, contributed to the data and initial draft; ogf contributed to data filtering and analysis; fof reviewed the concept, analyzed data, wrote, edited and reviewed the manuscript and took overall direction of the work. the authors completed the unified competing interest form at www.icmje.org/coi_disclosure.pdf (available upon request from the corresponding author), and declare no conflict of interest. key: cord- -py d rjq authors: thiaw, ibrahima title: archaeology of two pandemics and teranga aesthetic date: - - journal: afr archaeol rev doi: . /s - - - sha: doc_id: cord_uid: py d rjq the covid- pandemic has exposed how coloniality and racism are endemic to modern society. this was reflected in many early western discourses, french in particular, about the pandemic in africa. these discourses unveiled old colonial antagonism, projection, stigmatization, and paternalism. the articulation of such discourses among well-informed and sometimes well-meaning people calls for deeper introspection on archaeological practices and modalities of community engagement. building on archaeology’s multiple contributions to africa’s past and observed practices of resilience in senegal by ordinary people in the face of the spread of covid- , this essay reflects on the relevance of the archives, including the archaeological record, as usable resources for managing the problems of our times. résumé la pandémie du covid- a révélé à quel point la colonialité et le racisme sont endémiques dans la société moderne. au début de la pandémie, cela s'est reflété dans de nombreux discours occidentaux sur l'afrique, notamment en france, lesquels ont dévoilé de vieux antagonismes coloniaux, des projections, des stigmatisations et du paternalisme. l'articulation de tels discours, même chez des personnes bien informées et parfois bien intentionnées, appelle à une introspection et à une réflectivité plus profondes sur les pratiques archéologiques et les modalités de l'engagement communautaire. s'appuyant sur les multiples contributions de l'archéologie pour la connaissance du passé de l'afrique et sur les pratiques de résilience observées au sénégal par les individus ordinaires face à la propaga- our contemporary moment is plagued by two major pandemics: covid- on the one hand and racism and coloniality on the other. in this reflection on the present moment, i seek to exhume the way in which certain discourses on covid- attest to the interconnections between these two pandemics in the senegalese context. first, i start the essay with the western discourses on the novel coronavirus pandemic in africa. the strong colonial and racist foundations of those discourses call for an equally robust deconstruction but also for archaeological interventions to reassert africa's pivotal role in all historical processes of human development. then, i comment on how the performative responses of the senegalese state to the covid- pandemic were framed by the french colonial legacies. second, i reflect briefly on the kinds of reflexivity that archaeologists should develop when dealing with crises such as covid- in the communities where they work. finally, in the third part, i share the resilience strategies mobilized by senegalese society against covid- . these strategies are structured by the principles of teranga aesthetic's sociability, and they yield critical insights on how to perceive and understand disasters in archaeological contexts. the announcement of the first person tested and declared positive for covid- on senegalese soil occurred on march , . ironically, that "patient ," as to follow the nomenclature of senegalese health and social action ministry, was a frenchman who had just returned from a visit to france. that appearance of coronavirus disease in senegal sparked fear that reignited colonial trauma in the popular imagination. on march , the senegalese daily l'Évidence titled its front page "france is coronizing senegal" with the subtitle that posed this question: "slave trade, economic colonization, epidemiological colonization?" (maillard ) . on march , senegalese president, macky sall, announced two types of measures, the "barrack measures" (prohibitions, restrictions, repressions) on the one hand and the "belly measures" (distribution of rice, oil, sugar, and soap) on the other (sall ) . to parody foucault ( ) , these "nourish and punish" measures suggestively recalled the "stick and carrot" policy of the french colonial government. between the appearance of "patient " and the presidential address, the government took a series of measures, including the closure of schools, universities, and places of worship. during those two weeks, however, there were very few new covid- cases and zero deaths. yet, both the martial rhetoric, "we are at war," and the public staging involved, curiously recalled french president emmanuel macron's speeches on covid- . the eurocentric and mimetic nature of these measures gave rise to sharp public criticism. the criticism intensified when public opinion decried the exclusivity granted to institut pasteur, a private french biomedical research facility in dakar, during the first fortnight of the pandemic to carry out virological tests at the expense of university laboratories and private practices owned by senegalese nationals. although institut pasteur's monopoly was later broken, thanks to public opinion's pressure and perhaps due to a growing number of cases, the debate on neocolonialism picked up more strongly a few days later. particularly at stake in these debates was the issue of the sovereignty of the senegalese postcolonial state whose management of the pandemic and practices of authority appeared to be carbon copies of those of the former european imperial power, france. on april , french medical doctors, jean paul mira, head of the intensive care unit at the cochin hospital in paris, and camille locht, research director at the inserm (institut national de la santé et de la recherche médicale ([national institute for health and medical research]), recommended on a french television channel (lci) that a bacille calmette-guérin (bcg) vaccine against the coronavirus be tested on africans. in the controversial exchange, mira told locht: "if i can be provocative, shouldn't this study be done in africa, where there are no masks, no treatment, no intensive care, a bit like it is done elsewhere on certain studies like aids, or on prostitutes: we try things because we know they are highly exposed. what do you think?" and locht replied: "you are right, by the way. we are thinking in parallel to a study in africa with the same type of approach, that does not prevent us from thinking in parallel to a study in europe and australia" (france a, b). the racial contempt for africans and questionable comparisons that proposed the use of africans as guinea pigs in medical research during that television exchange brought back painful memories of colonial medical practice and gave rise to incredible but justified anger both in the social and in traditional media. a few days before the mira-locht exchange, there had been an ecstatic reaction to the march prediction of antonio guterres, the united nations general secretary, on france television channel and radio france international (rfi), that "even if the population [in africa] is younger than in developed countries, there will be necessarily millions of deaths" on the continent due to the covid- pandemic (france a, b). likewise, a memorandum from the french ministry of foreign affairs, dated march , and titled "the pangolin effect: the storm heading to africa" also forecasted a covid- apocalypse in the continent (mantelin ) . it predicted that the national health systems of african states will be declared "automatically saturated" and that african countries will not be able to protect their populations. so far, as i write this essay four months later, these predictions have not come to fruition. these representations and imaginations of africa by "highly educated" french medical doctors, euro-american scientists, and political experts, and by a top united nations diplomat, did not take place in a vacuum. rather, they are reflective of the dominant public opinion about africa in the west, informed by colonial fantasy and fetishization. in these imaginations and representations of africa, it is striking that the continent is still conflated with images of a land peopled by lesser human beings without problem-solving capacity. in this eurocentric pathology, african bodies are only good for laboratory testing and experiments to satisfy western curiosity and anxieties about the pandemic. we should worry about these enduring colonial legacies that continue to undermine the significance of decades of archaeological efforts that conclusively assert africa's strong contributions to all processes of human development, including the emergence of complex sociopolitical formations, food production, technological innovations, urban development, and much more. to me, the relevant questions for the present moment are: what can we learn from africa's resilience and long history of coping with pandemics? how can we harness africa's deep time experiences in handling human disasters and make it usable in the governance of covid- ? these questions are contrary to the paternalist and alarmist calls that inundated the media and projected the colonial mindset of the aforementioned interlocutors about africa. the fact that similar perspectives were aired on the society of africanist archaeologists listserv by well-meaning colleagues raised even more troubling questions. how do our political subjectivities shape our positionality? is archaeological knowledge about africa sufficiently accessible to diverse and global audiences, or is it still largely produced and consumed within the inner circle of professional archaeologists who brag about their finds and only thrive for career promotion? what kind of alternative archaeological practices, engagements, and interventions can these debates on covid- pandemic inspire? what can archaeologists bring to the ongoing debates on covid- pandemic, especially when it hits the communities we work with and to whom we have a strong attachment? i contend that the role of archaeologists in such contexts would be to deal with their own political subjectivities honestly. this would require selfreflection on the discourses and practices rooted in racism and coloniality and engage with communities not as experts but rather as students, listeners, and activists ready to lend our voices to fight paternalism and unsubstantiated projections on africa. the assumption that a global pandemic must be worse in africa relative to the global north implies the thought, even by wellmeaning people, that the continent has neither past nor present problem-solving capacity and initiative. this colonial mindset relegates africans to a state of animality and denies them their humanity, a contradiction of the teachings of african archaeology in the past few decades. one would be saved from this erroneous thought by paying attention to the archives of the past, including the archaeological record, and to the resilient strategies of the moment which are rooted in the needs and demands of african communities, our "ethical clients" (blakey and rankin-hill ) . tapping into material, documentary, and memory archives can enrich our understanding of the present and the self-awareness of the communities with whom we work. this must, however, be done with a sense of care, responsibility, and caution because there is a lot of pain embedded in those archives. the catastrophic narratives in the initial western discourses as they relate to the covid- pandemic in africa had parallels in the wretched attitudes and the mimicry of some african leaders' rhetorical and performative responses to the crisis. however, on the ground in many parts of africa, and senegal in particular, the strategies leveraged by the general populations have been different from the racialized attitudes of the global north. the management of the pandemic by the larger senegalese society revealed a resilience inspired by deep-time lived experiences and memories. although local populations generally followed the directives of the health authorities, they vehemently resorted to their culture, heritage, and religion to cope with the pandemic. they manufactured their own masks, especially when the western supply chains were broken; resorted to traditional therapy en masse; and gathered together to say prayers in ways that were inspired by the ancestral practices of coping, especially when the social body was threatened by illness and other crises. they resuscitated mythical figures, particularly in areas where the national police was not available to enforce restrictions on social gatherings. different communities also observed various forms of teranga aesthetic, a senegalese social value of "good hospitality" and sociability. in its mundane expression, teranga aesthetic prescribes treating guests with open arms (riley ) . in deeper meaning, it acts as a catharsis for vivre ensemble or living together by creating a space where solidarity and mutual aid, exchanges and donations, gender bonding, communal sovereignty, political and religious alliances, sharing and circulation of information, and much more are deployed. it structures the social, cultural, and linguistic landscape with its vocabularies, gestures, and habitus and reinforces social solidarity in the face of crisis and uncertainty. teranga aesthetic offers us possibilities for reading archaeological contexts that may relate to social stress and disasters, including pandemics. such contexts may have unique signatures of artifact assemblages, settlement patterns, material circulations, and cultural interactions. over the past few decades, archaeologists of the senegambia have been struggling to explain the rapid development of numerous short-term archaeological sites spanning - years on average, particularly after (canos-donay ; gueye ; richard ; thiaw thiaw , thilmans and ravisé ) . this pattern of nucleated small-scale, short-term settlements often - m distant from one another has been identified with the growing insecurity during the atlantic slave trade. however, recent experience is suggestive that this settlement pattern may be related to human disasters, including epidemics (altschul et al. ; thiaw et al. ) . a case in point is the bubonic plague that hit dakar from april to january , killing people out of a population of , inhabitants in less than a year. the french colonial government took a series of harsh decisions including the displacement and confinement of african populations in new neighborhoods, the imposition of new architectural standards with bricks and stones, the burning of huts and quarantine camps, issuance of movement passes for africans, and the establishment of sanitary cordons, among many other measures (bigon ) . in reaction to these, many africans moved to the outskirt of dakar, where they were welcomed with open hands by other africans in accordance with the principle of teranga. according to narratives collected in the area, when the plague ultimately hit the multi-secular settlement of dialaw in the outskirt of dakar, the local african populations split and reorganized themselves into small-scale settlements - m distant from one another as a social distancing measure (thiaw et al. ) . subsequent resettlement shows a movement toward the atlantic coast, but populations maintained affective and symbolic relations with one another as well as with the earlier site of dialaw. there still stands a baobab tree in dialaw where all newborns, descendants of the mythical thialaw sene, the founder of the town, must come for life protection against all sorts of harms. sites recorded in the area show great homogeneity in the material assemblages despite ethnic diversity. likewise, the material assemblages associated with post- short-term settlements across northern senegambia display the same kind of homogeneity. although diseases and epidemics might not be the sole causes of site abandonment, settlement dynamics conform to the principles of a teranga aesthetic in that it instructs people to maintain social bonds and mutual assistance at times of disaster and uncertainty. the community-building approach of teranga and its practices of resilience constitute the building blocks of senegalese culture. it is a heritage that senegal (and indeed many other parts of africa) can share with the rest of the world in crisis management. racism and racialization have their deep roots in the european imagination, especially beginning with the eighteenth-century enlightenment (curran ; quijano ) . it was built upon the negation of the humanity of non-european others. the dehumanization of black bodies in the context of the atlantic slave trade and colonization went hand in hand with the european exploitation of africa's human and natural resources. to attain and maintain this exploited relationship with africa, europe deployed complex strategies that were based on eurocentric knowledge production. the results have been ecological and natural disasters with major political and socioeconomic consequences. these disasters are the precursors of the anthropocene curse today (e.g., pollution, global warming, plundering of resources, overconsumption, environmental degradation, etc.). the covid- pandemic has exposed the vulnerability of coloniality and challenged its hegemonic pretensions (see also chakrabarty ) , but it also calls attention to teranga aesthetic as a decolonial praxis (rivera-santana ). this is one area where we can start our search for decolonial epistemology in african archaeology and about crisis management in general. a slave who would be king: oral tradition and archaeology of the recent past in the upper senegal river basin a history of urban planning and infectious diseases: colonial senegal in the early twentieth century the new york african burial ground: unearthing the african presence in colonial new york territories, fortresses, and shifting towns: archaeological landscapes of the upper casamance (senegal), th- th centuries provincializing europe: postcolonial thought and historical difference the anatomy of blackness: the science of slavery in the age of enlightenment surveiller et punir: naissance de la prison tester des vaccins en afrique. tollé et excuses après une interview polémique antonio guterres: avec le coronavirus, on risque des millions de morts en afrique poteries et peuplements de la moyenne vallée du fleuve sénégal du xvie au xxe siècle: approches ethnoarchéologique, archéologique et ethnohistorique covid- : médias et réseaux sociaux africains mettent en cause un virus venu d'ailleurs. le monde afrique, mars le covid- vu par les experts du quai d'orsay: "l'effet pangolin", une note confidentielle sur la crise africaine qui vient. le monde diplomatique «race » et colonialité du pouvoir, mouvements reluctant landscapes. historical anthropologies of political experience in siin terànga and the art of hospitality: engendering the nation, politics, and religion in dakar, senegal aesthetics of disaster as decolonial aesthetics: making sense of the effects of hurricane maría through puerto rican contemporary art déclration d'état d'urgence dans la cadre de la lute contre la maladie à coronavirus covid archaeological investigations of long-term culture change in the lower falemme (upper senegal region), a.d. - atlantic impact on inland senegambia: french penetration and african initiatives in eighteenth-nineteenth centuries gajaaga and bundu new multi-use port of dakar: archaeology and cultural heritage studies sinthiou bara et les sites du fleuve. dakar: mémoires de l'institut fondamental d'afrique noire key: cord- -ftwpys y authors: ondoa, pascale; kebede, yenew; loembe, marguerite massinga; bhiman, jinal n; tessema, sofonias kifle; sow, abdourahmane; sall, amadou alpha; nkengasong, john title: covid- testing in africa: lessons learnt date: - - journal: lancet microbe doi: . /s - ( ) - sha: doc_id: cord_uid: ftwpys y nan www.thelancet.com/microbe vol july e laboratory testing is a pillar of the covid- outbreak response. unlike the ebola epidemic, africa has reacted early and collectively to the covid- pandemic, ramping up severe acute respiratory syndrome coronavirus (sars-cov- ) diagnostic capacity from two to countries between february and april, . the africa centres for disease control and prevention (africa cdc)-led african task force for coronavirus preparedness and response (aftcor)-a coalition between the african union (au), au member states, the who regional office for africa, and other stakeholdershas been instrumental in this impressive achievement, promoting coordination and alignment for evidencebased public health action. aftcor has led covid- testing capacity scale-up as one of the key objectives under the africa joint continental strategy for covid- outbreak. aftcor collaborated with the south african national institute for infectious diseases, the senegalese institute pasteur of dakar, and the west african health organization to train expert staff from reference laboratories for molecular detection of sars-cov- . to date, · million tests donated by the jack ma foundation (hangzou, china), and more than million tests procured by africa cdc have been distributed across the au member states. by may , , africa had reported more than confirmed cases of covid- . the africa cdc pathogen genomics intelligence institute, which is also part of the joint continental covid- strategy, provides training and resources to au member states to generate up to sars-cov- whole-genome sequences and will enable the submission of these sequences to the global initiative on sharing all influenza data platform. , with africa currently contributing only % of all sequences submitted globally, this boost will support the design of locally relevant assays, therapeutics, and vaccines. to limit further spread of covid- , au member states must expand diagnostic capacity at the subnational level. africa cdc aims to increase the number of tests from to per million population, while supporting countries to use every positive result for case isolation, contact tracing and quarantine, and supportive care. pcr testing platforms' footprint within national disease control programmes, and the private and animal laboratory sectors offer an opportunity to make use of free testing capacity and sample referral routes for covid- diagnostics. access to this capacity could potentially yield up to million molecular tests annually. on may , , the nigeria centre for disease control activated covid- testing sites, using high-throughput hiv molecular testing and tuberculosis genexpert instruments. similarly, ethiopia increased its capacity to tests per day after abbott agreed to reconfigure its closed platform to accommodate covid- testing, and after academic and animal health laboratories were engaged. repurposing laboratory facilities for covid- testing is daunting for many governments. it is complex to ensure quality-assured testing; uninterrupted supply chains; workforce supervision; and prevention of the scale back of essential diagnostic services for hiv, tuberculosis, and malaria. pressure from the public or manufacturers has prompted some countries to decentralise covid- testing, using serology assays. whereas antibodydetecting and antigen-detecting serology tests could alleviate the pressure on pcr laboratories and support large-scale testing for diagnostic, surveillance, or epidemiology studies, who does not currently recommend their use in the absence of performance data. results of independent assay evaluations by find are awaited to inform the design of serology-based strategies for public health and to fast-track emergency use authorisations. africa's dependency on external suppliers considerably limits the expansion of covid- testing. africa has to compete with higher income nations to access covid- in vitro diagnostics and, despite the pooled procurement of tests facilitated by who global access to covid- tools, the continent remains underserved. to address these challenges, africa cdc launched the partnership to accelerate covid- testing on request from au heads of states, with the following key strategic areas: ( ) organising all au member states as one large customer and coordinating the continuous supply of test kits and commodities at a negotiated price and based on accurate forecast of needs; ( ) decentralising covid- testing through strategic planning that can guarantee laboratory quality, biosafety, and the establishment of robust sample referral systems; e www.thelancet.com/microbe vol july ( ) increasing the throughput of molecular testing by supporting automated pcr methods, validated protocols for pooled testing, and optimised laboratory workflows; and ( ) increasing the number and capacity of the laboratory workforce, including skill development to design and troubleshoot manual pcr testing protocols, and to understand validation and verification processes for new technologies. these various areas underscore persisting weaknesses in laboratory systems and networks. while maintaining its robust mobilisation against covid- , it is imperative that africa develops a vision that reaches beyond an immediate reaction. the quick wins and low-hanging fruit strategies need to give way to deep-rooted approaches towards sustainable and resilient laboratory systems. first, countries need to institutionalise knowledge and resources, to routinely collect and analyse information on the capacity and functionality of national laboratory networks. this will fast-track the selection of facilities most amenable to repurposing or upgrading testing services; calculation of fastest routes for transporting sample or supplies; and reduction of geographical areas with unmet demand for health services. the labmap project of the african society of laboratory medicine and africa cdc, collecting gis information on laboratory network capacity, and software such as labequip and supply chain guru from llamasoft are examples of resources that can support the quick, evidence-based remodelling, and optimisation of laboratory networks to respond to health emergencies. second, countries must implement national laboratory quality management policies to ensure routine provision of quality-assured results at all tiers of the national laboratory network, beyond the sole accreditation of central-level laboratories. finally, africa must reduce its dependency on external expertise for diagnostics. such a reduction requires options to reconfigure closed testing platforms to be made available, and expansion of africa's domestic capacity for the production of high-quality diagnostics. africa centres for disease control and prevention. africa joint continental strategy for covid- outbreak africa centres for disease control and prevention. covid- daily update global initiative on sharing all influenza data genomic epidemiology of novel coronavirus-africa-focused subsampling find evaluation update: sars-cov- immunoassays access to covid- tools (act) accelerator forlab laboratory quantification tool and labeqip software tool we declare no competing interests. key: cord- - zd fydo authors: sinkala, m.; nkhoma, p.; zulu, m.; kafita, d.; tembo, r.; daka, v. title: the covid- pandemic in africa: predictions using the sir model indicate the cases are falling date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: zd fydo since the earliest reports of the coronavirus disease - (covid- ) in wuhan, china in december , the disease has rapidly spread worldwide, attaining pandemic levels in early march . however, the spread of covid- has differed in the african setting compared to countries on other continents. to predict the spread of covid- in africa and within each country on the continent, we applied a susceptible-infectious-recovered mathematical model. here, our results show that, overall, africa is currently (may , ) at the peak of the covid- pandemic, after which we predict the number of cases would begin to fall in june . furthermore, we predict that the ending phase of the pandemic would be in mid-august and that decreasing cases of covid- infections would be detected until around december and january . our results also reveal that of the countries with reported covid- cases, only nine, including south africa, egypt and ethiopia, are likely to report higher monthly covid- cases in june than those reported in the previous months. overall, at the end of this pandemic, we predict that approximately , (about , future cases) individuals in africa would have been infected with the covid- virus. here, our predictions are data-driven and based on the previously observed trends in the spread of the covid- pandemic. shifts in the population dynamics and/or changes in the infectiousness of the covid- virus may require new forecasts of the disease spread. the novel coronavirus disease- (covid- ) , which was first reported in china in december , has quickly spread to become a global pandemic [ ] [ ] [ ] . as of th may , over . million people have tested positive for covid- [ ] . so far, global infections of the virus have been unevenly distributed across continents and countries; europe, north america and south america are among the most impacted. despite more than , cases reported in africa, the spread of covid has been surprisingly slow, and the disease has exhibited lower-case fatality rates in comparison to other continents [ ] . it was expected that the continent, with fragile health systems, barriers to testing, and potentially vulnerable populations, would report high numbers of cases and deaths. additionally, familiarity with infectious disease outbreaks and diseases leading to an educated immune system has been postulated as possible reasons for these observations [ , ] . recently, mathematical models have been applied to investigate the spread of covid- pandemic in various countries, among others, china [ ] , italy [ ] , and england [ ] . the predictions gleaned from these models have offered a platform for decision making aimed at controlling and/or mitigating the spread of covid- pandemic and the optimisation of lockdowns and treatment efforts [ ] [ ] [ ] . however, currently, most of the covid- modelling has been in high-income countries, and very few efforts have been made to model the spread of covid- in many african countries. mathematical models that have been employed to predict the spread of the pandemic include logistic models [ , ] and susceptible-infected-recovered (sir) models [ , ] . in modelling using the sir approach, we assume that the population is a compartment of interacting individuals in which the disease spread from the infected to the susceptible, and the infected either recover and build an immunity toward the infectious agent or succumb to the infection [ , ] . here, we use the sir model to predict the spread of the covid- positive cases on the african continent as a whole and in different countries on the continent. overall, we provide valuable intuition regarding the expected trajectory of the disease in africa. . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint we obtained a dataset of the global covid- cases from covid.ourworldindata.org. we found that out, as of may , , out of african counties have reported the number of covid- positive cases. we extracted information on covid- cases in african countries to show that south africa has reported the highest number of cases ( , ) , followed by egypt ( , ) and morocco ( , ; figure ). . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint to the steady growth phase around july , and the ending phase will begin around august . overall, based on the current data and the trajectory of covid- positive cases, we predict the covid- virus will infect another , individuals to bring the total number of covid- positive cases to about , . also, we predict that the pandemic would have ended on the dates between december and january (for more details, see supplementary table ). . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint start of steady growth -jul- start of ending phase -aug- end of the epidemic ( cases . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint we compared the reported covid- positive cases in the most affected countries in africa (south africa and egypt) to those in other countries that have been affected across the globe. here, we showed that the scale of the covid- cases was lower, even for the worst affected countries in africa than that in the united states of america, japan, china, italy, united kingdom and brazil (figure a ). this assertion remains valid even when we consider the number of reported covid- cases as a per cent for each of the country's population size (figure b) . . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint we have conducted a predictive analysis of the covid- pandemic in africa. our results show that the scale of the pandemic is low across many countries in africa. many experts have debated the reason why fewer cases of covid- are being reported in africa. some have pointed toward the lack of widespread testing of covid- [ ] [ ] [ ] [ ] , whereas others point towards the african climate [ , ] . we showed that, on average, most counties in africa, including zambia, malawi, togo and chad, have reported fewer than covid- cases. conversely, most european countries have reported, on average more than covid- cases. may is unlikely to be surpassed by those in the next few months. furthermore, whereas we predicted that the covid- pandemic would disproportionately affect different countries in africa, we expect that even the worst affected among these would report fewer covid- positive cases compared to other regions of the world. altogether, based on the current covid- pandemic data and the spread of disease, our predictions show that the peak pandemic is now (may , ) for most african countries. here, we caution that our results are only as good as the data and the previous trend observed in the spread of the covid- pandemic. . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint hence, these predictions may not be indicative of future trends where certain parameters, such as the population dynamics and covid- virus infectiousness, are shifted from those currently prevailing. therefore, we encourage everyone (including individuals in african countries) to adhere to the guidelines that are aimed at reducing the spread of the covid- virus as provided by the who and other relevant organisations. we analysed a covid- dataset representing the reported virus-positive cases in the world as of may , , obtained from https://covid.ourworldindata.org/data. we extracted the covid- cases reported in african countries and plotted these individually to show the trajectory of the covid- pandemic for each country. next, we aggregated all the reported covid- cases in africa since march , . then we used the susceptible-infected-removed (sir) mathematical model [ , ] briefly, we obtained the predicted number of covid- using the sir model. these predictions include multiple data points per day. therefore, we aggregated the . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint predictions made at irregular time intervals per day to yield a single prediction for each country per day by interpolation using the cubic spline algorithm [ , ] . also, to predict the number of cases of covid- infection of each country, we aggregated the predictions for each month (see figure a ). the data that support the findings of this study are available at covid.ourworldindata.org. all the matlab source code used to process, analyse, and reproduce the major finding of this report is from the following websites: https://www.mathworks.com/matlabcentral/fileexchange/ -covid- predictions-in-africa-using-the-sir-model supplementary file : predict cases of covid- using the sir model for each day across each country in africa. why is it difficult to accurately predict the covid- epidemic? covid- ): a perspective from china estimation of the final size of the coronavirus epidemic by the logistic model coronavirus update (live): , , cases and , deaths from covid- virus pandemic -worldometer n covid- : protecting health-care workers immunity, parasites, genetics and sex hormones: contributors to mild inflammatory responses in covid- ? epidemic analysis of covid- in china by dynamical modeling a modified sir model for the covid- contagion in italy a spatial model of covid- transmission in england and wales: early spread and peak timing predictive mathematical models of the covid- pandemic: underlying principles and value of projections with covid- , modeling takes on life and death importance generalized logistic growth modeling of estimation of the final size of the second phase of the coronavirus covid epidemic by the logistic model pdf) estimation of the final size of the coronavirus epidemic by the sir model. estim final size coronavirus epidemic by sir model the mathematics of infectious diseases notes on r the basic reproduction number in a nutshell will covid- be a litmus test for post-ebola sub-saharan africa covid- : are africa's diagnostic challenges blunting response effectiveness? access to lifesaving medical resources for african countries: covid- testing and response, ethics, and politics covid- on the african continent managing covid- in low-and middle-income countries temperature and latitude analysis to predict potential spread extending the sir epidemic model fitviruscovid -file exchange -matlab central a practical guide to spline a new method of interpolation and smooth curve fitting based on local procedures the authors declare that they have no competing interests key: cord- -v c vda authors: istúriz, raul e.; torres, jaime; besso, josé title: global distribution of infectious diseases requiring intensive care date: - - journal: critical care clinics doi: . /j.ccc. . . sha: doc_id: cord_uid: v c vda this article describes infectious diseases that are of special importance to intensivists. the emphasis on epidemiology notwithstanding, it also addresses clinical, diagnostic, and treatment issues related to each infection described. the discussion avoids terrorism-related aspects of these infections, because they were very well covered in the october issue of the critical care clinics. of standardized definitions in different areas of the world, and the lack of large-scale studies based on significant cohorts, do not permit epidemiologic certainty [ ] . estimates of the epidemiology of sepsis published rely mostly on discharge diagnosis data. annual incidence is high in the united states, around per , population and mortality is also high, % to % [ , ] . morbidity and mortality depend on the characteristics of the host and the infecting microbe. in terms of incidence and mortality, the situation regarding sepsis and severe sepsis in such areas as latin america [ ] , africa [ ] , and asia [ ] may be worse than in developed countries. although the average age of patients with the diagnosis of sepsis at the time of discharge is years, the attack rate is very high in children (over cases per , population per year), and low-weight newborns have the highest incidence. both incidence and mortality decrease after age year to increase gradually up to adulthood. infection originates in the lungs, abdomen, urinary tract, and skin in most studies [ ] [ ] [ ] [ ] . ventilatorassociated pneumonia is a leading cause of death from hospital-acquired infections in the icu setting [ ] . bacteremic patients frequently evolve and develop sepsis, severe sepsis, and septic shock with correspondingly increasing mortality [ ] . in adults, both in the united states and europe, most (around %) patients admitted in icus with the diagnosis of sepsis have already been hospitalized for other causes and come from the hospital wards [ , ] . severe bacteremia and sepsis caused by the classic pathogens neisseria meningitidis and streptococcus pyogenes is rarely found now, and has been replaced by sepsis caused by commensal microbes, which infect individuals with conditions that compromise their skin and mucosal barriers or their immune systems. advances in surgical techniques including transplant medicine, and increased survival of patients with trauma, splenectomy, and neutropenias are, in part, caused by advances in the treatment of sepsis associated with these conditions. in % of the patients no responsible microorganism is isolated, in most the organism isolated from blood or the infection site was one that usually does not cause infection in healthy persons, and frequently the infection is polymicrobial [ , ] . although for many years gram-negative bacteria were found in most bacteremic patients with severe sepsis, the percentage of cases associated with blood isolation of gram-positive pathogens has increased in the last decades and now staphylococcus aureus, coagulase-negative staphylococci, and enterococci are responsible for % to % of the cases. another recent tendency is to isolate fungi ( %- %), notably species of candida [ , ] . difficult-to-treat pathogens include pseudomonas aeruginosa, acinetobacter species, klebsiella pneumoniae, enterobacter species, resistant enterococci, and methicillin-resistant s aureus. a new syndrome of severe necrotizing pneumonia produced by infection by community-acquired methicillin-resistant s aureus led to icu admissions because of the severe manifestations [ ] . the organism is now also considered a hospital pathogen [ ] . the cumulative economic impact of resistant bacteria is enormous [ ] . candidemia commonly originates from catheters in colonized patients. species of candida, some resistant to antifungals, can spread by hematogenous seeding to lungs, liver, spleen, cardiac structures, bone, skin, and eyes. mortality is substantial. the introduction of new classes of antibiotics and antifungals, such as the oxazolidinones, the glycylglycines, and the equinocandins, has improved the ability to treat resistant pathogens. malaria continues to represent a leading cause of disease burden, in terms of death and disability, in a substantial part of the world. about % of the world's population lives in countries of africa, asia, central america, oceania, and south america where the disease is endemic. globally, . to . million malaria-related deaths occur annually. children are the worst affected group, especially children aged months to years. it may cause as many as % of all deaths in children in some endemic regions of sub-saharan africa. additionally, almost every country in the world experiences imported malaria. approximately cases and deaths caused by malaria are diagnosed every year in the united states. most of them ( %) are acquired outside the country. over half the cases originate from africa. plasmodia metabolize hemoglobin and other red blood cell proteins to create a toxic pigment called ''hemozoin.'' the parasites derive their energy solely from glucose, which they metabolize times faster than the red blood cells they inhabit; hypoglycemia and lactic acidosis are common findings. anemia is caused by lysis of both infected and uninfected red blood cells, suppression of hematopoiesis, and increased clearance of red blood cells by the spleen. over time, malaria infection may induce thrombocytopenia and hepatosplenomegaly. of the four species of plasmodium known to infect man, p falciparum is the most important. this is because the parasite is not only capable of infecting red cells of all ages and causing heavy parasite loads, but it also induces the production of proteinaceous knobs that bind to endothelial cells. these cytoadherent infected red blood cells tend to clump together within the small blood vessels in many organs and tissues, accounting for much of the damage incurred by the parasite. to a large degree, the damage observed in malaria by p falciparum seems to be related to damage inflicted by the host against itself, in response to the parasite. this is thought to be related to release of tumor necrosis factor; up-regulation of tumor necrosis factor receptors (type ); and consequent expression of adhesion molecules (intercellular adhesion molecule , especially). infected cells stick to endothelium using a large malarial protein called pfemp , which binds cd or thrombospondin. because p falciparum malaria is a potentially life-threatening disease, close clinical and laboratorial monitoring of patients is necessary. moreover, reliable criteria for icu admission should be defined and risk factors identified (box ). in children, the complications of severe malaria include metabolic acidosis, often caused by hypovolemia; hypoglycemia; lactic acidosis; severe anemia; seizures; and increased intracranial pressure. in adults, renal failure and pulmonary edema are more common causes of death. in contrast, concomitant bacterial infections occur more frequently in children and are associated with mortality in them. admission to critical care units or icus may help reduce the mortality, and the frequency and severity of sequelae related to severe malaria [ , ] . the mortality in acute renal failure without dialysis is % to %. early diagnosis of established renal failure and institution of dialysis are important in preventing mortality. a rapidly rising creatinine level is the most sensitive indicator of the need for dialysis. peritoneal dialysis reduces mortality, but hemofiltration is even more effective and is associated with an improved outcome [ ] . early icu monitoring should be attempted, especially under the following conditions: lack of clinical response to antimalarial treatment within hours or any signs of neurologic disturbance (hypoglycemia excluded). prospective multicenter trials and guidelines for supportive intensive care are urgently needed [ ] . the mortality can be reduced by early recognition of the features of severe malaria; prompt administration of appropriate antimalarials; and treatment of complications, preferably in an icu setting. clinicians must have a high index of suspicion, especially with travelers who have recently visited endemic areas. a high standard of nursing care and continued observation in the acute stage of the disease are important for reducing mortality [ ] . leptospirosis is a widespread infection transmitted among animals and occasionally from animals to humans. direct exposure to urine of infected animals or urine-contaminated water and soil, through recreational or occupational activities, represents the main source of infection for humans. in general, occupations with a greater risk include dairy farmers, sewer workers, and soldiers. the most common source of exposure in some developed countries is the dog or other household pets, followed by livestock, rodents, and other wild animals [ ] . although the distribution of leptospirosis is worldwide, tropical regions bear the brunt of its impact. moreover, the environmental conditions prevalent in most tropical and subtropical regions, including abundant rainfalls, nonacidic soil, and high temperatures, along with numerous natural water courses and an abundant biodiversity, are particularly favorable for the transmission of leptospira infection. the icteric form or weil's syndrome is associated with severe hepatic malfunction; marked jaundice; hemorrhages; and cardiac, hemodynamic, pulmonary, and neurologic alterations. weil's syndrome has a high mortality rate. frequently, serum bilirubin levels are above mg per cm . although hepatic malfunction is not a major cause of death, it is associated with a higher incidence of complications and higher mortality. renal involvement in severe leptospirosis is characterized by an increase in urea and creatinine levels, elevation of the sodium excretion fraction, and nonspecific abnormal findings in the urinalysis. these include leukocyturia, hematuria, proteinuria, and crystalluria. oliguria occurs with variable frequency. acute renal failure may be aggravated by hemodynamic alterations, such as dehydration and arterial hypotension. notably, metabolic acidosis occurs more frequently in oliguric patients [ ] . the use of dialysis methods to manage acute renal failure highly improves the survival of patients with severe leptospirosis [ ] . clinical cardiac involvement is frequent as a consequence of the concurrent myocarditis. metabolic disturbances, such as hypokalemia, may aggravate this condition. the most common manifestations are ekg alterations and cardiac arrhythmia. hemorrhagic phenomena are relatively common, and may occur in the skin, mucosae, or internal organs. over the past decade, pulmonary hemorrhage has been increasingly recognized throughout the world as a grave manifestation of leptospirosis. pulmonary hemorrhages may vary from ordinary hemoptoic sputum to massive pulmonary hemorrhage. gastrointestinal hemorrhages with variable degrees of severity may also occur, manifesting as melena, hematemesis, and enterorrhagia. pulmonary involvement is characterized by the presence of hemorrhagic interstitial pneumonia, with diffuse or localized pulmonary infiltrates. respiratory failure with decreased arterial pao is attributed to impaired oxygen diffusion at the alveolar-capillary membrane level as a result of edema and blood leakage into the pulmonary interstitium. leptospirosis associates with high lethality when complicated with organ dysfunction (r %). poor prognostic factors are male gender, alcohol dependence, age o years, a high multiple organ dysfunction score, acute respiratory distress syndrome, presence of metabolic acidosis, and need for mechanical ventilation. timely intervention and intensive therapy, however, may be lifesaving [ , ] . the excess morbidity and mortality associated with influenza epidemics and the increased hospitalization costs are secondary to severe cases of the disease [ ] . primary influenza pneumonia, secondary bacterial pneumonia, and mixed viral and bacterial pneumonia are critical human features of influenza virus infection. although children are among the groups most at risk for developing influenza and its complications and are more likely to spread the infection to others, complications of seasonal influenza occur most frequently among patients older than years and those with chronic comorbidities including diseases of the cardiovascular or pulmonary system, diabetes mellitus, hemoglobinopathies, renal insufficiency, and immunosuppression. pregnancy may also pose an added risk. recent information suggests that at least some avian influenza viruses may cause life-threatening and lethal disease in individuals without predisposing factors [ ] . other than differences in neuraminidase, the viral features that might make them more pathogenic for humans are unknown. despite the fact that influenza is in general worldwide in distribution, it tends to occur in partially confined outbreaks in communities of varying sizes with the prevalence of one viral strain. primary influenza pneumonia, more commonly caused by influenza a virus, is not common, but no reliable information exists as to the exact prevalence of complicated disease [ ] . estimates vary, but studies of sequential epidemics suggest an overall complication rate of close to %. complicated respiratory influenza begins abruptly with typical features of seasonal disease but progresses rapidly and relentlessly to the adult respiratory distress syndrome. diagnosis may be made aided by the epidemiology, rapid tests, viral isolation, culture, polymerase chain reaction, and serology, but in clinical practice is seldom documented on time for effective therapeutic measures to be taken. sputum bacteriology is not helpful. chest radiography typically shows bilateral infiltrates without consolidation, but localized pneumonia with segmental unilateral infiltrates occurs. there is no response to antibiotic treatment and mortality is high. pathology shows diffuse pneumonia with hemorrhage, hyaline membranes but little inflammation. the m ion channel inhibitors amantadine and rimantadine have activity against strains of influenza a but not b or c viruses. they are not active against the current h virus strain that threatens to become the precursor of the next pandemic. the neuraminidase inhibitors, extremely active against all influenza a strains, remain active against influenza b strains and the avian viruses of all neuraminidase subtypes, but resistant strains have been described. clinical information supporting the efficacy of antiviral drugs in severe influenza pneumonia is not available, and recommendations are made based on case reports. secondary bacterial pneumonia is usually suspected when a patient experiences an exacerbation of fever and respiratory symptoms after a period of improvement from influenza like-illness. this biphasic evolution may not be present. bacterial pneumonia may coincide with viral pneumonia in mixed viral and bacterial pneumonia. it may also be clinically indistinguishable from pneumonia in the absence of viral infection and separation is difficult during an influenza outbreak. streptococcus pneumoniae, haemophilus influenzae, s aureus, mycoplasma pneumoniae, and other pathogens can be responsible. severe acute respiratory syndrome is a serious, infectious, pulmonary illness that jumped species from semidomesticated animals to humans, and spread from china and hong kong in late . most of the affected individuals were cared for in china ( ) and hong kong ( ). cases were treated in countries including vietnam, singapore, thailand, taiwan, and canada, most in intensive care settings. approximately months after the first case, a coronavirus was identified as the causative organism [ ] . severe acute respiratory syndrome's main symptoms include high fever, myalgia, cough, and dyspnea progressing to the adult respiratory distress syndrome and multiple organ dysfunction [ ] . reverse-transcriptase polymerase chain reaction serology and culture are possible but have shortcomings making routine clinical use difficult. there is no specific anticoronavirus therapy and supportive care remains the principal therapeutic alternative. rivabirin and corticosteroids have been used but their efficacy has not been established. mortality is around %. infection control practices are extremely important in halting the progression of an outbreak. generalized tetanus, a protein-toxin mediated neurologic disorder caused by clostridium tetani, an obligate anaerobic, motile gram-positive rod with terminal spores has traditionally been, and continues to represent despite effective vaccine a common cause of intensive care admissions that are long and are associated with high mortality [ ] and cost. the global incidence of tetanus has been estimated at about million cases per year. in the united states the reported cases and deaths from tetanus have decreased substantially since the s because of successful vaccination efforts [ ] . the risk of developing clinical tetanus after an acute puncture or laceration is higher in patients older than years, a reflection of waning immunity, with a significant proportion of cases occurring in women [ ] , and a low mortality rate. injection drug users are a growing population at risk [ ] . in sharp contrast, the epidemiology of generalized tetanus in developing countries, where mortality figures may be up to times higher, follows closely the problem of lack of immunization efforts. in some areas, neonatal tetanus, occurring in the offspring of unvaccinated women, causes approximately % of the cases and mortality. even worse, mothers with a past history of babies suffering neonatal tetanus accounted for more than one third of all cases in one study [ ] . the disease is seen predominantly in rural areas, in areas where soil is cultivated, and in tropical regions or in summer months in template regions. in developed countries, neonatal tetanus must still be suspected, especially in populations that avoid standard vaccination and prenatal care. tetanus is one of the few diseases that are diagnosed only on clinical grounds (the only major differential diagnosis is strychnine poisoning), but in some difficult cases electromyography may assist the clinician. treatment, details of which are beyond the scope of this article, includes supportive therapy, attention to several clinical manifestations, and passive immunization. the role of antibiotics against c tetani remains controversial. mortality, even in experienced icus, may reach % in severe cases. tetanus is an inexcusable disease [ ] , because it is preventable with a three-dose series of an inexpensive and safe toxoid. the expanded program on immunization should be reinforced whatever the area of the world and age group. although the toxin produced by clostridium botulinum is structurally and functionally similar to that of c tetani, its clinical effects are entirely different, and in a sense opposite. whereas tetanus toxin produces muscular rigidity and spasms, botulinum toxins produce muscle weakness. human botulism also has a worldwide distribution, and foodborne disease is usually present in outbreaks. the epidemiology is different from that of tetanus and, at least in the united states, parallels the presence of the toxin type present in the spores of the environment [ ] . in countries and societies around the world, such as alaska, china, egypt, and mozambique, botulism may be linked to food preparation techniques [ ] [ ] [ ] [ ] [ ] [ ] , in others to religious practices [ ] . infant botulism, acquired through the consumption of spores rather than toxin and commonly attributed to consumption of honey and other sources [ ] , may present with constipation, feeding problems, hypotonia, and a weak cry. respiratory assistance is necessary when upper airway obstruction ensues; this is commonly followed by respiratory insufficiency of long duration [ ] . relapses have been described. clinically, and shortly after toxin ingestion, adult patients remain mentally intact but develop symmetric descending weakness acutely in the absence of fever or sensory deficit outside of the eyes [ ] . nausea, dry mouth, and diarrhea may accompany the neuropathy. several autonomic problems may also be present [ ] . patients requiring mechanical ventilation may necessitate long periods of treatment in the icu setting [ ] and prolonged intubation [ ] . toxin type may predict clinical manifestations [ ] ; disease caused by toxin a tends to be more severe than disease caused by toxin b. diagnosis must be suspected clinically, and is easier during an outbreak; the edrophonium test can be helpful to exclude myasthenia gravis and the absence of tick attachment helps rule out tick paralysis. the guillain-barreś yndrome and the miller fisher variant, the eaton-lambert myasthenic syndrome, acute poliomyelitis, and magnesium intoxication are in the usual differential diagnosis. anaerobic cultures and botulism toxin assays of serum, intestinal content, and suspect foodstuffs are useful when available as are electromyographic studies, especially the painful repetitive nerve stimulation. treatment consists of supportive care, including ventilator assistance, antitoxin treatment or human botulism immune globulin (for infant botulism), and surgical cleansing of wounds. laxatives are important to eliminate active luminal toxin. patient recovery is slow and muscular weakness and neuropsychiatric sequelae may remain. application of all aspects of correct food handling protocols remains the best prophylactic measure against botulism. an effective vaccine for widespread use is sorely needed. the epidemiology of human rabies closely follows that of animal rabies and is only partially understood [ ] . the degree of development of nations may predict the local transmission patterns. in general, in areas where dogs are not immunized, canine rabies exists, and most human cases result from dog bites. in contrast, in areas with successful immunization programs, most human cases derive from exposure to wild animal species. globally, rabies virus has a broad host range. dogs account for % of animal rabies and are the major reservoir, terrestrial mammals for %, and bats for %. although canine rabies is now rare in latin america, it remains uncontrolled in areas of africa and asia. other wild animals, such as mongooses in africa and asia, skunks, gray and red foxes, raccoons (the principal reservoir in the united states), coyotes, and jackals in america, europe, africa, and asia are reservoirs. ninety-nine countries reported animal rabies in ; reported having no cases [ ] . in the united states, the domesticated animal that causes more cases in humans is the cat, followed by the dog. cattle, equines, sheep, goats, and pigs also transmit rabies variants. in a wide variety of species of insectivorous bats, rabies occurs in north america, europe, africa, asia, and australia. no history of bite is obtained in a substantial proportion of bat-associated human rabies [ ] . worldwide, as many as , individuals die yearly and million receive postexposure prophylaxis. most of the doses of vaccine used for postexposure prophylaxis carry a risk of neurologic adverse effects. rabies virus is transmitted from salivary secretion through contact (usually bite) with an infected animal [ ] . after a variable incubation period, the virus replicates locally and later reaches entry into the central nervous system through centripetal motion in peripheral nerves. it causes encephalitis, leading to an almost invariably lethal, progressive neurologic disease, characterized by agitation, upper neuron motor paralysis, impaired responses to external signals, and other abnormal neurologic signs. infection of the salivary glands and possibly other tissues during the clinical stage leads to shedding of rabies virions and potential transmission. corneal and other organ transplant has been responsible for rare human-to-human transmission [ ] . the finding of rabies virus antibodies in the cerebrospinal fluid in a patient with encephalitis is diagnostic of rabies; reverse-transcriptase polymerase chain reaction in saliva and skin biopsy sample of the neck have high sensitivity for detection of genetic rabies virus material. brain tissue is used for postmortem definitive diagnosis. once clinical rabies develops, there is no specific treatment and despite optimal intensive care, almost all patients gradually die. even if intensive ventilatory support is applied, many complications develop. the survival, without the use of rabies vaccine, of a -year-old girl in whom clinical rabies developed month after she was bitten by a bat made news in june [ ] . she was treated by induction of coma and was supported in an icu environment while receiving ketamine, midazolam, ribavirin, and amantadine. the patient was discharged after days of hospital care. after months, she exhibited choreoathetosis, dysarthria, and unsteady gait. the same treatment protocol, modified for specific complications, has been applied to at least two more rabies patients but survival has not been achieved. the pre-exposure vaccination of high-risk individuals is strongly recommended, as is postexposure prophylaxis [ ] . they are very effective and constitute specific measures. acute bacterial meningitis remains an important cause of morbidity, mortality, and neurologic sequelae in the world. given the problems with reporting, it is unlikely that the world prevalence of the disease is less than the best united states estimates of approximately cases per , population per year. in areas of brazil, the attack rate might be as high as cases per , population per year. meningitis epidemics have a strong environmental component in africa, with the most severe epidemics occurring in the sahelian region known as the meningitis belt [ ] . mortality varies, but has been estimated between % and %. in countries where h influenzae vaccine coverage in children approaches that of developed societies, three major epidemiologic changes have occurred in regards to community-acquired bacterial meningitis: ( ) there has been a dramatic decrease in meningitis caused by h influenzae, ( ) bacterial meningitis has become a disease of adults, and ( ) s pneumoniae is the leading cause of meningitis. penicillin resistance may be very high [ ] . other bacterial pathogens responsible are n meningitidis, group b streptococci, and listeria monocytogenes. nosocomial bacterial meningitis also is a major problem, with case fatality ratio of approximately %. the case fatality rate for meningitis caused by enterobacteriaceae is much higher, approaching %. factors involved in the pathogenesis of meningitis include the ability to colonize mucosal surfaces, intravascular survival, meningeal invasion, and survival in the subarachnoid space. once replication is established in meningeal tissues, alterations in the blood-brain barrier, increased intracranial pressure, alterations in cerebral blood flow, and neuronal injury develops. severe neurologic damage and mortality to the host are the consequences. patients present with headache, fever, nuchal rigidity, and signs of cerebral dysfunction. kernig's or brudzinski's signs might be present on physical examination. prompt analysis of cerebrospinal fluid including cultures (and blood cultures) typically confirms the clinical diagnosis and guides empiric therapy. gram stain and culture are positive in up to % of the cases. dexamethasone plus age and immune status-dependent bactericidal empiric or specific antimicrobial therapy with penetration into the cerebrospinal fluid must be started at appropriate doses immediately. in patients with increased intracranial pressure, several methods are available to intensivists effectively to reduce pressure. the timely use of pneumococcal, meningococcal, and h influenzae vaccines is advocated. viral hemorrhagic fevers are a heterogeneous group of severe, life-threatening viral diseases [ ] that have as a common base a degree of vascular instability and permeability and decreased vascular integrity resulting in bleeding. thrombocytopenia may be a feature that aggravates the bleeding tendency. with the exception of dengue and possibly yellow fever, travel to rural areas is a frequent epidemiologic clue to the diagnosis. the diseases are mentioned as they occur or threaten to occur in nature and some only briefly, highlighting the epidemiologic features that might make an intensive care specialist come in contact with them. dengue fever and dengue hemorrhagic fever (dhf) are increasingly important public health problems in the tropics and subtropics. dengue has been called the most important mosquito-transmitted viral disease in terms of morbidity and mortality. about to billion people live in areas where dengue is endemic. the disease is now found in more than countries throughout the americas, africa, the eastern mediterranean, southeast asia, and the western pacific. an estimated to million cases of dengue fever and , to , cases of dhf are officially notified annually; however, the true incidence is not known. case fatality rates vary from % to % in some asian countries to . % in the americas [ , ] . in a small proportion of cases, the virus causes increased vascular permeability that leads to a bleeding diathesis or disseminated intravascular coagulation characteristic of dhf. secondary infection by a different dengue virus serotype has been confirmed as an important risk factor for the development of dhf. in % to % of dhf cases, the patient develops shock, known as the ''dengue shock syndrome.'' worldwide, children younger than years comprise % of dhf subjects; however, in the americas, dhf occurs in both adults and children [ ] . patients with dhf who develop signs of dehydration, such as tachycardia, prolonged capillary refill time, cool or blotchy skin, diminished pulse amplitude, altered mental status, decreased urine output, rise in hematocrit, narrowed pulse pressure, or hypotension, require admission for intravenous fluid administration. patients with shock may be classified into one of two groups according to the pulse pressure at admission. those with pulse pressure o and % mm hg are considered of moderate severity, whereas patients with pulse pressure % mm hg are considered to have severe shock [ ] . the following types of patients are at risk, so attending staff must be particularly alert: young infants ! year old dhf grade iv or prolonged shock overweight patients patients with massive bleeding patients with changes of consciousness (encephalopathy) patients with underlying diseases (eg, thalassemia, g- -pd deficiency, congenital heart disease, and so forth) referred patients these patients need special laboratory investigations because they may have complications, such as internal bleeding; severe hypoglycemia; electrolyte imbalance (hyponatremia, hypocalcemia); metabolic acidosis; liver failure; and renal failure. to assess a patient's condition, the following laboratory tests are considered essential: hematocrit blood gases and serum electrolytes studies liver function tests platelet count, prothrombin and thrombin time, and partial thromboplastin time dengue shock syndrome, being a medical emergency, must be dealt with promptly by administering intravenous fluid to increase plasma volume. patients, particularly children, may emerge in and out of shock during a -hour period. the patient must be monitored around the clock by medical staff. blood pressure, pulse, and respiration must be recorded every minutes (or more frequently, if required) until shock is overcome. hematocrit or hemoglobin levels have to be checked every hours for the first hours, and then every hours until stable. a fluid balance sheet must be maintained. it should contain details of the type of fluid and rate and volume of its administration. the volume and frequency of urine output must also be recorded here. most children with dengue shock syndrome respond well to cautious treatment with isotonic crystalloid solutions. early intervention with colloid solutions is not generally indicated. the fluid regimen of ringer's lactate at ml/kg over a period of hours is now supported by strong prospective evidence and should be recommended for children with moderately severe shock. for those with severe shock, the situation is less straightforward, and clinicians must continue to rely on personal experience, local availability of particular products, and cost. minor advantages in initial recovery has been observed with starch, and significantly more adverse reactions were associated with dextran, so if the use of a colloid is considered necessary, starch may be the preferred option [ , ] . yellow fever follows different transmission patterns in areas of sub-saharan africa and south america. in africa the epidemiology of yellow fever has been from outbreak to epidemic in nature. some studies have estimated that epidemics of the last two decades have been large [ ] . in south america, in sharp contrast, a low-grade endemic situation exists, with few cases reported per year, usually in young men, from rural forest areas in a jungle cycle. the potential for urbanization by migration of infected individuals to cities and for large-scale epidemics caused by the presence of vectors in those cities in both areas of the world exists. yellow fever varies greatly in clinical presentation and severity, from an asymptomatic infection; to undifferentiated febrile illness; to a typical biphasic (infection plus intoxication) illness; to a severe hemorrhagic fever with high mortality. the abrupt onset of fever, headache, myalgia, and hepatitis accompanied by leucopenia and albuminuria is typical but may not be present in all patients. prostration is common in severe disease and may progress to stupor and coma. patients must be treated in an intensive care facility and isolated from mosquitoes. hypotension and shock, renal failure, and metabolic acidosis are poor prognostic signs. severe yellow fever is a very serious disease, with case fatality ratios of % to %. secondary bacterial infections worsen the prognosis of many patients but are amenable to treatment. laboratory confirmation of yellow fever, serologically or from tissue samples, is very important epidemiologically and must be pursued. supportive measures are used as needed, but no treatment protocols or affective antiviral drugs have been developed. survival is associated with lifelong immunity. an arenavirus, lassa virus causes endemic and epidemic disease in nigeria, sierra leone, guinea, liberia, and possibly other areas of west africa [ ] . the virus reaches humans endemically year round and epidemically during dry seasons from rodents by aerosolized small particles. it can also be transmitted by close interhuman contact and by nosocomial exposure. the number of cases in africa is unknown, but in endemic countries, lassa fever is a common cause of admission. estimates place in tens of thousands of cases annually in africa. a febrile disease contrasts with dengue fever in its gradual onset, followed by severe fatigue and prostration. a maculopapular rash might be present or noted. bleeding is seen in % to % of the cases. elevated transaminase levels predict adverse outcomes, and are considered an indication for ribavirin treatment. convalescence is slow and associated with bilateral deafness in a significant number of cases. progress has been made toward a vaccine [ ] . diseases seen in rural areas of south america [ ] caused by junin, machupo, sabia, and guanarito arenaviruses have so far been local public health problems. clinically, they are similar to lassa fever but thrombocytopenia and central nervous system dysfunction are more common and severe. intensive care specialists outside of these areas are unlikely to see patients, but should suspect the diagnosis of the south american hemorrhagic fevers given the right epidemiologic exposures, which with the exception of sabia virus occur after contact with wild rodents in rural agricultural areas. hantavirus pulmonary syndrome is a disease that predominates in south (andes virus) and north america (sin nombre virus), in china, and in russia (seoul virus) [ ] . laboratory rats may be infected and transmit disease to humans. hantavirus epidemics have been associated with seasons or years of increased rodent populations. the viruses, basically parasites of wild rodents, produce severe pulmonary edema (secondary to increased vascular permeability), hemoconcentration, and shock in humans. the disease commonly starts with severe myalgia and abdominal pain. severe hypoxia and shock are managed in the icu and, if the patient survives, reversion of the vascular leak permits complete recovery. diagnosis is based on the fact that igm and igg antibodies are present very early in the illness and can be measured by elisa on admission. reverse-transcriptase polymerase chain reaction in blood samples and immunohistochemical staining of tissues may detect hantavirus. treatment consists of judicious administration of fluids, cardiotonic drugs, and other supportive measures. other viral hemorrhagic fevers of interest, but unlikely to be treated in icus outside of discrete areas of the world are crimean-congo fever, ebola and marburg virus hemorrhagic fevers, kyasanur, and omsk. laboratory confirmation is very important. approximately % of patients who develop symptoms of acute hepatitis without pre-existing liver disease progress to severe acute, so-called ''fulminant liver failure'' (flf) with hepatic failure (defined as the presence of encephalopathy) within weeks of the onset of symptoms. the term ''acute liver failure'' is used to describe the onset of encephalopathy within weeks of the onset of jaundice. there are considerable geographic variations in the etiology of acute and flf. the most common causes in japan and asia are related to viral hepatitis. hepatitis e is the leading cause in india, whereas hepatitis b virus infections are the leading cause in france and japan [ ] . temporal changes in the etiology of flf are evident. drug-induced (acetaminophen toxicity) fulminant hepatic failure is currently a leading cause of liver failure in western developed countries [ ] . many viruses other than hepatitis also are recognized causes of flf in childhood, including epstein-barr virus; cytomegalovirus; paramyxovirus; varicella-zoster virus; herpesvirus types , , and ; parvovirus; and adenovirus [ , ] . hepatitis b virus is the most common cause of flf in endemic areas. recognized sources of infection include women with positive antihepatitis b antigen who give birth, and carriers of subdeterminants of hepatitis b surface antigen who donate blood. hepatitis a virus infection is a well-known cause of flf in individuals of all ages, with an estimated prevalence rate of . % to %. diagnosis of hepatitis a virus infection is made by the presence of anti-hepatitis a virus igm in the patient's serum [ ] . the risk of developing flf is generally low but there are groups with higher risks. pregnant women with acute hepatitis e virus infection have a risk of flf of around %, with a mortality of %. the risk of developing flf in hepatitis a virus infection increases with age and with pre-existing liver disease. fulminant hepatitis b is seen in adult infection but it is relatively rare [ , ] . the pathogenesis of flf usually initiates with the exposure of a susceptible person to an agent capable of inducing severe hepatic injury, even though the exact etiology remains undisclosed in most cases of flf. similarly, the pathophysiologic mechanism involved in the occurrence of hepatic encephalopathy in children with flf has not been fully defined [ ] . viral agents may cause damage to hepatocytes either by direct cytotoxic effect or as a result of hyperimmune response. apparently, the interaction between the infectious agent and the host determines the incidence of flf. fulminant hepatic failure is an uncommon but devastating illness in which the liver fails in a short period of time (! weeks in the initial definition [ ] ) in the absence of chronic liver disease. it must be distinguished from the much more common acute decompensation that develops abruptly and without warning in patients with chronic liver disease. in fulminant hepatic failure, mortality rate is higher and significant morbidity results from cerebral edema and intracranial hypertension, which are rare in patients with chronic disease. fulminant hepatic failure is defined by the development of coagulopathy and encephalopathy and is associated with rapid progression of multiple organ system failure. acetaminophen has surpassed viral hepatitis as the leading cause of fulminant hepatic failure in the united states and accounts for % and perhaps as much as % of the cases [ , ] . mortality rate is high but recovery is possible in % to % of patients with supportive care. the decision to proceed to liver transplantation is complicated. although the course may be protracted, recovery is usually complete. liver transplantation remains the sole lifesaving option for many patients. patients who have fulminant hepatitis have a mortality of up to % and should be transferred immediately to a facility that offers liver transplantation [ ] . nevertheless, with an improved understanding and recognition of the syndrome, more aggressive medical therapy, intensive monitoring, and the advent of orthotopic liver transplantation as a treatment option, survival rates have improved considerably [ ] . flf constitutes a medical emergency with a tendency to evolve rapidly and the prompt response of experienced clinicians is imperative for a successful outcome to be achieved. epidemiology of sepsis: an update epidemiology of severe sepsis in the united states: analysis of incidence, outcome, and associated costs of care the epidemiology of sepsis in the united states from through a literature review of the epidemiology of sepsis in latin america incidence of clinically significant bacteriemia in children who present to hospital in kenya: community-based observational study positive blood cultures in pediatric emergency department patients: 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in cairo botulism from peyote isolation of clostridium botulinum from honey a large outbreak of botulism: the hazardous baked potato type f botulism due to neurotoxigenic clostridium baratii from an unknown source in an adult cardiovascular-reflex testing and single-fiber electromyography in botulism: a longitudinal study slow recovery from severe foodborne botulism clinical features of types a and b foodborne botulism epidemiology of human rabies in the united states world health organization. world survey of rabies for the year . geneva: world health organization canine rabies ecology in southern africa transmission of rabies virus from an organ donor to four transplant recipients survival after treatment of rabies with induction of coma management of rabies in humans evaluation of the meningitis epidemics risk model in africa high carriage rate of high-level penicillinresistant streptococcus pneumoniae in a taiwan kindergarten associated with a case of pneumococcal meningitis a 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fulminant hepatitis medical progress: acute liver failure fulminant hepatic failure key: cord- - h hhm authors: mazingi, dennis; ihediwa, george; ford, kathryn; ademuyiwa, adesoji o; lakhoo, kokila title: mitigating the impact of covid- on children's surgery in africa date: - - journal: bmj glob health doi: . /bmjgh- - sha: doc_id: cord_uid: h hhm nan an outbreak of the disease known as covid- , which originated in wuhan in the hubei province of china, has rapidly spread to all continents of the globe. first detected via local hospital surveillance systems as a 'pneumonia of unknown aetiology' in late december , the disease has since been declared a public health emergency of international concern by the who and reached pandemic status. it is uncertain what the eventual toll of the pandemic will be in africa; however, there has been a suspicion that the looming pandemic may hit harder than it has the rest of the world. africa has baseline weaknesses in healthcare resource allocation, and her fragile healthcare systems are particularly vulnerable to being overwhelmed by this illness. available statistics, to date, however, seem to show that the pandemic has been slow to begin. as of may, cases and deaths have been reported across the whole african continent, constituting % of all cases in the globe. african nations have had an opportunity to prepare for the coming onslaught, learn from the experience in other countries and choose interventions that are tailor-made for the unique socioeconomic context. while old age has consistently been associated with a higher risk of poor outcome, children appear to have escaped the worst of the disease. in a recent series from the chinese center for disease control and prevention, less than % of the cases were children below years of age. children of all ages may be affected, but they typically manifest mild or asymptomatic disease. this has important implications for the african pandemic: sub-saharan africa is the youngest continent in the globe with % of its population below the age of years. the demography of africa appears to portend a favourable course through the pandemic; however, it is unknown how the high prevalence of hiv infection, tuberculosis, malnutrition and the scourge of poverty will affect the human impact of the disease. the covid- pandemic has placed unprecedented strain on health services around the world, and paediatric surgical services are no exception. responses from surgical societies around the world thus far have focused on maintaining provision of emergency and urgent elective services while protecting healthcare workers (hcws). there is a risk of healthcare resources being diverted away from surgical care, potentially impeding progress towards global surgery goals for . paediatric surgical care may only be tangentially affected by this pandemic; however, there are unique considerations that deserve special attention. this article explores the wider implications for children's surgery in africa, drawing lessons from the past and giving recommendations for the current pandemic and future (table ). non-essential surgical and non-surgical activities should be curtailed to provide surge capacity for the expected pandemic-related influx. this is consistent with guidelines from many surgical societies worldwide ; however, heavy-handed shutdown policies have been discouraged in the african context because they risk exacerbating the already formidable surgical disease burden with disastrous consequences. elective surgical activity has been postponed in zimbabwe, south africa, kenya and malawi, among many other countries. negative effects should be anticipated if the past is anything to go by. during the severe acute respiratory syndrome-related coronavirus (sars-cov)- outbreak in toronto, stringent restrictions on non-essential surgical services were thought to have aggravated precipitous declines in surgical volume, with only small increases in surge capacity for the outbreak. postpandemic waiting lists for paediatric cancer are also expected to be sizeable. a recent modelling study from the 'covidsurg collaborative' paints a grim picture. twenty-eight million surgical operations are estimated to be cancelled and low-income and middle-income countries (lmics) such as africa will be hardest hit. the expectation that surgical volumes will bounce back rapidly is implausible, particularly in countries where there was already baseline fragility, and it may take longer than the weeks forecast to make up the backlog. current surgical rationing policies are based on a classification of the urgency of the patient's intervention, such as the national confidential enquiry into patient outcome and death system. effects on surgical practice paediatric surgical services in africa are characterised by significant delays in health-seeking and within the referral chain. the mobility restrictions imposed on patients by shelter-in-place measures, as well as reduced income during the pandemic, will presumably cause further delays in presentation that may adversely affect outcomes. the change to non-operative treatment in eligible patients for certain conditions, for example, appendicitis that is being contemplated, may find less success in africa, where a higher proportion of patients have complicated disease not amenable to non-operative treatment. it also has the potential to prolong hospital stay, which increases the chances of nosocomial transmission of the virus. preoperative screening and testing perinatal transmission of sars-cov- has not yet been demonstrated in recent small case series and a systematic review. [ ] [ ] [ ] this is consistent with findings during the sars-cov- and middle east respiratory syndrome (mers-cov) epidemics and should reassure surgeons working with neonates. however, neonates can still acquire infection from an infected mother's respiratory secretions. also, xu et al reported on eight infants who tested positive on rectal swabs even after having tested negative by nasopharyngeal swabs. this was thought to potentially represent faeco-oral viral transmission and has implications for surgeons of the gastrointestinal tract. sars-cov- has also been isolated in peritoneal fluid. larger studies are needed to determine the significance of these findings. airborne and contact precautions are indicated in all hcws working with children of all ages. experience from previous pandemics has demonstrated that hcws are the lynchpin of resilient surgical systems during an outbreak. during the ebola outbreak, the unfortunate death of % of the surgeons in one institution has led to a % reduction in surgical volumes, while trepidation on the part of hcws and lack of personal protective equipment have led to a reluctance to work during the sars-cov- , mers-cov and ebola outbreaks. this is particularly damaging in africa, where hcw morale is already low. hcw should be first in the minds of policy-makers because the axiom that there is no health without a workforce is as true during a pandemic as it is at any other time. children have been called 'the link in the transmission chain' because of their importance in facilitating and amplifying viral transmission. paediatric care in africa is typically characterised by significant involvement by guardians and other family members who support the child during hospital admission, assist the overburdened healthcare workforce and act as care advocates. they frequently live on the hospital grounds because of long distances from home and prohibitive transportation costs. a study from malawi showed that overcrowding in the hospital was a major issue due to the large population of guardians in the hospital. this is at odds with social distancing policies and has the potential to accelerate nosocomial transmission. guardians should be limited to the minimum practical number per patient (table ) . guardian policy should also take into account 'parental presence at induction of anaesthesia', a common practice that facilitates administration of anaesthesia but potentially places the parent at risk during an aerosolgenerating procedure. hospital visitors have been implicated as vectors in pathogen transmission during the sars-cov- outbreak of - , and hospital visitor policies were changed accordingly. the evidence linking restrictive visiting policies with prevention of nosocomial transmission during outbreaks is scant; however, it is a rational approach until better evidence comes to light. expert guidelines from the society for healthcare epidemiology of america give recommendations for guardian and visitor policy based on a systematic review of the literature and are incorporated in our recommendations (table ) . experiences from this and past epidemics show that in health emergencies children, the most vulnerable members of society suffer disproportionately. the 'agenda for action' recently announced by unicef is a timely intervention aimed at preventing the pandemic from becoming a child's-rights crisis. the incidence of family violence and accidental household trauma, for example, burn injuries, are anticipated to rise during the pandemic and is associated with shelter-in-place measures. paediatric surgeons have a unique role in management of the traumatic injuries, protection of children from a dangerous household and in tertiary prevention (minimising the effects of child physical abuse and preventing recurrence). churches, schools and shelters, which would otherwise be safe havens, may be closed and healthcare facilities may be the option of last report. bringing a child into a potentially hazardous hospital environment with the risks of nosocomial infection brings up difficult choices. impact on training surgical training programmes are an additional casualty of the social distancing measures and surgical rationing. the reduction in elective surgical cases and clinics, as well as contact between teachers and trainees, has brought challenges in the delivery of surgical education worldwide. [ ] [ ] [ ] academic training programmes have had to adapt rapidly to maintain the integrity of training programmes, ensure trainee welfare and comply with local laws. postgraduate qualifying examinations of the west and south african colleges of surgeons scheduled for april and july, respectively, have been postponed; however, the examination of the college of surgeons of east, central and southern africa (cosecsa) scheduled for november have not yet been impacted. a recent global review of paediatric surgical workforce density showed that a minimum of four paediatric surgeons per million children under years of age would be required to achieve a survival of > % for a group of four bellwether paediatric surgical conditions. this translates to a deficit of additional paediatric surgeons in lmics required to attend to the almost billion children living there. the paediatric surgical workforce deficit in africa is particularly large, and disruption of training programmes is likely to significantly affect achievement of workforce goals. the pandemic has also presented opportunities for surgical education. virtual didactics are poised to increase the size of the classroom and to allow easier collaborative learning between teams in different hospitals or countries. this is occurring all over the continent and the practice may persist long after the pandemic is over. the inexorable spread of covid- around the world continues unabated and threatens to affect every clinical specialty. children have unique needs and suffer disproportionately during health emergencies and therefore require enhanced protection. paediatric surgeons in africa have an important role during times such as these and should use tailor-made, context-appropriate strategies to minimise the impact on our patients and hcws. protection for hcws should be the foremost in the minds of policy-makers as they are a precious and irreplaceable resource. covid- pandemic in west africa early transmission 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events impacted on a single surgical institution in sierra leone fear of severe acute respiratory syndrome (sars) among health care workers an assessment of the level of concern among hospital-based health-care workers regarding mers outbreaks in saudi arabia the health impact of the - ebola outbreak job satisfaction and morale in the ugandan health workforce a universal truth: no health without a workforce. geneva: global health workforce alliance and world health organization covid- in children: the link in the transmission chain patient guardians as an instrument for person centered care parental involvement in the management of hospitalised children in kenya: policy and practice utilization of family members to provide hospital care in malawi: the role of hospital guardians sars in a hospital visitor and her intensivist sars transmission and hospital containment how severe acute respiratory syndrome (sars) affected the department of anaesthesia at singapore general hospital isolation precautions for visitors impacts of covid- on vulnerable children in temporary accommodation in the uk feeding lowincome children during the covid- pandemic should children with suspected nonaccidental injury be admitted to a surgical service an increasing risk of family violence during the covid- pandemic: strengthening community collaborations to save lives burn center function during the covid- pandemic: an international multi-center report of strategy and experience child abuse and the pediatric surgeon: a position statement from the trauma committee, the board of governors and the membership of the american pediatric surgical association public health models for preventing child maltreatment: applications from the field of injury prevention practical techniques to adapt surgical resident education to the covid- era together: a training program's response to the covid- pandemic the impact of covid- on medical student surgical education: implementing extreme pandemic response measures in a widely distributed surgical clerkship experience notice of postponement of west african college of surgeons (wacs) announcement to cmsa candidates defining the critical pediatric surgical workforce density for improving surgical outcomes: a global study the pediatric surgery workforce in low-and middle-income countries: problems and priorities key: cord- -hwds rja authors: sun, h.; dickens, b. l.; cook, a. r.; clapham, h. e. title: importations of covid- into african countries and risk of onward spread date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: hwds rja background the emergence of a novel coronavirus (sars-cov- ) in wuhan, china, at the end of has caused widespread transmission around the world. as new epicentres in europe and america have arisen, of particular concern is the increased number of imported coronavirus disease (covid- ) cases in africa, where the impact of the pandemic could be more severe. we aim to estimate the number of covid- cases imported from major epicentres in europe and america to each african country, as well as the probability of reaching , infections in total by the end of march, april, and may following viral introduction. methods we used the reported number of cases imported from the major epicentres in europe and america to singapore, as well as flight data, to estimate the number of imported cases in each african country. under the assumption that singapore has detected all the imported cases, the estimates for africa were thus conservative. we then propagated the uncertainty in the imported case count estimates to simulate the onward spread of the virus, until , infections are reached or the end of may, whichever is earlier. specifically, , simulations were run separately under two scenarios, where the reproduction number under the stay-at-home order was assumed to be . and . respectively. findings we estimated morocco, algeria, south africa, egypt, tunisia, and nigeria as having the largest number of covid- cases imported from the major epicentres. based on our , simulation runs, morocco and algeria's estimated probability of reaching , infections by end of march was close to % under both scenarios. in particular, we identified countries with less than cases in total reported by end of april whilst the estimated probability of reaching , infections by then was higher than % even under the more optimistic scenario. conclusion our study highlights particular countries that are likely to reach (or have reached) , infections far earlier than the reported data suggest, calling for the prioritization of resources to mitigate the further spread of the epidemic. abstract background the emergence of a novel coronavirus in wuhan, china, at the end of has caused widespread transmission around the world. as new epicentres in europe and america have arisen, of particular concern is the increased number of imported coronavirus disease (covid- ) cases in africa, where the impact of the pandemic could be more severe. we aim to estimate the number of covid- cases imported from major epicentres in europe and america to each african country, as well as the probability of reaching , infections in total by the end of march, april, and may following viral introduction. we used the reported number of cases imported from the major epicentres in europe and america to singapore, as well as flight data, to estimate the number of imported cases in each african country. under the assumption that singapore has detected all the imported cases, the estimates for africa were thus conservative. we then propagated the uncertainty in the imported case count estimates to simulate the onward spread of the virus, until , infections are reached or the end of may, whichever is earlier. specifically, , simulations were run separately under two scenarios, where the reproduction number under the stay-at-home order was assumed to be . and . respectively. findings we estimated morocco, algeria, south africa, egypt, tunisia, and nigeria as having the largest number of covid- cases imported from the major epicentres. based on our , simulation runs, morocco and algeria's estimated probability of reaching , infections by end of march was close to % under both scenarios. in particular, we identified countries with less than cases in total reported by end of april whilst the estimated probability of reaching , infections by then was higher than % even under the more optimistic scenario. conclusion our study highlights particular countries that are likely to reach (or have reached) , infections far earlier than the reported data suggest, calling for the prioritization of resources to mitigate the further spread of the epidemic. background in late december , a novel coronavirus (sars-cov- ) was identified among patients presenting with viral pneumonia in wuhan city, china . since then the number of coronavirus disease cases and deaths increased rapidly , , and the city was locked down by the chinese government on rd january . by late february, there had only been limited importations from and to places outside china . however, new epicentres in europe and america emerged shortly thereafter, causing a second wave of importations that further accelerated the spread of the pandemic . most countries have since then imposed travel restrictions to prevent further importation of covid- cases . by th april , over three million cases and , deaths had been confirmed worldwide . a particular area of focus has been on countries in africa, with worries about missed imported cases and what the impact will be of widespread transmission given the other heavy health burdens in these countries. the first confirmed case in africa was reported in egypt on th february , and two weeks later, the virus was found in sub-saharan africa with a reported case in nigeria . by the end of april, over , cases had been reported in the whole of africa, with substantial variation in the reported cumulative incidence across different countries . this inter-country heterogeneity can be due to a wide range of factors, such as the number of imported infections, the capacity to conduct tests for covid- , surveillance efforts, as well as travel and movement restrictions which vary widely from country to country depending on the local context . the reported data alone thus do not provide a clear depiction of the outbreak situation especially in countries with very limited surveillance capacities, and additional studies are needed to narrow the knowledge gap between the reported data and the real disease burdens. previous work has estimated the risk of importation from china at the early stage of the pandemic , assessed each african country's capacity to respond to outbreaks , systematically collated information on the importation events reported by the sub-saharan countries , and projected the spread of the epidemic seeded by the early cases represented in the world health organization situation reports . it is still unclear how many infections may have been introduced to africa from the new epicentres in europe and america, although the reported case data do suggest that the size of this second wave of importations has been much larger than the first wave of importations from china . in this study, we aim to estimate the number of covid- cases imported from the major epicentres in europe and america, and the magnitude of onward spread in each african country. this method is insensitive to the different testing and reporting systems that are in place in different countries. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . methods data we collated data on the daily number of imported cases in singapore reported by st march from the following epicentres: austria, belgium, france, germany, italy, netherlands, portugal, spain, switzerland, turkey, united kingdom, and united states, which accounted for over % of singapore's reported number of imported cases from countries outside of asia . these data will be used later to estimate the number of imported cases in africa. in addition, we obtained the total number of cases (imported and autochthonous combined) reported by each african country by end of march and april from the world health organization's situation reports . for each country, we collated the date on which each of the following policies came into force: ( ) banning non-citizens and non-residents from entry (the start date could vary depending on the epicentre country from which a visitor arrived); ( ) mandatory (self-) quarantine for travellers arriving from each of the epicentre countries mentioned earlier; ( ) stay-at-home order for all non-essential workers (hereinafter referred to as "stay-at-home order"). we reviewed the following sources: ( ) country-level internal and international restrictions collated by the international sos , ( ) oxford covid- government response tracker , ( ) international travel restrictions collated by the international air transport association , as well as ( ) wikipedia, where a separate page was available for each country containing information regarding the government response. for each wikipedia page, we manually reviewed the online reports listed in the references to exclude data with unconfirmed or unreliable sources. if stay-at-home order came into force in different states of the same country at different times, only the earliest date was recorded. we obtained the total number of air ticket bookings for each origin-destination route allowing for up to two connections during march from the official airline guide. this will be used later to estimate the ratio of air passenger volumes between pairs of origin and destination countries, which we assumed to be relatively stable over time. estimating the number of imported cases . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . for each african country , we denote the daily number of air passengers that arrived from an epicentre country by → ( ) ( = , + , … , → ), where refers to the start date of the covid- epidemic in the epicentre country , and → refers to the last day that non-citizens and non-residents travelling from country were allowed to enter country . each day the probability that an air passenger travelling from country to country was an imported case is denoted by ( ) , which we assume to be dependent on both the origin country and time , but independent from the destination country . hence, the total number of covid- cases imported from an epicentre country to an african country by the time the travel ban came into force (denoted by → below) can be approximated using a poisson distribution (refer to the supporting information for the derivation details): . we used the imported covid- case data reported by singapore as well as flight data to provide a conservative estimate for → , under the assumption that singapore, being one of the countries with the highest surveillance capacity , has detected all the imported cases. owing to the delay from infection to hospital admission, we considered all cases imported from country to singapore that were reported by date ( → + ) (hereinafter denoted as , ) based on linton et al.'s estimated mean incubation period and time from illness onset to hospital admission . we assumed that the ratio between the daily number of air travellers from epicentre to country and to here, , refers to the proportionality constant to be estimated using the reported value of , and flight data, and was assigned a uniform prior with support ( , ). we performed markov chain monte carlo to sample from the posterior distribution of , using the jags software , with , iterations burn-in and , iterations thinned for a posterior sample of size , . the posterior sample for all the model parameters was then used to estimate the uncertainty distribution of the total number of covid- cases imported from the major epicentres to each country. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . in march , a spike in the number of cases imported from united kingdom and united states was observed in singapore, which was partly due to the increase in the number of returning singaporean students studying overseas . this change in flight patterns, however, may not be applicable to all african countries. therefore, to be even more conservative, we also derived the imported case count estimates excluding united kingdom and united states from the epicentre countries previously considered. the resulting estimates were subsequently used in the simulations of the onward spread of sars-cov- to get our estimates of case numbers over time. stay-at-home order, was assumed to follow a negative binomial distribution with mean and dispersion parameter . . once the stay-at-home order came into force, we created two scenarios for the percentage reduction of the reproduction number: ( ) % reduction, and ( ) % reduction. to be conservative, we assumed that the stay-at-home order, once implemented, can be sustained up to the end date of our simulations. we ran the simulation algorithm following churcher et al. , and derived the estimated probability of reaching , infections by the end of march, april, and may respectively for each country. (refer to the supporting information for the implementation details) . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . we estimated morocco, algeria, south africa, egypt, tunisia, and nigeria as having the largest number of covid- cases imported from the new epicentres in europe and america (table and figure ). all of these countries had their lower bound estimate of the imported case count exceeding (table ) . by contrast, nine countries (e.g. lesotho, eswatini, and south sudan) were found to have a very low risk of importation, with the upper bound estimate of the imported case count below (table ). in a more conservative scenario where united kingdom and united states were excluded from the list of epicentre countries, the estimated number of imported cases did not change drastically for most countries, albeit with some exceptions such as kenya, whose estimate decreased from ( % ci: - ) to ( % ci: - ) ( table ) . based on our , simulations of the onward sars-cov- spread, both morocco and algeria's estimated probability of reaching , infections by end of march was close to % under both scenarios that we considered (figures a, d) , whilst the reported total number of cases in each country by end of march was ~ ( figure g ). under the assumption that stay-at-home order reduces the reproduction number to . , we found four african countries where the estimated probability of reaching , infections by end of march was higher than % ( figure a ). this number quickly rose to countries reaching this number of infections by the end of april, and countries by end may (figures b, c) . for the alternative scenario where the reproduction number is reduced to . by stay-at-home order, the numbers of african countries with a higher-than- % estimated probability of reaching , infections by end of march, april, and may were , , and respectively (figures d- f) . notably, four countries (angola, gambia, mozambique, and sao tome and principe) were found to have reported less than cases by end of april whilst the estimated probability of reaching , infections by then was higher than % even under the more optimistic scenario ( figures e, h ), suggesting that a very substantial number of cases may have been undetected. the percentiles of the uncertainty distribution for the date by which , infections are reached in each country under the two scenarios were shown in table . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . in the first wave of importations of infections from wuhan, china, to other places outside china we estimated that most places at risk were in asia, europe and usa . though there were links between china and african countries, these were fewer than those between china and the rest of asia, europe and usa . the shut down in china severely curtailed continuing importations out of china and so these importations rapidly stopped. lower initial importations into africa compared to asia and europe certainly tallies with what has been seen. there have been very few reported cases in africa in the first wave of importations, and no reports of onward transmission. there was much discussion at the time whether the lack of reported imported cases in africa was because imported cases were not being picked up. this may be some of the story, but our analysis would suggest that this was not the whole story, and it was more that the early risk of importation into africa was lower than other places . however the results we present in this paper estimate that this risk has dramatically increased with the spread of the virus in europe and the usa. this also tallies with what we have seen, as countries in africa started to report their first imported cases from europe and the usa . as of april th , south africa had reported the highest number of cases at , and we estimated south africa to have had one of the highest numbers of imported cases from the new epi-centres, although it was also rated highest at risk in africa of importations from china in previous analysis . senegal is one of the countries for whom the risk has notably increased from the risk of importation from china as estimated in previous analyses , . we only considered importations from the major epicentres in europe and america, and so the number of importations from all countries will be even higher. our study provides countries with information on the estimated timing of reaching , infections, which can be used for planning. under the assumption that stay-at-home order reduces the reproduction number from . to . , our estimates suggest that a number of african countries will reach (or have reached) , infections even earlier than the predictions of pearson et al. this could be due to a number of imported infections being undetected and hence not reflected in the situation reports, as well as the delay from infection to reporting, both of which were accounted for in our study. notably, we estimated two countries in north africa, namely algeria and morocco, as having the highest probabilities of reaching , infections by the end of march, which may . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint have occurred even prior to the lockdown. countries in sub-saharan africa having the earliest estimated timings of reaching , infections include angola, côte d'ivoire, senegal, and south africa. in countries where stringent social distancing measures have yet to be implemented at the time of writing (e.g. tanzania), the unfolding of the epidemic was estimated to be substantially faster than previous estimates suggest . on the other hand, we projected that countries such as seychelles will reach , infections later than pearson et al.'s forecasts owing to the stay-at- home order. the epidemic was found to be further slowed down in many countries when we assumed the reproduction number to be reduced by % due to stay-at-home order. many countries in africa have considerable experience in dealing with other infectious disease outbreaks, most notably ebola, and will be able to call upon that experience for covid- . countries hit in this third wave of transmission, including those in africa have some advantage as there have been a variety of responses from around the world from which to assess what to do or not to do. however there will need to be consideration of how effective measures can be adapted to different settings . issues such as high hiv prevalence in some countries, and a younger demographic may both affect the cases and deaths observed in different ways. this relationship however is yet to be determined and there will need to be rapid research in countries in africa to determine what the risk of disease is in different populations and how best to respond in light of many other competing health priorities. many countries in africa are on high alert for incoming cases from europe and usa, taking measures such as quarantine of arrivals or shutting down travel from affected countries. this is a sensible response given the vast amount of transmission on-going in these places. however as travel is either maintained or reopened between countries closer by, risk of importations from other countries should continue to be considered. close attention should therefore be paid to where will be the next epicentre, perhaps within africa, and how this could translate into imported cases for each country, particularly for those countries that we estimate to have experienced lower numbers of imported cases previously and therefore lower onward transmission. not accounted for in our study currently is the impact of less stringent interventions on the local sars-cov- spread, such as the effect of prohibiting large public gatherings, closure of social venues and schools, and restrictions on inter-district travels. it is still unclear as to whether and to what extent these interventions were effective in their local context, and hence in our simulations we only considered stay-at-home order for all non-essential workers as an effective intervention to reduce local transmission. future modelling work considering the impact of different interventions in different places will be vital for determining how each country can continue to respond. in addition, we have made simplifying assumptions about the change in travel patterns in response to the pandemic in each african country relative to that in singapore, due to the unavailability of . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . respectively. reproduction number in the absence of stay-at-home order in each country was assumed to be . reported total number of cases (g-h) were extracted from the world health organization's situation reports. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . table : estimated number of covid- cases (with % credible interval) imported from the new epicentres in europe and america (second column), and after excluding united kingdom and united states from the list of epicentre countries (third column) to create a more conservative estimate (refer to methods for more details). . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . table : summary statistics for the estimated date by which , infections are reached in each african country. reproduction numbers used for the simulation were . before, and . or . after stay-at-home order came into force in each country. simulations were performed until st may, or , infections are reached, whichever is earlier, based on , model runs. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . genomic characterisation and epidemiology of novel coronavirus: implications for virus origins and receptor binding of novel coronavirus-infected pneumonia clinical features of patients infected with novel coronavirus in wuhan . international sos. travel restrictions, flight operations and screening covid- : s'porean students abroad heading home after government advisory but a few plan to stay put a new framework and software to estimate time-varying reproduction numbers during epidemics serial interval of novel coronavirus (covid- ) infections measuring the path toward malaria elimination estimating number of global importations of covid- from wuhan, risk of transmission outside mainland china and covid- introduction index between countries outside mainland china. medrxiv limiting the spread of covid- in africa: one size mitigation strategies do not fit all countries estimated imported case count from epicentres estimated imported case count from epicentres key: cord- -kc pev authors: cohen, adam l.; sahr, philip k.; treurnicht, florette; walaza, sibongile; groome, michelle j.; kahn, kathleen; dawood, halima; variava, ebrahim; tempia, stefano; pretorius, marthi; moyes, jocelyn; olorunju, steven a. s.; malope-kgokong, babatyi; kuonza, lazarus; wolter, nicole; von gottberg, anne; madhi, shabir a.; venter, marietjie; cohen, cheryl title: parainfluenza virus infection among human immunodeficiency virus (hiv)-infected and hiv-uninfected children and adults hospitalized for severe acute respiratory illness in south africa, – date: - - journal: open forum infect dis doi: . /ofid/ofv sha: doc_id: cord_uid: kc pev background. parainfluenza virus (piv) is a common cause of acute respiratory tract infections, but little is known about piv infection in children and adults in africa, especially in settings where human immunodeficiency virus (hiv) prevalence is high. methods. we conducted active, prospective sentinel surveillance for children and adults hospitalized with severe acute respiratory illness (sari) from to in south africa. we enrolled controls (outpatients without febrile or respiratory illness) to calculate the attributable fraction for piv infection. respiratory specimens were tested by multiplex real-time reverse-transcription polymerase chain reaction assay for parainfluenza types , , and . results. of sari cases enrolled, ( . %) tested positive for any piv type: ( . %) were type ; ( . %) were type ; ( . %) were type ; and ( . %) had coinfection with piv types. after adjusting for age, hiv serostatus, and respiratory viral coinfection, the attributable fraction for piv was . % ( % ci [confidence interval], . – . ); piv contributed to sari among hiv-infected and -uninfected children < years of age and among individuals infected with piv types and . the observed overall incidence of piv-associated sari was ( % ci, – ) cases per population and was highest in children < year of age ( [ % ci, – ] cases per population). compared with persons without hiv, persons with hiv had an increased relative risk of piv hospitalization ( . ; % ci, . – . ). conclusions. parainfluenza virus causes substantial severe respiratory disease in south africa among children < years of age, especially those that are infected with hiv. parainfluenza virus (piv) is a paramyxovirus commonly detected in patients with respiratory illness, such as upper respiratory tract infections, laryngotracheobronchitis (croup), or pneumonia. there are distinct types: , , , and . parainfluenza virus infection is most common in childhood, and serologic surveys have shown that nearly all children have antibodies to piv by years of age [ , ] . parainfluenza virus is associated with %- % of hospitalized respiratory tract infections in children and adults [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . parainfluenza virus infections occur throughout the year, but there are recognized patterns of seasonality associated with different types [ ] . the clinical significance of identifying piv infection among patients with respiratory illness does not necessarily imply causation because the virus may be found in individuals without respiratory symptoms [ ] . in south africa, human immunodeficiency virus (hiv) is prevalent, which impacts respiratory disease burden [ ] . in , the national hiv prevalence estimate among children < years was . % and decreased to . % by ; the hiv prevalence among adults ≥ years of age was approximately . % during the same time [ ] . a study from soweto prior to availability of antiretroviral therapy (art) found that hiv-infected children with piv-associated lower respiratory tract infection had greater morbidity and mortality than hivuninfected children [ ] . a more recent study from cape town found that piv was associated with % of viral-associated pediatric intensive care unit admissions [ ] . previous studies from our group have detected piv in . % of adults and . % of children hospitalized with severe acute respiratory illness [ ] [ ] [ ] . little is known about the epidemiology of piv infection, including its association with illness and its clinical manifestation among both hiv-infected and -uninfected children and adults in south africa, especially in the era of art management. in this study, we aimed to describe the epidemiological and clinical characteristics of hiv-infected and -uninfected children and adults hospitalized with piv-associated pneumonia in south africa. in addition, we compared the prevalence of piv detection with controls for better interpretation of surveillance data. we conducted surveillance for children and adults hospitalized with pneumonia through the severe acute respiratory illness (sari) program, an active, prospective, sentinel hospitalbased surveillance system in provinces in south africa, as described previously [ ] . in february , sari surveillance began in of the provinces of south africa (chris hani-baragwanath academic hospital [chbah] , an urban site in gauteng province; edendale hospital, a periurban site in kwazulu-natal province; and matikwana and mapulaneng hospitals, rural sites in mpumalanga province). in june , an additional surveillance site was introduced at the klerksdorp-tshepong hospital complex, periurban sites in north west province. we stopped enrolling at chbah in december of . in addition to sari cases, controls were enrolled from may at outpatient clinics serving the same population as of the sari sentinel sites: edendale hospital gateway clinic, kwazulu-natal province, and jouberton clinic, north west province. the case definitions used and enrollment procedures for both sari cases and controls are described fully in the supplementary material. this surveillance, including testing for influenza and hiv, received human subjects review and ethics approval by the universities of the witwatersrand, kwazulu-natal, and pretoria, all of south africa. the centers for disease control and prevention (atlanta, ga) deemed this a nonresearch, surveillance activity. nasopharyngeal aspirates from patients aged < years and nasopharyngeal and throat swabs from patients aged ≥ years were placed in viral transport media, kept at - °c, and sent to the national institute for communicable diseases (nicd) in johannesburg within hours of collection. respiratory specimens were tested by multiplex real-time, reversetranscription polymerase chain reaction (pcr) assay for respiratory viruses (piv types , , and ; respiratory syncytial virus [rsv]; influenza a and b viruses; enterovirus; human metapneumovirus; adenovirus, and rhinovirus) [ ] . we did not test for piv type during the study period. we did not test for adenovirus from august to october because of unavailability of reagents. streptococcus pneumoniae was identified by quantitative real-time pcr detecting the lyta gene from whole blood specimens [ ] . when available, hiv-infection status data were obtained through routine standard of care testing at the treating hospital. when not available, hiv testing was implemented at nicd through anonymized, linked dried blood spot specimen testing by hiv pcr assay for children aged < months and by enzyme-linked immunosorbent assay for those aged ≥ months. we conducted multivariable logistic regression models. in our first analysis, we implemented univariate and multivariable logistic regression models to determine the association of piv infection with sari (for all types together and for each viral type separately) compared with controls enrolled from may to december at the sites in kwazulu-natal and north west provinces. for the estimation of association with sari, we conducted an overall analysis adjusting for age, hiv serostatus, respiratory viral coinfection, and underlying illness and subanalyses stratifying by age and hiv serostatus and adjusting for respiratory viral coinfection and underlying illness. then, we estimated the attributable fraction (af) from the odds ratio (or) obtained from the multivariable model using the following formula: af = (or- )/or × . in our second analysis, univariate and multivariable logistic regression was used to determine factors associated with hiv infection among patients with piv-associated sari from january to december at all sari sites. in our third analysis, we used multinomial regression to compare and contrast demographic and clinical characteristics and severity among patients infected with the piv types. for the multinomial analysis, we used piv type as the baseline category because type is most common. the second and third analyses models were built using manual backward elimination in which nonsignificant variables were removed from the model one at a time starting with the variables with smallest magnitude of effect until all remaining variables had a p value of <. . covariates with a p value of <. at univariate analysis were assessed for significance with multivariable analysis; statistical significance was assessed at p < . for all multivariable models. two-way interactions were assessed by inclusion of product terms for all variables remaining in the final additive models. for each univariate analysis, we used all available case information. for important variables in the hiv association and af analyses that had substantial missing data, namely hiv infection status, we multiply imputed that variable as well as any variables that were incomplete and associated with hiv using chained equation multiple imputation over iterations. when adjusting for respiratory viral coinfection in our models, we evaluated coinfection with each virus separately and also as a combined variable of coinfection with any of the tested viruses. calculation of observed incidence and incidence adjusted for af of piv-associated sari hospitalizations was done for study site (chbah) where population denominators were available, as described previously [ ] . a complete description of the incidence calculation methods can be found in the supplementary material. . of the sari cases tested for piv, ( . %) tested positive for any piv type: ( . %) were solely type , ( . %) were solely type , and ( . %) were solely type . coinfection with types of piv occurred in ( . %) patients: ( . %) tested positive for both types and , ( . %) for types and , and ( . %) for both and . children < years of age were more likely to test positive for piv ( . %, of ) than individuals aged ≥ years ( . %, of , p < . ). males were slightly more likely to test positive for piv ( . %, of ) than females ( . %, of , p = . ). the sari patients who died in hospital were less likely to test positive for piv ( . %, of ) than those who did not ( . %, of , p = . ). there were no differences in percentage testing positive by race or surveillance site (data not shown). human immunodeficiency virus status was determined for ( . %) of sari cases, of which ( . %) were infected with hiv. most of the patients with missing hiv status were children < years of age ( . % [ of ], compared with . % [ of ] for individuals ≥ years of age). on univariate analysis, sari patients that were hivinfected were less likely to test positive for piv ( . %, of ) than those that were hiv-uninfected ( . %, of , p < . ). during the time period when controls were enrolled (may -december ), sari cases were enrolled. for controls, were screened and ( . %) were enrolled. overall, ( . %) of the cases and ( . %) of the controls tested positive for piv ( table ). the overall piv af was . % ( % confidence interval [ci], . - . ), after adjusting for age, hiv serostatus, respiratory viral coinfection, and underlying illness, suggesting that more than two-thirds of pivassociated sari cases could be attributed to piv infection. a statistically significant af was seen among both hiv-infected ( . %; % ci, . - . ) and hiv-uninfected individuals of any age ( . %; % ci, . - . ); although the point estimates are different, the cis overlap. the af was highest among young children and older adults, although it was only statistically significant among children < years of age (for < year, . %, % ci, . - . ; for - years, . %, % ci, . - . ); this same association among children < years of age was seen among both hiv-infected and -uninfected individuals. we then calculated the af for piv types , , and separately. the af was . % ( % ci, . - . ) for piv type , . % ( % ci, - . ) for piv type , and . % ( % ci, . - . ) for piv type . the age and hiv-status subgroup analysis results for piv types and separately were similar to those found for parainfluenza overall, except that some subgroup analyses involved smaller numbers of subjects and were not statistically significant (data not shown). we did not conduct the subgroup analysis for piv type because it was not found to be statistically associated with disease. most ( . %, of ) patients with piv-associated sari were < years of age, the group for which we found a statistically significant and substantial af. twelve percent ( . %, of ) of children < years of age with piv-associated sari were infected with hiv ( tables and ). on multivariable analysis among individuals ≥ years of age with piv-associated sari, hiv-infected individuals were more likely to be young adults - years of age (aor . , % ci, . - . ), compared with children and young adults ( - years of age), and less likely to have an underlying illness other than hiv (aor . , % ci, . -. ; table ). when we compared epidemiologic and clinical characteristics of the piv types, we found statistically significant differences in age, year of infection, and coinfection with other respiratory viruses (supplementary table ). on multivariable multinomial analysis, patients with piv type infection were more likely to be < year of age and patients with piv type infection were more likely to be - years of age, compared with patients with other piv types. compared with sari patients with piv type infection, patients with either type or infection were more likely to be coinfected with rsv (for type , aor . , % ci, . - . ; for type , aor . , % ci, . - . ). in addition, patients with piv type infection were more likely to be coinfected with rhinovirus (aor . , % ci, . - . ) or enterovirus (aor . , % ci, . - . ) than patients with type infection. the overall observed incidence of piv-associated sari in soweto from to was ( % ci, - ) cases per population ( table ). the observed incidence was highest in children < year of age ( [ % ci, - ] cases per population) and lowest in those - years of age ( [ % ci, - ] cases per ). in all age groups, the observed incidence was higher among hiv-infected compared with hivuninfected individuals. the subgroup with the highest incidence was hiv-infected infants < year of age ( [ % ci, - ] cases per ). the overall incidence adjusted for the af was cases per ( % ci, - ); the age-specific adjusted incidences followed the same trend as the observed incidences ( table ). the age-adjusted relative risk of piv hospitalization by hiv status was . ( % ci, the piv serotypes ( , , and ) were found to cocirculate throughout the year and differed from year to year; seasonal peaks were observed for piv- between september and november, which is spring in south africa (figure ). the percentage of specimens testing positive for any piv type varied by year, with a higher proportion of sari positive for piv in parainfluenza virus is associated with a significant amount of severe respiratory disease in south africa among children < years of age, especially those that are infected with hiv. the evidence for this is based on of our findings: the af and the observed incidence. among children < years of age, a substantial amount of sari is attributable to piv, particularly types and . the observed incidence of piv in soweto, south africa, is much higher among hiv-infected individuals and is similar to other respiratory viral pathogens such as influenza and human metapneumovirus [ , ] . clinicians should recognize piv as a common cause of respiratory illness in children during the spring season, especially among children that are infected with hiv, and interventions should be developed to prevent and treat piv disease. as we found in south africa, studies from across the globe have found that piv is associated with up to % of inpatient respiratory illness, particularly among the very young. this has been found in bangladesh [ ] , china [ , ] , thailand [ ] , the united states [ , ] , and in multiple countries across the african continent. in kenya, . % of individuals ≥ years of age hospitalized with pneumonia had piv types - detected [ ] . in ghana, . % of children hospitalized with acute lower respiratory tract infection had piv types - [ ] . in mozambique, . % of infants < year and . % of children < years of age hospitalized with acute respiratory illness tested positive for piv [ , ] . it can be difficult to attribute respiratory disease to a specific pathogen. molecular tests may identify viruses in respiratory specimens that may not be causing illness, and coinfection with other potentially pathogenic respiratory viral infections was common in our population. we found that a majority of sari was attributable to piv types and in children, even when controlling for viral respiratory coinfection, but not all studies have found that piv is pathogenic. in fact, very few studies have adequately evaluated piv in the context of controls. two studies from kenya that compared patients with respiratory illness to controls did not find a statistically significant attributable risk for piv [ , ] . however, a study comparing children < years of age from thailand hospitalized with pneumonia to controls found findings similar to ours, specifically that infection with piv types or was associated with disease [ ] . the lower incidence and nonsignificant af from our data among individuals ≥ years of age suggests that piv infection may not be associated with respiratory disease in older children and adults. we did not find a significant af for patients infected with piv type , but we may not have been powered to detect this because type was the least common type. we found differences among patients infected with different types of piv and between patients infected and uninfected with hiv. in children, patients with piv-associated sari who were hiv-infected were more likely to be older and to be coinfected with pneumococcus; however, the af among adults was not statistically significant. the association between respiratory viral and pneumococcal infection, although not described previously for piv infection, is well described for other pathogens such as influenza [ ] and rsv [ ] . pneumococcal conjugate vaccine was introduced in the south africa childhood immunization system in , so it was available and being used during the entire time of this study. the seasonality of piv in south africa is similar to that seen in other temperate countries such as the united states, where piv circulates during the northern hemisphere spring and winter seasons [ ] . in contrast, in tropical and subtropical countries in africa, such as cameroon, ghana, and kenya, piv does not appear to have distinct seasonality [ , , ] . this is one of few studies that describe the epidemiology of piv in both children and adults over a long period and in the context of controls. however, there were some limitations to our study. not all children were tested for hiv, and we did not analyze piv in cases of milder outpatient influenza-like illness, which includes common presentations of piv illness such as croup. although it is uncommon and uncommonly tested for, we did not test for piv type , so our incidence estimates would be a minimum estimate. we also did not test for all viral respiratory pathogens, such as coronavirus and bocavirus. the large number of patients from chbah ( %) may bias results toward the epidemiology at that one site. our calculation of incidence was for only site and the calculation of af was conducted at , so these analyses may not be representative of all regions in south africa. the incidence may be an underestimate if patients did not seek medical care for their illness or sought care at a hospital other than chbah or died before reaching the hospital. the increased incidence of hospitalization among individuals infected with hiv may be due to a lower threshold for hospitalization compared with hiv-uninfected individuals. lastly, we did not have data on steroid use, which is a common treatment for croup in children, and for patients with hiv infection, we did not have information on art nor cd cell count. in conclusion, based on years of respiratory disease surveillance, piv is a common cause of sari among children < years in south africa. among children, the observed incidence of piv is higher in the hiv-infected population than the hivuninfected population. a vaccine to protect against piv is not currently available, but vaccine candidates are in the clinical testing phase [ ] . the findings of our study accentuate the need to target children for piv prevention strategies including vaccination, should a vaccine against piv become available. abbreviations: ci, confidence interval sari, severe acute respiratory illness preparedness and response to avian and pandemic influenza in south africa (cooperative agreement number: u /ip - ), and the national institute for communicable diseases, south africa. potential conflict of interest. h. d. has received honoraria from msd-south africa and novartis-south africa, honoraria from pfizer-south africa for speaking engagements a study of the antibodies against parainfluenza viruses in childrens' sera half-life of human parainfluenza virus type (hpiv ) maternal antibody and cumulative proportion of hpiv infection in young infants parainfluenza virus infection of young children: estimates of the population-based burden of hospitalization human parainfluenza virus-associated hospitalizations 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tract illness in rural thailand etiology and epidemiology of viral pneumonia among hospitalized children in rural mozambique: a malaria endemic area with high prevalence of human immunodeficiency virus incidence and etiology of acute lower respiratory tract infections in hospitalized children younger than years in rural thailand interaction between influenza virus and streptococcus pneumoniae in severe pneumonia association between respiratory syncytial virus activity and pneumococcal disease in infants: a time series analysis of us hospitalization data seasonal trends of human parainfluenza viral infections: united states viral etiology of influenza-like illnesses in cameroon progress in the development of human parainfluenza virus vaccines we thank the surveillance officers, severe acute respiratory illness programme team, and especially the patients. we also acknowledge dorothy supplementary material is available online at open forum infectious diseases (http://openforuminfectiousdiseases.oxfordjournals.org/). key: cord- -uo h ku authors: button, kenneth title: the economics of africa's floriculture air-cargo supply chain date: - - journal: j transp geogr doi: . /j.jtrangeo. . sha: doc_id: cord_uid: uo h ku this article examines the economics of africa's emerging air cargo supply chains, taking floriculture as a case study. floriculture is an important employer, and earner of foreign exchange for several regions of central/southern and eastern africa including more recently ethiopia. air transportation often plays a critical role when the supply-chain involves high-value, non-durable, relatively light-weight, and compact consignments such as flowers, and geographically when regions are difficult to access by other trunk modes. the success of air cargo chains, however, depend as much on the quality of surface modes serving various “last mile” access and egress functions, as well as efficient nodal interchange points and the availability of suitable airport and airline capacity. the last, because of the important role of belly-hold space, includes consideration of passenger as well as cargo specific services. to meet the needs of africa's floriculture sector, a variety of supply-chain models have emerged that embrace air and surface links, as well as storage at various points in the chain. the paper considers the nature of these chains, the reason d'être for their structures, and their limitations. the most dynamic trading regions are now those that have become linked into the network of global value chains. unfortunately, africa is not a significant player in these networks. drivers for the development of global value chains are considered to be low transportation costs; information and communication technologies; high quality telecommunication infrastructure; technological innovations; education and skills of the workforce; competitive labor costs; political, social, and cultural environments; stable legislation and ability to enforce contracts; proximity to supply sources; and proximity to market. in general, africa falls short in most of these. the focus of this paper is on the peculiar economic challenges associated with africa's floriculture aviation supply chains. the requirements of this industry differ considerably from the traditional view of supply chains in africa with their focus of bulk raw materials and cheap consumer goods. the modes used differ, the organization of the various links in the supply chain differ, the perishability of the products differ, the informational needs differ, the linking of the long and the short hauls differ, and so on. and, importantly, the aviation supplychain dominates the delivery of transportation to the floriculture industry. africa has the world's worst road, railroad, and airport infrastructures in terms of both quantity and quality (gwilliam, ; buys et al., ) . it also has the least number of commercial aircraft per capita. having said this, the forecasts for aviation activities are relatively optimistic. boeing commercial airplane ( ) predicts that intra-africa revenue passenger kilometers flown will grow an average annually by . % between and , and those between africa and the middle east and europe by . % and . % respectively. physically, air cargo is projected to grow between africa and europe by . % per year, between africa and east asia by . %, and between africa and north america by . % per year. but this is from a small base. this paper looks at the economic challenges that still confront aviation-based floricultural supply chains in africa, and how they are being confronted. this is done largely within a managerial-economics framework. i am much less concerned with the other significant challenges these supply chains encounter, such as culture and ethics issues (hughes, (hughes, , , although there is some discussion of the various forms of governance and government set within williamson's ( ) new institutional economics. methodologically, the article is an exercise in what used to be called "descriptive economics"; and which should not be taken as a pejorative term. it involves gathering and compiling data about the economy and entails economists making observations, noticing patterns and recording facts. descriptive economics is mainly qualitative and inductive in its nature. initially, the general characteristics africa's floriculture sector are outlined, and the aviation services available are described. i then move to the specific challenges of the floriculture supply chain. finally, attention is paid to the main african chains, with a focus on the alternative structural models in place. these chains involve the linking of short-haul domestic african routes and their interface with intercontinental, trunk-haul airline services as well as the air transportation itself. africa's modern commercial flower production began in the s. it has always been largely an export orientated industry. flowers are neither a major part of most african cultures nor used much in decoration. outside of africa, prior to the s demands for cut flowers in europe and north america were met by local production. in europe, which still has the largest per capita consumption of stems in the world, and about eight times that of the us, production was concentrated in the netherlands. with the coming of expedited movements within the eu, it also became possible to economically produce cut flowers in southern europe. the energy crisis in put producers in northern europe under further pressure because of the higher costs of greenhousing. subsequently, the supplying of cut flowers to european markets began to shift to lower cost producing regions with climates that allow continuous production without high-energy consumption. growing exportable floriculture products in africa then became concentrated in kenya and south africa, with uganda, tanzania, and especially ethiopia rising in importance over recent years. zimbabwe's output declined dramatically from the early s with the country's land reforms but there has been some recent recovery (english et al., ) . at the same time, new markets are being developed for floriculture products in east asia, the middle east, and the us. kenya's current t of daily exports of flowers, for example, end up in national markets. ethiopia's growers, and exporters, while continuing to encourage trade with traditional european partners, have also begun exporting to saudi arabia, qatar, and bahrain. accompanying this have been tighter controls imposed by importing markets and, in particular, on the quality of products and on the environmental implications of their cultivation (kuiper and gemählich, ) . this has increased costs of production, and particularly so for some of the newer regions. the traditional distribution channels, notably the flower auctions in amsterdam, are responding to this. the auction systems have been computerized and the auction houses have taken on new roles including acting as intermediaries between growers and buyers when flowers go directly to final consumers (mwangi, ) . competing auctions have also emerged, most notably in dubai (babalola et al., ) . despite these developments, africa's floriculture industry is at the micro-level, geographically specific. there are variations in the needs of the varieties of plant grown, with each depending on appropriate amounts of sunlight, a narrow temperature range, and water supply, as well as specific soil compositions. altitude can be important in some cases. there are also differences in the ideal agroecological conditions for cultivating plants and cuttings for export as opposed to stems. the regions around lake victoria are, for example, ideal for long-stemmed cut roses as are ha on lake tana in ethiopia, the source of the blue nile, and another ha on the blue nile itself. the majority of floriculture in africa is located within relatively short distances of international airports. most of ethiopia's floriculture is, for example, within a kms radius of addis ababa airport. similarly, kenya's flower farms are mainly situated around lake naivasha, about kms northwest of nairobi airport. from an employment perspective, however, they do not bring more farm jobs to rural areas, but rather work is focused close to major cities, reinforcing urbanization trends. one reason for this is the cost structure of the industry. although this can vary a lot according to location, climate, and product type and quality, for an -ha farm near lake naivasha the cost per stem was estimated in at $ . to $ . for growth and $ . to $ . for transportation. a stem would sell wholesale for $ . to $ . . given that production costs are largely fixed -wages are often already low and most operating capital is tied up in such as irrigation systems, cold storage, and ventilating systems -transportation is major variable element in the cost function. linked to this, another key factor influencing location is the lack of durability of stems. this means production has to be close to the trunk mode and there must be appropriate intermodal transfer facilities. flowers and cuttings, for example, need be at the retail market within days of cutting; e.g. roses last for three to five days, carnations seven to ten days, standard chrysanthemums seven to days, and pompon chrysanthemums ten to days. on average, for every extra day spent travelling flowers lose around % of their vase lives. africa's surface transportation infrastructure, despite considerable investment over the past decade, is seriously deficient in both quantity and quality. physical proximity to a major airport is, therefore, important to the floriculture industry. regarding regional economic effects, floriculture's impacts are highly geographically specific. unlike many other agricultural products, floriculture workers migrated to and live in areas that have become urbanized as the flower business has developed around them. as noted earlier, this has contributed to urbanization rather than slowed it as intended with agricultural retention programs (hall et al., ) . the industry is important because it creates employment and development possibilities, and especially because it provides relatively steady work throughout the year unlike other agricultural activities (mitullah et al., ; kabiru et al., ) . it is also a major employer of female labor, which constitutes about % of workers in kenya's flower production (kuiper, ) . although increasing over time, along with improved working conditions, farm workers' wages are in general still low. while the majority of those employed in floriculture in kenya earn wages above the agricultural legislated monthly minimum (dettmer et al., ) they still often fall below local poverty lines (kazimierczuk et al., ) . there are also often problems of displacement. in the lake victoria the approach has an established pedigree and is, for example, referred as one of several branches of economics by jevons ( ) , generally seen as the father of mathematical economics, in his seminal work on the theory of political economy. in doing this there are inevitable caveats regarding the quantity and quality of data. while global bodies, such as the world bank and the african development bank, and national governments, collect some aggregate statistics, much of the information regarding specific african supply chains is piece meal, often gained from case studies or profession bodies in individual countries, and sometimes from the grey literature. additionally, up-to-dated information can be found at the website of organizations cited in the text. individual cut flowers are "stems". https://www.floraldaily.com/article/ /zimbabwe-making-flowerexports-blossom-again/ https://gro-intelligence.com/insights/articles/east-african-floricultureblossoming taking kenyan shillings are about $ . region, for example, workers migrating to the area have led to tension with local society which has traditionally been supported by grazing. floriculture's dependence on lake waters and the need for farmland not only raises concerns over ecosystem preservation but results in competition for water access and for land with local masai herders. cultural, conflicts also exist between the herders and kikuyu flower growers (kuiper, ) . economic theory highlights the key market characteristics required for viable aviation networks, but africa is an awkward "shape" for any of these (scotti et al., ) . the us is good for hub-and-spoke systems with its contiguous states forming a virtual square embracing large populations at each corner that act as gateways for international traffic as well as large markets for domestic fights. major cities in the center act as domestic hubs. europe is ideal for discrete, short-haul, nonconnecting services emanating from bases, such as in ryanair's business model. the bulk of its population and economic activity is located a dense economic corridor stretching from north wales to northern italy; the "blue banana". china, with its concentration of economic activity in the south and west, in many ways, parallels that of europe. the linear networks found in such as norway facilitate "bus-stop routes", with planes maintaining their load factors by picking-up and dropping passengers as they move along routes. most of africa's human geography does not conform to any of these patterns. institutional structures have not helped the situation. until the s, intra-africa air services were regulated on a piece-meal basis by restrictive, bilateral national agreements with nearly all carriers stateowned and lacking a commercial focus. airlines were characterized by mismanagement, political interference, high operating costs, and outdated equipment. their focus was on inter-continental traffic, with the intra-africa network taking a secondary role. the yamoussoukro decision sought to readdress this. it was a commitment to deregulate air services and to open regional air markets to transnational competition. the expected gains have yet, however, to materialize on any scale, although in those regions where yamoussoukro has been implemented, frequencies have often increased and privately funded airlines have emerged (njoya, ) . but the impact is patchy. the creation of a single african air transport market (saatm), which has been planned since , may offer another opportunity for enlargement of air services. most analyses of africa's aviation supply chains have focused on tourism (e.g. sifolo, ; steyn and mhlanga, ) . this is not surprising given the overall economic contribution of the sector to africa's economy. the world travel and tourism council ( ) estimated that in tourism accounted for . % of the continent's gdp. but, as we have also seen a number of africa's regions have the geography to grow quality flowers in volume. like tourism, floriculture has a high labor content and its localized economic impacts are often where unemployment is high and labor productivity has been rather low. further, because africa's floriculture is almost exclusively an export industry, it is a major source of foreign exchange. fig. stylizes the stages in air cargo supply chains. it is conceptually identical for passengers with some differences in terminology; e.g. warehousing would be hotels and integrators would be inclusive package tour operators. basically, shippers can make all or some the decisions concerning modes of movement, routing, warehousing, distribution etc., or can engage integrators or forwarders to act as agents and carry out all or some of the stages. some of these decisions are of a purely technical nature (yang et al., ) , but other, partly due to market uncertainties, are more subjective. the generic pattern of air cargo logistics and the branches in the decision tree are similar irrespective of whether the logistics involves developed or developing countries. the range of options, however, tends to be smaller when developing countries are involved, and some of the options may be of lower quality. this is particularly so with cold chains that require actions and equipment designed to maintain a product within a specified low temperature range from harvest to consumption. an increase in temperature beyond four degrees at any point in the cold chain, for example, compromises the quality of cut flowers. at a more macro level, there are two broad frameworks typifying aviation supply chains, or at least to significant elements of then. one consists of a series of interacting free markets involving suppliers of various services and shippers -a set of standard neoclassical economic models. looking again at fig. , this does not mean that at each stage there is competition in selling services. in some cases, to minimize coasian transactions costs, or to reap various forms of economies of scale, there may be vertical integration of suppliers of logistics services. thus, as seen later, while kenya has a largely competitive chain, it falls short of the neoclassical ideal. the alternative is a more command-andcontrol approach with the government, or a quasi-state corporation, controlling the supply chain, or key links in it. this, although not completely, is the model ethiopia has adopted in its relatively recent move into floriculture. the authorities provide a considerable degree of "direction' in the chain. a challenge in developing efficient aviation-supply chains lies in the size of the market. economies of scale can be particularly pronounced, at least up to a point, in the provision of airport logistics centers (martín and voltes-dorta, ) and forwarder/integration services. economies of density, scope and other network features are relevant when providing airline services and regional distribution. in the african context, barros and wanke ( ) , for example, find economies of scope are the most important variables for explaining levels of airline efficiency, although the impact of fleet mix and public ownership are also important. this generally means that passengers fares (important when cargo is carried as a complementary revenue source in a plane's hold) and freight rates are higher for leaner markets combined with more spartan schedules. it also means that many air cargo services are indirect, collecting traffic along "bus-stop routes" rather than being direct between the flower growing regions and destinations. thinner markets also tend to be associated with less competitive airline conditions, affording users less opportunity to exercise any monopsony power they may have over fares and freight rates. there is something of a paradox here. while concentration of business in the hands of a few airlines and other actors along the aviation-supply chain can help reap the gains of various scale effects, lack of competition can lead to both allocative and x-inefficiencies, with suppliers having no incentive to minimize their rates. in this sense, the thin aviation markets found in much of africa are below the threshold required to bring about a reasonable level of competition between airlines. a recent change in africa has been the emergence of gulf and turkish carriers (pirie, ) . not only have these expanded dedicated freight services, but their extensive use of wide-bodied long-haul passenger jets has added belly-hold freight capacity on many corridors (heinz and o'connell, ) . inbound into africa, the gulf carriers have diverted traffic away from africa's airlines. this includes flying out of major european cities such as london and amsterdam, as well as their own hubs (pirie, ) . for example, emirates' cargo-only service flew to five african cities in . in the same year qatar airways launched a specialized freighter service into djibouti when already operating freighters to accra, entebbe, johannesburg, khartoum, lagos, nairobi, and etihad increased its freighter links to africa with the launch of a twice-weekly service between abu dhabi and brazzaville, via lagos. airports council international reports that africa had none of the world's top cargo airports in . the main african hubs are at johannesburg, addis ababa, cairo, and nairobi, with lagos and khartoum being somewhat smaller, and with much of their activity involving aid imports. other countries, such as uganda and ghana, have sought to increase their presence in the cargo market but suffer from inadequate landside facilities and poor access. most international air cargo operations confront challenges associated with asymmetric patterns of trade caused by natural market imbalances and institutional factors. these pose backhaul problems restricting maximum utilization of aircraft capacity and, given limited fifth-freedom rights, add to the risk of service withdrawal (behrensa and picard, ) . emirates' weekly inbound service to lilongwe transporting mainly merchandise and pharmaceuticals was, for example, near capacity in the mid- s, but very lightly loaded outbound, calling at nairobi to load additional cargo for europe. electronic items, often for onward regional distribution, dominate emirates' cargo into kenya while outbound traffic comprises mainly flowers and fish. the airline has also long flown pharmaceuticals from india, automotive parts from germany and general cargo from china into johannesburg, taking outbound loads of manufactured goods and fresh produce (campbell, ) . africa's air passenger capacity, jointly supplied with belly-hold capacity, has grown. the centre for aviation (capa) estimates intra-africa business grew from about million return seats in , to million in , to million in . added to this has been the growth in activities of foreign carriers. much of the expansion in intercontinental capacity between and was associated with middle east airlines that roughly doubling their share to about % with european carriers maintaining about a third. (pirie, (pirie, , . in particular, there was growth in inter-continental connections, much of which involved traditional hubs in europe. but the middle east also enjoyed increased connectivity. this has led to africa's airports becoming more dependent on a limited number of airlines which enjoy quasi-monopoly power (scotti et al., ) . the floriculture industry is highly sensitive to geography, and in particular to climate, water supply and altitude. unlike some more footloose industries, where transportation can have significant effects on their locations, transportation is largely a facilitator that releases the natural flower-growing potential of an area. but having an airport nearby is not sufficient, it has to be accessible and offer appropriate transit facilities. surface access to africa's airports, however, varies considerably. unlike seaports that require heavily engineered access routes, those serving flower farmers, both because of relatively infrequent truck movements and light loads, can be less-substantial and are generally built to a lower design standard. congestion and poorly maintained roads can, however, reduce the reliability of the local justin-time supply chain that floriculture relies on to connect to relatively infrequent flights. the temporal and temperature fragility of perishables normally means that a cold-supply chain is adopted. this involves rapid harvesting of the product when at the ideal stage in its life cycle, the movement of relatively small units, often in chilled containers, and storage at suitable consolidation facilities prior to long-distant movements to final customers. the perishable supply-chain, excepting capital outlays on the storage facilities, almost exclusively involves forward integration. from the perspective of economic development, this has major advantages in conservation of foreign exchange and in generating domestic jobs. the quality of the supply chain, and its associated labor, has also evolved as the floriculture sector has moved to higher value-added products. kenya, for example, has shifted away from exporting lower value to higher-value stems and onto bouquets (kuiper and gemählich, ) . the quality of any supply chain is dependent on its weakest link, and thus while aviation may be an important element in chains involving flowers, even good aviation infrastructure and services may not lead to successful flower production. in the case of the cold chains, the roles of large forwarders and agents are important (babalola et al., ) . delays often mean the loss of produce, and excessive storage time is costly in terms of ultimate shelf lives. in many cases, the trunkhaul aviation link is tied directly to local forwarders that own reefer trucks and warehouses. such forwarders are often, in turn, tied to larger, international companies active in the global supply chain that generate cost economies of scope and density, as well as ensuring quality control. dettmer et al. ( ) , using south africa's international trade data, shows air transportation generally has a comparative advantage when the trunk-haul movement is over relatively long distances, the perishables involved are light weight, low volume and high value items, and especially if the shelf-life of the product is short. in many cases, the aviation supply chains can be combined with those of other goods, or passenger supply chains. in the case of landlocked countries, or those with no easy access to major markets, the air transportation supply chain has considerable advantages for the export of perishables (world bank, a , b . the chain is, however, expensive, with estimates by africa's flower exporters, and particularly those in kenya, that logistics represent % to % of the cost of production of stems. the development of wide-bodied aircraft has produced significant economies of scope as larger planes can combine passengers and bellyhold cargo. this offers an alternative aviation product to specialized air freighters. the movement, albeit slow and incomplete towards more liberal markets, both within africa and inter-continentally, has led to passenger flights being more frequent, less expensive, and more widely available. but in the adherence to tight timetables, belly-hold cargo may get bumped at the pilot's discretion if it misses its loading time. freighters usually offer better temperature control, fewer inspections, and additional capacity, which is particularly valuable for large quantities of short-season goods. but dedicated freighters can be costlier, may fly less often and to fewer locations, and may sit until they reach capacity, endangering perishables. services with several stops are also common to increase the load factor. the aviation infrastructure in africa also often limits when and where large planes, both passenger and cargo, can operate, restricting the hubs and routes that may be served (world bank, a , b . being a network industry, cost minimization in cargo aviation involves consideration of economies of density as well as those of scope. this raises challenges of balancing two-way traffic flows. the majority of passengers make return journeys, whereas freight consignments are usually unidirectional. in the case of africa's trade, much of the cargo suitable for air transportation involves imports of such things as components and spare parts. these are generally higher value commodities than perishables such as flowers, less dependent on just-in-time services, and are more easily handled. in many cases, therefore, inbound freight is treated as the primary cargo, and capacity decisions based upon it, with exports of flowers seen as the marginal cargo -the return load. the development of hub-and-spoke networks has allowed consignments from diverse origins and destinations to be consolidated and transshipped to a wide range of destinations. again, however, there are trade-offs (chung and han, ) . trans-shipping consignments through hubs can, through help in traffic consolidation thus increasing load factors on planes and as a result, reduce costs. but consolidation and transshipment add to the time costs of a movement, increase the possibility of a consignment being damaged or mis-routed, as well as adding direct handling costs of transference. finally, there are technical reasons for having both light and heavy products on a plane to ensure balance. thus, there appears to be a strong incentive for the flower and vegetable industries of a country to collaborate in developing air cargo routes and negotiate prices with the airlines. producers of floriculture products sell their stems in two main ways. many still go through a competitive, spot-auction markets and especially the amsterdam flower market (the bloemenmarkt located in aalsmeer). there are, for example, floral cargo flights from kenya to amsterdam in a regular week. the alternative is to sell directly to retailers and wholesalers where the price is known in advance (hughes, ) . the latter has the advantage of facilitating a more certain supply chain for growers, with buyers largely taking the market risk, and offers opportunities for providing value-added services, such as labelling. it also avoids the costs of middlemen and usually gets the stems to the retailers more rapidly than through an auction, thus maintaining the quality of the product. in addition, if the business is regular, forwarders can arrange block space agreements with airlines that reserves capacity for the producer; this can reduce air cargo rates and guarantee capacity will be available, as well as ensuring revenue for the carriers. but direct selling may not realize the highest current price. prices are agreed before cutting. direct selling can have important cascade effects on floriculture supply chains (nolan et al., ; kuiper and gemählich, ) . in the flower industry, inter-firm coordination occurs when a supermarket chain acts as lead firm in partnering with a brand-name global consolidator-exporter. the aim is to ensure a consistent, high volume supply of quality, certified flowers by simplifying the supply chain seen in fig. by taking produce directly from farmers to supermarkets (riisgaard and gibbon, ) . more direct selling has, though, led to a wave of consolidation among farmers to counter the power of supermarkets. for the consolidator, as the main point of contact for the large supermarkets, consignment size matters. the large consolidators have developed deeply integrated, networks of growers to source from, and invested in innovative technical and logistical capabilities enabling them to meet demands consistently and on time. smaller consolidators are better suited to non-traditional markets which demand smaller quantities of niche varieties and can provide the types of relationships often desired by smaller producers and buyers. since the s, the traditional african floriculture producing areas have encountered challengers from new supplying areas. some of these, however, have been handicapped by major transportation problems. rwanda, for example, has been trying to develop its flower exporting industry, but it remains small (chantal et al., ) . it has the natural advantage of high altitude, ranging from to over m, fertile soils, plenty of rainfall throughout the year, cheap labor, and a relatively good road network. it has seen a joint venture between the rwandan government and kenya's shalimar flowers to bring kenyan expertise to rwandan undeveloped flower sector. but, along with lack of adequate quality controls and suitable labor, long-haul transportation remains a serious impediment to development. belly-hold capacity to amsterdam, brussels and dubai is available, but involves connecting flights, while the dedicated cargo capacity to amsterdam provided by martin air is via nairobi. some of the smaller suppliers are seeking to circumvent air transportation limitations by increasing the self-life of their products and reducing the associated high costs of transportation. they have begun growing variatals of flowers and plant materials suitable for drying. south africa has an established record in this market, and rwanda has recently been developing such products. durability means they can be exported using standard road and air services to a global market without the need for a cold chain. in summary, the floriculture supply chains in africa are technically challenging and, in many instances, lack adequate investment in hard, soft, and orgware. there is evidence that floriculture supply chains can be inflexible and susceptible to disruption because of difficulties in adapting to emerging international protocols, certification requirements, and to regulations (mckinnon et al., ) . the result has been, even for the more well-established growing regions, periodic squeezes on profits. the euro crises from was an example of the problem. more recently, the hoped-for pick-up in demand after the great recession did not materialized to the extent many had hoped, and the onset of covid- has resulted in collapses of many markets. https://www.flowerweb.com/, transportation damages attract "quality remarks" presented to bidders at dutch auctions that adversely affect sale prices by up to %. https://lot.dhl.com/kenyan-flower-exports-in-full-bloom/ steen and gjolberg ( ) while there are standard requirements to sustain a successful floriculture supply chain, there are several ways these requirements can be met. the role of government has been important in the choices that have been made. in particular in the role of the authorities in controlling elements of the chain and in providing public finance has proved significant. the two main growing areas have developed under somewhat different economic structures and with differing degrees and forms of government intervention in their supply chains. flower production in kenya goes back to british colonial times, and with this the application of the anglo-saxon approach to government intervention. the country's floricultural industry is largely market driven with state involvement only when this is seen to enhance outcomes. the support of the kenyan government in promoting the floriculture industry has been mixed and has not been the decisive factor in its development (kazimierczuk et al., ) . kenya's main comparative advantage derives from its climate and low labor costs, but it has benefitted from less stringent environmental regulation, government controls over land rights, and lower trade barriers (jaffee, ; rikken, ) . in addition, farmers utilize modern technologies including drip irrigation, fertigation systems, net shading, pre-cooling, cold storage facilities, bouqueting, recycling systems to prevent wastage, wetlands for waste-water treatment, artificial lighting, grading/ packaging sheds, and reefer trucks. the use of hydroponics reduces the water used in production and makes it independent of the soil quality (bolo, ) . as early as , kenya's industry exported , tons of floricultural produce, climbing to , tons in , , in , , in , but falling slightly to , in . it then rose to , tons in (mwangi, ) . the country's flower industry employs about , people directly and up to two million indirectly, mostly women. physical quantities are not, however, the whole story. the export-oriented nature of kenya's industry makes it is vulnerable to global macroeconomic cycles and shocks. the global economic crisis of , for example, led to significantly lower flower prices, and even when exports in / grew by %, the value of stems dropped by %. slow economic growth caused foreign consumers, and by extension their grocery stores, to encourage price wars between suppliers that depressedthe prices obtained by farmers. the problem was made worse in the short term by the higher air freight rates associated with the "icelandic ash cloud" (kazimierczuk et al., ) . subsequently, with eventual economic recovery, the kenya flower council estimated the country's flowers exports in contributed $ . billion in exports, compared with $ . billion in . although there are some commercial flower growers of all sizes, about % of such exports are produced by a few dozen large and medium producers. these larger farms are better equipped than rivals in other african countries to control their entire production process, allowing integration into complex, expansive product chains. as with many sectors of africa's trade, there has been a widespread adoption of thirdparty logistics service providers as part of the chains (sohail et al., ) . kenya is the largest external supplier to the european flower market with a % market share. its major competitors, colombia, ecuador, and israel each have only half this. about % of the exports by weight are shipped to the wholesale markets in the netherlands to be sold retail in other eu countries and the uk. as noted earlier, while the dutch auctions have historically been the most important channel, changes in consumption patterns and supermarket supply chain rationalizations have led to more direct contracts. currently, about % of the exports to europe are sold directly to uk and germany providing an opportunity for value added at source through sleeving, labelling, and bouquet production. table provides an indication of the geographical spread of sales by value. lake naivashasa's location permits year-round production and facilitates the growth of the medium-sized roses that are often found in the floral sections of eu supermarkets, as well as of larger blooms favored in russia. these natural advantages have been supplemented by governmental support for the sector through reduced duties and taxes on crucial imported inputs and facilitating cooperation with the industry. the availability of air freight, with nairobi airport being a regional cargo hub, and good surface transportation provides high levels of accessibility to markets. this is combined with a ready supply of workers; kenya had an unemployment rate in of about . % according to the international labor organization. cut flower exports began in the late s when wide-bodied jets were introduced and offered additional cargo capacity to the fresh produce industry. foreign investors and partners played a critical role in launching and expanding the floriculture industry in kenya. dutch and israeli advisors, for example, were important sources of technical support. although kenyans of foreign descent or members of the kenyan elite, were initially involved in developing the industry, smallholders were also present and remain so. in , approximately large flower farms and numerous smallholder farmers were involved in the flower production, although the former dominated output (zylberberg, ; kazimierczuk et al., ) . the latter generally cooperate with the larger producers who in turn coordinate the logistics of getting flower to market. the success of the industry is, to an extent, the result of the capacity of the private sector to develop independently from the state and its capacity to quickly adapt to changing circumstances (jaffee, ; tyce, ) . while the initial shipments were exclusively carried as belly-hold cargo, as demand grew, economies of scale made dedicated freighter services viable. the industry is well organized. in , the kenya flower council was established to coordinate the efforts of independent growers and exporters and ensure implementation of acceptable international standards. its members produce over % of the country's flower exports. about % of these are rose stems which make a fast supply chain particularly important. the larger forwarders block space on flights from kenyatta airport both on passenger airlines and freighters that offer day services to europe and the middle east. a range of aviation services are available at nairobi airport, provided both by domestic and foreign airlines. as much as % of the shipments to the uk are carried as belly cargo on kenyan airways with lufthansa cargo and cargolux, providing dedicated cargo space to frankfurt and maastricht. about % of the flowers are grown around lake naivasha, some to km northwest of nairobi. good road links allow, for example, flowers picked in the morning to reach amsterdam by evening. the airport handles the vast majority the there are few detailed comparative studies of south american floricultural supply chains. vega ( ) is an exception but it is dated. https://www.voanews.com/africa/kenyas-flower-producers-eye-us-market kenya grows a number of flower types. roses have the advantage of taking only weeks between flower to bloom whereas, carnations take , alstroemeria, , and lilies, . dansk chrysanthemum kultur (dck) drove kenya's flower exports during this period (english et al., ) . established in , dck's owner reputedly gave shares in its east african subsidiary to the agriculture minister and attorney general, which helped to secure a comprehensive support package that included a low-cost long-term lease on ha of land, unlimited expatriate work permits and a -year guarantee against changes to taxation and profit repatriation laws. for example, amiran brought consultants from israel to advise the future flower growers of kenya on the adoption of large-scale greenhouses. flowers exported. nairobi enjoys significant advantages over entebbe in terms of the scale and scope of the air services offered, its terminal facilities, and its land access. in the latter context, the main growing areas are served by the major road networks in kenya. the lake naivasha region is served by nairobi -nakuru highway, the thika region by the thika road while the athi river and kitengela areas are served by mombasa road (ong'uti, ) . these major routes, although not always well maintained, provide easy access into the city center and into the airport. the feeder roads into the interiors of growing regions that move the flowers to the integrators and forwarders as seen in fig. , are of lesser quality but went through some upgrading and improved maintenance in the s. there are both charter and scheduled carriers based at the airport. as an example of global access, kenya airways' passenger services directly link nairobi with african and intercontinental destinations including london and amsterdam, and together with its strategic partners provides a cargo network involving over destinations (amankwah-amoah and debrah, ) . the airport also has significant cold-chain capacity both within its perimeter and immediately outside, although rapid transfers from road to aircraft keeps down its use. where there have been issues these have been in cold-chain warehousing prior to movements to the airports. a report by tilisi developments ltd. based on warehouse owners and tenants questioned in found that almost two-thirds were facing capacity shortages. there were also issues of poorly ventilated spaces, leakages, power shortages, and poor structural planning. in addition, there was increased stock contamination, causing flower product deterioration during storage. added to this, a case study of equator flowers located in eldoret ( km from nairobi) found the most significant causes of disruptions to the supply chain were natural disasters, logistics process design, labor union actions such as slow-downs and strikes, and production function mechanics (kangogo et al., ) . in terms of the transportation supply chain, road movements seem to pose the biggest problems, with breakdowns and congestion leading to reductions in the vase life of flowers. there can also be periodic shortages of capacity, but to facilitate market access and minimize post-harvest losses, the horticultural crops directorate has provided stand-by capacity with reefer trucks for hire by farmers, built marketing centers, and collection depots this is coupled with damage done at the packaging stage of the chain, and when there is inadequate cold-storage capacity at times of peak demand. turning to uganda, like kenya and tanzania, it has perfect conditions for commercially growing flowers. the country's cut flower business dates to , with the cut rose business beginning in and shooting chrysanthemum production in . it steadily built up a floricultural industry during the s to become africa's fourth largest producer. various forms of assistance were given to the industry including a withholding tax exemption on interest, tax exemptions on raw material, plant and machinery and on time tax refunds. in , it exported nearly $ million of cut flowers and over $ million of live plants. despite early setbacks, including growing flowers that were not suited for the climate and not meeting the quality standards of recipient countries in the eu, the industry has become a significant contributor to the national economy. in the uganda flower exporters association recognized firms as involved in the flower industry. the majority of these are in the growing and exporting stages of the value chain, with two also being transporters with the rest outsourcing their transportation. one company is a broker and wholesaler while another is a grower and broker. there are no local breeders and only one freight forwarder that provide cold chain logistics forthe industry. while uganda's ten largest flower farms export about % of their production, worth $ million annually as well as directly employing some workers with another , indirectly dependent through industries like transportation and storage, they are small compared to kenya. the flower-growing area is about ha, compared to in kenya, and there are many fewer producers. this limits the economies of scale that can be reaped in the supply chain. given the small overall size of the industry, even using forwarders to get economies from consolidation still makes it difficult to negotiate block-spaced agreements with the airlines, and there are additional risks of suitable capacity not being available when needed. the largest market for uganda's chrysanthemum shoot cuttings is the netherlands, about % of roses are handled by european middlemen (msogoya and maerere, ) , witrhretailers in norway, the uk, sweden and germany taking most of the remainder. most flower farms are located near entebbe international airport. but landing taxes and the lack of dedicated air freight for flowers mean that flying costs are around $ per kilo of flowers higher than in neighboring kenya and tanzania where dedicated air cargo is available, as well as space on passenger airlines. as a consequence, about % of the flowers are moved through kilimanjaro international airport which can only offer belly-hold space, with the remainder being exported through nairobi which also has easier, if longer, surface transportation access as well as significantly more air cargo capacity, south africa is the most mature producer of floriculture products in africa, with an industry dating back to the s and s. partly because of its historic links with the netherlands, the country has a well-established bulb exporting industry that is not reliant on a coldsupply chain and can be shipped as general cargo. the cut flower industry has just under large and medium producers of roses, chrysanthemum cuttings, carnations, gypsophila, asiatics, and irises that are mostly located within km of o.r. tambo johannesburg international airport (reinten et al., ) . the airport is easily accessed using a high-quality road network and offers a global span of passenger and cargo airline options as well as cold storage and handling facilities. the flower export industry, however, has been in something of a plateau since , at about $ million per annum, after rapid growth following the demise of apartheid. in part this is because, despite a very good aviation-supply chain, with large capacity, good surface access, and a well-developed forwarder system, it is further from some of its markets than other producers, but mainly it is because of higher labor costs. there are also imports into south africa by both road and air from zimbabwe, kenya, and zambia of cut flowers varietals that cannot be produced locally. these amounted to about $ million in . the south african industry, besides its up-to-date logistics that enables produce to arrive in good condition, maintains itself largely through the sale of its indigenous flowers. to some extent counteracting the stagnation in the cut flower business, which by value is now about % of floriculture exports, there has been growth in the export of higher value seedling, foliage and decorative plants. these are, however, particularly sensitive to local conditions necessitating care in the transportation supply chain. ethiopia is a relatively newcomer to the floriculture industry and, as such, has benefitted from not being a first mover. it has profited from being able to learn from the experiences of established growing regions, and in particular recognizing the importance of meeting international standards (gebreeyesus, ) . the development of the necessary infrastructure for a successful export industry should also be set within the broader context of national priorities to improve the country's domestic logistic systems more generally (tefera et al., ) . ethiopian floriculture involves more state participation and direction than similar industries of the former british colonies. the economy is not as strictly controlled as it was under the former derg regime, but there is still a very large public sector, most notably involving banking, telecommunications, and land and air transportation. floriculture was begun by the derg in with the growth of hypercium, erigrinium, gypsophilia, and carnation on state farms for export. growth accompanied assistance from the world bank and from the dutch in the case of several local flower growing companies, but wilted towards the end of the s seemingly due to a lack of government interest (melese and helmsing, ) . the dutch program for emerging markets (psom) not only promoted the expansion of production through joint ventures but facilitated the establishment of supporting logistics; e.g. by financing the ethiopian perishables logistics company. both local and international transportation in particular has been coordinated with the development of floriculture as part of national economic planning -the state-owned national airline, for example, provides discounts to horticultural exporters -and there have been major investments in perishable handling facilities at addis ababa's international airport. the latter have been specifically designed for flower handling and largely funded by direct foreign investment. ethiopia is the second-largest flower exporter in africa, with about flower growers on the ha of land in production. the industry earned $ million from floriculture export in , some % it's foreign trade earnings. the region's climate is ideal for several forms of floriculture, with land south of addis ababa at m above sea level providing near perfect environment for growers. the country also has the advantage of a fairly flexible labor market (mano et al., ) . the relatively large size of the producers, partly due to the difficulties smaller producers have in raising finance, facilitates economies of scale throughout much of their supply-chains. this has also led to consolidation with significant numbers of take-overs (mano and suzuki, ) . most of the growers are large enough to have their own cooled processing and packing warehouses and reefer trucks (melese and helmsing, ) . problems have arisen in recent years, however, with attacks on producing units and the burning of crops by groups opposed to the government. unfavorable movements in currency exchange rates have also had adverse impacts (belwal and chala, ) . with few exceptions, first movers and early imitators were supported by the national government and foreign aid, and involved domestically owned firms. foreign growers, either by engaging in joint ventures or through full ownership, started to enter after . a significant number of the these came from other african countries, including kenya, uganda and zimbabwe, although more recently investment has come from a wider range of countries including the netherlands, the uk and india, and regional states such as nigeria, sudan and oman. to attract foreign direct investment, the government gave implicit guarantees of stability through its control of ethiopian airlines and bole airport, and initiated financial incentives including a five-year tax holiday, duty free imports, access to bank loans and farmlands, as well as a % exemption from payment of export customs duties (mushir and hailemariam, ; bekele, ) . the biggest market for ethiopian roses is the netherlands which takes about % of the country's exports, with state-owned ethiopian airlines offering in two cargo flights of flowers a day each carrying tons. the airline also moves horticultural products to other destinations in europe, the middle east and other areas on more than flights a week. addis's state-owned bole international airport has been through major enlargement and modernization, partly funded by chinese finance. it now has africa's largest perishable produce terminal including a , square meters cold storage unit complex that was completed in . the new airfreight facility can process about , tons of cargo a year mainly for transportation to europe. given the synergies in storage, the combination of floriculture and horticulture products, reduces the unit cost of pre-flight cold storage. the effects on the blue nile region's economy and population has been somewhat mixed. this was already an area with small scale farms. the arrival of the floriculture has involved taking land from established smallholders and putting it in the hands of large, often foreign owned producers. set against a typical smallholding of one hectare supporting a household consisting of five members, a hectare production of flowers can employ as many as fifty people. there are clear macro-economic benefits from the conversion, but it has the tendency to cause enclave formation and moves away from the country's objective of food selfsufficiency, or "endogenization". added to this, those displaced in recent years are among those engaged in civil unrest. one consequence of these actions has been burnings of rose crops. this paper has considered the important role that air transportation plays in africa's floriculture supply chains, and the technical, geographical, institutional, but primarily, economic complexities confronting those engaged in it. there is a particular focus on the important interface between short-distance, surface transportation at africa's end of the chain and the intercontinental air-transportation haul to markets in europe and, increasingly, asia. much of the account in qualitative. not only is there a dearth of data for conducting any comprehensive econometric analysis, but in practice qualitative factors tend to dominate many decisions along the supply chain. africa's nations are among the poorest on the planet. there are signs, however, that some of their economies are growing more robustly in recent years. much of this growth is through international trade, and the gradual evolution of aviation supply chains has played a part in this. https://www.cargoforwarder.eu/ / / /addis-ababa-airport-onway-to-challenge-dubai/ https://globalriskinsights.com/ / /radar-foreign-investors-attackethiopia/ the latter has been important in the growth of high export earning sectors such as tourism and "exotics", as well, as other industries that can make use of africa's abundant labor supply. the emerging problem is that other regions of the globe are also rapidly developing their tourism and flower production capacities; tourism often being a compliment to floriculture because of the belly-hold air cargo capacity it provides. generally, africa lacks competitive advantage in high export earning industries because its air transportation logistics are thin, fragile, and incomplete even for the sectors in which it has a comparative advantage in production. these weaknesses extend across hardware, software and orgware. changes are coming as foreign investment takes place, deregulation of the african aviation industries are occurring, and as the presence of non-african airlines is increasing. the emerging longterm challenge is to get sufficient investment, including human capital, into the air cargo supply chain; and to do this when unified-mega economies such as china and india, as well as some south america countries, are enjoying greater access to pertinent funding. it is also unclear at this point whether the longer-standing, free market approach to air transportation logistics pursued by traditional african supplying regions can compete with the more planned approach of emergent floriculture suppliers, notably ethiopia. while the former offers more flexibility, as well as incentives for innovation, the discrete nature of many elements in the floriculture aviation supply chain requires "chunky investments" that, even according to adam smith, are sometimes best provided with state financing. the developments around lake victoria and in ethiopia highlight some of the differences in development paths to date, but it is premature to offer conclusions as to eventual outcomes. what is also important, and still under researched, is the more general question of whether floriculture is an efficient way to expend scarce resources even if a nation has a comparative over other african countries. the market for flower production is becoming increasingly global, and perhaps africa as region has limited comparative advantages. looking forward, while the free market in african air services hoped for in has not materialized and air transportation across the continent is still far from seamless, some new impetus is promised. this comes from the signing in january of an agreement between state to cooperate in a saatm and in march by members of the africa union of a provisional agreement establishing the african continental free trade area. ratification, and subsequent operationalization of the agreements, would significantly improve the continents' aviation supply chains. this is a personal research paper. credits to referees etc. are contained in the paper. logistics and global value chains in africa. the impact on trade and development the evolution of alliances in the global airline industry: a review of the africa experience. thunderbird int cold chain logistics in the floral industry an analysis of african airlines efficiency with two-stage topsis and neural networks transportation, freight rates, and economic geography road and development in ethiopia catalysts and barriers to cut flower export: a case study of ethiopian floriculture 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from ethiopia a 'private-sector success story'? uncovering the role of politics and the state in kenya's horticultural export sector the transportation costs of fresh flowers: a comparison between ecuador and major exporting countries. inter-american development bank the new institutional economics: taking stock, looking ahead africa infrastructure country diagnostic: air transportation challenges to growth air freight: a market study with implications for landlocked countries an analytic network process approach to the selection of logistics service providers for air cargo bloom or bust? a global value chain approach to smallholder flower production in kenya an earlier version of this paper was presented as the keynote lecture to the german aviation research society's workshop on aviation in africa, held at the university of applied science, bremen in june . numerous useful comments for improving the paper were gratefully received. i would also like to thank both the editor of the journal and two reviewers of the paper for their views. the final product remains my responsibility. key: cord- -sp kys n authors: valensisi, giovanni title: covid- and global poverty: are ldcs being left behind? date: - - journal: eur j dev res doi: . /s - - - sha: doc_id: cord_uid: sp kys n the paper provides a preliminary assessment of covid- ’s impact on global poverty in the light of imf’s growth forecasts. it shows that the pandemic will erode many of the gains recorded over the last decade in terms of poverty reduction. our baseline case suggests that globally the number of people living below us$ . per day will increase by million in alone; this rise could however approach million, should the recession turn out to be more severe than initially expected, as many practitioners fear. without effective international support, this setback will pose a critical threat to the achievement of the united nations agenda for sustainable development. the fallout from the pandemic will also exacerbate the geographic concentration of poverty, to the extent that the least developed countries, with only % of the global population, are set to represent the main locus of extreme poverty worldwide. concentration géographique de la pauvreté, au point que les pays les moins avancés, qui ne représentent que % de la population mondiale, risquent de représenter le principal foyer d'extrême pauvreté dans le monde. as the number of covid- cases continues its rise, the global economy braces itself for a shock of unprecedented severity and complexity that is expected to trigger 'the worst recession since the great depression' (imf a: v) . in a global context already weakened by prolonged sluggishness, heightened inequalities, and policy uncertainties, the health emergency has quickly spread worldwide, triggering a simultaneous supply and demand shock, with direct ramifications into the financial sphere (baldwin and weder di mauro ; djankov and panizza ; unc-tad d) . on the one hand, sudden breaks in production, value chain disruptions, uncoordinated border closings, lower international trade flows, and travel bans have taken a toll on the level of activity. on the other, reduced working hours, layoffs, confinements, and heightened uncertainties have dampened aggregate demand. meanwhile, the need to increase public spending to cushion the impact of the downturn is likely to put pressure on government budgets, and bankruptcies loom large on a highly leveraged financial sector. for developing countries, the situation is compounded by dropping commodity prices (fuels and to a lesser extent minerals), falling fdi flows, capital flow reversals, and-in many cases-looming debt vulnerabilities (imf a; unctad unctad , a . against this background, if it is too early to predict the depth and duration of the crisis, it is nonetheless clear that its socio-economic costs cannot be overemphasized. the international labour organization (ilo) has recently warned that working-hour losses in the first half of could be equivalent to over million fulltime jobs worldwide, and that . billion workers in the informal economy are at immediate risk of seeing their livelihoods reduced (ilo a; b) . based on hybrid dsge/cge simulations, it has also estimated that in there could be between and million additional people in working poverty, most of them living in developing countries (ilo c; mckibbin and fernando ) . similarly, in a series of research blog posts, vos, laborde, and martin have analysed the potential impact of the pandemic on poverty using the ifpri's miragrodep model (laborde and martin ; laborde et al. ; vos et al. ) . in their latest analysis, the authors find that under a scenario corresponding to a % contraction in world output, and in the absence of any intervention, over million people could fall into extreme poverty in ). unlike the above-mentioned studies, which are based on computable general equilibrium simulations, other contributions utilize aggregate data from household surveys to assess the impact of covid- . sumner and co-authors simulate the impact of arbitrary consumption shocks of − %, − %, and − %, and find that the pandemic could increase the number of people living in poverty by roughly - million, using the us$ . /day poverty line, and up to million using the us$ . /day line (sumner et al. a, b) . using growth forecasts from various vintages of the world bank's global economic prospects (and in some cases from the international monetary fund -imf), other authors find that covid- could trigger an increase in the number of people living below us$ . /day by - million (gerszon mahler et al. a, b) . borrowing methodological elements from this last group of researches, this paper provides two main original contributions. first, it provides a preliminary assessment of the impact of covid- in the light of imf growth forecasts, for all commonly used international poverty lines, thus providing a broader and more nuanced picture than previous analyses. second, it examines the impact of the crisis on the least developed countries (ldcs), a subset of developing countries characterized by heightened structural vulnerabilities and deemed worthy of special international support. the paper is structured as follows. the next two sections respectively discuss the methodology and results. the special case of ldcs is analyzed in the fourth section, while the fifth presents a sensitivity analysis and explores a more pessimistic scenario than the one forecasted by the imf. finally, the last section summarizes and concludes. the methodological approach adopted here is the so-called "augmented poverty line", composed of three steps and essentially a simplified version of the technique developed to nowcast poverty (castaneda aguilar et al. ) . keeping in mind that the first covid- cases were reported in december , the first step entails a comparison of growth forecasts for gdp per capita (in constant international dollars) from two successive vintages of the imf's world economic outlook, namely the october and april full datasets (imf , a). the ldc category was established by the united nations in . ldcs are a group of developing countries characterized by heightened structural vulnerabilities and hence deemed worthy of various forms of international support measures over and beyond what is typically provided to developing countries. for further discussion refer to cdp and undesa ( ) and unctad ( ). due to inconsistencies in the regional groupings across institutions, growth rates were retrieved at individual country level and aggregated at regional level, where appropriate, following the povcalnet classification. the need to obtain data for individual countries explains why we could not utilize the january update of the world economic outlook. while ascribing the difference in growth forecasts between october and april only to covid- represents a clear approximation, the pandemic is unquestionably the main shock involved. indeed, the downward revisions between october and january were negligible (- . % worldwide) compared with what occurred between january and april . the latter forecasts for the year portend a % contraction in world output, and a substantial downward revision of the global gdp per capita growth estimates from + . to − . % (fig. ) . although the fallout from the pandemic is expected to affect all regions, its impact is somewhat differentiated. despite a sharp slowdown, asian economies appear able to avoid a decline in per capita income, whereas other regions, where growth was already much slower prior to the outbreak of covid- , are expected to face significant contractions of per capita income. in the second step, the above growth rates, pre-and post-covid- , are utilized to 'line up' the corresponding poverty estimates using povcalnet, the world bank's computational tool, which draws on more than household surveys from countries and contains the official estimates of poverty at country, regional, and global levels. the "augmented poverty line" procedure follows sumner et al. ( a, b) . denoting by z the poverty line in the reference year (typically ) and by x t the forecasted growth rate of gdp per capita in year t-in our case -the new poverty estimate is obtained by revising the poverty line as follows: clearly, this corresponds to an increase in the poverty line (z t )-hence, ceteris paribus, larger poverty measures-if the assumed growth rates (x i ) are negative, and a reduction in the value of the poverty line in the opposite case. ( ) the third step obtains the impact of covid- as the difference between the poverty measures obtained by applying the pre-and post-covid- growth estimates. in other words, this approach ascribes to the fallout from the epidemic the difference in poverty estimates consistent with the imf's revision of growth forecasts for the year , between the two vintages of the world economic outlook. population data for (drawn from the latest world population prospects (undesa )) are then utilized to translate changes in the headcount ratios into corresponding variations in the number of poor. the above methodology warrants a few caveats. first, the rationale for using the standard international poverty lines and related estimates from povcalnet database stems from the aim of adopting a global perspective, particularly one consistent with the ongoing international debate on covid- responses, as well as with agenda for sustainable development. while the reasonable degree of cross-country comparability of povcalnet figures is fundamental in this respect, it should be noted that their methodological underpinnings are not free from criticism. in particular, the following issues have been highlighted in the literature: (i) discrepancies in the methodologies followed by the different surveys (in terms of sampling, equivalence scales, treatment of incomplete answers, etc.); (ii) potential inaccuracies introduced by the combination of surveys based on consumption with those based on income; (iii) challenges underpinning purchasing power parity adjustments and their impact on poverty estimates; and (iv) bias introduced by the extrapolation of estimates to missing countries and/or non-represented groups (atkinson ; deaton and dupriez, ; united nations ) . second, the approach adopted implicitly assumes that gdp per capita growth is mirrored in an equivalent rise in households' welfare, as measured by surveys; that is, the consumption of all households is assumed to expand at the same rate as gdp per capita. while this is in line with the method used by the world bank to 'line up' poverty estimates from various years, empirical evidence shows that only a fraction of the growth in national accounting variables trickles down to households; hence, the effect of growth on poverty reduction might be over-estimated (deaton and kozel ; korinek et al. ; newhouse and vyas ). , in order to tease out the effect of the pandemic from that of routine revisions of growth rates during the year , in the pre-and post-pandemic scenarios, we modify the forecasted growth only for the year . more broadly, it is worth noting that povcalnet estimates do not reflect societal differences in the notion of a set of "basic needs" or "basic capabilities", they are not suitable to capture within-household inequalities hence gender-differentiated impacts, and their pertinence to "ordinary conception" of poverty has been questioned (united nations ). whenever possible, instead of using growth in gdp per capita, the line-up method adopted by the world bank utilizes the rate of growth of household final consumption expenditure. since no forecast is available for the latter, we resorted to the former. discrepancies between the growth of household final consumption expenditure (as reported in national accounting systems) and that of mean consumption in household surveys are probably linked to the fact that wealthier households are less likely to participate in surveys and are more prone to under-reporting their income (korinek et al. ; newhouse and vyas ) . third, the above methodology leaves unchanged the distribution of income. it is reasonable to expect, however, that some of the poorer segments of the population will be the hardest hit by the fallout from the epidemic, at least in urban areas. for example, strict social distancing is likely to exert a disproportionate effect on informal workers, daily labourers, own-account workers, and small businesses, which have meagre resources to weather the confinement without major disruptions. similar distributional concerns are surely relevant in this phase, and critical in the longer term in shaping the path and speed of poverty reduction, as well as in addressing within-country inequality (lakner et al. ) . in line with similar studies (for instance sumner et al. ( a, b) ), the working assumption of a distributionally-neutral shock is retained here mainly for practical reasons, since distributional aspects plausibly vary from country to country and do not easily lend themselves to generalizations. fourth, the negative impact of the pandemic on households' welfare may be felt through other transmission channels than the pure short-term income dimension analysed here, and adversely affect the attainment not just of the first sustainable development goal (sdg ) but also of other sdgs, notably those related to health and gender equality. what is more, some of the non-monetary channels may even trigger adverse long-term effects, and create path-dependency from 'transient poverty' into 'chronic poverty' (jalan and ravallion ) . for example, health-related problems may permanently lower productivity, or poor households being forced to take their kids out of school to cope with a temporary crisis might have lower income prospects over the long term, with knock-on effects that are not accounted for in the above simulations. finally, the above exercise is admittedly fraught with uncertainties, stemming from the forecasting of economic growth in a very volatile phase, compounded by the degree of noise introduced through the 'line-up' of the corresponding poverty measures. the heightened degree of uncertainty is openly acknowledged by all commentators, including the imf itself, in view of the unprecedented nature of the crisis and of the fact that future prospects are partly contingent on the policy responses adopted at national and international level (baldwin and weder di mauro ; imf a). moreover, some authors have also questioned imf's relatively optimistic forecasts in its april release, pointing to a seeming "discrepancy between the dire narrative and the less dire numbers, in particular for developing countries" (sandefur and subramanian , p. ) . some of the above methodological qualifications are further discussed along with the sensitivity analysis; here it suffices to say that in view of the above qualifications there are good reasons to believe that the figures presented below are-if anythingconservative estimates. given the heightened uncertainty, simulations are run only until the end of and hence do not incorporate any speculation on the potential impact of covid- beyond . yet, risk factors in this respect are all on the downside and there are growing concerns that the downturn could derail the world economy, possibly triggering balance of payment tensions and/or debt crises with long-lasting effects in the developing world (baldwin and weder di mauro ; djankov and panizza ; sandefur and subramanian ; unctad a). with such risks looming, the analysis presented in the next section cannot but be regarded as a preliminary conservative assessment of the immediate poverty impact of covid- . broadly speaking, the impact of covid- on poverty is explained by the interplay of three context-specific factors: . the severity of the health crisis, which largely determines the human and social costs, as well as the type and duration of policy responses (such as social distancing, confinement, and border closures); . the nature and magnitude of the economic fallout, in turn partly linked to structural issues, such as dependence on primary commodities or key markets/value chains hit by the downturn, availability of fiscal space, and outstanding debt; and . the relative weight of people clustered in the vicinity of each poverty line, who may be pushed into poverty by the decline in their per capita income. the scale of the economic fallout from covid- deserves particular attention, and in many developing countries it might arguably have greater significance than the health emergency itself. the pandemic has simultaneously triggered a supplyside shock-propagated along value chains due to the disruption of business activities and rising frictions in international trade-as well as a demand shock, whereby growing unemployment and heightened uncertainty reduce consumption and investment expenditure (baldwin and weder di mauro ). while it is too early to rigorously disentangle the various channels through which this situation is impacting households' welfare, there is growing evidence that it is primarily taking its toll on employment, especially in sectors highly reliant on global value chains (such as garment manufacture, transport, and tourism), as well as on declining revenues from informal activities, notably in the trade and retail sectors (aung et al. ; uneca ) . equally, preliminary evidence also suggests that strict social distancing has adversely affected income prospects for informal workers, and lowered capacity utilization rates and survival time for affected firms, all of which may increase poverty (uneca ; djankov and panizza ). moreover, international prices for primary commodities-especially oil and, to a lesser extent, other hard commodities-have suffered severe slumps in the first trimester of , due partly to commodity-specific fundamentals and partly to the contraction in global demand. in many developing countries, the emergence of covid- has thus been compounded by adverse terms of trade shocks, reductions in remittances and fdi flows, heightened debt vulnerability, and capital flight (baldwin and weder di mauro ; unctad b, c). the additional pressure on government budgets and balance of payments has thus further exacerbated the situation, constraining the space for an active policy response. given this premise, the short-term impact of coronavirus on poverty at the global level is depicted in figs. and , and reported in the appendix. in the case of the extreme poverty line, the global headcount ratio is estimated to increase by . percentage points (from . to . %), thereby wiping out the poverty-reduction progress made in the last - years. this translates into million additional people living below us$ . per day (in purchasing power parity). the impact is even more conspicuous in relation to the higher poverty lines, namely us$ . and us$ . per day. the corresponding headcount ratios increase by nearly percentage points (from . to . % in the former case, and from to . % in the latter), reflecting in both cases an increase of over million in the number of poor people worldwide. further clarity on the differential impact of covid- can be gauged from figs. and , depicting, respectively, the regional breakdown in the changes for each poverty measure and the long-term trends in headcount ratios up to (per post-covid- forecasts). critical to the understanding of these two graphs are the differentiated fallout from the pandemic (fig. ) and the relative positioning in the income distribution vis-à-vis any given poverty line. indeed, the more people are clustered just above a given poverty line, the greater the potential effect of a decline in per capita income on the corresponding poverty incidence. broadly speaking, three sets of regions can be identified in relation to covid- s impact: • in countries in europe and central asia, as well as in other high-income countries, the pandemic leads to large socio-economic costs, but since the overwhelming majority of the population enjoys living standards that are far higher than those implied by the international poverty lines, this translates into relatively small increases in poverty headcounts. • in south asia and east asia and pacific-where poverty reduction was progressing at a fairly rapid pace prior to covid- , but growth is expected to remain positive-the shock is felt essentially through a sharp slowdown in poverty reduction. • in the remaining regions, the crisis provokes an upsurge in poverty rates, thereby reversing earlier downward trends (in latin america and sub-saharan africa) or accentuating an already deteriorating situation (in the middle east and north africa). with reference to extreme poverty, sub-saharan africa stands out as the worst-hit region: the headcount ratio is estimated to increase by . percentage points in the wake of the pandemic, corresponding to an additional million people living in extreme poverty (fig. ) . the impact is also large in south asia, triggering a . % increase in the headcount ratio, compared with the ratio that would have prevailed in the absence of covid- . the middle east and north africa is another area witnessing a particularly adverse fallout from the coronavirus, the incidence of extreme poverty augmenting by more than . percentage point. these figures entail notice that, while at each point in time a higher poverty line implies a larger (or equal) headcount ratio, this relationship does not necessarily apply to the changes in the headcount ratio between the preand post-covid- scenarios. this explains why poverty estimates increase monotonically with the poverty line in fig. , but not in a discernible way in fig. . with the presumption that us$ . per day is arguably more representative of minimum living standards in middle-income countries. focusing on the us$ . per day poverty line, south asia is likely to suffer by far the largest slump, entailing a rise of nearly percentage points in the headcount ratio, equivalent to million additional poor, compared with what would have occurred if the pre-covid- growth forecasts had materialized (fig. ) . the incidence of poverty is also expected to significantly worsen in other developing regions, such as sub-saharan africa, middle east and north africa, and latin america and the caribbean, where headcount ratios increase, respectively, by . , . , and . percentage points. deteriorations in the remaining regions are expected to remain fairly circumscribed, with headcount ratios increasing by less than %. finally, our estimates suggest that the pandemic will exert a more visible and widespread impact on global poverty measures according to the us$ . per day poverty line. in this case, the sharp deceleration in the pace of poverty reduction in southern and eastern asia is such that they will both suffer setbacks in their headcount ratios of - % compared with what they would have experienced had pre-covid- forecasts materialized. given their population size, this implies that they will account for the bulk of the impact in terms of changes in the absolute number of poor people (fig. ) . the deterioration of the poverty headcount, however, will be conspicuous also in the middle east and north africa, latin america and the caribbean, and-albeit to a lesser extent-sub-saharan africa, which will witness a rise in the number of poor by roughly million each. economies in europe and central asia will also suffer some setbacks, with the headcount ratio expected to climb from . to . , while poverty levels in other high-income economies will increase only marginally, even against the us$ . per day poverty line. overall, there is no doubt that covid- will cause a troubling setback in efforts to eradicate extreme poverty (per sdg ), triggering the erosion of the progress achieved in the last - years at a global level, and even more prominent rollback in many developing regions. it also seems clear that the fallout from the epidemic will reinforce the geographic polarization of poverty, with sub-saharan africa and south asia accounting for the lion's share of the changes in the number of poor people, at least in relation to the two lowest poverty lines (fig. ) . moreover, given its intrinsic nature and related response policies, the crisis will likely impact on other sdgs, notably in the health and education spheres, as well as on gender equality. the gender dimension, in particular, intersects other axes of structural marginalization including economic status, membership to minority groups and the like, as women tend to be over-represented in vulnerable occupational categories (from health personnel to informal own-account workers) and in some of the value chains hardest hit by the crisis, such as tourism or textile and apparel. moreover, they tend to disproportionately shoulder the burden of carerelated tasks and be exposed to heightened risks of gender-based violence in the context of strict lockdown; all of which may likely widen gender gaps (world bank ). the pattern of changes in global poverty since the outbreak of covid- begs the question of how the latter will affect prospects for delivering on the agenda for sustainable development commitment to 'leave no one behind'. if admittedly it is too early to provide a definitive answer to this question, some disturbing hints can already be derived from the above analysis. as covid- is disrupting the preparation for the fifth united nations conference on the least developed countries (unldc v), it is also instructive to assess how ldcs have fared in relation to poverty over the last decade-under the so-called istanbul programme of action-and how the ongoing pandemic is likely to impact them. historically, as shown in fig. , the incidence of poverty in the ldcs was stubbornly high even before the emergence of covid- . after a decade of stagnation in the nineties, poverty rates-at least according to the us$ . and us$ . per day lines-dropped at a moderate pace during the first decade of the new millennium, but poverty reduction slowed down markedly in the aftermath of the - global financial and economic crisis. in this sobering context, the fallout from covid- is set to completely stall even this sluggish progress, essentially wiping out any advances in terms of poverty reduction made since (the last reference year available). this might seem remarkable considering that a number of ldcs-cambodia, ethiopia, myanmar, rwanda, and tanzania-have in recent years featured among the world's fastestgrowing economies (johnson ; unctad ; world bank , ). yet, forty-three ldcs are covered by at least one survey in povcalnet; the number of poor people is extrapolated using the average headcount ratio of the group to also account for the missing countries (afghanistan, cambodia, eritrea, and somalia). the headcount ratio at the us$ . per day poverty line barely moved throughout the period, going from to % between and (the last reference year for the sub-saharan african and south asian economies). it is precisely ldcs' intrinsic vulnerabilities that make them disproportionately susceptible to exogenous shocks, especially through balance of payment tensions. moreover, it is the very fact that a significant share of the ldc population was located just above the us$ . poverty line that determines the skewed geographical distribution of impacts depicted in fig. . against this background, the risk that ldcs will lag further behind in terms of poverty eradication (sdg ) is great indeed; all the more so if the downturn triggers further debt distress and balance of payment crises. this reading of the evidence is vindicated by fig. , which shows the ldc share of world poor according to the three international poverty lines (as well as the ldc share of population for reference purposes). even prior to the pandemic, ldcs were accounting for a rising proportion of the world's poor, due to the combined effect of persistently widespread poverty and rapid demographic growth. this trend has only been exacerbated by covid- , with ldcs accounting for nearly half of its impact in relation to the number of people living in extreme poverty globally. this situation is so pronounced that, on the eve of the unldc v conference, ldcs represent the main locus of extreme poverty worldwide. with barely % of the world's population, they account for % of the people living below us$ . per day and nearly % of those living on less than us$ . per day at global level. with the sharp reduction of fdi and remittances flows and the intensification of debt vulnerabilities, it is clear that a quick rebound of ldc economies from the covid- shock cannot but hinge upon much stronger international support, with aid playing a pivotal role in this phase; hence the importance of meeting longstanding aid targets (unctad ). in the longer term, the evidence presented here underscores how ldcs will represent the litmus test for the agenda for sustainable development, specifically for the promises to leave no one behind and reduce global inequality (unctad ) . the earlier discussion highlighted two crucial caveats applicable to the methodology followed here: the extent to which growth in gdp per capita translates into an expansion of households' surveyed consumption, and the heightened degree of uncertainty surrounding the global economic outlook. in relation to the former caveat, the previous analysis implicitly assumed that the consumption of all households would expand at the same rate as gdp per capita (in constant international dollars). empirical evidence, however, has questioned this assumption, and demonstrated that it would lead to an over-estimation of the pace of poverty reduction induced by economic growth. with reference to india, newhouse and vyas ( ) have recently estimated pass-through coefficients which, if applied to the growth of household final consumption expenditure, would replicate the poverty rates obtained from household surveys. their estimated values are . % for urban areas and . % for rural ones. in the light of this, to test the sensitivity of our findings, the adjustment to the poverty line is modified to explicitly add a pass-through coefficient α the impact of covid- on poverty rates is then quantified, assuming a degree of pass-through equal to % (i.e. the average of the above two values for rural and urban areas), and these results are compared with the previous ones, obtained for a unitary pass-through (α = ). before commenting on the sensitivity analysis, it is worth noting that, in this formalization, the pass-through acts symmetrically with respect to positive and negative gdp per capita growth. while in reality this may not necessarily be the case, this specification was retained to ensure full correspondence with the case of α = . the changes in headcount ratios resulting from the epidemic in the two cases are reported in table , by region and poverty line. as expected, the presence of a partial pass-through does somewhat reduce the size of the effects of covid- on global poverty rates, but it does not alter the two key messages of the previous analysis, namely the significance of the setback and its geographic polarization for the two lowest poverty lines. the incidence of extreme poverty, for instance, increases worldwide by 'only' . percentage points with the partial pass-through (instead of . as before), with sub-saharan africa, south asia, and to a lesser extent the middle east and north africa still bearing the brunt of the shock. the second critical consideration in relation to the assessment carried out so far pertains to the degree of uncertainty surrounding the imf's growth estimates. the latter have a track record of being over-optimistic in times of country-specific, regional, and global recessions; moreover, some authors have questioned the consistency of the relatively optimistic forecasts with dire narrative around the covid- outbreak (genberg and martinez ; sandefur and subramanian ) . in the light of this, it is instructive to examine the sensitivity of the poverty estimates to changes in growth performance in the context of a more pessimistic scenario, whereby gdp per capita growth in is assumed to be percentage points lower than the imf's april forecasts. interestingly, this pessimistic scenario, originally developed as a hypothetical setting designed to shed more light on the consequences of a deeper-than-expected recession, is very close to imf's own june assessment, in which growth forecasts have been revised downward, presaging a global recession of − . percentage points for the year (imf b). the comparison of this pessimistic scenario with the one consistent with the imf's april growth forecasts is depicted in fig. , which shows that a deeperthan-expected recession could have disastrous implications for much of the developing world. in sub-saharan africa and south asia, the extreme poverty outlook would considerably worsen, with headcount ratios increasing by a further . and . percentage points, respectively. the negative effects of a deeper recession appear more visibly in other regions (starting from the mena) once the higher poverty lines are considered. in relation to the us$ . per day poverty line, virtually all developing and transition economies would suffer a further deterioration of headcount ratios. translating the above figures into corresponding numbers of additional people falling into poverty gives a clearer idea of the devastating scale of the possible consequences (fig. ) . should the downturn prove to be deeper than initially expected, as more and more practitioners suggest, close to million additional people would fall into extreme poverty worldwide, of which nearly half would be in sub-saharan africa. this would be disastrous for the region, as the headcount ratio would then slide back to the levels of (entailing an even larger number of extreme poor than years ago, in the light of demographic growth). when considering the higher poverty lines-namely us$ . and us$ . per day-the pessimistic scenario indicates that approximately million additional people would fall into poverty, mainly in asia. again, the fact that even in the case of a pessimistic scenario, high-income countries do not appear to suffer visible setbacks in terms of poverty incidence speaks volumes in terms of the levels of global inequality. such a negligible effect is indeed chiefly related to the limited relevance of standard international poverty lines in relation to developed countries' standards of living, while the sizeable worsening of poverty and deprivation stemming from the covid- outbreak would emerge starkly from an analysis of national poverty lines. overall, the magnitude of the potential socio-economic costs of this pessimistic scenario underscores the fundamental importance of revitalizing international cooperation and doing 'whatever it takes' to effectively prevent a deeper and longer-lasting downturn. this conclusion is corroborated by the findings of other studies, investigating the impact of even deeper recessions (sumner et al. b) . beyond the depth of the recession, its duration is also critical: a prolonged downturn would inevitably provoke broader socio-economic strains and risk turning transient forms of poverty into chronic ones, especially if it inflicts protracted damage on productive sectors and micro, small, and medium enterprises. the analysis presented here provides a preliminary assessment of covid- 's immediate impact on global poverty, under the commonly used international poverty lines. more precise appraisals will require up to date "hard evidence", both in terms of household surveys and national accounts; besides, they may entail a shift from a global perspective-with all its methodological caveats-to a national focus, more suitable to capture the differentiated impact of the crisis across distinct segments of the population. promising directions for further research, in this respect, include the use of national poverty lines (lending themselves better to assessing the differential impact in urban and rural areas), as well as the adoption of a multidimensional approach to poverty, to disentangle the evolution in the patterns of deprivation across several dimensions. as the crisis unfolds, however, the usefulness of an early assessment of covid- impact on global poverty arguably justifies the set of simplifying assumptions discussed above. given the heightened uncertainties and the speed at which the socio-economic crisis evolves, this approach results admittedly in estimates that provide conservative, 'ball park' figures, not least because many of the recently adopted policy responses are not necessarily accounted for in this framework. even with these caveats, it is undisputable that the covid- crisis will have dramatic consequences, eroding many of the gains recorded over the last decade in terms of poverty reduction. our baseline case suggests that the number of people living in extreme poverty (below us$ . per day) could increase by million in alone. more likely than not, this number will rise to million, should the recession turn out to be deeper than the imf forecasted in april , as a growing number of projections suggest. even taking the imf's forecasts at face value, the 'great lockdown' will result in the first rise in worldwide headcount ratios since the late s. this represents a significant setback, posing immediate challenges to the achievement of the un agenda for sustainable development, in particular sdg . as the downturn exacerbates structural vulnerabilities and erodes precarious gains in terms of poverty reduction, sub-saharan africa and south asia will be the hardest hit regions, along with the middle east and north africa. nor will other regions be spared, even though adverse changes in poverty incidence there will be of a smaller magnitude, at least in relation to the two lowest poverty lines. the crisis can be expected to exacerbate the geographic concentration of poverty, particularly when compounded by the disparity in the financial and institutional means to roll out effective policy responses and social protection programmes. as further evidence that this polarization is jeopardizing the pledge to 'leave no one behind', we show that ldcs are among the worst hit by the covid- fallout and today represent the main locus of poverty. with barely % of the world's population, they account for % of the people living below us$ . per day at global level, and nearly % of those living on less than us$ . per day. mitigating the adverse effects of this dire global situation hinges on four policy priorities. first, the international community must support developing countries in mobilizing adequate resources to allow their health systems to cope with the emergency, while effectively assisting vulnerable segments of the population and small businesses. second, containing the social costs of the pandemic requires averting further damage, be it as a result of balance of payment crises, of food price hikes in net-importing countries, or of debt vulnerabilities. this calls for concerted action to provide adequate international liquidity, adopt a comprehensive debts standstill arrangement, and, where appropriate, extend renewed debt relief. third, it is crucial to avoid major disruptions to domestic and regional food and agricultural value chains, which would further strain vulnerable households. with the immediate socio-economic impact of the pandemic mainly affecting the urban population, the viability of agriculture is fundamental to preserve livelihoods in rural areas, contain price spikes for staple foods, and limit food import bills at a time when foreign exchange is scarce. fourth, national and international efforts to revitalize the economy should be directed into viable investments to foster structural transformation and spur the transition towards a low-carbon economy, as a key avenue to build resilience, generate employment, and establish/strengthen social protection programmes. needless to say, domestic policies have an important role to play with respect to the roll out of countercyclical macroeconomic policies and assistance programmes, in developed and developing countries alike. yet, the vast global disparity in financial and institutional means, and the lack thereof precisely in countries whose governments are facing more pronounced socio-economic risks, such as ldcs, inevitably call for bolstered international support to avoid an outcome whose socioeconomic costs could be disastrous. measuring poverty around the world all my dreams are shattered": coronavirus 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nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations the study was originally published in unu-wider's working paper series. the author is gratefully indebted to lisa borgatti, junior davis, adrian gauci, marco missaglia, andrew mold, ugo panizza, amelia santos paulino, andy sumner, rolf traeger, gianni vaggi, david vanzetti, and one anonymous referee for their useful comments; the usual caveats apply. the opinions expressed here are exclusively those of the author and do not necessarily reflect the views of the unctad secretariat or its member states. the corresponding author states that there is no conflict of interest. see table . key: cord- - d yloxp authors: tambo, ernest; ugwu, chidiebere e.; guan, yayi; wei, ding; xiao-ning,; xiao-nong, zhou title: china-africa health development initiatives: benefits and implications for shaping innovative and evidence-informed national health policies and programs in sub-saharan african countries date: journal: int j mch aids doi: nan sha: doc_id: cord_uid: d yloxp background and introduction: this review paper examines the growing implications of china’s engagement in shaping innovative national initiatives against infectious diseases and poverty control and elimination in african countries. it seeks to understand the factors and enhancers that can promote mutual and innovative health development initiatives, and those that are necessary in generating reliable and quality data for evidence-based contextual policy, priorities and programs. methods: we examined the china-africa health cooperation in supporting global health agenda on infectious diseases such as malaria, schistosomiasis, ebola, tb, hiv/aids, neglected tropical diseases (ntds) prevention, control and elimination spanning a period of years. we reviewed referenced publications, global support data, and extensive sources related to and other emerging epidemics and infectious diseases of poverty, programs and interventions, health systems development issues, challenges, opportunities and investments. published literature in pubmed, scopus, google scholar, books and web-based peer-reviewed journal articles, government annual reports were assessed from the first forum on china-africa cooperation (focac) in november to december third ministerial conferences. results: our findings highlight current shared public health challenges and emphasize the need to nurture, develop and establish effective, functional and sustainable health systems capacity to detect and respond to all public health threats and epidemic burdens, evidence-based programs and quality care outcomes. china’s significant health diplomacy emphasizes the importance of health financing in establishing health development commitment and investment in improving the gains and opportunities, importantly efficiency and value health priorities and planning. conclusions and global health implications: strengthening china-africa health development agenda towards collective commitment and investment in quality care delivery, effective programs coverage and efficiency, preparedness and emergency response is needed in transforming african health information systems, and local health governance structures and management in emerging epidemics. furthermore, innovative evidence of operational joint solutions and strategies are critical in advancing healthcare delivery, and further enhancing universal health care, and sustainable development goals to attain global health improvements and economic prosperity. in a rapidly globalizing world with increasing health and epidemiologic transitions, the international community and multilateralism have become highly active, coordinated and robust. the effectiveness of these initiatives depends on the effectiveness of regional and international cooperation on health challenges and issues. [ ] there are, however, little substantive information and knowledge gaps on how international cooperation and activities can best be used as tools for the management of global health and attainment of sustainable development goals (sdgs). [ , ] china-africa heath development initiatives is timely to address public health and health research gaps, south-south health development platforms and cooperation in shaping innovative national health evidence policies, priorities, programs and benefits in developing countries. international bilateral or multilateral cooperation on health development has been evolving rapidly since the late twentieth century to meet the increasing needs of vulnerable populations, moving forward effective universal health coverage (uhc) and sdgs. [ , ] in addition, to face the challenges of health and epidemiologic transitions, ageing and globalization challenges, collaborative diplomacy on health security have become more vital than ever in not only saving lives and improving public health but also in improving and providing long lasting benefits to both world's poorest and developed countries. at the same time, however, the rising concern on response and funding from international health actors (who, world bank, un/undp, etc.) remains challenging and requires more efforts and collaboration in harmonizing multilateral efforts and timely actions in emergencies situations. [ , ] while the news have often reported on the growth of chinese involvement in africa, there has been very little literature on its effects on public health. there is a need for deeper analysis on china's cooperation and efforts at improving public health large-scale development in africa. there are no statistics showing declines in mortality or disease burden. furthermore, it's still unclear exactly how the chinese approach differs from the western approach, as the difference between the "horizontal" and "vertical" approaches are never described practically or operationally. [ , , ] moreover, there is an urgent need to understand factors that can promote mutual and beneficial health development initiatives. [ , ] the growing trend and quest for chinese multilateral cooperation is increasingly paramount and imperative in tackling the persistent global financial crisis, reducing mass unemployment, and revamping the public burden of infectious diseases of poverty. [ , ] strategic and timely china-africa health development cooperation is much needed in training and capacity development, exchanges, technical assistance and technology transfer. also, strengthening health systems in scaling up health and medical skills transfer to achieve universal coverage, health equity and overall long-term benefits of improved quality healthcare delivery towards sustainable national development and growth. [ , , ] reciprocally, to support china in meeting up with the growing demand on natural resources and citizenry needs, international laws and declarations are critical areas for international cooperation. the current political environment and commitment to address health problems has created unprecedented opportunities for bilateral health cooperation. [ , ] furthermore, as china has become an increasingly important part of global health over the past decades, interest in china's international health cooperation has increased among public health professionals internationally and in china. [ , , ] thus, this systematic analysis of china-africa cooperation is timely in leveraging on infectious diseases and poverty alleviation health experiences and lessons learned in reshaping strategic health diplomacy formulation and enhancing successful approaches in health programs and networks in africa. [ , ] the importance of international, multilateral cooperation for health and disease prevention and control has been recognized as a vital approach and instrument in global health agenda. however, there is a dearth of literature on the potential impact of china strategic diplomacy and policy approaches on the global health inter-dependence, focusing mainly on aspects of existing and emerging threats from disease prevention and control to elimination programs and strategies. [ , ] few scholarly publications have paid attention to the behavior and politics of global actors. primarily, how china-africa health development will shape the global health priorities cooperation and collaboration requires further investigation. [ ] [ ] [ ] [ ] in china, there exists a few articles regarding international cooperation on health concerns aspects of social science. [ , , ] to address the operational and translation research to health policy and practice gaps, challenges and opportunities, more systematic analyses might be required in further understanding the importance of strategic and comprehensive engagement. [ , , ] jointly and mutually beneficial africa-china heath development initiatives could be the turning point for collaborative support and research projects, resource sharing and analysis for new public health policy dimensions and strategic impact. programmatic and robust partnerships are paramount in fostering context health and sustainable public health innovations for health information for all generations. it will, in turn, impact on communities and populations, fostering efficient and effective global health initiatives towards enhanced economic trade, growth and stability, promoting the course of human rights and equity, reinforcement of environmental and wildlife protection and regulations, access and use of health services and medical commodities in achieving uhc and mainstreaming of the sdgs. [ , ] this review paper examines the implications of china engagement in global health initiatives in africa particularly as it relates to the benefits in health systems strengthening and innovations, emerging epidemics and infectious diseases of poverty initiatives prevention, control and elimination. it seeks an understanding of the drivers and operational enhancers that can promote innovative health development initiatives necessary for reliable and quality data for evidencebased contextual policy, priorities and programs of global health impact. a systematic literature review examined chinese international health cooperation and global health agenda on infectious diseases prevention, control and elimination. in particular, challenges and opportunities related to ebola and other emerging epidemics as well as health systems development issues, global health investment and support were reviewed. referenced publications and extensive sources of data include books, pubmed, scopus, and google scholar and webbased peers reviewed journal articles, government annual reports and conference proceedings, policy reports and conference papers. the books reviewed were related to health, public policy and international cooperation. the journal articles concern all of this paper's research areas since the first forum on china-africa cooperation (focac) and the third ministerial conference from november, to december, . government documents came from the china-africa partnership members, related countries' government agencies (e.g. ministry of health) and other international agencies and organizations, such as global fund, world health organization (who), the world bank and the united nations (un). [ , ] all review materials were published, and experts 'reports were assessed. published papers on chinese foreign diplomacy and policy reports and previous chinese literature in relation to infectious diseases prevention and control and elimination programs, research and funding were reviewed to trace international health cooperation actions, information communication and strategies including forum on china-africa cooperation (focac) declarations on health development in and in beijing and cape town respectively. [ , ] furthermore, screened abstracts of the citations were identified for potentially relevant studies and full text documents were obtained for relevant publications. the articles were scrutinized to ensure that multiple publications from the same study related to trade and commerce, socio-economic, science and technology transfer were excluded. this systematic literature search which identified unique records were reviewed and records were excluded based on review of the title and abstract. overall, full publications and reports met the inclusion criteria and were analyzed ( figure ). www.mchandaids.org | © global health and education projects, inc. china-africa engagement represents a comprehensive view of the relationship at maintaining the momentum of high-level exchanges, mutual trust and practical cooperation in acknowledging the efforts and contributions made by china to support africa's peaceful and stable development. the year undoubtedly marked a milestone in sino-african relations, maintaining china's tradition in diplomacy by promoting special consultation in support of the south-south cooperation, sino-african trade and commerce bloc and intergovernmental authority on development (igad). the paradigm shift in the chinese global health is one of the most important geopolitical cooperation of our time. china's initiative at promoting peace and social justice enhanced the pace of chinese participation in helping african countries resolve conflicts. hence, the chinese government continues to work and support the international partnership and collaboration with african union in safeguarding peace and stability in africa, promoting the development of africa, and advancing the integration process of africa. the forum on china-africa cooperation (focac), continues to deepen the new type of china-africa strategic partnership by advancing economic and trade cooperation, and actively exploring a common path that reflects both china's and africa's realities in reducing the major causes of emerging threats and diseases in these countries. our findings showed that in the last two decades ( - ), the focac has been targeted at promoting win-win mutual aid under the multilateral framework, thus strengthening cooperation in health, agriculture and food security. focac has also improved the level of investment and finance cooperation, by supporting africa's infrastructure construction needs and capacity building in attaining uhc, from millennium development goals (mdgs) to attaining sdgs through china-africa "one health" strategy. for example, the west africa's ebola outbreak that affected sierra leone, liberia and guinea witnessed the importance of china partnership in fighting ebola, and the needs for economic and social reconstruction in the post-ebola period. the chinese government worked with international community, humanitarian agencies and frontline non-governmental organizations including african countries to contain and control ebola epidemics in west africa. compared to other developed countries, china provided a robust technical and non-technical assistance to countries in and around the affected west africa sub-region valued at about $ million (usd), and pledged an extra $ million (usd) to the un response multi-partner trust fund to support recovery and rehabilitation process of the affected countries. in addition, china also provided logistics in major affected provinces, including the supply and free distribution of ebola protection kits, mobile laboratory testing vehicles and building new national ebola research laboratories. also skills development of over , health workers and health professional were improved through training and capacity development. there was also post-ebola recovery and reconstruction plans and assistance in social and economic development projects in the most affected countries namely guinea, liberia and sierra leone. the china-africa relations has grown into a new development era with major pillars such as political equality and mutual trust, promoting win-win collaboration, mutually enriching cultural exchanges, mutual joint health projects, public safety and security, coordinated china-africa wider range solidarity for economic partnership, cooperative and interestingly, the second ministerial forum of china-africa health development was held in cape town, south africa in october . its theme was promoting the availability of healthcare service in africa in improving china-africa's cooperation in public health in post-ebola era. there were more than participants, including the health ministers of china and over african countries, as well as representatives from the au and international organizations such as the world health organization and unaids. the meeting adopted the cape town declaration and its implementation framework to promote china-africa collaboration in public health. it developed a roadmap for china and african countries to work together to address the key health problems affecting the african continent. the latter johannesburg summit was the second summit since the inception of focac years ago and the first held in africa. the timely conference resulted in upgrading new type of china-africa relationship into a comprehensive strategic and cooperative partnership. as a marked indication of this collaboration, china pledged to provide $ billion (usd) funding support for major china-africa cooperation plans to be implemented in health-related challenges and issues. these ranged from addressing poor access and availability of quality and essential medicines and medical devices, weak health systems and capacity development, lack of entrepreneurship and technology transfer, unreliable and inexistent monitoring and evaluation (m&e) programs/projects. noteworthy, weak regional approach and national sustained health policy reforms, inadequacies in skills and knowledge capabilities to tackle emerging epidemics and infectious diseases with limited resources were documented and should be addressed. the new plans also cover industrialization, agricultural modernization, infrastructure, financial cooperation, green development, trade and investment facilitation, poverty reduction, public health, cultural and people-to-people exchanges, upholding regional peace and security. ten ( ) cooperation plans were based on the blueprints to guide the african union (au) agenda on africa's development in the coming years towards meeting africa's needs and citizenry benefits. their aim will be to address the three bottlenecks holding back africa's development that is: inadequate infrastructure, lack of professional and skilled personnel, and funding shortage. each plan will have chinese financial, technical or material support and will provide a strong development impetus to future china-africa cooperation including africa-china young leaders' forum. strengthening china-africa cooperation in agricultural modernization, agricultural technology transfer and management requires investment in capacity building development at improving complete africa's agricultural production, to food auto-sufficiency value chain and productivity. building up capability is an important way to contribute to food security in africa, and should be given priority in the context of china-africa cooperation projects. the cooperation will enhance agricultural transformation upgrading, increase agricultural production and processing and safeguard food security in africa bearing in mind the prevailing malnutrition and food shortages that directly impact population health. strengthening weak capacity development and health systems is a major priority to tackle the bottlenecks hindering independent and sustainable development of africa. proactive china-africa concrete priorities and measures should be encouraged for chinese and african entrepreneurs, businesses and financial institutions to expand investment through various means, such as public-private partnership (ppp) and build-operate-transfer (bot), to support african flagship projects in african countries. these include, the programme for infrastructure development and the chinese presidential infrastructure championing initiatives in africa, in addition to building railroad, highway, regional aviation, ports, electricity, water supply, information and communication and other infrastructure projects. supporting african countries in establishing transportation facilitating infrastructure connectivity and economic integration in africa. furthermore, china plans to build transnational and trans-regional infrastructure www.mchandaids.org | © global health and education projects, inc. projects to achieve sub-regional connectivity and integration. both parties can combine the national development needs and demand in fostering economically-beneficial projects and drive africa's infrastructure construction in a balanced and orderly manner. adequate planning and coordination of health development initiatives, construction and renovation, and research collaborative networks in particular promoting construction of transnational highway networks has commenced. there is an urgent need to establish joint china-africa bureau for health development initiatives that will enhance coordination and evaluation of projects. likewise, establishing comprehensive human and infrastructure capacity building and transfer of technology is core. furthermore, china-africa businesses investment, construction and operation in africa should be explored. expansion in vaccine production and medical devices, agriculture and water resources, solar, wind and renewable energy, biomass power generation in power transmission and transformation and maintenance should be nurtured. while advancing its own development, china tries to offer what assistance it can to africa without setting any political conditions, and to benefit african people through developmental advances. in recent years, china has implemented measures adopted at the focac ministerial conferences. china has actively developed cooperation with africa in areas relating to public amenities, medical and health care, climate change and environmental protection, humanitarian aid, and other fields. china has also strengthened cultural and educational exchanges and scientific and technological cooperation in an effort to improve africa's ability to develop independently. china has offered assistance to africa in digging wells for water supplies, and in building affordable housing, broadcasting and telecommunications facilities, and cultural and educational sites in an effort to improve the productive and living conditions of local people. since , china has carried out dozens of welldigging projects in the sudan, malawi, zimbabwe, djibouti, guinea and togo, playing a positive role in easing water problems for local people. it has also provided support for the building of portable dwellings in south sudan, schools in benin, and rural schools in malawi, and in doing so, improved local living conditions and educational facilities. china's largest aid project in the central african republic is the construction of the boali no. hydropower station, which, after it was completed , greatly relieved electricity shortages in bangui and surrounding areas with potential usefulness in improving data access and information sharing for public health benefits. supporting cultural and educational exchanges make up an important part of the new type of strategic partnership between china and africa. by supporting young africans studying in china, sending young chinese volunteers to africa and developing joint research initiatives, china tries to promote mutual understanding between china and african countries and strengthening the social foundation of their friendship. holding human resource training programs and courses are important components of capacity building. from to , china held various training courses for countries and regions in africa; the courses involved a total of , officials and technicians, and covered topics relating to economics, foreign affairs, energy, industry, agriculture, forestry, animal husbandry and fishing, medicine and health care, inspection and quarantine, climate change, security, and some other fields. in addition, chinese medical teams, agricultural experts and enterprises located in africa have also trained local people in an effort to enhance local technological capabilities and upgrading china-africa cooperation in science and technology. from to , in advancing cooperation in medical and health care, china helped build hospitals in ghana, zimbabwe and other african countries. china has also sent medical teams to african countries and regions, treating over . million patients. in recent years, in addition to building hospitals, donating drugs and organizing medical training programs, china has also launched an initiative called "brightness or "evidence" action," to treat cataract patients and provided mobile hospitals. china also built bilaterally-run eye centers, and helped build demonstration and training centers for diagnosis and treatment technologies, thereby effectively advancing sino-african cooperation in medical and health care. china also gave african researchers the chance to do post-doctoral research in china and donated , yuan ($ , ) worth of research equipment to each of the researchers who had returned to their home countries to work upon completing their joint research projects in china. chinese aid and investment in africa health development have made substantial contributions to the continent's development over the last years. china-africa health development builds on the existing focac platform to coordinate health research program that aims to advance capacity and technology transfer to cutting-edge research. in advancing access, uptake and utilization of health commodities in tackling china and africa health needs and issues. filling these important gaps and challenges requires collection and production of real-time evidence care development trajectory. investing in priorities health needs, economic and political, scientific and technological development and empowerment inequalities should be addressed through this win-win mutual partnership with institutions and other international stakeholders in line with global health engagement in infectious and emerging diseases and epidemics especially in africa and china. further, this is necessary in strengthening international health commitment and investment towards new model of health bilateral development that is based on equality, accountability, mutual respect that is more balanced, stable, human rights, inclusive and harmonious society. industrialization, diversification of trade, infrastructure development, and regional economic integration are all the right ingredients for africa's sound economic future. however, in the near term, in light of china's own economic slowdown, questions do exist about the implications of china's economic ties with africa and the sustainability. china has implemented "african talents program" to train , african personnel in various sectors, offered , government scholarships, and build cultural and vocational skills training facilities in african countries. china and africa will deepen their cooperation in the health sector, step up high-level exchanges in health-related fields and hold a china-africa high-level health development programs and activities. china will continue to send medical workers to africa, while continuing to run the "brightness action" campaign in africa to provide free treatment for cataract patients. it will also help african countries enhance their capacity building in meteorological infrastructure and forest protection and management of potential threats and disasters. the research capacity of local partners in china-africa relations has reached a new historic level. africa, a continent full of hope and thirst for development, has become one of the world's fastest growing regions, while china, the world's largest developing country, and has maintained forward momentum in its development. with increasing common interests and mutual needs, the two sides have great opportunities to accelerate their economic and trade cooperation. currently, the chinese people are working hard to realize the chinese dream of national revival, while african people are committed to the african dream of gaining strength through unity and achieving development and renewal. with a spirit of mutual respect and win-win cooperation, china will continue to take concrete measures to build a sino-african community of shared destinies featuring all-round, diversified and deep cooperation. it will work to advance china-africa economic and www.mchandaids.org | © global health and education projects, inc. trade cooperation to help both sides make their respective dreams come true. china is also willing to enhance its cooperation with the rest of the world to promote africa's prosperity and development. china and africa should work together to promote the development of the "china-africa joint research centre" project and cooperate in biodiversity protection, prevention and treatment of desertification, sustainable forest management and modern agriculture demonstration. the chinese side will support africa in implementing clean energy and wild life protection projects, environment friendly agricultural projects and smart city construction projects. strengthening china-africa "one health" strategy cooperation through wildlife and environment protection will help african countries to improve their protection and conservation capabilities. there should be more efforts in building environmental capacities in african countries with training opportunities on environmental and ecological conservation. the possibility of cooperating on joint wildlife protection projects against the illegal trade of fauna and flora products, especially by addressing endangered species poaching, deforestation and environment, degradation and climate change impact on the african continent, should be explored. in its first -years of china-africa partnership implementation plans, china and africa share the view that the current development strategies of china-africa partnerships are highly compatible in fostering china centenary goals and africa union (au) agenda. the two sides shall make full use of their comparative advantages to transform and upgrade mutually beneficial cooperation focusing on better quality and higher efficiency to ensure the common prosperity of their peoples. [ , ] joint health research establishment is needed for a comprehensive strategic and cooperative partnership for china-africa mutual trust, win-win results and sustained economic growth. [ , , , [ ] [ ] [ ] health and medical technology capacity building and transfer, exchanges and mutual learning is needed in enhancing chinese and african citizenry, mutual assistance in public health security and safety. promoting healthcare solidarity and cooperation can be very supportive in enhancing national health planning and interventions implementation between china and african countries in international affairs. [ , , , ] moreover, improving and encouraging care delivery strategic mechanisms such as bilateral joint and strategic dialogues, foreign ministries' political consultations, and joint/mixed commissions on economic and trade cooperation is imperative; through exchanges and cooperation between the national people's congress of china and african national parliaments, regional parliaments, the pan-african parliament and the african parliamentary union, to consolidate the traditional medicines integration in china-africa friendship and promoting mutually beneficial cooperation. [ , , , , , ] our findings documented that china's commitment to continuously support africa in many areas include agriculture and health sector, trade and commerce, science and technology projects implementation. these included construction of regional and community hospitals and treatment centers, infrastructures and facilities to fight infectious diseases, support by chinese medical care delivery teams and improve capacities to respond to public health and sanitary crises throughout africa including dr congo, cameroon, togo, ivory coast, angola, namibia, mozambique, sudan, algeria, south africa, zambia, egypt, nigeria, ghana, liberia, guinea and sierra leone. these equipped ultramodern infrastructure and facilities investment include emergency, resuscitation, pediatrics, surgery, obstetric and gynecology, medical imaging, and related technical units worth billions of us dollars (figure ). these joint efforts are positive milestones to strengthen intercontinental cooperation in view of attaining a sustainable impact in achieving universal health coverage and access to basic medicine. in particular, accelerating the fight against hiv/aids, tb, malaria, schistosomiasis, maternal-child health, reproductive health and improving universal immunization coverage against vaccine preventable diseases across africa. [ ] [ ] [ ] [ ] chinese comprehensive and pragmatic efforts was once again documented when the chinese government immediately offered emergency relief to the three west african countries most affected by ebola and to their neighboring countries of ghana, mali, togo, benin, drc, the republic of congo, nigeria, cote d'ivoire, senegal and guinea-bissau. with the situation turning more serious and based on the needs of epidemic regions, china later announced three consecutive rounds of assistance. china has also promised that in so far as ebola persists in africa, her assistance will not stop. [ , , , , ] china stood shoulder-to-shoulder with the african people in fighting ebola to the final victory of global disease free generations. west africa ebola epidemics - led to net losses of $ . billion us dollars in the three most affected countries (liberia, sierra leone, guinea) in terms of gross domestic products (gdp). as these countries embark on recovery and reconstruction, china has promised assistance in health systems strengthening, capacity building, health infrastructures and equipment support, amongst others. [ , , , ] the urgent need for data and information sharing, material and technical transfer cannot be over emphasized in improving public health and medical resources access through mutual commitments and support. promoting health data and information sharing, educational exchanges and capacity development to support the establishment of robust infectious diseases surveillance-response systems in african countries and all remote provinces/cities is imperative in institutionalization of china-africa forum on cooperation between provinces or local governments. [ , , , , ] the china-africa development fund "cad-fund" is one of new methods for china-african new strategic partnership, which was fully controlled by the chinese government. cad fund is one of the eight measures which was announced by chinese government at the beijing summit of the focac in november th , aimed to support chinese companies to develop the cooperation with africa and enter the african market. [ , , ] distinctive characteristics in the capital nature, the business area, and operation mode is continually following the investment philosophy: to build up "bridge linking" and "connection" of the economic and trade cooperation between china and africa; to enhance self-develop capability of africa; to strictly fulfill the investment environment and social responsibility; to promote mutually beneficial and win-win between china and africa by market-oriented operation. [ , , ] cad-fund is a pioneering move in the process of mutual and beneficial china-africa cooperation. it remedied the gap under the traditional model of free aid and loans. with the increasing african countries double public health burden (chronic illnesses and infectious diseases), new investment models and market-oriented economic development and operation should be examined in achieving sustained and healthy dual or self-development. [ , , ] the direct investment is essential. improving people's livelihood for african regions by additional large scale (e.g.: network project) investment to african countries could be beneficial in long terms. [ , ] for instance, the chinese government officially approved the establishment of the cad-fund, with first-phase funding, usd billion, provided by china development bank. cad-fund operated independently based on market economy principles under a standardized corporate governance structure. china development bank (cdb), the shareholder, has a great wealth of experience in project review and management and is backed up with sound expert resources. having invested in five funds and three specialized fund management companies, the bank has developed sophisticated fund management and risk control systems. cdb has accumulated profound experience vis-à-vis investing in africa through its "going global" initiative. [ ] [ ] [ ] cdb, by virtue of its overall resources and advantages, will provide a high level of professional support. again, on the investment side, the ministry of commerce revealed that china's direct investment in africa stood at $ . billion (usd) in the first half of , falling over percent year on year. the downturn is attributed to the sluggish global economic recovery, international commodity fluctuations, and the ebola outbreaks. [ , , ] globalization and global health initiatives on infectious diseases of poverty associated consequences have shown the world is closely linked as emerging threats and epidemics of infectious diseases can strike anywhere at any time irrespective of race, religion and financial capacity of the country. these have precipitated growing opportunities in internationalization of south-south and south-north health cooperation in changing outcomes. [ , ] the advances in technological development and increases in global interconnections are increasingly being utilized inexpensive and prompt health information communication diffusion broadly and interdependence between different people, regions and continent benefits. [ , ] improvements in communication and information technologies has enabled international responses to health threats and disaster crisis more rapidly and in a coordinated fashion, [ ] bringing about greater sharing of information and increasing international interactions and collaboration. [ ] globalization requires increasing cooperation among countries to ensure the stability and security of the global system, a reason why implementation of international agreements and joint declarations has become important. [ , ] for instance, industrial demand and globalization coupled with intense urbanization have been generating new ecological, climate and environmental threats and associated consequences beyond local, regional boundaries and worldwide. these consequences and issues have raised the need for international cooperation and foreign assistance agreements either as direct delivery of services, capacity transfer or implementation of health interventions such as the global fund to fight aids, tuberculosis and malaria. [ , , , ] in today's more interdependent world, international cooperation, which involves the interaction of countries, international organizations and non-government actors, shapes values, policies and rules. as globalization continues to widen the gaps, development and implementation of comprehensive health models between developing and developed nations, the interest in global health partnership and foreign assistance effectiveness has grown in importance at improving funding on health systems priorities including scaling up access to essential medicines and service delivery, universal health coverage and building new primary healthcare facilities. [ , , , ] international mutual cooperation and aid is one of the most effective weapons in reshaping and transforming regional and national health capabilities which benefits through provision of global public goods, infectious disease control and alleviation of poverty. [ , ] the widespread influence of globalization has increased the need for international cooperation to address emerging opportunities for and threats to global health in improving the health status of populations in developing nations. [ , ] as of november , the majority of african exports to china remains in natural resources. according to the statistics by chinese customs, crude oil, iron ore, diamonds, and agricultural products together accounted for . percent of chinese imports from africa during the first three quarters of . and this number is on the low end because china's demand for raw materials has been suppressed by its economic slowdown this year. in this sense, china's intention of downplaying the importance of natural resources in sino-africa trade in its policy manifestation is clear, given the mutually understandable winwin image associated with sino-africa economic relations aspirations. china's international health development cooperation initiatives since the s, health privatization and reforms expectations and outcomes from international coalitions were formed to address the heavy global challenges, including national burden of infectious diseases, poverty and inequality. with the global funds support from early , the vertical approach to funding and aid has been gradually shifting to a horizontal approach and from mere bilateral efforts to multilateral organizations, local and international ngos, aimed at reshaping major funding, cooperation, new alliances and networks. [ , ] furthermore, boosting provision of aid or humanitarian assistance paradigm shift from a small-scale task plan to large multiple programs financial support projects and programs. multifaceted nature and complexity of health and the multi-sectorial interactions that influence it have induced an increasing number of organizations to become active in the health field. [ , ] broad-ranging partnerships are increasingly being set up to target specific health problems. [ , ] for example, to achieve roll back malaria or polio eradication a global partnership was formed with, among others, ministries of health in polio-endemic countries, rotary international, united nations children's fund (unicef), the governments of australia, canada, denmark, japan, the united kingdom and the united states. reciprocally, from to , the eu contributed € . million to hiv/aids prevention in china, setting up six provincial level regional training centers to provide technical assistance to medical personnel in hiv/aids prevention. [ , ] this collaborative support is advantageous for capacity building, educational exchanges between institutions of all levels and dual technology transfer. such efforts have been reported between china and the united kingdom (uk), the us, and australia in research and development and helpful in solving health issues and developmental challenges including climate changes and globalization of trade and travel. [ , , ] previously, the establishment of cooperation between china and other countries has been done through the signing of agreements and regular corporate communication. contemporary advances in implementation mechanisms are performed by joint engagement and participation in mutual win-win partnership and joint health programs funding or investment seeking based on local and national priorities and real time field interventions. [ , ] furthermore, china has dispatched more than medical teams and more than , medical personnel to african countries. chinese governments highly valued and appraised local people and the team's devotion, willingly and generosity in providing medical services, training and technical assistance, in strengthening health systems development through focac partnership. [ , , ] in contrast to previous international vertical health approach, chinese horizontal approach and process (people-people approach and relations) has been appraised in responding to the need of the populations. there is an urgent need for reliable and effective evidence in strengthening health systems development including constructing health care facilities, providing medicines and medical equipment, improving more targeted care access and utilization require contextual and scalable community-based programs and activities beneficial to both chinese and african citizenry. [ , , , , ] china's importance in sustainable development and global health goals, is aimed not only in fighting poverty and health inequality among the world's people, but in enhancing opportunities to live a free, healthy and fulfilled life. [ , , ] achieving health for all remains an important component of sdg targets and requires reducing national public health burden of infectious diseases of poverty. addressing knowledge gaps between the developing and developed countries require innovative international and multilateral cooperation with priorities on significant infectious diseases, emerging epidemics, the rise of obesity related cardiometabolic and other www.mchandaids.org | © global health and education projects, inc. chronic diseases. the mdgs, adopted and supported after the millennium summit of the united nations in september , provided a substantial progress in the reduction of poverty and marked improvements in infectious diseases and some neglected tropical diseases in most endemic countries through the global funds. it also offered other bilateral aid to the poorest and vulnerable populations worldwide by improving maternal health, reducing child mortality, while combating hiv/aids, malaria and other diseases. [ , , , [ ] [ ] [ ] attaining the sdgs and health for all by depends primarily on national efforts supported by domestic and regional public-private partnerships and global strategy of increasing access of the world's poor to essential health services. it also depends on support from international multilateral cooperation and collaboration within countries. [ , , ] further efforts should be devoted at reducing inequality and poverty in health aimed at accelerating progress towards the sdgs and should be a pubic priority. it is worth mentioning that there is still disproportionate health disparity between developing and developed countries. [ , ] for example children life expectancy chances are dramatically different depending on where they are born. in china life expectancy is longer than in african countries due to premature mortality ratio associated with malaria, tuberculosis and hiv/aids as well as chronic infections, mainly maternal-child and elderly healthcare delivery. [ , , , ] china's global solidarity and partnership support from national income and resources could be a role model on how to assist and work a win-win bilateral collaborative network, technical assistance during threats and epidemics disaster crisis for the safe of humanity, environment and ecosystem. china health expenditure increased more than fold and accounted for . % of the gross domestic product (gdp) in . [ , , ] who supported by other governments continues to provide necessary technical and financial support to china through renewed strategic cooperation agenda on transfer of know-how and skills to africa in tackling infectious diseases control towards elimination. [ , , , ] chinese cooperation is aimed at achieving global health responsibility, which entails strengthening health systems, improving universal health coverage and reducing morbidity and mortality from major infectious diseases of poverty. such recent efforts in the field of public health include multiple partnerships between the national institute for parasitic diseases (nipd), shanghai with several african institutions and universities in the areas of capacity development and training, technology transfer and exchanges coordination and leadership. [ , , ] most importantly, is the implementation of malaria and schistosomiasis elimination networks across africa (e.g., tanzania, zanzibar, sudan). [ , ] lessons learned and technical assistance from chinese researchers, ongoing consultation on strategic partnership could be very important in strengthening joint malaria and schistosomiasis projects network with sudan, cameroon, zimbabwe, south africa and mali are substantial opportunities. in addition, provision of technical support and colossal solidarity supply of personal protective equipment (ppe) in sierra leone, liberia and guinea were of tremendous assistance both to humanitarian frontline organizations as well as chinese teams and local community health benefits in west africa ebola containments and community rehabilitation. for example, china provides funding and technology, while who guides technical support and coordination. [ , , ] furthermore, in , the chinese government assisted in , to develop and implement strategic plans on snail control and elimination of schistosomiasis. it should be recalled that chinese experts have provide technical assistance to pakistan, nepal, lao, myanmar, vietnam, nigeria, tanzania, angola and namibia to assist in global polio eradication and global fund for malaria and hiv/aids and tuberculosis (gfmat) efforts. [ , , ] china is also reducing inequalities in health and contributing to strengthening global health through supporting collaboration in the global health arena. china is strengthening national and regional priorities in line with international health regulations (ihr) ( ), strengthening the asia pacific strategy for emerging diseases (apsed) network, global schistosomiasis alliance (gsa) to arboviralnet. [ , [ ] [ ] [ ] [ ] this will enhance capacity in health security and diplomatic power to create maneuver space for international multi-polar geopolitics and financial systems. china has become a giant economic power and vital component of the international commodity chain, allowing for more effective broad-based consultation and participation on global health issues and international finance via different channels by active support of multilateral diplomacy and politics. [ , , , ] the first world bank trust fund to end poverty was established in promoting growing china's interest and role in global health development, and china's health reforms leadership in reducing poverty and strengthening both health systems resource and infrastructure investment. [ ] this is essential in embracing and upholding performance-based to outcome-based financing in partners countries. some good examples of chinese initiatives in global health need further assessment including the use the new partnership in optimizing institutional governance, organizational structure, social and environmental benefits towards social cohesion, healthy life and living, wellbeing of all citizens and sustainable development at all levels. [ , , , , , , ] integration of china multilateral policies in projects and programs will be a tremendous boost with the increasingly geographic expansion and spread of emerging epidemics and climate changes impacts on global health concern. proactive china-africa leadership commitment and investment is needed in addressing in tie-bound manner evolving local or global threats and emergency situations in endangering collective health initiatives in upholding international health regulations (ihr). [ ] [ ] [ ] the sudden emergence in of severe acute respiratory syndrome (sars) in china was a vivid example of how international health cooperation in the future depends on a better appreciation of the meaning of modernization, as interpreted by each country, and recognition that modernization itself is a complexity of many factors. [ , ] future multilateral cooperation will be influenced by strategic innovative multi-sectoral partnerships, health programming and resource mobilization, bilateral to multilateral governance systems, creation of enabling institutional space, effectiveness and outcomes impact. new and advanced health diplomacy, and foreign health policy in public health systems is an important point of entry and worth pursuing by the joint china and africa interests and values. [ , , , ] health as an instrument of foreign diplomacy and policy presents several mutual gains both for community and its populations' protection. safety and security are health priorities that can be improved through further public health development cooperation. international multilateralism in health development under china-africa partnership holds great promise in increasing opportunities and businesses and diminishing traditional unilateralism over time. [ ] [ ] [ ] nurturing sustainable joint institutional projects that promote community-based programs could be vital for active engagement in policy discourse, participation and community empowerment. the un's sustainable development policy functions and goals coordination will be overtaken by global partnerships or other agencies to develop new international health norms and standards. [ , , , , , ] ultimately, the quality and effectiveness of china-africa health development initiatives and programs, when channeled through government and institutions partnerships, have the potential strengths in improving good governance and accountability in global health security. [ , [ ] [ ] [ ] [ ] china's economic importance in improving china-africa health development initiatives in strengthening contextual health priorities and programs is imperative. fostering china-africa innovative evidence-based national health policies and health operational joint solutions and strategies is critical in advancing healthcare delivery access to, availability and effective implementation. moreover, in shaping programs and interventions benefits in further improving uhc, sdgs in attaining global health and economic prosperity in africa. ethical considerations: this paper was based on the review of existing and publicly-available information. conflict of interest: the authors advances in addressing technical challenges of point-of-care diagnostics in resourcelimited settings. expert review of molecular diagnostics china's engagement in global health governance: a critical analysis of china's assistance to the health sector of africa the dragons' gift: the real story of 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evolution and chinese definition of global health considerations when disseminating american-developed, evidence-based health promotion programs in china china engages global health governance: processes and dilemmas an appeal to the global health community for a tripartite innovation: an «essential diagnostics list china's engagement in global health governance: a critical analysis of china's assistance to the health sector of africa the political origins of health inequity: the perspective of the youth commission on global governance for health china's distinctive engagement in global health ground-truthing" chinese development finance in africa china's provincial diplomacy to africa: applications to health cooperation key: cord- -yw uqfw authors: amadasun, solomon title: covid- palaver: ending rights violations of vulnerable groups in africa date: - - journal: world dev doi: . /j.worlddev. . sha: doc_id: cord_uid: yw uqfw this letter amplifies the rising spate of human rights violations exacerbated by the covid- pandemic in africa. it notes that while governments in the region have declared restrictions on social gathering, in a bid to curtail the deadly disease, violations of human rights of vulnerable groups by state security operatives are on the increase. it argues that the underlying rationale for such abuses emanates from the dearth of a rights-based approach to police-public relations combined with inadequate public health and social care infrastructures for large sections of the populace. policy implications are drawn out while suggestions are offered to social work professionals given their longstanding commitment to national security and national development. today, more than ever before, state political structures are premised on contractual agreements between the governing class and the governed. social contract theorists have long spoke about commensurate relations among the ruling class and the followers in which the former, via the ballot, determines the outcome of policy-making. from idealism to pragmatism (haack, ) , such contractual principle-under the auspices of a democratic architecture-have now become a normative venture across political dispensations and transitions in many regions of the world, including africa. with a history of colonialism and chequered but corrupt civilian rule, as well as tyrannical military regimes; many african countries have now successfully overcome these dark past through the enthronement of a relatively stable democratic structure in the polity. currently, with a minimum of more than a decade experience of democratic governance, does it portend an uphill task to anticipate a decline in human rights violations, typified by the highhandedness of law enforcement officials? since human rights reflects an integral aspect of democratic rule, how long will it have to take to become institutionalized in africa especially given that many state officials are quick to announce the entrenchment of democracy in their respective countries to the rest of the world? at about the time when these state-sponsored rhetoric was beginning to gain traction in global human rights discourses (amadasun, c) , the covid- pandemic has irrevocably shed light on the double standards and despotic dispositions of many african leaders. across the region, there are reported cases of violence against citizens by security forces who were deployed to enforce curfews and lockdowns (un, a; france , ) . suffice to say that such rights violations are not a matter of an isolated case since deaths and injuries resulting directly from these excessive use of force have been reported in many african countries including nigeria (human rights watch, ; afp, ; khalid, ), zimbabwe (ndangana, ) , kenya (odhiambo, ) , and south africa (siviwe, ; kunene, ) . pointedly, reports emerging from nigeria-africa's largest population and economy-indicate that more than one hundred cases of rights violations, resulting in eighteen deaths, have occurred between march and april alone (human rights watch, ). beyond this, gender-based violence have intensified in countries where promulgation of shutdown or stay-at-home orders have been implemented (un, b; odhiambo, ; beech, ) . in a strict sense, this comes as no surprise as prior evidence suggests that public health emergencies can exacerbate multiple forms of violence that women and girls already contend with (unicef, ) . again, if we expand on human rights to include social and economic rights which prioritizes access to pivotal healthcare services, then children's rights are equally being denied on a frightening scale (unicef, ). this situation is warrantless and poses legitimate concerns to social policy response and social work professionals (amadasun, a (amadasun, , b . in addition to the desirability of social justice, social policy response must address root causes that heightens the vulnerability of people to abuses. as have been noted, people who are most susceptible to abuses are those at the fringe of society (amadasun, c; amadasun and omorogiuwa, ) . in this regard, instituting framework for the retraining for law enforcement agents and which should address their compliance level, and that provides feedback from the citizens is cardinal to preventing and stymying future rights violations, and restoring trust among the public and security officials. on the other hand, providing accountable leadership that prioritizes investments in pivotal healthcare infrastructure and social protection programmes is a policy imperative. on their part, social work professionals-given their longstanding insistence on social justice and respect for human rights (amadasun, a) can form alliance with african human rights commission to challenge human rights abuses across the continent. this could be achieved through active involvement in policy practice and advocacy, from where they can lobby with policymakers. also, since human rights is a universal principle, social workers (through their national bodies) and other key stakeholders can liaise with regional and international voluntary, statutory, and/or quasi-government actors to call to order african leaders who directly or subtly abets violators. taken together, by instilling a rights-based consciousness among security officials (through seminars, workshops, and symposia, for instance), enlightening the public of their fundamental human rights (through the mass media), and promoting investments in public health and social infrastructures, the trenchant curve of human right violations of undervalued groups in africa may become flattened. the youngest democracy in africa is tunisia, and the country's path to democratic rule began in , following the self-immolation of mohammed bouazizi when the country's police-state tried to confiscate his vegetable cart. many african government, directly and indirectly, supports human rights abuses on their citizens either through their actions that openly gives moral to security operatives to continue the dastard acts or through their inactions which is construed as approval by law enforcement officials. kicking against violations connote calling out violators, at the minimum, in the stead of keeping mum. social work for social development in africa social work and covid- pandemic: an action call covid- pandemic in africa: what lessons for social work education and practice? sage submissions coronavirus and social work: blueprint to holistic intervention the covid- pandemic could have huge knock-on effects on women's health security forces use violent tactics to enforce africa's coronavirus shutdowns the pragmatist theory of truth coronavirus: security forces kill more nigerians than covid- south africa lockdown: they are riding around the country hunting the poor and vulnerable zadhr condemns human rights violations during lockdown tackling kenya's domestic violence amid covid- crisis: lockdown measures increase risks for women and girls south africans urged to 'respect human rights' amid covid- pandemic un raises alarm about police brutality in covid- lockdowns women: covid- and ending violence against women and girls gbv in emergencies: emergency responses to public health outbreaks children in the democratic republic of the congo at risk from killer measles, cholera epidemics: covid- latest challenge facing battered health services international human rights law in africa key: cord- -jlrzu wl authors: ayanlade, ayansina; radeny, maren title: covid- and food security in sub-saharan africa: implications of lockdown during agricultural planting seasons date: - - journal: npj sci food doi: . /s - - - sha: doc_id: cord_uid: jlrzu wl covid- pandemic movement restrictions as part of the control measures put in place by countries in sub-saharan africa (ssa) has implications on food security, as movement restrictions coincided with planting periods for most of the staple crops. the measures are affecting important staple crops in ssa, and are likely to exacerbate food security challenges in many countries. achieving adequate food supply in ssa requires developing better policies and packages to confronting the challenge of reducing hunger post covid- pandemic. the lessons learned after covid- crisis will be very important for african countries to rethink their strategies and policies for sustainable economic growth, as covid- many have significant impacts on all sectors of their economies. sub-saharan africa (ssa) is one of the most vulnerable regions to the social and economic impacts of covid- . vulnerability of ssa is attributed to several factors including; poor health facilities in many ssa countries and low capacity for testing, timely detection and response to covid- cases , . in particular, the initial movement restrictions (complete and partial lockdown) imposed by countries coincided with the planting periods (important in the agricultural calendar) for most of the staple crops in the region. ssa accounts for nearly % of the population globally, with the proportion of the population living in poverty and undernourished remains high among the rural communities . agriculture remains the main source of livelihood , and food security for majority of the rural population in ssa, with the climatic conditions favouring cultivation of diverse crops. agricultural production is mainly rainfed, with pockets of irrigated land. for example, western africa accounts for more than % agricultural output from the ssa, over the past years, but land degradation and climate change are now posing additional threats to agriculture [ ] [ ] [ ] . in terms of agricultural sector spending, less than % of the ssa countries have achieved their commitments as per the malabo declaration on accelerated agricultural growth and transformation and the comprehensive africa agriculture development programme (caadp) and the situation is likely to worsen with the covid- movement restrictions put in place by african countries. the movement restriction measures adds to the hardships and challenges faced by nearly . billion people in africa , especially those working in the informal sector, the larger percentage of these people rely on daily wages and are living in poverty, with less than one dollar a day . in particular, the months of march and april are the planting periods for some of the important staple crops in ssa and very significant in the cropping calendar, though there is temporal and spatial variability in planting time [ ] [ ] [ ] . many of the crops in ssa are cultivated under rain-fed conditions, thus the timing of the planting is very important and delay in planting during these months as may have been experienced as a result of the movement restrictions may significantly affect crop growth and lead to food shortage for the year. while planting periods vary by agro-ecological zones and determined by climate, they have the potential to affect agricultural production in ssa . currently, the potential impacts of covid- crisis on agriculture in ssa are unclear, including potential impacts on the agricultural value chain. what is obvious at present is that covid- is disrupting activities of farming communities, with potential negative impacts on agricultural production. over % of the households in ssa are mainly smallholder farmers, many are poor and vulnerable. thus, many african governments have developed some measures to help vulnerable households during the covid- lockdown. such measures include distribution of grains to vulnerable households, especially the poor households. the measures among others are aimed at meeting the urgent immediate food needs of the population. however, many farmers do not have access to critical inputs during the lockdown; this will have a negative impact on agricultural production. consequently, the covid- crisis may have potential negative impacts on food security in ssa countries. this paper examines the potential impacts of covid- movement restrictions on food security in ssa, focusing on the effects on planting days (season) for major staple crops, including effects through restricted access to important farm inputs. we examine the potential impacts of movement restrictions on planting dates of rice and maize in major producing countries in ssa (fig. ). rice and maize are widely cultivated crops for food and income, as they have a high market potential in ssa countries. both rice and maize are now fastest-growing staples food crops in africa , though there are problems of pathogens and pests on major food crops in the region . among the cereal crops produced, maize and rice have severe implications for economic development in most ssa countries, as their contribution to agricultural gdp is high. over the past decades, these crops have become important in the diets of many people in ssa. in recent years, african governments have developed initiatives to enhance rice cultivation and increase the production capacity of local farmers, especially in smallholder systems. as indicated in previous section, agricultural production systems in many ssa countries are mainly rain-fed. following the timely onset of seasonal rains, march to mid-april is the preferred planting period for many rice and maize farmers in ssa (fig. ) . the data for planting period used in this study were sourced from the crop statistics recorded by fao-faostat, while covid- data were collected from the africa cdc ( ) . there are regional differences in the relative crops' planting date and this reflects agro-ecological, climatic and cultural diversity. what is the hope for ample yield of rice hereafter covid- lockdown? production and supply of rice and maize in many ssa countries are expected to substantially decline due to projected global recession and higher transaction costs, as combined effects of covid- lockdown. maize and rice are important in the continent as the major staple crops for most ssa countries . while crop production practices in africa are diverse, what is clear is that in most cases the local production does not adequately meet the demand of the ever-increasing population. in recent years, nigeria is the largest rice-producing country in africa. the major drivers for the increase in rice production in recent years, in some ssa countries, are very clear. in nigeria, for example, expansion of rice production is as a result of government efforts in enhancing agrarian production in the country, with nearly % of the nigerian states engaging in rice cultivation. in eastern africa, increasing crop production and productivity is a top priority for economic development in kenya and tanzania. these countries are the main rice producers in east africa. despite the increase in rice crop production in recent years, many ssa countries still import rice and the countries majorly earn their total foreign exchange revenue from agriculture. the majority of the rice produced in ssa countries are consumed locally but the consumption rises by about % annually [ ] [ ] [ ] [ ] [ ] . despite being major staple crop in africa, studies have shown that the local rice production and yields are very low compared to other parts of the world, partly attributed to the fact that rice is mainly grown by smallholder farmers in many african countries , . for many african countries, the planting periods for rice and maize is usually in march to mid-april, a period overlapped with covid- movement restrictions (fig. ) . reports indicate that rice importation fluctuated substantially in recent years, still the demand for rice consumption in africa has surpassed the local production capacities and the covid- crisis, however, may add to this scenario in . overall, the lessons learned post covid- crisis will be very important for african countries to rethink their strategies and policies for sustainable economic growth, as covid- may have significant impacts on all sectors of the economies. the movement restrictions put in to reduce the spread of covid- period affect labour mobility and availability, especially for the predominantly labour-intensive agricultural production in ssa. the agricultural sector employs % of the total workforce in the region, making it the most important sector for livelihoods and economic development . the planting period is the period with the peak labour demand in the agricultural calendar . low labour supply or labour shortage, has significant implications on food security and the economy is likely to be severely negatively impacted . most of the countries in ssa implemented some form of border closure during the planting month of maize and rice, and this also prolonged the start of the harvest period ( figs. and ) . the data for the crop harvesting periods, used in this study, were sourced from the crop statistics recorded by fao. the crop statistics records of production quantities are available in http:// www.fao.org/agriculture/seed/cropcalendar/welcome.do; while the data on harvesting periods were collected also from statistics records of fao which are available in http://www.fao.org/faostat/ en/#data/qc/visualize. there is a high probability that the crop harvests will be compromised due to the restriction in movements during the covid- and low labour force. in addition, these measures also affected the supply or access to essential farm inputs such as fertilizers and pesticides. as labour shortages are imminent in the ssa, many people that derive their daily wages from farming and non-farm informal sector are therefore, likely to lose their jobs and income, with long-term implications and effects on the economy of the region. while border closures is an important measure to protect citizens, according to who almost all the countries in the ssa are major importers of food. some limited flights were allowed to facilitate the supply of protective and life-saving equipment to affected countries, allowing humanitarian cargo or emergency flights. in most cases, the border closures have led to the shortage of essential food supplies, while the price of the available food significantly increased. in addition, the border closures limit the supply and increase the price of related goods and services, including essential farm inputs such as supply seeds and agrochemicals, pesticides, and fertilizers majority of which are imported by ssa countries , . the long-term implications of border closures for key food commodities such as rice and maize cannot be overstated. the larger proportion of these food crops are still imported in many of ssa, with border closure likely to aggravate africa's fragile economic situation . the majority of the countries in ssa are particularly vulnerable to the covid- pandemic because of over-reliance on food imports (such as rice and maize), with high poverty rates. besides, border closures are likely to have adverse effects on the supply of seeds and agrochemicals, pesticides, and fertilizer as the majority of them are imported to ssa countries . the effects of the covid- pandemic is aggravated not only by border closure, which leads to low importation of food and raw materials, but also by the other environmental problems in the ssa. the most significant environmental challenges for maize and rice production include climate change and variability, pests, and other emerging crop diseases. these environmental challenges have impacts on food security for the region. for the agriculture sector, farmers have experienced change in climate in recent times. the adaptation measures to climate changes include; adjusting farm management practices as well as changing cropping calendars to optimize the use of available water for crop growth, but such changes do have impacts on crop yield for the year . hitherto, climate change has become a key challenge to the economies of different countries in ssa. rain-fed agriculture forms the major activity of livelihood for about % of the population . the variation in climate does not provide a conducive environment for farming as rainfall is the main source of water for the production of crops. with many economies depending on agriculture, most especially the ssa countries, the change affecting agriculture invariably affects the economy of the ssa countries. studies have reported that climate change and variability manifested in changing rainfall patterns and temperature, determines water availability for growth and production of crops with direct effects on crop yields [ ] [ ] [ ] [ ] . an increase in global temperature by °c, for example, can potentially lead to a % reduction in crop yields , , most especially those very sensitive crops, such as maize and rice, and this may result in reduction of yields in ssa , . in the case of maize for example, though the seed germinates at a temperature range of - °c, it can be grown in both rainy and dry seasons provided adequate water is available during germination and the first month of growth. thus, nearly % of the maize acreage is under rain-fed conditions during the monsoon when over % of the annual rainfall is received . depending on the climate and water availability, rice can be grown in all seasons (i.e., rainy and dry seasons). in addition, depending on the rice variety crop, duration of maturity varies from to days. rice cultivation is possible with a good rainfall ranging between and mm and about cm during the growing season but there must be less or no water at ripening stage. the temperature also should be fairly high ranging from to °c with maximum day time temperature not exceeding °c and minimum °c . since covid- has occasioned an emergency, rain-fed agriculture remains the main source of food production in africa and farming under uncertain climate variability has remained a challenge to the farmers as well discouragement to those who would have invested in farming because of the negative impacts of climate change [ ] [ ] [ ] . various strategies are used by farming communities in ssa to cope with climate change and variability and these include harvesting of rainwater for irrigation, soil and land conservation measures, intercropping, growing earlier maturing crops and crop varieties, crop diversification, migration of farmers to more productive areas among others. while ssa countries have very high potential for maize and rice production (fig. ) , the impacts of climate change [ ] [ ] [ ] and recent locust invasion , coupled with covid- movement restrictions are likely to reduce the production potential . fig. the production quantities maps and information on harvesting periods of rice and maize in ssa countries between and . nearly % of farmers in the ssa countries are smallholder farmers who harvest rice (a) and maize (b) mostly in july and december. harvesting periods is likely to be affected by covid- movement restrictions. a. ayanlade and m. radeny in addition to the environmental challenges highlighted above, the recent invasion of the desert locust, which were partly attributed to climate change, overlapped with the covid- movement restriction period. many ssa countries have been experiencing food insecurity resulting from drought and locust invasion, especially in the horn of africa, with effects on economic growth. the covid- movement restrictions may have longerterm implications. the situation for many smallholder farmers may perhaps even be more pressing and urgent, with the failure of this year's harvest (fig. ) , leading to a financial hardship that could significantly impact on the success of subsequent seasons, such as, insufficient capital for buying seeds, fertilizers, pesticides, and general land management. covid- movement restrictions limits social interactions and closure of certain sectors of the economy where farmers could get financial aid. since the majority of ssa countries are dependent on agriculture, there is a high probability that the region may be threatened by the first serious recession in the region in years, as the economic growth in the region will decline from . % in to − . to − . % in . it has been reported that many households in ssa, especially in rural communities, may be directly impacted by the predicted decline in economic growth, as the supply-side economic shocks such as those caused by the covid- pandemic . the is a need for governments at all level in ssa to develop better policies and strategies for reducing hunger post covid- pandemic in africa and improving food security [ ] [ ] [ ] . all counties in ssa need to act together immediately, under african union to respond and prepare a recovery plan post covid- pandemic, to improve food supply in the continent, as the un system, through undp, will provide support to the countries through international response [ ] [ ] [ ] . if appropriate actions are not taken, it is projected that some farmers may switch crop types, while some young farmers may move out of agriculture completely . farmers in ssa regions may need to adjust the seasonal calendar to be suitable to these changes, and organize planting calendar based on information from warning system and traditional knowledge in production is crucial to maximizing optimal conditions . this proposed option may not totally guaranty maximum yields of maize and rice this year ( ), as seems to be unsuitable for the current climate change condition. thus, the integrated approach to the meteorological science and crop science, with traditional/ indigenous knowledge in the early warning system, is the best way to determine the appropriate seasonal calendar. therefore, short-term seasonal weather forecasting is one of the options for adjusting the seasonal agricultural calendar suitable for the annual change [ ] [ ] [ ] . even though covid- is an unprecedented crisis, african leaders and governments are urged to use covid- pandemic crisis as an opportunity to offshoot 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's impacts on household food security african regional responses to covid- covid- pandemic in west africa covid- pandemic, a war to be won: understanding its economic implications for climate change impacts on agriculture and food security in egypt advancing polar prediction capabilities on daily to seasonal time scales the development of seasonal climate forecasting for agricultural producers short-term forecasting of daily reference evapotranspiration using the reduced-set penman-monteith model and public weather forecasts the authors are very grateful to the reviewers for the valuable feedback that greatly improved the article. this work was supported in part by the cgiar research program on climate change, agriculture and food security (ccafs), which is carried out with support from cgiar trust fund donors and through bilateral funding agreements. for details please visit https://ccafs.cgiar.org/donors. the views expressed in this document cannot be taken to reflect the views of ccafs or its sponsoring organizations. the authors also thank fao and africa cdc for providing data used in this study. a.a. and m.r. conceived and developed the initial idea. a.a. performed analyses and geodata processing. both authors contributed to the design of the study and contributed to the interpretation of results and the writing of the paper. the authors declare no competing interests. correspondence and requests for materials should be addressed to a. a.reprints and permission information is available at http://www.nature.com/ reprintspublisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.open access this article is licensed under a creative commons attribution . international license, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the creative commons license, and indicate if changes were made. the images or other third party material in this article are included in the article's creative commons license, unless indicated otherwise in a credit line to the material. if material is not included in the article's creative commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. to view a copy of this license, visit http://creativecommons. org/licenses/by/ . /. key: cord- -mso zfom authors: sunkari, emmanuel daanoba; korboe, harriet mateko; abu, mahamuda; kizildeniz, tefide title: sources and routes of sars-cov- transmission in water systems in africa: are there any sustainable remedies? date: - - journal: sci total environ doi: . /j.scitotenv. . sha: doc_id: cord_uid: mso zfom governments across the globe are currently besieged with the novel coronavirus (covid- ) pandemic caused by sars-cov- . although some countries have been largely affected by this pandemic, others are only slightly affected. in this regard, every government is taking precautionary measures to mitigate the adverse effects of covid- . sars-cov- has been detected in wastewater raising an alarm for africa due to the poor water, sanitation, and hygiene (wash) facilities. also, most countries in africa do not have resilient policies governing sanitation and water management systems, which expose them to higher risk levels for the transmission of sars-cov- . therefore, this study unearthed the likely sources and routes of sars-cov- transmission in water systems (mainly wastewater) in africa through a holistic review of published works. this provided the opportunity to propose sustainable remedial measures, which can be extrapolated to most developing countries in the world. the principal sources and routes of potential transmission of sars-cov- in water systems are hospital sewage, waste from isolation and quarantine centres, faecal-oral transmission, contaminated surface and groundwater sources, and contaminated sewage. the envisioned overwhelming impact of these sources on the transmission of sars-cov- through water systems in africa suggests that governments need to put stringent and sustainable measures to curtail the scourge. hence, it is proposed that governments in africa must put measures like improved wash facilities and public awareness campaigns, suburbanization of wastewater treatment facilities, utilizing low-cost point-of-use water treatment systems, legally backed policy interventions, and community-led total sanitation (clts). sars-cov- in water systems can be inactivated and destroyed by integrating ozonation, chlorination, uv irradiation, and sodium hypochlorite in low-cost point-of-use treatment systems. these proposed sustainable remedial measures can help policymakers in africa to effectively monitor and manage the untoward impact of sars-cov- on water systems and consequently, on the health of the general public. countries, especially in africa. although some countries have been largely affected by this pandemic, others are only slightly affected. owing to this, every government is taking precautionary measures to mitigate the adverse effects of covid- . some of the symptoms associated with covid- include fever, cough, diarrhoea, and breathing difficulties (who, ) . the world health organization (who) has mentioned that the main routes of exposure of the virus to humans are inhalation of droplets generated when an infected person coughs, sneezes, or exhales (who, ) . however, recent studies have shown that sars-cov- can be found in the faeces of infected symptomatic and asymptomatic patients (foladori et al., ; pan et al., ; randazzo et al., ; tang et al., ; xiao et al., ; zhang et al., a) . clinical experiments and researches have also reported evidence of sars-cov- in urine samples of infected patients (lescure et al., ; ling et al., ) , and hospital and urban sewage (medema et al., ; wu et al., ) . it can be inferred from these studies that the water systems, especially municipal wastewater of areas hit hard by covid- might contain the virus. recently, sars-cov- has been detected in untreated wastewater in australia, the netherlands, usa, and france (ahmed et al., ; medema et al., ; nemudryi et al., ; wurtzer et al., ) corroborating the assumption that the virus could be detected in wastewater. this raises serious concerns for the water systems in developing economies like most african nations. most countries in africa do not have resilient policies governing sanitation and water management systems, which expose them to higher risk levels for the spread of policies regulating the siting of pit latrines in communities but these have been widely not adhered to in most countries. such acts expose people to cross-contamination of the pit latrines with the groundwater sources. consequently, if there are covid- infected patients living in such communities that have their pit latrines closer to their drinking water sources, the risk of getting infected with the virus through oral ingestion of the virus-contaminated water is very high. similar observations about water-borne diseases such as diarrhoea and gastroenteritis in africa are very common (oppong et al., ; samie et al., ) . indiscriminate open defection around surface and groundwater sources in africa have also been reported in the literature (elisante and muzuka, ; anornu et al., ; back et al., ; abanyie et al., ; houéménou et al., ; mutono et al., ; owamah, ) . through open defecation, the carriers of the virus may unknowingly transmit it through their stool to drinking water sources, which can have a debilitating effect on consumers of such virus-contaminated water. there is also a high risk of exposure to the virus by people that use the same toilets (a common practice in africa) because the virus may remain in the aerosol or droplet generated during the use of shared toilets built in small spaces without aeration. on july , senior government medical officers reported in ghana that the commonly known symptoms of cough, cold, fever, and breathlessness often exhibited by covid- patients are not lately shown by covid- patients. now, covid- patients show stomach upset, vomiting, and diarrhoea because the virus attacks the gastro-intestines rather than the previously known lungs attack. these are not well known symptoms of the virus and as such patients may not suspect these to be indicative of the fact they have come in contact with the virus. in addition, since these new symptoms of the virus are oblivious to most doctors, the virus could escalate at the community level. these symptoms are also akin to waterborne diseases and go to buttress the possibility of the virus being transmitted through the domestic usage of the virus contaminated water. also, untreated wastewater is mostly discharged into the environment, which may interact with surface and groundwater resources, thereby contaminating these dwindling resources (williams et al., ) . overall, since most of the people living in africa, especially those dwelling in rural and peri-urban settlements depend on surface and groundwater resources for their domestic water supply, the risk of contracting covid- through sars-cov- contaminated water is very high and thus, the sources and routes of community spread of the virus, which is currently being reported must be critically re-examined. therefore, this review examines the potential sources and routes of sars-cov- transmission in water systems in africa with emphasis on wastewater management systems and proposes sustainable remedial measures to deal with the potential risk of community spread of sars-cov- via wastewater in africa. hence, the review will be a framework for african policymakers in dealing with the covid- pandemic. it will also add to the pool of existing literature on the possible transmission of sars-cov- through wastewater. according to the who, as at , about billion people in the world are still living without basic sanitation facilities (who, ). out of this, about million people representing % of the total number are living in africa. in contrast to the developed world, there is overreliance on non-sewered wastewater and sanitation systems in africa (street et al., ) . however, this goal is yet far from being achieved in africa. for example, in ghana, which is one of the biggest economies in west africa, only % of the population has improved sanitation systems in place (appiah-effah et al., ) , slightly below the improved basic sanitation coverage of % in sub-saharan africa (who, ) . elsewhere in south africa, which happens to be one of the biggest economies in africa, about % of the general public does not have a water-borne sewage system and thus, relies on bucket toilets, pit latrines, and chemical toilets as an alternative (street et al., ) . the same situation is common in most of the african countries. it is well documented in the literature that sub-saharan africa has most of its population sharing toilets vis-à-vis other nations in the world (rheinländer et al., ) . the situation is much worrying in the densely populated urban regions of sub-saharan africa, where public or shared toilets are common (morella et al., ) . gudda et al. ( ) studied pit latrine faecal sludge accumulation in nakuru, kenya and pointed out that all the pit latrines in households were communal and the average number of shared users of a pit latrine was persons. there have not been any reported cases of sars-cov- transmission via faecal-oral or waterborne routes and due to quarantine or self-isolation of persons suspected to be infected with covid- , it is argued that infection through this route is unlikely (amirian, ). nevertheless, this might not hold for shared or communal spaces and the risk of faecal-oral transmission might be common in confined places of abode like hotels and places that are overcrowded . within the next decade (dos santos et al., ) . majority of the population growth is in informal and peri-urban areas, which usually do not have basic amenities like water and sanitation, as a result, urban access to water has been impeded overtime. current estimates reveal that approximately two-thirds of sub-saharan africa's urban residents live in informal settlements and only in nairobi, kenya, these areas contribute about % of urban growth (dos santos et al., ) . the access to water by residents of these informal areas is really appalling when compared to the core urban areas, thus, rapid population growth will only compound the situation (adams, ) . bain et al. ( ) revealed that during the period between and , the annual rate of change of total population with access to basic drinking water amenities in sub-saharan africa was . % and in north africa, it was . %. moreover, the annual rate of change of total population with access to basic sanitation in sub-saharan africa was reported as . % and . % in north africa (bain et al., ) . in terms of hygiene, sub-saharan africa recorded a positive change of . % whereas it was . % in north africa (bain et al., ) . even with positive changes in hygiene, the records suggest that access to basic water, sanitation and hygiene amenities still remains very low in sub-saharan africa. in addition, nhamo et al. ( ) , studied the chances of africa to achieve the sdg by using a composite index approach with three indicators of the sdg ; proportion of the population using safely managed drinking water amenities, proportion of the population using safely managed sanitation amenities, and level of water stress. the results indicate that most of the countries are at various stages of achieving the targets set out in the sdg ( table ). the fact that many of the african countries show declining trends of wash is a clue that it will be difficult for africa to reach the sdg targets by (nhamo et al., ) . j o u r n a l p r e -p r o o f there are several routes through which sars-cov- can enter the water systems, which can eventually lead to its transmission through the water medium ( figure ). some of these routes include wastewater discharged from hospitals, government-approved quarantine and isolation centres and houses used as quarantine and isolation centres. faecal contaminations can be transmitted through water supply network systems, which end up in contaminating the water (arslan et al., ; foladori et al., ) . in africa, domestic water supply is usually from surface and groundwater sources and these also serve as potential routes for transmission of sars-cov- . for example, wastewater is often discharged directly into surface water sources without pre-treatment or proper treatment. if the wastewater discharged into the surface water sources contains fragments of sars-cov- , which is the causative organism of covid- , then it is possible that the water will be contaminated and there is a potential risk of community transmission since most rural dwellers in africa rely on surface water sources for their domestic water supply. in the same way, groundwater sources can also serve as conduits for transmitting sars-cov- if the discharged wastewater that contains fragments of the virus is introduced into the aquifer. the virus contamination can as well occur during groundwater recharge. generally, groundwater contains lesser microbial contaminants known as pathogens than surface water, but the biological integrity of groundwater cannot be underestimated (alley and alley, ). governments to partner with the private sector to deal with the situation. there is the need to provide efficient but cheap sanitation services to the citizenry, especially for the poorest of the poor. the best solution to this menace is the application of financial solutions to support the access of households to improved wash amenities and to encourage wash-related entrepreneurial activities. if governments provide easy access to funds by households and private individuals through microcredit, loans, and micro enterprise financing, this will facilitate the provision of wash amenities for the poor. another important measure for dealing with the possible transmission of sars-cov- through wash-related activities is public awareness through regular behavioural change campaign to revolutionize the thinking of most africans on myths associated with wash activities. if all these measures are put in place in africa, the likelihood for the transmission of sars-cov- and other human enteric viruses that may originate from the stool of infected persons will be very low. adequate and centralized wastewater treatment facilities are a major problem in africa. as explained before, in most african countries, huge amount of the untreated wastewater generated is usually released directly into surface water sources. the adverse effects of this attitude on public health is unquestionable. it is even worrying to know that the quarantine and isolation centres of health care facilities used for testing and treating suspected and confirmed covid- carriers have a common sewerage system with the coterminous communities and cities (adelodun et al., ) . this situation exposes the people to the tendency of using water from surface water sources that might be contaminated with sars-cov- and thus, making them vulnerable to the virus. one of the ways of contracting sanitary-related diseases is through leakage of sewerage systems when conveying wastewater j o u r n a l p r e -p r o o f journal pre-proof contaminated with pathogens and excretes (gormley et al., ) . the best antidote to this threat is separating the sewerage systems and wastewater treatment facilities of the health care centres from that of the urban central systems to facilitate viral removal during treatment process. wastewater treatment facilities should be located in at least each city. this will ameliorate the situation and stop people from indiscriminately discharging wastewater into surface water bodies. wastewater generated in most industries in africa, unfortunately do not pass through the entire cycle or pathway of wastewater flow (figure ). mostly after generation, due to financial or infrastructural challenges, the wastewater does not get treated but is discharged with no benefit (figure ). however, with the needed finances and infrastructure in place, the wastewater generated must be properly treated and discharged or reused. some of the ultimate uses of treated wastewater are for portable water supply, irrigation, and hydro energy ( figure ). governments are overwhelmed with several equally important developmental works but there should be a willpower in dealing with the wastewater treatment issue in africa. to augment the situation, the private sector should be motivated to focus on investing in waste-to-value projects in parts of africa, where waste treatment or recycling facilities are absent. this will help improve the sanitary conditions around physical locations and also improve the health of the people. from water systems using cheaper low-cost point-of-use treatment devices such as zerovalent iron filter, iron-oxide bio-sand filter, nanocellulose-based filter, gravity-based ultrafilter, and many more (bradley et al., ; shi et al., ; chaidez et al., ; mautner, ) . these devices can be effectively used for inactivating and destroying the sars-cov- genetic material, especially in africa where there are no effective wastewater treatment systems. moreover, in view of the recent findings of researches that suggest that sars-cov- can be completely eliminated in water systems by the use of ozonation, chlorination, uv irradiation, and sodium hypochlorite (rosa et al., ; quevedo-león et al., ; wang et al., b) , there is the need for african countries to start integrating them into their low-cost point-of-use treatment systems. the model for such an integration is schematically presented in figure . in this schematic diagram, it can be observed that when the different disinfection techniques are integrated and control measures are put in place to prevent the water from being re-contaminated, the integrity and reliability of the reclaimed water can be enhanced. such an integrated approach of disinfecting contaminated water and wastewater can withstand influent flow and water quality fluxes. the current times require policy interventions that have legal support to direct the attitude of people living in africa. even with the advent of the covid- pandemic, some people living in africa believe covid- is a western disease and that the confirmed cases in their countries are only political gimmicks of their governments who they think largely depend on the western world. in these abnormal times, surface water sources such as streams and rivers, which hitherto were used as domestic water supply sources in some villages have to be j o u r n a l p r e -p r o o f protected from encroachment by the rural people. in this regard, governments have to find alternative ways of meeting the water supply needs of rural people. by doing so, sanctions can be meted out to violators. at this critical point in time, wastewater should be treated before discharge into the environment. hence, there must be stringent measures regulating wastewater treatment and culprits should be punishable by law. employees in wastewater treatment facilities must thus take maximum precaution to prevent themselves from possible infection. at least, it is encouraging that some african countries like ghana, nigeria, cameroon, south africa, angola, benin, burkina faso, equatorial guinea, ethiopia, gabon, guinea, kenya, liberia, rwanda, dr congo, sierra leone, zambia, and morocco, have already put law-supported punitive measures in place for people who do not wear masks in public places in the wake of the covid- pandemic. this sets the basis for others to follow suit if only they want to fight the covid- pandemic. however, the safety protocols provided by the who and ministries in charge of health in all countries should be strictly adhered to and people who violate them in public places should be sanctioned. this is an innovative way of allowing communities to initiate their own actions towards addressing their own problems. the aim is to help improve wash practices and it is currently being implemented in many developing countries through the guidance and support of non-governmental organizations. in africa, it is difficult for governments to be able to spearhead every developmental project. this calls for active participation of community members themselves and important stakeholders in society. one of the primary targets of the since previous approaches to curtail sanitation problems only set high standards with subsidies as incentives to rural people. overtime, this never became sustainable due to the uneven adoption and partial use of the toilet facilities. moreover, it has made rural dwellers over reliant on subsidies, which are not also regular. in this regard, faecal-oral transmission through open defecation persisted leading to the spread of waterborne diseases. so instead of merely providing the 'hardware' for wash practices, there is the need for behavioural change to ensure sustainable improvement and this can only be done through clts. investing in community mobilisation should be at the heart of the clts programs such that the focus on toilet construction for individual households will be shifted to making sure villages and communities are actually open defecation-free. through awareness creation with the message that the continuous practice of open defecation by even the minority in the community will expose everyone to the risk of diseases, clts will prompt the community's crave for collective change, will push people into taking actions and development of innovative ideas, will provide mutual support and proffer suitable local solutions to local problems, which in the end will lead to complete ownership and sustainability. the impact of the covid- pandemic is currently felt everywhere in the world and in all aspects of the economy. the impact is even envisioned to be more severe in the developing world like africa, which is still struggling to meet the basic necessities of life for the people living 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hydrogeochemical controls and human health risk assessment of groundwater fluoride and boron in the semi-arid north east region of ghana isolation of -ncov from a stool specimen of a laboratory confirmed case of the coronavirus disease (covid- ) the first author thanks the scientific and technological research council of turkey (tÜbİtak) for the continuous support as a doctoral fellow of bideb graduate scholarship program for international students. the editors, especially prof. damià barceló and the anonymous reviewers, are also sincerely acknowledged for their useful reviews that improved the quality of this paper. key: cord- - gqonmf authors: nguimkeu, pierre; tadadjeu, sosson title: why is the number of covid- cases lower than expected in sub-saharan africa? a cross-sectional analysis of the role of demographic and geographic factors date: - - journal: world dev doi: . /j.worlddev. . sha: doc_id: cord_uid: gqonmf unlike initially predicted by who, the severity of the novel coronavirus pandemic has remained relatively low in sub-saharan africa, more than two months after the first confirmed cases were identified. in this paper, we analyze the extent to which demographic and geographic factors associated to the disease explain this phenomenon. we use publicly available data from a cross-section of countries worldwide, and we employ a regression analysis that accounts for possible misreporting of covid- cases, as well as a ramsey-type specification that preserves degree of freedom. we found that proportion of population aged +, population density, and urbanization are significantly positively associated with high numbers of active infected cases, while mean temperature around the first quarter (january-march) is negatively associated to this covid- outcome. these factors are those for which africa has a comparative advantage. in contrast, factors for which africa has a relative disadvantage, such as income and quality of health care infrastructure, are found to be insignificant predictors of the spread of the pandemic. these results hold even when accounting for possible underreporting, as well as differences in the duration of the epidemic in each country, as measured by the time elapsed since the first confirmed case occurred. we conclude that differences in demographic and geographic characteristics help understand the relatively low progression of the pandemic in sub-saharan africa as well as the gap in the number of active cases between this region and the rest of the world. we also found, however, that this gap is insignificant beyond these factors, and is expected to narrow over time as the pandemic evolves. these results provide insights for relevant urban policies and kinds of development planning to consider in the fight against disease spreads of the coronavirus type. the coronavirus disease caused by a novel sars-cov- that emerged in china last year, and has since spread to all regions of the world, is causing major ravages worldwide as reported by the world health organization (who). since the burst of this disease, experts have been announcing a drastic surge and dramatic consequences of the epidemic in sub-saharan africa (ssa), a region already plagued by poverty and lack of health infrastructure. however, more than two months after the first confirmed case in the continent, the transmission and severity of the novel coronavirus pandemic has remained relatively low in sub-saharan africa, while other regions of the world (such as europe and usa) have been more seriously hit . sub-saharan africa is indeed the least affected region, with , infected cases and deaths recorded as of april , (our world in data ). understanding why the severity of covid- in sub-saharan africa remains comparatively low in spite of the weak health-care system, inadequate surveillance and laboratory capacity, scarcity of public health human resources, and limited financial means (nkengasong and mankoula ) is therefore a question that merits attention. although there is no clear consensus about this seemingly puzzling situation, a number of hypotheses have been posited to try to explain the low numbers observed in sub-saharan africa. one argument that emerged was that, since very few african countries have sufficient and appropriate diagnostic capacities, the number of cases are largely underreported. however, as explained by dr john nkengasong, head of the african center of disease control and prevention, the fact that health facilities are still not overwhelmed by patients may rule out this hypothesis. other hypotheses build from recent clinical studies (e.g. china, italy) that have identified the presence of pre-existing noncommunicable diseases such as cerebrovascular diseases (cvd), diabetes, hypertension, and cancer, as the main comorbidities associated with infected and death cases (driggin et al. , yang et al. ). on the other hand, while it has been documented that dense communities, urban congestions or colder weather may favor the transmission of viruses of respiratory syndrome such as influenza, measles, tuberculosis, coronavirus (alirol et al , van de poel et al. , recent clinical studies show that individuals aged years or older are at higher risk of contamination and death , who, . against this backdrop, the present study aims to analyze the role of demographic and geographic (dg) factors in explaining the low severity of the epidemic in sub-saharan africa (ssa) compared to other regions. we employ a regression analysis that estimates the number of active infected cases where these dg factors are used as explanatory variables. based on the related literature, the demographic indicators considered are the median age and the proportion of population aged +, whereas geographical factors include population density, urbanization rate and mean first quarter temperature. both these demographic and geographic factors are found to be significantly and positively associated with the number of active covid- cases. given that ssa countries exhibit relatively lower magnitudes in these factors compared to the rest of the world, they thus have a comparative advantage from these perspectives. in contrast, factors in which sub-saharan africa has a considerable disadvantage such as income and quality of health infrastructure (measured by gdp per capita, and health expenditure), turn out to be insignificant predictors of the spread of the epidemic. measures of epidemiological factors, especially the prevalence of diabetes, are also found to have no significant association with this covid- outcome, possibly for endogenous behavioral reasons that we further discuss in section . the only source of covid- data available to us for this exercise is a publicly available one whose quality is, unfortunately, very uncertain. our econometric specification attempts to solve this uncertainty by explicitly accounting for possible underreporting in the official number of confirmed cases used, as well as for the lag in the disease introduction in each country, as measured by the time elapsed since the first confirmed case was detected. the latter also allows to capture the learning effect, as countries that experience the epidemic relatively later are likely to learn from successful coping strategies adopted by those that experienced it relatively earlier. to test whether and by how much the estimated effects of the dg factors differ between sub-saharan africa and the rest of the world, we employ a ramsey-type device that preserves degrees of freedom. this consists in assessing whether an interaction between a ssa dummy and these factors help explain the outcome variable. subject to the above-mentioned data quality caveats, our results provide conclusive evidence that the relatively low progression of the epidemic in sub-saharan africa and the gap observed in the number of active cases compared to the rest of the world can be partly explained by the differences in demographic and geographic factors. however, this gap narrows down with the duration of the epidemic and is not significant beyond these factors. these results call for strategies to implement mitigation efforts and containment measures that pertain to ssa situation, and provide insights on policies and program interventions that could be considered to prevent the spreads of disease of coronavirus type. this paper is organized as follows. section discusses the background and descriptive statistics. section presents the estimation approach and the results of the regression analysis. section concludes. the data consists of a cross-section of countries affected by the coronavirus pandemic. we collated the most recent data available from various sources including worldometer coronavirus ( ), world development indicators (wdi), global health observatory (gho), world bank climate change knowledge portal, world population prospects ( ) and the institute for health metrics and evaluation (ihme). data on covid- spread includes the total number of confirmed cases, the total number of deaths and the total number of active cases (which is the total number of confirmed cases net of recoveries and deaths). figure compares the trends in the average number of active cases in sub-saharan africa versus the average of the rest of the world for the first days since the pandemic has erupted in the given regions. overall, this trend has been consistently lower in sub-saharan africa compared to the rest of the world, even when adjusting for the lag in the timing of disease occurrence in both regions. source: author's construction from our world in data ( ). table presents descriptive statistics of the variables of interests in our whole sample. we denote by duration, the variable that accounts for differences in the timing of disease eruption, i.e. the number of days elapsed since the first case of covid- to the observed date. the first panel summarizes the characteristics of the covid- , including the total number of cases, total number of deaths, the total number of active cases, and the duration of the epidemic from our data source. the second panel summarizes the epidemiological factors including the prevalence of cvd and the prevalence of diabetes (i.e. the proportion of people aged - that have type or type diabetes). the choice of these variables are based on who ( ) report emphasizing that those with such pre-existing medical conditions (i.e. cerebrovascular disease, diabetes, chronic respiratory disease, and cancer) are at higher risk. while covid- infects people of all ages, zhou et al. ( ) recently found that older people (e.g. + years) are at higher risk of the disease. we therefore consider the proportion of the population aged + as a fraction of the total population (denoted pop +), and the median age of the population as our main demographic indicators, whose statistics are summarized in the third panel of the table. as for geographic factors which are given in the fourth panel of the table, we consider three indicators: urbanization (i.e. the proportion of people living in urban areas), population density (i.e. number of people per squared kilometer, km ), mean temperature (in celsius degrees) of the first quarter of the year (january-march). table presents summary statistics of our variables of interest by region. it shows that compared to all other regions, sub-saharan africa has the lowest prevalence of cvd and diabetes, the lowest proportion of population aged +, the youngest population i.e. lowest median age, one of the lowest urbanization rate (apart from south asia), one of the lowest population density (apart from north america), and the highest average temperature around the first quarter of the year. in particular, the pop + and median age in sub-sahara is . % and years, compared to . % and years in north america. this is a huge difference in terms of age-related vulnerability. there is also a huge difference in the average temperature across regions. while ssa experiences an average of o c during the months of january through march, other regions experience much lower temperature, especially europe and central asia with an average of . o c, as well as north america with a negative average of - . o c (see table ). following related literature, we use gdp per capita as a measure of income, and health expenditure per capita as a measure of healthcare infrastructure. both can be understood as economic indicators. for these factors, sub-saharan africa is very disadvantaged, and has the lowest scores along with south asia. for example, gdp per capita in sub-saharan africa is about times lower than in north america. the observed differences in these summary statistics suggests, as it will become clearer in the regression analysis below, that there should be important differential effects of the corresponding factors between ssa and the other regions. this section presents the regression model and the estimation approach, and discusses the associated results. we consider the log total number of active infected cases of covid- as our response variable, which is the total number of cases net of total deaths and recovered. we use a linear regression model framework to analyze the relationship between disease outcome and demographic and geographic factors while controlling for epidemiologic, economic and health system infrastructure indicators: * = * + * + + where denotes the true covid- outcome variable in country (e.g., log active cases); is a binary indicator * (dummy variable) for sub-saharan africa, which equals if country is a sub-sahara african country, and equals otherwise; is the duration of the epidemic in country (i.e. the number of days elapsed since the first confirmed case was reported in country ); is a vector of explanatory variables including epidemiological, = [ ,…, ] demographic, environmental, economic and health infrastructure factors in country ; is the total number of explanatory variables (excluding the dummy variable ). the error term, is assumed to be mean zero and captures * , all other factors driving the outcome that are not accounted for by our model specification. unfortunately, the true covid- outcome variable is unobserved due to uncertainties in data quality and we can * only observe a possibly misreported surrogate defined as where is the measurement error, or the amount of underreporting. if we assume that, for the reasons already evoked, data from sub-saharan africa are possibly more underreported than those of other regions, then we can write represents the average amount of excess underreported log number of active cases in ssa compared ≥ to other regions (whose average amount of underreporting is ), and is the residual measurement error that is ≥ assumed to be uncorrelated with and . we therefore have , and the relationship , = * - - between the reported cases and the factors of interest to be estimated can be summarized as: where is the reported number of active cases in country . the coefficient is the intercept and = * - = * is the average difference in outcome between sub-saharan africa and the rest of the world, both exacerbated by - the amounts of misreporting and , respectively, conditional on the vector of factors the coefficient is the . average ceteris paribus effect of the length of the pandemic on the outcome, whereas captures how this duration effect varies between sub-saharan africa and the rest of the world. these coefficients also capture the "learning" effect, given that countries that experienced the epidemic relatively later may have learned and adopted the most successful strategies adopted by those that faced it earlier. average ceteris paribus effect of the specific factor on the outcome . notice that the new error term, has an , increased variance as it includes both the measurement error component and the original error expected in the regression. overall, if this model is correctly specified, the outcome of the regression will be an unbiased estimate of , but with reduced precision in these estimates, lower -statistics and a reduced [ , ,…, ] . since a focus in this study is on the conditional comparison of the outcome of sub-saharan africa with the rest of the world, a useful modification of model ( ) is to interact the sub-saharan africa dummy variable, , with all the explanatory variables of the model, and add these interaction terms, as = [ ,…, ] additional regressors to the model to assess heterogeneity in the effects of the initial factors. however, this would significantly reduce the degree of freedom of the model (which is already low), and thus lead to low power in the significance testing of the coefficients. to overcome this issue, we adopt a device similar in spirit to the ramsey reset test, which allows us to assess whether the interaction terms significantly explain , while ,…, conserving in degrees of freedom. this consists in augmenting the interaction between and the ols fitted values as an additional regressor of the model to see whether it significantly explains the response variable. specifically, recall that the fitted values from equation ( ) is defined by where the components with "hat", represent the ols estimates of their underlying quantities. these fitted values are therefore just linear functions of the independent variables. if we interact the fitted values with the dummy variable, , we get a particular function of the desired interactions terms, , and this suggests estimating ,…, . a model of the form where stands for the fitted values obtained above. notice that model ( ) is equivalent to a "reduced-form" regression model of the form where the relationship between the two last sets of coefficients is given by = ; = + ( + ); = ; = + ( + ); = ; = ; ≥ ( ) the sign and significance of the coefficient can therefore be used to assess how the effects of on = [ ,…, ] the outcome variable differ between sub-saharan africa and the rest of the world. once equations ( ) and ( ) have been estimated, the coefficients of the reduced form model given by equation ( ) can be inferred using the formulas given by equation ( ), and their standard errors can be approximated using the delta method. notice that the coefficients of the main baseline factors and do not change across specifications, but only the coefficients of the terms interactions with are likely to change across specifications. our ultimate targets are those from the reduced form relationship given by equation ( ), although in this case, we are really only interested in computing and , which can be readily obtained from the estimation of equation ( ) using the formulas in equation ( ). in addition, given that is an estimate of the expected value of given , and , using equation ( ) to estimate , the outcome variable is also useful to correct for potential heteroscedasticity, in case the error variance in equation ( ) is thought to change with , and . in summary the estimation method proceeds as follows. , step : estimate the model given by equation ( ) by ols, and obtain the fitted values . compute the interaction terms . step : run the regression model given by equation ( ) average difference in outcome and the differential effect of on the disease outcome between ssa and the rest of the world, conditional on all other factors. given the small size of the sample, classic standard errors may not be correctly estimated from the usual asymptotic variance-covariance matrix. we therefore use the bootstrap method as a complementary estimation approach for these standard errors. to account for possible heteroscedasticity in the error term given in equations ( ) and ( ), we also compute robust standard errors. an obvious limitation of this econometric model is its inability to account for endogenous behavioral response to the disease outcome, which could be substantial. for instance, it is possible that people at higher risk are responding to the disease in a way that could mitigate the initially perceived impact. this is issue is especially true for epidemiologic factors. addressing it would require ancillary information about the underlying behavior and possibly a different methodological approach. the empirical results for these factors should therefore be taken with extra caution. in contrast, demographic and geographic factors are less responsive to outbreaks so that the effect from these dg factors should be the most meaningful estimates in the empirical assessment. the regression results of the baseline estimates with log total number of active cases as the main dependent variable are presented in table . the estimation results for this outcome are summarized in columns ( ) through ( ). the first column presents the baseline estimates without the ssa regional dummy. the second column presents the estimates that include the ssa dummy variable (corresponding to equation ( )), while the third column presents these results where this dummy variable is interacted with the fitted values of the regressions in column ( ) which corresponds to equation ( ). preliminary analysis has shown strong pairwise correlation between cvd and diabetes prevalence, as well as median age and pop +, respectively. these strong correlations have also been noticed in earlier work such as halter et al ( ) . hence, to avoid multi-collinearity, only one of these factors was included in the main regressions. in particular, table presents the results using the variables that have less missing values among highly correlated alternatives. this means that we focused on results with diabetes prevalence and pop + in our main discussion. those with the alternative measures, i.e., cvd prevalence and median age, were less conclusive because of poor fit and statistical power (some due, e.g., to high rates of missing values), but are available from the authors. several functional forms were also considered (e.g., which explanatory variables to include in log form) and the reported results are based on those that gave the highest fit in terms of adjusted r-squared and/or pseudo-log likelihood value. all the values reported in columns ( ) , ( ) and ( ) indicate global significance at %. the epidemiological predictors we use to assess the spread of the pandemic are the duration of the pandemic and the prevalence of diabetes in the country. while recent clinical studies suggest that cerebrovascular diseases and diabetes are some of the most distinctive comorbidities among patients under intensive care of covid- (e.g. fang et al., ; yang et al. ), our current cross-country data does not provide enough evidence to support this hypothesis. our regression estimation results show no statistical significance in the association between diabetes prevalence and the number of active covid- cases worldwide. one possible explanation for this puzzling result, as already mentioned in the methodological discussion, is the presence of endogenous behavioral responses among diabetes and cerebrovascular diseases patients. being more at risk, these individuals are likely to be more careful in adopting safety and social distancing measures than others, which could eventually cancel their higher mortality or contamination risk and lead to no significance in an empirical assessment. our econometric model does not deal with this important issue. on the other hand, as one would expect, the duration of the pandemic appears to be a strong predictor of the disease spread. we estimate that any additional day in the duration of the epidemic is associated with a % increase in the number of active cases, and this effect is significant at % (see columns ( ) - ( )). although the first cases of coronavirus occurred in sub-saharan africa relatively later than other parts of the world (e.g. china, europe, usa), the interaction between the ssa dummy and the duration of the epidemic shows that the longer the epidemic would last, the more severe the consequence would be for sub-saharan africa countries compared to the rest of the world, everything else equal. in particular, our results show that any additional day of the epidemic is associated with a . % increase in the number of active cases in ssa, and this effect is significant at %. this duration effect is much higher in ssa compared to the rest of the world. our most meaningful findings are those related to demographic and geographic factors. the results show that the proportion of population aged and above, an important demographic indicator capturing population ageing, is positively associated to the number of active cases, and this correlation is significant across all specifications. specifically, everything else equal, a percent increase in the fraction of this population is associated with about . percent increase in the number of active cases on average. this result is in line with recent evidence suggesting that relatively older adults are at a higher risk of covid- (e.g. zhou et al. ; who ) . since sub-saharan africa has an extremely young population (e.g., half of the population is aged below , and only . % are above ), they are likely at a relatively lower risk on this dimension. all the geographic factors considered are also significantly associated with the severity of the disease. the coefficient for log population density is estimated to range between . and . across specifications, implying that a % increase in the density of the population is associated with a . %- . % increase in the number of active cases. indeed, higher population density would tend to increase the likelihood of inter-community contagion, even under social distancing measures. alirol et al. ( ) explain that this is particularly true for diseases transmitted via respiratory and fecal-oral routes (such as influenza, measles, tuberculosis, severe acute respiratory syndrome, etc.), given the increase in the amount of shared airspace. these authors also showed that cities are becoming important hubs for the transmission of infectious diseases, not only because of international travel and migration, but also because urbanization is associated with negative health outcomes and utilization (e.g., stillwaggon, ; greif et al., ) . consistently with these findings, our results show that a percentage point increase in the urbanization rate is associated with about . % to . % increase in the number of active covid- cases. given that population density and urbanization rates remain relatively low in sub-saharan africa countries (see figure ), these countries thus have an important advantage in coping with the virus spread compared to other parts of the world from a spatial perspective. average temperature around the first quarter of the year (january-march) is also another relevant geographic factor, not only because recent research has suggested that temperature and climatological factors could influence the spread of this novel coronavirus in general (de Ángel solá et al. ; liu et al., ) , but also because this particular quarter of the year corresponds to when the novel coronavirus has been initially spreading. we found this indicator to be negatively associated with the pandemic spread in our estimations, showing that a o c decrease in average temperature around this quarter is associated with about . % increase in the number of active cases of covid- . this result means that countries with relatively higher temperature at this time of the year, such as sub-sahara african countries, would tend to have a relatively lower number of cases, everything else equal. source: un world urbanization prospects ( ) an important aspect of this regression analysis is that it allows to formally assess how the effects of the demographic and geographic factors discussed above differ between ssa and the rest of the world. the key parameter for this assessment is the coefficient of the interaction term between ssa and the predicted values of the regression in column ( ), presented in column ( ). this parameter is estimated at - . and is significant at %. it implies that any factor that is positively associated with the spread of covid- worldwide would have, on average, a . % lower effect on the number of active cases in sub-saharan africa compared to the rest of the world, for any percent shift. this is the case for all demographic and geographic factors considered. however, when we control for all these factors, the number of active cases in sub-saharan africa is not significantly different from those of other parts of the world. this is evidenced from the non significance of the ssa dummy in both the reduced form estimate and in the specification given in column ( ). this implies that any assumption about ssa being relatively safer through unobserved heterogeneity such as some pre-existing immunity (e.g. guerrini et al. ) should be taken with great caution. this may also mean that any number of cases by which ssa is exceeding the rest of the world is being offset on average by the amount of underreporting, conditional on the dg factors. the last set of indicators whose role are examined in this analysis are those related to income and the quality of the health system. a large body of the health economics literature shows that these factors contribute to improving health outcomes (cutler et al., ) . however, our estimation results show that gdp per capita, our measure of aggregate income, is insignificant in all our specifications (see columns ( ) - ( )). this means that, although this factor provides the opportunity to improve material conditions, subsidize effective containment measures such as social distancing, and improve related public goods as shown by many research (e.g. marmot , condliffe and link, ) , it is not associated with a significantly lower level of covid- spread, when demographic and geographical factors are controlled for. thus, given these dg factors, the fact that ssa is relatively poor compared to other regions of the world does not seem to be a crucial issue in addressing the pandemic in the continent, unlike initially thought. another important issue that has spurred concerns about this pandemic for the african continent is the fragile health systems in most sub-saharan african countries, and the fear that new or re-emerging disease outbreaks such as the current covid- pandemic could potentially paralyze health systems at the expense of primary healthcare requirements using the formulas in ( ) and the delta method, the reduced form coefficient for the ssa dummy is inferred from estimates in columns ( ) and ( ) is computed at , with a standard error of . . = - . - . * ( - . + . ) = . (velavan and al., ) . however, using public health expenditure as a recognized indicator for the quality of healthcare infrastructure (see ssozi, and amlani, ; gallet and doucouliagos, ; obrizan and wehby, ) , we found no statistically significant association with the active spread of covid- , or its containment thereof. this suggests that the relative fragility of health infrastructure in ssa countries and their relatively week capacity to diagnose and handle outbreaks compared to other regions does not constitute a significant catalyst of the covid- spread. the results discussed above are subject to the caveats of data quality already raised in section , which may remain pending even after attempting to mitigate it with our econometric strategy. the results on epidemiologic indicators (i.e. prevalence of diabetes or cvd) can not bear a causal interpretation given the possible underlying endogenous behavioral adjustment discussed in the estimation section and unaccounted by our model. our most credible estimates are the effects of demographic and geographic factors which are largely exogenous and are found to be significant and robust across all our specifications. they provide compelling evidence that may help understand why the number of infected cases of covid- has been growing slower in sub-saharan africa and has remained relatively low compared to other regions of the world. these findings are however credible to the extent that the measurement errors in the dependent variable are uncorrelated with these factors as is usually assumed in the econometric literature (see bound et al , hausman . otherwise, a more sophisticated model of misreporting is needed and may require other methodological investigations that are beyond the scope of this work. the goal of this paper was to assess the role of demographic and geographic factors in explaining the spread of covid- , with the aim of understanding why the epidemic is progressing relatively slower in sub-saharan africa. we employ a ramsey-type device that preserves degrees of freedom in a regression analysis framework that accounts for possible misreporting to estimate the number of active covid- cases as a function of these factors. we found that the proportion of population aged +, population density and urban population rate are positively associated with the number of active cases, whereas average temperature around the first quarter of the year (january-march) is negatively associated with this epidemic outcome. because sub-sahara african countries exhibit both lower rates of the former factors and higher levels of the latter, they are less affected than other countries by these drivers. as a consequence, these factors are found to have lower marginal effects on the number of active cases in sub-saharan africa compared to the rest of the world. these results help understand the relatively low progression of the pandemic in sub-saharan africa, compared to the rest of the world. however, this advantage that sub-saharan africa seems to have regarding the spread of covid- disappears once we take away demographic and geographic characteristics. this suggests that any assumption that sub-sahara african countries could be benefiting from pre-existing immunity conditions beyond the above-mentioned factors should be taken with caution. while the number of active cases increases with the duration of the epidemic, our results show that the perverse effect of time is exacerbated in sub-sahara african countries compared to the rest of the world, in spite of the former having a learning advantage. this means that the comparative advantage that ssa seems to have now could narrow and possibly reverse in the future as the pandemic evolves amid no medical solutions. this therefore calls for awareness and strategies to implement mitigation efforts and containment measures that pertain to the ssa situation. our results provide insights for policies that could be implemented to overcome disease spreads of the coronavirus type. in particular, given that geographic factors such as urbanization and dense populations appear to have the largest and most significant impacts in our analysis, successful policies and programs to address the spread and severity of such diseases should leverage on geographical eco-system. this includes sensible planning of the expansion of cities as well as the integration of health and social distancing concerns into urban policies. urbanisation and infectious diseases in a globalised world. the lancet infectious diseases measurement error in survey data the relationship between economic status and child health: evidence from the united states the determinants of mortality weathering the pandemic: how the caribbean basin can use viral and environmental patterns to predict, prepare and respond to covid- cardiovascular considerations for patients, health care workers, and health systems during the coronavirus disease pandemic are patients with hypertension and diabetes mellitus at increased risk for covid- infection? the lancet respiratory medecine the impact of healthcare spending on health outcomes: a meta-regression analysis urbanisation, poverty and sexual behaviour: the tale of five african cities potential link between anti malaria prophylaxis and the prevention of covid- infection diabetes and cardiovascular disease in older adults: current status and future directions mismeasured variables in econometric analysis: problems from the right and problems from the left impact of meteorological factors on the covid- transmission: a multi-city study in china the influence of income on health: views of an epidemiologist looming threat of covid- infection in africa: act collectively, and fast health expenditures and global inequalities in longevity data retrieved from our the effectiveness of health expenditure on the proximate and ultimate goals of healthcare in sub-saharan africa revision of world urbanization prospects is there a health penalty of china's rapid urbanization the covid- epidemic. tropical medicine and international health coronavirus disease (covid- ): situation report united nations, department of economic and social affairs clinical course and outcomes of critically ill patients with sars-cov- pneumonia in wuhan, china: a single-centered, retrospective, observational study. the lancet respiratory medicine clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study the most evident limitation of our analysis is the quality of the publicly available data that we used and the associated misreporting in the outcome variable. econometric approaches to deal with these issues such as the one we employed may not fully mitigate it or fully identify some relevant components of the relationship, especially if the measurement errors are correlated with explanatory factors. another important limitation is the inability of the model to measure the endogenous behavioral responses of some of the key explanatory variables. addressing these concern would require better quality data as well as ancillary information about these behavioral responses. these considerations are left as possible avenues of future research. key: cord- -drwvzw l authors: eyawo, oghenowede; viens, a. m. title: rethinking the central role of equity in the global governance of pandemic response date: - - journal: j bioeth inq doi: . /s - - - sha: doc_id: cord_uid: drwvzw l our initial response to covid- has been plagued by a series of failures—many of which have extended inequity within and across populations, especially in low- and middle-income countries. the global health governance of pandemic preparedness and response needs to move further away from the advocacy of a one-size-fits-all approach that tends to prioritize the interests of high-income countries towards a context-sensitive approach that gives equity a central role in guiding our pandemic preparedness and response strategies. while the global governance of pandemic preparedness and response often touts the importance of equity as a moral value and policy goal, our reaction to the covid- pandemic should lead us to call this into question. on the one hand, we find the failure of omission-the progression of the covid- crisis threatens to disproportionately impact low-and middle-income countries (lmics) with vulnerable healthcare systems. on the other hand, we find the failure of commission-high-income countries (hics) battle to buy out ventilators, personal protective equipment, and diagnostic tests on the global market, which freezes out any real possibility of lmics getting these resources. this lack of collective action is a moral failure that risks losing the gains made in promoting health and health equity globally, and risks calling into question the usefulness of equity-based arguments for responsible governance that were used to justify actions to achieve these gains. we argue that much of pandemic preparedness and response remains focused on the interests, resources, and capacities of hics and, in the case of covid- , requires more than a one-sizefits-all approach. the practicality of any proposed pandemic response measures needs to be strongly reconsidered in light of the flawed expectations surrounding the context, capacity, and governance arrangements in lmics. we maintain that this requires us to rethink how we can strengthen the role equity plays in guiding the global governance of pandemic preparedness and response, and its wider potential impact for global health governance more generally. it is widely accepted that equity is central to global health and should be the guiding principle in global efforts to improve the health and lives of all people around the world (fee and gonzalez ; plamondon and bisung ) . the current global response to covid- -which has been mostly inward looking and nationalistic-calls this premise into question. the global health governance response to the covid- pandemic has been largely modelled from the perspective of hics without due consideration for how and whether it provides a feasible parallel strategy for lmics. a predominant reliance on extemporaneous prevention measures, such as stay at home orders, frequent handwashing, long-term social distancing, and business closures cannot be easily or effectively translated into the lmic context without major political and economic changes. how can families in most lmics effectively implement social distancing and self-quarantine when they live together in close quarters and operate within a culture where mingling is the norm? it is a challenge at best and an impossibility in many cases. most people do not have access to running water at home; they need to go out into the community to fetch water from a public tap or stream-which makes regular handwashing challenging to implement. in some communities, there is no access to safe water at all-a problem that also disproportionately affects certain populations in hics, as evidenced by some indigenous and black communities in north america (waldron ) . many people also need to go to work in an informal setting on a daily basis in order to be able to afford food to eat the next day. they cannot so easily stock up on supplies and stay at home. many have no personal savings and live from hand to mouth, and there is no steady power supply to keep the fridge running, even if they somehow managed to fill it. furthermore, the food supply chain relies primarily on daily supplies and deliveries to local markets, since storage facilities are not very functional in these settings due to regular power interruptions. under a lockdown strategy with insufficient contingency plans including temporary income and an active supply chain, food supplies will run out quickly for families and communities. hunger will set in, crime may increase, and people may begin to die of starvation even before covid- or another disease gets them. this practical reality must be included at the forefront of our moral theorizing about the global ethical dimensions of covid- . decades of chronic health underfunding, largely driven by political corruption, has weakened the health system in most lmics. before the covid- pandemic, the healthcare systems in these settings were at best already fragile, vulnerable, and ill-equipped to mount a quick and efficient response proportionate to the magnitude of a pandemic such as covid- (viens and eyawo ) . while the experience with responding to ebola in some african countries may provide some clues on how to respond and mobilize, covid- is different, given its high transmissibility and mode of transmission. therefore, while the experience will be useful in these countries, it will not be sufficient to help them address this crisis. reports from early on in the pandemic suggested that the number of covid- cases in africa could surge to up to ten million in as little as six months (al jazeera and news agencies ). however, the reported figures so far appears to be much lower than projected (world health organization ); although this needs careful observation given the uncertain and evolving nature of the pandemic. to date, much of the focus on responding to covid- has been around the use of restrictive measures (i.e., quarantine, social distancing, school and business closures, travel restrictions) as the primary avenue to minimize or prevent community-level transmission. without an effective antiviral or vaccine, it is claimed, our best chance to save as many lives as possible and prevent healthcare systems from being overwhelmed is to lockdown society-encouraging or requiring everyone to stay home to prevent as much contact as possible, limiting trips outside of the home to essential work or to obtain essential supplies only. this strategy has been coupled with a push to increase the testing capacity and the number of covid- tests being conducted by local public health authorities in affected countries. while these measures have been the dominant approach in most hics, we should be sceptical of whether this will be an effective and feasible response for lmics, especially in africa. this is because little or no consideration has been placed on the unique challenges and opportunities in these settings-challenges that can impede the successful implementation of any response strategy. for instance, it is noteworthy that alongside the restrictive measures that include school and business closures to facilitate social distancing, most hics have created and rolled out a temporary income support benefit to its citizens and residents; something that most lmics do not have the capacity to do. canada, for example, which has an existing institutionalized unemployment insurance scheme, has set up a new response benefit to provide $ (cad) per month for up to four months to those who stopped work because of covid- (government of canada ). african countries cannot provide anywhere near the level of funding that is necessary to expect people to stop working and endure long periods of self-confinement. in comparison, some african countries have offered temporary covid- assistance in form of cash (in nigeria, , naira-approximately $ usd), food transfers, or unemployment insurance (as in south africa, the continent's most advanced economy) (dafuleya ; runciman ), amidst concerns that it may not reach the people that desperately need it (human rights watch ). this kind of palliative measure for staying at home is key to the successful implementation of such restrictive measures in any setting. the question is: will the economies in most lmics have the capacity to institute complementary income support measures for tax-paying workers who are part of the formal economy-at a level that is sufficient to support people during the extended lockdown? an even greater concern has to do with the fact that many individuals in lmics, particularly in africa, are either unemployed or are part of an informal economy where they are engaged as day labourers, handymen, petty traders, and local farmers/fishermen. these individuals live from hand to mouth and earn their living on a day-to-day basis as part of this informal economy. unlike hics, where the vast majority of residents are fully accounted for in the system and therefore a systematic rollout of support is feasible, most lmics will not be in a position to support such residents who rely on this informal economy and are unaccounted for in the system (akwagyiram and toyana ) . at the time of writing, nigeria, south africa, and kenya have already imposed a full or partial lockdown response strategy in its major cities. the majority of workers in the informal sector-which accounts for more than per cent of the workforce on the african continent-have been told to stay home (akwagyiram and toyana ) . most people are faced with the tragic and stark choice of either staying at home and risking starvation or going out to work and risking infecting themselves and their loved ones. these issues are further compounded by a confluence of other factors resulting from contextual features that render this situation an unmitigated disaster with massive moral implications: an increase in crime and social disobedience; oppressive regimes using the pandemic as an opportunity to further clamp down on dissenters; citizens unable to collect any of the government's meagre pandemic assistance because of a lack of bank or mobile money accounts; already weak health systems at risk of collapse; and food becoming expensive and scarce during lockdowns, especially since there is no government oversight or control against price gouging. unsurprisingly, poverty is strongly associated with hunger in africa, with sub-saharan african countries already having the highest levels of hunger and undernutrition of all the lmics, which leads to childhood wasting and stunting, higher risk of illness, poor physical and cognitive development, and high mortality rates (klaus et al. ; otekunrin et al. ) . the arrival of covid- and the fact that it will exacerbate hunger and poverty provide the potential for this to be a real humanitarian catastrophe that morally requires urgent attention. according to the africa centres for disease control and prevention, it has been difficult for many african countries to scale up their testing programs in response to covid- (nkengasong ) . while in some cases this stems from not having the technical capacity, a major reason is that these countries are having trouble securing the chemical reagents needed to process tests. since africa does not currently produce their own testing reagents, they need to compete on the world market against hics for this crucial, yet limited, material. africa has not been able to get into the market to get muchneeded diagnostics due to global protectionism-over seventy countries have imposed restrictions on export of essential diagnostic supplies. given the established supply chains and purchasing power of hics, their ability to buy up most of the supplies prevents african countries from taking essential steps to protect themselves from covid- . according to john nkengasong, director of africa's centres for disease control, "the collapse of global co-operation and a failure of international solidarity has shoved africa out of the diagnostics market" (nkengasong ) . in these contexts, where it is not lack of capacity or resources that is the source of the harm but the actions of hics, we find one of many illustrations of where hics are violating their justice-based duties not to unduly harm others by participating in institutions and taking individual actions that have a causal role in the generation and persistence of ill health and health inequality (pogge ) . we have a general moral duty not to cause harm to others; and where we are causally implicated in the commission of that harm, we have a specific moral duty as a matter of justice to alleviate the harm that we have contributed to. these illustrations reinforce the need to revise the structure and function of global health governance systems so as to eliminate the disproportionate and exploitative power relations that have led to the current state of global health and health inequalities. covid- provides an opportunity to reset the structure, function, and aims of global health governance. as far and wide as possible, we should take this opportunity to reinvigorate and re-establish an approach to global health governance with a true central focus on equity. there are a few ways within the global governance of covid- response and global health governance more generally to bring equity back as a central component: & strengthen collective action and global cooperation to assure the conditions in which people can be healthy (e.g., universal health coverage, wage subsidies so people can stay home) & reduce the dominant focus on individual responsibility for health (washing hands, staying home from work, etc.) and focus on how structural factors act as social determinants of health & enhance coordination of response activities so that the actions of hics do not prevent the ability of lmics to promote health and reduce health inequities (e.g., at least prevent hoarding by hics once sars-cov- vaccines start rolling out and at best coordinate global distribution to ensure affordable access for everyone) & develop structures and mechanisms that allow for the prioritization of local response and control in the global response to pandemics and other global health threats & hics should not be completely self-protectionist in orientation when responding to pandemics (e.g., while the united states sought to defund/leave the world health organization, canada increased its foreign aid budget) we believe that the current approach to pandemic preparedness and response-one that is overly driven by the interests, resources, and capacities of hicsundermines the central role of equity in global health and limits our collective ability to effectively address important global health challenges-which as covid- has reminded us, does not respect borders or social status. we argue that our approach to global health governance must equally consider the context and capacity in hics and lmics alike. strengthening the role of equity in guiding the global governance of pandemic response is a sine qua non if we truly want to successfully confront current and future global health challenges. lockdowns: saving lives, but ruining livelihoods in africa africa coronavirus cases could hit million in six months: who explainer: why covid- provides a lesson for africa to fund social assistance. the conversation government of canada. . canada's covid- economic response plan: support for individuals nigeria: protect most vulnerable in covid- response global hunger index: africa edition let africa into the market for covid- diagnostics how far has africa gone in achieving the zero hunger target? evidence from nigeria the ccghr principles for global health research: centering equity in research, knowledge translation, and practice world poverty and human rights gaps in south africa's relief scheme leave some workers with no income. the conversation covid- : the rude awakening for the political elite in low-and middle-income countries there's something in the water: environmental racism in indigenous and black communities coronavirus disease (covid- ) situation report - publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations key: cord- -wawui fd authors: tulchinsky, theodore h.; varavikova, elena a. title: communicable diseases date: - - journal: the new public health doi: . /b - - / - sha: doc_id: cord_uid: wawui fd publisher summary in a world of rapid international transport and contact between populations, systems are needed to monitor the potential explosive spread of pathogens that may be transferred from their normal habitat. the potential for the international spread of new or reinvigorated infectious diseases constitute threat to mankind akin to ecological and other man-made disasters. public health has addressed the issues of communicable disease as one of its key issues in protecting individual and population health. methods of intervention include classic public health through sanitation, immunization, and well beyond that into nutrition, education, case finding, and treatment, and changing human behavior. the knowledge, attitudes, beliefs, and practices of policy makers, health care providers, and parents is as important in the success of communicable disease control as are the technology available and methods of financing health systems. together, these encompass the broad programmatic approach of the new public health to control of communicable diseases. important for all health providers and public health personnel so as to be able to cope with the scale of these problems and to absorb new technologies as they emerge from scientific advances and experience, and their successful application. lived. it was to be observed, indeed, that it did not come straight on toward us; for the city, that is to say within the walls, was indifferently healthy still; nor was it got over the water into southwark; for though there died that week , of all distempers, whereof it might be supposed above died of the plague, yet there was but in southwark, lambeth parish included; whereas in the parishes of st. giles the agent-host-environment triad, discussed in chapter , is fundamental to the success of understanding transmission of infectious diseases and their control, including those well known, those changing their patterns, and those newly emerging or escaping current methods of control. infection occurs when the organism successfully invades the host body, where it multiplies and produces an illness. a host is a person or other living animal, including birds and arthropods, who provides a place for growth and sustenance to an infectious agent under natural, as opposed to experimental, conditions. some organisms, such as protozoa or helminths, may pass successive stages of their life cycle in different hosts, but the primary or definitive host is the one in which the organism passes its sexual stage. the secondary or intermediate host is where the parasite passes the larval or asexual stage. a transport host is a carrier in which the organism remains alive, but does not develop. an agent of an infectious disease is necessary, but not always sufficient to cause a disease or disorder. the infective dose is the quantity of the organism needed to cause clinical disease. a disease may have a single agent as a cause, or it may occur as a result of the agent in company with contributory factors, whose presence is also essential for the development of the disease. a disease may be present in an infected person in a dormant form such as tuberculosis, or a subclinical form, such as poliomyelitis or hiv. the virulence or pathogenicity of an infective agent is the capacity of an infectious agent to enter the host, replicate, damage tissue, and cause disease in an exposed and susceptible host. virulence is indicated by the severity of clinical disease and case fatality rates. the environment provides a reservoir for the organism, and the mode of transmission, by which the organism reaches a new host. the reservoir is the natural habitat where an infectious agent lives and multiplies, from which it can be transmitted directly or indirectly to a new host. the reservoir refers to the natural habitat of the organism, which may be in people, animals, arthropods, plants, soil, or substances in which an organism normally lives and multiplies, and on which it depends for survival or in which it survives in a dormant form. contacts are persons or animals who have been in association with an infected person, animal, or contaminated inanimate object, or environment that might provide an opportunity for acquiring the infective agent. persons or animals that harbor a specific infectious agent, often in the absence of discernible clinical disease, and who serve as a source of infection or contamination of food, water, or other materials, are carriers. a carrier may have an inapparent infection (a healthy cartier) or may be in the incubation or convalescent stage of the infection. communicable diseases may be classified by a variety of methods: by organism, by mode of transmission, by methods of prevention (e.g., vaccine preventable, vector controllable), or by major organism classification, that is, viral, bacterial, and parasitic disease. a virus is a nucleic acid molecule (rna or dna) encapsulated in a protein coat or capsid. the virus is not a complete cell and can only replicate inside a complete cell. the capsid may have a protective envelope of a lipid containing membrane. the capsid and membrane facilitate attachment and penetration of a host cell. inside the host cell, the nucleic molecule may cause the cell's chromosomes to be changed in its own genetic material or so that there is cellular manufacture and virus replication. viroids are smaller rna structures without capsids which can cause plant disease. prions are recently discovered (stanley prusiner, nobel prize, ) variants of viruses or viroids which are the infective agents cause of scrapie in sheep, and similar degenerative central nervous system diseases in cattle and in man (mad cow disease or creutzfeld-jakob disease in humans). bacteria are unicellular organisms that reproduce sexually or asexually, grow on cell-free media, and can exist in an environment with oxygen (aerobic) or in one lacking oxygen (anaerobic). some may enter a dormant state and form spores where they are protected from the environment and may remain viable for years. bacteria include a nucleus of chromosomal dna material within a membrane surrounded by cytoplasm, itself enclosed by the cellular membrane. bacteria are often characterized by their coloration under gram's stain, as gram-negative or gram-positive, as well as by their microscopic morphology, colony patterns on growth media, by the diseases they may cause, as well as by antibody and molecular (dna) marking techniques. bacteria include both indigenous flora (normal resident) bacteria and pathogenic (disease causing) bacteria. pathogenic bacteria cause disease by invading, overcoming natural or acquired resistance, and multiplying in the body. bacteria may produce a toxin or poison that can affect a body site distant from where the bacterial replication occurs, such as in tetanus. bacteria may also initiate an excessive immune response, producing damage to other body tissues away from the site of infection, e.g;, acute rheumatic fever and glomerulonephritis. parasitology studies protozoa, helminths, and arthropods that live within, on, or at the expense of a host. these include oxygen-producing, flagellate, unicellular organisms such as giardia and trichomonas, and amoebas such as entamoeba important in enteric and gynecologic disorders. sporozoa are parasites with complex life cycles in different hosts, such as cryptosporidium or malarial parasites. parasitic disease usually refers to infestation, with fungi, molds, and yeasts that can affect humans. helminths are worms that infest humans especially in poor sanitation and tropical areas. transmission of diseases is by the spread of an infectious agent from a source or reservoir to a person (table . ). direct transmission from one host to another occurs during touching, biting, kissing, sexual intercourse, and projection via droplets, as in sneezing, coughing, or spitting, or by entry through the skin. indirect transmission includes via aerosols of long-lasting suspended particles in air, fecal-oral transmission such as food and waterborne as well as by poor hygenic conditions with inanimate materials, such as soiled clothes, handkerchiefs, toys, or other objects. vector-borne diseases are transmitted via crawling or flying insects, in some cases with multiplication, and development of the organism in the vector, as in malaria. the subsequent transmission to humans is by injection of salivary gland fluid during biting, e.g., congenital syphilis, or by deposition of feces, urine or other material capable of penetrating the skin through a bite wound or other trauma. transmission may occur with insects as a transport mechanism, as in salmonella on the legs of a housefly. airborne transmission occurs inderectly via infective organisms in small aerosols that may remain suspended for long periods of time and which easily enter the respiratory tract. small particles of dust may spread organisms from soil, clothing, or bedding. vertical transmission occurs from one generation to another, or from one stage of the insect life cycle to another stage. maternal-infant transmission occurs during pregnancy (transplacental), delivery, as in gonorrhoea, breast-feeding, e.g., hiv, with transfer of infectious agents from mother to fetus or newborn. resistance to infectious diseases is related to many host and environmental factors, including age, sex, pregnancy, nutrition, trauma, fatigue, living and socioeconomic conditions, and emotional status. good nutritional status has a protective effect against the results of an infection. vitamin a supplements reduce complication rates of measles and enteric infections. tuberculosis may be present in an individual whose resistance is sufficient to prevent clinical disease, but the infected person is a cartier of an organism which can be transmitted to another or cause clinical disease if the person's susceptibility is reduced. immunity is resistance to infection resulting from presence of antibodies or cells that specifically act on the microorganism associated with a specific disease or toxin. immunity to a specific organism can be acquired by having the disease, that is, natural immunity, or by immunization, active or passive, or by protection box . vaccines and prevention "the greeks had two gods of health, aesculapius and hygeia, therapy and prevention, respectively. medicine in the twentieth century retains those two concepts, and vaccination is a powerful means of prevention. what follows is information on the vaccines that together with sanitation, make modem society possible, and that if wisely used will continue to bestow on mankind the gift of prevention, which according to proverb is worth far more than cure." source: plotkin, s. a., mortimer, e. a. . vaccines. second edition. philadelphia: wb saunders (with permission). infectious agent: a pathogenic organism (e.g., virus, bacteria, rickettsia, fungus, protozoa, or helminth) capable of producing infection or an infectious disease. infection: the process of entry, development, and proliferation of an infectious agent in the body tissue of a living organism (human, animal, or plant) overcoming body defense mechanisms, resulting in an inapparent or clinically manifest disease. antigen: a substance (e.g., protein, polysaccharide) capable of inducing specific response mechanisms in the body. an antigen may be introduced into the body by invasion of an infectious agent, by immunization, inhalation, ingestion, or through the skin, wounds, or via transplantation. antibody: a protein molecule formed by the body in response to a foreign substance (an antigen) or acquired by passive transfer. antibodies bind to the specific antigen that elicits its production, causing the infective agent to be susceptible to immune defense mechanisms against infections e.g., humoral and cellular. immunoglobulins: antibodies that meet different types of antigenic challenges. they are present in blood or other body fluids, and can cross from a mother to fetus in utero, providing protection during part of the first year of life. there are five major classes (igg, igm, iga, igd, and ige) and subclasses based on molecular weight. anfisera or antitoxin: materials prepared in animals for use in passive immunization against infection or toxins. source: jawetz, melrick, and adelberg, medical microbiology, . through elimination of circulation of the organism in the community. immunity may be by antibodies produced by the host body or transferred from externally produced antibodies. the body also reacts to infective antigens by cellular responses, including those that directly defend against invading organisms and other cells which produce antibodies. the immune response is the resistance of a body to specific infectious organisms or their toxins provided by a complex interaction of antibodies and cells including a. b cells (bone marrow and spleen) produce antibodies which circulate in the blood, i.e., humoral immunity; b. t cell-mediated immunity is provided by sensitization of lymphocytes of thymus origin to mature into cytotoxic cells capable of destroying virusinfected or foreign cells; c. complement, a humoral response which causes lysis of foreign cells; d. phagocytosis, a cellular mechanism which ingests foreign microorganisms (macrophages and leukocytes). surveillance of disease is the continuous scrutiny of all aspects of occurrence and spread of disease pertinent to effective control of that disease. maintaining ongoing surveillance is one of the basic duties of a public health system, and is vital to the control of communicable disease, providing the essential data for tracking of disease, planning interventions, and responding to future disease challenges. surveillance of infectious disease incidence relies on reports of notifiable diseases by physicians, supplemented by individual and summary reports of public health laboratories. such a system must concern itself with the completeness and quality of reporting and potential errors and artifacts. quality is maintained by seeking clinical and laboratory support to confirm first reports. completeness, rapidity, and quality of reporting by physicians and laboratories should be emphasized in undergraduate and postgraduate medical education. enforcement of legal sanctions may be needed where standards are not met. surveillance of infectious diseases includes the following: . morbidity reports from clinics to public health offices; . mortality reports from attending doctors to vital records; . reports from selected sentinel centers; . special field investigations of epidemics or individual cases; . laboratory monitoring of infectious agents in population samples; . data on supply, use, and side effects of vaccines, toxoids, immune globulins; . data on vector control activities such as insecticides use; . immunity levels in samples of the population at risk; . review of current literature on the disease; . epidemiologic and clinical reports from other jurisdictions. epidemiologic monitoring based on individual and aggregated reports of infectious diseases provide data vital to planning interventions at the community level or for the individually exposed patient and his contacts, along with other information sources such as hospital discharge data and monitoring of sentinel centers. these may be specific medical or community sites that are representative of the population and are able to provide good levels of reporting to monitor an area or population group. a sentinel center can be a pediatric practice site, a hospital emergency room, or other location which will provide a "finger on the pulse" to assess the degree and kind of morbidity occurring in the community. it can also include monitoring in a location previously known for disease transmission, such as hong kong in relation to influenza. epidemiologic analysis provided by government public health agencies should be published weekly, monthly, and annually and distributed to a wide audience of public health and health-related professionals throughout the country. feedback to those in the field on whose initial reports the data are based is vital in order to promote involvement and improved quality of data, as well as to allow evaluation of the local situation in comparison to other areas. in a federal system of government, national agencies report regularly on all state or provincial health patterns. state or provincial health authorities provide data to the counties and cities in their jurisdictions. such data should also be readily available to researchers in other government agencies, universities, and other academic settings for further research and analysis both on internet and hard-copy publications. notifiable diseases are those which a physician is legally required to report to state or local public health officials, by reason of their contagiousness, severity, frequency, or other public health importance (table . ). public health laboratory services provide validation of clinical and epidemiologic reports. they also pro- vide day-to-day supervision of public health conditions, and can monitor communicable disease and vaccine efficacy and coverage. in addition, they support standards of clinical laboratories in biochemistry, microbiology, and genetic screening. nosocomial or hospital-acquired infections constitute a major health hazard associated with care in institutions. in the united states, they occur in - % of hospital admissions and are the cause of lengthening of hospital stay and an estimated , deaths per year. in developing countries, nosocomial infection rates may occur in up to % of hospitalizations. this category of infectious disease most commonly includes infections of the urinary tract, surgical wounds, lower respiratory tract (pneumonias), and blood poisoning or septicemias. in the united states, up to % of hospital-acquired infections are caused by multidrug resistant organisms. staphylococcus infections resistant to many current antibiotics, for example, methicillin and vancomycin, are a notable cause of prolongation of hospitalization or even death. the increasing number of immunodeficient patients has increased the importance of prevention of nosocomial infections. where standards of infection control are lacking, in both developed and developing countries, hospital staff are vulnerable to serious infection. in developing countries, deadly new viruses, such as ebola and marburg viruses mainly affect nursing, medical, and other staff as secondary cases. surveillance and control measures are important elements of hospital management. hospital epidemiologists and infection control staff are part of modem hospital staffing. the cost to the health system of nosocomial infections is a major consideration in planning health budgets. reducing the risk of acquiring such infections in hospital justifies substantial expenditures for hospital epidemiology and infection control activities. with diagnostic related group payment for hospital care (by diagnosis rather than by days of stay) the good manager has a major incentive to ensure that the risk of nosocomial infections is minimized, since they can greatly prolong hospital stays, raising patient dissatisfaction and health care costs. an endemic disease is the constant usual presence of a disease or infectious agent in a given geographic area or population group. hyperendemic is a state of persistence of high levels of incidence of the disease. holoendemic means that the disease appears early in life and affects most of the population, as in malaria or hepatitis a and b in some regions. an epidemic is the occurrence in a community or region of a number of cases of an illness in excess of the usual or expected number of cases. the number of cases constituting an epidemic varies with the disease, and factors such as previous epidemiological patterns of the disease, time and place of the occurrence, and the population involved must be taken into account. a single case of a disease long absent from an area, such as polio, constitutes an epidemic, and therefore a public health emergency because a clinical case may represent a hundred carriers with nonparalytic or subclinical poliomyelitis. in the s, two to three or more cases of measles linked in time and place may be considered sufficient evidence of transmission and presumed to be an epidemic. a pandemic is occurrence of a disease over a very wide area, crossing international boundaries, affecting a large proportion of the population. each epidemic should be regarded as a unique natural experiment. the investigation of an epidemic requires preparation and field investigation in conjunction with local health and other relevant authorities. verification of cases and the scope of the epidemic will require case definition and laboratory confirmation. tabulation of known cases according to time, place, and person are important for immediate control measures and formulation of the hypothesis as to the nature of the epidemic. an epidemic curve is a graphic plotting of the distribution of cases by the time of onset or reporting, which gives a picture of the timing, spread, and extent of the disease from the time of the initial index cases and the secondary spread. epidemic investigation requires a series of steps. this starts with confirmation of the initial report and preliminary investigation, defining who is affected, determining the nature of the illness and confirming the clinical diagnosis, and recording when and where the first (index) and follow-up (secondary) cases occurred, and how the disease was transmitted. samples are taken from index case patients (e.g., blood, feces, throat swabs) as well as from possible vectors (e.g., food, water, sewage, environment). a working hypothesis is established based on the first findings, taking into account all plausible explanations. the epidemic pattern is studied, establishing common source or risk factors, such as food, water, contact, environment, and drawing a time line of cases to define the epidemic curve. how many are ill (the numerator) and what is the population at risk (the denominator) establish the attack rate, namely, the percentage of sick among those exposed to the common factor. what is a reasonable explanation of the occurrence; is there a previous pattern, with the present episode a recurrence or new event? consultation with colleagues and the literature helps to establish both a biological and epidemiologic plausibility. what steps are needed to prevent spread and recurrence of the disease? coordination with relevant health and other officials and providers is required to establish surveillance and control systems, document and distribute reports, and respond to the public's fight to know. the first reports of excess cases may come from a medical clinic or hospital. the initial (sentinel or index) cases provide the first clues that may point to a common source. investigation of an epidemic is designed to quickly elucidate the cause and points of potential intervention to stop its continuation. this requires skilled investigation and interpretation. epidemiologic investigations have defined many public health problems. rubella syndrome, legionnaire's disease, aids, and lyme and hantavirus diseases were first identified clinically when unusually large numbers of cases appeared with common features. the suspicions that were raised led to a search for causes and the identification of control methods. a working hypothesis of the nature of an epidemic is developed based on the initial assessment, the type of presentation, the condition involved, and previous local, regional, national, and international experience. the hypothesis provides the basis for further investigation, control measures, and planning additional clinical and laboratory studies. surveillance will then monitor the effectiveness of control measures. communication of findings to local, regional, national, and international health reporting systems is important for sharing the knowledge with other potential support groups or other areas where similar epidemics may occur. the centers for disease control and prevention (cdc), originally organized in as the office for malaria control in war areas, is part of the u.s. public health service. as of , the cdc had a budget of $ . billion, and employees include epidemiologists, microbiologists, and many other professionals. the cdc includes national centers for environmental health and injury control, chronic disease prevention and health promotion, infectious diseases, prevention services, health statistics, occupational safety and health, and international health. the epidemic intelligence service (eis) of the cdc in the united states is an excellent model for the organization of the national control of communicable diseases. young clinicians are trained to carry out epidemiologic investigations as part of training to become public health professionals. eis officers are assigned to state health departments, other public health units, and research centers as part of their training, carrying out epidemic investigation and special tasks in disease control. the cdc, in cooperation with the who, has developed and offers free of charge, a personal computer program to support field epidemiology, including epidemic investigations (epi-info), which can be accessed and down-loaded from the worldwide web. this program should be adopted widely in order to improve field investigations, to encourage reporting in real time, and to develop high standards in this discipline. cdc's morbidity and mortality weekly report (mmwr) is a weekly publication of the cdc's epidemiologic data, also available free on the internet. it includes special summaries of reportable infectious diseases as well as noncom- although an infectious disease is an event affecting an individual, it is communicable to others, and therefore its control requires both individual and community measures of protection. control of the disease is a reduction in its incidence, prevalence, morbidity, and mortality. elimination of a disease in a specified geographic area may be achieved as a result of intervention programs such as individual protection against tetanus; elimination of infections such as measles requires stoppage of circulation of the organism. eradication is success in reduction to zero of incidence of the disease and presence in nature of the organism, such as with smallpox. extinction means that a specific organism no longer exists in nature or in laboratories. public health applies a wide variety of tools for the prevention of infectious diseases and their transmission. it includes activities ranging from filtration and disinfection of community drinking water to environmental vector control, pasteurization of milk, and immunization programs (see table . ). no less important are organized programs to promote self protection, case finding, and effective treatment of infections to stop their spread to other susceptible persons (e.g., hiv, sexually transmitted diseases, tuberculosis, malaria). planning measures to control and eradicate specific communicable diseases is one of the principal activities of public health and remains so for the twenty-first century. treating an infection once it has occurred is vital to the control of a communicable disease. each person infected may become a vector and continue the chain of transmission. successful treatment of the infected person reduces the potential for an uninfected contact person to acquire the infection. bacteriostatic agents or drugs such as sulfonamides inhibit growth or stop replication of the organism, allowing normal body defenses to overcome the organism. bacteriocidal drugs such as penicillin act to kill pathogenic organisms. traditional medical emphasis on single antibiotics has changed to use of multiple drug combinations for tuberculosis and more recently for hospital-acquired infections. antibiotics have made enormous contributions to clinical medicine and public health. however, pathogenic organisms are able to adapt or mutate and develop resistance to antibiotics, resulting in drug resistance. wide-scale use of antibiotics has led to increasing incidence of resistant organisms. multidrug resistance constitutes one of the major public health challenges at the end of the twentieth century. antiviral agents (e.g., ribovarin) are important additions to medical treatment potential, as are "cocktails" of antiviral agents for management of hiv infection. antibiotic use is a health problem requiting attention of clinicians and their teachers as well as the public health community and health care managers, representing the interaction of health issues across the entire spectrum of services. organized public health services are responsible for advocating legislation and for regulating and monitoring programs to prevent infectious disease occurrence and/or spread. they function to educate the population in measures to reduce or prevent the spread of disease. health promotion is one of the most essential instruments of infectious disease control. it promotes compliance and community support of preventive measures. these include personal hygiene and safe handling of water, milk, and food supplies. in sexually transmitted diseases, health education is the major method of prevention. each of the infectious diseases or groups of infectious diseases have one or more preventive or control approaches (table . ). these may involve the coordinated intervention of different disciplines and modalities, including epidemiologic monitoring, laboratory confirmation, environmental measures, immunization, and health education. this requires teamwork and organized collaboration. very great progress has been made in infectious disease control by clinical, public health, and societal means since in the industrialized countries and since the s in the developing world. this is attributable to a variety of factors, including organized public health services; the rapid development and wide use of new and improved vaccines and antibiotics; better access to health care; and improved sanitation, living conditions, and nutrition. triumphs have been achieved in the eradication of smallpox and in the increasing control of other vaccine-preventable diseases. however, there remain serious problems with tb, stds, malaria, and new infections such as hiv, and an increase in multiple drug-resistant organisms. vaccines are one of the most important tools of public health in the control of infectious diseases, especially for child health. vaccine-preventable diseases ta b l e . annual incidence of selected vaccine-preventable infectious diseases in rates per , population selected years, united states, - disease the body responds to invasion of disease-causing organisms by antigenantibody reactions and cellular responses. together, these act to restrain or destroy the disease-causing potential. strengthening this defense mechanism through im-box . definitions of immunizing agents and processes vaccines: a suspension of live or killed microorganisms or antigenic portion of those agents presented to a potential host to induce immunity to prevent the specific disease caused by that organism. preparation of vaccines may be from: a. live attenuated organisms which have been passed repeatedly in tissue culture or chick embryos so that they have lost their capacity to cause disease but retain an ability to induce antibody response, such as polio-sabin, measles, rubella, mumps, yellow fever, bcg, typhoid, and plague. b. inactivated or killed organisms which have been killed by heat or chemicals but retain an ability to induce antibody response; they are generally safe but less efficacious than live vaccines and require multiple doses, such as polio-salk, influenza, rabies, and japanese encephalitis. c. cellular fractions usually of a polysaccharide fraction of the cell wall of a disease-causing organisms, such as pneumococcal pneumonia or meningococcal meningitis. d. recombinant vaccines produced by recombinant dna methods in which specific dna sequences are inserted by molecular engineering techniques, such as dna sequences spliced to vaccinia virus grown in cell culture to produce influenza and hepatitis b vaccines. toxoids or antisera: modified toxins are made nontoxic to stimulate formation of an antitoxin, such as tetanus, diphtheria, botulism, gas gangrene, and snake and scorpion venom. immune globulin: an antibody-containing solution derived from immunized animals or human blood plasma, used primarily for short-term passive immunization, e.g., rabies, for immunocompromised persons. antitoxin: an antibody derived from serum of animals after stimulation with specific antigens and used to provide passive immunity, e.g., tetanus. munization is one of the outstanding achievements of public health, as treatment of infectious diseases by antimicrobials is a major element of clinical medicine. immunization (vaccination) is a process used to increase host resistance to specific microorganisms to prevent them from causing disease. it induces primary and secondary responses in the human or animal body: a. primary response occurs on first exposure to an antigen. after a lag or latent period of - days (depending on the antigen) specific antibodies appear in the blood. antibody production ceases after several weeks but memory cells that can recognize the antigen and respond to it remain ready to respond to a further challenge by the same antigen. b. secondary (booster) response is the response to a second and subsequent exposure to an antigen. the lag period is shorter than the primary response, the peak is higher and lasts longer. the antibodies produced have a higher affinity for the antigen, and a much smaller dose of the antigen is required to initiate a response. c. immunologic memory exists even when circulating antibodies are insufficient to protect against the antigen. when the body is exposed to the same antigen again, it responds by rapidly producing high levels of antibody to destroy the antigen before it can replicate and cause disease. immunization protects susceptible individuals from communicable disease by administration of a living modified agent, or subunit of the agent, a suspension of killed organisms or an inactivated toxin (see table . ) to stimulate development of antibodies to that agent. in disease control, individual immunity may also protect another individual. herd immunity occurs when sufficient persons are protected (naturally or by immunization) against a specific infectious disease reducing circulation of the organism, thereby lowering the chance of an unprotected person to become infected. each pathogen has different characteristics of infectivity, and therefore different levels of herd immunity are required to protect the nonimmune individual. the critical proportion of a population that must be immunized in order to interrupt local circulation of the organism varies from disease to disease. eradication of smallpox was achieved with approximately % world coverage, followed by concentration on new case findings and immunization of contacts and surrounding communities. for highly infectious diseases, such as measles, immunization coverage of over % is needed to achieve local eradication. immunization coverage in a community must be monitored in order to gauge the extent of protection and need for program modification to achieve targets of disease control. immunization coverage is expressed as a proportion in which the numerator is the number of persons in the target group immunized at a specific age, and the denominator is the number of persons in the target cohort who should have been immunized according to the accepted standard: vaccine coverage = no. persons immunized in specific age group • no. persons in the age group during that year immunization coverage in the united states is regularly monitered by the national immunization survey by a household survey in all states, as well as selected urban areas considered to be at high risk for undervaccination. an initial telephone survey is followed by confirmation, where possible, from documentation from the parents or health care providers. the survey for july -june examined children born between august and november (i.e., aged - months, median age months). the results show improving coverage, with % having received three or more doses of dpt (diphtheria, pertussis, and tetanus), % with three or more doses of opv (oral polio vaccine), % with three or more doses of haemophilus influenzae, type b (hib), but only % with three or more doses of hepatitis b. however, only % had received all recommended vaccines at the recommended ages. eases that still cause millions of deaths globally each year. other important infectious diseases are still not subject to vaccine control because of difficulties in their development. in some cases, a microorganism can mutate with changes. viruses can undergo antigenic shifts in the molecular structure in the organism, producing completely new subtypes of the organism. hosts previously exposed to other strains may have little or no immunity to the new strains. antigenic drift refers to relatively minor antigenic changes which occur in viruses. this is responsible for frequent epidemics. antigenic shift is believed to explain the occurrence of new strains of influenza virus necessitating, for example, annual reformulation of the influenza vaccine associated with large scale epidemics and pandemics. new variants of poliovirus strains are similar enough to the three main types so that immunity to one strain is carded over to the new strain. molecular epidemiology is a powerful new technique used to specify the geographic origin of organisms such as poliomyelitis and measles viruses, permiting tracking of the source of the virus and epidemic. combinations of more than one vaccine is now common practice with a trend to enlarging the cocktail of vaccines in order to minimize the number of injections, and visits required. this reduces the number of visits to carry out routine immunization saving staff time and costs, as well as increasing compliance. there are virtually no contraindications to use of multiple antigens simultaneously. examples of vaccine cocktails include dpt (diphtheria, pertussis, and tetanus) in combination with haemophilus influenzae b, poliomyelitis, and varicella, or mmr (measles, mumps, and rubella) vaccines. interventions in the form of effective vaccines save millions of lives each year and contribute to improved health of countless children and adults throughout the world. vaccination is now accepted as one of the most cost-effective health interventions currently available. continuous policy review is needed regarding allocation of adequate resources, logistical organization, and continued scientific effort to seek effective, safe, and inexpensive vaccines for other important diseases such as malaria and hiv. new technology of recombinant vaccines, such as that of hepatitis b, holds promise for important vaccine breakthroughs in the decades ahead. internationally, much progress was made in the s in the control of vaccinepreventable diseases. at the end of the s, fewer than % of the world's children were being immunized. who, unicef, and other international organizations mobilized to promote an expanded programme on immunization (epi) with a target of reaching % coverage by . immunization coverage increased in the developing countries, preventing some million child deaths annually. bacillus calmette-gu rin (bcg) coverage rose from to %; poliomyelitis with opv (three doses) from to %, and tetanus toxoid for pregnant women from to %. since , there has been a decline in coverage in some parts of the world, mainly in sub-saharan africa. the challenge remains to achieve control or eradication of vaccine-preventable diseases, thus saving millions of more lives. part of the hfa stresses the epi approach, which includes immunization against diphtheria, pertussis, tetanus, po-liomyelitis, measles, and tuberculosis. an extended form of this is the epi plus program which combines epi with immunization against hepatitis b and yellow fever and, where appropriate, supplementation with vitamin a and iodine. the success in international eradication of smallpox is now being followed by a campaign to eradicate poliomyelitis and other important infectious diseases. diphtheria. diphtheria is an acute bacterial disease of the tonsils, nasopharynx, and larynx caused by the organism corynebacterium diphtheriae. it occurs in colder months in temperate climates where the organism is present in human hosts and is spread by contact with patients or carriers. it has an incubation period of - days. in the past, this was primarily an infection of children and was a major contributor to child mortality in the prevaccine and preantibiotic eras. diphtheria has been virtually eliminated in countries with well-established immunization programs. in the s, an outbreak of diphtheria occurred in the countries of the former soviet union among people over age . it reached epidemic proportions in the s, with , cases ( - ) with deaths in in russia alone. this indicates a failure of the vaccination program in several respects: it used only three doses of dpt in infancy; no boosters were given at school age or subsequently; the efficacy of diphtheria vaccine may have been low, and coverage was below %. efforts to control the present epidemic include mass vaccination campaigns for persons over years of age with a single dose of dt (diphtheria and tetanus) and increasing coverage of routine dpt vaccines to four doses by age years. the epidemic and its control measures have led to improved coverage with dt for those over years, and % coverage among children aged - months. who recommends three doses of dpt in the first year of life and a booster at school entry. this is considered by many to be insufficient to produce long-lasting immunity. the united states and other industrialized countries use a four-dose schedule and recommend periodic boosters for adults with dt. pertussis. pertussis is an acute bacterial disease of the respiratory tract caused by the bacillus bordetella pertussis. after an initial coldlike (catarrhal) stage, the patient develops a severe cough which comes in spasms (paroxysms). the disease can last - months. the paroxysms can become violent and may be followed by a characteristic crowing or high pitched inspiratory whooping sound, followed by expulsion of a tenacious clear sputum, often followed by vomiting. in poorly immunized populations and those with malnutrition, pneumonia often follows and death is common. pertussis declined dramatically in the industrialized countries as a result of widespread coverage with dpt. however, because the pertussis component of the vaccine caused some reactions, many physicians avoided its use, using dt alone. during the s in the united kingdom, many physicians recommended against vaccination with dpt. as a result, pertussis incidence increased with substantial mortality rates. this led to a reappraisal of the immunization program, with insti-tution of incentive payments to general practitioners for completion of vaccination schedules. as a result of these measures, vaccination coverage, with resulting pertussis control, improved dramatically in the united kingdom. pertussis continues to be a public health threat and recurs wherever there is inadequate immunization in infancy. a new acellular vaccine is ready for widespread use and will be safer with fewer and less severe reactions in infants, increasing the potential for improved confidence and support for routine vaccination. use of the new vaccine is spreading in the united states and forms part of the u.s. recommended vaccination schedule. tetanus. tetanus is an acute disease caused by an exotoxin of the tetanus bacillus (clostridium tetani) which grows anaerobically at the site of an injury. the bacillus is universally present in the environment and enters the human body via penetrating injuries. following an incubation period of - days, it causes an acute condition of painful muscular contractions. unless there is modem medical care available, patients are at risk of high case fatality rates of - % (highest in infants and the elderly). antitetanus serum (ats) was discovered in and during world war i, ats contributed to saving the lives of many thousands of wounded soldiers. tetanus toxoid was developed in . the organism, because of its universal presence in the environment, cannot be eradicated. however, the disease can be controlled by effective immunization of every child during infancy and school age. adults should receive routine boosters of tetanus toxoid once very decade. newborns are infected by tetanus spores (tetanus neonatorum) where unsanitary conditions or practices are present. it can occur when traditional birth attendants at home deliveries use unclean instruments to sever the umbilical cord, or dress the severed cord with contaminated material. tetanus neonatorum remains a serious public health problem in developing countries. immunization of pregnant women and women of childbearing age is reducing the problem by conferring passive immunity to the newborn. the training of traditional birth attendants in hygienic practice and the use of medically supervised birth centers for delivery also decreases the incidence of tetanus neonastorum. elimination of tetanus neonatorum by the year was made a health target by the world summit of children in . in that year, the number of deaths from neonatal tetanus was reported by unicef as , infants worldwide, declining to , in . immunization of pregnant women increased from under % in to % in - . despite progress, coverage is still too low to achieve the target of elimination. poliomyelitis. polio virus infection may be asymptomatic or cause an acute nonspecific febrile illness. it may reach more severe forms of aseptic meningitis and acute flaccid paralysis with long-term residual paralysis or death during the acute phase. poliomyelitis is transmitted mainly by direct person-to-person contact, but also via sewage contamination. large-scale epidemics of disease, with attendant paralysis and death, occurred in industrialized countries in the s and s, engendering widespread fear and panic and thousands of clinical cases of "infantile paralysis". growth of the poliovirus by john enders and colleagues in tissue culture in led to development of the first inactivated polio vaccine by jonas salk in the mid- s and gave hope and considerable success in the control of the disease. the development of the live attenuated oral poliomyelitis vaccine by albert sabin, licensed in , added a new dimension to its control because of the effectiveness, low cost, and ease of administration of the vaccine. the two vaccines in their more modern forms, enhanced strength inactivated polio vaccine (eipv), and triple oral polio vaccine (topv), have been used in different settings with great success. oral polio vaccine (opv) induces both humoral and cellular, including intestinal, immunity. the presence of opv in the environment by contact with immunized infants and via excreta of immunized persons in the sewage gives a booster effect in the community. immunization using opv, in both routine and national immunization days (nids) has proven effective in dramatically reducing poliomyelitis and circulation of the wild virus in many parts of the world. use of the enhanced strength ipv (eipv) produces early and high levels of circulating antibodies, as well as protecting against the vaccine-associated disease. in rare cases opv can cause vaccine-associated paralytic poliomyelitis (vapp), with a risk of case per , with initial doses, and case per over million with subsequent doses. approximately eight to ten cases of vapp occur annually in the united states, with clinical, ethical, and legal implications. use of ipv as initial protection eliminates this problem. experience in gaza and the west bank in the s and s, and later in israel, showed that a combination of ipv and opv is effective in overcoming endemic and imported poliovirus. opv requires multiple doses to achieve protective antibody levels. where there are many enteroviruses in the environment, as is the case in most developing countries, interference in the uptake of opv may result in cases of paralytic poliomeylitis among persons who have received or even doses of adequate opv. controversy as to the relative advantages of each vaccine continues. the opv program of mass repeated vaccination in control of poliomyelitis in the americas established the primacy of opv in practical public health, and the momentum to eradicate poliomyelitis is building. a combined schedule of ipv and opv would eliminate the wild virus and protect against vaccine-associated disease. the sequential use of ipv and opv was adopted as part of the routine infant immunization program in the united states in , but ipv alone was adopted in . there are concerns that exclusive use of either vaccine alone will not lead to the desired goal of eradication of polyomyelitis. progress in global eradication of polio has been impressive. global coverage of infants with three doses of opv reached % in as compared to % in . the african region of who had an increase in opv coverage from % in to % in . national immunization days (nids) were conducted in countries in and in , covering million children in . mopping up operations to reinforce coverage of children in still endemic areas is proceeding along with increased emphasis on acute flaccid paralysis (afp) monitoring. confirmed polio cases reported continued at - , per year in - . with continued national and international emphasis, and support of who, rotary international, unicef, donor countries, and others, there is a real prospect of a world without polio, if not by the year , then or shortly thereafter. measles is an acute disease caused by a virus of the paramyxovirus family. it is highly infectious with a very high ratio of clinical to subclinical case ratio ( / ). measles has a characteristic clinical presentation with fever, white spots (koplik spots) on the membranes of the mouth, and a red blotchy rash appearing on the rd- th day lasting - days. mortality rates are high in young children with compromised nutritional status, especially vitamin a deficiency. the measles virus evolved from a virus disease of cattle (rinderpest) some - years ago, becoming an important disease of humans with high mortality rates in debilitated, poorly nourished children, and significant mortality and morbidity even in industrialized countries. in the prevaccine era, measles was endemic worldwide, and even in the late s it remains one of the major childhood infectious diseases. it is one of the commonest causes of death for school age children worldwide. despite earlier predictions that measles deaths would be halved to , by , who reported . million measles deaths in that year and over million in . eradication in the first decade of the next century is a feasible goal, provided that there is an adequate international effort. measles immunization increased from under % worldwide in to % in - , but % in sub-saharan africa. single-dose immunization failed to meet control or eradication requirements even in the most developed parts of the world. a live vaccine, licensed in , was later replace by a more effective and heat stable vaccine, but still with a primary vaccination failure rate (i.e., fails to produce protective antibodies) of - %, and secondary failure rate (i.e., produces antibodies but protection is lost over time) of %. a two-dose policy incorporates a booster dose, usually at school-age, in addition to maximum feasible infant coverage of children in the - month period (timing varies in different countries). catch-up campaigns among schoolage children should be carried out until the routine two-dose policy has time to take full effect. nearly universal primary education in developing countries, offers an opportunity for mass coverage of school age children with a second dose of measles and a resulting increase of herd immunity to reduce the transmission of the virus. the two-dose policy adopted in many countries, should be supplemented with catch-up campaigns in schools to provide the booster effect for those previously immunized and to cover those previously unimmunized, especially in developing countries. the cdc considers that domestic transmission in the united states has been interrupted and that most localized outbreaks were traceable to imported cases. south america and the caribbean countries are now considered free of indigenous measles, based on their successful use of nids, although a large epidemic occurred in in brazil. it now appears that eradication has become a feasible target during the early part of the next century, with a strategy of levels of coverage in in-fancy with a two-dose policy, supplemented by catch-up campaigns to older children and young adults, and outbreak control. mumps. mumps is an acute viral disease characterized by fever, swelling, and tenderness usually of the parotid glands, but also other glands. the incubation period ranges between and days. orchitis, or inflammation of the testicles, occurs in - % of postpubertal males and oophoritis, or inflammation of the ovaries, in % of postpubertal females. sterility is an extremely rare result of mumps. central nervous system involvement can occur in the form of aseptic meningitis, almost always without sequelae. encephalitis is reported in - per , cases with an overall case fatality rate of . %. pancreatitis, neuritis, nerve deafness, mastiffs, nephritis, thyroiditis, and pericarditis, although rare, may occur. most persons born before are immune to the disease, because of the nearly universal exposure to the disease before that time. the live attenuated vaccine introduced in the united states in is available as a single vaccine or in combination with measles and rubella as the measlesmumps-rubella (mmr) vaccine. it provides long-lasting immunity in % of cases. mumps vaccine is now recommended in a two-dose policy with the first dose of mmr given between and months of age and a second dose given either at school entry or in early adolescence. mmr in two doses is now standard policy in the united sates, sweden, canada, israel, the united kingdom, and other countries. the incidence of mumps has consequently declined rapidly. local eradication of this disease is worthwhile and should be part of a basic international immunization program. rubella. rubella (german measles) is generally a mild viral disease with lymphadenopathy and a diffuse, raised red rash. low grade fever, malaise, coryza, and lymphadenopathy characterize the prodromal period. the incubation period is usually - days. differentiation from scarlet fever, measles, or other febrile diseases with rash may require laboratory testing and recovery of the virus from nasopharyngeal, blood, stool, and urine specimens. in , norman gregg, an australian ophthalmologist, noted an epidemic of cases of congenital cataract in newborns associated with a history of rubella in the mother during the first trimester. subsequent investigation demonstrated that intrauterine death, spontaneous abortion, and congenital anomalies occur commonly when rubella occurs early in pregnancy. congenital rubella syndrome (crs) occurs with single or multiple congenital anomalies including deafness, cataracts, microophthalmia, congenital glaucoma, microcephaly, meningoencephalitis, congenital heart defects, and others. moderate and severe cases are recognizable at birth, but mild cases may not be detected for months or years after birth. insulin-dependent diabetes is suspected as a late sequela of congenital rubella. each case of crs is estimated to cost some $ , in health care costs during the patient's lifetime. prior to availability of the attenuated live rubella vaccine in , the disease was universally endemic, with epidemics or peak incidence every - years. in unvaccinated populations, rubella is primarily a disease of childhood. in areas where children are well vaccinated, adolescent and young adult infection is more apparent, with epidemics in institutions, colleges, and among military personnel. a sharp reduction of rubella cases was seen in the united states following introduction of the vaccine in , but increased in , following rubella epidemics in - . a further reduction in cases was followed by a sharp upswing of rubella and crs in [ ] [ ] [ ] . an outbreak of rubella among the amish in the united states, who refuse immunization on religious grounds, resulted in cases of crs in . it is now thought that vaccination of sufficient numbers in the united states reduced circulation of the virus and protected most vulnerable groups in the population. in the past, immunization policy in some countries was to vaccinate school girls aged to protect them for the period of fertility. the current approach is to give a routine dose of mmr in early childhood, followed by a second dose in early school age to reduce the pool of susceptible persons. women of reproductive age should be tested to confirm immunity before pregnancy and immunized if not already immune. should a woman become infected during pregnancy, termination of pregnancy previously recommended is now managed with hyperimmune globulin. the infection of pregnant women during their first trimester of pregnancy is the primary public health implication of rubella. the emotional and financial burden of crs, including the cost of treatment of its congenital defects, makes this vaccination program cost-effective. its inclusion in a modem immunization program is fully justified. elimination of crs syndrome should be one of the primary goals of a program for prevention of vaccine-preventable disease in developed and developing countries. adoption of mmr and the two-dose policy will gradually lead to eradication of rubella and rubella syndrome. viral hepatitis. viral hepatitis is a group of diseases of increasing public health importance due to their large scale worldwide prevalence, their serious consequences, and our increasing ability to take preventive action. viral hepatic infectious diseases each have specific etiologic, clinical, epidemiologic, serologic, and pathologic characteristics. they have important short-and long-term sequelae. vaccine development is of high priority for control and ultimate eradication. hepatitis a. hepatitis a (hav) was previously known as infectious hepatitis or epidemic jaundice. hav is mainly transmitted by the fecal-oral route. clinical severity varies from a mild illness of - weeks to a debilitating illness lasting several months. the norm is complete recovery within weeks, but a fulminating or even fatal hepatitis can occur. severity of the disease worsens with increasing age. hav is sporadic/endemic worldwide. improving sanitation raises the age of exposure, with accompanying complications. it now occurs particularly in persons from industrialized countries when exposed to situations of poor hygiene, or among young adults when traveling to areas where the disease is en-demic. common source outbreaks occur in school-aged children and young adults from case contact, or from food contaminated by infected handlers. hepatitis a may be a serious public health problem in a disaster situation. prevention involves improving personal and community hygiene, with safe chlorinated water and proper food handling. hepatitis a vaccine has been recently licensed for use in the united states, and will probably soon be recommended for routine vaccination programs, as well as for persons traveling to endemic areas. hepatitis b. hepatitis b (hbv) once called serum jaundice, was thought to be transmitted only by injections of blood or blood products. it is now known to be present in all body fluids and easily transmissible by household and sexual contact, perinatal spread from mother to newborn, and between toddlers. however, it is not spread by the oral-fecal route. hepatitis b virus is endemic worldwide and is especially prevalent in developing countries. carrier status with persistent viremia varies from < % of adults in north america to % in some parts of the world. carders have detectable levels of hbsag, the surface antigen (i.e., australian antigen), in their blood. high risk groups in developed countries include intravenous drug users, homosexual men, persons with high numbers of sexual partners, those receiving tattoos, body piercing or acupuncture treatments, and residents or staff of institutions such as group homes and prisons. immunocompromised and hemodialysis patients are commonly carders of hbv. hbv may also be spread in a health system by use of inadequately sterilized reusable syringes, as in china and the former soviet union. transmission is reduced by screening blood and blood products for hbsag and strict technique for handling blood and body fluids in health settings. hbv is clinically recognizable in less than % of infected children but is apparent in - % of infected adults. clinically hbv has an insidious onset with anorexia, abdominal discomfort, nausea, vomiting, and jaundice. the disease can vary in severity from subclinical, very mild to fulminating liver necrosis, and death. it is a major cause of primary liver cancer, chronic liver disease, and liver failure, all devastating to health and expensive to treat. hepatitis b virus is considered to be the cause of % of primary cancer of the liver in the world and the most common carcinogen after cigarette smoking. the who estimates that more than billion people alive today have been infected with hbv. it is also estimated that million persons are chronic carriers of hbv, with an estimated - . million deaths per year from cirrhosis or primary liver cancer. this makes hepatitis b control a vital issue in the revision of health priorities in many countries. strict discipline in blood banks and testing of all blood donations for hbv, as well as hiv, and hepatitis c, is mandatory, with destruction of those with positive tests. contacts should be immunized following exposure with hbv immunoglobulin and hbv vaccine. the inexpensive recombinant hbv vaccine should be adopted by all countries and included in routine vaccination of infants. catch-up immunization for older children is also desirable. immunization programs should include those exposed at work, such as health, prison, or sex workers and adults in group settings. hbv immunization has been included in who's epi-plus expanded program of immunization. hepatitis c. first identified in , and previously known as non-a, non-b hepatitis, hepatitis c (hcv) has an insidious onset with jaundice, fatigue, abdominal pain, nausea, and vomiting. it may cause mild to moderate illness, but chronicity is common going on to cirrhosis and liver failure. the cdc estimates that million americans are chronically infected with hcv, with - , resulting deaths per annum, and the main cause of liver transplants. hcv is transmitted most commonly in blood products, but also among injecting drug users ( % of intravenous drug users were hcv positive in a vancouver study in ), and is also a risk for health workers. the disease may also occur in dialysis centers and other medical situations. person-to-person spread is unclear. prevention of transmission includes routine testing of blood donations, antiviral treatment of blood products, needle exchange programs, and hygiene. the who in has declared hepatitis prevention as a major public health crisis, with an estimated million persons infected worldwide ( ) , stressing that this "silent epidemic" is being neglected and that screening of blood products is vital to reduce transmission of this disease as for hiu hcv is a major cause of chronic cirrhosis and liver cancer. no vaccine is available at present, but an experimental vaccine is undergoing field trials. interferon and ribavirin treatment is reportedly effective in % of cases. hepatitis d. hepatitis d virus (hdv) also known as delta hepatitis, may be self-limiting or progress to chronic hepatitis. it is caused by a viruslike particle which infects cells along with hbv as a coinfection or in chronic carriers of hbv. hdv occurs worldwide in the same groups at risk for hbv. it also occurs in epidemics and is endemic in south america, africa, and among drug users. prevention is by measures similar to those for hbv. management for hdv is by passive immunity with immunoglobulin for contacts and high risk groups, and should include hbv vaccination as the diseases often coincide. there is currently no vaccine for hdv. hepatitis e. hepatitis e virus has an epidemiological and clinical course similar to that of hav. there is no evidence of a chronic form of hev. one striking characteristic of hev is its high mortality rate among pregnant women. the disease is caused by a viruslike particle with an incubation period of - days and is most common in young adults. sporadic cases as well as epidemics have been identified in india, pakistan, burma, china, russia, mexico, and north africa. hev results from waterborne epidemics or as sporadic cases in areas with poor hygiene, spread via the oral-fecal route. it is a hazard in disaster situations with crowding and poor sanitary conditions. prevention is by safe management of water supplies and sanitation. disease management is supportive care; passive immunization is not helpful and no vaccine is currently available. teria which causes meningitis and other serious infections in children under months of age. before the introduction of effective vaccines, as many as in children developed invasive hib infection. two-thirds of these had hib meningitis, with a case fatality rate of - %. long-term sequelae such as hearing impairment and neurological deficits occurred in - % of survivors. the first hib vaccine was licensed in , based on capsular material from the bacteria. extensive clinical trials in finland demonstrated a high degree of efficacy, but less impressive results were in seen in postmarketing efficacy studies. by , a conjugate vaccine based on an additional protein cell capsular factor capable of enhancing the immunologic response was introduced. several conjugate vaccines are now available. the conjugate vaccines are now combined with dpt as their schedule is simultaneous with that of the dpt. although the hib vaccine has been found to be cost-effective, despite initially being as costly as all the basic vaccines combined (i.e., dpt, opv, mmr, and hbv). for this reason, its use thus far has been limited to industrialized countries. the vaccine is a valuable addition to the immunologic armamentarium. it showed dramatic results in local eradication of this serious early childhood infection in a number of european countries and a sharp reduction in the united states. impressive field trials in the gambia showed a sharp reduction in mortality from invasive streptococcal diseases. the price of the vaccine has also fallen dramatically since the mid s. as a result, in , the world health organization recommended inclusion of hib vaccine in routine immunization programs in developing countries. influenza. influenza is an acute viral respiratory illness characterized by fever, headache, myalgia, prostration, and cough. transmission is rapid by close contact with infected individuals and by airborne particles with an incubation period of - days. it is generally mild and self-limited with recovery in - days. however, in certain population groups, such as the elderly and chronically ill, infection can lead to severe sequelae. gastrointestinal symptoms commonly occur in children. during epidemics, mortality rates from respiratory diseases increase because of the large numbers of persons affected, although the case fatality rates are generally low. over the past century, influenza pandemics have occurred in , , , and , while epidemics are annual events. the influenza pandemic of caused millions of deaths among young adults, by some estimates killing more than had died in world war i. it was the fear of recurrence of this pandemic which led the cdc to launch a massive immunization program in the united states in to prevent swine flu (the virus was a strain antigenically similar to that of the pandemic influenza) from spreading from an isolated outbreak in an army camp. the effort was stopped after millions of persons were immunized with an urgently produced vaccine when serious reactions occurred (guillain-barre syndrome, (i.e., a type of paralysis), and when no further cases of swine flu were seen. this demonstrated the difficulty of extrapolating scenarios from a historical experience. each year, epidemiologic services of the who and collaborating centers such as the cdc recommend which strains should be used in vaccine preparation for use among susceptible population groups. these vaccines are prepared with the current anticipated epidemic strains. the three main types of influenza (a, b, and c) have different epidemiological characteristics. type a and its subtypes, which are subject to antigenic shift, are associated with widespread epidemics and pandemics. type b undergoes antigenic drift and is associated with less widespread epidemics. influenza type c is even more localized. active immunization against the prevailing wild strain of influenza virus produces a - % level of protection in high risk groups. the benefits of annual immunization outweigh the costs, and it has proven to be effective in reducing cases of influenza and its secondary complications such as pneumonia and death from respiratory complications in high-risk groups. pneumococcal disease. pneumococcal diseases, which are caused by streptococcus pneumoniae, include pneumonia, meningitis, and otitis media. the capsular types of pneumococci selected out of known types of the organism for the vaccine are those responsible for % of pneumococcal pneumonia cases and - % of all pneumonia cases in the united states, and are responsible for some , deaths per year. this vaccine has been found to be cost-effective for high risk groups, including persons with chronic disease, hiv carriers, patients whose spleens were removed, the elderly, and those with immunosuppressive conditions. it should be included in preventive-oriented health programs, especially for long-term care of the chronically ill. because pneumococci cause bacterial meningitis, pneumococcal vaccine may be a future candidate for use in routine immunization programs for children (over age ). varicella is an acute, generalized virus disease caused by the varicella zoster virus (vzv). despite its reputation as an innocuous disease of childhood, varicella patients can be quite ill. a mild fever and characteristic generalized red rash lasts for a few hours, followed by vesicles occurring in successive crops over various areas of the body. affected areas may include the membranes of the eyes, mouth, and respiratory tract. the disease may be so mild as to escape observation or may be quite severe, especially in adults. death can occur from viral pneumonia in adults and sepsis or encephalitis in children. neonates whose mothers develop the disease within days of delivery are at increased risk with a case fatality rate of up to %. long-term sequelae include herpes zoster or shingles with a severely painful, vesicular rash along the distribution of sensory nerves, which can last for months. its occurrence increases with age and it is primarily seen in the elderly. it can, however, occur in immunocompromised children (especially those on cancer chemotherapy), aids patients, and others. some % of a population will experience herpes zoster during their lifetimes. reye's syndrome is an increasingly rare but serious complication from varicella or influenza b. it occurs in children and affects the liver and central nervous system. congenital varicella syndrome with birth defects similar to congenital rubella syndrome has been identified recently. varicella vaccine is now recommended for routine immunization at age - months in the united states, with catch-up for children up to age years and for occupationally exposed persons in health or child care settings. varicella vaccine is also recommended for nonpregnant women of child bearing years. cost-benefit studies indicate a : ratio if both direct and indirect costs are included (see chapter ). varicella vaccine is likely to be added to a "cocktail vaccine" containing dpt, polio (ipv), and hib. meningococcal meningitis. meningococcal meningitis, caused by the bacterium neisseria meningitides, is characterized by headache, fever, neck stiffness, delirium, coma, and/or convulsions. the incubation period is - days. it has a case fatality rate of - % if treated early and adequately, but rises up to % in the absence of treatment. there are several important strains (a, b, c, x, y, and z). serogroups a and c are the main causes of epidemics, with b causing sporadic cases and local outbreaks. transmission is by direct contact and droplet spread. meningitis (group a) is common in sub-saharan african countries, but epidemics have occurred worldwide. during epidemics, children, teenagers, and young adults are the most severely affected. in developed countries, outbreaks occur most frequently in military and student populations. in , meningococcal meningitis spread widely in the "meningitis belt" in central africa. epidemic control is achieved by mass chemoprophylaxis with antibiotics (e.g., rifampin or sulfa drugs) among case contacts, although the emergence of resistant strains is a concern. vaccines against serotypes a and c (bivalent) or a, c, w, and y are available. their use is effective in epidemic control and prevention institutions and military recruits, especially for a and c serogroups. vaccination is one of the key modalities of primary prevention. immunization is cost-effective and prevents wide-scale disease and death, with high levels of safety. despite the general consensus in public health regarding the central role of vaccination, there are many areas of controversy and unfulfilled expectations. a vaccination program should aim at % coverage at appropriate times, including infants, school children, and adults. immunization policy should be adapted from current international standards applying the best available program to national circumstances and financial capacities (table . ). public health personnel with expertise in vaccine-preventable disease control are needed to advise ministries of health and the practicing pediatric community on current issues in vaccination and to monitor implementation and evolution of control programs. controversies and changing views are common to immunization policy, so that discussions must be conducted on a continuing basis. policy should be under continuing review by a ministerially appointed national immunization advisory committee, including professionals from public health, academia, immunology, laboratory sciences, economics, and relevant clinical fields. bduring , the recommendation for polio virus was changed to doses of ipv in infancy. vaccine supply should be adequate and continuous. supplies should be ordered from known manufacturers meeting international standards of good manufacturing practice. all batches should be tested for safety and efficacy prior to release for use. there should be an adequate and continuously monitored cold chain to protect against high temperatures for heat labile vaccines, sera, and other active biological preparations. the cold chain should include all stages of storage, transport, and maintenance at the site of usage. only disposable syringes should be used in vaccination programs to prevent any possible transmission of blood-borne infection. a vaccination program depends on a readily available service with no barriers or unnecessary prerequisites, free to parents or with a minimum fee, to administer vaccines in disposable syringes by properly trained individuals using patientoriented and community-oriented approaches. ongoing education and training on current immunization practices are needed. incentive payments by insuring agency or managed care systems promote complete, on-time coverage. all clinical encounters should be used to screen, immunize, and educate parents/guardians. contraindications to vaccination are very few; vaccines may be given even during mild illness with or without fever, during antibiotic therapy, during convalescence from illness, following recent exposure to an infectious disease, and to persons having a history of mild/moderate local reactions, convulsions, or family history of sudden infant death syndrome (sids). simultaneous administration of vaccines and vaccine "cocktails" reduces the number of visits and thereby improves coverage; there are no known interferences between vaccine antigens. accurate and complete recording with computerization of records with automatic reminders helps promote compliance, as does co-scheduling of immunization appointments with other services. adverse events should be reported promptly, accurately, and completely. a tracking system should operate with reminders of upcoming or overdue immunizations; use mail, telephone, and home visits, especially for high risk families, with semiannual audits to assess coverage and review patient records in the population served to determine the percentage of children covered by second birthday. tracking should identify children needing completion of the immunization schedule and assess the quality of documentation. it is important to maintain up-to-date, easily retrievable medical protocols where vaccines are administered, noting vaccine dosage, contraindications, and management of adverse events. all health care providers and managers should be trained in education, promotion, and management of immunization policy. health education should target parents as well as the general public. monitoring of vaccines used and children immunized, individually and by category of vaccination can be facilitated by computerization of immunization records, or regular manual review of child care records. where immunization is done by physicians in private practice, as in the united states, determination of coverage is by periodic surveys. inspection of vaccines for safety, purity, potency, and standards is part of the regulatory function. vaccines are defined as biological products and are therefore subject to regulation by national health authorities. in the united states, this comes under the legislative authority of the public health service act, as well as the food, drug and cosmetics act, with applicable regulations in the code of federal regulations. the federal agency empowered to carry out this regulatory function is the center for drugs and biologics of the federal food and drug administration. litigation regarding adverse effects of vaccines led to inflation of legal costs and efforts to limit court settlements. the u.s. federal government enacted the child vaccine injury act of . this legislation requires providers to document vaccines given and to report on complications or reactions. it was intended to pay benefits to persons injured by vaccines faster and by means of a less expensive procedure than a civil suit for resolving claims. using this no-fault system, petitioners do not need to prove that manufacturers or vaccine givers were at fault. they must only prove that the vaccine is related to the injury in order to receive compensation. the vaccines covered by this legislation include dtp, mmr, opv, and ipv. development of vaccines from jenner in eighteenth century to the advent of recombinant hepatitis b vaccine in , and of vaccines for acellular pertussis, varicella, hepatitis a, and rotavirus in the s, has provided one of the pillars of public health and led to enormous savings of human life. vaccines for viral in-fections in humans for hiv, respiratory syncytial virus, papilloma, epstein-barr virus, dengue fever, and hantavirus are under intense research with genetic approaches using recombinant techniques. the potential for the future of vaccines will be greatly influenced by scientific advances in genetic engineering, with potential for development of vaccines attached to bacteria or protein in plants, which may be given in combination for an increasing range of organisms or their harmful products. recombinant dna technology has revolutionized basic and biomedical research since the s. the industry of biotechnology has produced important diagnostic tests, such as for hiv, with great potential for vaccine development. traditional whole organism vaccines, alive or killed, may contain toxic products that may cause mild to severe reactions. subunit vaccines are prepared from components of a whole organism. this avoids the use of live organisms that can cause the disease or create toxic products which cause reactions. subunit vaccines traditionally prepared by inactivation of partially purified toxins are costly, difficult to prepare, and weakly immunogenic. recombinant techniques are an important development for production of new whole cell or subunit vaccines that are safe, inexpensive, and more productive of antibodies than other approaches. their potential contribution to the future of immunology is enormous. molecular biology and genetic engineering have made it feasible to create new, improved, and less costly vaccines. new vaccines should be inexpensive, easily administered, capable of being stored and transported without refrigeration, and given orally. the search for inexpensive and effective vaccines for groups of viruses causing diarrheal diseases led to development of the rotavirus vaccine. some "edible" research focuses on the genetic programming of plants to produce vaccines and dna. vaccine manufacturers, who spend huge sums of money and years of research on new products, tend to work on those which will bring great financial rewards for the company and are critical to the local health care community. this has led to less effort being made in developing vaccines for diseases such as malaria. yet industry plays a crucial role for continued progress in the field. since the eradication of smallpox, much attention has focused on the possibility of similarly eradicating other diseases, and a list of potential candidates has emerged. some of these have been abandoned because of practical difficulties with current technology. diseases that have been under discussion for eradication have included measles, tb, and some tropical diseases, such as malaria and dracunculiasis. eradication is defined as the achievement of a situation whereby no further cases of a disease occur anywhere and continued control measures are unnecessary. reducing epidemics of infectious diseases, through control and eradication in selected areas or target groups, can in certain instances achieve eradication of the disease. local eradication can be achieved where domestic circulation of an organism is interrupted with cases occurring from importation only. this requires a strong, sustained immunization program with adaptation to meet needs of importation of carriers and changing epidemiologic patterns. smallpox was one of the major pandemic diseases of the middle ages and its recorded history goes back to antiquity. prevention of smallpox was discussed in ancient china by ho kung (circe ao ), and inoculation against the disease was practiced there from the eleventh century ad. prevention was carried out by nasal inhalation of powdered dried smallpox scabs. exposure of children to smallpox when the mortality rate was lowest assumed a weakened form of the disease, and it was observed that a person could only have smallpox once in a lifetime. isolation and quarantine were widely practiced in europe during the sixteenth and seventeenth centuries. variolation was the practice of inoculating youngsters with material from scabs of pustules from mild cases of smallpox in the hope that they would develop a mild form of the disease. although this practice was associated with substantial mortality, it was widely adopted because mortality from variolation was well below that of smallpox acquired during epidemics. introduced into england in (see chapter ) it was commonly practiced as a lucrative medical specialty during the eighteenth century. in the s, variolation was also introduced into the american colonies, russia, and subsequently into sweden and denmark. despite all efforts, in the early eighteenth century smallpox was a leading cause of death in all age groups. toward the end of the eighteenth century an estimated , persons died annually from smallpox in europe. vaccination, or the use of cowpox vaccinia virus to protect against smallpox, was initiated late in the eighteenth century. in , a cattle breeder in yorkshire, england, inoculated his wife and two children with cowpox to protect them during a smallpox epidemic. in , edward jenner, an english country general practitioner, experimented with inoculation from a milkmaid's cowpox pustule to a healthy youngster, who subsequently proved resistant to smallpox by variolation (see chapter ). vaccination, the deliberate inoculation of cowpox material, was slow to be adopted universally, but by , over , persons in england were vaccinated. vaccination gathered support in the nineteenth century in military establishments, and in some countries which adopted it universally. opposition to vaccination remained strong for nearly a century based on religious grounds, observed failures of vaccination to give lifelong immunity, and because it was seen as an infringement of the state on the rights of the individual. often the protest was led by medical variolationists whose medical practice and large incomes were threatened by the mass movement to vaccination. resistance was also offered by "sanitarians" who opposed the germ theory and thought cleanliness was the best method of prevention. universal vaccination was increasingly adopted in europe and america in the early nineteenth century and eradication of smallpox in developed countries was achieved by the mid twentieth century. in , the soviet union proposed to the world health assembly a program to eradicate smallpox internationally and subsequently donated million doses of vaccine per year as part of the million needed to promote vaccination of at least % of the world population. in , who adopted a target for the eradication of smallpox. a program was developed which included a massive increase in coverage to reduce the circulation of the virus through person-to-person contact. where smallpox was endemic, with a substantial number of unvaccinated persons, the aim of the mass vaccination phase was % coverage. increasing vaccination coverage in developing countries reduced the disease to periodic and increasingly localized outbreaks. in , countries were considered endemic for smallpox, and another experienced importation of cases. by , the number of endemic countries was down to , and by only countries were still endemic, including india, pakistan, bangladesh, and nepal. in these countries, a new strategy was needed, based on a search for cases and vaccination of all contacts, working with a case incidence below per , . the program then moved into the consolidation phase, with emphasis on vaccination of newborns and new arrivals. surveillance and case detection were improved with case contact or risk group vaccination. the maintenance phase began when surveillance and reporting were switched to the national or regional health service with intensive follow-up of any suspect case. the mass epidemic era had been controlled by mass vaccination, reducing the total burden of the disease, but eradication required the isolation of individual cases with vaccination of potential contacts. technical innovations greatly eased the problems associated with mass vaccination worldwide. during the s, there was wide variation in sources of smallpox vaccine. in the s, efforts to standardize and further attenuate the strains used reduced complication rates from vaccinations. the development of lyophilization (freeze-drying) of the vaccine in england in the s made a heat-stable vaccine that could be effective in tropical field conditions in developing countries. the invention of the bifurcated needle (bernard rubin ) allowed for easier and more widespread vaccination by lesser trained personnel in remote areas. the net result of these innovations was increased world coverage and a reduction in the spread of the disease. smallpox became more and more confined by increasing herd immunity, thus allowing transition to the phase of monitoring and isolation of individual cases. in the last case of smallpox was identified in somalia, and in the who declared the disease eradicated. no subsequent cases have been found except for several associated with a laboratory accident in the united kingdom in . the who recommends that the last stores of smallpox virus should be destroyed in . the cost of the eradication program was $ million or $ million per year. worldwide savings are estimated at $ billion annually. this monumental public health achievement set the precedent for eradication of other infectious diseases. the world health assembly decided to destroy the last two remaining stocks of the smallpox virus in atlanta and moscow in . destruction of the remaining stock was delayed in to because of concern that illegal stocks may be held by some states or potential bioterrorists for potential use in weapons of mass destruction, concern regarding the appearance of monkeypox and a wish to use the virus for further research. in , the who established a target of eradication of poliomyelitis by the year . global immunization coverage with three doses of opv increased from some % in to over % in , with a slight decline in the period - . support from member countries and international agencies such as unicef and rotary international has led to widescale increases in immunization coverage throughout many parts of the world. the world health organization promotes use of opv only as part of routine infant immunization or national immunization days (nids). this strategy has been successful in the americas and in china, but india and the middle east remain problematic. eradication of wild poliomyelitis by the year will require flexibility in vaccination strategies and may require the combined approach, using opv and ipv, as adopted in the united states in to prevent vaccine-associated clinical cases. the combination of opv and ipv may be needed where enteric disease is common and leads to interference in opv uptake, especially in tropical areas where endemic poliovirus and diarrheal diseases are still found. the world bank estimated that achievement of global eradication would save $ million annually in the united states alone. since the eradication of smallpox, discussion has focused on the possibility of similarly eradicating other diseases, and a list of potential candidates has emerged. some of these have been abandoned because of practical difficulties with current technology. diseases that have been under discussion for eradication have included measles, tb, and tropical diseases such as malaria and dracunculiasis. eradication of malaria was thought to be possible in the s when major gains were seen in malaria control by aggressive case environmental control, case finding, and management. however, lack of sustained vector control and an effective vaccine has prevented global eradication. malaria control suffered serious setbacks because of failure in political resolve and capacity to continue support needed for necessary programs. in the s and s, control efforts were not sustained in many countries, and a dreadful comeback of the disease occurred in africa and asia in the s. the emergence of mosquitoes resistant to insecticides, and malarial strains resistant to antimalarial drugs, have made malaria control even more difficult and expensive. renewed effort in malaria control may require new approaches. use of community health workers (chws) in small villages in highly endemic regions of colombia resulted in a major drop in malaria mortality during the s. the chws investigate suspect cases by taking clinical histories and blood smears. . scientific feasibility a. epidemiologic vulnerability; lack of nonhuman reservoir, ease of spread, no natural immunity, relapse potential; b. effective practical intervention available; vaccine or other primary preventive or curative treatment, or vectoricide that is safe, inexpensive, long lasting, and easily used in the field; c. demonstrated feasibility of elimination in specific locations, such as an island or other geographic unit. . political will/popular support a. they examine smears for malaria parasites and a diagnosis is made. therapy is instituted and the patient is followed. quality control monitoring shows high levels of accuracy in reading of slides compared to professional laboratories. in the late s, there was widespread discussion in the literature of the potential for eradication of measles and tb. measles eradication was set back as breakthrough epidemics occurred in the united states, canada, and many other countries during the s and early s, but regional eradication was achieved combining the two-dose policy with catch-up campaigns for older children or in national immunization days, as in the caribbean countries. tuberculosis has also increased in the united states and several european countries for the first time in many decades. unrealistic expectations can lead to inappropriate assessments and policy when confounding factors alter the epidemiologic course of events. such is the case with tb, where control and eradication have receded from the picture. this deadly disease has returned to developed countries, partly in association with the hiv infection and multiple-drug-resistant strains, as well as homelessness, rising prison populations, poverty, and other deleterious social conditions. directly observed therapy is an important recent breakthrough, more effective in use of available technology and will play a major role in tb control in the twenty-first century. a decade after the eradication of smallpox was achieved, the international task force for disease eradication (itfde) was established to systematically evaluate the potential for global eradicability of candidate diseases. its goals were to identify specific barriers to the eradication of these diseases that might be surmountable and to promote eradication efforts. the subject of eradication versus control of infectious diseases if of central public health importance as technology expands the armamentarium of immunization and vector control into the twenty-first century. the control of epidemics, followed by interruption of transmission and ultimately eradication, will save countless lives and prevent serious damage to children throughout the world. the smallpox achievement, momentous in itself, points to the potential for the eradication of other deadly diseases. the skillful use of existing and new technology is an important priority in the new public health. flexibility and adaptability are as vital as resources and personnel. selecting diseases for eradication is not purely a professional issue of resources such as vaccines and manpower, organization and financing. it is also a matter of political will and perception of the burden of disease. there will be many controversies. the selection of polio for eradication while deferring measles when polio kills few and measles kills many may be questioned. the cdc published criteria for selection of disease for eradication are shown in box . . the who, in a review of health targets in the field of infectious disease control for the twenty-first century, selected the following targets: eradication of chagas' disease by ; eradication of neonatal tetanus by ; eradication of leprosy by ; eradication of measles by ; eradication of trachoma by ; reversing the current trend of increasing tuberculosis and hiv/aids. in , a conference in atlanta, georgia, reviewed the subject, which is still very much in a state of flux. table . summarizes the selection of diseases which are presently seen as controllable and those considered to be potentially eradicable. the subject will be under review in the years ahead. mycobacterium tuberculosis in humans and m. bovis in cattle. the disease is primarily found in humans, but it is also a disease of cattle and occasionally other primates in certain regions of the world. it is transmitted via airborne droplet nuclei from persons with pulmonary or laryngeal tb during coughing, sneezing, talking, or singing. the initial infection may go unnoticed, but tuberculin sensitivity appears within a few weeks. about % of those infected enter a latent phase with a lifelong risk of reactivation. approximately % go from initial infection to pulmonary tb. less commonly, the infection develops as extrapulmonary tb, involving meninges, lymph nodes, pleura, pericardium, bones, kidneys, or other organs. untreated, about half of the patients with active tb will die of the disease within years, but modern chemotherapy almost always results in a cure. pulmonary tb symptoms include cough and weight loss, with clinical findings on chest examination and confirmation by findings of tubercle bacilli in stained smears of sputum and, if possible, growth of the organism on culture media, and changes in the chest x-ray. tuberculosis affects people in their adult working years, with - % of cases in persons between the ages of and . its devastating effects on the work force and economic development contribute to a high cost-effectiveness for tb control. the tubercle bacillus infects approximately . billion people in the world today, causing over million cases and nearly million deaths in . during , new cases of tb included . million ( %) in southeast asia and the western pacific regions of who, with . million cases in india, and . million in indonesia. by , the incidence of tb may increase to . million new cases per year, a % increase over . between and , who estimates there were million new cases of tb, of which million cases were in association with hiv infection. during the s, an estimated million persons died of tb, including . million with hiv infection. a new and dangerous period for tb resurgence has resulted from parallel epidemiologic events: first, the advent of hiv infection and second, the occurrence of multiple drug resistant tb (mdrtb), that is, organisms resistant at least to both isoniazid (inh) and rifampicin, two mainstays of tb treatment. mdrtb can have a case fatality rate as high as %. hiv reduces cellular immunity so that people with latent tb have a high risk of activation of the disease. it is estimated that hiv negative persons have a - % lifetime risk of tb; hiv positive people have a risk of % per year of developing clinical tuberculosis. drug resistance, the long period of treatment, and the socioeconomic profile of most tb patients combine to require a new approach to therapy. directly observed treatment, short-course (dots), has shown itself to be highly effective with patients in poor self-care settings, such as the homeless, drug users, and those with aids. the strategy of dots uses community health workers to visit the patient and observes him or her taking the various medications, providing both incentive, support, and moral coercion to complete the needed to month therapy. dots has been shown to cure up to % of cases, at a cost of as little as $ per patient. it is one of the few hopes of containing the tb pandemic. in , who released a new strategy for control of tuberculosis over the next decade. the plan calls for new guidelines for control, new aid funds for developing countries, and enlistment of ngos to assist in the fight. the new guidelines stress short-term chemotherapy in well-managed programs of dots, stressing strict compliance with therapy for infectious cases with a goal of an % cure rate. even under adverse conditions, dots produces excellent results. it is one of the most cost-effective health interventions combining public health and clinical medical approaches. tuberculosis incidence in the united states decreased steadily until , increased in , and has declined again since. from to , there was an excess of , cases over the expected rate if the previous decline in case incidence had continued. this rise was largely due to the hiv/aids epidemic and the emergence of mdrtb, but also greater incidence among immigrants from areas of higher tb incidence, drug abusers, the homeless, and those with limited access to health care. this is particularly true in new york city, where mdrtb has appeared in outbreaks among prison inmates and hospital staff. from to , tb incidence in the united states declined by % and in some states, including new york, by % or more. this turnaround was due to stronger tb control programs that promptly identified persons with tb and initiated and ensured completion of appropriate therapy. aggressive staff training, outreach, and case management approaches were vital to this success. concern over rising rates among recent immigrants and the continued challenge of hiv/aids and coincidental transmission of hepatitis a, b, and c among drug users and marginal population groups show that continued support for tb control is needed. bacillus calmette-gurrin (bcg) is an attenuated strain of the tubercle bacillus used widely as a vaccination to prevent tb, especially in high incidence areas. it induces tuberculin sensitivity or an antigen-antibody reaction in which antibodies produced may be somewhat protective against the tubercle bacillus in % of vaccinees. although the support for its general use is contradictory, there is evidence from case-control and contact studies of positive protection against tb meningitis and disseminated tb in children under the age of . in some developed, low-incidence countries, it is not used routinely but selectively. it may also be used in asymptomatic hiv-positive persons or other high risk groups. the bcg vaccine for tuberculosis remains controversial. while used widely internationally, in the united states and other industrialized countries, it is thought to hinder rather than help in the fight against tb. this concern is based on the usefulness of tuberculin testing for diagnosis of the disease. where bcg has been administered, the diagnostic value of tuberculin testing is reduced, especially in the period soon after the bcg is used. studies showing equivocal benefit of bcg in preventing tuberculosis have added to the controversy. while those in the field in the united states continue to oppose the use of bcg, internationally it is still felt to be of benefit in preventing tb, primarily in children. a metaanalysis of the literature of bcg carried out by the technology assessment group at harvard school of public health concluded: on average, bcg vaccine significantly reduces the risk of tb by %. protection is observed across many populations, study designs, and forms of tb. age at vaccination did not enhance predictiveness of bcg efficacy. protection against tuberculous death, meningitis, and disseminated disease is higher than for total tb cases, although this result may reflect reduced error in disease classification rather than greater bcg efficacy. [colditz et al., jama, .] box . control of tuberculosis . identifying persons with clinically active tb; . diagnostic methods--clinical suspicion, sputum smear for bacteriologic examination, tuberculin skin testing, chest radiograph; . case finding and investigation programs in high risk groups; . contact investigation; . isolation techniques during initial therapy; . treatment, mainly ambulatory, of persons with clinically active tb; . treatment of contacts; . directly observed treatment, short-course (dots), where compliance suspect; . environmental control in treatment settings to reduce droplet infection; . educate health care providers on suspicion of tb and investigation of suspects. currently, the who recommends use of bcg as close to birth as possible as part of the expanded programme of immunization (epi). tuberculosis control remains feasible with current medical and public health methods. deterioration in its control should not lead to despair and passivity. the recent trend to successful control by dots despite the growing problem of mdrtb suggest that control and gradual reduction can be achieved by an activist, community outreach approach. the who in made tb control one of its major priorities, expressing grave concern that the mdr organism, now widely spread in countries of asia, eastern europe, and the former soviet union, may spread the disease much more widely. the disease constitutes one of the great challenges to public health at the start of the new century. acute infectious diseases caused by group a streptococci include streptococcal sore throat, scarlet fever, puerperal fever, septicemia, ersypelas, cellulitis, mastoiditis, otitis media, pneumonia, peritonsillitis (quinsy), wound infections, toxic shock syndrome, and fasciitis, the "flesh eating bacteria." streptococcus pyogenes group a include some serologically distinct types which vary in geographic location and clinical significance. transmission is by droplet, person-to-person direct contact, or by food infected by carriers. important complications from a public health point of view include acute rheumatic fever and acute glomerulonephritis, but also skin infections and pneumonia. acute rheumatic fever is a complication of strep a infection that has virtually disappeared from industrialized countries as a result of improved standards of living and antibiotic therapy. however, outbreaks were recorded in the united states in , and an increasing number of cases have been seen since . in developing countries, rheumatic fever remains a serious public health problem affecting school age children, particularly those in crowded living arrangements. longterm sequelae include disease of the mitral and aortic heart valves, which require cardiac care and surgery for repair or replacement with artificial valves. acute glomerulonephritis is a reaction to toxins of the streptococcal infection in the kidney tissue. this can result in long-term kidney failure and the need for dialysis or kidney transplantation. this disease has become far less common in the industrialized countries, but remains a public health problem in developing countries. the streptococcal diseases are controllable by early diagnosis and treatment with antibiotics. this is a major function of primary care systems. recent increases in rheumatic fever may herald a return of the problem, perhaps due to inadequate access to primary care in the united states for large sectors of the population, along with increased social hygiene problems. where access to primary care services is limited, infections with streptococci can result in a heavy burden of chronic heart and kidney disease with substantial health, emotional, and financial tolls. measures to improve access to care and pub-lic information are needed to assure rapid and effective care to prevent chronic and costly conditions. zoonoses are infectious diseases transmissible from vetebrate animals to humans. common examples of zoonoses of public health importance in nonindustrialized countries include brucellosis and rabies. in industrialized countries, salmonellosis, "mad cow disease" and influenza have reinforced the importance of relationships of animal and human health. strong cooperation between public health and veterinary public health authorities are required to monitor and to prevent such diseases. brucellosis is a disease occurring in cattle (brucella abortus), in dogs (br. cahis), in goats and sheep (br. melitensis), and in pigs (br. suis). humans are affected mainly through ingestion of contaminated milk products, by contact, or inhalation. brucellosis (also known as relapsing, undulant, malta, or mediterranean fever) is a systemic bacterial disease of acute or insidious onset characterized by fever, headache, weakness, sweating, chills, arthralgia, depression, weight loss, and generalized malaise. spread is by contact with tissues, blood, urine, vaginal discharges, but mainly by ingestion of raw milk and dairy products from infected animals. the disease may last from a few days to a year or more. complications include osteoarthritis and relapses. case fatality is under %, but disability is common and can be pronounced. the disease is primarily seen in mediterranean countries, the middle east, india, central asia, and in central and south america. brucellosis occurs primarily as an occupational disease of persons working with and in contact with tissues, blood, and urine of infected animals, especially goats and sheep. it is an occupational hazard for veterinarians, packinghouse workers, butchers, tanners, and laboratory workers. it is also transmitted to consumers of unpasteurized milk from infected animals. animal vectors include wild animals, so that eradication is virtually impossible. diagnosis is confirmed by laboratory findings of the organism in blood or other tissue samples, or with rising antibody titers in the blood, with confirmation by blood cultures. clinical cases are treated with antibiotics. epidemiologic investigation may help track down contaminated animal flocks. routine immunization of animals, monitoring of animals in high risk areas, quarantining sick animals, destroying infected animals, and pasteurizing milk and milk products prevents spread of the disease. control measures include educating farmers and the public not to use unpasteurized milk. individuals who work with animals (cattle, swine, goats, sheep, dogs, coyotes) should take special precautions when handling animal carcasses and materials. testing animals, destroying carriers, and enforcing mandatory pasteurization will restrict the spread of the disease. this is an economic as well as public health problem, requiring full cooperation between ministries of health and of agriculture. rabies is primarily a disease of animals, with a variety of wild animals serving as a reservoir for this disease, including foxes, wolves, bats, skunks, and raccoons, who may infect domestic animals such as dogs, cats, and farm animals. animal bites break the skin or mucous membrane, allowing entry of the virus from the infected saliva into the bloodstream. the incubation period of the virus is - weeks; it can be as long as several years or as short as days, so that postexposure preventive treatment is a public health emergency. the clinical disease often begins with a feeling of apprehension, headache, pyrexia, followed by muscle spasms, acute encephalitis, and death. fear of water ("hydrophobia") or fear of swallowing is a characteristic of the disease. rabies is almost always fatal within a week of onset of symptoms. the disease is estimated to cause , deaths annually, primarily in developing countries. it is uncommon in developed countries. rabies control focuses on prevention in humans, domestic animals, and wildlife. prevention in humans is based on preexposure prophylaxis for groups at risk (e.g., veterinarians, zoo workers) and postexposure immunization for persons bitten by potentially rabid animals. because reducing exposure of pets to wild animals is difficult, immunization of domestic animals is one of the most important preventive measures. prevention in domestic animals is by mandatory immunization of household pets. all domestic animals should be immunized at age months and revaccinated according to veterinary instructions. prevention in wild animals to reduce the reservoir is successful in achieving local eradication in settings where reentry from neighboring settings is limited. since , the use of oral rabies immunization has been successful in reducing the population of wild animals infected by the rabies virus. rabies eradication efforts, using aerial distribution of baits containing fox rabies vaccine in affected areas of belgium, france, germany, italy, and luxembourg, have been underway since . the number of rabies cases in these affected areas has declined by some %. switzerland is now virtually rabies-free because of this vaccination program. the potential exists for focal eradication, especially on islands or in partially restricted areas with limited possibilities of wild animal entry. livestock need not be routinely immunized against rabies, except in high risk areas. where bats are major reservoirs of the disease, as in the united states, eradication is not presently feasible. salmonella, discussed later in this chapter under diarrheal diseases, is one of the commonest of all infectious diseases among animals and is easily spread to humans via poultry, meat, eggs, and dairy products. specific antigenic types are associated with food-borne transmission to humans, causing generalized illness and gastroenteritis. severity of the disease varies widely, but the diseases can be devastating among vulnerable population groups, such as young children, the elderly, and the immunocompromised. epidemiologic investigation of common food source outbreaks may uncover hazardous food handling practices. laboratory confirmation or serotypes helps in monitoring the disease. prevention is by maintaining high standards of food hygiene in processing, inspection and regulation, food handling practices, and hygiene education. bacillus anthracis causes a bacterial infection in herbivore animals. its spores contaminate soil, worldwide. it affects humans exposed in occupational settings. transmission is cutaneous by contact, gastrointestinal by ingestion, or respiratory by inhalation. it has gained recent attention (iraq, ) as a highly potent agent for germ warfare or terrorism. limited supplies of vaccine are available. creutzfeld-jakob disease is a degenerative disease of the central nervous system linked to consumption of beef from cattle infected with bovine spongiform encephalopathy. it is transmitted by prions in animal feed prepared from contaminated animal material and in transplanted organs. this disease was identified in the united kingdom linked to infected cattle leading to a ban on british beef in many parts of the world and slaughter of large numbers of potentially contaminated animals. the tapeworm causing diphyllobothriasis (diphyllobothrium latum) is widespread in north american freshwater fish, passing from crustacean to fish to humans by eating raw freshwater fish. it is especially common among inuit peoples and may be asymptomatic or cause severe general and abdominal disorder. food hygiene (freezing and cooking of meat) is recommended; treatment is by anthelminthics. leptospiroses are a group of zoonotic bacterial diseases found worldwide in rats, raccoons, and domestic animals. it affects farmers, sewer workers, dairy and abattoir workers, veterinarians, military personnel, and miners with transmission by exposure to or ingestion of urine-contaminated water or tissues of infected animals. it is often asymptomatic or mild, but may cause generalized illness like influenza, meningitis, or encephalitis. prevention requires education of the public in self protection and immunization of workers in hazardous occupations, along with immunization and segregation of domestic animals and control of wild animals. vector-borne diseases are a group of diseases in which the infectious agent is transmitted to humans by crawling or flying insects. the vector is the intermediary between the reservoir and the host. both the vector and the host may be affected by climatic condition; mosquitoes thrive in warm, wet weather and are suppressed by cold weather; humans may wear less protective clothing in warm weather. the only important reservoir of malaria is humans. its mode of transmission is from person to person via the bite of an infected female anopheles mosquito (ronald ross, nobel prize, ) . the causative organism is a single cell parasite with four species: plasmodium vivax, p malariae, p falciparum, and p ovale. clinical symptoms are produced by the parasite invading and destroying red blood cells. the incubation period of approximately - days, depending on the specific plasmodium involved. some strains of p vivax may have a protracted incubation period of - months and even longer for p ovale. the disease can also be transmitted through infected blood transfusions. confirmation of diagnosis is by demonstrating malaria parasites on blood smears. falciparum malaria, the most serious form, presents with fever, chills, sweats, and headache. it may progress to jaundice, bleeding disorders, shock, renal or liver failure, encephalopathy, coma, and death. prompt treatment is essential. case fatality rates in untreated children and adults are above %. an untreated attack may last months. other forms of malaria may present as a nonspecific fever. relapse of the p ovale may occur up to years after initial infection; malaria may persist in chronic form for up to years. malaria control advanced during the s- s through improved chlovaquine treatment and use of ddt for vector control with optimism for eradication of the disease. however, control regressed in many developing countries as allocations for environmental control and case findings/treatment were reduced. there has also been an increase in drug resistance, so that this disease is now an extremely serious public health problem in many parts of the world. the need for a vaccine for malaria control is now more apparent than ever. the world health organization estimated that, in , sub-saharan africa (ssa) had million new malaria cases, with % of children up to age . over million deaths occur annually from malaria more than two-thirds of them in ssa. large areas, particularly in forest or savannah regions with high rainfall, are holoendemic. in higher altitudes, endemicity is lower, but epidemics do occur. chloroquine-resistant p. falciparum has spread throughout africa, accompanied by an increasing incidence of severe clinical forms of the disease. the world bank estimates that % of all disability-adjusted life years (dalys) lost per year in ssa are from malaria, which places a heavy economic burden on the health systems. in the americas, the number of cases detected has risen every year since , and the who estimates there to have been . - . million cases in . the nine most endemic countries in the americas achieved a % reduction in malaria mortality between and . southeast asian region reports some . million cases of malaria in and deaths from tb. this accounts for more than one-third of all non-african malaria cases. there is an increase in resistant strains to the major available drugs and of the mosquitoes to insecticides in use. vector control, case finding, and treatment remain the mainstay of control. use of insecticide-impregnated bed nets and curtains, and residual house spraying, and strengthened vector control activities are important, as are early diagnosis and carefully monitored treatment with monitoring for resistance. control of malaria will ultimately depend on a safe, effective, and inexpensive vaccine. attempts to develop a malaria vaccine have been unsuccessful to date due to the large number of genetic types of p. falciparum even in localized areas. a colombian-developed vaccine is being field-tested with partial effectiveness. research in vaccines for malaria has also been hampered by the fact that it is a relatively low priority for vaccine manufacturers because of the minimal potential for financial benefit. research on malaria concentrates on the pharmacological aspects of the disease because of increasing drug resistance. in , who has initiated a new campaign to "roll back malaria" and maintain the dream of eradication in the future. effective low technology interventions include community-based case finding, early treatment of good quality, insecticide use, and vector control. the use of community health workers in endemic areas, has shown promising results. local control and even eradication can be achieved with currently available technology. this requires an integration of public health and clinical approaches with strong political commitment. the rickettsia are obligate parasites, i.e., they can only replicate in living cells, but otherwise they have characteristics of bacteria. this is a group of clinically similar diseases, usually characterized by severe headache, fever, myalgia, rash, and capillary bleeding causing damage to brain, lungs, kidneys, and heart. identification is by serological testing for antibodies, but the organisms can also be cultured in laboratory animals, embryonic eggs, or in cell cultures. the organisms are transmitted by arthropod vectors such as lice, fleas, ticks, and mites. the diseases caused millions of deaths during war and famine periods prior to the advent of antibiotics. these diseases appear in nature in ways that make them impossible to eradicate, but clinical diagnosis, host protection, and vector control can help reduce the burden of disease and deal with outbreaks that may occur. public education regarding self-protection, appropriate clothing, tick removal, and localized control measures such as spraying and habitat modification are useful. epidemic typhus, first identified in , is due to rickettsia prowazekii. spread primarily by the body louse, typhus was the cause of an estimated million deaths, i.e., during war and famine, in poland and the soviet union from - . untreated, the fatality rate is - %. typhus responds well to antibiotics. it is currently largely confined to endemic foci in central africa, central asia, eastern europe, and south america. it is preventable by hygiene and pediculicides such as ddt and lindane. a vaccine is available for exposed laboratory personnel. murine typhus is a mild form of typhus due to rickettsia typhi, which is found worldwide and spread in rodent reservoirs. scrub typhus, also known as tsutsugamushi or japanese river fever, is located throughout the far east and the pacific islands, and was a serious health problem for u.s. armed forces in the pacific during world war ii. it is spread by the rickettsia tsutsugamushi and has a wide variation in case fatality according to region, organism, and age of patient. rocky mountain spotted fever is a well-known and severe form of tick-borne typhus due to rickettsia rickettsii, occurring in western north america, europe, and asia. q. fever is a tick-borne disease caused by coxiella burnetii and is worldwide in distribution, usually associated with farm workers, in both acute and chronic forms. regular anti-tick spraying of sheep, cows, and goats helps protect exposed workers. protective clothing and regular removal of body ticks help protect exposed persons. arthropod-borne viral diseases are caused by a diverse group of viruses which are transmitted between vertebrate animals (often farm animals or small rodents) and people by the bite of blood-feeding vectors such as mosquitoes, ticks, and sandflies and by direct contact with infected animal carcasses. usually the viruses have the capacity to multiply in the salivary glands of the vector, but some are carried mechanically in their mouthparts. these viruses cause acute central nervous system infections (meningoencephalitis), myocarditis, or undifferentiated viral illnesses with polyarthritis and rashes, or severe hemorrhagic febrile illnesses. arbovirus diseases are often asymptomatic in vertebrates but may be severe in humans. over antigenetically distinct arboviruses are associated with disease in humans, varying from benign fevers of short duration to severe hemmorhagic fevers. each has a specific geographic location, vector, clinical, and virologic characteristics. they are of international public health importance because of the potential for spread via natural phenomena and modem rapid transportation of vectors and persons incubating the disease or ill with it, with potential for further spreading at the point of destination. arboviruses are responsible for a large number of encephalitic diseases characterized by mode of transmission and geographic area. mosquito-borne arboviruses causing encephalitis include eastern and western equine, venezuelan, japanese, and murray hill encephalitides. japanese encephalitis is caused by a mosquito-borne arbovirus found in asia and is associated with rice-growing areas. it is characterized by headache, fever, convulsions, and paralysis, with fatality rates in severe cases as high as %. a currently available vaccine is used routinely in endemic areas (japan, korea, thailand, india, and taiwan) and for persons traveling to infected areas. tick-borne arboviruses causing encephalitis include the powassan virus, which occurs sporadically in the united states and canada. tickborne encephalitis is endemic in eastern europe, scandinavia, and the former soviet union. an epidemic of mosquito-borne encephalitis in new york city in included cases and deaths, due to the west nile fever virus, never before found in the united states. other insect vectors. it affects animals and humans who are in direct contact with the meat or blood of affected animals. the virus causes a generalized illness in humans with encephalitis, hemorrhages, retinitis and retinal hemorrhage leading to partial or total blindness, and death ( - %). it also causes universal abortion in ewes and a high percentage of death in lambs. the normal habitat is in the rift valley of eastern africa (the great syrian-african rift), often spreading to southern africa, depending on climactic conditions. the primary reservoir and vector is the aedes mosquito, and affected animals serve to multiply the virus which is transmitted by other vectors and direct contact with animal fluids to humans. an unusual spread of rvf northward to the sudan and along the aswan dam reservoir to egypt in - caused hundreds of thousands of animal deaths, with , human cases and deaths. rvf appeared again in egypt in . this disease is suspected to be one of the ten plagues of egypt leading to the exodus of the children of israel from egypt during pharaonic-biblical times. in , an outbreak of rvf in kenya, initially thought to be anthrax, with hundreds of cases and dozens of deaths, was related to abnormal rainy season and vector conditions. satellite monitoring of rainfall and vegetation is being used to predict epidemics in kenya and surrounding countries. animal immunization, monitoring, vector control, and reduced contact with infected animals can limit the spread of this disease. arboviruses can also cause hemorrhagic fevers. these are acute febrile illnesses, with extensive hemorrhagic phenomena (internal and external), liver damage, shock, and often high mortality rates. the potential for international transmission is high. yellow fever. yellow fever is an acute viral disease of short duration and varying severity with jaundice. it can progress to liver disease and severe intestinal bleeding. the case fatality rate is < % in endemic areas, but may be as high as % in nonendemic areas and in epidemics. it caused major epidemics in the americas in the past, but was controlled by elimination of the vector, aedes aegypti. a live attenuated vaccine is used in routine immunization endemic areas and recommended for travelers to infected areas. determining the mode of transmission and vector control of yellow fever played a major role in the development of public health (see chapter ). in , the who reported , cases and , deaths from yellow fever globally. dengue hemorrhagic fever. dengue hemorrhagic fever is an acute sudden onset viral disease, with - days of fever, intense headache, myalgia, arthralgia, box . dengue fever and dengue hemorrhagic fever, dengue fever, a severe influenza-like illness, and dengue hemorrhagic fever are closely related conditions caused by four distinct viruses transmitted by aedes aegypti mosquitos. dengue is the world's most important mosquito-borne virus disease. a total of , million people worldwide are at risk of infection. an estimated million cases occur each year, of whom , need to be hospitalized. this is a spreading problem, especially in cities in tropical and subtropical areas. major outbreaks were reported in colombia, cuba, and many other locations in . source: world health organization. . world health report gastrointestinal disturbance, and rash. hemorrhagic phenomena can cause case fatality rates of up to %. epidemics can be explosive, but adequate treatment can greatly reduce the number of deaths. dengue occurs in southeast asia, the pacific islands, australia, west africa, the caribbean, and central and south america. an epidemic in cuba in included more than , cases, and deaths. vector control of the a. aegypti mosquito resulted in control of the disease during the s- s, but reinfestation of mosquitoes led to incresased transmission and epidemics in the pacific islands, caribbean, central and south america in the s and s. outbreaks in vietnam included , cases in , another , cases in , and a similar sized outbreak in . indonesia had over , cases in with deaths, and in over , cases (january-may) with at least deaths. in , epidemics of dengue were reported in fiji, the cook islands, new caledonia, and northern australia. the who estimates , deaths and . million cases worldwide in . monkeys are the main reservoir, and the vector is the a. aegypti mosquito. no vaccine is currently available, and management is by vector control. lassa fever. lassa fever was first isolated in lassa, nigeria, in and is widely distributed in west africa, with , - , cases and deaths annually. it is spread by direct contact with blood, urine, or secretions of infected rodents and by direct person-to-person contact in hospital settings. the disease is characterized by a persistent or spiking fever for - weeks, and may include severe hypotension, shock, and hemorrhaging. the case fatality rate is %. marburg disease. marburg disease is a viral disease with sudden onset of generalized illness, malaise, fever, myalgia, headache, diarrhea, vomiting, rash, and hemorrhages. it was first seen in marburg, germany, in , following ex-posure to green monkeys. person-to-person spread occurs via blood, secretions, organs, and semen. case fatality rates can be over %. ebola fever. ebola fever is a viral disease with sudden onset of generalized illness, malaise, fever, myalgia, headache, diarrhea, vomiting, rash, and hemorrhages. it was first found in zaire and sudan in in outbreaks which killed more than persons. it is spread from person to person by the blood, vomitus, urine, stools, and other secretions of sick patients, with a short incubation period. the disease has case fatality rates of up to %. an outbreak of ebola among laboratory monkeys in a medical laboratory near washington, d.c., was contained with no human cases. the reservoir for the virus is thought to be rodents. an outbreak of ebola in may in the town of kikwit, zaire, killed persons out of cases ( % case fatality rate). this outbreak caused international concern that the disease could spread, but it remained localized. another outbreak of ebola virus occurred in gabon in early , with cases, of whom had direct exposure to an infected monkey, the remainder by human-to-human contact, or not established; of the cases died ( %). this disease is considered highly dangerous unless outbreaks are effectively controlled. in zaire, lack of basic sanitary supplies, such as surgical gloves for hospitals, almost ensures that this disease will spread when it recurs. lyme disease is characterized by the presence of a rash, musculoskeletal, neurologic, and cardiovascular symptoms. confirmation is by laboratory investigation. it is the most common vector-borne disease in the united states, with , cases reported between and . it primarily affects children in the - age group and adults aged - . lyme disease is preventable by avoiding contact with ticks, by applying insect repellant, wearing long pants and long sleeves in infected areas, and by the early removal of attached ticks. several u.s. manufacturers produced vaccines which are approved for animal and human use. in the mid s, a mother of two young boys who were recently diagnosed with arthritis in the town of lyme, connecticut, conducted a private investigation among other town residents. she mapped each of the six arthritis cases in the town, cases which had occurred in a short time span among boys living in close proximity. this suggested that this syndrome of "juvenile rheumatoid arthritis" was perhaps connected with the boys playing in the woods. she presented her data to the head of rheumatology at yale medical school in new haven, who investigated this "cluster of a new disease entity." some parents reported that their sons had experienced tick bites and a rash before onset of the arthritis. a tick-borne, spiral shaped bacterium, a spirochete, borrelia burgdorferi, was identified as the organism, and ticks shown to be the vector. cases repond well to antibiotic therapy. in over , cases ( . per , ) were reported from states, an increase from , in and , in . cases were mainly located in the northeast, north central, and mid-atlantic regions. the disease accounts for over % of vector-borne disease in the united states and was the ninth leading reported infection in . lyme disease has been identified in many parts of north america, europe, the former soviet union, china, and japan. a newly licensed vaccine is effective for people exposed to ticks but not general usage. personal hygiene for protection from ticks and environmental modification are important to limit spread of the disease. source: cdc, , mmwr, : - ; and cdc, , mmwr, , no. . lyme disease website http://www.cdc.gov/ncidad/disease/lyme/lyme.htm medically important parasites are animals that live, take nourishment, and thrive in the body of a host, which may or may not harm the host, but never brings benefit. they include those caused by unicellular organisms such as protozoa, which include amoebas (malaria, schistosomiasis, amebiasis, and cryptosporidium), and helminths (worms), which are categorized as nematodes, cestodes, and trematodes. public health continues to face the problems of parasitic diseases in the developing world. increasingly, parasitic diseases are being recognized in industrialized countries. giardiasis and cryptosporidium infections in waterborne and other outbreaks have occurred in the united states. parasitic diseases are among the most common causes of illness and death in the world, e.g., malaria. milder illnesses such as giardiasis and trichomoniasis cause widespread morbidity. intestinal infestations with worms may cause of severe complications, although they commonly cause chronic low-grade symptomatology and iron deficiency anemia. echinococcosis (hydatid cyst disease) is infection with echinococcus granulosus, a small dog tapeworm. the tapeworm forms unilocular (single, noncompartmental) cysts in the host, primarily in the liver and lungs, but they can also grow in the kidney, spleen, central nervous system, or in bones. cysts, which may grow up to cm in size, may be asymptomatic or, if untreated, may cause severe symptoms and even death. this parasite is common where dogs are used with herd grazing animals and also have intimate contact with humans. the middle east, greece, sardinia, north africa, and south america are endemic areas, as are a few areas in the united states and canada. the human dis-ease has been eliminated in cyprus and australia. while the dog is the major host, intermediate hosts include sheep, cattle, pigs, horses, moose, and wolves. preventive measures include education in food and animal contact hygiene, destroying wild and stray dogs, and keeping dogs from the viscera of slaughtered animals. a similar, but multilocular, cystic hydatid disease is widely found in wild animal hosts in areas of the northern hemisphere, including central europe, the former soviet union, japan, alaska, canada, and the north-central united states. another echinococcal disease (echinococcus vogeli) is found in south america, where its natural host is the bush dog and its intermediate host is the rat. the domestic dog also serves as a source of human infection. surgical resection is not always successful, and long-term medical treatment may be required. control is through awareness and hygiene as well as the control of wild animals that come in contact with humans and domestic animals. control may require cooperation between neighboring countries. tapeworm infestation (taeniasis) is common in tropical countries where hygienic standards are low. beef (taenia saginata) and pork (t. solium) tapeworms are common where animals are fed with water or food exposed to human feces. freezing or cooking meat will destroy the tapeworm. fish tapeworm (diphyllobothrium latum) is common in populations living primarily on uncooked fish, such as inuit people. these tapeworms are usually associated with northern climates. toddlers are especially susceptible to dog tapeworm (dipylidium caninum), which is present worldwide, and domestic pets are often the source of oral-fecal transmission of the eggs. the disease is usually asymptomatic. similarly, dwarf tapeworm (hymenolepis nana) is transmitted through oral-fecal contamination from person to person, or via contaminated food or water. rat tapeworm (hymenolepis diminuta) also mostly affects young children. onchocerciasis (fiver blindness) is a disease caused by a parasitic worm, which produces millions of larvae that move through the body causing intense itching, debilitation, and eventually blindness. the disease is spread by a blackfly that transmits the larva from infected to uninfected people. it is primarily located in sub-saharan africa and in latin america, with over million persons at risk. control is by a combination of activities including environmental control by larvicidal sprays to reduce the vector population, protection of potential hosts by protective clothing and insect repellents, and case treatment. a who-initiated program for onchocerciasis control started in is sponsored by four international agencies: the food and agriculture organization (fao), the united nations development program (undp), the world bank, and who. it covers countries in sub-saharan africa, focusing on control of the blackfly by destoying its larvae, mainly via insecticides sprayed from the air. prevalence in was reported by who as over million persons. the program has been successful in protecting some million persons and helping . million infected persons to recover from this disease. who estimates that the program will have prevented , cases of blindness by the year and has freed million hectares of land for resettlement and cultivation. the program cost $ million. this investment is considered by the world bank to have a return of - % in terms of large scale land reuse and improved output of the population. a who program, the african program for onchocerciasis control (apoc), started in , uses a new drug (ivermectin) and selective vector control efforts by spraying. this involves countries in africa, and in a similar program in south america. see website http://www/who.int/ocp and is financed by many donor countries, internation organizations, merck & company, and ngos. dracunculiasis (guinea worm disease) is a parasitic disease of great public health importance in india, pakistan, and central and west africa. it is an infection of the subcutaneous and deeper tissues caused by a large ( cm) nematode, usually affecting the lower extremities and causing pain and disability. the nematode causes a burning blister on the skin when it is ready to release its eggs. after the blister ruptures, the worm discharges larvae whenever the extremity is in water. the eggs are ingested in contaminated water and the larva released migrate through the viscera to locate as adults in the subcutaneous tissue of the leg. incubation is about months. the larva released in water are ingested by minute crustaceans and remain infective for as long as a month. prevention is based on improving the safety of water supplies and by preventing contamination by infected persons. education of persons in endemic areas to stay out of water sources and to filter drinking water reduces transmission. insecticides remove the crustaceans. chlorine also kills the larvae and the crustaceans which prologue larval infectivity. there is no vaccine. treatment is helpful, but not definitive. dracunculiasis was traditionally endemic in a belt from west africa through the middle east to india and central asia. it was successfully eliminated from central asia and iran and has disappeared from the middle east and from some african countries (gambia and guinea). the world health organization has promoted the eradication of dracunculiasis. major progress has been made in this direction. worldwide prevalence is reported to have been reduced from million cases in to million in , , in , and , cases in . eradication was anticipated for the year , and in the who established a commission to monitor and certify eradication in formerly endemic areas. india's reported cases fell from , in to in , and the country was free of transmission in . in , formerly high prevalence countries such as kenya reported no cases in , while chad, senegal, cameroons, yemen, and the central african republic less than cases each. eradication of this disease appears to be imminent. the who eradication program was developed successfully as an independent program with its own direction and field staff, but further progress will require the integration of this program with other basic primary care programs in order to be self-sustaining as an integral part of community health. community-based surveillance systems for this disease are being converted to work for monitoring of other health conditions in the community. schistosomiasis (snail fever or bilharziasis) is a parasitic infection caused by the trematode (blood fluke) and transmitted from person to person via an intermediate host, the snail. it is endemic in countries in africa, south america, the caribbean, and asia. there are an estimated million persons infected worldwide and more than million at risk for the disease. the clinical symptoms include fever, nausea, vomiting, abdominal pain, diarrhea, and hematuria. the organisms schistosoma mansoni and s. japonicum cause intestinal and hepatic symptoms, including diarrhea and abdominal pain. schistosoma haematobium affects the genitourinary tract, causing chronic cystitis, pyelonephritis, with high risk for bladder cancer the ninth most common cause of cancer deaths globally. infection is acquired by skin contact with freshwater containing contaminated snails. the cercariae of the organism penetrate the skin, and in the human host it matures into an adult worm that mates and produces eggs. the eggs are disseminated to other parts of the body from the worm's location in the veins surrounding the bladder or the intestines, and may result in neurological symptoms. eggs may be detected under microscopic examination of urine and stools. sensitive serologic tests are also available. treatment is effective against all three major species of schistosomiasis. eradication of the disease can be achieved with the use of irrigation canals, prevention of contamination of water sources by urine and feces of infected persons, treatment of infected persons, destruction of snails, and health education in affected areas. persons exposed to freshwater lakes, streams, and rivers in endemic areas should be warned of the danger of infection. mass chemotherapy in communities at risk and improved water and sanitation facilities are resulting in improved control of this disease. leishmaniasis causes both cutaneous and visceral disease. the cutaneous form is a chronic ulcer of the skin, called by various names, e.g., rose of jericho, oriental sore, and aleppo boil. it is caused by leishmania tropica, l. brasiliensis, l. mexicana, or the l. donovani complex. this chronic ulcer may last from weeks to more than a year. diagnosis is by biopsy, culture, and serologic tests. the organism multiplies in the gut of sandflies (phlebotomus and lutzomi) and is transmitted to humans, dogs, and rodents through bites. the parasites may remain in the untreated lesion for - months, and the lesion does not heal until the parasites are eliminated. prevention is through limiting exposure to the phlebotomines and reducing the sandfly population by environmental control measures. insecticide use near breeding places and homes has been successful in destroying the vector sandflies in their breeding places. case detection and treatment reduce the incidence of new cases. there is no vaccine, and treatment is with specific antimonials and antibiotics. visceral leishmaniasis (kala azar) is a chronic systemic disease in which the parasite multiplies in the cells of the host's visceral organs. the disease is characterized by fever, the enlargement of the liver and spleen, lymphadenopathy, anemia, leukopenia, and progressive weakness and emaciation. diagnosis is by culture of the organism from biopsy or aspirated material, or by demonstration of intracellular (leishman-donovan) bodies in stained smears from bone marrow, spleen, liver, or blood. kala azar is a rural disease occurring in the indian subcontinent, china, the southern republics of the former u.s.s.r., the middle east, latin america, and sub-saharan africa. it usually occurs as scattered cases among infants, children, and adolescents. transmission is by the bite of the infected sandfly with an incubation period of - months. there is no vaccine, but specific treatment is effective and environmental control measures reduce the disease prevalence. this includes the use of antimalarial insecticides. in localities where the dog population has been reduced, the disease is less prevalent. sleeping sickness. sleeping sickness a disease caused by trypanosoma brucei, transmitted but the tsetse fly, primarily in the african savannahs, affecting cattle and humans. some million persons are at risk in sub-saharan africa. who reported , new cases, a total prevalence of , cases, and , deaths from this disease in . prevention depends on vector control, and effective treatment of human cases. chagas disease is a chronic and incurable vector and blood transfusion borne parasitic disease (trypanosoma cruzi) which causes disability and death. it affects some million persons mainly in latin america, with some , new cases and , deaths occurring annually. about % of affected persons develop severe heart disease. brazil, which accounts for % of the cases prevalent in latin america, achieved elimination of transmission in , after uruguay ( ) and venezuela ( ) and followed by argentina ( ) . elimination of transmission is projected by who by the year . control is difficult, but control measures include reducing the animal host and vector insect population in its habitat by ecological and insectiside measures, education of the population in prevention by clothing, bednets, and repellents, and with chemotherapy for case management. amebiasis. amebiasis is an infection with a protozoan parasite (entamoeba histolytica) which exists as an infective cyst. infestation may be asymptomatic or cause acute, severe diarrhea with blood and mucus, alternating with constipation. amebic colitis can be confused with ulcerative colitis. diagnosis is by microscopic examination of fresh fecal specimens showing trophozoites or cysts. transmission is generally via ingestion of fecal-contaminated food or water containing cysts, or by oral-anal sexual practices. amebiasis is found worldwide. sand filtration of community water supplies removes nearly all cysts. suspect water should be boiled. education regarding hygienic practices with safe food and water handling and disposal of human feces are the basis for control. ascariasis. ascariasis is infestation of the small intestine with the roundworm ascaris lumbricoides, which may appear in the stool, occasionally the nose or mouth, or may be coughed up from lung infestation. the roundworm is very common in tropical countries, where infestation may reach or exceed % of the population. children aged - years are especially susceptible. infestation can cause pulmonary symptoms and frequently contributes to malnutrition, especially iron deficiency anemia. transmission is by ingestion of infective eggs, common among children playing in contaminated areas, or via the ingestion of uncooked products of infected soil. eggs may remain viable in the soil for years. vermox and other treatments are effective. prevention is through education, adequate sanitary facilities for excretion, and improved hygienic practices, especially with food. use of human feces for fertilizer, even after partial treatment, may spread the infestation. mass treatment is indicated in high prevalence communities. pinworm disease or enterobiasis. pinworm disease (oxyuriasis) is common worldwide in all socioeconomic classes; however, it is more widespread when crowded and unsanitary living conditions exist. the enterobius vermicularis infestation of the intestine may be symptomless or may cause severe perianal itching or vulvovaginitis. it primarily affects schoolchildren and preschoolers. more severe complications may occur. adult worms may be seen visually or identified by microscopic examination of stool specimens or perianal swabs. transmission is by the oral-fecal ingestion of eggs. the larvae grow in the small intestine and upper colon. prevention is by educating the public regarding hygiene and adequate sanitary facilities, as well as by treating cases and investigating contacts. treatment is the same as for ascariasis. mass treatment is indicated in high prevalence communities. ectoparasites. ectoparasites include scabies (sarcoptes scabiei), the common bed bug (cimex lectularius), fleas, and lice, including the body louse (pediculus humanis), pubic louse (phthirius pubis), and the head louse (pediculus humanus capitis). their severity ranges from nuisance value to serious public health hazard. head lice are common in schoolchildren worldwide and are mainly a distressing nuisance. the body louse serves as a vector for epidemic typhus, trench fever, and louse-borne relapsing fever. in disaster situations, disinfection and hygienic practices may be essential to prevent epidemic typhus. the flea plays an important role in the spread of the plague by transmitting the organism from the rat to humans. control of rats has reduced the flea population, but during war and disasters, rat and flea populations may thrive. scabies, which is caused by a mite, is common worldwide and is transmitted from person to person. the mite burrows under the skin and causes intense itching. all of these ectoparasites are preventable by proper hygiene and the treatment of cases. the spread of these diseases is rapid and therefore warrants attention in school health and public health policy. legionnelae, a gram-negative group of bacilli, with species and many serogroups. the first documented case was reported in the united states in , and the first disease outbreak was reported in the united states in among participants of a war veterans convention. general malaise, anorexia, myalgia, and headache are followed by fever, cough, abdominal pain, and diarrhea. pneumonia followed by respiratory failure may follow. the case fatality rate can be as high as % of hospitalized cases. a milder, nonpneumonic form of the disease (pontiac fever) is associated with virtually no mortality. the organism is found in water reservoirs and is transmitted through heating, cooling, and air conditioning systems, as well as from tap water, showers, saunas, and jaccuzzi baths. the disease has been reported in australia, canada, south america, europe, israel, and on cruise ships. prevention requires the cleaning of water towers and cooling systems, including whirlpool spas. hyperchlorination of water systems and the replacement of filters is required where cases and/or organisms have been identified. antibiotic treatment with erythromycin is effective. leprosy (hansen's disease) was widely prevalent in europe and mediterranean countries for many centuries, with some , leprosaria in the year . leprosy was largely wiped out during the black death in the fourteenth century, but continued in endemic form until the twentieth century. leprosy is a chronic bacterial infection of the skin, peripheral nerves, and upper airway. in the lepromatous form, there is diffuse infiltration of the skin nodules and macules, usually bilateral and extensive. the tuberculoid form of the disease is characterized by clearly demarcated skin lesions with peripheral nerve involvement. diagnosis is based on clinical examination of the skin and signs of peripheral nerve damage, skin scrapings, and skin biopsy. transmission of the mycobacterium leprae organism is by close contact from person to person, with incubation periods of between months and years (average of - years). rifampicin and other medications make the patient noninfectious in a short time, so that ambulatory treatment is possible. multidrug therapy (mdt) has been shown to be highly effective in combating the disease, with a very low relapse rate. treatment with mdt ensures that the bacillus does not develop drug resistance. mdt is covering % of known cases in , according to who reports, as compared to only % in . the increase has been associated with improved case finding. bcg may be useful in reducing tuberculoid leprosy among contacts. investigation of contacts over years is recommended. the disease is still highly endemic primarily in five countries, india, brazil, indonesia, myanmar, and bangladesh, and is still present in some countries in southeast asia, including the philippines and burma, sub-saharan africa, the middle east (sudan, egypt, iran), and in some parts of latin america (mexico, colombia) with isolated cases in the united states. world prevalence has declined from . million cases in , . million in , to less than million cases in . the world health organization expects to eliminate leprosy as a public health problem by the year , defined as prevalence of less than per , population, or less than , cases. trachoma is currently responsible for million blind persons or % of total blindness in the world. the causative organism, chlamydia trachomatis, is a bacteria which can survive only within a cell. it is spread through contact with eye discharges, usually by flies, or household items (e.g., handkerchiefs, washcloths). trachoma is common in poor rural areas of central america, brazil, africa, parts of asia, and some countries in the eastern mediterranean. the resulting infection leads to conjuncfival scarring and if untreated, to blindness. who estimates there are million cases of active disease in endemic countries. hygiene, vector control, and treatment with antibiotic eye ointments or simple surgery for scarring of eyelids and inturned eyelashes prevent the blindness. a new drug, azithromycin, is effective in curing the disease. the who is promoting a program for the global elimination of trachoma using azithromycin and hygiene education in endemic areas. chlamydia (chlamydia pneumonia) is suspected of playing a role in coronary artery disease by intraarterial infection, with plaque formation and occlusion of the artery by thrombi consisting mainly of platelets. if borne out, this will provide potential for low cost intervention to reduce the burden of the leading worldwide cause of death. sexually transmitted diseases (stds) are widespread internationally with an estimated million new cases per year, with . million new cases, over million total cases, and . million deaths ( ), aids has captured world attention over the past decade. the global burden of stds is enormous (table . ), and the public health and social consequences are devastating in many countries. sexually transmitted diseases, especially in women, may be asymptomatic, so that severe sequelae may occur before patients seek care. infection by one std increases risk of infection by other diseases in this group. syphilis is caused by the spirochete treponema pallidum. after an incubation period of - days (mean - ), primary syphilis develops as a painless ulcer or chancre on the penis, cervix, nose, mouth, or anus, lasting - weeks. the patient may first present with secondary syphilis - weeks (up to weeks) after infection with a general rash and malaise, fever, hair loss, arthritis, and jaundice. these symptoms spontaneously disappear within weeks or up to months later. tertiary syphilis may appear - years after initial infection. complications of tertiary syphilis include catastrophic cardiovascular and central nervous system conditions. early antibiotic treatment is highly effective when given in a large initial dose, but longer term therapy may be needed if treatment is delayed. gonorrhea (gc) is caused by the bacterium neisseria gonorrhoeae. the incubation period is - days. gonorrhea is often associated with concurrent chlamydia infection. in women, gc may be asymptomatic or it may cause vaginal discharge, pain on urination, bleeding on intercourse, or lower abdominal pain. untreated, it can lead to sterility. in men, gc causes urethral discharge and painful urination. treatment with antibiotics ends infectivity, but untreated cases can be infectious for months. drug resistance to penicillin and tetracycline has increased in many countries so that more expensive and often unavailable drugs are necessary for treatment. prevention of gonococcal eye infection in newborns is based on routine use of antibiotic ointments in the eyes of newborns. chancroid. chancroid is caused by haemophilus ducreyi. in women chancroids may cause a painful, irregular ulcer near the vagina, resulting in pain on in-tercourse, urination, and defection, but it may be asymptomatic. in men it causes a painful, irregular ulcer on the penis. the incubation period is usually - days, but may be up to days. an individual is infectious as long as there are ulcers, usually - months. treatment is by erythromycin or azithromycin. herpes simplex. herpes simplex is caused by herpes simplex virus types and and has an incubation period of - days. genital herpes causes painful blisters around the mouth, vagina, penis, or anus. the genital lesions are infectious for - days. herpes may lead to central nervous system meningoencephalitis infection. it can be transmitted to newborns during vaginal delivery, causing infection, encephalitis, and death. cesarian delivery is therefore necessary when a mother is infected. anti-viral drugs are used in treatment, orally, topically, or intravenously. chlamydia. chlamydia is caused by chlamydia trachomatis. in women, it is usually asymptomatic but may cause vaginal discharge, spotting, pain on urination, lower abdominal pain, and pelvic inflammatory disease (pid). in newborns, chlamydia may cause eye and respiratory infections. in men, chlamydia causes urethral discharge and pain on urination. the incubation period is - days and the infectious period is unknown. treatment for chlamydia is doxycycline, azithromycin, or erythromycin. chlamydia infection, not necessarily venereal in transmission, may be transmitted to newborns of infected mothers. chlamydia pneumoniae, presently under investigation as a possible cause or contributor to coronary heart disease, and is widespread in poor hygenic conditions. trichomoniasis. trichomoniasis is caused by trichomonas vaginalis. the incubation period is - days (mean = ). in women, trichomoniasis may be asymptomatic or may cause a frothy vaginal discharge with foul odor, and painful urination and intercourse. in men, the disease is usually mild, causing pain on urination. treatment is by metronidazole taken orally. without treatment, the disease may persist and remain infectious for years. (hpv). it is a sporadic disease which may be associated with cervical neoplasia and cancer of the cervix. hpv includes many types associated with a variety of conditons. the search for a hpv vaccine to prevent cancer of the cervix looks promising. in areas where a full range of diagnostic services is lacking, a "syndromic approach" is recommended for the control of stds. the diagnosis is based on a group of symptoms and treatment on a protocol addressing all the diseases that could possibly cause those symptoms, without expensive laboratory tests and repeated visits. early treatment without laboratory confirmation helps to cure persons who might not return for follow-up, or may place them in a noninfective stage so that even without follow-up they will not transmit the disease. std incidence between and is shown in table . , with decline overall except around , with subsequent further fall in incidence. screening in prenatal and family planning clinics, prison medical services, and selected years - disease syphilis ( [ ] [ ] [ ] [ ] [ ] [ ] and subsequent decline by more than % in reported cases includes all three stages of the disease as well as congential syphilis. rates are cases per , population, rounded. in clinics serving prostitutes, homosexuals, or other potential risk groups will detect subclinical cases of various stds. treatment can be carried out cheaply and immediately. for instance, the screening test for syphilis costs $ . and the treatment with benzathine penicillin injection costs about $ . in . partner notification is a controversial issue, but may be needed to identify contacts who may be the source of transmission to others. control of stds through a syndrome approaach based on primary care providers is being promoted by who. health education directed at high risk target groups is essential. providing easy and cost-free access to acceptable, nonthreatening treatment is vital in promoting the early treatment of cases and thereby reducing the risk of transmission. promoting prevention through the use of condoms and/or monogamy requires long-term educational efforts that are now fostered by the hiv/aids pandemic. increased use of condoms for hiv prevention is associated with reduced risk of other stds. training medical care providers in std awareness should be stressed in undergraduate and continuing educational efforts including personal protection as care givers. human immunodeficiency virus (hiv) is a retrovirus that infects various cells of the immune system, and also affects the central nervous system. two types have been identified: hiv , worldwide in distribution, and the less pathogenic hiv , found mainly in west africa. hiv is transmitted by sexual contact, exposure to blood and blood products, perinatally, and via breast milk. the period of communicability is unknown, but studies indicate that infectiousness is high, both during the initial period after infection and later in the disease. antibodies to hiv usually appear within - months. within several weeks to months of the infection, many persons develop an acute self-limited flulike syndrome. they may then be free of any signs or symptoms for months to more than years. onset of illness is usually insidious with nonspecific symptoms, including sweats, diarrhea, weight loss, and fatigue. aids represents the later clinical stage of hiv infection. according to the revised cdc case definition ( ), aids involves any one or more of the following: low cd count, severe systematic symptoms, opportunistic infections such as pneumocystis pneumonia or tb, aggressive cancers such as kaposi's sarcoma or lymphoma, and/or neurological manifestations, including dementia and neuropathy. the who case definition is more clinically oriented, relying less on often unavailable laboratory diagnoses for indicator diseases. aids was first recognized clinically in in los angeles and new york. by mid- it was considered an epidemic in those and other u.s. cities. it was primarily seen among homosexual men and recipients of blood products. after initial errors, testing of blood and blood products became standard and has subsequently closed off this method of transmission. transmission has changed markedly since the initial onslaught of the disease, with needle sharing among intravenous drug users, heterosexual, and maternal-fetal transmission becoming major factors. comorbidity with other stds apparently increases hiv infectivity and may have helped to convert the epidemiology to a greater degree of heterosexual transmission. the disease grew exponentially in the united states (table . ), but incidence of new cases nas declined since . aids has become a major public health problem in most developed and developing countries, reaching catastrophic proportions in some sub-saharan african countries affecting up to % of the population. hiv-related deaths were the eighth leading cause of all deaths in in the u.s., the leading cause among men aged - years of age, and the fourth leading cause for women in this age group. by , aids had been diagnosed in , persons and , had died. it is estimated that up to million persons are hiv infected in the united states. globally, deaths from aids totalled . million in , with an estimated . million person having died from this pandemic up to . in , an estimated . million person were hiv infected with . million new infection in . the declining incidence of new cases in the industrialized countries may be the result of greater awareness of the disease and methods of prevention of transmission. improving early diagnosis and access to care, especially the combined therapy programs that are very effective in delaying onset of symptoms, are important parts of public health management of the aids crisis. until an effective vaccine is available, preventive reliance will continue to be on behavior risk-reduction and other prevention strategies such as needle and condom distribution among high risk population groups. throughout the world, hiv continues to spread rapidly, especially in poor countries in africa, asia, and south and central america. the united nations reports that million persons are living with hiv/aids, % of them in developing countries, where transmission is % by heterosexual contact. every day, more than persons are infected, including children. in thailand, person in is now infected. in sub-saharan africa person in is infected, and in some cities as many as person in carries the virus. estimations of new infections per year in sub-saharan africa range from to million persons, while in asia the range is from . to . million new infected persons per year. lessons are still being learned from the aids pandemic. the explosive spread of this infection, from an estimated , people in to an anticipated million persons hiv infected, shows that the world is still vulnerable to pandemics of "new" infectious diseases. enormous movements of tourists, business people, truck drivers, migrants, soldiers, and refugees promote the spread of such diseases. widespread sexual exchange, traffic in blood products, and illicit drug use all promote the international potential for pandemics. war and massive refugee situations promote rape and prostitution, worsening the aids situation in some settings in africa. hiv has arrived in almost every country. however, there is the somewhat hopeful indication that the rate of increase, has slowed in the united states. this may be an indication either of higher levels of self-protective behavior, or that the most susceptible population groups have already been affected and the spread into the general population is at a slower rate. it is also possible that this may yet prove to be only a lull in the storm, as heterosexual contact becomes a more important mode of transmission. the eleventh international conference on aids, held in vancouver, canada, in july , reported signs that combinations of several drugs from among a number of antiretroviral medications are showing promise to suppress the aids virus in infected people. at a current annual price of $ , - , per patient, these sums well beyond the capacity of most developing countries. development of methods of measuring the hiv viral load have allowed for better evaluation of potential therapies and monitoring of patients receiving therapy. in developed countries, transmission by blood products has been largely controlled by screening tests; transmission among homosexuals has been reduced by safe sex practices; transmission to newborns has been reduced by recent therapeutic advances. safe sex practices and condom use may have helped in reducing heterosexual transmission. further advances in therapy and prevention with a vaccine are expected over the next decade. the hiv/aids pandemic is one of the great challenges to public health for the st century due to its complexity, its international spread, its sexual and other modes of transmission, its devastating and costly clinical effects, and its impact on parallel diseases such as tuberculosis, respiratory infections, and cancer. the cost of care for the aids patient can be very high. needed programs include home care and community health workers to improve nutrition and self-care, and mutual help among hiv carriers and aids patients. the ethical issues associated with aids are also complex regarding screening of pregnant women, newborns, partner notification, reporting, and contact tracing, as well as financing the cost of care. diarrheal diseases are caused by a wide variety of bacteria, parasites, and viruses (table . ) infecting the intestinal tract and causing secretion of fluids and dis- solved salts into the gut with mild to severe or fatal complications. in developing countries, diarrheal diseases account for half of all morbidity and a quarter of all mortality. diarrhea itself does not cause death, but the dehydration resulting from fluid and electrolyte loss is one of the most common causes of death in children worldwide. deaths from dehydration can be prevented by use of oral rehydration therapy (ort), an inexpensive and simple method of intervention easily used by a nonmedical primary care worker and by the mother of the child as a home intervention. in , diarrheal diseases were the cause of almost million child deaths, but by this had declined to . million, largely under the impact of increased use of ort. diarrheal diseases are transmitted by water, food, and directly from person to person via oral-fecal contamination. diarrheal diseases occur in epidemics in situations of food poisoning or contaminated water sources, but can also be present at high levels when common source contamination is not found. contamination of drinking water by sewage and poor management of water supplies are also major causes of diarrheal disease. the use of sewage for the irrigation of vegetables is a common cause of diarrheal disease in many areas. salmonella are a group of bacterial organisms causing acute gastroenteritis, associated with generalized illness including headache, fever, abdominal pains, and dehydration. there are over serotypes of salmonella, many of which are pathogenic in humans, the most common of which are salmonella typhimurium, s. enteritidis, and s. typhi. transmission is by ingestion of the organisms in food, derived from fecal material from animal or human contamination. common sources include raw or uncooked eggs, raw milk, meat, poultry and its products, as well as pet turtles or chicks. fecal-oral transmission from person to person is common. prevention is in safe animal and food handling, refrigeration, sanitary preparation and storage, protection against rodent and insect contamination, and the use of sterile techniques during patient care. antibiotics may not eliminate the carrier state and may produce resistant strains. shigella are a group of bacteria that are pathogenic in man, with four groups: type a = shigella dysenteriae, type b = s. flexneri, type c = s. boydii, and type d = s. sonnei. types a, b, and c are each further divided into a total of serotypes. shigella are transmitted by direct or indirect fecal-oral methods from a patient or carrier, and illness follows ingestion of even a few organisms. water and milk transmission occurs as a result of contamination. flies can transmit the organism, and in nonrefrigerated foods the organism may multiply to an infectious dose. control is in hygienic practices and in the safe handling of water and food. escheria eoli e. coli are common fecal contaminants of inadequately prepared and cooked food. particularly virulent strains such as o :h can cause explosive outbreaks of severe (enterohemmorhagic) diarrhoeal disease with a hemolytic-uremic syndrome and death, as occurred in japan in with cases and deaths due to a foodborne epidemic. other milder strains cause travellers diarrhoea and nursery infections. inadequately cooked hamburger, unpasturized milk, and other food vectors are discussed under food safety in chapter . cholera is an acute bacterial enteric disease caused by vibrio cholerae, with sudden onset, profuse painless watery stools, occasional vomiting, and, if untreated, rapid dehydration, and circulatory collapse, and death. asymptomatic infection or carrier status, and mild cases are common. in severe, untreated cases, mortality is over %, but with adequate treatment, mortality is under %. diagnosis is based on clinical signs, epidemiologic, serologic and bacteriologic confirmation by culture. the two types of cholera are the classic and el tor (with inaba and ogawa serotypes). in , a large scale epidemic of cholera spread through much of south america. it was imported via a chinese freighter, whose sewage contaminated shellfish in lima harbor in peru (box . ). the south american cholera epidemic has caused hundreds of thousands of cases and thousands of deaths since . prevention requires sanitation, particularly the chlorination of drinking water, prohibiting the use of raw sewage for the irrigation of vegetable crops, and high standards of community, food, and personal hygiene. treatment is prompt fluid therapy with electrolytes in large volume to replace all fluid loss. oral rehydration should be accomplished using standard ort. tetracycline shortens the duration of the disease, and chemoprophylaxis for contacts following stool samples may help in reducing its spread. a vaccine is available but is of no value in the prevention of outbreaks. viral gastroenteritis can occur in sporadic or epidemic forms, in infants, children, or adults. some viruses, such as the rotaviruses and enteric adenoviruses, af- in the s, peruvian officials stopped the chlorination of community water supplies because of concern over possible carcinogenic effects of trihalomethanes, a view encouraged by officials of the u.s. environmental protection agency (epa) and the u.s. public health service. in january , a chinese freighter arrived in lima, peru, and dumped bilge (sewage) in the harbor, apparently contaminating local shellfish. consumption of raw shellfish is a popular local delicacy (ceviche) and associated with cases of cholera seen in local hospitals. contamination of local water supplies from sewage resulted in the geometric increase in cases, and by the end of the pan american health organization (paho) reported an epidemic of , cases and deaths. the epidemic spread to countries, and in there were a further , cases and deaths spreading over much of south america, continuing in . in the united states, cases of cholera were reported in ; of these, cases and death were among passengers of an airplane flying from south america to los angeles in which contaminated seafood was served. in , cases of cholera were reported in the united states which were unrelated to international travel. these occurred mostly among persons consuming shellfish from the gulf coast with a strain of cholera similar to the south american strain, also possibly introduced in ship ballast. cholera organisms are reported in harbor waters in other parts of the united states (promed, , promed, . fect mainly infants and young children, and may be severe enough to cause hospitalization for dehydration. others such as norwalk and norwalk-like viruses affect older children and adults in self-limited acute gastroenteritis in family, institution, or community outbreaks. rotaviruses cause acute gastroenteritis in infants and young children, with fever and vomiting, followed by watery diarrhea and occasionally severe dehydration and death if not adequately treated. diagnosis is by examination of stool or rectal swabs with commercial immunologic kits. in both developed and developing countries, rotavirus is the cause of about one-third of all hospitalized cases for diarrheal diseases in infants and children up to age . most children in developing countries experience this disease by the age of years, with the majority of cases between and months. in developing countries, rotaviruses are estimated to cause over , deaths per year. the virus is found in temperate climates in the cooler months and in tropical countries throughout the year. breastfeeding does not prevent the disease but may reduce its severity. oral rehydration therapy is the key treatment. a live attenuated vaccine was approved by the fda in and adopted in the u.s. recommended routine vaccination programs for infants. adenoviruses. adenoviruses, norwalk, and a variety of other viruses (including astrovirus, calcivirus, and other groups) cause sporadic acute gastroenteritis worldwide, mostly in outbreaks. spread is by the oral-fecal route, often in hospital or other communal settings, with secondary spread among family contacts. food-borne and waterborne transmission are both likely. these can be a serious problem in disaster situations. no vaccines are available. management is with fluid replacement and hygienic measures to prevent secondary spread. giardiasis. giardiasis (caused by giardia lamblia) is a protozoan parasitic infection of the upper small intestine, usually asymptomatic, but sometimes associated with chronic diarrhea, abdominal cramps, bloating, frequent loose greasy stools, fatigue, and weight loss. malabsorption of fats and vitamins may lead to malnutrition. diagnosis is by the presence of cysts or other forms of the organism in stools, duodenal fluid, or in intestinal mucosa from a biopsy. this disease is prevalent worldwide and affects mostly children. it is spread in areas of poor sanitation and in preschool settings and swimming pools, and is of increasing importance as a secondary infection among immunocompromised patients, especially those with aids. waterborne giardia was recognized as a serious problem in the united states in the s and s, since the protozoa is not readily inactivated by chlorine, but requires adequate filtration before chlorination. person-to-person transmission in day-care centers is common, as is transmission by unfiltered stream or lake water where contamination by human or animal feces is to be expected. an asymptomatic carrier state is common. prevention relies on careful hygiene in settings such as day-care centers, filtration of public water supplies and the boiling of water in emergency situations. cryptosporidium. cryptosporidium parvum is a parasitic infection of the gastrointestinal tract in man, small and large mammals and vertebrates. infection may be asymptomatic or cause a profuse, watery diarrhea, abdominal cramps, general malaise, fever, anorexia, nausea, and vomiting. in immunosuppressed patients, such as persons with aids, it can be a serious problem. the disease is most common in children under years of age and those in close contact with them, as well as in homosexual men. diagnosis is by identification of the cryptosporidium or-ganism cysts in stools. the disease is present worldwide. in europe and the united states, the organism has been found in < to . % of individuals sampled. spread is common by person-to-person contact by fecal-oral contamination, especially in such settings as day-care centers. raw milk and waterborne outbreaks have also been identified in recent years. a large waterborne disease outbreak due to cryptosporidium occurred in milwaukee in described in chapter . management is by rehydration and prevention is by careful hygiene in food and water safety. helicobacter pylori. helicobacter pylori, first identified in , is a bacterium causally linked to duodenal ulcers and gastritis, contributing to high rates of gastric cancer (chapter ). it is an important example of the link between infection and chronic disease. this has enormous implications for prevention of cancer of the stomach, chronic peptic ulcers and large-scale use of hospitals and other medical resources (see chapter ). the control of diarrheal diseases requires a comprehensive program involving a wide range of activities, including good management of food and water supplies, education in hygiene, and, particularly where morbidity and mortality are high, education in the use of oral rehydration therapy (ort). oral rehydration therapy (ort) is considered by unicef and who to have resulted in the saving of million lives each year in the s. proper management of an episode of diarrhea by ort (table . ), along with continued feeding, not only saves the child from dehydration and immediate death, but also contributes to early restoration of nutritional adequacy, sparing the child the prolonged effects of malnutrition. the world summit for children (wsc) in called for a reduction in child deaths from diarrheal diseases by one-third and malnutrition by one-half, with em- phasis on the widest possible availability, education for, and use of ort. this requires a programmatic approach. public health leadership must train primary care doctors, pediatricians, pharmacists, drug manufacturers, and primary care health workers of all kinds in ort principles and usage. they must be backed by the widest possible publicity to raise awareness among parents. oral rehydration therapy is an important public health modality in developed countries as well as in developing countries. diarrhoeal disease may not cause death as frequently in developed countries, but it is still a significant factor in infant and child health and, even under the most optimal conditions, can cause setbacks in the nutritional state and physical development of a child. use of ort does not prevent the disease (i.e., it is not a primary prevention), but it is excellent in secondary prevention, by preventing complications from diarrhoea, and should be available in every home for symptomatic treatment of diarrheal diseases. an adaptation of ort has found its place in popular culture in the united states. a form of ort, marketed as "sports drinks," is used in sports where athletes lose large quantifies of water and salts in sweat and insensible loss from the respiratory tract. the wider application of the principles of ort for use in adults in dry hot climates and in adults under severe physical exertion with inadequate fluid/salt intake situations requires further exploration. management of diarrheal diseases should be part of a wider approach to child nutrition. the child who goes through an episode of diarrheal disease may have a faltering in growth and development. supportive measures may be needed following the episode as well as during it. this involves providing primary care services that are attuned to monitoring individual infant and child growth. growth monitoring surveillance is important to assess the health status of the individual child and the child population. supplementation of infant feeding with vitamins a and d, and iron to prevent anemia are important for routine infant and child care, and more so for conditions affecting total nutrition such as a diarrheal disease. in the developing world, respiratory infections account for over one-quarter of all deaths and illnesses in children. as diarrheal disease deaths are reduced, the major cause of death among infants in developing countries is becoming acute respiratory infections (aris). in industrialized countries, aris are important for their potentially devastating effects on the elderly and chronically ill. they are also the major cause of morbidity in infants in developed countries, causing much anxiety to parents even in areas with good living conditions. cigarette smoking, chronic bronchitis, poorly controlled diabetes or congestive heart failure, and chronic liver and kidney disease increase susceptibility to aris. aris place a heavy burden on health care systems and individual families. improved methods of management of such chronic diseases are needed to reduce the associated toll of morbidity, mortality, and the considerable expenses of health care. acute respiratory infections are due to a broad range of viral and, to a lesser extent, bacterial infections. it is the latter which can progress to pneumonia with mortality rates of - %. acute viral respiratory diseases include those affecting the upper respiratory tract, such as acute viral rhinitis, pharyngitis, and laryngitis, as well as those affecting the lower respiratory tract, tracheobronchitis, bronchitis, bronchiolitis, and pneumonia. aris are frequently associated with vaccine-preventable diseases, including measles, varicella, and influenza. they are caused by a large number of viruses, producing a wide spectrum of acute respiratory illness. some organisms affect any part of the respiratory tract, while others affect specific parts and all predispose to bacterial secondary infection. while children and the elderly are especially susceptible to morbidity and mortality from acute respiratory disease, the vast numbers of respiratory illnesses among adults cause large-scale economic loss from work absence. bacterial agents causing upper respiratory tract infection include group a streptococcus, mycoplasma pneumonia, pertussis, and parapertussis. pneumonia or acute bacterial infection of the lower respiratory tract and lung tissue may be due to pneumococcal infection with streptococcus pneumoniae. there are known types of this organism, distinguished by capsule characteristics; account for % of pneumococcal infections in the united states. an excellent polyvalent vaccine based on these types is available for high risk groups such as the elderly, immunodeficient patients, and persons with chronic heart, lung, liver, blood disorders, or diabetes. opportunistic infections attack the chronically ill, especially those with compromised immune suystems, often with life-threatening aris. mycoplasma (primary atypical pneumonia) is a lower respiratory tract infection which sometimes progresses to pneumonia. tb and pneumonocytis carynia are especially problematic for aids patients. other organisms causing pneumonias include chlamydia pneumoniae, h. influenza, klebsiella pneumonia, escherichia coli, staphylococcus, rickettsia (q fever), and legionella. parasitic infestation of lungs may occur with nematodes (e.g., ascariasis). fungal infections of the lung may be caused by aspergillosis, histoplasmosis, and coccidiomycosis, often as a complication of antibiotic therapy. access to primary care and early institution of treatment are vital to control excess mortality from aris. in developed countries, aris as contributors to infant deaths are largely a problem in minority and deprived population groups. because these groups contribute disproportionately to childhood mortality, infant mortality reduction has been slower in countries such as the united states and russia than in other industrialized countries. the continuing gap in mortality rates between white and black children in the united states can, to a large extent, be attributed to aris and less access to organized primary care. children are brought to emergency rooms for care when the disease process is already advanced and more dangerous than had it been attended to professionally earlier in the process. many field trials of ari prevention programs have been proved successful involving parent education and training of primary care workers in early assessment and, if necessary, initiation of treatment. this needs field testing in multiple settings. reliance on vaccines to prevent respiratory infectious diseases is not currently feasible. aris are caused by a very wide spectrum of viruses, and the development of vaccines in this field has been slow and limited. the vaccine for pneumococcal pneumonia has been an important breakthrough, but it is still inadequately utilized by the chronically ill because of its limitations, costs, and lack of sufficient awareness, and it is too expensive for developing countries. improvements in bacterial and viral vaccine development will potentially help to reduce the burden of aris. a programmatic approach with clinical guidelines and education of family and care givers is currently the only feasible way to reduce the still enormous morbidity and mortality from aris on the young and the elderly. the success of sanitation vaccines and antibiotics led many to assume that all infectious diseases would sooner or later succumb to public health and medical technology. unfortunately, this is a premature and even dangerous assumption. despite the longstanding availability of an effective and inexpensive vaccine, the persistence of measles as a major killer of million children per year represents a failure in effective use of both the vaccine and the health system. the resurgence of tb and malaria have led to new strategies, such as managed or directly observed care, with community health workers to assure compliance needed to render the patient noninfectious to others and to reduce the pool of carriers of the disease. current successes in reducing poliomyelitis, dracunculiasis, onchocerciasis, and other diseases to the point of eradication has raised hopes for similar success in other fields. but there are many infectious diseases of importance in developed and developing countries where existing technologies are not fully utilized. oral rehydration therapy (ort) is one of the most cost-effective methods of preventing excess mortality from ordinary diarrheal diseases, and yet is not used on sufficient scale. biases in the financing and management of medical insurance programs can result in underutilization of available effective vaccines. hospital-based infections cause large-scale increases in lengths of stay and expenditures, although application of epidemiologic investigation and improved quality in hospital practices could reduce this burden. control of the spread of aids using combined medical therapies is not financially or logistically possible in many countries, but education for "safe sex" is effective. community health worker programs can greatly enhance tuberculosis, malaria, and std control, or in aids care, promote prevention and appropriate treatment. in the industrialized and mid-level developing countries, epidemiologic and demographic shifts have created new challenges in infectious disease control. prevention and early treatment of infectious disease among the chronically ill and the elderly is not only a medical issue, it is also an economic one. patients with chronic obstructive lung disease (copd), chronic liver or kidney disease, or congestive heart failure are at high risk of developing an infectious disease followed by prolonged hospitalization. public health has addressed, and will continue to stress the issues of communicable disease as one of its key issues in protecting individual and population health. methods of intervention include classic public health through sanitation, immunization, and well beyond that into nutrition, education, case finding, and treatment, and changing human behavior. the knowledge, attitudes, beliefs, and practices of policy makers, health care providers, and parents is as important in the success of communicable disease control as are the technology available and methods of financing health systems. together, these encompass the broad programmatic approach of the new public health to control of communicable diseases. in a world of rapid international transport and contact between populations, systems are needed to monitor the potential explosive spread of pathogens that may be transferred from their normal habitat. the potential for the international spread of new or reinvigorated infectious diseases constitute threat to mankind akin to ecological and other man-made disasters. the eradication of smallpox paved the way for the eradication of poliomyelitis, and perhaps measles, in the foreseeable future. new vaccines are showing the capacity to reduce important morbidity from rubella syndrome, mumps, meningitis, and hepatitis. other new vaccines on the horizon will continue the immunologic revolution into the twenty-first century. as the triumphs of control or elimination of infectious diseases of children continue, the scourge of hiv infection continues with distressingly slow progess an effective vaccine or cure for the disease it engenders. partly as a result of the hiv/ aids, tb staged a comeback in many countries where it was thought to be merely a residual problem. at the same time an old/new method of intervention using directly observed short-term therapy has shown great success in controlling the tb epidemic. the resurgence of tb is more dangerous in that mdrtb has become a widespread problem. this issue highlights the difficulty of keeping ahead of drug resistance in the search for new generations of antibiotics, posing a difficult challenge for the pharmaceutical industry, basic scientists as well as public health workers. the burden of infectious diseases has receded as the predominant public health problem in the developed countries but remains large in the developing countries. with increases in longevity and increased importance of chronic disease in the health status of the industrial and mid-level developing nations, the effects of infectious disease on the care of the elderly and chronically ill is of great importance in the new public health. long-term management of chronic disease needs to address the care of vulnerable groups, promoting the use of existing vaccines and antibiotics. most important is the development of health systems that provide close monitoring of groups at special risk for infectious disease, especially patients with chronic diseases, the immunocompromised, and the elderly. the combination of traditional public health with direct medical care needed for effective control and eradication of communicable diseases is an essential element of the new public health. the challenge is to apply a comprehensive approach and management of resources to define and reach achievable targets in communicable disease control. access to e-mail and the internet are vital to current practice of public health and nowhere is this more important than in communicable diseases. there are many such information sites and these will undoubtedly expand in the coming years. several sites are given as examples. the internet has great practical implications for keeping up to date with rapidly occurring events in this field. outstanding encyclopedia database on infectious diseases (available via mdcassoc@ix.netcom.com at reduced price for promed users, and free to sub-saharan african sites) promed is an excellent, free report on current events in communicable diseases internationally; join via owner-promed @usa recommended readings centers for disease control. . update: international task force for disease eradication addressing emerging infectious disease threats: a prevention strategy for the united states. executive summary update: trends in aids incidence--united states one thousand days until the target date for global poliomyelitis eradication tuberculosis morbidity--united states measles--united states, . morbidity and mortality weekly report national adult immunization awareness week--october - , recommended readings ; and influenza and pneumococcal vaccination levels among adults aged --- years impact of the sequential ipv/opv schedule on vaccination cover-agemunited states advances in global measles control and elimination: summary of the international meeting recommended childhood immunization schedulemunited states impact of vaccines universally recommended for childrenmunited states progress toward global poliomyelitis eradication global disease elimination and eradication as public health strategies childhood immunizations rotavirus vaccines: who position paper. weekly epidemiologic record infectious diseases of humans: dynamic and control vaccines and world health: science, policy, and practice control of communicable diseases manual jawetz, melnick and adelberg's medical microbiology, twenty-first edition preventive medicine and public health, second edition efficacy of bcg vaccine in the prevention of tuberculosis. meta-analysis of the published literature manson's tropical diseases vaccination and world health principles and practice oflnfectious diseases immunization of adolescents: recommendations of the advisory committee on immunization practices, the american academy of pediatrics, the american academy of family physicians and the combination vaccines for childhood immunization: recommendations of the advisory committee on immunization practices, the american academy of pediatrics, the american academy of family physicians and the poliomyelitis prevention: revised recommendations for use of inactivated and live oral poliovirus vaccines diphtheria outbreakmrussian federation rubella and congenital rubella syndrome~united states compendium of animal rabies control, : national association of state public health veterinarians progress toward elimination of haemophilus influenzae type b disease among infants and children in the united states tetanus surveillance~united states, - recommendations and reports--vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of measles: recommendations of the advisory committee on immunization practices national, state and urban area vaccination coverage levels among children aged - months~united sates varicella related deaths among children--united states progress toward global poliomyelitis eradication ten great public health achievements--united states a ten-year experience in control of poliomyelitis through a combination of live and killed vaccines in two developing areas measles control in developing and developed countries: the case for a two-dose policy integration of vitamin a supplementation with immunization. weekly epidemiological record update cholera--western hemisphere, . morbidity and mortality weekly report isolation of vibrio cholerae o from oystersmmobile bay, - estimates of future global tuberculosis morbidity and mortality arbovirus disease--united states ~:~ other communicable diseases update: outbreak of legionnaire's disease associated with a cruise ship rift valley fever--egypt the role of bcg vaccine in the prevention and control of tuberculosis in the united states: a joint statement by the advisory council for the elimination of tuberculosis and the advisory committee on immunization practices update: trends in aids incidence--united states case definition for infectious conditions under public health surveillance guidelines for treatment of sexually transmitted diseases primary and secondary syphilis--united states global tuberculosis incidence and mortality during the th century pandemic: need for surveillance and research escherichia coli o :h diarrhoea in the united states: clinical and epidemiologic features the state of the world's children the rational use of drugs in the management of acute diarrhoea in children world health organization. . the malaria situation in aids: images of the epidemic. geneva: who. world health organization progress toward the elimination of leprosy as a public health problem the world health report : fighting disease, fostering development the world health report health for all in the twenty-first century. eb / . geneva: who. world health organization. . the world health report : life in the twenty-first century: a vision for all world health organization. . the world health report : making a difference key: cord- -rxypdzri authors: umaru, farouk a. title: scaling up testing for covid- in africa: responding to the pandemic in ways that strengthen health systems date: - - journal: afr j lab med doi: . /ajlm.v i . sha: doc_id: cord_uid: rxypdzri nan in the midst of responding to the coronavirus disease (covid- ) pandemic, public health practitioners, agencies and the private sector are partnering to provide urgent emergency solutions to the ongoing crisis. in the words of world health organization director general, dr tedros ghebreyesus, a critical component of this response is to 'test, test and test'. this need for testing continues to spur multiple innovations in testing techniques, strategies and applications. as of april , more than different in vitro diagnostic devices for covid- diagnosis were listed on the world health organization website under the international medical devices regulatory forum jurisdiction as having received emergency use authorization (eua) from nine countries, with china authorising devices or technologies (including antibody test kits). although no country in africa has issued an eua on any of these devices, it is very likely that most of these devices may be marketed or distributed on the continent. while developed countries like the united states, italy and spain have struggled to cope with large-scale testing on multiple devices, many countries in africa are disproportionately hit by the need for testing because of severe limitations in testing technologies. the lack of africa-issued euas on emerging technologies specific to severe acute respiratory syndrome coronavirus (sars-cov- ), the virus responsible for covid- , may continue to handicap africa's response to the pandemic. but, should african regulatory agencies or the africa centres for disease control and prevention (cdc) begin to issue euas for emerging technologies, with limited validation information in response to the covid- pandemic? african union member states, through the efforts of africa cdc and partners, have received technical support to use existing real-time polymerase chain reaction (rt-pcr) instruments to conduct testing, mostly at national reference or equivalent laboratories. although this technology may be inadequate to entirely meet the scale of testing required for covid- (because of limited numbers of instruments), these instruments are within the existing tiered laboratory network. leveraging existing rt-pcr instruments for covid- diagnosis is an important step in strengthening health systems on the continent for future emergency pandemics. responding to the current pandemic in ways that strengthen health systems and that go beyond emergency solutions to consider long-term solutions will benefit the continent as a whole. the ebola outbreak in west africa provides useful lessons on how emergency responses can impact health systems. during the ebola outbreak, novel technologies were provided to countries without consideration to the existing tiered laboratory network. as a consequence, some countries have been unable to incorporate those novel technologies into their laboratory networks, which impacts the overall sustainability of their health systems. it is time to remind both national and regional communities on the continent to think beyond the current covid- pandemic so that when africa emerges on the other side, its health systems will be stronger and more prepared to respond to the next one. central questions to keep in mind during the covid- response include: how will countries absorb multiple novel technologies within their health systems post-covid- ? how will emergency-use-authorised in vitro diagnostics be part of national tiered laboratory systems postpandemic? what role will manufacturers play in initiating long-term evaluation procedures for covid- technologies? will these technologies be left to countries to manage without adequate support, guidance or capacity? answers to these questions are critical now. it is therefore imperative that national regulatory agencies, diagnostics manufacturers and national diagnostics technical working groups not 'rush' into issuing or adopting euas for new scan this qr code with your smart phone or mobile device to read online. and untested devices outside their networks, but to consider the long-term impact of those technologies on their health systems. some of these approaches may include: • update the current rt-pcr instruments to incorporate covid- testing. as the gold standard for viral testing, countries must work with their existing rt-pcr technology manufacturers to upgrade reagents, kits and software to accommodate covid- . these strategies and others, supported by national stakeholders, will support african countries in strengthening systems and improve preparedness for emerging pandemics, while building sustainable laboratory systems to help support better healthcare across the continent. world health organization. in vitro diagnostics and laboratory technology: prequalification of ivds and medical devices world health organization; c health-system resilience: reflection on the ebola crisis in western africa emergency use listing (eul), weekly update united states food & drug administration (fda) the manuscript went through internal united states pharmacopeia technical and editorial process workflow. no need to mention individuals. this research received no specific grant from any funding agency in the public, commercial or not-for-profit sector. data sharing is not applicable to this article as no new data were created or analysed in this study. the views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of any affiliated agency of the author. the author has declared that no competing interest exists. this article followed all ethical standards for research without direct contact with human or animal subjects. key: cord- -guhrtz h authors: cleaveland, sarah; hampson, katie title: rabies elimination research: juxtaposing optimism, pragmatism and realism date: - - journal: proc biol sci doi: . /rspb. . sha: doc_id: cord_uid: guhrtz h more than years of research has now been conducted into the prevention, control and elimination of rabies with safe and highly efficacious vaccines developed for use in human and animal populations. domestic dogs are a major reservoir for rabies, and although considerable advances have been made towards the elimination and control of canine rabies in many parts of the world, the disease continues to kill tens of thousands of people every year in africa and asia. policy efforts are now being directed towards a global target of zero human deaths from dog-mediated rabies by and the global elimination of canine rabies. here we demonstrate how research provides a cause for optimism as to the feasibility of these goals through strategies based around mass dog vaccination. we summarize some of the pragmatic insights generated from rabies epidemiology and dog ecology research that can improve the design of dog vaccination strategies in low- and middle-income countries and which should encourage implementation without further delay. we also highlight the need for realism in reaching the feasible, although technically more difficult and longer-term goal of global elimination of canine rabies. finally, we discuss how research on rabies has broader relevance to the control and elimination of a suite of diseases of current concern to human and animal health, providing an exemplar of the value of a ‘one health’ approach. for thousands of years, people have lived in fear of rabies transmitted from domestic dogs, and more than half of the world's population still do so today. from the time of the first written reference to rabies in the rd century bc, the link between the bite of a mad dog and the risk of human death has been well recognized [ , ] . although many mammalian hosts can be infected with the rabies virus, the domestic dog remains to this day by far the most important species causing human rabies deaths and tens of thousands of people die from canine-mediated rabies each year [ , ] , mostly in asia and africa where the disease is maintained in domestic dog reservoirs. in developing the first vaccines against rabies, louis pasteur recognized the potential for eliminating human rabies deaths, and considered that 'to solve the problem of rabies would be a blessing for humanity' [ ] . the need for and feasibility of rabies elimination through interventions in the dog population has also been recognized for more than a century. since the first large-scale implementation of canine vaccination in the s, canine rabies has now been eliminated in several parts of the world, for example in island and peninsula states of asia (e.g. japan, taiwan), in the usa, western europe and across parts of latin america [ , , ] . in this review, we address the reasons why, despite the long history of rabies research and earlier successes in canine rabies elimination, new research has been needed to tackle the problem of rabies in low-and middle-income countries (lmics) of africa and asia. we demonstrate how research has generated optimism about the feasibility of achieving global targets of zero human deaths from dogmediated rabies, guided pragmatism in the design of dog vaccination strategies in lmics, and instilled realism in the path towards global canine rabies elimination. while the first decades of rabies research focused on the problem in domestic dogs, the successful control of canine rabies in many of the world's richer countries shifted emphasis towards the growing problem of wildlife rabies. during world war ii, the red fox (vulpes vulpes) emerged as the main rabies reservoir in europe, and the disease spread rapidly affecting most of western and southeastern europe by the mid- s [ ] . in response, rabies research efforts focused on development of oral rabies vaccines and vaccination strategies for wildlife (figure ), with large-scale distribution of oral bait vaccines across western europe in the s and s [ ] . over years, oral vaccination of foxes has resulted in the elimination of the rabies virus from western europe, with rapid progress being made towards elimination in eastern europe [ ] . over this same time period, canine rabies was being brought under control in north america, and research efforts independently became directed to the emerging problem of wildlife rabies focusing on control of rabies in terrestrial carnivore reservoirs [ ] . a further concern in north america related to bat-transmitted rabies [ ] , coinciding with a growing interest in bats as hosts of a wider range of lyssaviruses, [ ] and other emerging pathogens of global concern, such as sars coronavirus, ebola virus and mers coronavirus. it is not surprising that set against this backdrop, research into the control of canine rabies in lmics received only limited attention during the latter part of the twentieth century (figure ). however, this resulted in a deficit of data and understanding of the burden and scale of the disease in poorer parts of the world and limited interest in potential solutions, reinforcing a cycle of neglect [ ] . it has always been known that dog bites are an important source of human rabies exposures worldwide, but reliable data have been lacking on the number of dog-mediated human rabies deaths [ ] , with the few hundred deaths officially reported in the african region [ ] widely recognized to be a major underestimate. an initial approach to estimating human rabies deaths in africa used a probability decision tree model that incorporated data on the incidence of bite injuries from suspected rabid dogs and availability of post-exposure prophylaxis (pep) [ ] . this was first applied in tanzania and then used to generate country-and regional-level estimates of human deaths across africa and asia [ ] [ ] [ ] [ ] [ ] and to assess the economic impacts of canine rabies [ ] . further refinements resulted in more detailed and comprehensive estimates of global disease burden by country [ ] . these studies indicated that more than % of canine-mediated rabies deaths occurred in africa and asia, with a global estimate of ( % confidence interval (ci) - ) deaths in [ ] . other approaches have been adopted by the global burden of disease (gbd) collaborators, including a cause of death ensemble modelling approach, which have generated estimates ranging from deaths ( % ci - ) in , ( % in , ( % ci - ) in , and in ( % ci - ) [ , , ] . it is well recognized that these modelling approaches all have limitations, particularly in the degree of extrapolation from data that is of variable quality, from a limited geographical area or that has been generated indirectly [ ] . for several neglected tropical diseases (ntds), gbd figures are thought likely to represent an underestimate of current disease burden [ ] . for rabies, there is no evidence that control measures have been implemented on a scale that would explain the dramatic recent decline in deaths indicated by the gbd estimates [ , ] . gbd estimates rely on vital registration and verbal autopsy data and these are very limited or absent in many of the countries where rabies and other ntds are most prevalent [ ] . another critical issue is the appropriate modelling of pathways from infection to disease and death [ ] . while the rabies probability tree study [ ] was also limited by data quality and availability, this analysis incorporated detailed data from disease-specific research in rabies-endemic countries and was based on a well-defined series of steps from rabies exposure to death. we draw further the pep data used in the probability tree model also provided important information for demonstrating the economic burden of canine rabies, indicating that $ . billion direct costs were incurred annually in providing pep for million dog-bite victims in canine-endemic countries [ ] (figure ). regionally, the highest expenditure is seen in asia ($ . billion annually) reflecting a continuing high demand for pep in areas where canine rabies has not been brought under control, and contrasting with latin america where, despite much lower annual expenditure on pep ($ million), the region is on the brink of eliminating canine-mediated human rabies as a result of relatively modest investments in mass dog vaccination ($ million) [ ] . these data contribute to a growing body of evidence that the most cost-effective preventive strategies are those underpinned by mass dog vaccination rather than reliance on pep alone [ ] [ ] [ ] . compiling data for the global burden study also highlighted pep availability as a major determinant of human rabies deaths, with cases occurring disproportionately in impoverished rural communities. detailed contact tracing studies reveal the extent to which people have struggled to obtain pep and the consequences of the resulting delays [ , ] , which invariably include intense anxiety as bite victims await an uncertain outcome and, in some cases, the development of a horrifying and fatal disease. while human deaths and high pep costs dominate in burden of disease studies, several other components of disease burden are also of concern, including livestock losses, which still remain poorly quantified but can have important impacts [ , ] and wildlife conservation, with canine rabies threatening several endangered wildlife populations including the ethiopian wolf (canis simensis) and african wild dog (lycaon pictus) [ ] (figure ). a considerable body of research now exists to demonstrate the feasibility of canine rabies elimination. the basic reproductive number, r , a key parameter used to understand the effectiveness of control interventions, is usually measured from the growth rates of epidemics. applying this approach to canine rabies demonstrates that r is typically between and in populations that differ in density by an order of magnitude [ ] [ ] [ ] . alternative approaches to estimating transmission are all consistent with this low value of r [ , , , ] suggesting that rabies should be easily controlled through mass dog vaccination and, conversely, that approaches based on reducing dog density are likely to be ineffective [ ] . theoretical and empirical research has demonstrated that rabies can be eliminated where % coverage is sustained [ , ] . by contrast, attempts to reduce dog population density through indiscriminate culling have consistently failed to control rabies outbreaks [ ] and, in some cases, have increased disease spread through humanmediated dog movements [ ] . muzzling, restriction of dog movements, and selective removal or euthanasia of unowned dogs have historically been part of successful dog rabies control, including in the uk and usa [ , ] , but these measures are distinguished from indiscriminate culling operations in being specifically targeted to reduce rabies transmission risk rather than to reduce dog population size or density. the question of rabies reservoir dynamics has long been debated [ , [ ] [ ] [ ] [ ] [ ] , and is of major importance in sub-saharan africa where the abundance of wildlife has been seen as an obstacle for canine rabies control that would render elimination efforts futile [ ] . however, despite the fact that rabies can infect all mammalian species, only a few hosts are capable of maintaining infection as reservoirs, with ecological and genetic factors both likely to be important determinants of rabies reservoirs [ , ] . while rabies virus variants are typically maintained by only a single mammalian host species, multiple variants may circulate in an area [ ] . however, this need not be an insurmountable obstacle to canine rabies elimination, as shown by countries in latin america and in the usa, where canine rabies has been brought under control or eliminated even though rabies variants circulate in wild mammal populations. the overlapping circulation of multiple variants does, however, introduce different surveillance requirements for verifying the elimination of the canine rabies variant. establishing the reservoir of multi host pathogens is not easy and typically requires integration of multiple lines of evidence [ , ] . in the serengeti ecosystem, tanzania, inference from both epidemiological and genetic data supports the idea of rabies being maintained in domestic dogs not wildlife, with occasional spillover from domestic dogs into wildlife resulting in short-lived chains of infection that are not sustained [ ] [ ] [ ] . the conclusion from these studies is that control of canine rabies should eliminate infection in dogs, wildlife and people. it is unclear the extent to which the serengeti scenario is generalizable more globally, but currently there is no clear evidence that, in areas with domestic dog reservoirs, the canine rabies virus variants circulating in dogs are maintained independently in wildlife. in south africa, a canine variant circulates in jackals in the limpopo region [ ] , but it is still unknown whether this cycle will be sustained in the absence of canine rabies, which has now been well controlled in the area. if so, vaccination of jackals may be needed to achieve canine rabies elimination, but this is likely to be feasible given the demonstration of the safety, efficacy and feasibility of oral vaccination in jackals from earlier work in zimbabwe and israel [ ] [ ] [ ] [ ] . demonstration of the operational feasibility of mass dog vaccination provides a further cause for optimism. evidence now exists to show that, contrary to widely held perceptions, the vast majority of dogs in africa have owners, dog accessibility is higher than often recognized, and achieving target levels of vaccination coverage is feasible [ , ] . in south and southeast asia, the situation may be more challenging as a result of a larger population of less accessible community or 'street' dogs, but target levels of vaccination coverage have also been achieved in these communities where campaigns are well organized [ , , ] . in summary, the last decade has seen a rapid expansion of research into canine rabies vaccination and canine rabies elimination (figure ) generating optimism that canine rabies can be effectively controlled, and ultimately eliminated, through mass dog vaccination and that this is the underpinning strategy needed to reach the target for elimination of human deaths from canine-mediated rabies [ ] . the health and economic benefits would be substantial [ ] (figure ). while it is often recommended that a detailed understanding of dog ecology is needed for effective canine rabies control, the consistency of research findings generated over the past years allows us to be confident in concluding that mass dog vaccination is feasible across a wide range of settings and campaigns can and should be initiated without delay. in some cases, more nuanced understanding may be required to improve coverage, but these insights can be often be gained through implementation of control measures and used to progressively improve the design and delivery of subsequent interventions. key considerations include the nature and degree of community engagement, timing of campaigns, placement of vaccination stations and whether or not to charge owner fees [ ] [ ] [ ] . the costs of implementing campaigns free of charge may exceed those readily available to government veterinary services [ ] , but many approaches can still be explored to improve affordability, acceptability and cost-effectiveness [ ] . while there is widespread agreement about the central importance of mass dog vaccination in canine rabies control and elimination, the role of dog population management remains the subject of debate [ ] . there is a rich literature around fertility control for management of roaming dog and wildlife populations [ , ] . however, as rabies transmission varies little with dog density, reproductive control measures carried out with the aim of reducing dog density are not likely to be effective for rabies control. in theory, reducing population turnover (e.g. through improving life expectancy and/or reducing fecundity) could help sustain population immunity between campaigns and improve cost-effectiveness. however, there is little empirical evidence that dog population management tools have been able to achieve this [ ] . furthermore, even in populations with a high turnover, achieving a % coverage during annual campaigns has been sufficient to sustain population immunity above critical thresholds determined by r [ ] . the relatively high cost of sterilization also means that strategies which combine vaccination and sterilization are less cost-effective in terms of achieving human health outcomes than strategies based on dog vaccination alone, even in populations with a large proportion of roaming dogs [ ] . improved dog population management is undoubtedly a desirable longer-term goal for animal health and welfare and may have important secondary benefits for rabies control, for example by enhancing community or political support [ ] . however, a focus on mass dog vaccination currently remains the most pragmatic and cost-effective approach to canine rabies control and elimination. the limited availability and quality of routine animal rabies surveillance data in lmics [ ] has been an obstacle to the application of the analytical approaches from which we have learned so much about wildlife rabies. 'gold standard' surveillance data based on laboratory-confirmed diagnosis is hampered not only by limited laboratory infrastructure but also by the practical challenges of locating, sampling and submitting specimens [ ] . however, pragmatic approaches to improving rabies rspb.royalsocietypublishing.org proc. r. soc. b : surveillance have yielded rich insights. in addition to providing a foundation for burden of disease estimates, data on animalbite injuries have been a used as a reliable indicator of canine rabies incidence, revealing new understanding of rabies metapopulation dynamics [ ] , as well as improving detection of animal rabies cases, the management of animal bites and the cost-effectiveness of pep [ , ] . pragmatic solutions are also being found to improve rabies diagnosis in settings with limited laboratory infrastructure, including techniques to support decentralized laboratory testing (e.g. direct rapid immunohistochemical test, drit) [ ] [ ] [ ] [ ] and field diagnosis (e.g. immunochromatographic tests) [ ] [ ] [ ] . these have great potential for empowering field staff to engage in rabies surveillance and respond more effectively to surveillance data, but standardization and quality control of field diagnostic kits still needs improvement [ ] . given the rapid advances in metagenomic sequencing methods [ ] , future approaches may include real-time genomic surveillance. however, even simple technologies such as mobile phones can serve as leapfrogging technology that can dramatically improve the extent and resolution of rabies surveillance data [ ] . while operational research on dog vaccination provides grounds for optimism, awareness is growing about the challenges, complexities and time scales of moving from control to elimination (figure ). given the low r for rabies, deterministic models of transmission predict that rabies should be eliminated very rapidly [ , , [ ] [ ] [ ] . but, these dynamic models typically assume that dog vaccination campaigns consistently achieve high and uniform levels of coverage. by contrast, analyses of rabies surveillance and control data indicate that vaccination coverage implemented during campaigns is often patchy and that time to rabies elimination is prolonged [ , , ] . once assumptions about the implementation of vaccination campaigns are more realistic, and rabies is considered on a spatial landscape, predictions about the time scale to elimination are tempered [ ] . the disparities between theory and practice demand approaches that capture realism. it may be argued that the feasibility and effectiveness of mass dog vaccination should have been self-evident given the successes in latin america but the road to elimination has been accompanied by substantial challenges [ ] . progress in latin america has required decades of investment in large-scale dog vaccination programmes and builds on effective regional coordination. sustaining such coverage, particularly across large geographical areas, is difficult and requires an investment in rabies control that focuses on the dog population and is over and above levels seen to date in africa and asia [ ] . local leadership is also an important factor. for example, canine rabies in north america was primarily controlled at the municipal level through dog licensure. legislation and by-laws relating to rabies control and dog vaccination exist in many canine rabies-endemic countries, but there is still a need for greater engagement of local authorities to ensure appropriate and sensitive enforcement of relevant legislation. empirical evidence from wildlife rabies elimination programmes show that once controlled to less than % of endemic incidence, the time required to eliminate rabies is as long again [ ] , a lesson that should be heeded for canine rabies. once rabies has been reduced to low levels, the remaining foci by their nature are persistent and in 'hard-to-reach' communities, socially, economically and geographically, and new challenges come to the fore [ ] . increasingly the importance of metapopulations has been recognized for the persistence of rabies [ , ] and genomic signatures in rabies-endemic countries highlight the frequent human-mediated movement of dogs [ ] [ ] [ ] . the implications of this movement are evident when rabies invades previously uninfected areas [ ] , and without maintained vigilance, rabies can re-emerge rapidly if control measures are no longer implemented effectively [ ] . the long-term implications of figure . hypothetical timeline of rabies control and elimination highlighting policy targets and epidemiological milestones, illustrating relative rapid progress to zero human deaths but the need for sustained effort to reach elimination of canine rabies and sustained surveillance to identify the causes of cases. in this example, drawn from a scenario typical of latin america, human cases following declaration of zero human deaths from dog-mediated rabies might occur as a result of (i) an incursion of canine rabies (in which case the rabies-free status of the country would be reset); and (ii) vampire bat rabies and (iii) an imported human case (in which cases the status of the country as being free of dog-mediated rabies would not change). cases of canine rabies are shown in grey and human cases in red. rspb.royalsocietypublishing.org proc. r. soc. b : these incursions to the persistence of rabies are not yet fully understood but will, undoubtedly prolong elimination efforts, and highlight the need for coordinated control at scale and across international boundaries as well as realistic projections of the investment required to eliminate rabies [ ] . recent research has contributed pivotal evidence in making the case for rabies to be considered a priority ntd and, in , rabies was included within the world health organization (who) accelerated roadmap for ntds [ ] . in , the tripartite partnership (who, the world organization for animal health (oie), and the food and agriculture organization of the united nations (fao), together with the global alliance for rabies control, declared a goal of zero human deaths from dog-mediated rabies by [ ] , underpinned by an investment case incorporating data on the human health and economic burden of canine rabies [ , ] . this purposely sets dog-mediated human rabies deaths as the first target, both because of its public health importance, but also its shorterterm feasibility (figure ) through a combination of mass dog vaccination and improved pep provision to under-served communities. the longer-term goal of disrupting transmission and eliminating canine rabies will require more time. nonetheless, the example of latin america demonstrates that it is within reach [ ] . the control and elimination of canine rabies provides an exemplar of 'one health' interventions, that is, interventions in animal populations that generate human health benefits. although challenges remain in the operationalization of one health [ ] , these approaches not only provide the most cost-effective strategy for preventing human rabies deaths but also offer a more equitable approach than relying only on interventions directed at humans only (i.e. pep) [ ] . interventions that effectively reduce the force of infection from the animal reservoir convey benefits to all without regard to socioeconomic status. by contrast, under a strategy of reliance on pep, the social, political and economic factors constraining access to healthcare are likely to prevail, with rabies deaths continuing to affect the most disadvantaged communities well beyond . it is perhaps understandable that the medical sector emphasizes prevention of human rabies through pep. but this approach can lead to neglect of the problem at sourcein the dogs-and impede progress towards large-scale mass dog vaccination programmes. this is true even in upper middle-income countries which have clear capability to implement mass dog vaccination but, without effective programmes, still suffer a high burden of human deaths and an escalation in pep demand, with costs amounting to tens of millions of dollars every year [ ] . recent research on rabies has generated a strong body of evidence for the feasibility of elimination of canine rabies through mass vaccination of domestic dogs. global momentum is now building towards implementation of large-scale programmes to achieve first, the elimination of human deaths mediated by canine rabies, and second, disruption of transmission within the dog population and the elimination of canine rabies entirely. however, time is short to reach these global targets [ ] and there is no cause for further delay. the history of rabies four thousand years of concepts relating to rabies in animals and humans, its prevention and its cure global and regional mortality from causes of death for age groups in and : a systematic analysis for the global burden of disease study estimating the global burden of 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coverage in rural and urban communities in tanzania. front vet. sci. , tribulations of the last mile: sides from a regional program towards the endgame and beyond: complexities and challenges for the elimination of infectious diseases transmission dynamics of rabies virus in thailand: implications for disease control phylodynamics and humanmediated dispersal of a zoonotic virus elucidating the phylodynamics of endemic rabies virus in eastern africa using whole genome sequencing. virus evol. , vev barriers to dog rabies vaccination during an urban rabies outbreak: qualitative findings from arequipa implementing pasteur's vision for rabies elimination accelerating work to overcome the global impact of neglected tropical diseases-a roadmap for implementation operationalizing the one health approach: the global governance challenges one health contributions towards more effective and equitable approaches to health in low-and middle-income countries acknowledgements. the views expressed here have been developed through many years of collaborative research with colleagues working on rabies around the world, and with international organizations, including the world health organization, the world organization for animal health, the food and agriculture organization of the united nations and the global alliance for rabies control. for s.c., this includes over years of interactions with colleagues at the institute of zoology, london, the london school of hygiene and tropical medicine, the university of edinburgh and the university of glasgow; and, for k.h., years of interactions with colleagues at princeton university and the university of glasgow. we are very grateful to support from tanzanian institutions, particularly the tanzania wildlife research institute, tanzania national parks, ifakara health institute and sokoine university of agriculture as well as national and local governments. we thank many colleagues for support, stimulating research and debate, but particularly acknowledge chris dye, dan haydon, tiziana lembo, jonathan dushoff, magai kaare, felix lankester, rudovick kazwala, darryn knobel, michelle morters and louise taylor. key: cord- - nq fvfh authors: le grange, lesley title: covid- pandemic and the prospects of education in south africa date: - - journal: prospects (paris) doi: . /s - - -w sha: doc_id: cord_uid: nq fvfh the covid- pandemic has caused havoc in the world, radically changing our lives and raising new and old questions, both existential and educational. this pandemic has revealed the underbelly of south african society in general and its education system more specifically—it has laid bare the gross inequalities that are the legacies of apartheid and the consequences of neoliberal capitalism. drawing on ideas articulated in the four introductory chapters of the international handbook of curriculum research, edited by william pinar in , this article discusses covid- and the prospects of education in south africa. the article shows how understanding the wisdom of indigenous traditions along with the moral dimensions of education, race, and the new technologies of surveillance, neoliberalism, and education can provide a nuanced awareness of the nature of the covid- pandemic. it then explores the implications of such insights for the field of curriculum studies and, where relevant, for the school curriculum. it concludes by showing how these broad themes intersect and gel around the notion of ubuntu-currere. time. and also, the enduring curriculum question, first raised by herbert spencer ( ) : what knowledge is of most worth? other education questions that we could invoke are: how ought we to teach/learn? what are the prospects for education during and after the covid- pandemic? what is education for in troubled times? is knowledge enough? we are witnessing emerging responses to these questions, and i shall touch on these questions in various ways in this article. for the most recent international handbook of curriculum research, pinar ( ) commissioned four introductory chapters to challenge accounts on curriculum studies presented by authors from different nations. in the first chapter, autio ( ) highlights the moral dimension of education and makes the point that it is education's implicit morality that makes it educative. autio's use of "morality" is not meant in a didactive sense but is more akin to ethics: a commitment to engage, in an ongoing basis, with the worthiness of knowledge-that is, with the worthiness of what education programmes include and/or exclude. according to pinar ( , p. ) , it is this sense of the moral that informs our "profession's ethics, our commitment to study, and teach as we engage in academic research to understand curriculum". moreover, it also involves understanding curriculum as a complicated conversation that occurs among scholars of the field and between scholars and students. in the second chapter, mccarthy, bulut, and patel ( ) discuss the reconfiguration of power that globalization accelerates, with a particular focus on race. they point out that race cannot be viewed in isolation but needs to be understood in contemporary times as structured through contradictory processes of globalisation, localisation, migration, and technologies of surveillance. the technologies of surveillance that the authors refer to are biometric technologies of information: face scanning; finger printing; dna sampling; and so on. mccarthy et al. ( ) focus particularly on race, but their discussion can be extrapolated to other forms of discriminations that globalizations and new technologies hasten or reconfigure. in the third chapter, smith ( ) assesses the influence of neoliberalism on education, which includes, among other things, privatization, standardized assessments, and the use of technologies to make teaching/learning more efficient. he asks a pertinent question: how might we reimagine education given that neoliberalism brings into question the very assumptions that education is based on? smith ( ) suggests that we need to analyze and interrogate neoliberalism on an ongoing basis in order to work through it, and that the inspiration for this ongoing examination could be drawn from the wisdom traditions, be they indigenous, religious, or philosophical. in chapter , wang ( ) focuses on nonviolence, which she explicates as an embodied sense of interconnectedness among humans, affirming compassion and a positive affiliation with others-in other words, our common humanity. she finds support for her argument from several philosophical, religious, and ethical traditions, including the african notion of ubuntu, the chinese notion of tao, and indigenous peace-making traditions in north america. in this article, i use the ideas articulated in these four chapters as a broad frame for advancing my thoughts. accordingly, i divide the rest of the article into the following sections: the moral dimension of education; race, technologies of surveillance, and bio-informationism; neoliberalism and the prospects of education after the covid- pandemic; and why we need ubuntu-currere. although my focus here is on the scholarly field of curriculum studies, i do at times explore implications for the school curriculum. when referring to the school curriculum, i make reference to the school subject that i know best, school biology. education is by definition a moral enterprise, but the covid- pandemic has given rise to particular moral dilemmas for all people involved in education. governments had to make decisions on school closings and also on when to reopen them. these are not easy decisions, and neither are the consequent choices that those impacted have had to make. in south africa, schools are more than places where knowledge is exchanged between teacher and learner. for children from vulnerable communities, they are also places of safety and security: among other things, more than million children receive meals per day at school as part of the national school nutrition programme (nsnp). but during the lockdown period and level of the government's risk-adjusted approach, the nsnp was temporarily suspended. this left these children at risk of being underfed and/or malnourished during periods of school closures. gontsana ( ) reports that during the lockdown period the government of the western cape, one of the nine provinces in south africa, made emergency funding available to provide meals to children in vulnerable communities. (the western cape is the only province not governed by the ruling party, the african national congress [anc] . it is governed by the nation's official opposition, the democratic alliance [da].) thus, some schools opened their gates, arranged for learners to sit in open fields at a distance from one another, and gave them meals. however, the country's largest teachers union, the south african democratic teachers union (sadtu), opposed this action. sadtu is affiliated to the congress of south african trade unions, which, together with the south african communist party, is in a tripartite alliance with the anc. sadtu stated that the da was going against the president's plans to curb the spread of the virus, and although the union was concerned about the welfare of working-class learners and their families, it was opposed to learners being given meals on the school grounds because this would place them and their communities at increased risk. in this instance, one might argue that two entities with different political motives were using learners as a political football. the teacher in this situation is faced with a difficult moral dilemma. assuming that the teacher is a member of sadtu and is also acutely aware that learners are not receiving adequate nutrition during the lockdown period, does the teacher support his/her union or does the teacher assist with feeding learners at the school? at the time of writing this article, the south african minister of basic education announced a phased reopening of schools. learners who returned to schools first were those at the exit points of primary and high schools-grades and learners, respectively. this happened in june , which was the beginning of winter in the southern hemisphere, and the disease was predicted to peak in south africa around august/september . thus, learners returned to schools at arguably the most vulnerable time for them in terms of the spread of the pandemic. the government has said that parents can decide themselves whether to allow their children to return to school or to do home schooling. this is a difficult moral decision for any parent to make. it is an even more difficult decision for poor and working-class families, who do not have the facilities and capacity to support their children to do home schooling and who may need to find childcare if they have to return to work themselves. role players in education have only difficult choices, as these two instances illustrate. and decisions of this kind might best be left to parents, free of coercion. but what should the response of scholars who engage in the study of curriculum be at this time? what is their moral obligation during the covid- pandemic? autio ( ) refers to the sense of "moral" as a "professional ethics" that relates to our commitment to study, teach, and engage in academic research aimed at understanding curriculum. during the covid- pandemic, though we might be isolated and unable to engage with one another through traditional face-to-face means, our commitment to study, teach, and engage in academic research should not weaken. in fact, at this time we need a deeper commitment to this sense of ethics. this means that we should use new technologies to engage in complicated conversations about curriculum-related matters. as with many other conferences, the annual conference of the south african education research association (saera) was cancelled, but members have been encouraged to engage with one another through their special interest groups (sigs), facilitated through use of technology. members of the curriculum studies sig, for example, have had complex conversations about the curriculum challenges facing south africa during and after the covid- pandemic. the sig released a statement that invites a broader audience to take part in such ongoing discussions. these conversations have not been chitchats of the kind aoki ( ) cautions against, nor have they been simple exchanges of information; instead, they have been robust, often involving disagreement, but always with a sense of mutual belonging and a commitment to the intellectual life of the field. i have been privileged to enjoy such exchanges in transnational spaces, in the way in which pinar ( , p. ) suggests that such spaces can be productive. he points out that, in transnational spaces, scholars of the field should distance themselves from their own national cultures and politics, and listen respectfully to others, thus creating "a global public space for dissension, debate, and on occasion solidarity". at this time, we need such often-difficult conversations to intensify-we do not need social distancing but social solidarity in national and transnational spaces that new technologies and the commitment of curriculum scholars make possible. in other words, we need physical distancing, not social distancing. again, with reference to the moral dimension of education, autio ( ) also refers to the need for conversations and debates on the worthiness of knowledge. that is, we need to ask critical questions about what knowledge is of most worth when it comes to the school curriculum during and after the covid- pandemic. here, i turn to school biology as an example. since its inception, a feature of school biology has been the debate on whether it is a "science of life" or a "science of living" (le grange ). few would disagree that school biology has to include both of these dimensions, but the pendulum has swung back and forth over the years concerning where we should place the emphasis. from the last half of the twentieth century to the twenty-first century, school biology has been largely characterized by the force-feeding of learners of a diet of "theory", regurgitated on tests and examinations-content is often irrelevant to the needs of learners or of society. in other words, during that time schools have emphasized biology as a "science of life" (le grange ). less than % of south african school leavers continue with careers in biology-related fields. therefore, for the majority of learners who take biology at school, the current subject content is largely unrelated to their lives. this is true despite its potential relevance to many contemporary issues facing society; among them, human diseases, including virus-causing diseases such as covid- ; human trafficking involving the sale of body parts; biodiversity loss; commodification of the genetic code; threats of biological warfare. instead of traditional unifying themes such as "structure and function" or "evolution", the curriculum could revolve around more relevant themes, such as sustainability, for example. such themes also reinforce connections between many other school subjects. here, the notion of sustainability does not have to do with policy goals but with cultivating a frame of mind that enables lifelong learning. to continue with sustainability as an example, using it as a unifying theme in biology classrooms could prove to be productive. instead of learners studying animals only in relation to themes such as structure and function, they could investigate what sustains an animal in fulfilling its ecological role, or occupying its niche, for example. it involves a way of getting learners to think about biology differently, to develop frames of mind focused on sustainability. bonnett ( , p. ) avers that a frame of mind is a "general mode of engagement with the world through which the world as a whole is revealed to us. … [i]t is more or less a conscious way of being in the world". this requires a specific cognitive/ conceptual outlook-but also involves our sensing of things and encapsulates the affective, moral, aesthetic, imaginative, and other receptions and responses that bonnett ( , p. ) refers to as "a mode of sensibility". it is a mode of sensibility toward sustainability that might be cultivated in biology classrooms after the covid- pandemic. not as a quick fix but as a habit of mind that might develop over time as the world of biology is "revealed" to learners through a conscious focus on sustainability. in their chapter, mccarthy et al. ( ) challenge scholars of curriculum to take seriously the reconfiguration of power as globalization quickens, and in particular how technologies of surveillance-such as biometric technologies, face scanning, finger printing, dna sampling, etc.-can be used to advance or sustain racism. subtle forms of racism might emerge as technologies of surveillance are used after the covid- pandemic, because these technologies provide fertile ground for racism's growth and consolidation. the pandemic will probably accelerate racism and other forms of discrimination, for several reasons-and there is already evidence of this. but the covid- pandemic has also exposed the underbelly of racial inequalities in such countries as the us, the uk, and south africa. devakumar, shannon, bhopal, and abubakar ( ) point out that outbreaks such as covid- create fear, and that fear is the key ingredient for racism and xenophobia to flourish. they go on to say that the pandemic has exposed the social and political fractures within communities, with racialized responses, that have affected marginalized groups disproportionately. devakumar et al. ( ) note that we have already witnessed microaggressions or overt violence targeting chinese people and barring them from establishments. moreover, political leaders have exploited the covid- pandemic to buttress racial discrimination by hardening border polices and conflating public health curtailments with anti-migrant rhetoric. for example, italy's prime minister cynically linked the covid- pandemic to african asylum seekers, and the us president referred to sars-cov- as "the china virus" (devakumar et al. ). these developments create fertile ground for racism, which is now also advanced through the technologies of surveillance that mccarthy et al. ( ) identify. the advances in technologies accelerated by covid- -and the powers that governments have to subject citizens, and particularly foreign nationals, to a range of tests under the guise of protecting public health interests-could be further aiding and abetting this situation. the covid- pandemic has also laid bare racial inequalities in the us, uk, and south africa. in the us, the death rate among african americans is three times that of white americans because of poor living conditions, poor nutrition, lack of access to healthcare facilities, and comorbidities (begley ) . moreover, african americans are also bearing the brunt of the devastating economic impact of the covid- pandemic (rodgers ) . we have also observed this disproportionate negative effect of the covid- pandemic on black and asian people in the uk. andrews ( ) points out that this should not surprise us, and that it is a mistake to look at these racial differences through the lens of biology, because the issue is not a genetic but a social one. it is the consequence of sustained discrimination at systemic levels-economic, political, and social. in south africa, this pandemic has revealed the extent of the country's gross inequalities. recent statistics show that million south africans do not have reliable access to running water in their homes (ellis ) ; the government had to deliver thousands of water tanks to communities in a desperate attempt to slow the spread of the virus. and in the informal settlements where millions of black south africans live, social distancing is a near impossibility. these vulnerable south african communities are also likely to bear the brunt of the economic impact of the pandemic. mccarthy et al. ( ) have reminded us of the importance of bringing race-and its reconfiguration as globalization accelerates-into our curriculum conversations and actions. race and racism-if they are currently blind spots or blank spots in our work-need to become key concerns in educational arenas. according to wagner ( ) , blank spots are what scientists know enough about to question but do not know how to answer, and blind spots are what they don't care about or know enough about. to return for a moment to school biology: when it emphasizes a "science of life" approach, then race becomes a genetic topic and the conclusion is that there is only one human race, one species, homo sapiens. however, this approach can create a blind spot to race as a social construct and its sustained negative impact on people of colour across the globe. and it is this blind spot that has also made race science endure for more than a century and why we are seeing its growth in contemporary times (for more details, see le grange a). if school biology is to address issues related to race, then an emphasis on a "science of living" approach is more apposite than a "science of life" approach. lastly in this section, i shall turn briefly to the issue of bioinformationalism. bioinformationalism relates to parallels between the propagation of fake news in social media echo chambers, and the evolution and transmission of infectious diseases (peters, mclaren, and jandrić ) . peters et al. ( ) point out that the covid- pandemic is the first instance in which a biological virus has become dialectically intertwined with nonbiological viral information. what the authors are suggesting is that a biological virus and nonbiological viral information are working in tandem to accelerate the spread the virus. in other words, when fake news about the pandemic goes viral-such as "covid- does not affect africans" (a myth circulated across the african continent [padayachee and du toit ])-it influences peoples' behaviour in a manner that results in the spreading of the biological virus. and when the viral spread of fake news has racial connotations, such as linking the biological virus to african asylum seekers, then it also spreads racism. the coterminous nature of biological and nonbiological-information viruses adds to the complexity of issues related to the reconfiguration of race that globalization quickens and, consequently, to the complexity of curriculum scholars' work. to return to school biology for the moment: the imbrication of biological viruses and the viral spread of nonbiological information could certainly be a topic for inclusion in school biology classroom conversations, and learners could be asked to generate as many similarities and differences between biological viruses and nonbiological viruses generated through itcs as possible. in his chapter, smith ( ) reminds curriculum scholars of the pervasiveness of neoliberalism in education and emphasizes the need to analyze neoliberalism and its effects on an ongoing basis. neoliberalism can be traced back to seventeenth-century liberal perspectives, which became marginalized as a result of the rise of welfare-state liberalism (late nineteenth century) and keynesian economics (twentieth century). the revival of neoliberalism in the late twentieth century is associated with the emergence of the new right in europe and the us, often referred to as "thatcherism" and "reaganism" after two of its key proponents (le grange ). although neoliberalism has different strands, all neoliberals embrace the following three basic principles: a commitment to individual liberty and a reduced state; a shift in policy and ideology against government intervention; and a belief that market forces should be allowed to be self-regulating (for a comprehensive discussion on the ascendancy of neoliberalism, see olssen, codd, and o'neill ) . many western governments floundered when covid- resulted in a global pandemic because their health systems were unable to cope with the pandemic's demands. governments found themselves in a precarious position because of their underspending on healthcare-consequent on adopting neoliberal policies. moreover, some scholars have gone as far as to link an increase in relatively unknown and highly infectious viruses to neoliberal capitalism. as mckinley ( ) writes: [t]he increased occurrence of largely unknown and ever-more-virulent viruses is directly linked to the nature/character of land use and food production under the neoliberal model of capitalism; to the contemporary dominance of an "industrial model" of agriculture that is umbilically tied to the never-ending search for maximum profits, whatever the human, social and/or environmental consequences. just as the covid- pandemic as a public health crisis needs to be understood against the backdrop of neoliberalism, so, too, does the education crisis that has deepened during the pandemic in south africa. in the late s, the outgoing apartheid government of south africa adopted neoliberal education policies and introduced new models for white schooling that involved the semi-privatization of these state schools under the guise of racially integrating them. the school model that survived into south africa's democratic dispensation was the model-c school; today, many elite and middle-class public schools in south africa are commonly referred to as "former model-c schools". at their inception, the model-c schools were fee-paying schools, and they were allowed to sell excess land, which enabled them to accumulate capital. these resources enabled these schools to appoint additional teachers to their staffs and, by doing so, improve the quality of education provided. after , south africa's democratically elected government continued the neoliberal trend and maintained what has become a grossly unequal public school system. the government's attempts to make the schools in economically poor communities non-fee paying-by dividing them into different quintiles-have done little to arrest the inequalities that characterize the south african schooling landscape (see le grange, reddy, and beets ). when south africa went into lockdown during the pandemic and closed its schools, the unequal education system in south africa was exposed even further. learners in private schools as well as in affluent and middle-class public schools migrated relatively easily to emergency remote learning, because these learners had access to devices and connectivity, as well as support from teachers and parents. access to any form of online learning for the majority of school learners remains a pipedream; thus, the covid- pandemic has likewise laid bare the severity of the digital divide in south africa (davids ) . moreover, when schools reopen as the country moves to lower levels of its risk-adjusted approach, learners who attend schools in economically poor communities will be at greater health risk. such schools lack basic sanitation and water infrastructure; moreover, their inferior facilities will make physical distancing a challenge. although learners in south africa's bimodal schooling system have the same explicit curriculum, the curriculum-as-lived by the two sets of learners is radically different. the covid- pandemic will further reduce the life chances of a learner from a school in an economically poor community relative to those of a learner in a private or affluent public school. additionally, as affluent and middle-class schools pivot toward online learning and governments invest in technology infrastructure to make online learning more widely available after the covid- pandemic, we must be aware of the dangers regarding these developments in the context of neoliberal capitalism. it is my contention that we should view new technologies (and in the context of education, online teaching/learning) dialectically. in other words, we need to recognize both their productive potential to advance the goals of social justice and the dangers of their consolidating inequities. in the context of neoliberal capitalism, not only will the digital divide widen, as noted, but also the migration to online learning could result in greater privatization of schooling as for-profit intermediaries become involved in developing online programmes/courses. this is because public schools do not have the capacity to develop such programmes or courses-platform pedagogy morphs into platform capitalism (for a more detailed discussion on such developments, see hall ; le grange ). in this context, instrumentalist approaches to education would thrive and policy makers would cement standardized tests to improve efficiencies. performativity regimes-including surveillance of both teachers and learners-are likely to increase. if there is a lesson to be learned from the covid- pandemic, it is that communities in south africa radically reconfigure and resource their schools. such a reconfiguration needs to make those who inhabit schools (learners and teachers) the central concern, and to open up the pathways for the becoming of their lives (in relationship with one another). it is with this in mind that i turn to a discussion of the notion of ubuntu-currere. the covid- pandemic will probably not be the last global crisis facing humanity in the twenty-first century. if another virulent virus is not the cause of such crisis, then the cause could be an environmental catastrophe-that is, if humanity continues on its unsustainable course and neoliberal capitalism continues to thrive. it is sobering to note that global crises have not led to the weakening of neoliberal capitalism, as evident in the case of the / financial crisis. hall ( ) points out that it was not surprising that uber and airbnb had their genesis during that financial crisis, in the years and , respectively. these for-profit, "sharing"-economy, platform-based companies have taken neoliberalism to an ideal form. customers benefit from the services offered, but, for the on-demand worker in these industries, rights and benefits have become eroded as these businesses escape state regulation (see hall ; le grange ) . and so, there is a danger that, in the wake of the current pandemic, we might see greater privatization of several sectors, including healthcare and education. smith ( ) , in his chapter, averred that, to get beyond neoliberalism, we need to analyze it on an ongoing basis. he goes on to say that in our critical engagement with neoliberalism we might find inspiration in wisdom traditions, be they indigenous, religious, or philosophical. it is this part of smith's chapter that connects to wang's ( ) -the fourth introductory chapter in pinar's ( ) edited handbook-where she promotes nonviolence through the invocation of indigenous and peace-making traditions such as the african notion of ubuntu and the chinese notion of tao. given the violence perpetrated against humans (particularly those on the margins of societies) that the covid- pandemic has laid bare, we could find inspiration from the traditions that wang ( ) refers to. therefore, following on from smith ( ) and wang ( ) , i propose that the notion of ubuntu-currere might provide the inspiration and motive force for ridding ourselves of the shackles of neoliberal capitalism and its effects on education. i invoked the idea of ubuntu-currere in a keynote address at the fifth triennial conference of the international association for the advancement of curriculum studies (iaacs) (le grange ). the idea brings together insights from the african value of ubuntu and william pinar's ( ) autobiographical method currere, which was extended by wallin ( ) . ubuntu, derived from aphorisms in the nguni languages of southern africa, means that our being and becoming is dependent on others. in contrast to descartes's cogito ergo sum, "i think, therefore i am", ubuntu means "because we are, therefore i am". some have misconstrued the meaning of ubuntu, arguing that it is, by definition, speciesist. however, what we need to understand is that relationality between humans (ubuntu) is emblematic of the relatedness of all things in the cosmos. i point out that ubuntu is the concrete expression of the shona concept ukama, which mean relatedness of all things in the cosmos (le grange ). in other words, ubuntu is a microcosm of ukama. moreover, ramose ( ) has argued that ubuntu is antihumanist and involves the ongoing unfolding of the human in relationship with the other-that the human being is in-becoming. forty-five years ago, pinar ( ) first invoked the etymological root of "curriculum": the latin currere, "to run the course". in doing so, he refocused curriculum on the significance of individual experience, "whatever the course content or alignment with society or the economy" (pinar , p. xii) . currere privileges the individual and pinar ( , p. ) argues that it is a complicated concept, because each of us is different in our genetic makeup, our upbringings, our families, and, more broadly, our race, gender, class, and so on. put simply, currere shifts the attention away from the concept of a predetermined course to run, to a focus on how the course is run by each individual, given each one's unique makeup, context, hopes, aspirations, and interactions "with other human beings and the more-than-human world" (le grange b, pp. - ). in other words, each person has her or his own life story, and the understanding of one's own story through academic study is at the heart of curriculum. pinar ( ) develops currere as an autobiographical method with four steps or moments-regressive, progressive, analytical, and syntheticalthat depict both temporal and reflective moments for autobiographical research of educational experience. both ubuntu and currere affirm the importance of human experience-the being and becoming human-and the unfolding of the human as the world is revealed to it. but le grange ( , b) brings the two notions together to shift the emphasis from the individual to a subject that is ecological-a subject that is embodied, embedded, and enacted. i invigorated lines of connections between emerging (post)human theories to create a new concept: ubuntu-currere. i wrote: ubuntu-currere shifts our registers of reference away from the individual human being to an assemblage of human-human-nature. in other words, subjectivity is ecological. moreover, the subject is always in becoming and the becoming of a pedagogical life is relational-the subject becomes in relation to other humans and the more-than-human-world. the notion in-becoming ensures that the human cannot be defined nor have fixity and therefore ubuntu-currere is anti-humanist. put differently, ubuntu-currere negates the construction of a molar identity that is a screen against which anything different is othered in a negative sense. ubuntu-currere has resonance with new materialist post-human theory in that it embraces an ontology of immanence-that there is a material immanent plane that connects everything in the cosmos and from which all actualised forms unfold/become. ubuntu-currere opens up multiple coursings for developing post-human sensibilities driven by the positive power of potentia that connects, expresses desire and sustains life. … but, it also makes possible conversations with the more-than-human so that we can listen to the rhythm and heartbeat of the earth-so that our conversations do not happen on the earth but are bent by the earth. (le grange b, pp. - ; italics in original) ubuntu-currere affirms the importance of caring for other humans beings-"humanness" does not mean humanism and is antithetical to it. the subject of education informed by ubuntu-currere is not egoistic and holds no ontological privilege, but is placed on an immanent plane with all living beings. the actions (ethics) of this subject in the world are to release the power that is within-in contrast to the power that imposes or acts upon the other. this power of potentia is within all life and connects all modes of life. it is this same power that we see when humans perform generous acts of caring for others during the covid- pandemic, when they unselfishly give up their lives to save or feed another. this power is counter to the negative power of postestas that imposes, that engages in othering, that colonizes, that controls, etc. if we are to have a different post-covid- world, then its actualization depends on invigorating potentia. education informed by ubuntucurrere involves supporting learners to release potentia so that actions in the world are about enhancing life. the ideas advanced in the four introductory chapters of the international handbook of curriculum research that frame this article are connected to one another and crystalize in the notion of ubuntu-currere. the moral dimension of education speaks to our sense of belonging to something bigger than our individual selves and the need for our ongoing commitment to engage in complicated conversations with one another, and more so in troubled times. and in such conversations, we should understand and investigate how the ongoing discriminations of all kinds that continue to plague us are amplified and accelerated. the covid- pandemic has laid bare how those on the margins of society bear the brunt of the pandemic-and that the underlying cause of much of this reality of inequality is the dominance of neoliberal capitalism. if we are to avoid the damaging effects of crises such as the current one, then we need perform currere to free ourselves from the fetters of neoliberal capitalism. and if we are to live in harmony with one another and the more/other-than-human world, then we need to fuse currere with ubuntu. ubuntucurrere makes possible an education that is a life-long affair of experimentation with the real-experimentation constrained only by life itself. put differently, our experimentation with life should be curtailed only when we hurt other humans or the more/other-thanhuman world. under covid- , racism in britain and the world is a matter of life and death. daily maverick layered understanding of orientations in social studies program evaluation the internationalization of curriculum research to understand who's dying of covid- , look to social factors like race more than pre-existing diseases education for sustainable development: sustainability as a frame of mind maybe the coronavirus will set sa on a path to a more equitable education system racism and discrimination in covid- responses covid- : exposing a water crisis in the making. daily maverick lockdown: school feeding scheme reopens in western cape to assist "desperate communities the uberfication of the university quality assurance in south africa: a reply to john mammen the history of biology as a school subject and developments in the subject in contemporary south africa ubuntu, ukama, environment and moral education keynote address delivered at the th triennial conference of the international association for the advancement of curriculum studies a comment on criticisms of the article "age-and education-related effects on cognitive functioning in colored south african women currere's active force and the concept of ubuntu could the covid- pandemic accelerate the uberfication of the university? socially critical education for a sustainable stellenbosch by race and education in the age of digital capitalism coronavirus and capitalism: structural foundations and opportunities for systemic change. daily maverick education policy: globalization, citizenship and democracy debunking nine common covid- myths doing the rounds in africa: some of the false claims being made about the coronavirus are harmless. others can be potentially dangerous a viral theory of post-truth the method of currere. paper presented at the annual meeting of the american educational research association (aera) the character of curriculum studies: bildung, currere and the recurring question of the subject international handbook of curriculum research african ethics: an anthology of comparative and applied ethics black americans bearing the brunt of coronavirus recession: this should come as no surprise. the conversation wisdom responses to globalisation what knowledge is of most worth ignorance in educational research: or, how can you not know that? educational researcher a deleuzian approach to curriculum: essays on a pedagogical life a nonviolent perspective on internationalising curriculum studies publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.lesley le grange is distinguished professor in the faculty of education at stellenbosch university, south africa. he is also vice-president of the international association for the advancement of curriculum studies (iaacs), a fellow of the royal society of biology (uk), a member of the academy of science of south africa, and rated as an internationally acclaimed researcher by the national research foundation in south africa. he has published more than articles and serves on editorial boards of nine peer-reviewed journals. he has delivered more than academic presentations and is recipient of several academic awards and prizes; the most recent is the south african education research association (saera) honours award ( ) for outstanding contribution to educational research in south africa. key: cord- -lter hy authors: lewis, shantel; mulla, fathima title: diagnostic radiographers’ experience of covid- , gauteng south africa date: - - journal: radiography (lond) doi: . /j.radi. . . sha: doc_id: cord_uid: lter hy introduction as of july , south africa (sa) had the fifth highest number of covid- infections in the world, with the greatest contributor of these infections, being the province of gauteng. diagnostic radiographers in gauteng providing chest ct, chest radiograph and mri services are frontline workers experiencing these unprecedented times. therefore, this study undertook to explore diagnostic radiographers’ experiences of covid- . methods a qualitative approach using an asynchronous opened-ended online questionnaire was used to explore diagnostic radiographers’ experiences of covid- . responses from purposively sampled diagnostic radiographers in gauteng sa, underwent thematic analysis. results sixty diagnostic radiographers representing both the private and public health sector responded to the questionnaire. thematic analysis revealed three themes: new work flow and operations, effect on radiographer well-being and radiographer resilience. conclusion besides experiencing a shift in their professional work routine and home/family dynamics, diagnostic radiographers’ well-being has also been impacted by covid- . adapting to the “new way of work” has been challenging yet their resilience and dedication to their profession, providing quality patient care and skill expertise is their arsenal to combat these challenges. implications for practice understanding the impact of covid- on diagnostic radiographers will allow radiology departments’ management, hospital management, professional bodies and educational institutions to re-evaluate provision of resources, training, employee wellness programs as well as policies and procedures. note: a graphical abstract has been submitted for consideration: the stick person (non-gender, non-race) represents the radiographer, pushing up the boulder of emotions and experiences as the covid- infections continue to raise in sa. yet radiographers draw on the positives and soldier on hence the use of the super hero cape. in the spanish flu killed approximately south africans in six weeks. since , hiv/aids has claimed in excess of three million south africans. , south africa (sa) also remains one of eight countries that contribute to two thirds of the total global tuberculosis (tb) infections. now, in addition to its burden of existing diseases, sa like the rest of the world, faces a novel pandemic. since december when the first case of a new coronavirus was reported the disease coronavirus (covid- ) caused by the severe acute respiratory syndrome coronavirus , has spread to countries and territories worldwide. - sa reported its first covid- patient on march and on the th march the country went into a day national lockdown with confirmed positive cases. the aim of the lockdown was to reduce the rate of transmission and to allow health care facilities to prepare for the anticipated infection surge. , sa's healthcare sector consists of a public and a private sector. sa's public healthcare sector is government funded but under-resourced, supporting approximately % of the population. the private healthcare sector, paid through medical aid schemes and individuals is well-resourced, catering for the remaining % population. news reports indicate that the private healthcare sector may accommodate covid- patients from the public health sector at an agreed price. , background the severe acute respiratory syndrome (sars) coronavirus resulted in an increased need for medical imaging services and stringent infection control practices. radiographers working through the sars outbreak, experienced sars as being stressful. low staff morale, inadequate infection control and poor risk management skills were highlighted as contributing factors. however, after the outbreak, radiographers found the experience to be a valuable opportunity to reflect on their role as radiographers, radiography practice and professionalism. seventeen years later, the covid- pandemic has had a similar impact on medical imaging services. chest computed tomography (ct), lung ultrasound, magnetic resonance imaging (mri) and chest radiographs, performed by radiographers, play a pivotal supportive role in the diagnosis, management and treatment of covid- . [ ] [ ] [ ] [ ] [ ] [ ] as a result, medical imaging departments had to introduce new work flow and operations. measures included the use of personal protective equipment (ppe), social distancing and stringent equipment sanitization. staff allocations were also amended to mitigate spread among staff while ensuring continued service. infection of staff would mean that the workload on remaining staff would increase. [ ] [ ] [ ] [ ] [ ] [ ] besides these changes to the working environment, enforced lockdown protocols resulted in furloughs, loss of jobs, reduced work hours and children needing to be schooled at home. [ ] [ ] [ ] adjusting to this new way of work and life has resulted in emotional, physical, financial and mental stress. [ ] [ ] [ ] [ ] [ ] the impact of these multitude of changes needs to be explored. therefore, this study undertook to explore diagnostic radiographers' experience of covid- . the study was conducted in gauteng, sa. [ ] [ ] [ ] [ ] [ ] [ ] method a qualitative approach using an open-ended online questionnaire was used to explore gauteng's diagnostic radiographers' experiences of covid- . diagnostic radiographers (hereafter referred to as radiographers) employed in gauteng, sa were purposively sampled. demographic data was obtained and answers to a single j o u r n a l p r e -p r o o f question: "how has your experience been during covid- ?" underwent thematic analysis. radiographers' responses were read and reread to obtain a general sense of the information; the data was coded and categorised and then themes were generated. due to covid- restrictions preventing face to face interviews, telephonic or video calls could have been used, but considering changes to radiographers' work and home life, the option to have an online open-ended questionnaire was favoured. asynchronous qualitative online, open-ended questionnaires are not commonly used for qualitative research but were selected for use in this study so as not to burden participants in time-locked obligations. radiographers choosing to participate in the study could do so at any time they found suitable without being burdened by contact at a specific time. also invitations to participate in the study asked radiographers to share their experiences in as little or as many words as they liked. written responses allow for self-reflection and focused answers. measures of trustworthiness included member checking and reflexivity to ensure credibility. , themes were shared with radiographers that participated in the study to establish if it portrayed the truth value of their experience of covid- . , the authors kept research diaries of their own to allow continuous reflection. , dependability and transferability of the study was ensured by a detailed description of results along with providing direct quotations from participants. , , confirmability of a study is ensured by an audit trail. , questionnaire responses from the study is preserved to allow for independent auditing. ethical clearance and consent to conduct the study were obtained (rec- - ). diagnostic radiographers were invited to participate in the study through email and messaging applications as well as through the head of radiology departments. data collection continued until data saturation was achieved. sixty radiographers from gauteng's public and private sector responded to the questionnaire. both sectors were represented in the study with radiographers working in public hospitals, working in private hospitals and the remaining radiographers working in both public and private hospitals. the study information letter outlined the purpose of the study as well as provided the opportunity for radiographers to express their experiences of covid- without the demographic data of participants is presented in radiographers' responses to the question ""how has your experience been during covid- ?" were read and reread to obtain a general sense of the data. the data was then coded and categorised yielding three themes: new work flow and operations, effect on radiographer well-being and radiographer resilience. medical imaging departments' operations were affected by the decrease in imaging referrals at the onset of the lockdown. even though it has been viewed as an opportunity to address "overuse and overdiagnosis" , the reduction in imaging referrals, has resulted in some radiographers in the private sector experiencing pay cuts: j o u r n a l p r e -p r o o f "…since the lockdown patients were advised not to come to the hospital unnecessarily and with that in private sector, we were affected economically. less patient=less profit to the company then salaries we cut off" r radiographers' experiences confirm the introduction of new work flow and operations as well as the need to conform to new changes. [ ] [ ] [ ] [ ] the quotes below convey radiographers' experiences of the changes: "during this pandemic we've also had to work extended hours at the hospital ( hour shifts for days and then days off which i feel also adds to the exhaustion." r "…so my experience has been okay and at times difficult as we divided ourselves into teams" r comparably, worldwide medical imaging departments have adapted operations to mitigate cross-contamination and staff shortages. [ ] [ ] [ ] however, an hour work week as indicated by r , despite the time off, constitutes prolonged working hours. prolonged working hours raise concern of health and safety as well as increasing the risk of respiratory disease. , j o u r n a l p r e -p r o o f radiographers shared their experience of medical imaging departments implementing stringent infection control measures that affected work flow and operations. [ ] [ ] [ ] their responses ranged from having access to sufficient ppe to lack of ppe; lack of disinfectants as well as delayed testing and provision of results. radiographers' experiences of infection control measures are shared through these direct quotes: "… at least we have ppe." radiographers routinely wear gloves and practice handwashing in daily practice however now continuous use of masks and face shields was described as "stifling" and as "not being able to breathe properly". radiographers describe being sad, terrified, confused, stressed, scared, exhausted, anxious, overwhelmed, frustrated, uncertain and panicked. their "roller coaster" of mixed emotions has stirred up an "emotional war" draining them emotionally, physically, financially and mentally. [ ] [ ] [ ] seeing patients out of breath, deteriorate, being ventilated and dying; in the same way, seeing colleagues falling ill and some dying, take a toll on radiographer's mental health. radiographer's mental health is marauded even further by not being able to see family and friends coupled with the anxiety of contracting and transmitting the disease. [ ] [ ] [ ] there is also the notion that healthcare workers are not human and therefore should cope. these descriptions are reflected in the following quotes: yet some radiographers report being told that "staff" are overreacting. during the sars epidemic radiographers were motivated through the crisis by reassurance. "i, for one know that at work, we were often told "staff is overreacting" so i fought this and i felt a lot of emotional and mental strain on myself" r not being considered frontline workers, a concern echoed by professional bodies impacts allocation of resources as well as radiographers' well-being: [ ] [ ] [ ] [ ] [ ] [ ] [ ] "it has been rather negative, as we do not get proper personal protective equipment (ppe), we are not recognized as frontline workers, and we are not considered by our hospital." r "very nerve wrecking. it's a learning curve so you have to be on guard all the time. being a radiographer, you are essential but not considered total frontline. with everyone testing the waters it's difficult to have proper guidelines." r there was also concern about the volumes of covid- information. information overload coupled with misinformation and conspiracies results in psychological distress. , "at the beginning there was very limited factual information about the virus itself and an overload of information about different theories/conspiracies about covid- and this has in turn resulted in so much confusion and difficulty to find the path of how to deal with the situation and find a way forward. there were many arguments and different opinions of how one should go about doing things." r south african radiographers already work in stressful environments that is now exacerbated by covid- . despite the impact of changes and the burden on their well-being, experiences shared by radiographers reveal their ability to find the positives even in these anomalous times. these experiences indicate an initiation of strategies towards resilience. radiographers in gauteng, sa are exposed to the highest number of covid j o u r n a l p r e -p r o o f the story of south africa's five most lethal human diseases protecting south africa's elderly world health organization. south africa. country cooperation strategy at a glance pdf;jsession id= bfd dcb ce d a a ?sequence= world 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indian hospital -safety of the radiographers, the frontline warriors how to safely and sustainably reorganise a large general radiography service facing the covid- pandemic dealing with covid- : initial perspectives of a small radiology department mexico city. . adaptation and teamwork, the lessons of the pandemic: health personnel isrrt response document -appropriate and safe use of medical imaging and radiation therapy with infection control measures considered in addition to standard radiation protection procedures management of patients with suspected or confirmed covid- the frontline as a radiographer during covid- all health care workers are heading towards a breakdown, notwithstanding the outer facade of calm. be patient with them radiographer on frontline in coronavirus fight covid- in africa: care and protection for frontline healthcare workers minimising catching covid- from patients: working practices and ppe coping with stress during the -ncov outbreak covid- ) caused by a novel coronavirus (sars-cov- ) guidelines for case-finding, diagnosis, management and public health response in south africa covid- outbreak in south africa: guidance to health practitioners department of health. guidelines for quarantine and isolation in relation to covid- exposure and infection the association between resident physician work hour regulations and physician safety and health risk factors of healthcare workers with corona virus disease : a retrospective cohort study in a designated hospital of wuhan in china spread in radiology: experience from a singapore radiology department after severe acute respiratory syndrome the society of radiographers (sor). evans, r. letter concerns from radiography professionals on the covid- frontline to m. hancock. available from american society of radiologic technologists. state leaders urged to address "inequitable" louisiana law new poll: radiographers concerned about covid ppe, testing & supplies personal protective equipment during the covid- pandemic-a narrative review camrt position statement personal protective equipment for medical radiation technologists during the covid- crisis international society of radiographers and radiologic technologist. position statement healthcare employers responsibilities in recognising radiographers/radiological technologists as key frontline healthcare workers frontline-workers-final-version-for-approval-from-isrrt-bom.pdf that's insight: a letter from the president of the kansas society of radiologic technologists pushes for recognition of rad techs and radiation therapists as essential personnel in the fight against covid- . the piece was the novel coronavirus (covid- ) outbreak: amplification of public health consequences by media exposure analysts are tracking false rumours about covid- in hopes of curbing their spread reality shock in radiography: fact or fiction? findings from a phenomenological study in durban reducing the burden of injury in high-risk communities the burden of trauma at a district hospital in the western cape province of south africa the lived experiences of radiographers in gauteng. the sa radiographer thematic review of social and occupational factors associated with psychological outcomes in healthcare employees during an infectious disease outbreak j o u r n a l p r e -p r o o f moreover, they face mental, physical, emotional and financial challenges. however, honing the positives, they have initiated strategies towards resilience. thank you to all the radiographers working in the frontline, who shared their experiences during this pandemic.the authors would like to acknowledge maxine maistry, first year wits undergraduate fine arts student, for graphically representing this study. key: cord- -t l zii authors: mayer, j.d. title: emerging diseases: overview date: - - journal: international encyclopedia of public health doi: . /b - - . - sha: doc_id: cord_uid: t l zii emerging infectious diseases are diseases that are either new, are newly recognized, or are increasing in prevalence in new areas. resurgent diseases are also usually grouped in this category, as is antimicrobial resistance. these diseases have been given formal recognition in the past two decades, although a historical outlook demonstrates that the phenomenon has probably been persistent, although largely undetected, through recorded history. emergence has accelerated recently, driven by factors such as demographic change, land use change, increased rapidity and frequency of intercontinental transportation, and other mostly social trends. continued infectious disease emergence poses, and will continue to pose, significant challenges for public health and for basic science. emerging and re-emerging infectious diseases have been major features of contemporary societies. indeed, there is evidence that history has been characterized by the constant interplay of humans and pathogens (mcneill, ) . however, it is impossible to say when the terms 'emerging infection' or 'emerging infectious diseases' were first used to describe new infectious diseases, or diseases that meet the criteria that are described in this article. the belief in the s that the threat of infectious diseases had been eliminated in developed countries was unfounded. a broader view of history would have demonstrated this. one possible reason for the optimism is that the s was a decade of optimism in general. in the united states, social programs were instituted to address inequities; humankind had not only orbited the earth, but landed on the moon; the gains of science and technology were impressive; economic expansion was equally impressive; poliomyelitis had been all but eliminated in the united states; and the sense of 'control' was widespread. beyond the borders of the united states, however, in africa, asia, latin america, and elsewhere, malaria proved to be a huge challenge to life, although its prevalence was decreasing, and diarrheal diseases continued to take their toll, particularly among the young. transportation links created the potential for transmission of infection between tropical regions and developed countries such as the united states. the potential for new diseases to emerge in the united states was there, and it took just a few years until this happened, catching the medical and public health communities by surprise. in discussions of emergence, both 'emerging infections' and 'emerging infectious diseases' are commonly found. while the two are closely related, they are not synonymous. an infection does not necessarily represent a state of disease. 'infection' suggests that an agent (usually a microbe) has become resident in the host. usually that agent is replicating in the host. however, the host need not show any sign of disease, in the sense that it can conduct its normal activities without hindrance. 'disease' is a state in which the normal functioning of the host is impaired, and both signs and symptoms are present -indeed, they are what limit normal function. an infectious disease is therefore a disease that is due to a pathogen. appeared de novo, or are being experienced in a region with greater intensity, or for the first time. some authors have used a more specific definition of emerging to diseases and have specified five types of emerging diseases: ( ) diseases that arise de novo, ( ) diseases that are newly recognized, ( ) diseases that have not previously existed in a specific area, ( ) diseases that had not yet made a species jump to humans until the present, and ( ) diseases that are increasing in prevalence. there are other definitions as well. the simplest definitions are frequently the most useful, and thus morse's definition will be used in this article. re-emerging infectious diseases are frequently thought of as being closely related phenomena to emerging infectious diseases. whereas emerging diseases denote diseases that are being experienced for the first time in a given location, re-emerging diseases are diseases that are reappearing in regions from which they have disappeared. usually eradication is due to deliberate efforts on the parts of government and public health agencies. for example, malaria control programs following the end of world war ii were instrumental in the elimination of malaria from some areas of the world, such as italy and spain. sometimes, malaria eradication was eliminated as part of multisector development programs. for example, the tennessee valley authority, created during the s primarily for flood control, hydroelectric power, and economic development, also had an explicit aim of malaria control. this resulted in the drainage of most swamps, and the elimination of malaria from this part of the united states. just as malaria was disappearing from many regions in the s, the next decade saw the resurgence of malaria, and the global prevalence of malaria has been increasing ever since. there are multiple reasons for this. these include anopheline spp. resistance to ddt, banning of ddt because of suspected environmental effects, and the development of resistance to chloroquine. malaria, then, is a re-emerging disease. another is tuberculosis. in many societies, tb had been nearly eliminated, but with the appearance of hiv/aids, immunocompromised individuals were much more susceptible to tb reactivation. tb, therefore, is also considered to be a re-emerging disease. the public and the medical and public health communities gradually came to realize that their complacency over the potential threat of infectious diseases was misplaced, and that new and emerging diseases constituted one foci of concern over health threats to the public. this change in attitude came gradually, and can be thought of as a series of historical 'moments,' each of which refocused attention on infectious diseases. while it is impossible to be exhaustive here, this section takes a roughly chronological approach in describing the events that led the public and professional communities to realize that infectious diseases had not been 'conquered.' the bicentennial of the united states was celebrated in , and there were many gala events around the nation in july. one was the meeting of the pennsylvania chapter of the american legion. the events surrounding this meeting were the first to bring the attention of both the population and the broad scientific and medical communities to the argument that infectious diseases in the united states had been 'conquered,' and both alarmed the public and aroused the curiosity of the scientific and medical communities because this appeared to be a new disease. indeed, before legionellosis was identified and antimicrobial treatment identified, legionellosis was called a 'monster disease. ' over members of the american legion who had attended the meeting developed an unusual respiratory illness, and it became clear that it was of bacterial etiology, although it was initially thought to be viral, due to its close clinical resemblance to influenza. approximately people died as a result of this outbreak. however, two things remained unclear. first, the pathogen could not be identified with conventional methods, and second, no common source of exposure could be identified initially, although the fact that the number of incident cases followed a typical epidemic curve suggested very strongly that there was some sort of common exposure to the pathogen. the news media seized upon this medical 'mystery,' and the public knew that they were dealing with an unknown infectious disease. this constituted a historical moment in contemporary american history, because it had been decades since something like this had happened. six months later, the bacterium was finally identified. legionella was not a new bacterium. stored samples from outbreaks as early as tested positive for legionella spp. however, the bacterium had not been identified in these outbreaks because it had not yet been described and characterized. in retrospect, most renowned is an outbreak that occurred in pontiac, michigan in , although the symptoms were milder than in the legionella outbreak in philadelphia. in fact, mild legionellosis with a nonpneumonic form is often called 'pontiac fever.' this is not the place to review the epidemiology, pathophysiology, and clinical aspects of legionellosis in depth. briefly, though, it usually has an acute onset, and is usually caused by legionella pneumophila, although other species are also pathogenic. in fact, there are species of the genus, and numerous serotypes. epidemiologically, l. pneumophila is by far the dominant species in human disease. the major reservoirs are bodies of freshwater, and the main mode of transmission is through small droplets that are inhaled from the environment. in the philadelphia outbreak, the source was finally traced to the air conditioning system in the hotel in which most attendees were lodged; the attendees were inhaling small particles in certain parts of the building. dozens of subsequent outbreaks have been traced to similar mechanisms. these have been not only air conditioners but also shower heads, aerosolizers in sinks, and whirlpools. virtually anything that aerosolizes fresh water is a potential mechanism by which legionellosis may be transmitted. symptoms of classic legionnaires disease are nonspecific and include fever, malaise, headaches, and myalgias. frequently, rigors will develop, as will a productive cough (in about half the cases). dyspnea (shortness of breath) is almost invariably present, and chest pain is common, as is a relative bradycardia for the elevated temperature. there are a number of abnormalities in laboratory tests, and chest films are markedly abnormal. a urine antigen test is available for one serotype, so laboratory diagnosis must frequently rely on more complex and time-consuming laboratory methods such as dfa. sputum cultures or cultures from bronchoalveolar lavage have been the mainstay of laboratory diagnosis. since laboratory methods do not show a definitive diagnosis until a minimum of days following onset, diagnosis is usually made on clinical grounds, and treatment is initiated based upon index of suspicion. erythromycin proved to be effective in , and other macrolides (azithromycin, clarithromycin) are highly effective. tetracycline and doxycycline are frequently used, as are the fluoroquinolones, such as levofloxacin. in hosts who are not immunocompromised, the prognosis is generally positive. there is no doubt that legionellosis was an emerging disease when it was first identified. its particular significance lies in its historical context -in the fact that this was the first occurrence that began shaking the optimism of the s and early s that infectious diseases had been conquered, and also in the fact that the etiology of an obviously infectious syndrome with a reasonably high case fatality ratio remained unknown for a number of months. chronologically, the next event to bring infectious disease to the attention of the public was another emerging infectious syndrome. in late and , a number of women in the united states became seriously ill with a syndrome characterized by high fever, shock, rash, hypotension, and capillary leak. this syndrome had been first described as such years earlier, although in retrospect it had been noted in the medical literature in the s. the paper identified toxic shock syndrome in males, females, and children -and the females were both menstruating and not menstruating. the outbreak was associated with menstruating women, many of whom were using superabsorbent tampons. although this was a major risk factor in the - outbreak, much of the public and many physicians were under the erroneous impression that toxic shock syndrome (tss) was necessarily associated with menstruating women who were using superabsorbent tampons. although tss is not necessarily associated with menstruating women, this does remain a risk factor in the epidemiology of tss. as with legionnaires disease, tss was a rare disease, yet the public's perception of it was out of proportion to its true prevalence -the risk was exaggerated. this is something that social scientists have called the 'social amplification of risk' in the context of new events that are potentially dangerous, but that nonetheless carry with them a low risk. amplification takes place as a result of media coverage, and as a result of intrapsychic processes that tend to amplify the threat of novel threats when the locus of control over the event is external to the individual. during the outbreak of toxic shock syndrome, newspapers were full of stories about tss and the sometimes deadly consequences of developing the syndrome. these were frequently on 'page above the fold' and necessarily caught the attention of the public. the same was true of television news. once this outbreak of tss appeared to be concentrated in one single group -menstruating women using superabsorbent tampons -the general public's fear of tss began to diminish, and the federal government mandated the withdrawal of those tampons from the market. the number of incident cases began a rapid decline, and was back to baseline of about cases per year by . some reports demonstrated that there was a decrease in the use of all tampons -not just superabsorbent tampons. it was already known in that toxic shock syndrome was caused by staphylococci (specifically, s. aureus). in these cases, treatment is threefold: removal of the tampon, indwelling tampon, or other hypothesized environmental cause; aggressive fluid resuscitation; and rapid use of antistaphylococcal antibiotics. other bacterial species can cause toxic shock syndrome. in rare cases, other staphylococcus species have been associated with toxic shock syndrome, and because they are coagulase-negative, they are difficult to treat. at this time, coagulase-negative staphylococci constitute the most common cause of hospital-acquired bacteremia. this sometimes results in endocarditis, and usually the only effective treatment is surgical valve replacement, particularly in the case of those who have had earlier valve replacement. aggressive antibiotic therapy is occasionally effective. should toxic shock syndrome be considered to be an emerging disease? it certainly was in , when the public was so concerned with its appearance. now, in , years after it was first described, this label is more questionable. what was most significant about toxic shock syndrome, however, was its historical significance. it followed the outbreak of legionnaires disease so closely that it turned the public's attention, once again, to infectious diseases, and to infectious diseases that had been unknown. it also reminded the biomedical community that infectious diseases had not been conquered. the issue at the time was whether legionnaires disease and toxic shock syndrome were anomalies, whether the assumption of the conquest of infectious diseases had clearly been erroneous, or whether these two outbreaks were harbingers of a new stage in 'epidemiologic history'a historical period during which emerging infections would become common and would catch the attention of the public, the public health community, the medical community, and government agencies. the public health and medical communities were divided on this. it would soon become clear, however, that the latter would hold true -that emerging infectious diseases would come to the forefront of public health, epidemiology, and the medical community. in the cases of legionnaires disease and tss, the social amplification of risk exaggerated perceived threats. nonetheless, the public became more attentive to infection. two other phenomena would solidify this attention. one was the appearance of hiv/aids in the united states, and the other was public attention that was drawn to hemorrhagic fevers, mostly in africa. the details of hiv/aids are covered elsewhere in this encyclopedia, and there will be no attempt here to duplicate this material. rather, this discussion concentrates on the significance of hiv/aids. when hiv/aids first appeared in several urban areas in the united states in , it appeared to be an anomalous syndrome. it was not called 'aids' until , when the centers for disease control (cdc) gave the syndrome that label. in the same year, researchers at cdc also linked one of the pathways of transmission to blood and blood products, causing a great deal of public concernif it was possible to contract aids through a frequently used medical practice, it had the potential of affecting millions of people. until then, aids was thought to be restricted to the gay community. in , blood banks were warned by the cdc that blood and blood products could definitely transmit aids, and surgeons and other medical personnel began rethinking the criteria necessary for transfusion. by , it was clear that the exponential increase in the number of incident cases was a definite trend. in and , two teams discovered that the pathogen causing aids was viral, and although it had a different nomenclature at first, there was a great deal of relief that the causal agent had been discovered. it is an interesting study in the sociology of science to analyze the competing claims by luc montagnier at the institut pasteur and robert gallo in the united states concerning their respective claims that they discovered hiv. it is now clear that montagnier discovered the virus. shortly after the virus was discovered and characterized, an antibody test was developed to detect hiv in vivo. this was quickly used to screen blood products as well as to detect hiv in individuals. whereas some people decried the slowness of the u.s. government's response to hiv, the time from the first presentation of a group of males with kaposi's sarcoma or oral thrush until the antibody test for a recently identified virus was only years. granted, the president of the united states, ronald reagan, had not even mentioned aids, and funding was less impressive than it could have been, but the time was quite short. the real challenge with hiv has been to find an effective vaccine, or to find a 'cure,' although antivirals have been effective in suppressing viral load in the majority of cases since - . the prevalence and mortality data are well-known. the best estimates are that globally, over million people are living with hiv/aids, and approximately million have died of hiv/aids. currently, about - million of those living with hiv/aids are women, and in developing countries, particularly in sub-saharan africa, hiv/aids is becoming, increasingly, a disease of women. currently, approximately two-thirds of those living with hiv/aids are in sub-saharan africa, but the increasing prevalence and incidence of hiv/aids in asia -and particularly, in india and china -are making east asia and south asia regions of tremendous concern. this is because each country has over billion people, and the prevalence rates do not have to be high to result in large numbers of infected people. the global significance of hiv/aids is that it, by itself, has altered demographic trends, and the political economy of nations and regions, not to mention the human suffering that this disease has exacted. in botswana and swaziland, for example, the gains in life expectancy during the th century have not only been completely reversed, but the life expectancy at birth is lower now than it was at the beginning of the th century. in the context of this article, hiv/aids is an emerging infectious disease par excellence. a generation ago, it was literally unheard of. now in all developed countries and in many developing countries, hiv/aids shapes many behaviors, is responsible for significant stigma, is feared, and causes a significant percentage of deaths. globally, hiv/aids is the fourth leading cause of death, although in many parts of africa, it is the leading cause of death. hiv/aids is an emerging infectious disease because of the historical rapidity with which it moved from an unknown localized zoonotic complex in west and central africa to the most prevalent infectious disease in the world. while the scientific evidence suggests that there were a number of species jumps of both hiv- and hiv- that occurred in africa, these were so localized and the societies isolated enough from the rest of the world that hiv went unnoticed. thus, it appeared as though the disease went from nonexistence to a major pandemic in a matter of a few years. and there is another major significant dimension. since hiv/aids appears to have originated in africa -'out there,' away from northern europe and north america -some have argued that hiv/aids acquired a certain nefariousness -a disease emerging from the dark, foreign, isolated jungle -the stereotypical cauldron of new diseases. viral hemorrhagic fevers have been in the public eye since , when there was a major outbreak of a hemorrhagic fever in the jos plain of nigeria. the disease came to be called lassa fever, caused by an arenavirus (lassa) that seemed particularly undesirable to the public. the virus is named after the town in which this outbreak occurred. like all hemorrhagic fevers, including dengue in some cases, one of the characteristics of lassa fever is that it can disturb the clotting/coagulation mechanism, resulting in disseminated intravascular coagulation (dic) and diffuse hemorrhage. the outbreak was publicized in the united states through the news media, perhaps because it was an 'exotic' or newsworthy event, and once again, the social amplification of risk was responsible for exaggerated fears of 'what if it spreads here?' that this outbreak occurred in sub-saharan africa, which, in the eyes of the north american public, may have been thought to be all 'jungle' (the jos plain is not rain forest) probably also contributed to the amplification of risk. serologic tests demonstrate that exposure to lassa virus is common in west africa. for example, in parts of nigeria, seroprevalence is positive in % of those tested; in sierra leone, the figure varies from - % depending on the region (richmond and baglole, ) . it is now known that humans are dead-end hosts, and that the rat species mastomys natalensi is the natural host. these rats are extremely common throughout sub-saharan africa. people become infected by inhaling aerosols from rat excreta, and risk is increased by eating them, which is a very common practice in west africa. modern modes of travel have allowed infected individuals who are either symptomatic or asymptomatic at time of entry to travel to other continents, where they require treatment for lassa fever. these cases have not been numerous, but cases have appeared in the united states and japan, as well as in several european countries. this has caught some clinicians unprepared, since they were not trained in tropical medicine and were unaware of how to diagnose or manage a viral hemorrhagic fever. the prevalence rate of lassa fever is much higher than was initially thought. in one series, lassa fever accounted for % of adult deaths in sierra leone, and as many as % of hospital admissions (richmond and baglole, ) . following the outbreak in , it took some time to investigate adequate treatment protocols, but now, aggressive fluid replacement and the use of antiviralsparticularly ribavarin -are the treatments of choice. ebola hemorrhagic fever and closely related marburg virus are both single-stranded rna viruses, as are other viruses that cause hemorrhagic fevers. ebola and marburg are filoviruses; ebola virus is actually a genus and there are four species. it was first described in the sudan in , and estimates are that mortality from this virus has now exceeded people. the case fatality ratio exceeds %, and may be as high as % in some cases. transmission is different than lassa fever. it is usually through direct contact with blood and bodily secretions from individuals who are ill with ebola fever, or from nonhuman primates who are also infected. evidence points to bats as the natural reservoir of ebola virus, but this is not certain. in several studies, however, bats have been shown to be infected by the virus (leroy et al., ) . this is highly suggestive, but it is not conclusive proof. like so many other viral hemorrhagic fevers, the symptomatology of ebola is very nonspecific and typical of viral syndromes in general. the clinician needs to have a high index of suspicion. at this point, the only certain treatment is supportive, and from a public health point of view, quarantine is of the utmost importance, since ebola fever is so contagious. this was well-documented by the news media in the outbreak in kikwit, democratic republic of the congo (drc, then zaire) in . this was so well-documented that once again it led to exaggerated perceptions of risk, with overtones of the 'exotic disease' from sub-saharan africa and its possible spread to the united states. recent advances in understanding the pathogenesis of ebola and the role of proinflammatory cytokines has led to the use of some recombinant products that block the progression of the inflammatory cascade to dic in some animal models. nonetheless, this approach has not been used in humans as of . there are three notable points that need to be mentioned concerning ebola. first is that it appears to be increasing in prevalence in africa. this may be because detection is better and the disease has been better described, both epidemiologically and pathophysiologically. second is that there is significant concern that ebola virus could be used as a biological weapon. it has thus been placed on the highest level (category a) of potential biological weapons by the cdc. finally, ebola, more than any other emerging infectious disease, typifies in the mind of the public the sort of dangerous, threatening disease risk that is associated with tropical areas, the 'jungle,' and the threats that are associated with a more interconnected world. bovine spongiform encephalopathy (bse), or 'mad cow disease' in nontechnical terms, is another infectious disease that focused public awareness on emerging infections. the pathogen in this case was unusual not only in the sense that it had not been described elsewhere, but also because the whole class of pathogens -prionshave been very rare. like another neurologic disease, kuru, bse turned out to be due to a prion. essentially, prions are very simple since they are just unusually folded and self-replicating proteins. they cannot even be described as organisms. the source of the prion is not known, although many speculate that it is somehow derived from sheep infected with scrapie. in , an unusual disease seemed to be affecting cattle in the united kingdom, and by the end of the year, over cattle had died because of spongiform encephalopathy. since it was apparent that the disease was contagious, over million cattle were intentionally slaughtered to limit contagion and ensuing effects on the cattle industry. by the mid- s, there was a clear epidemiologic association between bse and a variant of a neurodegenerative disease in humans that had been described in the middle of the th century: creutzfeldt-jakob disease (cjd). however, there were some notable differences between cjd and the disease that was affecting humans in the s. the median age of this new syndrome was much younger than in classical cjd; the median duration of survival from onset of symptoms was longer than in classical cjd; and pathological differences and differences on mri were apparent with this new variant. accordingly, the cjd associated with bse first was named 'new variant creutzfeldt-jakob disease' or 'nvcjd;' as time progressed, nvcjd was renamed 'variant cjd' or 'vcjd.' although there were very few cases of vcjd in the uk human population, the threat of this disease was great according to public perception. according to the world health organization (who), as of november , there had been cases of vcjd in the united kingdom, six in france, and one each in several other countries (who, ) . nearly all of those with vcjd died or would die within years. because of the realistic fear of contagion, several steps have been taken to limit the spread of vcjd. feeding practices for cattle have changed so that it is no longer legal to feed animal protein that might contain any tissues proximal to the central nervous system to other cattle. in the united kingdom, there was a ban on cattle over months old from entering the commercial food supply. in the united states, individuals who have lived in the united kingdom or who have spent more than months in the united kingdom are banned from being blood donors on the assumption that they might have consumed infected beef during their stay(s) in the united kingdom. a ban was instituted on importing cattle and cattle feed from the united kingdom, and, occasionally, from canada, in an attempt to prevent bse from spreading to the united states (kuzma and ahl, ) . while the number of incident cases of vcjd and bse have decreased in a typical epidemic curve pattern, the effects of the bse 'scare' have been tremendous. the very credibility of the uk government was threatened. the whole cattle and meat industries were severely hurt. on the other hand, surveillance techniques and understanding of cattle food chains were vastly improved. severe acute respiratory syndrome (sars) proved to be of great import in both the public awareness of emerging infectious diseases and in the testing and real-time construction of both domestic and international systems of public health surveillance and response. it was particularly important in terms of public awareness because it spread very rapidly on the international and intercontinental scales. sars apparently began as a few cases of a viral pneumonia in guangdong province in southeastern china in late . however, this was not immediately apparent to the global public health communities because it was not publicized by the chinese government. what catapulted sars to international attention in the media and in the public health community was the appearance and rapid increase of incident cases in guangdong in february (zhao, ) . sars spread rapidly to hong kong, where contact tracing eventually identified one night in a specific hotel where the index case stayed as being the epidemic focus. the index case infected at least others who were in the hotel at one time or another during that night. sars spread from hong kong to other areas of hong kong and to singapore, vietnam, and canada (toronto, ontario). the spread of all these cases has been traced to airplane travel, followed by localized spread by an index case. a case definition was developed based upon clinical presentation, which typically consisted of fever, initially, followed by lower respiratory signs and symptoms, sometimes resulting in acute respiratory distress syndrome and respiratory distress typical of acute lung injury as a response to the inflammatory cascade. just over cases were identified worldwide, and died, for a case fatality ratio just < %. a disproportionate degree of contagion occurred in intensive care units and areas of hospitals in which hospital personnel were exposed to respiratory excretions; close proximity -within m -to an infected patient who was undergoing endotracheal intubation was the single greatest risk factor for contracting sars. local measures to control the spread of sars consisted largely of quarantine and containment. in china, for example, separate quarters for sars patients were constructed very rapidly. in singapore, arriving and departing passengers were required to pass through automated temperature detectors, and anybody with a fever was required to undergo further medical evaluation. the same was true at most points of entry in most developed countries. since most cases were contracted in hospitals and health facilities, rigorous contact control procedures were instituted, and in some cases, hospitals were closed to visitors and new admissions. the identification of the pathogen causing sars constitutes a textbook example of how international cooperation in science and public health may occur when the willpower is there and the scientific capability exists. by mid-march , many leading laboratories with advanced virologic capabilities had agreed to cooperate in a network that was coordinated by the world health organization. within weeks, a pathogen was identified as a novel coronavirus, using a combination of methods: molecular polymerase chain reaction, culture, and electron microscopy, and shortly thereafter, the criteria of koch's postulates were met. thus, the evidence was quite clear that the new coronavirus was the pathogen. the virus was named the sars coronavirus, or, almost always, sars cov. the ecology of sars was not understood as quickly as the pathogen was identified. some features were identified within a number of months. first was the phenomenon of superspreaders, which is a concept that previously had received scant attention. in this case, it became apparent that a small number of individuals spread sars to a disproportionately large number of people. it is not clear whether this is because of behavioral factors, host-pathogen interaction, or environmental factors. what is fairly clear is that were it not for superspreaders, the epidemic would not have affected nearly as many people as it did. this is because the r , or number of people who one individual could infect, was inflated by superspreaders. thus there was a domino effect of contagion. in , bats were identified as the reservoir of sars cov. there had previously been some speculation about bats being the reservoir, but there was no solid evidence, and the reservoir had been a mystery. some had suggested that proximity of people to avian species could possibly be a factor in the pathogenesis of sars, because of the importance of this process in avian influenza. however, this turned out not to be the case with sars. sars is a prototype of an emerging infectious disease (berger et al., ) . there is no evidence that sars cov existed in the human population prior to the outbreak of late - . the specific syndrome surprised the public health and medical communities, yet its general features did not, and the emergence of new diseases had been a familiar concept since the u.s. institute of medicine report of . at the same time, the rapidity of the appearance of sars and its very rapid spread at every scale fueled public apprehension, and even hysteria in some cases. evidence exists that history has been punctuated by relatively regular influenza epidemics and pandemics. the rapidity of epidemic spread, leading to pandemics, is largely determined by the velocity of the prevailing transportation modes. severe epidemics and pandemics are caused by genetic shift, whereby the viral genome expressing surface antigens (hemagglutinin and neuraminidase) undergoes relatively major change. relatively minor epidemics occur because of genetic shift, in which the surface antigens undergo minimal yet detectable changes in their configuration. following genetic shift, people have minimal immunity to the virus, and are susceptible. in one sense, each year influenza constitutes an emerging infection, because the precise genome of the influenza viruses and the surface antigens undergo change. similarly, whenever a pandemic occurs, influenza represents a more significant emerging infection. on the other hand, influenza represents a disease entity that is not new to the population. thus, it is a matter of semantics whether to consider influenza to be an emerging infection. avian influenza may constitute the next serious pandemic threat. it has been known for decades that genetic reassortment occurs in southeastern china because of the proximity of humans, avian species, and swine. an unusual number of influenza epidemics appear to arise there. however, the concern over avian influenza arises from a slightly different situation. it has been known for some time that no less than influenza subtypes -different configurations of surface antigens -can infect aquatic bird species. it has been wellestablished that several of these subtypes can infect humans, although recent experience suggests that all subtypes that circulate in avian species may have the potential to infect humans. this is one of the reasons that has given rise to concern over the possibility of an avian influenza pandemic. this theoretical concern moved closer to reality in hong kong in , when one influenza strain (h n ) was transmitted directly from poultry to humans. this took place in 'wet markets' -markets in which live poultry are densely packed, and where people co-mingle with their intended purchases. the transmission in appears to have been limited: only cases were confirmed. however, the case fatality ratio was high. six of the people died. transmission also occurred with another strain - h n -in , and in and there was widespread transmission and mortality among chickens in hong kong. because of a concern over possible transmission to humans, and because of the devastating economic potential in the poultry industry, containment of this epidemic in poultry was partly obtained by the slaughter of millions of chickens and other poultry. avian influenza viruses have shown some propensity, since , for transmission to humans. so far, human cases of influenza that have been identified as avian strains have been limited to approximately , and these have all been in asia. human-to-human transmission has been implicated in only a few cases. if this is the case, what is the concern over avian influenza? because of the tendency for influenza viruses to mutate, many virologists and epidemiologists predict that there is a high likelihood that a mutation could occur that would facilitate human-to-human transmission of h n and other avian subtypes that have been transmitted to humans. if this occurs, then there is little doubt that this strain would spread rapidly among the human population, and would spread locally, nationally, and between continents in a manner similar to sars. other epidemiologists and virologists are more circumspect in their predictions, and argue that the probability of a mutation that would increase the propensity of avian influenza to spread from human to human is unknown. a minority of authorities argue that the probability is low. thus, in assessing the overall threat of avian influenza, the crucial question is whether the virus will spread readily from human to human. at this point (mid- ) , it is unknown whether this will occur. however, it is prudent public health policy to bolster surveillance systems, and governments are stockpiling neuraminidase inhibitors, which are medications that can moderate the course of influenza if taken early in the course of clinical disease, or sometimes prevent the onset of symptoms if taken prophylactically. similarly, there has been great emphasis on vaccine development and stockpiling. in response to growing public concern over emerging infectious diseases, both domestically and internationally, as well as to both interest and concern in the medical and public health communities, a major conference on emerging viruses was held at rockefeller university in . the conference was cosponsored by several government agencies. the conference participants reached many conclusions, but two of them were that emerging infections had become a major focus for scientific research and that emerging infectious diseases had become and would remain a major public health challenge for the united states. accordingly, the institute of medicine of the national research council of the united states took a proactive role and sought funding for a major study of emerging infections. the study was funded by a number of government units, and in early , a high-powered committee met in washington for the first time to: identify significant emergent infectious diseases, determine what might be done to deal with them, and recommend how similar future threats might be confronted to lessen their impact on public health. (institute of medicine, : vi) the committee issued a report in that quickly became a standard scientific and policy reference on emerging infectious disease. emerging infections: microbial threats to health was the first major comprehensive discussion of how emerging infections arise, and how they might be addressed by the public health community. the committee also identified the six 'factors' or causes of emergence. briefly, the factors that this committee identified were the following: human demographics and behavior; technology and industry; economic development and land use; international travel and commerce; microbial adaptation and change; and the breakdown of public health measures. it is notable that five of these six factors are social factors that are consequences of changes in society. even microbial adaptation and change, such as the development of antimicrobial resistance as a response to selective pressure, has a large behavioral dimension. this is partly a response to a technical innovation -the development of antimicrobials -and partly a response to a behaviorthe prescribing of those antimicrobials. of course, one dimension of this factor is the nonselective and improper prescribing of antimicrobials. this has several dimensions: the prescription of antibiotics when none are needed, the prescription of broad-spectrum antibiotics when narrowspectrum antibiotics are sufficient, the free availability of antibiotics in many developing countries on the street and in pharmacies where no prescription is needed, and the free use of late-generation antibiotics in the food industry to promote the growth of cattle, chickens, and other animals intended for human consumption. so, in fact, all of the six factors of emergence are social and behavioral in nature. it is ironic that despite the fact that both institute of medicine reports concluded that the major causes of emergence have been social, there have been very few social analyses of emerging infections. for example, emerging infectious diseases, a new journal founded in in response to the growing importance of emerging infections, has an explicit aim of including a social understanding of emerging infections in its contents, yet there have been very few articles written by social scientists in this journal, and very few articles with any social content have been published. the main point is that the overwhelming understanding of emerging infections has been 'biomedical.' this is not a criticism of either the journal or of any field in public health or medicine. in large part, this is the result of the sociology of knowledge and science. for whatever reason, few social scientists have become involved in research on emerging infections, whereas the same cannot be said about chronic diseases. some researchers have asked the question of why emerging infectious diseases are emerging now and in the societies where they are emerging, and have sought a more contextual understanding of emerging infections. david bradley asks a very penetrating question: [a]ttaching a microbiological label to an outbreak. . .does not answer either the micro-scale questions such as ''why is there an outbreak here, now, of this size, affecting these people?'' nor does it answer the macro-questions such as ''why are there more (or fewer) outbreaks this decade than last?'' nor does it answer the question ''what drives the overall worldwide trends in such problems?'' (bradley, : ) for example, a number of individuals have argued that emerging infections may represent another stage in the epidemiologic transition. our understanding of emerging infections has not been totally devoid of social analysis. inequality and poverty have become a major focus for the social analysis of health and disease. the argument is that through a complicated series of pathways that are yet to be fully understood, both poverty and inequality result in poor health status. this has not been applied extensively to emerging infectious diseases, although paul farmer's ( ) insightful work has been applied to emerging infections. in his critical analysis of emerging infection, farmer asks, ''emerging for whom?'' in other words, the diseases that westerners might label as emerging may have been present or endemic in poorer societies for a long time: if certain populations have long been afflicted by these disorders, why are the diseases considered ''new'' or ''emerging''? is it simply because they have come to afflict more visible -read more ''valuable'' persons? this would seem to be an obvious question from the perspective of the haitian or african poor. (farmer, : ) in other words, farmer argues, the concept of emerging infectious diseases is one of epistemology -the theory of knowledge. how do emerging diseases come to be categorized as 'emerging'? by implication, many of these diseases have been present in poorer societies for a long time. the evidence affirms this. hiv was probably present in small foci in central africa for decades to centuries; ebola was similarly endemic in west africa for an unknown period, as was lassa fever. what is novel about the past few decades is greater interconnection between places, allowing diseases, and news of diseases, to spread; better methods of detection; and changing settlement geographies that have brought people into different forms of contact with animal reservoirs. the root cause of the infectious disease emergence is human action, both intentional and unintentional. most of this action is the result of cumulative individual acts on a mass scale. for example, the mass urbanization of society in poorer countries is the sum of millions of individuals who move from rural to urban areas. this is largely the result of the perceived economic opportunities in urban areas, and the 'push' factor of lack of opportunity in rural areas. yet, taken together, millions of individual moves result in urbanization, and this urbanization facilitates the spread of diseases by the respiratory route, the fecal-oral route, and many other modes of transmission. the institute of medicine committee also developed a set of policy recommendations. these concentrated in two areas: the need for vastly increased resources for interdisciplinary training in infectious diseases because of the depleted workforce resources in this area; and the need to develop new surveillance and public health response systems, since the committee had determined that emerging infections did, indeed, constitute a major public health threat to the united states. this report was issued with a great deal of publicity. the u.s. public's attention was already focused on emerging infectious diseases as a result of legionnaires disease, viral hemorrhagic fevers, and toxic shock syndrome. now there was a major quasi-governmental report by a group of the nation's leading scientists who issued the sobering conclusion that: even with unlimited funds, no guarantee can be offered that an emerging microbe will not spread disease and cause devastation. (institute of medicine, : ) part of the institute's report identified specific microbes and diseases that could possibly threaten public health in the future. three of these were e. coli :h , cryptosporidiosis, and hantavirus. the report was prescient, because within a few years there were serious outbreaks of all of these. in , which was the year after the iom report was issued, there was a major outbreak of cryptosporidiosis on the south side of milwaukee, wisconsin. it caused diarrhea, ranging from mild to severe, in over people. cryptosporidium parvum is a protozoan parasite; evidence in animal models is that ingestion of even one oocyst can result in severe gastrointestinal symptoms. in humans, as few as oocysts can produce these effects (king and monis, ) . it is impervious to usual methods of water treatment, and only recently has an effective medication become available. the milwaukee outbreak was probably due to groundwater absorption of cattle feces, subsequent runoff due to both heavy rains and snow melting, transport of the oocysts to river tributaries, and movement of the oocysts into lake michigan, which serves as the water supply for the south side of milwaukee. the filtration plant for that water was ineffective in eliminating the oocysts. many of these events are putative, but together they constitute a logical chain. meanwhile, research is still proceeding on the ecology of cryptosporidiosis. understanding is progressing, but it is still incomplete. e. coli :h was also mentioned in the iom report as being an emerging disease. in january , the washington state department of health ascertained that an outbreak of :h was occurring in the state, and this outbreak was associated with having eaten at jack in the box fast-food restaurants. subsequently, it became apparent that the epidemic was not limited to washington, but also included idaho and nevada. the epidemiologic investigation of this outbreak was intricate, and implicated a chain of events. first, because meat inspection in the united states was inadequate, one theory is that e. coli :h from the bowels of cattle had gotten into meat that was sent to market when cattle were slaughtered, and the bowel was probably nicked or severed. another is that under stress, cattle defecate over one another, and fecal matter from one cow can contaminate the hides of other cattle. second, when this meat was ground into hamburger, it increased the surface area of the meat by several orders of magnitude, thereby allowing the pathogen a great deal of exposure. third, once this hamburger meat was shipped to jack in the box restaurants, it appears that hamburgers were being systematically undercooked, below industry standards. this allowed the e. coli to survive and enter the hosts' systems. the consequences of such infection can be severe, and were in , with those who were symptomatic frequently suffering from bloody diarrhea, fever, cramps, and, in the worst case, hemolytic uremic syndrome. the pathogenesis of this disease was only partially understood in , but understanding is more complete in . the third disease that was mentioned in the iom report that occurred shortly after its publication was hantavirus. in may , in the four corners area of arizona, new mexico, california, and utah, several males who were otherwise in good health developed a sudden serious respiratory disease that was thought to be a rapidly progressing acute respiratory distress syndrome, since this was the immediate cause of death. however, it was noted that these cases had formed a cluster, and investigators tried to find some sort of common source to explain a possible environmental exposure to explain this serious and sometimes fatal syndrome. though hantavirus had never been described in the united states, serologic tests in patients showed a surprising seropositivity to hantavirus. it was apparent that this was the pathogen that had caused the dozen deaths associated with the outbreak. the chain of events that led up to the outbreak is now fairly clear. winter was unusually warm in the four corners area as a result of el nino, and the spring was also unusually rainy. these two conditions led to the rapid and plentiful growth of pinon trees, which provided food for a number of rodents. there is consensus that the deer mouse (peromyscus maniculatus) population increased by an order of magnitude. testing demonstrated that about % of the mice that were trapped after this epidemic were infected with hantavirus, and studies demonstrate that households from which infected individuals came were far more likely to have heavy rodent infestations than were households of controls. more rigorous studies eventually showed that transmission occurred from rats to humans, and that many of the cases, in this instance, were associated with crawling under houses and other places in which rodent exposure was likely to occur. by , many of the predictions of the first institute of medicine report ( ) had been realized, and understanding of emerging infectious diseases had improved. there was greater focus on globalization as a process of disease spread, and the attacks on the world trade center and pentagon on september , focused attention on terrorism. a new institute of medicine committee was formed to consider the nature of microbial threats and emerging diseases, and the report of this committee was issued in (institute of medicine, ) . this report represented a rethinking of the factors of emergence, and presented a more nuanced understanding of the causes of emerging diseases, most of which were still social at one level or another. bioterrorism ('intent to harm') was specifically mentioned as a factor of emergence, as was lack of political will. policy recommendations for surveillance, response, and training were more detailed than in the report, and there was a more urgent tone to the need to respond to emerging threats. in this report, the emphasis on biological and social interaction was strong: genetic and biological factors allow microbes to adapt and change, and can make humans more or less susceptible to infections. changes in the physical environment can impact on the ecology of vectors and animal reservoirs, the transmissibility of microbes, and the activities of humans that expose them to certain threats. human behavior, both individual and collective, is perhaps the most complex factor in the emergence of disease. emergence is especially complicated by social, political, and economic factors. . .which ensure that infectious diseases will continue to plague us. (institute of medicine, : ) increasing resistance to antibacterials, antivirals, and other antimicrobials is frequently grouped under the heading of 'emerging infections.' resistance is certainly a constantly growing and very major public health problem, but this is of importance to emerging infections only in the sense that diseases that were once highly treatable with first-and second-generation antimicrobials are no longer treatable by them. the selective pressures exerted by antimicrobials have made numerous pathogens resistant to even the newest antimicrobials due to mechanisms that are now understood. for example, many respiratory pathogens are no longer treatable by b-lactam antibiotics since their b-lactam rings are cleaved by b-lactamases. there are fluoroquinolone-resistant strains of neisseria gonorrhoeae, resistant strains of staphylococcus aureus, and so on. the problem is most severe in hospitals, where severe infections once responsive to vancomycin are now resistant to this glycopeptide. several new antimicrobials have been developed, in part to address vancomycin resistance, but resistance to these medications developed within a few years of their introduction. thus, antimicrobial resistance is both a community problem and a hospital problem. there is great concern over multiple drug-resistant tuberculosis, which is defined as tuberculosis that is resistant to two first-line medications, and extensively resistant tuberculosis, which has a more complex definition specifying several medications. there is not space in this article to explore antimicrobial resistance in greater depth. the relationship between people and pathogens has been an integral part of history, and will continue to be. the progress in the diagnosis, detection, and clinical management of infectious diseases has been substantial. indeed, fauci ( ) has gone so far as to argue that: the successful diagnosis, prevention, and treatment of a wide array of infectious diseases has altered the very fabric of society, providing important social, economic, and political benefits. nonetheless, infectious diseases, aggregated together, constitute the second leading cause of death worldwide, and in many regions, they account for the dominant cause. moreover, emerging diseases will continue to emerge, because of constantly changing social and demographic conditions, as well as selective pressures. the prototypical emerging infectious disease, hiv/aids, has an uncertain future in the long run. perhaps a vaccine will be developed that will be inexpensive, and perhaps distribution systems will be developed that will transport the vaccine to points of demand. perhaps antiretrovirals will become extremely inexpensive, and perhaps the failure rate for antimicrobials of % will be overcome. however, it is unlikely under present conditions that all of these improvements will occur. thus, the future of hiv/aids is more sobering. the same is true of antimicrobial resistance. in an age of optimism when antimicrobials were developed and used successfully -perhaps the first years of antimicrobial use -concern over resistance was minimal. however, the fact that organisms adapt to changing environmental conditions and threats is something that has not been realized only recently. the inevitability of adaptation is undeniable, and the only way to meet the challenges of resistance is through a combination of appropriate antimicrobial use (including the use of narrow-spectrum antibiotics as soon as possible in the clinical course of an individual) and the development of new antimicrobials, as well as new understanding in the physiology and genetics of microorganisms, which might lead to the development of new technologies in addressing the pathogenic basis of disease. see also: aids, epidemiology and surveillance; antimicrobial resistance; severe acute respiratory syndrome (sars); transmissible spongiform encephalopathies; tuberculosis: overview; west nile disease. acromegaly a condition produced by overproduction of growth hormone, leading to excessive growth of the hands, feet, and jaw in postpubertal individuals and giantism in prepubertal children. adrenal glands two endocrine organs situated above the kidneys that make a series of hormones: cortisol (stress hormone), aldosterone (salt-retaining hormone), and catecholamines (stress hormones). autoimmunity a situation in which part of the body, often an endocrine organ, is recognized as 'foreign,' triggering an immune response that tends to lead to destruction of the endocrine gland. cushing syndrome excessive production of cortisol with loss of the normal circadian variation leading to weight gain, hypertension, and type diabetes mellitus. g protein proteins within the cell that transfer the hormone message from the receptor to specific parts of the cell. graves disease a combination of thyroid overactivity due to an autoimmune disorder and eye problems. hypothalamus part of the brain containing control centers for appetite, thirst, and pituitary hormone secretion. pituitary major regulator of hormone production. secretion of hormones regulated by the hypothalamus. severe acute respiratory syndrome (sars): paradigm of an emerging viral infection new and resurgent infectious: prediction, detection, and management of tomorrow's epidemics infections and inequalities: the modern plagues infectious diseases: considerations for the st century emerging infections: microbial threats to health in the united states microbial threats to health critical processes affecting cryptosporidium oocyst survival in the environment living with bse fruit bats as reservoirs of ebola virus plagues and peoples factors in the emergence of infectious diseases lassa fever: epidemiology, clinical features, and social consequences variant creutzfeldt-jakob disease sars molecular epidemiology: a chinese fairy tale of controlling an emerging zoonotic disease in the genomics era the coming plague: newly emerging diseases in a world out of balance new and resurgent infections: prediction, detection, and management of tomorrow's epidemics the changing face of disease: implications for society the challenge of emerging and re-emerging infectious diseases an emptying quiver: antimicrobial drugs and resistance the politics of emerging and resurgent infectious diseases disease in evolution: global changes and emergence of infectious diseases endocrine diseases: overview p c hindmarsh key: cord- -kummh g authors: nachega, jean b.; leisegang, rory; kallay, oscar; mills, edward j.; zumla, alimuddin; lester, richard t. title: mobile health technology for enhancing the covid- response in africa: a potential game changer? date: - - journal: am j trop med hyg doi: . /ajtmh. - sha: doc_id: cord_uid: kummh g mobile health technology for enhancing the covid- response in africa: a potential game changer? the who africa region is experiencing an increase in the number of novel covid- cases. as of may , , , cases with , deaths ( . % case fatality) have been reported from countries. although these numbers are small compared with those in united states or europe, the who recently estimated that up to , people could die of covid- in africa if the pandemic is not controlled. these projections are threatening the already overstretched health services in africa, where governments have been implementing mitigating strategies to flatten epidemic curves at manageable levels. these include education, personal hygiene practices, social distancing, travel bans, and partial or total lockdowns. however, as lockdowns and social distancing measures are currently being lifted in stages by most african countries, governments will need to ensure that public health infrastructure and needed resources are put in place for community surveillance to identify cases and clusters of new infections through active case finding, large-scale testing, and contact tracing. cost-efficient testing strategies with rapid turnaround and community-based contact-tracing approaches are cornerstones for containment during epidemics. to do so at scale and over the anticipated prolonged course of this pandemic, african countries will need to capitalize on digital health innovations. [ ] [ ] [ ] the global system for mobile communication association reports that % of africans own mobile phones and that % are internet-connected, numbers which are rapidly increasing, and approach % access when phone-sharing is considered. mobile phone technology (mhealth) platforms are effective in improving service delivery and outcomes for many health conditions in africa and globally, including hiv infection, tuberculosis, and chronic noncommunicable diseases. [ ] [ ] [ ] [ ] in the context of covid- , mhealth solutions offer opportunities to directly support public education, case management, and contact tracing, and to perhaps even provide geolocation and exposure notification. , with the support of global mobile technology companies and small and medium enterprises within africa, mhealth offers opportunities ranging from text messaging to mobile apps to mitigate the spread of covid- . the use of mobile phones reduces the need for physical contact, exchange of materials, and movement by health workers, and thus maximizes safety. several ongoing digital and mobile initiatives related to covid- have been identified across africa ( figure ). district health information software is an open-source, web-based health management information system platform already used by low-and middle-income countries. district health information software has a covid- -specific application package that several african countries are using for field data collection. in rwanda and uganda, the weltel virtual care system serves as a real-time remote monitoring platform. covid- cases and contacts in home isolation receive semi-automated daily text message check-ins via sms for weeks using an open language format, allowing self-reporting of new symptoms or issues. responses are viewed by health officials on a dashboard, and patients are triaged much faster than would be the case with traditional field outreach or telephone calls, saving critical human resource capacity. novel natural language processing computing tools promise to reveal insights into the issues that patients face during home quarantine. the provision of monitoring packaged with interactive support helps people undertake home isolation/quarantine most effectively. in ghana, a short ussd code (* * #) dialed on mobile phones allows residents to respond electronically to questions about their symptoms, who they have been in contact with, and their travel history. the opine health assistant compiles the results into maps and graphs to make it easier to understand, monitor, and share. in senegal, sms services are used to broadcast good hygiene practices to rural communities to disrupt the spread of covid- . in south africa, community screening, referral for testing, and communication of results of using an mhealth platform are being rapidly expanded to more than , trained community health workers. mobile phones and apps also support livelihoods and enable remote access to critical services such as education and food. in kenya, transaction fees for using m-pesa, a cashless, mobile money platform with million users, have been waived to provide a safe method by which to transfer funds within community settings. in south africa, mobile data costs of accessing some teaching and learning websites have been waived by major cellphone providers to ensure that primary and secondary school and university students can continue to access learning materials. globally, mobile counseling, support hotline, and social media platforms are assisting with public health information as well as mental health counseling, food relief, domestic violence concerns, and other support. government and private alignment within these platforms should be encouraged, as oversight by public health agencies will ensure accurate content. in conclusion, there appears to be a limited window of opportunity in which to contain the spread of covid- in africa and keep economies afloat. there is a significant body of innovation and evidence to inform mhealth best practices that have emerged from africa over the past decade. - mhealth may be a game changer if it is introduced swiftly and widely in this pandemic. to succeed, barriers to access to and use of mobile phones and the latest technologies need to be defined, and there must be cooperation among all stakeholders to enable rapid deployment and scale-up of promising or evidencebased solutions. if mhealth is rigorously implemented, scaledup, and evaluated through implementation science, then africa will reap the benefits of this technology for the remainder of the covid- crisis and be better positioned for future pandemics and for improving all aspects of public health. publication charges for this article were waived due to the ongoing pandemic of covid- . coronavirus disease (covid- ) situation reports new who estimates: up to people could die of covid- in africa if not controlled the late arrival of covid- in africa -mitigating pan-continental spread effects of a mobile phone short message service on antiretroviral treatment adherence in kenya (weltel kenya ): a randomised trial sub-saharan africa-the new breeding ground for global digital health africa: opportunities for growth mobile phone penetration through sub-saharan africa covid- surveillance digital data package get virtual care for your covid- response institute of ict professionals ghana. . how ussd code is breaking grounds in ghana -part covid- : our response in senegal south africa is hunting down coronavirus with thousands of health workers mobile phone-delivered reminders and incentives to improve childhood immunisation coverage and timeliness in kenya (m-simu): a cluster randomised controlled trial a hybrid mobile approach for populationwide hiv testing in rural east africa: an observational study controlling ebola through mhealth strategies covid- and mobile health technology in africa key: cord- -u rzp h authors: barrett, claire l. title: primary healthcare practitioners and patient blood management in africa in the time of coronavirus disease : safeguarding the blood supply date: - - journal: afr j prim health care fam med doi: . /phcfm.v i . sha: doc_id: cord_uid: u rzp h the coronavirus disease (covid- ) pandemic has highlighted various weaknesses in global healthcare services. the blood supply in africa is a critical element of the healthcare service that may be significantly affected by the pandemic. by implementing principles of patient blood management, primary healthcare practitioners may play an important role in the resilience of the blood supply during the covid- pandemic. tomorrow belongs to the people who prepare for it today. (african proverb) the world health organization (who) defines resilience in the context of the provision of essential health and health-related services as 'the inbuilt capacity of the system to sustain provision of essential health and health-related services even when challenged by outbreaks, disasters or other shocks'. the coronavirus disease (covid- ) pandemic will undoubtedly test the global resilience of the blood supply, and significantly so in africa. the primary healthcare practitioner plays a crucial role in reducing the burden of anaemia, thus safeguarding the blood supply in africa. the covid- pandemic showcases weaknesses, shortcomings and lack of resilience in global healthcare services. whilst commendable work has been performed in health disaster risk management in africa, and recommendations made on how to maintain the blood supply during infectious outbreaks and the covid- pandemic, , no recommendation can entirely safeguard the blood supply. many countries have well-established healthcare systems and access safe blood, yet this is not true for most of africa. although the demand for blood is high, blood donation rates are very low, especially in low and lower middle-income countries in africa. a third of maternal deaths in sub-saharan africa are because of maternal haemorrhage, and this region has the highest maternal mortality in the world. access to blood may have prevented up to a quarter of these deaths. , in spite of this, many countries in africa collect less than donations per population, the target recommended by the who. twenty-two african countries depend on family, replacement or paid donors, and these donations account for more than % of the blood supply. these challenges, although important, are unlikely to be resolved in the midst of the pandemic. blood donation may well be further reduced because of donor illness, countries imposing travel restrictions and donor fear of contracting the virus by visiting donor centres. the who has published guidelines to ensure the safety of blood donors and staff during the pandemic, and donors should be reassured that they are unlikely to contract the novel coronavirus by donating blood when correct procedures are followed. road safety has improved as a result of covid- because of enforced travel restrictions, which has translated to fewer road traffic accidents (rtas) in south africa , and abroad. although little data are available on the indications for the use of blood and blood products in africa, infectious diseases, obstetric haemorrhage, sickle cell disease and the broad term anaemia are the most common indications for transfusion. in south africa, relatively few blood products are issued for general surgery and trauma, ( . % and . %, respectively), and the bulk of blood products are issued to medical patients, obstetrics and gynaecology and intensive care units the coronavirus disease (covid- ) pandemic has highlighted various weaknesses in global healthcare services. the blood supply in africa is a critical element of the healthcare service that may be significantly affected by the pandemic. by implementing principles of patient blood management, primary healthcare practitioners may play an important role in the resilience of the blood supply during the covid- pandemic. keywords: blood supply; patient blood management; africa; covid- ; resilience; transfusion. read online: scan this qr code with your smart phone or mobile device to read online. note: special collection: covid- . ( . %, . % and . %, respectively), which is in agreement with previous observation. these data suggest that even though lockdown may reduce the number of rtas, the need for blood will persist. this emphasises the need for a sustained blood supply that relies on uninterrupted blood donation, component production, appropriate clinical use of blood and blood products, as well as the implementation of patient blood management (pbm) programmes to alleviate anticipated shortages of donor blood. implementation of the principles of pbm may prove to be a vital step in maintaining a sustainable blood supply in africa in the face of the pandemic. patient blood management is defined by the who as 'a patientfocussed, evidence-based and systematic approach to optimise the management of patient and transfusion of blood products for quality and effective patient care'. in addition, the who emphasises that pbm should minimise unnecessary exposure to blood products and, through health promotion and screening, prevent conditions that may result in the need for transfusion. patient blood management is built on three pillars: optimisation of erythropoiesis, minimisation of blood loss, and bleeding and harnessing and optimising physiological reserve of anaemia. whilst pbm has been shown to be reduce the need for transfusion, reduce costs and improve patient safety and clinical outcomes, the implementation thereof has lagged behind. , , for the most part, where pbm has been adopted, it has been incorporated into the practice of anaesthetists, surgeons, physicians, intensivists, and obstetricians and gynaecologists. in these disciplines, the focus has been on the identification and management of anaemia and bleeding risk, appropriate and conservative use of blood products and alternatives to transfusion. these are the key elements of pbm; however, conservative transfusion triggers are the norm in most of africa, and the traditional approach to pbm may only aid a minority of patients who have access to hospital and specialist care. in spite of efforts by the who, the burden of anaemia is high in africa, particularly east sub-saharan africa. iron deficiency, malaria, schistosomiasis, hookworm, sickle cell disease and thalassemia are the main causes of anaemia in africa. many of these conditions are managed by the primary healthcare practitioner, who should thus play a pivotal part in the implementation of pbm in the outpatient setting. table is adapted from the three-pillar approach from isbister and spahn, , reworked for use by primary healthcare practitioners in the outpatient setting in africa. these recommendations are contextualised in light of the pandemic and can be applied to all patients who access who-compliant priority services, including the care of pregnant women, and patients who access care for emergency conditions, vaccination and the acceptable auxiliary services. whilst it is acknowledged that transfusion cannot be avoided in patients with certain conditions and that many patients will still require transfusion as part of their standard care, the application of these principles may reduce the number of transfusions a potential transfusion recipient would need, and may thereby safeguard the blood supply for those who need it most. the 'common-sense' principles that underpin pbm have been recommended to address regional and national shortages of blood during the pandemic. primary healthcare practitioners may play an important role in the resilience of the blood supply during the covid- pandemic. the principles of pbm outlined in this article are inexpensive and relatively easy to implement. if these principles are applied to all patients who receive primary healthcare during the pandemic, the blood supply may be safeguarded for those who need it most. world health organization. the state of health in the who african region: an analysis of the status of health, health services and health systems in the context of the sustainable development goals strengthening health disaster risk management in africa: multi-sectoral and people-centred approaches are required in the post-hyogo framework of action era protecting the blood supply during infectious disease outbreaks world health organization. maintaining a safe and adequate blood supply during the pandemic outbreak of coronavirus disease (covid- ): interim guidance world health organization and international federation of red cross and red crescent societies. towards % voluntary blood donation: a global framework for action van look pf. who analysis of causes of maternal death: a systematic review trends and gaps in national blood transfusion services - sub-saharan african countries geneva: who sa records road crashes with fatalities over easter weekend. the citizen fikile mbalula reports easter road death toll plunges % california covid- traffic report finds silver lining | uc davis. sci tech [serial online blood transfusion in sub-saharan africa: understanding the missing gap and responding to present and future challenges towards the future of blood transfusion -the south african national blood service's perspectives on cellular therapeutic services and products the essential role of patient blood management in a pandemic: a call for action anesth analg global forum for blood safety: patient blood management (pbm) structured observations the three-pillar matrix of patient blood management -an overview patient blood management -a new paradigm for transfusion medicine? multimodal patient blood management program based on a three-pillar strategy: a systematic review and meta-analysis a systematic analysis of global anemia burden from to alternatives to blood transfusion. lancet [serial online the isth bleeding assessment tool and the risk of future bleeding operational guidance for maintaining essential health services during an outbreak prof. colleen aldous for encouraging me to write the article. the author has declared that no competing interest exists. i declare that i am the sole author of this research article. this article used data and information from the public domain and primary authors are cited where appropriate. this research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. data sharing is not applicable to this article as no new data were created or analysed in this study. the views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of any affiliated agency of the author. key: cord- -p svmfr authors: mehtar, shaheen; preiser, wolfgang; lakhe, ndèye aissatou; bousso, abdoulaye; tamfum, jean-jacques muyembe; kallay, oscar; seydi, moussa; zumla, alimuddin; nachega, jean b title: limiting the spread of covid- in africa: one size mitigation strategies do not fit all countries date: - - journal: lancet glob health doi: . /s - x( ) - sha: doc_id: cord_uid: p svmfr nan limiting the spread of covid- in africa : one size mitigation strategies do not fit all countries on march , , when coronavirus disease (covid- ), caused by severe acute respiratory syndrome coronavirus (sars-cov- ), was declared a pandemic by who, there were comparatively few cases reported from africa. our comment draws on early imported covid- cases in south africa, senegal, democratic republic of the congo, and egypt as case studies to discuss important mitigation strategies of covid- in africa. early covid- cases in africa were mostly imported from europe, due to the higher volume of business and tourism airline traffic between african countries and europe, and less from china. the first confirmed case was reported in egypt on feb , , (an adult male whose contacts tested negative) and prompted african preparedness efforts. , in south africa, on feb , , a group of nine adult travellers returned from a skiing holiday in italy, where the covid- epidemic was rampant. after developing a flu-like illness, one traveller tested positive for covid- , which was confirmed by rt-pcr on march , ; his wife was asymptomatic but tested positive on march , . overall, seven of the nine travellers were positive for covid- , five of whom were asymptomatic. in senegal, the first covid- case was reported on march , , in a traveller returning from italy. contact tracing identified a cluster of transmission of cases within his immediate household. democratic republic of the congo confirmed its first case of covid- on march , : an adult male who tested positive in the capital city of kinshasa after developing a cough and fever, days after returning from france. these early index cases show the imported nature of the epidemic in africa among young affluent adult travellers from europe. however, the majority of covid- cases currently being identified and reported from african countries are due to local transmission. early estimates of case fatality rates (cfrs) also seem to vary substantially. as of april , , south africa had reported cases with deaths (cfr · %) and senegal had reported cases with deaths (cfr · %). these cfrs seem lower than in most european countries (eg, italy had reported cases with deaths; cfr · %). since mortality rates are generally higher in older people, it could be assumed that a younger african population distribution will lessen the death rate of covid- on the continent. however, it is too early to predict the death rate as africa is at the ascending phase of the epidemic curve. furthermore, the high prevalence of hiv, tuberculosis, hypertension, and diabetes, coupled with weak healthcare systems in africa, might lead to high mortality rates among comorbid populations. indeed, egypt ( cases with deaths; cfr · %) and democratic republic of the congo ( cases with deaths; cfr · %) have reported much higher cfrs than south africa and senegal. since the emergence of covid- on the continent, african governments have had to decide whether, in addition to following who recommendations to test widely, contact trace, and quarantine, they would adopt draconian measures such as total lockdowns, stay at home to save lives campaigns, and travel and movement restrictions as has been done in european and asian countries. physical distancing and handwashing, globally adopted interventions to combat the spread of covid- , remain a major challenge in the context of overcrowding, poverty, and weak health-care systems. a combination model of countryspecific economic estimates of the benefits of disease avoidance and epidemiological projections of the spread of covid- raises several possible issues. first, the benefits of physical distancing could be substantially smaller in low-income countries due to the smaller proportions of older people and because, although physical distancing and lockdowns flatten the epidemic curve and reduce pressure on health systems, this effect is less apparent in countries with already overwhelmed and weak health-care systems. second, the economic value in terms of lives saved by physical distancing policies is likely to be much higher in high-income countries than countries in which these policies have more detrimental effects on incomes. although physical distancing slows the transmission of the virus, it exacts a heavy toll on the informal economic and casual labour sector. in search of income for the day-to-day livelihood of extended families, many africans could be forced to ignore concerns about contracting covid- and fend for their survival. furthermore, the effect of ongoing lockdowns (eg, partial in senegal and democratic republic of the congo vs total in south africa) and case-finding mitigation strategies will depend on each country's political leadership, socioeconomic realities, and epidemic stage. early evidence of flattening the epidemic curve through a proactive, -day total lockdown and physical distancing is being documented in south africa. however, before physical distancing measures can be eased, it is crucial to have in place a robust and functioning public health infrastructure to scale up case finding through testing, isolation, and contact tracing to ultimately interrupt coronavirus transmission. to reduce the rate of infections, the south african national health laboratory service is planning to administer rt-pcr-based tests per day by the end of april and more than trained community healthworkers will be sent house-to-house in susceptible communities for screening, testing, and contact tracing using mobile phone technology assisted by médecins sans frontières. notably, point-of-care rt-pcr-based xpert xpress sars-cov- testing with a fast turnaround ( min) using small genexpert machines (cepheid, sunnyvale, ca, usa), ideal for mass community testing, will be available in south africa by the end of april, . as covid- spreads across africa, causing disruption of already fragile health systems, it is becoming clear that responses require action beyond the health sector and must be tailored to the local situation. lacking governmental financial support, as is being provided for populations and businesses in europe and usa, most of africa's poorest citizens will ignore quarantine directives and continue to engage in communal activities to earn incomes for their families. some countries must also provide for other vulnerable populations such as migrants, stateless people, and forcibly displaced refugees. as larger datasets are generated by increasing case numbers in africa and while vaccines are awaited, factors which underlie asymptomatic or milder clinical presentations and any differences of mortality or severe disease between geographical regions of africa need to be investigated further to find local solutions. possible factors include innate immune mechanisms, hla types, effects of the bcg vaccination, cross-protective immunity due to repeated infections with other coronavirus species that cause mild upper respiratory tract infections or locally prevalent parasitic infections. these factors could ultimately provide clues to the development of preventive and therapeutic interventions for covid- relevant to africa and beyond. in conclusion, while african leaders ponder covid- mitigation strategies to reduce risks of transmission versus the deprivation and hunger that will result from prolonged economic disruption, the quest for solutions must continue. some countries are investing in low-cost preventive measures to improve physical distancing, such as stopping international travel, reducing the number of people at religious and social gatherings, and universal masking using non-medical cloth masks for the community. other measures could focus on protecting older people, allowing individuals restricted working hours for income generation, information campaigns for personal hygiene, physical distancing, and handwashing. as lockdowns and physical distancing measures are eased, proactive surveillance, case detection, and contact tracing with isolation will be required to prevent a dramatic resurgence of covid- cases. sm and wp are members of the ministerial advisory committee on covid- in south africa. jbn is supported by the us national institutes of health (nih) and national institutes of allergy and infectious diseases (grant number u ai ; stellenbosch university clinical trial unit of aids clinical trial group; and nih or fogarty international center grant numbers r tw - and d tw - a ); is a co-principal investigator of together, an adaptive randomised clinical trial of novel agents for treatment of high-risk outpatient covid- patients in south africa, supported by the bill & melinda gates foundation; is the chair of the research committee of the african forum for research and education in health; and is a senior fellow alumni of the european developing countries clinical trial partnership (edctp). az is a co-principal investigator of the pan-african network on emerging and re-emerging infections, which is funded by the edctp , the european union horizon framework programme for research and innovation; and is also in receipt of a nih research senior investigator award. ms is a member of the covid- task force response in senegal. j-jmt is leading the covid- task force response in the democratic republic of the congo. nal, ab, and ok declare no competing interests. infection control africa network, cape town, south africa (sm); national health laboratory service tygerberg service de maladies infectieuses et tropicales centre des opérations d'urgences sanitaires du sénégal ); department of epidemiology and international health director-general's opening remarks at the media briefing on covid- - who. coronavirus disease (covid- ) situation reports looming threat of covid- infection in africa: act collectively, and fast is africa prepared for tackling the covid- (sars-cov- ) epidemic. lessons from past outbreaks, ongoing pan-african public health efforts, and implications for the future the global impact of covid- and strategies for mitigation and suppression imperial college covid- response team scientific and ethical basis for social-distancing interventions against covid- should low-income countries impose the same social distancing guidelines as europe and north america to halt the spread of covid- ? safeguarding access to healthcare during covid- covid- ) update: fda issues first emergency use authorization for point of care diagnostic the prospects for the sars-cov- pandemic in africa key: cord- -d uem authors: hatefi, shahrokh; smith, farouk; abou-el-hossein, khaled; alizargar, javad title: covid- in south africa: lockdown strategy and its effects on public health and other contagious diseases date: - - journal: public health doi: . /j.puhe. . . sha: doc_id: cord_uid: d uem nan the current global pandemic of the novel coronavirus (covid- ) is severely affecting the global health system. there is no treatment or vaccine available for covid- yet. since the world health organization (who) announced the pandemic of covid- , many countries have announced new social distancing and lockdown rules to control the spread rate of the deadly covid- virus. according to the international health regulation (ihr) monitoring and evaluation framework, some african countries such as south africa, egypt, and algeria have demonstrated the highest risk of importation rate, and an average risk profile to fight against highly contagious diseases [ ] . african countries, with previous experiences on the outbreaks of other infectious disease and pandemic situations, including hiv, malaria, and ebola, have limited financial, physical, and medical resources. in addition, there have been major problems related to the weak public healthcare and healthcare management systems in countries across africa [ ] . in many low-and middle-income countries, the lockdown strategy were implemented to decrease the rate of the covid- outbreak. although lockdown strategies across many countries have been effective for decreasing the spread rate of contagious viruses, there have been other negative impacts reported globally; these concerns become worse in countries across africa, including south africa. for example, it has been reported that hiv care has been negatively affected by the current covid- pandemic. additionally, hiv transmission accelerated among poorer people and young women during lockdown [ ] . there are also psychological problems associated with long-term lockdown strategies [ ] . in south africa, the government announced a national-wide lockdown to manage the pandemic situation and decrease the spread rate of the covid- outbreak. however, due to limited available resources, as well as negative impacts of the lockdown strategy, the lockdown levels have been eased, twice. with regard to the current global situation during the covid- pandemic, different concerns in the public health system of south african people have been raised. the major concerns are summarized as follows: first, south africa's national lockdown started on the th of march. due to various deficiencies, limited resources and financial means, the south african government has no other option but to ease the lockdown strategy and related rules. currently, the level of lockdown in south africa is at level three out of five levels of severity. however, according to the south africa national institute for communicable diseases (https://nicd.ac.za), the spread rate of the covid- outbreak is increasing. second, the lockdown strategy, social distancing rules, and community containment measures for covid- have negatively impacted the diagnosing and treatment of other contagious diseases, including hiv and malaria [ , ] . in addition, in this pandemic situation, allocating resources for hiv care, including antiviral medication and allocating hospital beds for hiv patients, would be more limited. third, more than children under the age of have tested covid- positive already. the covid- pandemic is severely affecting the young population of south africa, including maternal and infant children [ ] . fourth, in south africa the winter season is starting. studies already undertaken reported the correlation between the sunlight and the rate of covid- recovery [ ] ; the studies suggest that sunlight exposure increase the rate of recoveries in covid- patients. therefore, a longer recovery period for patients is anticipated. with regard to the concerns raised and the results of analyzed data, it can be predicted that the situation of south africa in fighting against covid- will become worse in the future. the daily fatality rate as well as the number of daily confirmed covid- cases is starting to increase dramatically. therefore, we urge a global collaboration in terms of providing essential resources and developing novel solutions to fight the covid- pandemic in south africa. we recommend that all governments and organizations start an international collaboration to maintain the healthcare plans across the world, in order to avoid disruption of the routine healthcare services. covid- is a global pandemic; the reaction to this situation should be at global levels. science and state-of-the-art technologies in all the scientific as well as social fields need to be combined to produce effective solutions to fight the covid- pandemic. many low-and middle-income countries, including african and middle eastern countries lack essential resources. in the covid- pandemic, increasing the outbreaks of viral infections in any country would affect the global health system negatively. therefore, measures, prevention solutions, resources, medical equipment, and medication should be developed and provided to people equally all across the world. the authors declare that there are no competing interests. limiting the spread of covid- in africa: one size mitigation strategies do not fit all countries. the lancet global health covid- response in the middle east and north africa: challenges and paths forward. the lancet global health three lessons for the covid- response from pandemic hiv. the lancet hiv early estimates of the indirect effects of the covid- pandemic on maternal and child mortality in low-income and middle-income countries: a modelling study. the lancet global health maintaining hiv care during the covid- pandemic. the lancet hiv diagnosing malaria and other febrile illnesses during the covid- pandemic. the lancet global health sunlight exposure increased covid- recovery rates: a study in the central pandemic area of indonesia key: cord- - dfob wi authors: estrada, alejandro; garber, paul a.; chaudhary, abhishek title: current and future trends in socio-economic, demographic and governance factors affecting global primate conservation date: - - journal: peerj doi: . /peerj. sha: doc_id: cord_uid: dfob wi currently, ~ % of extant primate species (ca species) distributed in countries in the neotropics, mainland africa, madagascar, south asia and southeast asia are threatened with extinction and % have declining populations as a result of deforestation and habitat loss resulting from increasing global market demands, and land conversion for industrial agriculture, cattle production and natural resource extraction. other pressures that negatively impact primates are unsustainable bushmeat hunting, the illegal trade of primates as pets and as body parts, expanding road networks in previously isolated areas, zoonotic disease transmission and climate change. here we examine current and future trends in several socio-economic factors directly or indirectly affecting primates to further our understanding of the interdependent relationship between human well-being, sustainable development, and primate population persistence. we found that between and ca mha of tropical forest ( % canopy cover) were lost as a result of human activities in the five primate range regions. forty-six percent of this loss was in the neotropics (mexico, central and south america), % in southeast asia, % in mainland africa, % in madagascar and % in south asia. countries with the greatest losses (ca % of total tree cover loss) were brazil, indonesia, drc, china, and malaysia. together these countries harbor almost % of all extant primate species. in , the world human population was estimated at ca bn people, ca % of which were found in primate range countries. projections to and to indicate continued rapid growth of the human populations in these five primate range regions, with africa surpassing all the other regions and totaling ca bn people by the year . socioeconomic indicators show that, compared to developed nations, most primate range countries are characterized by high levels of poverty and income inequality, low human development, low food security, high levels of corruption and weak governance. models of shared socioeconomic pathway scenarios (ssps) projected to and showed that whereas practices of increasing inequality (ssp ) or unconstrained growth in economic output and energy use (ssp ) are projected to have dire consequences for human well-being and primate survivorship, practices of sustainability-focused growth and equality (ssp ) are expected to have a positive effect on maintaining biodiversity, protecting environments, and improving the human condition. these results stress that improving the well-being, health, and security of the current and future human populations in primate range countries are of paramount importance if we are to move forward with effective policies to protect the world’s primate species and promote biodiversity conservation. a growing global human population and expanding economic activities are exerting unsustainable demands on natural resource extraction and the conversion of forested land for industrial agriculture, cattle production, and the expansion of urban centers (rockström et al., ; crist, mora & engelman, ; crist, ; https://populationmatters.org/the-issue). these pressures are negatively impacting critical global commons needed to sustain life on earth through air, water, and soil pollution, carbon emissions, deforestation and the critical loss of biodiversity (rockström et al., ; otero et al., ; ungef, ) . for example, the atmosphere is being degraded by increased greenhouse gas emissions, ocean acidification is increasing, and tropical forests are being cut at a rate of ca million ha per year (rockström et al., ; steffen et al., ; gfw, ) . regrettably, recent estimates indicate that some one million animal and plant species are threatened with extinction as a result of human activities (ipbes, ) . this includes many of the world's non-human primates, our closest living biological relatives. primates represent the third most speciose mammalian radiation (ca species; estrada et al., ) after bats and rodents. they (prosimians, tarsiers, monkeys and apes) are distributed across countries, principally in the neotropics, mainland africa, madagascar, south asia and southeast asia, and are a critical part of our planet's biodiversity ( fig. ; table s ). primates are essential models for understanding human evolution, behavior and health (phillips et al., ) . the activities of lemur, lorises, tarsiers, monkeys and apes sustain a range of community-wide ecological functions and services (e.g., seed dispersal, pollination, predator-prey relationships) in tropical and temperate forests, that also benefit local human communities (estrada et al., ) . alarmingly, % of primate species are threatened with extinction and % have declining populations as a result of relentless human pressures on natural environments leading to widespread loss and degradation of tropical forests (estrada et al., ; iucn red list, ) (table s ) . a major driver of primate population decline is land use changes driven by global market demands. this has resulted in the widespread loss of primate habitats in order to expand agricultural and cattle production, and the extraction of natural resources (e.g., minerals, oil, wood) to feed and sustain a growing global human population (now ca billion set to approach ca billion by ; https://www.un.org/en/sections/ issues-depth/population/) and a rapidly expanding global middle-class diet that emphasizes greater meat consumption (ungef, ) . hunting for bushmeat, the illegal primate trade, infectious disease transmission among humans-domesticated animals-wild animals, and the spread of invasive species constitute important additional pressures that negatively impact primate populations (iucn red list, ; estrada et al., ; lappin et al., ) . recent evidence suggests that the human population has expanded beyond the earth's sustainable means and that we are using resources faster than our planet can regenerate, with devastating consequences (steffen et al., ) . it took humanity ca , years to go from an estimated population size of a few hundred thousand to a population size of one billion, and just years to go from one billion to a population size of almost eight billion (population matters, ) . at present we are adding close to million people each year, as the world moves towards a human population that may exceed billion by (undesa, a). while a growing global human population and activities associated with land conversion have historically been the major factors contributing to global biodiversity loss via deforestation, habitat degradation and resource extraction activities (ipbes, ) , it is clear that initiatives solely designed to limit human population growth as a means to solve immediate environmental problems are largely unrealistic (bradshaw & brook, ) . for example, brazil, a country suffering significant deforestation in past decades has one of the lowest population growth rates among the countries that harbor primates. also, extensive deforestation in brazil has occurred in both highly populated areas (i.e., the atlantic forest, the cerrado), as well as in areas of extremely low population density figure geographic distribution of primate species richness. species richness in the main regions where primates are naturally found: the neotropics, mainland africa (includes small associated islands), madagascar, south asia, and southeast asia. the country colors indicate the number of primate species in each country. number by each region indicates the regional number of primate species. madagascar stands out with its rich and endemic lemur fauna. black dots in open spaces between continents are small islands. source of information: (estrada et al., ; iucn red list, ) . raw data in table s . full-size  doi: . /peerj. / fig- such as the amazon. the reasons for deforestation and consequent biodiversity impacts in brazil and other countries represent a combination of historical, economic, political and social factors. here we use the i = pat framework, which examines the environmental impact (i) as a function of population (p), affluence (a) and technology (t) (see for example, dietz & rosa, ) . to further our understanding of the interdependent relationship between human well-being and primate population persistence, we examine current and future trends in several socio-economic, ecological and demographic indicators in countries within primate range regions. these are: tropical forest loss, human population, gdp per capita, human development index (hdi), extreme poverty, food security, corruption, governance quality and civil unrest/conflict status. we acknowledge that our review of these indicators is by no means complete and primate conservation requires global action to limit both the long-term environmental and economic footprint of the world's human population, and the overconsumption of natural resources from the tropics by citizens in a small number of developed nations (estrada, garber & chaudhary, ) . finally, by focusing on the level of primate regions rather than individual countries, our manuscript emphasizes broad patterns rather than country-specific historical, demographic, cultural, and religious factors that affect primate survivorship. it is in light of these considerations that we present our evaluation. the information we present is based on a review of the literature and analysis of information from several open access databases. these latter sources are listed below. our analysis of these databases included information on each of the countries that harbor wild primate populations. for purposes of this evaluation we consider the following regions as discrete entities due to their unique primate fauna: the neotropics (mexico, central and south american tropics), mainland africa (including small islands off its atlantic coast), madagascar, south asia and southeast asia. because madagascar harbors a nonoverlapping set of the world's nonhuman primate species (i.e., some endemic lemur species), the result of over million years of isolation from the african continent, it merits separate evaluation. information on the conservation status of living primates is from estrada et al., and from the international union for the conservation of nature https://www.iucnredlist.org/ (iucn red list, ). we report human population growth from to in each primate range country (n = ) based on information from the world bank (https://data.worldbank.org/ indicator/sp.pop.totl) and from the un population division (https://population.un. org/wpp/download/standard/population). human population growth projections for and were obtained from the un population division (https://ourworldindata. org/grapher/un-population-projection-medium-variant). additional information on population growth trends was obtained from the un e-handbook of statistics (https://stats.unctad.org/handbook/population/total.html). we describe the extent of tropical forest loss in primate range countries from to using data from the open access global forest watch database (http://www.globalforestwatch.org/). these estimates are based on remote sensing procedures. we use the gross domestic product per capita (gdppc) for the period from to as an indicator of economic progress in each primate range country. this metric was obtained from the world bank socioeconomic indicators (https://data.worldbank.org/ indicator/ny.gdp.pcap.cd). we are aware of the limitations of using the gdppc as a measure of economic development. this indicator is an average, and consequently overlooks the distribution of incomes across each country. in this regard, the gdppc of a country may be high or above that of another country, however, most of that wealth could be concentrated in a relatively small number of individuals or families, with the overwhelming majority of citizens extremely poor. examples of high levels of income inequality in primate range nations include china, brazil and drc (estrada et al., ) . we used information from the international institute for applied systems analysis (iiasa) sspd database (https://tntcat.iiasa.ac.at/sspdb/dsd?action=htmlpage&page=about) (table s ) to model future projections of gdppc for all primate hosting countries under different shared socioeconomic pathways scenarios (ssps). data used to examine human development in primate range countries ( - ) were from the un hdi, which represents a combined measure of life expectancy, school enrollment, literacy, and income. hdi ranges from (lowest) to (highest) (http://worldpopulationreview.com/countries/hdi-by-country/). we used the world bank percent of the population living on <us $ . a day as an indicator of extreme poverty in primate range regions. data were sourced from the world bank and include information for europe and north america (us and canada) and the world average (https://data.worldbank.org/indicator/si.pov.dday). as a complementary indicator of poverty, we used the under-five mortality rate in primate range countries. data were harvested from the world bank (https://data.worldbank.org/indicator/sh.dth.mort). we assessed food security in primate range regions by using the internationally accepted standard, the global food security index (gfsi) of the economist intelligence unit limited (https://foodsecurityindex.eiu.com/index). the index integrates the core issues of affordability, availability, quality and safety into a quantitative and qualitative model that evaluates these drivers of food security in developing and developed countries. the index also considers a country's exposure to the impacts of a changing climate; its susceptibility to natural resource risks; and how the country is adapting to these risks. the gfsi is based on data from countries and ranges from zero (lowest food security) to (highest food security) (https://foodsecurityindex.eiu.com/index). to document patterns of corruption, we gathered information for each primate range country from the corruption perceptions index (cpi) of transparency international (https://www.transparency.org). we evaluated governance quality in primate range regions for using the values of four indicators of governance quality (political stability and absence of violence/ terrorism, government effectiveness, rule of law, and control of corruption) provided by the world bank (http://info.worldbank.org/governance/wgi/index.aspx#reports). we compared these values to the average values of high-income countries. we examined civil conflict in primate range countries by using the global peace index (gpi) of the institute for economics and peace (https://economicsandpeace.org/) as an indicator of the level of civil conflict for countries in primate range regions. the gpi ranks independent states and territories according to their level of peacefulness. the gpi is the world's leading measure of global peacefulness. the gpi covers . per cent of the world's population, using qualitative and quantitative indicators, and measures the state of peace using three thematic domains: the level of societal safety and security; the extent of ongoing domestic and international conflict; and the degree of militarization. future projections of population parameters under five shared socio-economic pathway scenarios (ssps) from to for countries in each primate region were obtained from the iiasa ssp database (https://tntcat.iiasa.ac.at/sspdb/dsd? action=htmlpage&page=about). these scenarios define future socioeconomic tendencies that encompass a variety of likely effects and comprise: a world of sustainability and fairness (ssps ); a business as usual scenario following historical trends (ssps ); a divided world of growing nationalism (ssps ); a world of continually and growing inequality (ssps ); and a world of unrestrained economic growth with high levels of energy use (ssps ) (riahi et al., ) . for a discussion of limitations of the ssp scenarios see chen et al. ( ) and shuhui & xuefeng ( ) . we acknowledge that the information contained in these large datasets may differ in their level of trustworthiness and impartiality. for example, some publicly accessible data by international agencies such as the united nations food and agriculture organization (fao) denote general estimates. likewise, data from the iucn red list on the population, distribution, and conservation standing of cryptic, rare, or highly inaccessible primate species may be incomplete. in other instances, however, the data were acquired through careful examination by an impartial organization (e.g., un population division, transparency international) or were objectively certified using remote sensing (e.g., global forest watch). each of the organizations we used as sources of data indicate in their portals the constraints of the information presented. habitat loss is a major driver of the local extinction of primate species. information from global forest watch (gfw, ) indicates that mha of tropical forest (defined as > % canopy cover) were lost between and as a result of human activities in the five primate range regions (figs. and ). this represents an area equivalent to ca % of the eu land mass. forty six percent of this loss was in the neotropics followed by southeast asia ( %), mainland africa ( %), madagascar ( %) and south asia ( %). (figs. and ; table s ). madagascar is home to more than species of lemurs (second richest primate country after brazil), and over % of lemur species are threatened with extinction. current estimates indicate that madagascar has lost some % of its original forest (estrada et al., ) . countries with the highest losses of tree cover between and were brazil ( . mha), indonesia ( . mha), drc ( . mha), china ( . mha) and malaysia ( . mha). these five countries totaled . mha or ca % of total tree cover loss ( mha) in primate range regions (fig. s ). together these countries harbor about % of extant primate species. a region by region examination indicates that between and , the neotropics lost . mha of forest ( fig. s a) , with brazil, the primate richest country in the world ( species) accounting for % ( . mha). during the same period, indonesia, the third primate richest country accounted for % of southeast asian forest loss (fig. s b ). an estimated % of indonesian primate species are threatened with extinction. countries such as china, malaysia, myanmar, lao, vietnam, cambodia and thailand, accounted for an additional % of forest loss. each of these countries has a high proportion of primate species listed as vulnerable, endangered or critically endangered (table s ). we note that in other countries, for example, madagascar, so much native forest has already been cut, that even small amounts of new forest loss will have a dramatic impact on primate survivorship. the primary drivers of continued forest loss in the five primate range regions include subsistence and industrial agriculture, commodity-driven deforestation, and the expansion of urban areas (estrada et al., (estrada et al., , chaudhary & kastner, ; chaudhary & brooks, ; estrada, garber & chaudhary, ) . this is unfolding in the context of expanding global economic activities driven principally by the exploitative practices of a small set of multinational corporations and the over-consumption of citizens in a small number of consumer nations who are disproportionately contributing to climate change, pollution, food insecurity, habitat destruction, and income inequality worldwide (estrada, garber & chaudhary, ; chaudhary & kastner, ; chaudhary & brooks, . the world´s human population has grown exponentially over the past several decades and a significant segment of this growth has occurred in primate regions (fig. ) . in table s for country data. full-size  doi: . /peerj. / fig- there were . bn people in primate habitat countries and this number reached . bn by . currently human populations in primate range regions account for % of the world's population. united nations' population division estimates predict that fully % of the world's population by (total human population estimated at . bn) and % by (total human population estimated at . bn) will reside in primate habitat countries (fig. ). significant human population growth is expected in all primate regions up to , after which africa will surpass the other four regions with accelerated human population growth continuing to the year ( fig. ) . populations in south asia and southeast asia are expected to exhibit reduced growth after . populations in the neotropics and madagascar will grow exponentially, but in the neotropics growth is expected to decrease slightly after (fig. ) . demographic models indicate that primate range countries, and especially those with developing economies, are driving the world's population growth. the population of africa is increasing at a particularly rapid rate. in , the population growth rate in africa averaged . %, which was more than double the world average ( . %) (undesa, a; unctad, ). several central and east-central african countries, such as niger, uganda, equatorial guinea, angola and the democratic republic of the congo recorded growth rates well above per cent. several of these countries are among the most primate species-rich in africa. rates slightly above the world average were found in south and southeast asia ( . %), with the neotropics ( . %) below the world average (world bank, ). significantly, population growth in primate range regions is expected to occur in urban areas with populations in rural areas declining dramatically (fig. ) . a sizeable segment of the population in the neotropics ( %) and southeast asia ( %) will reside in urban areas by . the values for mainland africa are %, for madagascar %, and for south asia also % (fig. ). while more than half of the increase in the urban population in primate harboring countries is caused by in situ population increase, migration from rural areas into cities also is a contributing factor (hecht et al., ) . while cities cover < % of the earth's surface, they use about % of the energy produced, including large quantities of nonfood and food products, much of which is wasted, adding to environmental pressures locally and globally (ulgiati & zacaro, ) . urbanization produces land-cover changes (grimm et al., ) that drive habitat loss, air and water pollution, and the extinction of local animal and plant populations (hahs et al., ) . urban growth entails the movement of goods and services into and out of cities, necessitating the construction of extensive road and rail networks, and the conversion of nearby forests for purposes of agricultural production and industry (seto, kaufmann & woodcock, ; seto et al., ) . a study of countries in the humid tropics found that forest loss was positively associated with both urban population growth and the export of agricultural products (e.g., cattle, crops) and non-food crops (e.g., palm oil, corn and sugar cane for biofuels), much of which were sold to international markets (defries et al., ). as cities grow, so do job opportunities. however, many of the new immigrants to large urban centers are the rural poor, who are under-educated and only qualify for low paying jobs in agriculture, manufacturing, and the service sector (sánchez-triana et al., ) . moreover, there is evidence indicating that urban expansion near protected areas pose important conservation challenges to biodiversity, as protected areas become islands or isolated refuges with limited buffer zones and barriers to animal migration and gene flow (seto et al., ) . the continued growth and expansion of urban areas is expected to exacerbate the negative consequences that deforestation and habitat fragmentation, bushmeat hunting, and capture for the local, regional and international pet trade will have on primate population decline. given recent assessments that the capture, killing, and trade of wild animals in urban "wet markets" likely represents the source point for the covid- pandemic (shereen et al., ) , it is clear that establishing and enforcing laws that promote reforestation in order to expand the physical separation between urban areas and wildlife refuges, and the strict control of unsustainable hunting and live animal capture, are essential components of a successful urban planning strategy. such a strategy also must include the development of new technologies to increase agricultural yields on non-forested lands and to reduce food waste to more efficiently satisfy the demands for agricultural products in urban areas (defries et al., ; seto et al., ) . additional forest loss has resulted from the expansion of dams and mega dams to supply water and electricity to urban areas and nearby industries and to agricultural land (laurance et al., ; benchimol & peres, ) . this has been accompanied by expansion of road and rail networks to transport people, goods and services to resident human populations in urban areas (alamgir et al., ; clancy, ; laurance, ; unstats, ) . moreover, the establishment of irregular or unauthorized settlements in the vicinity of cities is an additional factor adding to the cities' footprint, increasing human-primate conflict and primate population decline (boyle, ) . although cities harbor poverty, they also are places of innovation and knowledge, and can offer economic opportunities in terms of employment and improved living and health conditions (https://sustainabledevelopment.un.org/topics/sustainablecities). cities also offer spaces for social and political involvement and the fusion of cultures, reasons why city life is more desirable to some people, especially young adults. for example, a study of countries in sub-saharan africa demonstrated that for the average child under five years of age, living in a rural area and isolated from basic health services and adequate sanitation, the mortality rate (deaths per , live births) was . % compared to . % for children living in urban areas (issaka, agho & renzaho, ) . unfortunately, rapid urbanization in primate range countries has resulted in a growing number of slum dwellers, a reduction in food security, and inadequate and overburdened infrastructure and services (such as waste collection and water and sanitation systems, roads and transport), leading to unhealthy levels of air and water pollution and unplanned urban sprawl (unstats, ). crowding also can have a devastating effect on disease transmission, especially in developing nations (hotez, ) . we found that the proportion of the urban population living in slums is high in primate harboring nations when compared with developed nations. in madagascar, % of the urban population lives in slums, in sub-saharan africa %, in south asia %, in southeast asia % and % in the neotropics. in contrast, in canada, the united states, and the eu, the percentage of the population living in slums is less than % (world bank, a). while cities and metropolitan areas are centers of economic growth-contributing about per cent of global gdp, they also account for some per cent of global carbon emissions and over per cent of resource use (li et al., ; unstats, ) . policy decisions and urban planners need to prioritize reducing the ecological footprint of city residents and industry in order to promote 'green' cities, reduce the urban footprint on biodiversity, and actively engage in programs designed to restore native forests (butler & laurance, ) . unsurprisingly, the increase in human population size means that more food, water, energy, living space and public health services are required together with additional housing, transportation hubs and networks, road building, and other essential services (crist, mora & engelman, ). at the same time, while the human population in developed economies is not growing as rapidly, their economies continue to expand in order to sustain and increase the quality of life of their citizens (undesa, a). this has important consequences for biodiversity conservation because these developed nations are characterized by overconsumption and excessive waste (neff, spiker & truant, ) of agricultural and nonagricultural commodities, much of which are produced in primate range countries (estrada, garber & chaudhary, ) . this pattern of "colonial" exploitation, that is, the over-extraction of resources, taking advantage of cheap labor, and environmental degradation, has significantly taxed the natural resources of most primate range nations, and resulted in food insecurity as food is grown to support global supply chains rather than for local consumption (chaudhary & kastner, ; chaudhary & mooers, ). successful and longstanding primate conservation requires economic resources, satisfactory conservation strategies, efficient implementation of environmental law, public interest, and the practice of sustained and long-term conservation-oriented research. however, if poverty and income inequality are prevalent in the population, primate conservation will not be a primary social concern. information on the growth of gdppc between and indicates an enormous gap between countries in primate range regions and the top developed nations of the world ( fig. ; table s ). and although there has been a gradual increase in the average gdppc between and in countries in primate range regions, only the neotropics and southeast asia have experienced gains that closely match the world average (fig. ) . in contrast, in mainland africa, madagascar and south asia the level of gdppc has remained stagnant since , with a small increase between and ( fig. ; table s ), probably the result of increased exports of agricultural and nonagricultural commodities (estrada, garber & chaudhary, ). yet, in many cases gains in gdppc in primate range countries such as brazil, argentina, indonesia, malaysia and china have occurred at the cost of severe and on-going environmental degradation (table s ; estrada et al., ; estrada, garber & chaudhary, ) . in general, weak per capita income growth is anticipated over the next few years in mainland africa, madagascar and south asia, regions that harbor a significant part of the global population living in extreme poverty (undesa, b). the steep growth curve in the gdppc for the top developed nations in the world is notable, indicating significant improvements in the standard of living of their populations, and table s for country data. full-size  doi: . /peerj. / fig- significant differences in the quality of life between citizens in primate range nations and citizens in developed nations (fig. ) . data on the gdppc for all primate countries at a decadal interval ( - ) under five different shared socioeconomic pathway models (ssp- to ssp- ) (samir & lutz, ) show that the highest increase in gdppc is forecasted under the ssp- scenario, which assumes rapid and unconstrained growth in economic output, energy use, and environmental degradation. however, relatively high gdppc for primate range countries also is predicted under the ssp- scenario, which is based on sustainability-focused growth and greater income equality (see table s ). similar to projections of population growth, the ssp- scenario is a win-win for human development and primate conservation because the growth in gdppc under this scenario minimizes tropical deforestation and biodiversity loss estrada, garber & chaudhary, ) . information from the un hdi (a combination of life expectancy, school enrollment, literacy, and income, with the lowest human development = and the highest = . ) indicates that while the average hdi has increased over the past decades in all primate regions, madagascar and countries in mainland africa and south asia have remained consistently low and below the world's average (fig. ) . the hdi for the neotropics and southeast asia has tended to increase, but this has been driven by a small set of countries including japan, brunei, singapore, taiwan, argentina, and costa rica (fig. ) . table s for country data. full-size  doi: . /peerj. / fig- these are among the least primate-rich countries per region. in contrast, the average hdi values for the top developed nations in the world have consistently increased over the same period and are well above the average of all primate range regions (fig. ) . citizens of the nations that rank higher on this index have a higher level of education, a longer lifespan, and a higher gross national income per capita than citizens of nations with a lower hdi (undp, ). low levels of development are commonly associated with political instability, extreme income inequality, and limited environmental protection (alsamawi et al., ; undp, ) . thus, it is clear that despite the enormous biological wealth and natural resources of primate range countries, poverty, deep-rooted income inequality, illiteracy, low levels of education, political instability, and over-exploitation of their natural resources by the consumer nations of the world make the task of preserving primates and their habitats extremely difficult (alsamawi et al., ; undp, ) . the challenges of devoting sufficient resources to environmental and biodiversity conservation in the majority of primate range countries is further underscored by the percentage of the population living on less than us $ . a day, an internationally recognized indicator of extreme poverty (world bank, b). the world bank indicates that in madagascar had the largest percentage ( %) of the population living on less than us $ . a day, followed by mainland africa ( %) and in south asia ( %) (fig. a) . individuals in the neotropics ( . %) and in southeast asia ( . %) have fared better, and are below the world's average ( %). in europe (n = ), the us and canada the proportion of the population living on less than us$ . a day was essentially zero (world bank, b; fig. a ). moreover, low human development and high poverty levels in primate range regions are related to high levels of mortality for children under five years of age. in , under-five mortality in mainland africa was . million. in south asia, it totaled . million children (fig. b ). in the neotropics and in southeast asia under-five mortality was significantly lower, . million and . million, respectively. in contrast, in developed nations under-five mortality was . million ( fig. b ; table s ) (world bank, c; unigme, ). high levels of poverty and its consequences for under-five mortality underscore the challenges faced in prioritizing primate conservation in primate range regions. poor governance promotes poverty, civil unrest, food insecurity unsustainable use of natural resources, hunting, the illegal wildlife trade, and the necessity to colonize intact forest areas, including legally designated protected areas, thus expanding pressure on primate habitats and populations (adams & hutton, ; kates & dasgupta, ) . food security in primate range countries is a critical factor affecting primate conservation. high levels of population growth, poverty, inequality, and corruption, accompanied by extensive loss of natural capital, have a direct impact on food security. the world food summit of defined food security as the situation in which people have physical, social and economic access to sufficient and nutritive food that meets their dietary requirements for a healthy and active life (http://www.fao.org/wfs/). using this internationally accepted standard, the gfsi of the economist intelligence unit limited (gfsi, ; https://foodsecurityindex.eiu.com/index) has integrated the core issues of affordability, availability, quality and safety into a quantitative and qualitative model that evaluates these drivers of food security in developing and developed countries. the index also considers a country's exposure to the impacts of a changing climate; its susceptibility to natural resource risks; and how the country is adapting to these risks. the gfsi is based on data from countries and ranges from zero (lowest food security) to (highest food security) (https://foodsecurityindex.eiu.com/index). the gfsi for primate range countries for which the index is available indicates that lowest values are found for madagascar and mainland africa, followed by south asia, the neotropics, and southeast asia. a few southeast asian nations such as japan, singapore and malaysia have food security indices comparable to those of western nations. the average value of the index for primate range regions was . , while the gfsi for of the most developed nations in the world was . ( fig. ; table s ). the united nations expects that in , of primate range countries ( %), the majority of which are in africa, will encounter acute food insecurity (gnafc/fsin, ). given the economic effects of the coronavirus, it is likely that food insecurity in other primate regions also will increase (torero-cullen, ). human populations in primate range countries lag far behind developed nations in gdppc, in human development, and in food security despite the fact they produce billions of metric tonnes of food per year. this is a direct result of land use practices that are controlled by a small set of multinational corporations and a system of industrial agricultural production for global export (including beef) to satisfy overconsumption by developed and developing nations rather than for domestic consumption (estrada, garber & chaudhary, ; chen, chaudhary & mathys, ). here it is important to note that poverty, corruption, poor governance, and income inequality in many primate range countries, along with debt that must be repaid in dollars, have led countries to allow large areas of their land converted to agricultural and nonagricultural commodities production (e.g., soy fields, oil palm and rubber plantations and the extraction of minerals, fossil fuels and gems) mainly for global markets (bradshaw & brook, ; chen et al., ; dietz & rosa, ; estrada, garber & chaudhary, ) . land use dedicated to the production and export of food and nonfood commodities by primate range nations has not increased local food security, human safety, or political stability (fao, a (fao, , b . adding to the global challenges of income inequality, access to adequate food and health care, conflict, climate impacts, and unforeseen events like the covid- pandemic are figure food security in primate range regions. global food security index (gfsi) in for primate range regions (zero is lowest food security to which is highest food security). also shown is the value of the gfsi for the top most developed nations in the world for which gfsi data are available. see table s for a list of countries and their fsi. numbers in parentheses represent the number of countries per region for which data are available. see table s for country data. full-size  doi: . /peerj. / fig- expected to have a greater negative impact on health and food security in primate range nations than in more prosperous countries (gnafc/fsin, ). covid- is expected to overwhelm civil society, increase food insecurity, and devastate the healthcare systems and livelihoods of millions of citizens who work in the informal agricultural and nonagricultural sectors of the economy across the globe (gnafc/fsin, ) . the covid- pandemic has resulted in the disruption of local and global food chains and this may result in scarcities of food and higher prices (torero-cullen, ), which in turn may lead to increased hunting of bushmeat and an expansion of wildlife trade in many primate range nations (lappin et al., ) . clearly, primate-range countries must develop a more balanced set of national priorities to build their internal economies in order to ensure food security for their growing human populations. these same countries must also safeguard their biodiversity by building their economies using sustainable practices, green technologies, reducing water, air and soil pollution, and mitigating the effects of climate change on their citizens and environment (estrada et al., ; sillman et al., ) . while poverty, food security and protection of primate habitats are intricately linked, there are other social factors at play that impede human well-being, protecting biodiversity, and prioritizing primate conservation. these are corruption and poor governance. corruption is a major threat to humans, biodiversity, and the environment because it destabilizes democratic institutions, causes governmental and societal uncertainty, and destroys public trust. corruption rewards criminal activity, weakens economic development, promotes inequality, and hinders country-wide prosperity (undoc, ). corruption adversely affect human communities and leads to policies and practices that foster habitat degradation and loss of biodiversity. it also contributes to poverty and to social and political volatility. the more a country's political system is affected by corruption, the poorer the country's environmental performance (murshed & mredula, ; transparency international, ) . the corruption perceptions index (cpi), which has been released annually by transparency international since , ranks countries by their perceived levels of public sector corruption, as validated by expert evaluations and attitude surveys. the cpi defines corruption as "the misuse of public power for private benefit" (table s ). the perception corruption index (pci) of transparency international (https://www.transparency.org; = most corrupt, = least corrupt) for primate range countries, for which pci scores are available, and for the top most developed countries indicates that high levels of corruption are widespread in primate range nations compared to the top economies (fig. a) . the distribution of the pci scores across primate range countries and in the developed nations is shown in fig. b . in , the least corrupt country in the neotropics was costa rica (cpi: ) followed by argentina (cpi: ) and suriname (cpi: ). the most corrupt country was venezuela (cpi: ) ( fig. b; table s ). in mainland africa, botswana, rwanda and namibia were the least corrupt (cpi: > ) and the most corrupt were somalia (cpi: ), south sudan (cpi: ), equatorial guinea (cpi: ), sudan (cpi: ), congo dr (cpi: ), guinea-bissau (cpi: ), burundi (cpi: ) and republic of congo (cpi: ) . for the remainder of mainland african countries, the cpi ranged from - . primates species-rich madagascar had a cpi score of , indicating very high levels of corruption ( fig. b; tables s ) . in south asia the cpi ranged from in yemen to in bhutan. in southeast asia the cpi ranged from myanmar/lao to in singapore ( fig. b ; table s ). corruption is a major contributor to primate population decline because it results in incentives to misrepresent the negative consequences of environmental degradation table s for the complete list. source of data to build map: transparency international www.transparency.org/cpi. consulted march . no data are shown for non-primate range countries (shown in gray). see table s for country data. full-size  doi: . /peerj. / fig- and/or not comply with environmental laws. this has resulted in illegal deforestation and land speculation fostering poverty and criminal activities by individuals and corporations. in many cases these criminal enterprises are associated with the mining of precious metals and gems, which pollutes streams, lakes, rivers, and soil and promotes hunting, logging in protected areas and outside of government concessions, poaching, and the illegal primate pet trade (human rights watch, ; laurance, ; estrada et al., ; estrada, garber & chaudhary, ) . corruption hinders the conservation efforts of ngos, governments, and local communities and undermines the capacity of guards and law enforcement to combat drivers of primate habitat loss and local species extirpation (ivory, ; packer & polasky, ) . in many cases, laws are disregarded through bribery and extortion. in madagascar, the illegal harvest and export of rosewood in protected areas has been enabled by political ineffectiveness and corruption (freudenberger, ; gore, ratsimbazafy & lute, ; randriamalala & liu, ; schwitzer et al., ) . bushmeat and the trade for body parts are important drivers in the population decline of great ape species-bonobos, chimpanzees, and gorillas in africa and orangutans in indonesia (iucn red list, ). it was estimated that the domestic trade in primates for pets and bushmeat in peru is likely to number in the hundreds of thousands per year, with larger-bodied primates being the main targets (shanee, mendoza & shanee, ) . trading orangutans in indonesia is a felony, but confiscations in the last years have led to only seven convictions with light sentences (nijman, ) . in short, corruption at various levels of society render ineffective the laws that protect wildlife and feed a vicious cycle across many levels of society. high levels of corruption seem to have an important impact on the quality of governance in primate range regions and make social reforms needed to enhance the health, income, and well-being of average citizens, impossible. good governance entails justly implementing the practices and laws that maintain the institutions and constitution of the country. this involves the process by which governments are chosen, scrutinized and replaced; the capability of the government to successfully create and apply sound policies; and the respect of people and the state for the institutions that govern social and economic interactions (world bank, d; european commission, ). an examination of four key world bank indicators of governance quality in (political stability and absence of violence/terrorism, government effectiveness, rule of law and control of corruption) found that all countries in primate range regions ranked significantly below the average value for high-income countries. sub-saharan africa and madagascar ranked lowest among primate regions (fig. ) . a global study showed that high governance scores frequently relate to lower rates of deforestation (fischera, giessenb & günterc, ) . rule of law and control of corruption are critical factors in successfully establishing effective conservation programs. countries will not be successful in implementing policies of conservation and environmental protection if government effectiveness and political stability are low. irrespective of environmental laws and public sentiment, weak governance fosters the inability of environmental institutions to protect animal and plant biodiversity, safeguard ecosystems health, and promote a green economy. tropical forests are one of the earth's last frontiers. they are rich in natural resources, and they enable residents to maintain their traditional beliefs, economies, and cultures in balance with the environment. many indigenous cultures view tropical forests as sacred places and view their role as stewards of the environment (fuentes, ) . tropical forests are places of dynamic social, ecological, political, and economic change, which in some cases has led to armed conflict over forest resources and land (mcneely, (mcneely, , . here we examine the gpi of the institute of economics and peace (https://economicsandpeace.org/). the gpi covers . per cent of the world's population and uses qualitative and quantitative indicators to measure the state of peace using three thematic domains, ongoing domestic and international conflict (odic), societal safety and security (sss) and militarization (iepgpi, ). the gpi (one most peaceful, five least peaceful) for countries harboring primates had, on average, higher values (gpi: . ) than did the top high-income nations in the world (gpi: . ) ( fig. ; table s ), suggesting that primate countries more commonly face sustained civil conflict. countries in south asia and mainland africa maintain the greatest conflict, followed by countries in the neotropics. among primate range nations, countries of southeast asia (gpi: . ) and madagascar had the lowest values of the gpi (gpi: . ) (fig. ) . civil conflict negatively affects primate population persistence due to random bombing, the use of toxic chemicals and defoliants, increased availability of firearms, and the upsurge in bushmeat hunting both by soldiers and displaced people as local supply chains breakdown (douglas & alie, ; loucks et al., ) . for example, the poaching of bonobos (pan paniscus) and gorillas (gorilla gorilla and gorilla beringei) increased considerably in drc and rwanda as a result of ongoing civil wars (douglas & alie, ). in cambodia, armed conflicts have severely affected populations of the black-shanked douc (pygathrix nigripes) (loucks et al., ) . heavily armed militias in drc are currently fighting for ethnic and political control and, jointly with illegal miners, prospect for "conflict minerals" (e.g., coltan, tin, tantalum, tungsten and gold) and diamonds, and hunt primates for bushmeat (gavin, ; nellemann, redmond & refisch, ) . likewise, past border conflicts in southeast asia, including the war in vietnam which lasted some years, caused significant damage to the forest and wiped out entire wildlife populations (mcneely, ) . at present % ( / ) of primate species in vietnam are considered threatened (table s ). civil conflict also alters traditional land use patterns and can lead to increased unregulated forest conversion. in northern sumatra, between and human conflicts combined with forest fires and illegal and legal logging caused major reductions in forest cover (> %) (margono et al., ) . disputes over land rights, actions by corporation, and governmental policies also have led to forest burning and land-clearing in several primate range regions in southeast asia, africa and the neotropics endangering many primates (lanjouw, ; meijaard & nijman, ; supriatna et al., ; human rights watch, ) . clearly, civil unrest, inter-country wars, terrorism, and continued militarization contribute to the dislocation of the large numbers of innocent civilians resulting in refugee crises, increased poverty, insecurity, the spread of disease, environmental damage, and reduced food security. under these conditions, primate conservation is not a priority and the lack of security and personal safety of citizens in these countries are amplified by prevailing corruption and low-quality governance (figs. and ). decadal interval data ( - ) compiled and modeled from all primate countries under five different shared socioeconomic pathways (ssp- to ssp- ) (samir & lutz, ) showed that the lowest human population increase is forecasted under conditions of rapid and unconstrained growth in economic output and energy (ssp- ) that would significantly harm the environment as well as under conditions of sustainability-focused growth and economic equality (ssp- ). the greatest increase in human population growth in the five primate range regions is projected under the ssp- scenario, in which globalization is fragmented and countries around the world see a "resurgence of nationalism" (fig. ; table s ) (samir & lutz, ) . the ssp- (sustainability-taking the green road) scenario represents a world that together respects and protects the environment and is shifting towards a green and sustainable path. under this scenario, tropical deforestation is reduced due to strict regulations, crop yields and international trade increase, people reduce their consumption of meat, adopt healthier diets, and obtain the benefits of a cleaner environment . past studies have gathered both quantitative and qualitative evidence on several local and national interventions that can generate positive outcomes for primates and biodiversity in general. for example, shifting to diets (sustainable consumption) with fewer animal-based products and thus a reduced environmental footprint can relieve some of the existing pressure on species' habitat, resulting in lower species extinction risk (see willett et al., ; machovina, feeley & ripple, ; chaudhary & krishna, ) . similarly, adopting sustainable tropical forest management practices such as reduced impact logging, can reduce species losses and environmental degradation (chaudhary et al., ) . in the agriculture sector, improved technology, reduced food loss and sustainable intensification farming practices leading to higher yields can result in the release of more land for biodiversity conservation (krause & ness, ; willett et al., ) . assuming that continued human population expansion results in a significant increase in the demand for food, in tropical regions characterized by water scarcity, the cultivation of bioengineered drought-tolerant crops can result in increased production without expanding farming into forested areas (rosa et al., ) . no net loss (nnl) biodiversity policies, which are design to reconcile the increased need for infrastructure development with biodiversity conservation are also being formulated (https://tntcat.iiasa.ac.at/sspdb/dsd?action=htmlpage&page=about). these pathways include: (a) a world of sustainability-focused growth and equality (ssp ); (b) a "middle of the road" world where trends broadly follow their historical patterns (ssp ); (c) a fragmented world of "resurgent nationalism" (ssp ); (d) a world of ever-increasing inequality (ssp ); and (e) a world of rapid and unconstrained growth in economic output and energy use (ssp ). see ( )). under the ssp- (fossil fueled development-taking the highway) scenario, there is rapid technological progress, increase in crop yields and international trade and diets are unhealthy with high food waste. tropical deforestation continues, but at more modest yearly rates in response to recognition of the need for regulation, however the resulting habitat reduction and fragmentation leads to significant declines in biodiversity, including many primate species . although the rate of human population increase is similar in both the ssp- and ssp- scenarios, the ssp- scenario forebodes better outcomes for environmental justice, human health and global primate conservation (table s ) . we note that by , there will be ca million more people in primate range countries under the ssp- (business-as-usual, middle of the road scenario where development happens along historical patterns) scenario compared with ssp- scenario (table s ) . under the worst case ssp- scenario (regional rivalry-a rocky road), the increase will be even more severe and there will be ca . billion additional people in primate hosting countries compared to ssp- scenario (see supplemental excel). the ssp- scenario is characterized by trade barriers, nationalism, limited technology transfer leading to stagnant crop yields, almost no land use change regulations and the figure socioeconomic challenges in primate range regions and primate conservation. diagram summarizing key socioeconomic challenges facing primate range regions that affect the conservation of their primate fauna. the relative importance of population and governance aspects vary from country to country, but in general these challenges are common to all primate range nations, except japan, brunei and singapore which rank high in gross domestic product per capita (gdppc) and in the human development index (hdi) (see tables s and s ) . full-size  doi: . /peerj. / fig- prevalence of unhealthy diets high in food waste and meat products . this will certainly be the most disastrous scenarios for primates and humans on earth. from these population projections under different ssp scenarios, one can infer that unless sustainability measures associated with the ssp- scenario are adopted in the coming decade, the activities of the human population will exert harmful pressures on primates leading to a large number of species extinctions by as early as . however, it also is important to consider that while it is generally assumed that global biodiversity and sustainability policies should be designed to promote economic growth, a recent evaluation has pointed out that increased economic growth may not be required to protect biodiversity and increase human prosperity (ipbes, ; otero et al., ) . as we have stressed throughout this manuscript, many historical, socio-economic, political, demographic and cultural factors, in addition to population size, affect patterns of resource consumption, environmental degradation and biodiversity loss. the immediate challenges for primate conservation lie in developing sustainable methods of food production, reducing meat consumption, moving toward a greener lifestyle, limiting the threat of emerging diseases, implementing programs of reforestation, reducing food instability and income inequality, and better governance. that said, the increase in human population size predicted for africa by the end of the century (estimated population size of billion people), will have an extremely negative impact on primate population persistence, especially for old world monkeys and apes, and will require very different solutions for environmental protection and human well-being than faced in other parts of the world. our review reveals that the well-being, health, and security of the human population in primate range countries is of paramount importance if we are to move forward with effective and long-lasting policies to promote primate conservation. however, high levels of poverty, inequality, food insecurity, and the loss of natural wealth triggered by weak governance, and corruption, along with widespread land-cover changes driven by profiteering and the global market demands of a small number of consumer nations and multinational corporations are the catalysts driving both the primate extinction crisis and the persistence of low human development and poverty (estrada, garber & chaudhary, ) . according to the un department of economic and social affairs, the human cost of climate change disasters will fall devastatingly on low-income and lowermiddle-income countries (undesa, b). most of these are primate range nations in africa, south asia, and southeast asia (xu et al., ) . solutions to these challenges should involve global approaches to slow human population growth, advance health, lower poverty and improve education, empower women, develop sustainable land-use programs, maintain traditional ways of life of indigenous communities, and adopt green policies of food and natural resource production and consumption, as delineated in the un sustainable development goals (https://sustainabledevelopment.un.org/#) (fig. ) . based on the ssps- model we can accomplish these goals, if global citizens and consumer nations adopt green environmental, economic, and social policies moving forward (fig. ) . by , the global population is projected to surge from ca to ca billion, and estimates are that food production will need to rise from the current . billion tonnes per year to almost . billion tonnes (fao, ) . the human population in primate range regions is projected to increase from ca bn in to ca bn by adding to the pressures of ensuring food security while at the same time preserving tropical forests to avoid extinctions (davila & dyball, ; willett et al., ) . in the face of globalized market demands, we need global actions to limit the long-term environmental and economic footprint of overconsumption of natural resources from the tropics by citizens in a small number of developed nations as well as an imperative for governments of primate habitat countries to promote human development and well-being (xu et al., ) . this will require substantial changes in human behavior in order to provide economic opportunities for the world's poor by reducing our emphasis on global supply chains and promoting local food production, local manufacture, and local distribution of goods for local markets and consumers. similarly, we must act to protect tropical forests and the ecosystem services on which agriculture and sustainable use of natural resources depend (fao, (fao, , (fao, , (fao, , a (fao, , b willett et al., ) . while each region differs from each other in their primate richness and taxonomic diversity, countries in each region have several socioeconomic and sociopolitical traits in common. our review indicates that all primate range regions are losing tropical forests, and thus natural resources at an alarming rate. moreover, low human development, low levels of food security and low governance quality are predominant across these regions (fig. ) . although some primate conservation issues, such as climate change, are common to many primate range countries, it is also true that underlying causes of primate population decline vary from country to country, region to region, and differ across primate taxa. hence, each country will need to identify the set of effective conservation policies and practices required to conserve populations of primate species and their habitats. moreover, political instability and within country and between country civil unrest are also factors that acting in synergy with other drivers, jeopardize primate conservation, human well-being and the integrity of protected areas (hammill, ) . despite the collective actions of the world's countries and international institutions such as the iucn, un, world bank and the un international court of justice, among others, which have led to policies such as the international convention on biological diversity (https://www.cbd.int/) and the paris climate agreement (https://unfccc.int/process-andmeetings/the-paris-agreement/the-paris-agreement), biodiversity continues to decline at an accelerated rate (ipbes, ). if corrective measures are not soon implemented, we will reach a tipping point and lose our closest living biological relatives along with the complex ecosystem services and benefits they provide to forests and people. we also will lose the social, historical, and cultural relationships that have persisted between human primates and nonhuman primates over millennia (chandra, ; fuentes, ; voigt et al., ) . moreover, in any discussion of the conservation of natural resources, we need to consider the role played by indigenous peoples. according to the un department of economic and social affairs and the world bank there are about million indigenous peoples worldwide, living in some countries (most of them in the tropics) (garnett et al., ; fa et al., ; undesa, ; world bank, e) . indigenous people inhabit a quarter of the world's land area and many live in biologically vulnerable environments (e.g., rain forests). indigenous peoples hold vital traditional knowledge, and for millennia have sustainably used local natural resources, even in the face of natural disasters (garnett et al., ; fa et al., ; el bizri et al., ; jarrett, cummins & logan-hines, ) . and while they represent about five percent of the world's population and protect about percent of the world's biodiversity, they account for some % of the extreme poor, and their life expectancy is years lower than the life expectancy of nonindigenous peoples worldwide (fao, ; world bank, d) . acknowledging and protecting the rights of indigenous peoples' to their lands and traditional ways of life are critical if we are to maintain local, regional, and global biodiversity and achieve primate conservation targets (garnett et al., ) . our review indicates that as human populations are expanding across primate range regions, high levels of poverty, food insecurity and income inequality, among other forces, directly or indirectly, weaken the ability of primate habitat countries to protect tropical forests and biodiversity (fig. ) . the world community must adopt green technologies and green policies that improve the lives and well-being of poor-and middle-income people and contribute to protect their natural environment. primates are our closest living biological relatives and as they decline the ecological communities they inhabit also will decline. we are at a historic moment in which urgent local and global action must be taken to reverse the impending extinction of the world's primates (estrada et al., ) . if we can put in place the changes required to save the world's primates, then we will have put the changes in place to save humans as well. people, parks and poverty: political ecology and biodiversity conservation economic, socio-political and environmental risks of road development in the tropics the inequality footprints of nations: a novel 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development report : beyond income, beyond averages, beyond todayinequalities in human development in the st century human development report: human development index un global environment facility (ungef) united nations global environmental facility estimates developed by the united nations inter-agency group for child mortality estimation sustainable cities and economy energy, land-use and greenhouse gas emissions trajectories under a green growth paradigm bornean orangutans food in the anthropocene: the eat-lancet commission on healthy diets from sustainable food systems population growth rates population living in slums (% of urban population world bank. b. poverty. consulted world bank. d. worldwide governance indicators world bank. e. indigenous peoples future of the human climate niche the role of no net loss policies in conserving biodiversity threatened by the global infrastructure boom paul a. garber is forever grateful to jennifer a. garber, sara a. garber, dax h. garber, and chrissie mckenney for inspiring him to redirect his efforts to protecting the world's threatened primate populations. alejandro estrada is thankful to erika and alex for always supporting his interests in primate field research and conservation. we are grateful to anaid cardenas navarrete for her special help in updating figs. and . abhishek chaudhary was funded by the initiation grant of indian institute of technology (iit) kanpur, india (project number ). the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. the following grant information was disclosed by the authors: initiation grant of indian institute of technology (iit) kanpur, india: . the authors declare that they have no competing interests. alejandro estrada conceived and designed the experiments, performed the experiments, analyzed the data, prepared figures and/or tables, authored or reviewed drafts of the paper, and approved the final draft. paul a. garber conceived and designed the experiments, performed the experiments, analyzed the data, prepared figures and/or tables, authored or reviewed drafts of the paper, and approved the final draft.abhishek chaudhary conceived and designed the experiments, performed the experiments, analyzed the data, prepared figures and/or tables, authored or reviewed drafts of the paper, and approved the final draft. the following information was supplied regarding data availability:the raw measurements are available in the supplemental files. supplemental information for this article can be found online at http://dx.doi.org/ . / peerj. #supplemental-information. key: cord- -s psqth authors: mukandavire, zindoga; nyabadza, farai; malunguza, noble j.; cuadros, diego f.; shiri, tinevimbo; musuka, godfrey title: quantifying early covid- outbreak transmission in south africa and exploring vaccine efficacy scenarios date: - - journal: plos one doi: . /journal.pone. sha: doc_id: cord_uid: s psqth the emergence and fast global spread of covid- has presented one of the greatest public health challenges in modern times with no proven cure or vaccine. africa is still early in this epidemic, therefore the extent of disease severity is not yet clear. we used a mathematical model to fit to the observed cases of covid- in south africa to estimate the basic reproductive number and critical vaccination coverage to control the disease for different hypothetical vaccine efficacy scenarios. we also estimated the percentage reduction in effective contacts due to the social distancing measures implemented. early model estimates show that covid- outbreak in south africa had a basic reproductive number of . ( % credible interval [cri] . – . ). a vaccine with % efficacy had the capacity to contain covid- outbreak but at very higher vaccination coverage . % ( % crl . – . %) with a vaccine of % efficacy requiring . % ( % crl . – . %) coverage. social distancing measures put in place have so far reduced the number of social contacts by . % ( % crl . – . %). these findings suggest that a highly efficacious vaccine would have been required to contain covid- in south africa. therefore, the current social distancing measures to reduce contacts will remain key in controlling the infection in the absence of vaccines and other therapeutics. the coronavirus disease (covid- ) originated in wuhan, china, in december and has rapidly spread around the world [ ] . as this is a new and novel virus, there is a huge scientific evidence gap and therefore limited understanding of the epidemiology of sars--cov- , the pathogen that causes the disease covid- . currently, the epicentre of the virus is a a a a a in europe and new york in the united states of america [ ] . in africa, the virus is just starting to set its foothold, with south africa now reporting the majority of cases in the continent. the first case of the covid- in south africa was reported on the th of march [ ] . measures to contain the epidemic culminated in the declaration of the state of disaster leading to a national lockdown on the th of march with gauteng, western cape, kwazulu-natal and the free state provinces reporting most of the covid- cases. the map in fig shows the distribution of covid- confirmed cases in south africa before the government mandated a lockdown. gauteng province appeared to be the "epicentre" of covid- in south africa for a number of reasons. first, the province has the largest population density [ , ] and the urban population is poor with % of its population being food insecure [ ] . second, gauteng province has two international airports including or tambo international airport handling over million passengers annually [ ] . third, the volume of people that use public transport runs into millions daily creating social networks and patterns that are key in accelerating the spread of the disease. finally, the province is the country's economic hub, and many people (including international visitors) travel in and out of the province daily [ ] . with the majority of confirmed cases early in the outbreak having been linked to international travel [ ] , it is not surprising that the most affected provinces (gauteng, western cape and kwa-zulu-natal) have international airports with direct flights to affected global regions (fig ) . the cases in the free state province have mainly been attributed to a cluster transmission resulting from a mega church gathering [ ] . with covid- having been declared a global pandemic [ ] and the urgent need to have an effective vaccine to control the pandemic [ ] , there is a need to understand the utility of mass vaccination campaigns for this pandemic. critical in the early stages of the disease is the need to clearly understand the spectrum of disease severity and transmission characteristics of the disease in order to identify optimal control measures. many of the control measures suggested for this pandemic have been attributed to the lessons learnt in wuhan, china [ ] . the challenges associated with real-time analysis of an evolving epidemic are well articulated in [ ] . these include testing capacity and delayed appearance of symptoms and asymptomatic carriage. the impact of covid- on south africa may differ from that on china and other regions such as europe and north america. south africa has unique circumstances, for example, it has the highest numbers of people living with hiv, with a significant proportion not on treatment, and one of the largest tuberculosis (tb) burdens in the world [ , ] . moreover, underlining disease conditions such as diabetes, hypertension and chronic obstructive pulmonary disease are prevalent in south african and these are known to be risk factors for covid- infection and mortality [ ] . the age distribution for south africa is also different from china and europe as its young population accounts for the majority of the population [ ] . data from china and other settings have shown that sars-cov- is more infectious than influenza, and has an incubation period of about days (median time) and a doubling time of days [ , ] . however, we have a limited understanding of the infectiousness of the virus in settings with different populations and a huge burden of other chronic conditions such as africa. mathematical models provide important insights in the understanding of emerging infectious diseases and informing public health policies. several mathematical models have been used to understand covid- transmission dynamics and inform public health policy [ , , , , ] . the reproductive numbers of the covid- epidemic in china have been determined in several modelling studies (table ) . here, we adapt a susceptible-exposed-infected-removed (seir) compartmental model to quantify early transmissibility of covid- in south africa and explore the potential utility of a vaccine in containing the disease. the seir model has been used to model respiratory infections including middle east respiratory syndrome (mers) [ , ] , covid- in wuhan china [ ] , influenza [ , ] and global tracking of covid- [ ] . in addition, we estimate the reduction in effective contacts after the implementation of the severe and extreme shutdown of the society, and this is critical in determining the impact of social distancing in the south african context. we use a standard deterministic compartmental seir model to simulate covid- in south africa. the model classifies the human population into four epidemiological compartments at any time t, the susceptible s(t), exposed e(t), infected i(t) and the recovered r(t). the total population is thus given by susceptible individuals are infected upon interaction with infectious covid- individuals and the rate of daily generation of newly infected cases is given by λ(t) = βs(t)i(t)/n, where the parameter β is the effective contact rate, i.e. the contact that will result in an infection. the lockdown effect is modelled with parameter, � ( , ) where �' implies an ineffective lockdown and �' implies a completely effective lockdown. the effective contact reduction term multiplies the effective contact rate in the model to give ( −�)β. exposed individuals in the e(t) compartment become infectious at a constant rate σ and move to the i(t) class. infected individuals i(t), recover at a constant rate γ to the removed class r(t). the schematic model flow diagram is presented in s fig. the model assumptions result in the following system of differential equations. following a similar approach in [ ] , we use a markov chain monte carlo (mcmc) within a bayesian framework (in r fme package [ ] ) to fit the model to the cumulative data of confirmed covid- cases in south africa and estimate the magnitude of the epidemic using the basic reproductive number and quantify required vaccines' attributes to stem similar outbreaks. we used data on covid- cases published by the south african department of health from the th of march to march prior to the lockdown to estimate the basic reproductive number [ ] . we set the model lockdown effect parameter � = when estimating the basic reproductive number. the percentage reduction in effective contacts after the lockdown � was estimated by fitting the model to cumulative covid- cases reported a week after the lockdown (from th march to th april ). cumulative data for covid- cases reported in south africa from the th march to th april is shown in s table. in the fitting, we set the lockdown effect parameter � = and varied β, σ, γ (within parameter ranges in s table) and initial infected population in order to estimate the basic reproductive number. in estimating the lockdown effect, we varied � and kept parameters used to estimate the basic reproductive number constant. gaussian likelihood was used to draw model parameter posteriors assuming uniform non-informative priors while the variances were regarded as nuisance parameters. the mcmc chain was generated with at least runs for the final fitting excluding the burn-in period. chain convergence was examined visually and using the coda r package [ ] . uncertainty of each estimated parameter was evaluated by analysing the mcmc chains and calculating the . % and . % quantiles to give the % credible interval (cri). the basic reproductive number (r ), is as a measure of the average number of secondary cases generated by a primary case and is an important statistic for quantifying intervention programmes [ , ] . using an intuitive mathematical approach, the reproductive number of model system ( ) is given by r = β/γ. the corresponding minimum vaccination coverage (c) for covid- vaccine for different vaccine efficacy scenarios was estimated using the mathematical expression c � ð À r À Þ=s where s the proportional reduction of the susceptibility for individuals partially immunized. estimates of effective contact rate (β), the incubation period ( /σ), infectious period ( /γ), the percentage reduction in effective contacts (�) and the basic reproductive number, r for south africa are shown in table . the mathematical model (of the seir type) was fitted to the cumulative covid- cases for south africa at the national level (fig (a) ). we estimated an effective contact rate . ( % crl . - . ) per day, incubation period of . days ( % crl . - . days), infectious period of . days ( % crl . - . days) and r of . ( % crl . - . ) before the lockdown. the result r > clearly shows disease sustainability in the country. estimates of r were used to conduct sensitivity analysis based on different covid- vaccines' efficacy assumptions to explore possible scenarios that may arise from mass vaccination campaigns, as scientists attempt to develop effective vaccines for covid- [ , ] . the vaccine efficacy scenarios were assumed to vary in the range of - % (fig (b) ). the results suggest that a vaccine with more than % efficacy could have the potential to contain the covid- outbreak in south africa but at extremely high vaccination coverage rates of . % ( % crl . - . %). as expected, vaccination coverage for epidemic control decreases with an increase in vaccine efficacy, with a vaccine of % efficacy requiring table before lockdown [ ] . we also quantified the percentage reduction in effective contacts as a result of the lockdown mandated by the government of south africa. fig shows that the epidemic is slowing down after the implementation of a lockdown. the results showed that the lockdown resulted in . % ( % crl . - . %) reduction in effective contacts ( table ) and consequently resulted in a reduction in the number of covid- cases reported in the first two weeks of implementation. this confirms results in china that demonstrated the importance of quarantine, social distancing, and isolation in containing the pandemic [ ] . covid- has spread rapidly globally assisted by air travel in an increasingly connected world [ , ] . globally most countries, including south africa, have adopted one form or another of the lockdown approaches in an attempt to curb disease transmission within their borders [ , , ] . our model estimate of r > confirms covid- persistence in south africa and indicate that the outbreak has the momentum to rapidly spread and spill over to other geographic regions of the country, in particular if the coming winter season (may to july) presents ideal environmental conditions for persistence of the virus. the estimate of r for south africa is in a similar range published for covid- in other modelling studies (table ) . hypothetical scenarios on vaccine efficacy demonstrated that, a vaccine of at least % efficacy would have been sufficient to contain the spread of covid- in south africa although at high vaccination coverage. however, it is important to note that expectations that the development of a highly effective vaccine for the novel-coronavirus will be achieved in the coming months are extremely optimistic, especially when considering that a vaccine has still not been successfully created for viruses like hiv, severe acute respiratory syndrome (sars) and mers, with the hiv vaccine being in development for many years [ , ] . nevertheless, the huge global interest in quickly identifying an effective vaccine could increase the possibility that a successful vaccine candidate can be developed in the coming months [ ] . even when a safe and effective vaccine becomes available, there are several logistical and operational challenges that need to be addressed for successful deployment and for the vaccine to achieve the desired coverage [ , ] . the modelled lockdown demonstrated . % reduction in effective contacts, showing that it is an effective measure to bring the disease under control. however, the reduction in the number of daily reported cases should be interpreted with caution as this could also have been a result of many other factors such as reduced international travel to high-risk regions and behaviour change. as the epidemic continues to unfold, it remains to be seen what trend the epidemic will follow if local transmissions are sustained within south africa. the implementation of this society shut down is not sustainable in the long run as it is unlikely to be tolerated for too long by the population. a vaccine would be an ideal preventative strategy for covid- but it appears that it should be complemented with prevention approaches such as isolation, quarantine, personal hygiene and limitations of public gatherings in order to achieve optimal protection of the population in south africa. the economic and social burden of the disease continues to be felt and this likely to be enhanced by an extension of the current lockdown of days by a further weeks [ ] . however it is unclear whether a stringent lockdown could be maintained for a longer period given the socio-economic challenges of the country where a significant percent of adults are involved in informal employment and others have jobs that do not allow them to work from home. this could affect the effectiveness of the lockdown in many of the townships as individuals will have to ease lockdown conditions in order to be economically active and prevent financial woes on individuals in urban communities. while the epidemic seems to have slowed down as a results of the lockdown (fig ) , there is need for continued scientific investigation including explorations through mathematical models to monitor the trend with the aim of informing public health policy in the short-term. the study has some limitations. the estimate of the reproductive number is based on available data and this estimate could possibly change depending on the quality of the data from the start of the epidemic (with possible under-reporting of cases in the initial phases of the epidemic). we note that spatial modelling mainly in the affected provinces would have been ideal but we did not have good data on a finer resolution to effectively parameterise a spatial model but as the epidemic evolves, nascent data on local covid- transmission in south africa is becoming available. we used a simple mathematical model without other population demographics as these were not important for short-term prediction [ ] and such models are also important when epidemiological and clinical disease characteristics of the disease are not well established as is the case for covid- [ ] . the simple model is only intended to give preliminary estimates for an epidemic that is evolving and whose trend has the potential to change dramatically overtime. however, it would be interesting to see how our results will change when a more complicated model is used. despite these shortfalls, findings in this study are important in understanding the transmissibility of the virus and informing the development of robust covid- prevention and control programmes in south africa and outlining mass vaccination expectations. the covid- pandemic has continued to spread and causing many deaths than any infectious disease we have seen in recent years and this calls for an urgent and well-coordinated timely and effective public health response. currently there is no proven treatment or vaccines for covid- and countries have embraced quarantine, social distancing, and isolation of infected individuals to contain the pandemic. thus, as more setting-specific data about the transmission dynamics of the virus become available, the building of suitable mathematical models to weight out the impact of current public health control measures and explore the potential utility of anticipated biomedical interventions such as vaccines is paramount. supporting information s fig. schematic covid- model diagram outlining infection progression. the arrows connecting compartments denote covid- infection at rate βs(t)i(t)/n, progression to infectiousness σe and recovery rate γi respectively. 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operational challenges of vaccination, th annual african vaccinology course (aavc) nationwide lockdown extended by two weeks is modelling complexity always needed? insights from modelling prep introduction in south africa epidemiological and clinical aspects of covid- ; a narrative review key: cord- - yardtss authors: jephcott, freya l.; wood, james l. n.; cunningham, andrew a. title: facility-based surveillance for emerging infectious diseases; diagnostic practices in rural west african hospital settings: observations from ghana date: - - journal: philos trans r soc lond b biol sci doi: . /rstb. . sha: doc_id: cord_uid: yardtss the aim of this study was to better understand the effectiveness of integrated disease surveillance and response (idsr) facility-based surveillance in detecting newly emerging infectious diseases (eids) in rural west african settings. a six-month ethnographic study was undertaken in in the techiman municipality of the brong-ahafo region of ghana, aimed at documenting the trajectories of febrile illness cases of unknown origin occurring within four rural communities. particular attention was paid to where these trajectories involved the use of formal healthcare facilities and the diagnostic practices that occurred there. seventy-six participants were enrolled in the study, and complete episodes of illness were documented. while participants routinely used hospital treatment when confronted with enduring or severe illness, the diagnostic process within clinical settings meant that an unusual diagnosis, such as an eid, was unlikely to be considered. facility-based surveillance is unlikely to be effective in detecting eids due to a combination of clinical care practices and the time constraints associated with individual episodes of illness, particularly in the resource-limited settings of rural west africa, where febrile illness due to malaria is common and specific diagnostic assays are largely unavailable. the success of the ‘one health' approach to eids in west africa is predicated on characterization of accurately diagnosed disease burdens. to this end, we must address inefficiencies in the dominant approaches to eid surveillance and the weaknesses of health systems in the region generally. this article is part of the themed issue ‘one health for a changing world: zoonoses, ecosystems and human well-being'. emerging infectious diseases (eids) represent a major threat to global health. in recent years, re-emerging and newly emerging wildlife-associated zoonoses such as ebola virus in west africa, severe acute respiratory syndrome (sars), human immunodeficiency virus (hiv) and numerous novel strains of influenza have led to substantial economic and human losses [ ] . prior to constituting a major outbreak, many zoonoses may exist within communities for some time as isolated or small clusters of cases [ , ] . such cases represent an important opportunity for early intervention but often proceed undetected due to a range of poorly defined clinical and social factors, many of which are exacerbated by the remote and tropical environments in which wildlife-associated spillover events tend to occur. west africa has been identified as an environment particularly prone to zoonotic spillover and as such requires special attention for this role in global health [ ] . the recent west african ebola epidemic exemplifies this. the integrated disease surveillance and response (idsr) programme is a centers for disease control and prevention (cdc) and world health organization (who) devised template for domestic infectious disease control infrastructure. in common with much of sub-saharan africa, west african countries rely on the idsr to implement the revised international health regulations (ihr, ) . the revised ihr include mandated surveillance and reporting requirements for 'any event of potential international public health concern, including those of unknown causes or sources' [ ] . previously, the ihr only required cases of three named diseases (cholera, plague and yellow fever) to be reported. substantial changes to reporting and surveillance requirements were triggered by the international spread of sars in , a previously unidentified zoonosis. the idsr primarily relies on facility-based surveillance for the detection of individual or small numbers of cases [ ] . this approach involves a healthcare worker, typically a doctor, identifying a significant disease within their normal professional activities treating patients. as often noted, rare or novel conditions such as an eid are difficult to detect through this approach, especially in a resource-limited clinical setting where there is a high burden of routine infectious diseases. here, we elucidate some of the sociomedical mechanisms that have an impact on facility-based surveillance in an under-resourced rural west african setting. we explore clinical diagnostic processes and their implications for the unseen emergence of novel pathogens. this context places this study of how novel zoonoses may be diagnosed (or not) at the centre of real world one health issues; if diseases are not diagnosed, they will remain neglected. the assumption is often made that important zoonoses can be detected and responded to 'at source', although the lack of reporting of single cases or isolated clusters of important human diseases like ebola is evidence that primary cases that do not spread are almost invariably missed. it is of great concern that current systems must be missing a significant burden of disease. for this study, we set out to explore the effectiveness of facility-based surveillance in rural west africa by undertaking a -month ethnographic study aimed at documenting complete trajectories of cases of cryptic febrile illness arising in the rural community of buoyem in the techiman district of the brong-ahafo region of ghana. buoyem is a rural agricultural community comprising a central town with a population of approximately and a collection of around smaller satellite villages accounting for another inhabitants. the study involved participants recruited from nine households in the buoyem area (table ). of the participants enrolled, came from three households in the main town and from six households taken from peripheral villages selected for their progressive remoteness, as measured by distance to a paved road (an established determinant of formal healthcare utilization) [ ] . enrolled households were visited approximately twice a week for the duration of the fieldwork so that febrile illness episodes could be detected early on and followed in their entirety. during the course of the study, of the enrolled participants developed fevers of unknown origin and were thus incorporated into the research as case studies. the criterion for inclusion as a case study was a self-reported fever of unknown origin occurring within the previous h. fever (a body temperature exceeding . c) is a fairly universal symptom in response to infection. it was reasoned therefore that health-seeking behaviours in response to fever with any combination of other symptoms should provide a good insight into how eids might progress in a remote environment. when a participant self-reported a fever, they were observed throughout the illness episode with particular attention being paid to their health-seeking behaviours and, where the episode involved formal healthcare settings, the processes of nosology. in addition to participant observation in clinical settings, subsequent interviews with the involved healthcare workers and the collection of data from secondary sources, such as patient files and hospital records, took place. sixteen of the recorded illness episodes were deemed 'routine', meaning they were perceived as non-life-threatening and resolved within days with only informal local treatment. this typically comprised the use of licensed pharmaceuticals leftover from previous illness episodes or purchased from a local drug seller, sometimes in combination with a homemade herbal preparation. of the eight participants who had illness episodes that were categorized as 'severe' or 'enduring', meaning they were perceived to be life-threatening or else failed to resolve within days of informal treatment, all used a nearby hospital. three participants belonging to town households attended the town's nurse-run clinic prior to presenting at a hospital (figure ). participants coming from village households tended to shun the clinic, claiming it was too costly relative to the effectiveness of the treatments available there. as all of the cases deemed 'severe' or 'enduring' ultimately ended up presenting to a hospital, shortcomings with facility-based surveillance are therefore likely not a consequence of the health-seeking behaviours of rural populations. rather, if facility-based surveillance is not working, the dysfunction must be within the healthcare setting. as such, our discussion is focused on our observations of the nature and effect of the diagnostic processes within clinical settings. across the eight patients and illness episodes that involved hospital treatment and consultation with a doctor, the observed diagnostic processes were extremely diverse and apparently vulnerable to the interactions of numerous material and human factors. with little or no available literature on the drivers of diagnosis in resource-limited settings, a discussion, even one based on this limited sample, is insightful and important. as expected for any clinical setting, the doctors within the study reported employing a differential diagnostic approach to choosing treatment strategies for their patients. a differential diagnosis is commonly perceived as a systematic and exhaustive process. the three basic steps of a differential diagnosis are examining the patient, compiling a list of candidate conditions and testing candidate conditions in order of perceived likelihood until the underlying condition, or rstb.royalsocietypublishing.org phil. trans. r. soc. b : conditions, has been identified. what follows is a description of the most obvious impediments to accurate diagnosis of a patient presenting to a regional ghanaian hospital with a febrile illness, organized in terms of the three primary steps of differential diagnosis. the following description reveals that, when performed in a resource-limited clinical setting, the diagnostic process is often neither linear nor conclusive. the first step in performing a differential diagnosis involves the physician gathering the relevant information about the patient and their condition. this often involves the taking of a medical history and sometimes a physical examination of the patient. in this study, however, this step was limited to a nurse measuring the patient's temperature, weight and blood pressure and the doctor prompting the patient for a list of their current symptoms. this limited interaction comprised all of the communication during the consultation for all of the eight case studies. all participants remained unaware of their diagnosis and the nature of the drugs that were prescribed, which is consistent with findings from other studies of ghanaian clinical settings [ ] . this lack of communication was associated with poor doctor-patient relationships and perhaps reflected a low doctor-to-patient ratio (about doctors served a population of approximately people in ) [ ] . for seven of the eight cases, this lack of communication-in particular a tendency for patient records to be maintained but not reviewed-led to doctors unknowingly prescribing treatments that had already been prescribed to, and taken by, the patient following earlier visits to formal healthcare facilities, such as the hospital and town clinic. this resulted in therapeutically and diagnostically redundant visits and additional costs to the patient. following the assessment of the patient, the next stage of the differential diagnosis process involves the doctor compiling a list of possible candidate conditions. in theory, these are organized according to likelihood based on the presentation of the patient and the doctor's knowledge of local disease prevalence. in practice, all eight participants who presented to a clinic or hospital with a fever or a reported history of fever were initially diagnosed with, and treated for, malaria. no diagnostic tests, including malaria rapid diagnostic tests (rdts), which were available at some sites, were employed. this practice of presumptive treatment of fever cases for malaria can be linked to a now superseded set of who guidelines on the treatment of malaria in children. however, a growing body of research suggests that it is still commonplace in clinical settings across much of africa [ , ] . as revealed in interviews with the doctors, where antimalarial treatment failed to relieve the symptoms of the patient, the next recourse was the prescription of a broad-spectrum antibiotic. this unofficial treatment protocol was observed in five of the eight case studies. one doctor explained that this was due to the availability of broad-spectrum antibiotics and that it was often a successful strategy. given that a primary role of doctors in this setting is to treat successfully as many patients as possible within severe material and time restraints, the identification of a particular disease aetiology is not always necessary or pursued. the presumptive diagnosis of malaria and subsequent presumptive diagnosis of bacterial infection were both hurdles for the consideration of other candidate conditions. these would not have caused such significant setbacks to the diagnostic process if the testing and discrediting of candidate diagnoses had been done with diagnostic tests and not through the trial and error of different treatments. from the limited number of case studies presented, we cannot establish any patterns of utilization for the diagnostic tests available at the hospitals. there were significant financial disincentives to the use of diagnostic tests, however, both for the hospital and for the patient. patients had to coordinate their own testing, often requiring multiple trips to the hospital at their own expense. uninsured patients were required to pay for diagnostic tests, and the national health insurance scheme (nhis) would provide only limited reimbursement to the hospital for insured patients. the morespecialized tests required to identify any uncommon eid, should a relevant test exist, would be even less accessible and unlikely to be used. it was apparent through the case studies that diagnostic technology is not routinely used when managing a febrile illness, at least not in the early stages. as this resulted in most candidate conditions being tested through the patient's response to various treatments, often only one diagnosis could be considered or discredited at each visit. this had particularly severe repercussions for the rural villagers seeking hospital treatment. the increased associated transport costs the villagers faced and the lower average income and likelihood of nhis membership meant they had to source money communally for their trip and treatment. this typically limited them to no more than two hospital attendances per episode of illness. participants from the town experienced fewer financial restrictions than the villagers and were able to pursue hospital treatment across lengthy courses of illness. they typically only ceased hospital care when failure to resolve the illness led them to doubt the efficacy of the biomedical approach. it was often at this point that a participant would engage a professional traditional healer such as a spiritualist. both the villagers and the townsfolk were largely unaware that many of their hospital visits were redundant. however, these repetitive and often unproductive visits were instrumental in the decision of both groups to not return to the hospital. within the differential diagnosis process, there was no mechanism for feedback to notify the doctor of a successful diagnosis and treatment of a patient. it was therefore impossible to differentiate between a successful and failed diagnosis. correct diagnosis, spontaneous recovery, premature exit resulting from lack of funds or lack of faith in the biomedical approach or death all produced a final untested diagnosis. for example, one of the participants was diagnosed and treated for malaria twice at a hospital in the week prior to his admission as a suspected meningitis case. he died the day following admission. during his admission, a diagnosis of meningitis was rejected and replaced by a tentative diagnosis of hepatic encephalopathy that was not explored. as the illness episode concluded, this diagnosis was recorded as the cause of death without laboratory testing. another factor reducing any consideration of an uncommon diagnosis is the disproportionate representation of diseases perceived to be common locally. in the course of a single episode of illness, multiple disease labels were generated across multiple hospital attendances. for instance, in the case above, the hospital recorded two cases of malaria and one case of hepatic encephalopathy. such a process distorts doctors' perceptions of local epidemiology by skewing disease surveillance data towards already common conditions and further prejudicing them against unusual or less well-established diagnoses. the exact combination of factors that reduced the reliability of the differential diagnosis process varied between cases. in all eight cases, however, confounding factors were sufficient to precipitate an early departure from the process. not one of the eight participants captured in the study ceased to pursue hospital treatment because they had been successfully treated. many of the factors implicated in the consistent failure to diagnose participants are improving across ghana. healthcare and transport infrastructure are improving, there is a decreasing burden of many common infectious diseases and there are interventions aimed at improving doctorpatient relationships [ , ] . many of the recurring problems in identifying early cases of eids are not unique to ghana or west africa. the diagnosis of a rare condition within the time restrictions of a single episode of illness is problematic in any clinical setting. this difficulty is due primarily to the differential diagnosis process being based on a likelihood model and the uncommon (by definition) nature of eids. the processes of identifying and labelling diseases via clinical diagnosis therefore make facility-based surveillance unsuitable as a primary source of eid surveillance. the use of facility-based surveillance for eids within the idsr framework is likely by default rather than by design. the idsr technical guidelines were originally developed to tackle major burdens of infectious disease and, as such, do not include specific instructions for eid surveillance. this results in the task of eid surveillance being absorbed by the system in place for identifying and controlling common infectious diseases. as the idsr is the elected vehicle for the revised ihr ( ) in most of africa, an effective eid surveillance system needs to be developed, especially in environments prone to eids. a more suitable alternative to facility-based surveillance could be the establishment of specialized national diagnostic laboratories that are able to receive and test samples without the patient or local health clinic incurring additional costs or crippling bureaucracy. a number of studies have shown that the existence of a previously unknown pathogen within a human population often does not signal an impending pandemic. indeed, some novel zoonoses have been found to cause only a single case or a small number of cases before apparently disappearing from the population entirely [ ] [ ] [ ] . taking a slower approach to detection, one that exceeds the length of an episode of illness, might be a possible solution. a similar approach is already employed in ghana for influenza surveillance, where regional hospitals act as sentinel sites routinely sending samples to a specialized laboratory to monitor the strains circulating within the country. an archival approach to eid surveillance has utility by slowly contributing to a more nuanced knowledge of the local epidemiology. this characteristic, however, is at the expense of the immediate utility promised by facility-based surveillance in containing the threat of an outbreak, a function it may serve in response to larger and more sudden spillover and outbreak events. as such, the introduction of a laboratory-based system for eid detection should not usurp the place of the facility-based system within the idsr framework but, rather, complement it by providing a more systematic and reliable approach to surveillance. such a reformed system needs to be targeted at regions, such as central and west africa, which are particularly susceptible to zoonotic spillover and therefore likely to see the emergence of a new infectious disease. regardless of the exact approach taken, the creation and incorporation of a dedicated system of eid surveillance into african countries' national disease control infrastructure is imperative. this is not to say that there is not also a need to address the various factors confounding healthcare providers' use of differentials diagnoses in resource-limited settings, which are crucial to the delivery of effective clinical care. however, the success of the one health approach to eids in west africa is predicated on characterization of accurately diagnosed disease burdens. we must attend, therefore, to the inefficiencies in our dominant approaches to eid surveillance in west africa or we will be unable to effectively set public health priorities and prevent future disease outbreaks such as the recent ebola epidemic. ethics. this work was conducted with approval of the noguchi memorial institute for medical research institutional review board ( permit # / - ), the university of cambridge human biology research ethics committee ( permit #hbrec. . ) and the zoological society of london ethics committee (human impacts ref. wle ). the perpetual challenge of infectious diseases epidemic dynamics at the human-animal interface avian influenza a viruses: from zoonosis to pandemic global trends in emerging infectious diseases international health regulations technical guidelines for integrated disease surveillance and response in the african region modelling and understanding primary health care accessibility and utilization in rural south africa: an exploration using a geographical information system perceived quality of healthcare delivery in a rural district of ghana techiman municipal health directorate annual report improved diagnostic testing and malaria treatment practices in zambia guidelines and mindlines: why do clinical staff over-diagnose malaria in tanzania? a qualitative study ministry of health (ghana) the health sector in ghana: facts and figures human viruses: discovery and emergence nosocomial outbreak of novel arenavirus infection b-virus (cercopithecine herpesvirus ) infection in humans and macaques: potential for zoonotic disease competing interests. we have no competing interests. key: cord- -reoa kcw authors: botreau, hélène; cohen, marc j. title: gender inequality and food insecurity: a dozen years after the food price crisis, rural women still bear the brunt of poverty and hunger date: - - journal: nan doi: . /bs.af s. . . sha: doc_id: cord_uid: reoa kcw the global food price crisis of – had devastating impacts for the world's poorest people, especially for smallholder farmers and in particular for women, who face discrimination and a heavy burden of household responsibility. the international policy response to the crisis saw the launch of numerous new initiatives and instruments, but funding has been insufficient and policies have failed to address the structural deficiencies in the global food system. a dozen years on, in light of climate change and increased conflict, new policies are needed to reorient the food system so that it prioritizes smallholder communities, with a renewed focus on the needs and aspirations of women. . introduction . underlying structural factors and their impacts on women . what led to the food price crisis? . impacts and long-term effects on women smallholder farmers . how effective was the global response in tackling the structural causes of the crisis? . the global response after - . responding to the crisis with business as usual . a lack of coherent governance for global food security . addressing women's food insecurity in a (more) unstable and broken food system . increased challenges for food and nutrition security for women . what changes have there been in the institutional and funding agenda to address women's food insecurity? . closing the gender gap: transforming rather than mainstreaming . conclusion and recommendations . guarantee participation and inclusiveness . increase aid to agriculture . increase national public investments in agriculture in developing countries . ensure women's access to resources, competitive markets and farmers' rights the global food price crisis of - underscored how fragile livelihoods are among the world's extremely vulnerable people, as it drove million people in developing countries into poverty (world bank, ) . in the aftermath of the crisis, in the food and agriculture organization of the united nations (fao) estimated in a that almost billion people worldwide were undernourished (fao, a) . as this chapter will show, the crisis disproportionately affected women. in the un world food programme (wfp) calculated that women and girls accounted for % of chronically hungry people around the world (wfp, ; see also scott-villiers et al., ) . the flurry of policy action in the months and years following the price spike brought some hope that the world's governments were prepared to tackle the structural factors behind the crisis, which had a severe impact on vulnerable people's resilience to shocks. the effects proved especially severe for women small-scale agricultural producers. a dozen years later, despite the international commitment to sustainable development goal (sdg) of zero hunger, too many of the policies that precipitated the food price crisis remain in place (wise and murphy, ) . the united nations food, agriculture, and health agencies estimate that the number of hungry people in the world increased by million in , and rose by million over the preceding years (fao et al., ) . viewing food insecurity through a somewhat different lens, the agencies also a following these estimates of hunger, the committee on world food security (cfs) recommended that fao revise its much-criticized methodology for counting the number of undernourished people. this new methodology included updated population estimates and household surveys on food consumption, and took into account food waste at the distribution level. it was used for the first time in the state of food insecurity security in the world (sofi ) (fao, ) report, and the hunger trends observed showed significant changes. the methodology has been under constant revision since then, with new indicators added to make it more complete. therefore, it is not possible to compare figures across annual volumes of the sofi report. estimated that over billion people ( . % of the world's population) cannot afford a healthy diet (fao et al., ) . women smallholder farmers are among the worst affected, and remain far from realizing their human right to adequate food. looking back in , reconsideration of the long-term impacts of the food-price crisis and the impacts of the policy response is long overdue. it has become clear that we will not achieve sdg , given that the structural causes of hunger remain unaddressed and that additional issues have become more salient since . this chapter will proceed as follows: • reflecting on how the existing challenges faced by women smallholder farmers were exacerbated by the structural causes of the food price crisis; • examining major policy responses from governments and the private sector and analyzing their effectiveness in addressing the structural causes of the crisis; • setting out the lessons learned from the major failures of this policy response; • identifying key challenges and gaps in financial aid to women smallholder farmers and, more specifically, looking at the level of official development assistance (oda) targeted to them since ; and • providing policy recommendations to address all of these issues. the challenges and questions raised by this chapter remain substantial, diverse and context-specific. although we cannot explore these topics exhaustively, we hope to contribute to renewed calls for justice and the right to food for the hundreds of millions of people who remain hungry in a time of plenty. their impacts on women . what led to the food price crisis? the term "global food price crisis" usually refers to one of the biggest price surges (de schutter, ) in a period of extreme volatility for primary commodities, mainly the most widely consumed cereals, which had peaks in the second half of and the first half of and another spike in - . between march and march prices rose %, those of soybeans jumped % and wheat prices ballooned % (fao and oecd, ) . the price of rice climbed fourfold during january-april , as several major exporters embargoed foreign sales of this lightly traded commodity (fao and oecd, ) . b global food prices declined from their peak in june , as the world economy fell into recession (fig. ) . prices remained relatively stable until the first half of and then began rising again, reaching an all-time high in february (fao, ) (fig. ). severe drought in major exporting countries was the key short-term factor contributing to this second spike (trostle, ) . as a study by the institute of development studies conducted for oxfam noted, the rise in prices pushed low-income people, who precrisis frequently spent % or more of their incomes to buy food, further into poverty and increased their difficulties in maintaining basic consumption levels: people for whom securing food has already absorbed a large share of their resources and energies before the food crisis came under intense pressure to alter their relationship to food and thus to the economy-to spend more time earning more money to cover basic provisioning and to extract more value from whatever they consumed. scott-villiers et al. ( ) . in other words, the crisis posed a severe threat to the right to adequate food for millions of people (de schutter, ) . . . a broad variety of causes led to the - food price crisis, and views on the weight to give to long-term trends vary in the literature (scott-villiers et al., ) . nevertheless, as olivier de schutter, then the un special rapporteur on the right to food, observed in , "the disaster which results from the increase of international prices of food commodities is a man-made disaster. the causes are identifiable" (de schutter, ) . the agri-food system and its contradictions contain a number of hidden causes of the crisis, what we call "structural factors": liberalization of agriculture and trade, concentration of distribution and inputs marginalizing smaller production units and decreases in investments in agriculture and development assistance to the sector in a context of increasing climate change. these long-term trends made smallholder farmers more vulnerable to shorter-term "conjunctural factors" experienced in the more immediate run-up to the crisis. these conjunctural factors consist mainly of an evolution of fundamentals of the market-supply and demand (bricas and goïta, ; clapp and cohen, )-and marked an increased level of globalization (scott-villiers et al., ) , creating an even more unfavorable economic context for smallholder farmers. in the decade prior to the crisis and following adoption of the world trade organization (wto) agreement on agriculture of and the world food summit in , there was a major shift in global food and agriculture, with lower trade barriers and more open markets. however, countries with weak market infrastructures and those that relied on a small number of export commodities did not gain from liberalization and faced risks associated with increases in world food prices, which would mean considerably higher import bills, potentially requiring them to spend their foreign-exchange reserves (trueblood and shapouri, ) . for farmers, this shift encouraged less production of traditional food cropswhich frequently were the crops that women farmers produced-in favor of crops for domestic and export markets, increasing their exposure to the volatility of those markets and their dependence on purchased inputs (un women, ) . most low-income countries moved rapidly away from self-sufficiency in food and in turn opened their domestic markets to external produce. from , sub-saharan africa became a net food importer (fig. ) , despite an impressive increase in regional production of major crops. between and , only one-fifth of african food exports stayed in african countries, and % of agricultural imports came from other continents (rakotoarisoa et al., ) . west africa tripled its rice imports in the s (fig. ) (oecd, ) . outside of africa, haiti reduced its tariff on imports of rice-the daily staple for most haitians-from % to %. from near self-sufficiency, the country went to importing % of its rice consumption, and has now become the second largest market for us rice (cohen, ; oxfam, ) . liberalization policies have also facilitated the overwhelming market supremacy of a small number of large companies, from farm inputs to sales of food to consumers. as mckeon ( ) has observed, "corporate power in food chains has continued to grow unabated, with the mega-mergers of major agribusiness multinationals threatening a further concentration'" over the past few decades, four firms, known as the abcd companies-archer daniels midland (adm), bunge, cargill and louis dreyfus-have come to virtually control trade in grain and oilseeds plume, ) . such concentrated market power is often seen in low-income countries that typically have at best insubstantial market regulation. in the agrochemical sector in the late s, the top companies accounted for % of global sales. by , seven companies controlled the same market share (humphrey and memedovic, ) . in , as a result of the mega-mergers that mckeon highlights, three companies (bayer, dowdupont c and chemchina) stood poised to claim a % share of global commercial seed and agro-chemical sales (friends of the earth europe et al., ). however, the ability of these firms to administer the prices of seeds, for example, varies according to crop and country context (cavero and galiá, ; oecd, a) . the rate of growth of public spending on agriculture slowed dramatically during - , and it stagnated in africa. however, spending rose steadily in asia, and doubled during the two decades after . in the absence of public funding, smallholder producers, particularly women farmers, had little ability to bargain with large agribusiness firms, middlemen or credit providers (un women, research is unlikely to address the problems facing low-income farmers, given the unlikelihood of a sufficient return on investment in the shortto-medium term. . . . decreased aid to agriculture the public expenditure trend was not offset by oda to agriculture. the period between and was marked by low food prices and a sharp reduction in aid to agricultural development and investments from oecd countries and multilateral agencies ( fig. ; see also hlpe, ) . most of the aid that there was continued to focus on staples productivity; greater support for fruits, vegetables and legumes could have benefited smallholders (pingali, ) . by , agriculture's share of bilateral aid had fallen to a quarter of its former level, and the trend was similar for multilateral agencies: agriculture fell from % of world bank lending in to just % in - (brock and paasch, ). climate change is resulting in more frequent and more severe heat waves, droughts and floods, which can decimate farm production. its effects contributed to food price increases in - and also in , with severe droughts in australia, canada, argentina and the united states, all major cereals producers (fao and oecd, ) . there were droughts in east africa in , (bailey, . the last of these affected more than million people and resulted in the famine in somalia that killed , people (news centre, crops to weather indicate that global maize and wheat yields between and may have been, respectively, . % and . % lower than they would have been without the effects of climate change (lobell et al., (mittal, )-growth in food crop production slowed from the mid- s. for cereals, which cover over half of the world's farm land, yield growth fell from % annually in the s to a little more than half of that in the s, then increased to nearly % in the s (fao, a). . . . . escalating crude oil prices have led to rising farm production costs in the st century, increases in the prices of fertilizer and oil, which are key farm inputs, have exceed those for agricultural produce (fig. ). this has created further financial difficulties for farmers, as most developing country governments have reduced or eliminated subsidies on inputs and assistance with credit and marketing for smallholders (un women, (world bank, ) , and this was associated with a growing urban middle class. food consumption habits evolved and all regions in the world saw increased meat consumption and thus a rising demand for grains for animal feed (see fig. ). during this same period, global food trade concentrated on just four main crops: rice, maize (this, in particular, is an important animal feed as well as a major direct source of human food in sub-saharan africa and parts of latin america) and wheat, plus soybeans (directly consumed by humans, an input into processed foods, an animal feed and also a source of biodiesel) (mccreary, ) . the trends of dependence on the three major global cereals and on imports for food supplies have been simultaneous and mutually reinforcing. in sub-saharan africa and south asia-which are home to the majority of the world's food insecure people and thus constitute hunger's center of gravity-consumption of these cereals has steadily displaced traditional staples such as millet, sorghum, bananas, cassava, potatoes, sweet potatoes and beans over a long period. the trend was remarked on by people interviewed during the - crisis, who repeatedly mentioned the decline of "traditional" foods due to reduced availability, higher cost and longer preparation time (scott-villiers et al., ) . . . . . rapid expansion of biofuels production the expanded production of biofuels was a key driver of the food price crisis: increased biofuel demand in the united states, due to legal mandates to blend ethanol into petrol, pushed up maize prices and probably also those of soybeans, while eu and european expansion of oilseed production for biofuel led to higher wheat prices ( fig. ; see also headey and fan, ) . governments across the world attempted to reduce dependency on oil, increase the use of renewable energies and halt declines in farm income, and approved legislative instruments that encouraged the biofuels industry. those policies, led mainly by rich countries, created a demand shock in international markets (wise and murphy, ) . during a very short period before the crisis, % of the global maize supply was diverted to the us ethanol program. moreover, biofuels have direct impacts on land use and land rights, compromising food security. the eu's bio-energy policy helped biofuels industries to prosper, but the , km of eu land devoted to biofuels crops in could have grown enough food for million people that year (herman and mayrhofer, ) . . . . . declining stocks a low "stock-to-use" ratio due to low stocks, high demand or both creates upward price pressure (fao, b) . low stocks are a vulnerability factor, especially for countries already at high risk vis-à-vis prices, since reserves provide a buffer against both rising prices and poor harvests (wise and murphy, ) . in - the world cereal stockto-use ratio stood at an all-time low of . % (fao, b). . . . . dollar devaluation depreciation of the us dollar also played a role in food price escalation. in general, a weaker dollar is associated with commodity price increases (fao, b; headey and fan, ) . for countries that tie their currency to the dollar or that have a weaker currency, dollar depreciation makes food imports more expensive (fao, b). . . . . increasing speculation in commodities dollar depreciation also made food commodities attractive to investors, especially as technology and housing "went bust" (clapp, ). the growth of food commodities investment became mixed up with the financial crisis of - , which persuaded many noncommercial traders (whether considered "investors" or "speculators") to move their money away from collapsing stock, bond and property markets and into the commodity futures trade (fao, b) . such large-scale speculation contributes to commodity price volatility and gives inappropriate market signals to agricultural producers (fao, b). from the beginning of the food price crisis, the rice market came under pressure because some governments imposed bans on exports (such as restrictions on non-basmati exports by india, e a leading exporter) (usda/fas, ) and major importers such as the philippines made large-scale purchases, seeking to lock in prices as a hedge against further increases (childs and kiawu, ) . like the diversion of maize to biofuels, all this created distrust on the global markets and exacerbated upward pressure on prices. because of the large amount of international trade in wheat and maize at a time of extremely low global stocks, the price increases quickly spread to many national markets. however, transmission of world market prices to domestic markets varied greatly from country to country: in china and india, domestic prices were virtually unaffected; in brazil and south africa e india lifted this ban, imposed in april , in . during the period of the ban, thailand, pakistan and vietnam, among others, moved in to replace indian exports. it served to keep rice affordable for indian consumers, but adversely affected (albeit marginally) india's foreign exchange earnings. since lifting the ban, india has become the world's largest exporter of rice. the authors are grateful to ranu bhogal of oxfam india for pointing this out. prices increased in line with international markets; but in ethiopia and nigeria domestic prices increased dramatically. in general, according to one analysis, there were "higher price transmission rates for import dependent countries, including rice in senegal, mali, burkina faso, niger… and uganda, maize in malawi and uganda, and wheat in ethiopia" (baltzer, ) . the degree of price transmission was affected by domestic and trade policies in importing countries. f the events of - brought into plain view the cracks in an unsustainable food system that was already having severe negative effects on the basic livelihoods of smallholder farmers (murphy and schiavoni, ) . the structural factors outlined above (liberalization of the agri-food system, concentration in input and output markets, a decrease in public investments in agriculture, declining aid to agriculture) showed how unbalanced the system had become, privileging big agri-food businesses and making low-income people even more vulnerable to the conjunctural factors of the crisis. these short-term factors triggered the crisis and further impoverished the poorest people, denying them their human right to adequate food and nutrition and illustrating the global food system's failures (murphy and schiavoni, ) . rural people, and especially farmers, were on the front line. people living in rural areas are among the poorest in the global south and at the time of the crisis three-quarters of them were living on less than the equivalent of $ a day, and spending up to % of their earnings on food (coon, ) . already precarious rural livelihoods (due to geographic, economic and political isolation, poor access to markets, limited opportunities for work, low productivity and seasonal and long-term migration) (coon, ) amplified the threat of soaring agricultural prices, which affected not only consumers and urban dwellers but also food producers. the overwhelming majority of small-scale farmers are also net food purchasers, with very high exposure to price increases (murphy and schiavoni, ) . in theory, higher prices offered opportunities to farmers who are net food sellers, but price increases for agricultural inputs (fertilizers, fuel etc.) offset this possibility (quisumbing et al., ) . f according to baltzer ( ) , 'much of this variation [in the price transmission patterns] can be explained by price stabilization policies, public policy failure, incomplete market integration, and coinciding domestic shocks.' . . women smallholder farmers have been disproportionately affected because gender inequalities remain very strong in agriculture, women farmers are particularly at risk of food insecurity, especially in times of crisis (fao, ). rural women account for one in four people on earth and on average for nearly half the agricultural labor force in developing countries (fao, a) . women play crucial food-security roles, which include farming, food processing, marketing and ensuring household consumption and nutrition (fao, a) . nevertheless: • they face discrimination and frequently are in a weak bargaining position. in addition, other forms of discrimination (based on, e.g., race, class, caste or religion) often intersectionally reinforce gender inequality (un women, ). • the diminished state role in agriculture in the s and s added to female farmers' marginalization, as it reduced their access to inputs, resources and services (un women, ) . rural women also face unequal power relations within both the household and wider society, which have impacts on many aspects of food security. at the level of society: social inequalities come from socially constructed barriers to accessing productive and financial resources that also hinder social participation and political representation. patriarchal norms leading to power imbalances between women and men create disadvantages for women in agriculture, specifically in land rights (small plots, difficulties accessing ownership, discriminatory inheritance rights), productive resources (no access to credit markets, extension services or inputs), unpaid work, insecure employment and low levels of participation in decision making (sexsmith et al., ) . in the household: cultural practices and intra-household bargaining power can also determine the allocation of household incomes to food and care needs. women's weaker position within the family and social standards that favor boys over girls lead to poorer nutrition among women and girls (fao, a; lourme-ruiz et al., ) . . . . the challenges already facing women smallholder farmers were exacerbated by the food price crisis even though there is as yet inadequate research on the gender differentiated impacts of the food price crisis, it is clear that women bore the brunt of it and came under the most pressure to cope with its effects (quisumbing et al., ) . as hossain and green ( ) have observed: the effects differ by gender…women come under more pressure to provide good meals with less food, and feel the stresses of coping with their children's hunger most directly. these stresses push women into poorly paid informal sector work, competing among themselves for ever more inadequate earnings. the crisis really was a matter of inequalities in achieving the right to adequate food and nutrition, and the short-term factors involved in it exacerbated all the gendered dynamics of the food system (un women, ). discrimination against women at these different levels affects their capacity to respond to shocks and cope with food crises (fao, ; un women, ) . because of the constraints they face in accessing extension services and financial and agricultural resources, limited legal benefits and protection, heavy time burdens and limited decision-making power, women have fewer options for overcoming any crisis and face more risks than men of losing their assets or formal sector jobs. price spikes have particularly negative effects on women heads of household, for several reasons: they suffer labor market discrimination, which confines them to informal, vulnerable and casual employment; they often receive less pay than men doing the same work and they usually spend a higher share of their income on food than male household heads (holmes et al., ) . when looking at intra-household dynamics, it is crucial to highlight women's food-security roles: they usually have the primary responsibility for procuring and preparing food within the household (ford, ) . with regard to nutrition, they play an important role in providing dietary diversity through their vegetable gardens (which are often not considered "agriculture"), and also because they grow a large share of the cereal or root crops that the household consumes (doss et al., ) . during - , improvements in women's education and social status accounted for more than % of the substantial reductions in child malnutrition that occurred (smith and haddad, g ). in times of crisis, poor rural households face losses in assets, productivity and income. men use their income to pay past debt and seek new farm production loans. when women's intra-household bargaining position is weak, g here is the methodology used: 'ifpri…examined the factors that helped reduce child malnutrition by % in the developing world between and . the evidence shows that increases in women's education accounted for % of the total reduction in child malnutrition, by far the largest contribution. improvements in women's status accounted for another %. improvements in food availability came in a distant second to women's education, contributing % to the rate of reduction.' the frequent result is less spending on nutrition and children's wellbeing. indeed, when poor households face a decline in food purchasing power, their coping strategies often include buying cheaper items and moving to less diverse diets, depriving pregnant and nursing women and young children of essential nutrients (holmes et al., ) . women often turn to extreme coping strategies: reducing their food consumption to make more available to others in the family (quisumbing et al., ) , collecting wild food or even migrating in distress or selling assets (holmes et al., ) . during the food crisis in chad, khadija khazali, a widow with seven children from azoza village, said, "we have reduced the number of meals daily, and women are digging in anthills to recover grainsa practice which our community has not had to resort to for a very long time" (ford, ) . women may also take unsafe jobs to boost their incomes, at the expense of their own security and health, e.g. working in mines (quisumbing et al., ) or going into prostitution (cohen and smale, a) . men have more access to social capital and have more pathways out of a crisis, whereas women often face severe time burdens, given the pressure on them to ensure the household's food security. therefore they do not enjoy the same opportunities (ford, ) . men can migrate more easily to find a job in urban areas, and this affects the coping capacity of the women who are left behind: they now must manage the family farm, but may still have to get approval from their absent husbands on key agricultural decisions (coon, ) . the structural causes of the crisis? . . putting food security back on the political front burner the crisis and the subsequent media coverage created an opportunity to put food and agriculture back at the core of global development policies, following years of neglect. after - there was a flurry of action, from countries and regions on the front line of the crisis to oda, multilateral initiatives for reinvestment in agriculture and intergovernmental action, to elevate the place of food security on the global policy agenda. as noted in table , in the first years following the crisis the global policy responses and funding commitments focused on macro-level relief such as support for production, food aid and preventing export bans (quisumbing et al., ) . help million africans get out of poverty by . source: authors' analysis; specific sources for each initiative indicated in the relevant row. the fao was the first institution to react, establishing the initiative on soaring food prices in december , with a budget of $ . bn. this provided countries with technical advice through fao's guide for policy and programmatic actions at country level to address high food prices (maetz et al., ) . then in april world bank president robert zoellick pushed for a "new deal for a global food policy" and established the global food crisis response program (gfrp), with a view to the "expedited processing" of assistance and an initial budget of $ . bn. similar to fao's initiative, the gfrp provided technical and policy advice to severely affected, low-income countries (world bank, ). the first coordinated international response was the high-level conference on world food security, held in rome in june and attended by over heads of state from the global south and north. a group of international organizations produced the comprehensive framework for action (cfa), which was launched at the conference; this called for an additional $ bn-$ bn per year for food aid and oda for agriculture and social protection, and advocated allocating % of international aid to agriculture for the next years. the conference resulted in greater collaboration among the rome-based un food and agriculture agencies, but it also led to greater fragmentation of food-related international institutions as yet more new ones were created. then the world summit on food security in rome in november agreed to the rome principles for sustainable global food security, which called for better coordination and more stable funding (fao, c) . both the group of (g ) "leading" countries and the larger group of (g ) then agreed to food security initiatives, including at every annual g /g summit meeting from to . at the g summit in l'aquila, italy member governments pledged $ bn, but it turned out that a large part of this consisted of recycled promises or even money previously spent. in september the pittsburgh g summit asked the world bank "to work with interested donors and organizations to develop a multilateral trust fund to scale-up agricultural assistance to low-income countries" (g information centre, ). the resulting global agriculture and food security program (gafsp) (world bank, a) currently is providing $ . bn to countries through two windows: one focused on supporting public sector action in developing countries, and the other providing loans, guarantees and equity to the private sector to support investment in agricultural development (gafsp, ). following the second spike of the crisis in , there was an additional set of global responses. this time there was a greater focus on long-term agricultural investments, especially through partnerships with other actors like the private sector, whereas in - the response was mainly through the public sector. reflecting on the policy responses to soaring food prices, de schutter ( ) commented: today, too many [governments] continue to see hunger as a problem of supply and demand, when it is primarily a problem of a lack of access to productive resources such as land and water, of unscrupulous employers and traders, of an increasingly concentrated input providers sector, and of insufficient safety nets to support the poor. too much attention has been paid to addressing the mismatch between supply and demand on the international markets […] while comparatively too little attention has been paid both to the imbalances of power in the food systems and to the failure to support the ability of small-scale farmers to feed themselves, their families, and their communities. . responding to the crisis with business as usual . . addressing supply and demand factors: increasing productivity as a major solution, but neglecting the issue of marginalization the marginalization of whole segments of the population in attaining food security and nutrition throughout the food price crisis made it clear that the main issues were access and inequality, rather than food production. however, the policy discussion tended to focus on the need to double production, both to dampen short-term price increases and also to meet projected population growth through to . efforts and plans tended to focus on this perceived need for increased production, even though supplies were already in substantial surplus (bricas and goïta, ) . between june and july , wfp provided short-term food aid valued at $ . bn, nearly double the $ . bn in agricultural aid mobilized by the world bank, fao and the international fund for agricultural development (ifad) (brock and paasch, ). wfp's big fundraising push sought to compensate for the effects of rising food prices on its ability to procure commodities (golay, ) , but in fact global food aid volumes in - were below those of - , as a direct result of the and price spikes (brock and paasch, ) . although some of the early initiatives did provide resources to smallholder agriculture, not all smallholders benefitted equally. thus, these programs fell short on delivering fully on the promise that smallholder-led agricultural development was back prominently on the development agenda. for example, an actionaid assessment showed that gafsp projects successfully targeted small-scale food producers. some projects emphasized women's empowerment, through income-generating opportunities for women and strengthening women's organizations. however, the study also pointed out that women were not adequately consulted in project design and activity planning, and their under-representation prevented them from receiving information about projects (actionaid, ). in addition, much of the funding provided to address the crisis aimed to promote the growth of productivity in staple grains. this was true of the majority of grants from gafsp and the us feed the future (ftf) program for example, with much less attention paid to horticulture crops (pingali, ) , even though horticulture production had the potential to boost the livelihoods and food security of smallholders, including women farmers (ulrich, ) . as table shows, targeting women was not a priority for most of the initiatives that sought to address the food price crisis. for those that did aim to make gender equality a high priority, such as the cfa, the gafsp and ftf, the impacts were limited because these initiatives focused on enhancing the productivity of "market-ready" farmers, who frequently tend to be male. although the cfs champions tackling gender inequalities in food security and nutrition, some member states have sought to weaken it over the past decades, leaving it with less influence. the g responded to the price spikes by encouraging the development of the agricultural marketing information system (amis). this initiative seeks more transparent commodity markets and information exchange among producer and consumer countries. however, amis has no control over many of the drivers of price volatility, and it is not able to monitor privately held stocks (e.g., those of grain traders) (murphy and schiavoni, ) . equally, it cannot tackle all the major market failures that lay behind the crisis. global policy makers largely failed to enact needed reforms to financial markets to prevent destabilizing speculation in commodity markets, due to pressure from industry lobbyists to maintain the status quo (see, for example, fang, ) . the high-level conference on world food security in , the g summit and the world food summit all pointed to the potential table attention to gender issues in initiatives undertake to tackle the food price crisis. gender focus? no mention of gender inequalities or specific focus on women in the guide. comprehensive framework for action (cfa) recognizes the disadvantages that women face in the food price crisis and their disproportionate vulnerability, especially to the long-term effects. the "menu of actions" recommends that "channeling food assistance via women should be encouraged and opportunities to improve program efficiency should be pursued." global food crisis response program (gfrp) no information found. purchase for progress (p p) takes a "gender transformative approach, directly focusing on women to ensure that they benefit from the project source." hokkaido, japan g summit no mention of gender inequalities. committed to a rights-based approach to support small-scale food producers, gender mainstreaming and ecological sustainability. feed the future the usaid forward policy framework and the feed the future guide, which support ftf operations, emphasize gender equality. the policy framework seeks to ensure women's engagement throughout the project cycle. the guide makes gender a cross-cutting priority, and aims to recognize women's often unsung contributions in agriculture, rights to resources and needs as food producers. l'aquila, italy g summit only one mention of women farmers as food security actors. makes "gender, food security and nutrition" a pillar of cfs work. the committee urged member states to undertake policy reforms to ensure gender equality in achieving the right to adequate food and nutrition, and to include women in food security decision making at all levels. it also asked member states to produce gender-disaggregated data. continued role that food reserves could play in the international response to the crisis (gubbels, ) . in the early s, under pressure from the international financial institutions due to the high cost, many developing country governments had abandoned the use of food stocks to counter physical shortages or reduce price fluctuations (see, for example, devereux, ) . but as prices rose in - , some countries sought to collaborate on a regional basis to create reserves to dampen the effects: new regional stocking systems were set up in west africa by the economic community of west african states (ecowas) and in southeast asia by the association of southeast asian nations (asean) (lines, ) . many governments reacted to the crisis, sometimes without efforts to coordinate their actions. however, many low-income, food-importing countries had limited capacity to respond (golay, ) and they also suffered impacts from the actions of other countries, such as export bans. gafsp directly supports achievement of sdg , encouraging gender equality. beyond increasing productivity and linking farmers to markets, gafsp's sustainable agriculture interventions have an impact on gender equality issues, such as women's agricultural empowerment, job creation on and off the farm and the enhancement of women's and girls' nutritional status. agricultural action plan mostly gender-blind, with a single "add women and stir" line in the action plan: "focus on the ultimate client, especially women." gender-blind: does not address gender issues, and evaluated by fao as "neutral" on gender, with no specific gender component or strategy. no mention of gender. weak on the recognition of women's rights and women's empowerment. source: authors' analysis; see table for specific sources for each initiative. in west africa in the majority of states lowered tariffs and taxes on some cereals, and some decided to control their domestic prices. although such measures can ease the food price burden on consumers, including politically restive urban populations, they cannot ensure efficiency and sustainability or target all vulnerable people, and may be very costly to maintain (cohen and smale, b; hathie, ) . most of the programs implemented after the crisis only targeted cereal production to reach national sufficiency and did not target other segments of the value chain. this strategy was conducted through national agricultural investment plans (naips), which originally were meant to tackle structural constraints and encourage sustainable agricultural growth as part of national development planning processes but which led to dependency on input subsidies and created a higher dependence on external markets (hathie, ) . fao examined the measures taken in more than countries from to , and found that policy decisions paralleled those of - ( fig. ) (see also maetz et al., ) . these measures included support for farmers' access to inputs and facilitating access to credit. however, such policies do not necessarily favor smallholder production, and many of the policies that on paper targeted small-scale producers excluded those considered to be nonviable economically, leaving many out (wise and murphy, ) . moreover, some of the policies emphasized inclusion of small-holders in export value chains without evaluating the environmental and economic risks (wise and murphy, ) . such policies often had disastrous impacts on small-scale farmers, especially on women farmers who relied on production of non-staple crops. these are key sources of micronutrients, but were crowded out by efforts to promote staple production with fertilizer and credit subsidies and price supports. in many instances, this led to increased prices for non-staples, such as fruit and vegetables (pingali, ) . . . . . liberalization of agricultural trade trade-oriented measures evolved as a medium-term trend. some exporting countries still observed export restrictions after to keep their domestic prices low but several countries, in contrast, put in place export facilitation measures (maetz et al., ) . h in addition, some governments lowered tariffs on imported food in order to improve food access (maetz et al., ) . overall, the policy responses did not reverse the direction of global agricultural trade liberalization. governments continued to reduce agricultural tariffs, and many offered preferential market access via bilateral agreements. world agricultural trade grew an average of . % per year during the two decades following enactment of the wto agreement on agriculture, i.e., (beckman et al., . . . . . acquisition of large tracts of land and biofuel policies one consequence of the food price crisis was a scramble to gain control of large tracts of land in developing countries. wealthy-country governments and private companies acquired much of the land in question. between and , the five leading investor countries were malaysia, singapore, cyprus, the united kingdom and china (grain, ; nolte et al., ) . large-scale land acquisitions (in excess of hectares) often dispossessed smallholders (geary, ; wise and murphy, ) . in most instances, these investments focused on export production rather than growing food h these countries included argentina, brazil, chile, ecuador and paraguay in south america, syria and yemen in the middle east and asian nations including china, pakistan and thailand, as well as india to some extent. countries limiting exports included cambodia, china, india, pakistan and vietnam. crops for local consumption, often with little regard to environmental consequences (geary, ) . two-thirds of these acquisitions occurred in countries facing significant food insecurity (geary, ) . usually, investors sought to acquire land in order to produce biofuel crops such as sugarcane, soy and jatropha for export (geary, ) . meanwhile, biofuels policies in rich countries remain largely unchanged. the united states, the main producer of maize-based ethanol, continues to require the blending of ethanol into petrol (bracmort, ) . legislative work to install a ceiling on the share of biofuels coming from food crops has continued at the eu level over the past decade. however, the eu's renewable energy directive (red ii) of still allows member states to burn massive amounts of food as fuel (oxfam international, ) . . . . . national public investments in agriculture continue to fall short food security and agriculture also gained regional and national policy salience after the food price crisis. for example, the comprehensive africa agriculture development program (caadp) (see box ), the comprehensive africa agriculture development program (caadp) (au, a) seeks to promote agricultural development, food security and good nutrition on the continent. it was endorsed at the au's summit meeting under the maputo declaration in (au, b) . from the start, it grabbed headlines by setting a target for every african government to devote a minimum of % of its budget to agriculture. the program is intended to end a long-ingrained habit of dependence on external resources. as a oxfam report noted, "international aid has long represented the bulk of agricultural sector financing in many west african countries. in , it accounted for % of the domestic agriculture budget of niger [and] over % in ghana…." (guereña, ) . oda remains a key source of finance for burkina faso's agriculture budget. i this situation has led the work of governments in unusual directions. thus, "national agriculture co-ordination bodies do exist…, but they serve more to exchange information than to actually co-ordinate interventions on the ground" (guereña, ) . by agriculture's share of public expenditure by african governments was just . %, although the share differed greatly from country to (anisimova, ) , and few have done so consistently. the au agreed to a new agenda in , marking years since the foundation of the organisation of african unity. its call to action for the next years included the following among its targets for african agriculture and agro-businesses by the time of the th anniversary: • achieve zero hunger; • lower food imports while boosting intra-africa food and agricultural trade to % of total agricultural trade; and • increase women's access to land and agricultural inputs, and allocate at least % of agricultural finance to women (au, ) . one year later in , the malabo declaration introduced a system of biennial reviews of countries' achievements under caadp (au, ). the first review, covering and , found that au members' expenditure on agriculture ranged from . % to . % of their budgets. ten countries met the % target, but this was no more than in , when the star performers were zimbabwe, malawi and ethiopia. however, malawi had fallen back from . % in to . %, ethiopia to . % and zimbabwe to . % (au, ). there are concerns that the review process is excessively "state-centric." popular narratives dwell on the argument that if the review process is there to ensure accountability, it must provide for inclusivity and the participation of all stakeholders. j indeed, the caadp framework remains very weak in terms of gender inclusion: the only caadp commitment related to gender is about women's involvement in agribusiness. in other words, the caadp commitments themselves are largely gender-blind. and although the technical guidance of caadp asks countries to collect gender-disaggregated data, there is minimal reporting on how women smallholder farmers are progressing under these commitments. . % of their expenditures that year to the military (world bank, ), despite the role played by conflict in increasing hunger in the region. despite renewed policy attention to agriculture, current public investment levels remain woefully inadequate. the un conference on trade and development (unctad) estimates an annual investment gap in developing country agriculture of $ bn over the period - (out of a total annual sdg financing gap of $ . trillion) (unctad, ). an analysis of national government and aid donor investments in ethiopia, ghana, nigeria, pakistan, the philippines and tanzania was unable to trace the flow of funds to women farmers. it found diversion of resources away from smallholders, and a lack of government capacity to ensure support for small-scale producers (either men or women) (mayrhofer and saarinen, ) . social safety nets put in place by governments are often efficient in targeting vulnerable populations; however, their efficiency is limited depending on the objective (e.g., assistance through cash transfers during lean periods) and there are multiple approaches (a short-term approach providing food assistance or long-term approaches aimed at strengthening resilience and fighting poverty). while donors' efforts to target support for social protection programs based on poverty criteria show decent results (schnitzer, ) , there could be better inclusion of women by adding gender-specific requirements (e.g., direct inclusion of female heads of household or women with children under the age of five). investments in r&d and in infrastructure have often focused on export agriculture and cereals at the expense of food crops oriented toward the consumption of local communities (de schutter, ) . the consultative group for international agricultural research's (cgiar) r&d expenditures on wheat, maize and rice, for example, more than doubled from $ m in to $ m annually during - (pingali, ) . the share of oda dedicated to food security and nutrition (fsn) has remained largely constant (fig. k ) : oecd data show that this kind of aid grew at the same rate as total oda, without major increases in response to the food price spikes. k we use the same methodology as presented in mowlds et al. ( ) to calculate gross oda disbursements for food and nutrition security (fns). we therefore consider all aid reported under agriculture, agro-industries, forestry, fishing, nutrition and development food aid/food security assistance as being aid for fns. while this approach will include some aid that is not specifically targeted to fns and will also exclude some that is, we feel that in the absence of a specific fns classification it provides a reasonable picture of trends in aid in this area. although the $ bn pledge made in l'aquila in did lead to additional oda resources for agriculture, the increase in funds for fsn was modest, as less than one-third of the pledges ($ . bn) represented additional money above spending that donors had already planned. also, the funds promised at l'aquila were one-time pledges, not multiyear commitments of additional money (mowlds et al., ; wise and murphy, ) . as the global economy fell into recession in the second half of , donors turned to austerity measures that limited oda increases (wise and murphy, ) . analyzing two major donors, the eu and the us, over a period of years shows that they are far from delivering. smallholders are central to the eu's international food security policy (ec, ) and its $ bn food facility, launched in , had a specific focus on small-scale producers. however, mayrhofer and saarinen ( ) found that less than one-quarter of eu aid for agriculture between and explicitly targeted small-scale producers. only %- % of eu agricultural funding promoted gender equality, and there was little attention to environmental sustainability. furthermore, with the exception of just year ( due to the food facility), the eu's agricultural oda has consistently supported industrial and export crops with significantly higher budgets than food crops. the destination of oda can also contradict aid effectiveness principles when it does not match policy commitments. in contrast with the eu commitment to target a substantial share of its aid to africa, oda for agricultural fig. ). the us created a -year, $ . bn agriculture, food security and nutrition initiative, feed the future (ftf), after l'aquila. since , the program has continued with funding of about $ bn annually. ftf has attempted to integrate the principles of aid effectiveness, particularly country ownership, into its programming, along with women's empowerment and sustainable natural resource management. its main emphasis is on working with "market-ready" smallholders who have high potential to engage in commercial agriculture, often however at the expense of farmers who have the least access to resources (land, labor, capital). also, the focus is more often on approaches to yield gains that require high levels of external inputs. the gains have been impressive: farm outputs in ftf focus countries over the period - exceeded those of other low-and low-middle-income countries by $ bn (feed the future, ). however, it is not clear whether these gains are sustainable once us aid ends. there also appears to be a real trade-off between aligning aid with national development plans missing out on small is beautiful: the eu's failure to deliver on policy commitments to support smallholder agriculture in developing countries. oxfam briefing paper. https://policy-practice.oxfam.org.uk/publications/missing-out-onsmall-is-beautiful-the-eus-failure-to-deliv-er-on-policy-commitme- . on the one hand and some other aspects of country ownership on the other, such as broad consultation with stakeholders and provision of resources through local systems and actors (muñoz and tumusiime, ) . . . . . growing role for multinational enterprise since the food price crisis, global policy has given more space to the private sector: for instance, the g launched its new alliance for food security and nutrition in africa in may , with a goal of "unleashing the potential of the private sector." developing country governments, bilateral and multilateral aid agencies, and multinational firms have all joined in promoting private investment in agriculture in the global south. but there is a big risk that this emphasis will bypass smallholder farmers (see box ). the g launched the new alliance on the eve of its camp david meeting in . this initiative represents a major scaling back of public funds provided by g countries for global agricultural development, leaving africa much more reliant on public-private partnerships (ppps) and private capital. the alliance has been denounced as "the new colonialism" by some organizations in the region (provost et al., ) . the new alliance has benefited the biggest agribusiness multinationals through legal changes and new investor frameworks in african countries, while family and smallholder farming is to a great extent excluded. of new alliance projects, only three are led by producers' organizations (one each in burkina faso, benin and malawi). the agricultural model supported resembles that of the green revolution of the s and s, i.e., monoculture, mechanization, very heavy dependence on purchased inputs, long distribution channels and production for export. it also puts considerable emphasis on the role of biotechnology. by focusing narrowly on technology-driven productivity gains, this approach misses much of the complexity that underlies hunger, and ignores the ways that the interests of powerful actors affect food and agriculture. there is evidence that the alliance has supported the enactment of laws conferring intellectual property rights to plant breeders; this impinges on traditional farming practices such as saving, reusing and trading seeds (qiu, ) . a uk government fact sheet on the new alliance makes no mention of gender or women's roles in food security (dfid, n.d.), and a new alliance progress report published in points out that only % of smallholder farmers taking part in new alliance projects are women (acf et al., ) . a new trend in development finance is private finance (pf) blending: during the past years, donors and international agencies have increasingly sought to engage the private sector in development, using oda to "leverage" private finance through "blending" the latter with public resources. the data on how much oda is going into pf blending arrangements remain unclear (eurodad, ) . although the absolute figures appear still to be relatively low, it is expected that they will increase rapidly over the coming years. such a financing mechanism could benefit smallholders in low-income developing countries, including women, by de-risking the provision of credit for on-and off-farm activities. for example, ftf in ghana has worked with a local financial institution to expand the provision of microcredit in the northern part of the country, which has higher poverty rates than the national average (saarinen and godfrey, ) . a study of pf blending programs in agriculture found serious data limitations (both quantitative and qualitative). it concluded that "donors have more work to do to ensure that private finance blending is an effective tool for financing smallholder agriculture and promoting inclusive and sustainable transformation in the sector" (saarinen and godfrey, ). the following broad conclusions have been drawn from a analysis by eurodad and oxfam (which is not specific to agriculture and food security). pf blending poses risks to the quality of aid (eurodad, ): • it is less transparent and accountable than other forms of aid. • development finance institutions (dfis) that engage in pf blending often do not operate according to the principles of development effectiveness, particularly country ownership. • so far, there is inadequate evidence on impacts and inadequate monitoring and evaluation. • pf blending opens up the possibility of supporting donor-based commercial interests, rather than local smallholders. this increases the risk that it will support tied aid. blending also could drain oda resources from high priority development programs and is unlikely to offer an effective means to finance development in poorer countries or for the poorest farmers. based on return on investment considerations, pf blending resources tend to go to middle-income countries and are geared toward better-off farmer groups who already have access to resources and knowledge (eurodad, ; see also saarinen and godfrey, ) . a recent study by the overseas development institute (odi) reinforces these concerns. it found that, despite donor claims of high leverage ratios, each $ . of blended development finance from multilateral development banks and dfis in fact leverages just $ . in private finance. the figure falls to $ . for lowincome countries (attridge and engen, ). adaptation to climate change is also an issue that needs high-level funding if the world is to reach zero hunger. the united nations environment program (unep) has found that developing countries' annual adaptation costs could reach $ bn-$ bn by (unep, ), with much of those costs agriculture-related. pearl-martinez ( ) found that adaptation finance still accounts for less than half of all climate finance. only a very small share is targeted to smallholders; in , the figure was just $ m. the food price crisis of - generated a strong reaction and opened the door to civil society and the scientific community to push for a radical transformation of agri-food systems that would take account of environmental, social and health challenges and would promote fairness and sustainability, through balanced governance (bricas and goïta, ) . despite these opportunities, however, the governance of global food security is under threat and its shake-up after the food price crisis has not led to smooth coordination, coherence or convergence among the multiple stakeholders. multilateralism and global governance are more and more hybrid and fragmented: numerous parallel and overlapping initiatives and platforms deal with food security and operate without coordination. so far, they have not proved able to converge to attain sdg (zero hunger), (gender equality) or (combat the impacts of climate change). since the food price crisis, the decision-making center has shifted uncertainly between the cfa, the high-level task force on global food and nutrition security (hltf), the g , the g and the world bank and the international monetary fund (imf), with strong influence from the private sector. the decision-making power of the cfs has been reinforced since its restructuring, but its recommendations to member states remain purely advisory. paradoxically, food security governance has also been more concentrated among just a few actors since the food price crisis. after the crisis, we can identify four relevant types of international agency involved in food security governance: • general political direction: the g /g and the g . these groupings are powerful as they are dominated by richer countries, include all the main aid donors and can take big decisions at moments of crisis. even in the more broadly based g , the representatives of the global south are either bigger countries (e.g., indonesia), members of the brics group (e.g., south africa) or both (e.g., brazil, china and india). africa is represented only by south africa, while small island states, which are extremely vulnerable economically and climatically, are not represented at all. • development aid: e.g., wfp, the world bank, ifad, usaid, eu institutions, such private foundations as the bill & melinda gates foundation and the rockefeller foundation and private ventures like the alliance for a green revolution in africa (agra). the world bank and the imf wield outsized influence on countries through their loans, conditionalities, policy advice and technical assistance, much of which is followed by bilateral aid agencies as well (eurodad, ; stichelmans, dispute settlement mechanism is currently in crisis due to a withdrawal of cooperation by the us, which is seen in some quarters as an effort to undermine the organization (bey, ) . other analysts see us obstruction as part of that country's negotiating posture tied to its trade disputes with china, and note that the us continues to win a substantial share of the complaints it brings to the disputes body (hanke and von der burchard, ; lamy, ) . this fragmentation leads to a lack of coordinated policies and coherent governance, with strong competing perspectives. the un system has promoted a rights-based approach to food security through the cfs, encouraging the implementation of more holistic tactics to achieve the sdgs, advocating for sustainable food systems and agroecology, launching the un decade of family farming ( - ) and, in , adopting the un peasants' rights declaration ( un news, ) . on the opposite side, some aid donors have provided short-term responses that have not always been consistent with long-term needs. and in terms of policy, the response to the food price crisis served to reinforce the emphasis on productivity and producing more food "to feed billion by ," failed to address ecological challenges and the rights and practices of small-scale farmers and practically ignored gender inequalities (duncan and margulis, ) . increased multinational corporate influence within the governance landscape has resulted in a limited interpretation of sustainability. for example, some global supermarket firms include in their sustainability plans the integration of smallholder farmers into their value chains, including training in sustainable agriculture techniques. at the same time, the growing market power of these firms allows them to enforce production standards within those value chains and to determine contract terms (barling and duncan, ) . such private power often contradicts and undermines efforts undertaken by civil society actors and some states to promote a rights-based approach to food security (duncan and margulis, ) , and raises accountability questions. states continue to play a key role in global food security governance across the different platforms of engagement and at multiple scales (duncan and margulis, ) . however, the increased complexity of governance can permit states to pursue contradictory policy goals. they may place food security high on their policy agendas, strongly advocate for it in forums like the g or the g and provide contributions of aid for agriculture, but at the same time they may try to limit the political influence of the cfs and its multi-stakeholder process, prevent institutionalization of the human right to food as a fundamental principle of food security and pursue aggressive trade liberalization policies vis-à-vis developing countries (duncan and margulis, ) . the body that was supposed to give general political direction is the cfs, which was reformed in the wake of the food price crisis to be a broad, multistakeholder platform for food security governance, incorporating civil society organizations, in particular organizations and movements of the people seriously affected by hunger and undernutrition, as part of the decisionmaking procedures with the status of empowered (though non-voting) participants (mckeon, ) . this process is facilitated through the civil society and indigenous peoples' mechanism (csm). member states remain the principal decision makers and accountable stakeholders (mckeon, ) . this structural reform qualifies as a significant effort to address the underlying causes of the food crisis. however, the cfs faces a multitude of challenges, despite evaluations that find its work positive and pertinent; this is symptomatic of a global contraction of civil-society space in all governance platforms. the challenges concern (mckeon, ): • the actors-some governments do not wish to be held accountable; big corporate actors seek a privileged place at the expense of smallholders and civil society organizations (csos). • the process-some states favor technical and institutional solutions that privilege investments over public policies and make extra use of their red lines to prohibit discussion of certain topics. • the finances-inadequate funding of the platform constrains its potential. • the content-the agenda is overly influenced or controlled by a few states with strong vested interests in expanding current agriculture models while civil society voices and farmers organizations are marginalized. it took the csm several years to bring agro-ecology before the cfs, and debate on contentious questions such as food sovereignty, climate change, biofuels and the food and nutrition impacts of international trade liberalization remain taboo. in contrast, the g expanded its area of influence after the food price crisis, seeking to coordinate the global response. the g action plan did not address the root causes of the problem, however, and au countries criticized it for fostering continuing dependence on food imports in an era of volatile global prices. these countries demanded policies to support food self-reliance (wise and murphy, ) . the g includes the governments of some of the world's wealthiest and most powerful countries, as well as those of middle-income and developing countries that have no mandate to speak for other countries. this arrangement poses a problem of legitimacy, especially when the countries representing the global south in the group are major net food exporters, such as brazil (wise and murphy, ) . since the food price crisis the private sector, another key player, has acquired increasing influence over food security governance, adding another layer of complexity to the panorama of actors and decision making. the rhetoric of mobilizing "billions to trillions" to finance achievement of the sdgs (world bank, ) elevates the private sector and private finance to an ever more privileged position. a analysis examined the key elements of the growing influence of agri-food multinationals in discussions on the fight against hunger at a governance level (acf et al., ) and syngenta (now owned by bayer and chemchina, respectively) established or ramped up their philanthropic arms to engage in advocacy in international forums, including the cfs, as well as in discussions on trade and the environment. • multinational firms have proved influential in development discussions through their corporate social responsibility activities. their public relations efforts highlight the convergence of corporate and government interests and priorities. a good example is the food company nestl e's decade-long emphasis on "creating shared value" which, according to the firm, reflects "our ongoing commitment to achieving the un sustainable development goals…." (nestl e, ). • undertakings such as the new alliance and grow africa seek to mobilize private funds to overcome public sector disinvestment in the agricultural sector in developing countries. donors have established these entities to offer the private sector vehicles to promote their approaches, technologies and policy prescriptions. large philanthropies such as the rockefeller foundation and the bill & melinda gates foundation in particular have a great deal of financial clout: between and private foundations spent $ . bn on agricultural development, and % of these funds went to africa. over the same period, private foundations spent $ . bn on agricultural research, primarily on inputs and specifically seeds (mainly hybrids and genetically modified organisms (gmos)) (inter-r eseaux, ). their financial clout and investment mean that they exert influence over the agricultural models that developing countries adopt. organizations that have received substantial foundation funding, such as agra, have sought to shape the design of policies in africa: in ghana, the agra working group on seeds drafted corporateoriented amendments to the national seed policy that were submitted to the ministry of food and agriculture (inter-r eseaux, ). as the influence of private sector actors in food security policy has grown, it has tended to overwhelm that of small and family-owned business. corporate actors usually promote technological approaches to development, including high-external-input agriculture, and generally steer clear of any holistic rights-based approach. multinational firms also structure their own governance along top-down lines, leaving out farmers' organizations, organizations of rural women and women's rights organizations, national private sectors and civil society in general (inter-r eseaux, ). unstable and broken food system the lack of progress on realization of the right to adequate food for all-and specifically for women smallholder farmers-and thus on achieving sdg by results from instability in the factors that contribute to achieving food security, and this has led to food price volatility. all this is largely the consequence of gender-blind political choices that have failed to tackle the broken agri-food system. twelve years after the - food price spike, the main structural factors that marginalized women smallholder farmers have still not been addressed and the most likely food security scenarios do not seem to have become any more optimistic. according to the un report on the state of food security and nutrition in the world (sofi ), the number of hungry people globally rose by million in and by million over a -year period. looking at food insecurity thorough a different optic, the report also found that more than billion people ( . % of the world's population) cannot afford a healthy diet (fao et al., ) . the number of people facing acute food insecurity rose to million in (fsin, ). the number of african countries relying on external food aid rose from in to in (caramel, ) . early projections of the effects of the coronavirus pandemic suggest that it will have catastrophic food security consequences. sofi reports that covid- could add million- million people to the ranks of the hungry, depending on the depth and duration of the resulting global recession (fao et al., ) . the virus, combined with insecurity, extreme weather, desert locusts and economic instability will likely contribute to increased acute food insecurity as well (fsin, ) . violent conflict is the key factor in the severe food crises in south sudan and yemen (fsin, ) . according to the latest intergovernmental panel on climate change (ipcc) report (ipcc, ), there is already evidence of farmers migrating as temperatures increase, exacerbating inequality as those least able to cope are forced to uproot their lives. marginalized communities-including indigenous, pastoral, agricultural and coastal communities-will suffer the most as food and water become less available, health risks increase and their lives and livelihoods are jeopardized. women farmers remain on the razor edge of extreme shocks to the system and in a warming world, with a growing number of hungry people and more conflicts, they face ever greater risks. indeed, according to fao, "women are slightly more likely to be food insecure than men in every region of the world" (fao et al., : ) , especially if they live in rural areas, where poverty and food insecurity are very much linked, and especially in a context of increased reliance on markets and a decrease in subsistence agriculture. current food stresses are linked to prices and access to markets rather than to production (gaye et al., ) , but women are vulnerable in all dimensions of food security: availability, access, utilization and stability. twelve years on, food production has increased and remains adequate to feed all of the increased population in all of the world's regions. per capita food availability has increased globally over the past years (un women, ). nevertheless, climate change and its impacts on agriculture constitute a substantial threat to food availability. fao projects that global average cereal yields will decrease by %- % for each degree of warming . africa and a belt stretching from the middle east through south asia to mainland south-east asia and on into indonesia and the philippines are forecast to be the regions worst affected by disasters caused by natural hazards associated with climate change . this is likely to cause severe harm to harvests and external trade, among other things . it is also forecast to increase food prices, most of all in west africa and india; people's purchasing power is expected to decline by nearly % in west africa and . % in india (fao, ). reduced buying power will have severe impacts on rural poor people . climate variability and extreme weather events can have negative local impacts even when overall national food production figures look good, and this can lead to serious hunger problems in the affected areas . rural people in developing countries, who usually have low carbon footprints (pearl-martinez, ) and depend on renewable natural resources, are acutely vulnerable to climate shocks and natural hazards, which can result in devastating production losses and undermine their food security and nutrition . women have especially high vulnerability as they tend to have less access than men to the resources that can facilitate climate change adaptation, such as social capital, land, finance, credit, health, education, information, mobility and formal employment, and they frequently lack a seat at the decision making table pearl-martinez, ; quisumbing et al., ) . climate change related drought and water scarcity add to their gender-related workloads, such as collecting fuel wood and water (fao, ). even when food is available, poor and marginalized people may lack the resources to access it through purchase or production, and too often neither public social protection programs nor private charity reach them, if these even exist in poor countries (drèze and sen, ) . most often women are expected to find ways to cope with their families' hunger (un women, ) . within concentrated global and domestic value chains, women farmers are at risk because of their weak bargaining position: global food industries and supermarket chains play an increasingly prominent role in food supply, and access to food depends on income, price levels and social transfers, factors over which women have no power or in which they face discrimination (un women, ) . smallholders find that they are being driven out of markets, squeezed by corporate entities on both the input side (seeds, machinery) and the buyer side (traders, food industry, supermarket chains). willoughby and gore ( ) found that in the context of patriarchal norms and social practices, women feel the effects most severely. they are relegated to low-paying and often informal work within agri-food systems, are denied most socioeconomic and political rights and are under the threat of sexual harassment and violence. all these factors constrain their ability to access food. a survey of south african grape farm workers in found that over % said that they did not have enough to eat during the prior month. nearly a third said that they or someone in their family had missed at least one meal in that month (willoughby and gore, ) . when policies have been implemented to give women better access to markets, they have not necessarily been beneficial. entering into market relations usually brings large changes-negative or positive-to the ways that people live. these changes can alter relations within the household, to the benefit or detriment of women. in general, it is widely thought that direct access to income increases a woman's autonomy, but in the household economy it is not always that simple (britwum, ) . within farming households, there are often gender differences in revenue earning from crops. men tend to produce high-value crops, leaving women to cultivate traditional produce which may be rich in critical micronutrients but has been neglected by post-crisis policies that have primarily targeted cereal production to reach national sufficiency. an fao analysis of gender and cash crop production in ghana found that women cocoa farmers are as productive as men. but because they tend to be more cash strapped than male producers, women cultivators tend to use more labor-intensive and less high-tech approaches than men, which adds to their workloads (fao, c) . conflict also has gendered impacts on food security (fao et al., ) : • men tend to do the bulk of the fighting, leaving women in charge of household livelihoods and wellbeing. • violence can directly harm women, and can also reduce their capacity to provide for their families. • conflict related displacement also is a major reason for food insecurity, and affects women and children disproportionately. at the household level, women are frequently the ones who eat least, last and least well. increased poverty in female-headed households affects women's nutrition: to adjust to the decline in their capacity to purchase or grow highquality, diverse foods, they often shift to cheaper and less diverse diets, which frequently lack the key nutrients that pregnant women and young children require. as fao (n.d.) has observed, "more often than not, the face of malnutrition is female." in , global food insecurity rose for the third consecutive year , and women were the most affected: a third of the world's women of reproductive age suffer from anemia, usually due to iron-deficient diets. this also means risks for the health and nutrition of their children (fao et al., ) and has long-term impacts on development. worldwide, anemia is a contributing or sole cause of %- % of maternal deaths. anemic women are twice as likely to die during or shortly after pregnancy as nonanemic mothers . because anemia caused by iron deficiency results in reduced learning capacity and less productive workers, it is estimated to reduce gross domestic product (gdp) by % annually, particularly in african and south-east asian countries (world bank, ) . women's malnutrition frequently stems from poverty and unequal intrahousehold relations. women who have access to financial resources enjoy greater dietary diversity, and in rural areas women farmers who control resources tend to have better-quality diets (lourme-ruiz et al., ) . even when food is available and relatively accessible, people may not fully meet their nutritional needs. in countries where the calorie supply is adequate, there are still high levels of child stunting, e.g., bangladesh, burkina faso, ghana, mali and nepal (dury and bocoum, ; un women, ) . climate shocks, conflicts and social factors that increase women farmers' work burdens put their own health at risk and limit their ability to engage in recommended feeding practices for infants and young children . in many developing countries staples price volatility has persisted, with fresh spikes in and , and prices have remained above the level of the early s. in the face of volatile prices, people shift their income from other necessities to maintain their access to food, and this means that stable prices are a crucial element of food security (fao, ; murphy and schiavoni, ) . instability on the dimensions of food security over the past years has driven the failure to attain the right to adequate food. this is largely due to political choices concerning food security but also to funding, in terms of quantity, quality, targets and accountability. funding agenda to address women's food insecurity? . . an institutional step forward some major institutions have shifted their narratives to factor gender into their policies and strategies. the un agencies in particular have worked toward the empowerment of rural women and have helped reframe the agricultural development narrative. after the food price crisis, the rome-based un agencies developed their own gender strategies: • wfp-in wfp implemented its policy on gender equality for all its programs and projects through an action plan for operability in the field. the objectives were to bring an adapted approach to food aid considering specific needs, increase women's participation in program design, empower women and girls in decision making and protect women from sexual and gender-based violence (wfp, ). • fao-in march fao adopted its policy on gender equality. the objective was to better target women across all programs through disaggregated gender data and norms and standards in project formulation (fao, b). • ifad-ifad's gender strategy implemented in was articulated around three objectives: promote women's economic empowerment, ensure equal participation and influence within institutions and rural organizations and guarantee equity in workloads and in the share of extension services and economic value (ifad, ) . • in the cfs produced gender and nutrition policy recommendations (cfs, ), which included: affirmative action for women. enhancing women's role in food security decision making. enacting legislation to guarantee women's access to resources and services. • in october , fao, ifad, un women and wfp launched their joint initiative on accelerating progress toward the economic empowerment of rural women (un women, ) . it seeks greater leadership opportunities, better food security and higher incomes for women, as well as to foster greater gender awareness. in the face of inaction by governments, the un has taken a step further in legislating around gender inequalities in rural and agricultural sectors over the past years: the committee on the elimination of discrimination against women (cedaw) recognized the myriad challenges facing rural women in , noting that in many cases, the situation has worsened. the committee also indicated that states should therefore ensure, among other things, that macroeconomic policies, including trade, fiscal and investment policies, as well as bilateral and multilateral agreements, are responsive to the needs of rural women and strengthen the productive and investing capacities of small-scale women producers. they should address the negative and differential impacts of economic policies, including agricultural and general trade liberalization, privatization and the commodification of land, water and natural resources, on the lives of rural women and the fulfillment of their rights. the cfs forum on women's empowerment has pointed to significant gaps in policy implementation: countries have at least one law restricting women's economic opportunities, countries exclude women altogether from certain jobs and leave it to husbands to determine if their wives can work. this forum has urged states to uphold their commitments to rural women's rights under the convention on the elimination of all forms of discrimination against women (fao, c) . in , the cfs began work on a set of voluntary guidelines on gender equality and women's empowerment in the context of food security and nutrition. the un declaration on the rights of peasants and other people living in rural areas, adopted by the general assembly in , calls on states to take all appropriate measures to eliminate all forms of discrimination against peasant women and other women working in rural areas and to promote their empowerment in order to ensure, on the basis of equality between men and women, that they fully and equally enjoy all human rights and fundamental freedoms and that they are able to freely pursue, participate in and benefit from rural economic, social, political and cultural development. the world bank's world development report : agriculture for development recognized the importance of smallholder farmers, and especially women. it emphasized the significance of investment in smallholder-led agricultural development for poverty reduction after decades of development processes bypassing small-scale farmers, particularly women cultivators (world bank, ) . in the ensuing years, two broad agendas have emerged, with tools that call for more responsible investment in agriculture and tackling gender inequalities: the voluntary sustainability standards (vss), targeting mainly the private sector, and the responsible investment frameworks in agriculture (rifs), targeting mainly governments. important gaps remain in addressing gender inequality and empowering women farmers, and these tools have to be used in the appropriate context so that they work (sexsmith et al., ) . also in , the bill & melinda gates foundation established a gender policy for the agricultural projects that it supports. this seeks to ensure that women benefit and to track project impacts on women and their children and communities (coon, ) . however, since the food price crisis, there is scant evidence that policy responses have taken gender differentials into account, and research in this area is still patchy. decades of rhetoric about the greater vulnerability of women have borne limited results in policy action. this neglect is reflected in aid expenditures. oecd data show that overall bilateral aid targeting gender equality and women's empowerment as either a significant (secondary) or principal (primary) objective in all sectors combined was higher than ever before in - , corresponding to % of total aid. however, the aid activities marked with the principal objective remained consistently below a total of $ bn per year, representing only % of total bilateral allocable aid from development assistance committee (dac) members in - . dedicated support focused on gender equality and women's empowerment as the principal objective in the economic and productive sectors-which encompass agriculture and rural development-decreased from $ m on average annually in - to only $ m on average in - , representing less than % of aid to these sectors (oecd, b) . nevertheless, it is worth noting that out of that $ m, more than half ($ m) was committed to agriculture and rural development. even though agriculture is the main economic and productive sector for targeting gender equality, making gender a principal objective of aid to agriculture and rural development is still not high on donors' agendas. furthermore, it is important to bear in mind that even when donors tag their aid projects with the oecd gender equality markers, this does not necessarily mean that the projects advance gender equality or empower women. grabowski and essick examined aid projects carrying the markers and found that only two of them actually met all of the oecd's minimum criteria for using the gender equality project marker (grabowski and essick, ) . also, although strong women's rights organizations and movements are recognized as being particularly effective actors in bringing about sustained changes toward gender equality, aid going to these organizations remains extremely modest. in - , an annual average of $ m went specifically to women's nongovernmental organizations (ngos), and women's organizations in developing countries received just $ m of this (oecd, b). in agriculture in - , there was little attention to the gender-disaggregated effects of the food price crisis, including its nutritional impact, coping strategies such as withdrawing girls from school and worsening poverty among female-headed households. the work of agnes quisumbing and ruth meinzen-dick and their colleagues at ifpri (quisumbing et al., ) and fao's ( ) sofi are major exceptions. there is still no access to sex-disaggregated data in food security programs (see box ) (un women, ) . of fao's indicators on food security determinants and outcomes, just one is gender related (anemia among pregnant women) (un women, ) . lack of sex-disaggregated data on rural populations also hampers implementation of cedaw's provisions on the rights of rural women. data are also lacking in terms of donors' actual funding to support women in farming and adapting to climate change, and not all donors systematically report to the oecd creditor reporting system. moreover, oecd gender equality markers only indicate if a project targets gender equality and whether it is a mainstreamed objective or fundamental to a project's design and expected results. the markers do not distinguish the nuances between projects that target resources to women and those that aim to transform gender relations (grabowski and essick, ) . as pearl-martinez notes, because aid recipient countries fail to gather sexdisaggregated data, it is impossible to track whether oda reaches women box collecting high-quality, sex-disaggregated data for better prevention tools: the case of the harmonized framework. l since , the permanent interstate committee for drought control in the sahel (comit e permanent inter-etats de lutte contre la s echeresse dans le sahel, or cilss) has been developing and refining its harmonized framework (cadre harmonis e) for the analysis and identification of risk areas and vulnerable groups in the sahel and west africa. the framework is a tool for food crisis prevention and management, and can identify and analyze zones with populations at high risk of food and nutrition insecurity. the results of these analyses allow the classification of food insecurity on a severity scale and estimates of the most affected populations, as well as projections for lean periods. this tool, targeted at decision makers, could be more qualitative with the inclusion of gender analysis, for example by systematically collecting sex-disaggregated data and evidence. this first step could help characterize food insecurity through a gender lens, and thereby help to better target vulnerable populations. farmers (pearl-martinez, ) . tools exist that can be used to measure gender empowerment, e.g., the women's empowerment in agriculture index, which the us ftf initiative helped create. m such empowerment is essential for transforming rural women's roles in agriculture and food security, as well as for addressing the structural causes of hunger (coon, ) . more investments in agricultural development, even if they target small family farms, do not automatically benefit women and food security. the key questions related to whether agricultural development promotes gender equality include whether women are able to access resources, whether they actually can make decisions about the fruits of productivity and income gains and whether development efforts help them to meet their needs and aspirations (huyer, ) . the international institute for sustainable development (iisd) showed in that men and women do not benefit equally from foreign investments in agriculture (sexsmith et al., ) . though its analysis looks at private investments, some of the faults detailed are also found in publicly funded development programs: • foreign investors tend to reinforce existing inequality in land ownership and control by working only with men who have formal land rights. this can reduce rural women's ability to use common lands to meet household needs. • women frequently have difficulties accessing credit and extension services, and so may be excluded from contract farming schemes. these factors also prevent them from benefitting from agricultural innovations. • investors tend to overlook women's needs and thereby increase their workload, including their unpaid labor. foreign investments can increase household incomes, helping women to ensure that their families are food-secure, but if this requires producing export crops instead of food crops for the household's own consumption, it entails new food security risks, e.g., greater vulnerability to volatile global commodity prices and increased competition. • investment projects reinforce rather than transform gender divisions of labor, with women remaining in insecure and often informal jobs. m for further detail, the weai resource center at http://weai.ifpri.info/. • projects also tend to fail to change women's under-representation in cooperatives and agricultural worker organizations, and particularly in leadership roles in these groups. gender integration in agricultural development and food security policies and programs requires ex ante impact assessment to ensure respect for the "do no harm" principle, considering local social and cultural contexts and how these shape women's ability to participate in development activities. in particular, projects must consider who controls assets within the household and seek to redress inequities. failing to do so will simply reinforce existing gender norms and inequalities (quisumbing et al., ) . poorly designed agricultural development interventions can lead to the increased marginalization of women in decision making. too often, projects require beneficiaries to have minimum levels of education and access to credit, for example, prerequisites that wind up excluding women (dury et al., ) . a gender strategy can help project staff better understand the potential gendered impacts of their interventions, and who is likely to benefit (quisumbing et al., ) . boxes and discuss gender integration efforts in rural development projects in haiti and nigeria. haiti is the poorest country in the western hemisphere and has one of the most unequal income distributions on the planet. agriculture remains central to development in the country, accounting for % of employment and % of gdp. yet poverty pervades the haitian countryside, with % of the population living below the poverty line (compared with an overall national poverty rate of %) (ifad, n.d.; world bank, ). hunger and malnutrition go hand in hand with low incomes: % of all haitian households experience food insecurity and % of pre-school children are chronically malnourished (usaid-haiti, ) . rural women in haiti are especially vulnerable. according to a study for usaid, % of all haitian women are anemic. women are percentage points more likely than men to be unemployed, and on average they earn more than % less than men. in the countryside, rural women have inadequate access to land and participate less than men in high-value agricultural activities. box case study-food insecurity among rural haitian women. n -cont'd this affects the quantity and quality of the food that they are able to consume. in addition, nearly half of rural haitian women should be considered "not empowered," due to their heavy workloads (including many unpaid household responsibilities), lack of ability to make decisions related to agriculture and lack of membership in groups such as farmers' associations or cooperatives (rames et al., ) . in , the us government made haiti one of its ftf "focus countries." according to an assessment of avanse, the feed the future north project in haiti, the project provided women with %- % of the benefits (anglade et al., ) . so avanse can be characterized as "gender-sensitive," in that project staff explicitly sought to mainstream gender and include women and their organizations in activities (avanse, ). however, the project was not gender-transformative, as it did not challenge traditional gender roles in rural northern haiti. it engaged women in what is locally considered "women's work," e.g., small-scale, wholesale marketing of farm produce and the heavy manual labor of building soil and water conservation structures such as terraces and retaining walls. participating farmers at various project sites told the assessment team that "kek grenn fanm" (just a few women) were engaged in growing rice through avanse. the assessment recommended that agricultural development efforts in rural haiti such as avanse make more concerted efforts to consult with women farmers about their needs and priorities, and give them the opportunity to participate in all project activities, including production of all kinds of crops and livestock. box increasing disposable income for women's food security and empowerment in nigeria. food prices in nigeria have trended upwards since (samuels et al., ) , reaching a peak in that negatively affected poor consumers' access to food. in a country very dependent on imports of commodities, the agriculture sector represents a large part of the economy, employing % of working nigerians, mainly as smallholders with below poverty line incomes (matemilola and elegbede, ) . women farmers have less access than male cultivators to land, inputs, paid labor and extension services, and this means that they tend to grow and earn less. in response, many national and international programs have been implemented in nigeria (matemilola and elegbede, ) , but not many have targeted smallholder farmers and women. at a national level, nigeria is far from the % caadp target for agriculture's share of the national budget, with the figure remaining below % as of (mwanzia, ) . very little attention is given box increasing disposable income for women's food security and empowerment in nigeria.-cont'd to specific budget lines for women, youth and marginalized segments of communities. in , gender and youth were lumped together in the budget and only % of proposed projects for them were funded (mwanzia, ) . international initiatives have not tackled this issue either, but some programs, like the one described below, have tried to recognize the productive capacity of female small-scale producers and empower them to significantly reduce food insecurity. since , oxfam has led a village savings and loans (vsl) o program in nigeria, allowing small groups of - villagers to create a common savings fund from which all group members can take loans. one of the main goals of these groups is to increase women's access to financial resources, and eventually to empower women economically, socially and politically. women represent % of program participants. a - baseline study examined the vsl program's impacts on women's empowerment. one of the direct impacts is on community food security. in , some of the respondents, mostly women, reported having fewer than three meals per day in some villages, but in all respondents in all villages reported three meals per day. this improvement can be directly linked to the increased financial capacities of women participants. the following assertion from a woman beneficiary in the village of kebbi shows that vsl allowed her to diversify her household's sources of income, and gave her more choices in buying food to ensure household food security: "before joining the vsl group, i needed to seek permission to buy even soup condiments because the money comes from my husband. but after joining vsl, i am empowered and don't need to seek permission before making little purchases." the program has indeed had a positive impact on joint decision making at the household level because women now contribute fully to expenditures. "i now contribute with money to support my husband, and this is possible because i joined vsl," said a woman from adamawa state. another, from guyuk village, added: "when my husband sells a goat, we discuss how to spend that money. i am very happy, everything has changed." vsl has also contributed to a change of perceptions on women's social role and has reinforced their participation in community political decision making. a woman from kebbi reported: "since i joined vsl, i am being respected by all. often times, i am being included as an executive member of most committees constituted in my community." o the vsl is a methodology invented by care international in . since then, the vsl methodology has been implemented worldwide by several ngos, including oxfam. the authors are grateful to oxfam in nigeria for providing information on the program used here. a study analyzing policy documents in uganda found that the rhetoric of "gender mainstreaming" was well integrated, but that this was insufficient to advance gender equality, given the lack of concrete implementation efforts. the study also found that the documents used mainstreaming in a way that tended to depoliticize gender (acosta et al., ) . multiple food supply and demand factors triggered the food price crisis of - . price spikes also revealed how the structural evolution of the global food system has fomented inequalities in accessing food. the food price crisis denied the right to adequate food to whole categories of people who have suffered long-term impacts. women have experienced disproportionate effects because they face discrimination at both the societal level and within their own households, with profound effects on their right to food. the global response to the crisis has been very visible, with many actors involved and numerous commitments, new initiatives and instruments launched by intergovernmental bodies, countries, global donors and private stakeholders. however, funding has been insufficient and the policy response has mainly targeted production issues instead of focusing on the right to food, especially of women. after years, global food security governance is highly fragmented, with the power of a small number of actors increasing dramatically. those actors include major multinational corporations, the world bank and the imf and the g governments. the voices of the people who have been left food-insecure are seldom heard in policy discussions. funding targeted at women in agriculture is insignificant compared with other official funding, and this public disinvestment opens the door to other actors, such as multinational companies, which have taken a "business as usual" approach and make gender equality in agriculture a low priority at best. especially in light of climate change and increased conflicts, failing to address the structural causes of the food price crisis has put women even more at risk on all dimensions of food security. in order to start tackling these challenges, we offer the following recommendations: • developing country governments and donors should support inclusive agricultural transformation and create an enabling environment for both female and male farmers to exercise their rights. this should include reducing power imbalances and supporting national-level land reforms. • governments and donors must make women's economic empowerment in agriculture a high priority. actions should include greater support for women farmers' organizations and for developing markets for crops that women tend to produce. p • local communities, farmer organizations, rural women's organizations and other relevant civil society actors should be involved in the design of food and agricultural policies. governments and donors need to take a rights-based approach, including ex ante target group identification, ex ante gender analyses and affirmative action addressing the needs of women (e.g., extension services reaching out to them and employing female extension agents). special attention should be paid to ensuring that women participate in decision making at all levels. • policies and funding should support and promote women smallholder farmers in achieving sdg by facilitating the self-organization of women and women's organizations. • donors should encourage multilateral agencies, such as the world bank and ifad, to increase the share of their agricultural spending that supports gender equality. • development aid providers should increase the quantity and quality of aid and support to focus on women smallholders, promoting low-input, climate-resilient practices, particularly soil restoration, crop diversification and water conservation and management. • investments in small-scale agriculture should be combined with and complementary to other initiatives that seek to restore the rights and decision-making power of women smallholder farmers, including initiatives that seek to increase women's access to education and encourage families to share the responsibilities of unpaid care work, as well as legal efforts to give women the same rights as men. • developing country governments should increase public investment in agriculture, with a focus on both women and men smallholder farmers and sustainable, climate-resilient approaches to agricultural p for more on this recommendation, see willoughby ( ) . development, and should include specific line items in their agriculture budgets to support women farmers. • governments should ensure that women farmers' associations and women's rights organizations are able to participate in budget decision making. • african governments should make meeting and then exceeding their caadp pledges on allocating % of national budgets to agriculture a top priority. these budgets should emphasize public investment rather than recurrent spending such as salaries for public officials. • developing country governments should adopt national policies that prioritize food production and discourage the diversion of farmland to large-scale production of crops for export and biofuels. q • governments should create public databases on land ownership and the terms and conditions of large-scale land transactions. • donors should help strengthen developing country governments' capacity to negotiate with investors in large-scale land transactions. • governments should facilitate the participation of civil society, farmers' organizations and women's organizations in the development and governance of food reserves. bilateral and multilateral donors should provide financial and technical assistance to establishment of reserves. • agriculture policies should facilitate women's access to inputs, resources and services. • governments should develop accountability mechanisms to ensure that national and transnational companies do not violate land rights and should ensure gender equality in land governance. • governments should enact or enforce existing competition or antitrust legislation to regulate excessive private power in markets. governments should cooperate on a regional and global basis to enforce competition policies. • national seed policies and legislation on plant breeders' rights should ensure the right of women and men smallholder farmers to save, reuse, exchange and sell seeds. q for more detail, see bernabe ( ) . • developed country governments should increase climate change adaptation financing. • donors should increase efforts to promote gender equality through their bilateral climate adaptation finance by significantly increasing the share of adaptation projects that have gender equality as a principal (dac marker ) or significant (marker ) objective. collect sex-disaggregated data to assess gender inequalities in agriculture • research institutions and agrarian and economic policy forums should seek quality sex-disaggregated data, with strong gender indicators, from all actors, and especially from governments and donors 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trends and consequences of non-native livestock introgression in developing countries date: - - journal: glob food sec doi: . /j.gfs. . sha: doc_id: cord_uid: mqcgqwrb importation of livestock genetic resources from industrialized countries for introgression of specific traits and other forms of crossbreeding is often indicative of a shift in production systems toward greater intensification and specialization. in developing countries, imported genetic resources are regarded as both a solution to improve the performance of local livestock and as one of the main threats to local populations. using international databases, censuses and technical reports, we investigate ongoing trends and consequences of these two phenomena in countries from africa, asia and latin america. in these countries, the share of locally adapted breeds within species has decreased by an average of . % per year over the last years. the corresponding increase has been distributed between pure exotic breeds and crossbred animals, with differences across regions. in several countries, increased utilization of exotic cattle breeds and crossbreeding has been accompanied by a trend in increased milk yield per cow. the shift from local genetic resources to crossbred and exotic animals must be considered in the context of challenges such as food security, erosion of agrobiodiversity, interactions with other agricultural production, reduction of poverty and provision of ecosystem services, as well as resilience to and mitigation of climate change. global production of livestock is expected to increase substantially, driven by increasing demand from developing regions. by , global milk and meat production are expected to be and percent, respectively, above current levels (fao, ) . in this context, and considering limited availability of land, water and other natural resources, livestock farmers from those developing regions need to increase the production and productivity of their animals (mayberry et al., ) . genetic improvement is an important lever for improvement of livestock production traits (miglior et al., ; tallentire et al., ) . livestock in industrialized countries have undergone generations of intense selection and their genetic merit for production in their usual production environment usually is superior to local breeds in developing countries. therefore, crossbreeding and replacement of local livestock by exotic breeds are often seen as attractive solutions to close yield gaps. crossbreeding strategies usually require less investment in capital, infrastructure and technical know-how than within-breed genetic improvement (leroy et al., a) . as a consequence, national livestock authorities in developing countries frequently integrate the extensive use of exotic livestock in their development strategies aiming at increasing the productivity of their livestock production systems (see for instance daph, ; goi, ; shapiro et al., shapiro et al., , . abundant literature documents the theoretical and practical impacts of crossbreeding and breed replacement at the local level (galukande et al., ; getachew et al., ; roschinsky et al., ; wilkes et al., ) . various studies have shown that in appropriate production environments, milk yield of crossbred cattle can be to . times greater than of pure indigenous breeds, with associated increases in farmers' income (galukande et al., ; hegde, ) . on the other hand, outcomes of the many initiatives to replace and/ or crossbreed local livestock breeds have been variable (madalena et al., ; marshall, ) . failures generally relate to limited adaptedness of exotic livestock breeds, poor infrastructure and technical capacity, lack of long-term commitment of institutional partners, and limited preparatory involvement of the small-scale livestock keepers (lemke et al., ; leroy et al., a) . murray et al. ( ) showed that exotic breeds of cattle and their crossbreeds with zebu cattle show reduced resistance to endemic diseases. the use of exotic breeds and indiscriminate crossbreeding have been reported as the two main factors causing erosion of local genetic resources (fao et al., ) . animal genetic resources are an essential component of sustainable food systems. therefore, monitoring and maintaining locally adapted livestock are essential. the putative importance of local breeds is reflected in the un sustainable development goals (sdg), for which target . addresses maintenance of the genetic diversity of domesticated animals (https://unstats.un. org/sdgs/metadata?text=&goal= &target= . , fao, ). despite the abundance of literature on individual projects, little is known on the trends and consequences of crossbreeding and breed replacement on a larger scale. using data from international databases, agricultural censuses and technical reports, we investigate the recent trend in the global share of locally adapted, crossbred and exotic livestock in countries. we also investigate the relationship between those proportions and estimates of average milk yield per cow for countries, as well as the trends of national breed populations considered as locally adapted, and discuss issues regarding sustainability. to obtain data on the relative importance of locally adapted, crossbred and exotic livestock populations, information from agricultural censuses and technical reports from the years between and were used. these data originated from african, asian, and latin american countries and the five main livestock species (cattle, chicken, goat, pig, sheep) (see supplementary table ). in two countries (senegal and niger), the domestic animal diversity information system (dad-is) was used as the source of information, because the dad-is breed population data corresponded closely to the total species population reported in faostat (http://www.fao.org/faostat) for ruminants (± %), this decision was made following discussion with corresponding national coordinators officially nominated by these countries as focal points for animal genetic resources. from those different sources, country/species/year combinations were formed, representing country/species combinations (see supplementary table ). the classification system differed according to countries and species and the three following categories were used in our analysis (see box for terminologies): in some cases, only one category was differentiated from the other two (i.e. locally adapted versus non-locally adapted or exotic versus non-exotic). for this reason, the three categories were analyzed independently from each other. average milk yields (number of l per cow and per year) for cattle were extracted from faostat or provided by national coordinators to compute linear regressions on either the proportion of exotic breeds or the proportion of exotic + crossbred (according to data available) for countries that had provided either information on populations described as dairy cattle (algeria, chile, egypt, ethiopia, iran, morocco, tunisia) or on general cattle populations oriented toward milk (bhutan, india, nepal, and jordan) (see supplementary table ) . to analyze demographic trends at breed level, a third data set was extracted from dad-is, containing information on the population size of national breed populations reported at different points in time during the period - . only data from local breeds or regional transboundary breeds were included as proxies for locally adapted breeds, as in dad-is information regarding geographical adaptation is provided for fewer than % of national breed populations from africa, asia, and box terminologies used for breeds and populations. breed: either a sub-specific group of domestic livestock with definable and identifiable external characteristics that enable it to be separated by visual appraisal from other similarly defined groups within the same species, or a group for which geographical and/or cultural separation from phenotypically similar groups has led to acceptance of its separate identity. crossbred: animals produced through the mating of individuals from different breeds, either following a specific strategy (such as terminal crossing, rotational crossing or synthetic breed creation) or through an indiscriminate process. synthetic breeds are excluded from this definition once the population has reached an equilibrium state at which all animals have the same proportion of genetics from the original breeds. in this study, the crossbred category is restricted to the cross between locally adapted and exotic breeds. exotic: animals originating from breeds that have not been continuously present in a country for sufficient time to be adapted to the prevailing environmental conditions. exotic breeds comprise both recently introduced breeds and continually imported breeds. in this study, exotic breeds correspond essentially to highly productive breeds originating from developed countries. local: breeds that occur only in one country. locally adapted: breeds which have been in the country for a sufficient time to be genetically adapted to one or more of traditional production systems or environments in the country. indigenous breeds, also termed autochthonous or native breeds and originating from, adapted to and utilized in a particular geographical region, form a sub-set of the locally adapted breeds. national breed population: a subpopulation of a breed found in a given country. international transboundary: breeds that occur in more than one country in more than one region. regional transboundary: breeds that occur in more than one country in one region. source: adapted from fao ( ). latin america. national breed populations with at least two population size estimates (as the average of minimal and maximal population sizes provided in dad-is) were extracted from countries of those three regions ( in africa, in asia, in latin america), for a total of population size estimates (to be confirmed). the proportions of the species populations belonging to each of the three categories were analyzed independently for each category, considering a linear mixed-effect model (r lme function). the three regions and five species were included as explanatory factors. year, as well as interactions of year x region and year x species were considered as covariables. species/country combination was added as a random effect, as well as an autocorrelation structure component of order with the year covariate (corcar ). explanatory variables were removed stepwise until minimizing the bayesian information criterion (bic), but keeping region, year and species/country random effects as explanatory variables. a linear mixed model was also utilized for the second data set containing milk yield per cow per year as the dependent variable (r lme function). in absence of information on animal husbandry (e.g. diet and veterinary care) and production environment, year was used as a proxy and considered in the model as a covariable. the proportion of exotic/ crossbred animals was used also as a covariable, while an explanatory factor indicating whether animals were % exotics or a combination of exotics and crossbreds was also included. country was included as a random effect, as well an autocorrelation structure component of order with year covariate (corcar ). explanatory variables were removed stepwise until minimizing the bic, keeping year, proportion of exotic/ crossbred animals and country random effects in the model as explanatory variables. considering the large differences in population sizes among dad-is national breed populations, the third data set was simplified by computing the linear regression coefficient of population size over years for each national breed population, then comparing the number of populations with a positive trend (i.e. positive regression coefficient) to the numbers of populations with null or negative trends, according to regions. the country x species cases studied here covered the past years and originated from africa ( countries), asia ( countries) and latin america ( countries) (see fig. ) , and from the five main livestock species, with cases for cattle, for chicken, for goat, for pig, leroy et al. global food security ( ) and for sheep. the different cases represented a wide range of situations and contexts, with shares of national species populations ranging from to % for locally adapted breeds, from to % for crossbreds, and from to % for exotic breeds, according to years, species and countries (fig. ) . according to the models utilized, the trends observed revealed that the average share of locally adapted breeds has decreased by . % per year, compared to yearly increases of . % for crossbreds and . % for exotic breeds (table ). the estimates for the respective proportions of locally adapted, crossbred and exotic breeds were . , . and . % for africa; . , . and . % for asia; and . , . and . % for latin america. the three estimates within a region do not correspond to the exact same combinations of countries and species, so they do not sum to %. proportions of locally adapted (exotic) breeds were significantly greater (smaller) in africa than in asia and latin america (p < . ). at the national level, our results on impacts of proportions of nonlocal genetics on milk yield from countries suggest very different outcomes depending on the country, as illustrated by fig. . in ethiopia for instance, the share of exotic and crossbred dairy cows has remained very small, increasing from . to % between and , with average milk yield remaining low at around l per cow per year. in contrast, data from jordan show the results of efforts to intensify the dairy industry that initiated in the s (alqaisi et al., ) . the share of exotic and crossbred cattle (almost entirely purebred holstein) was already % in and increased to % by . annual milk yield per cow passed above l during this period, i.e. values comparable to some european countries. our analyses demonstrate a positive relationship between the relative proportion of crossbred and exotic breeds among all dairy cattle and average milk yield. both time and the percentage of exotic/crossbred livestock were found to have a significant relationship with average milk yield, which increased by . l per year (p = . ) and . l per % of increase in improved/crossbred livestock (p = . ). to assess more precisely the consequences for local livestock, we estimated the proportion of local and regional transboundary breeds with positive demographic trends, using national breed populations extracted from dad-is. a large majority ( . %) of local national breed populations from africa showed positive trends in population size (table ) , which was ***p < . . small letters represent non-significantly differentiated regions at p = . . the same letters represent non-significantly differentiated regions at p = . . significantly higher (p < . ) than in asia ( . %) and latin america ( . %). between and , the absolute number of livestock, measured in terms of tropical livestock units (tlu) to account for species differences, increased at a much higher rate in africa (+ %) than in asia (+ %) and latin america (+ %). in the case of africa, the absolute increase in tlus compensated for the relative decrease in the proportion of locally adapted breeds such that populations of most local breeds did not decrease in size. by contrast, in latin america, a majority of local and regional breeds decreased in population size despite increases in the overall livestock population. in the last hundred years, multiple initiatives to improve food security in developing countries have aimed to cross or replace local livestock populations with more productive ones (madalena et al., ; marshall, ; leroy et al., a) . our results show that this trend is still ongoing and that locally adapted livestock still represent the largest share of livestock populations in africa and asia, while exotic breeds have become the majority in latin america. various factors may be responsible for these regional differences. for example, many african countries lack the logistic capacity to allow the diffusion, use and maintenance of exotic germplasm. in latin america, the locally adapted criollo breeds are themselves the products of crosses among various populations imported over the last centuries, so continued importation and crossing may be more culturally and scientifically accepted than in other regions. the regression model that optimised the bic did not include a species effect, although it's plausible that species-based economic, technological and logistic differences across production systems (such as artificial insemination in cattle, or provision of fertilised chicken eggs) could allow crossbreeding and breed replacement to occur more quickly for some species. heterogeneity in the yield gaps between industrialized and developing countries may also play a role in species differences, as selection programmes for chickens, pigs and dairy cattle tend to be more advanced in industrialized countries relative to those for sheep, goats and beef cattle. interpretations of the definitions of exotic, crossbred and locally adapted animals and knowledge of genetic composition may vary among countries and among people within countries and even evolve through time, impacting the classification of breeds into the different categories and thus perhaps affecting our results. genomics may offer a solution to inconsistencies in definition of breed type, which could consequently improve the inferences if our study were to be repeated in the future. depending on species, breeds and locations, extent of influence from exotic (generally of european descent) breeds due to recent admixture has been found to range from negligible to predominant in local populations (leroy et al., ; murray et al., ; buzanskas et al., ; selepe et al., ; ben jemaa et al., ; zhang et al., ) . although incomparably more precise to assess genetic origins of individuals than other sources of information, molecular approaches are currently limited in their coverage of livestock populations. nevertheless, both molecular and census studies describe a wide diversity of situations according to species and countries. the aim of the various crossbreeding, introgression and breed replacement projects has generally been to improve the production and productivity of local livestock (i.e. milk and egg production, growth, or prolificacy for instance) and in turn to increase both livestock production at the national level and income of farmers. this strategy is supported by the results of a wide number of studies showing positive impacts of crossbreeding on productive traits at local level, both in research stations and on farms (galukande et al., ; getachew et al., ) . within countries, our results showed a positive association between average milk yield per cow and the proportion of exotic or crossbred genetics the national herd. those results must be considered with caution, however, and cannot be entirely attributed to genetic differences, given the fact that the model did not directly account for factors such as changes in production systems and environment/inputs (e.g. quality and quantity of feed, health care and housing), which are likely to have occurred and contributed positively to the average milk yield of animals. in absence of information about possible changes in inputs and the costs related to such changes, conclusions on the impact of these trends in terms of costs and benefits and more generally in terms of the overall economic efficiency of the system (acosta and de los santos-montero, ) cannot be drawn. karugia et al. ( ) concluded that crossbreeding of cattle had a positive effect on the kenyan economy and social welfare, although they speculated that the introduction of exotic genes may have not been beneficial at farm level, because improved animal productivity also involved accrued input costs. by contrast, hegde ( ) reported positive economic impacts of crossbreeding for indian cattle farmers, with the number of above-poverty-line families increasing by % over a ten-year period. in senegal, marshall et al. ( ) found that under good management, % indigenous zebu by bos taurus crossbreds for dairy production provided greater net economic benefits to households than did alternative options involving pure indigenous, highly introgressed (with bos taurus) or alternative crosses. most studies concur with the notion that the success or failure of crossbreeding is associated with financial and logistic conditions enabling access to inputs and extension services. overall, marshall ( ) concluded that the socio-economic benefits to households of keeping a specific breed type depend largely on the production systemsand also vary according to the type of livestock keepers within a system. a related factor to consider is that exotic livestock and their crosses require greater nutritional inputs to achieve their genetic potential for milk or meat production. above a certain level of genetic potential for production, ruminant-livestock producers in mixed crop-livestock systems may have difficulty to produce the sufficient high quality forage and may need to purchase feed (mcdermott et al., ) . on a larger scale, this may have consequences on the dependency of countries on importation of nitrogen and other nutrients, which constitutes a growing issue for many regions with developing or emerging economies (lassaletta et al., ) . our results suggest that in africa, and to a lesser extent in asia, the general increase in the overall livestock population over the past years has compensated for the decreasing proportion of locally adapted animals within species, allowing sizes of local populations to remain relatively stable. on the other hand, the population sizes of a majority of local and regional breeds have decreased in latin america, while the overall livestock population has increased less in size than in africa. the increased presence of exotic and crossbred animals does not necessarily mean replacement of local populations, especially if the new animals are not raised in the same production environments (for instance, if new, peri-urban farms are developed). however, even if the importation of exotic animals is not intended to directly replace locally adapted breeds, they may nevertheless remain a threat as they enter in competition with traditional breeds and herds for resources and market share. erosion of the diversity of local animal genetic resources is especially problematic given the phenotypes of interest that are possessed by those breeds (leroy et al., b) and the ecosystem services they and their production systems provide (leroy et al., ) . in relation to their capacity to withstand endemic diseases and harsh climate conditions, survive on low-quality diets and walk long distances to access food and water, locally adapted ruminant breeds are especially well suited for the valorization and maintenance of pastoral rangelands, which constitute a large share of the global agricultural area ( billion ha, of which . billion ha is not convertible to cropland according to mottet et al., ) and therefore of critical importance for food security and livelihoods. more generally, the increased number of crossbred and exotic animals is indicative of a shift in production systems toward greater intensification and specialization. this process may impact negatively on landscapes and use of resources, as illustrated by magnani et al. ( a) . they showed that the sedentarisation of pastoralists and promotion of exotic breeds over local ones resulted in land fragmentation of the middle valley of the senegal river. also, considering the specific adaptive potential and robustness of locally adapted breeds, breed replacement may reduce the resilience of livestock production systems. the use of mixed herds and modifying herd composition to favour more resistant species or breeds are components of a classical strategy of herders facing long-term droughts (blench and marriage, ) and the use of locally adapted breeds has been suggested as an option to cope with constraints (drought, feed shortage, disease) induced by climate change (musemwa et al. ; bettridge et al., ) . considering the short and long term impact that the covid pandemic will have on food and agriculture in general and livestock in particular (e.g. shortage of labor and animal feed, zhang, ) , both the adaptedness of locally adapted breeds to less-intensive and/or short supply chains, and their general resistance to zoonotic diseases (marshall et al., ) give them potential competitive advantages relative to exotic ones. considering the specific issue of mitigation of climate change, locally adapted breeds tend to perform poorly relative to exotic breeds with regard to intensity of ghg emissions, due to their inferior production. however, standard measures of intensity are somewhat biased, as they typically consider only the ratio of ghg emissions to yield of a single commodity, ignoring other ecosystem services usually associated with locally adapted breeds and their production systems. single-commodity measures of ghg intensity also fail to account for the differences among breeds in their ability to survive while consuming poor quality forage and converting it into human-edible food (hoffmann, ) . in the second report on the state of the world's animal genetic resources for food and agriculture (fao et al., ) , countries, especially those of developing regions, reported indiscriminate crossbreeding and introduction or increased use of exotic breeds as the two main causes of genetic erosion. our results provide for the first time an objective assessment of the situation and the rate at which the relative proportion of locally adapted genetic resources is decreasing in those regions. we also discuss how this phenomenon connects to various challenges on the national scale, such as food production and security as well as agrobiodiversity. these discussions are far from exhaustive, however, inasmuch as locally adapted livestock breeds and their production systems are also associated with various aspects of sustainability, including poverty reduction, resilience to climate change and landscape management. our analyses are also limited to the national scale, whereas local-level heterogeneity in constraints associated with environmental conditions and access to markets influence the fit of a given genetic resource to a certain locale. for instance, herold et al. ( ) proposed a stratified organizational scheme for pig production in vietnam, with farmers close to markets raising crossbreds of exotic males and locally adapted sows, the latter of which would be provided by farmers from more remote areas, for whom crossbred genotypes would be of limited interest due to environmental constraints and lack of access to inputs such as high-energy feeds and veterinary care. strategic planning is required to ensure the conservation of the unique alleles possessed by the local breeds, either by complementary in situ or ex situ conservation of the breeds themselves or by breeding programmes to ensure conservation of these alleles in the gene pools of new synthetic breeds. moreover, because of the influence that context has on the success of using exotic breeds, a livestock development policy involving these genetic resources requires strategic thinking that goes beyond the simple technical dimension of breed improvement or conservation (magnani et al., b) . as illustrated by fig. , animal genetic resources can be regarded as the centre of a complex social, environmental and economic system, so policies need to address the challenges related to sustainability in a holistic manner, accepting trade-offs where necessary, and considering, at different scales, the relationships and dynamics between the animals, their herders, the production systems, agroecosystems, and the market. the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. what is driving livestock total factor productivity change? a persistent and transient efficiency analysis current situation and the development of the dairy industry in jordan, saudi arabia, and syria inferring the population structure of the maghreb sheep breeds using a medium-density snp chip the role of local adaptation in sustainable production of village chickens drought and livestock in 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heterozygosity and exotic introgression the impact of climate change on livestock production amongst the resource-poor farmers of third world countries: a review smallholder experiences with dairy cattle crossbreeding in the tropics: from introduction to impact genetic structure of south african nguni (zulu) sheep populations reveals admixture with exotic breeds ethiopia livestock master plan breeding for efficiency in the broiler chicken: a review is crossbreeding with indigenous sheep breeds an option for climate-smart agriculture? widespread introgression in chinese indigenous chicken breeds from commercial broiler chinese livestock farms struggle under covid- restrictions the authors would like to thank the french government for providing for the secondment of dr gregoire leroy to fao, national coordinators of countries for information provided, and veronique ancey and alejandro acosta for their useful comments. supplementary data to this article can be found online at https://doi. org/ . /j.gfs. . . the views expressed in this information product are those of the authors and do not necessarily reflect the views or policies of fao. g.l., p⋅b., b⋅b., and r.w. designed the study. g.l., c.r.p. collected the data. g.l. and f.j. conducted the statistical analysis. p.b., b⋅b., and r.w. assisted with data preparation and interpretation. g.l. wrote the manuscript, which was edited and approved by all authors. key: cord- -ibli rq authors: to, kelvin k.w.; chan, jasper f.w.; tsang, alan k.l.; cheng, vincent c.c.; yuen, kwok-yung title: ebola virus disease: a highly fatal infectious disease reemerging in west africa date: - - journal: microbes infect doi: . /j.micinf. . . sha: doc_id: cord_uid: ibli rq ebolavirus can cause a highly fatal and panic-generating human disease which may jump from bats to other mammals and human. high viral loads in body fluids allow efficient transmission by contact. lack of effective antivirals, vaccines and public health infrastructures in parts of africa make it difficult to health workers to contain the outbreak. ebolavirus has been known to cause outbreaks of severe hemorrhagic fever with high fatality in africa since [ ] . however, ebolavirus has been out of the spotlight of the clinical and scientific community because it mainly affects remote villages involving at most few hundred people, and these outbreaks often stopped spontaneously. in , a large ebolavirus outbreak occurred in west africa. this outbreak was first reported from guinea in march , although epidemiological investigation suggested that the first fatal case had occurred in december [ ] . the outbreak then spread to liberia, sierra leone, nigeria, senegal, and mali in africa. the first case diagnosed outside africa was reported from usa on september , [ ] . in october , three nurses acquired ebolavirus locally in the united states and spain which has generated huge media attention and public panic. the west africa ebolavirus outbreak is unprecedented in many ways. firstly, this is the largest ebolavirus outbreak recorded in history, with over , cases and a mortality rate of . % [ ] . secondly, the outbreak involved major cities, including conakry in guinea, free-town in sierra leone, monrovia in liberia, and lagos in nigeria [ , ] . the involvement of major cities increases the risk of rapid local dissemination, spread to neighboring countries, and transcontinental spread by air travel, and therefore presenting a major health threat to the entire world [ ] . here, we review the basic science, epidemiology and clinical aspects of ebolavirus which are relevant for the control of the current outbreak. ebolavirus, together with marburgvirus and cuevavirus, are the three genera belonging to the family filoviridae in the order mononegavirales [ ] . four species within the ebolavirus genus can cause fatal human disease, including sudan gabon, which are located in central and east africa. zaire and sudan ebolavirus are responsible for most outbreaks, and these species are associated with highest case-fatality rates, ranging from e % and e %, respectively. taï forest ebolavirus caused illness in an ethnologist who performed a necropsy on an infected chimpanzee in in cote d'ivoire of west africa [ ] . bundibugyo ebolavirus has only been associated with two outbreaks since , with relatively low case-fatality rate [ ] . reston ebolavirus can cause disease in pigs and be fatal in monkeys [ ] , but has not been definitively associated with any human disease, although asymptomatic infection, diagnosed with serological test, was identified in persons with contacts with infected monkeys and pigs [ , ] . in addition to clinically apparent evd outbreaks, seroepidemiology studies showed that there is a high prevalence seropositive individuals, suggesting that asymptomatic or mild infection can occur [ ] . in a study testing blood samples collected from individuals from randomly selected village in gabon between and , . % of samples were found have ebolavirus-specific antibodies using elisa [ ] . ebolavirus-specific antibodies can also be found in individuals from areas without apparent evd outbreak. for example, ebolavirus-specific antibodies, detected using indirect immunofluorescence slide test, were found in . % of healthy individuals from a rainforest area of liberia in the early s [ ] . though these serological test results have not been confirmed by neutralization antibody study, it is highly likely that asymptomatic and mildly symptomatic infections are much more common than severely symptomatic and fatal illness. the current west africa evd outbreak started in december , when cases first appeared in meliandou village, gu eck edou of guinea (table ) [ ] . the index patient was a -year-old child with fever, black stool, and vomiting, with symptom onset on december , , and died days later. the disease then spread to other villages of the gu eck edou district, and also macenta and kissidougou district. the first peak occurred in march when patients were diagnosed with evd in liberia. the second peak occurred in may and june , coinciding with the first report of cases from sierra leone. contact tracing found that the initial cases in sierra leone attended a funeral of a highly respected "traditional healer", who has treated patients with evd in guinea [ , ] . there was a large increase in cases since july . the first case in nigeria was a traveler from liberia, who has caused an outbreak involving laboratoryconfirmed cases from july to september [ ] . senegal and mali reported the first imported cases on august and october , , respectively [ ] . the first case of evd diagnosed outside africa was confirmed on september , [ ] . the patient, from liberia, arrived in usa on september , and developed symptoms on september . a separate evd outbreak, also caused by zaire ebolavirus, has occurred in drc since july [ ] . as of october , , the drc outbreak has involved cases with deaths [ ] . together with these epidemiological data, viral genomic data has provided important information on the origin and the transmission dynamics of the west africa ebolavirus strain. phylogenetic analysis using the whole genome sequences of ebolavirus strains from patients revealed that the west africa evd outbreak is caused by a zaire ebolavirus lineage that is most closely related to the one causing the evd outbreak in drc [ ] . molecular dating suggested that this west african lineage likely diverged from the central african lineage in [ ] . analysis of the ebolavirus strains from guinea and sierra leone showed that they are highly similar, which is in agreement with the findings from contact tracing (fig. ) . however, there are two distinct lineages of ebolavirus in sierra leone which were estimated to have diverged in april . this finding suggests that the virus has further mutated either in guinea or in sierra leone [ ] . on the other hand, the ebolavirus strain causing the drc evd outbreak in july is another zaire strain most closely related to drc outbreak zaire strain [ ] , confirming that this is a separate outbreak. before , the largest evd outbreak affected less than people. however, in the current outbreak, there are already , cases and deaths as of october , [ ] . further studies must be undertaken to understand the viral and environmental factors that contribute to the unprecedented scale of this outbreak. it is still uncertain at this stage whether the virus has become more transmissible in human or has increased environmental stability. it is unclear why zaire ebolavirus suddenly appear in west africa. the only human case of ebolavirus infection in west africa before the outbreak occurred years ago. epidemiological investigation suggested that the first patient was a -year-old child in meliandou village, gu eck edou. one postulation is the spread of the virus by fruit bats from central africa [ ] , but this will require confirmation by further field studies. humans can acquire the infection from infected animals or infected persons. the index patients of evd outbreaks are usually persons working in forests, caves or mines. many of these index patients are bushmeat hunters with direct contact with animals. in the natural setting, transmission from animals usually involves direct contact with the animal or handling of the carcasses. however, most humans acquire the infection through direct person-to-person transmission that can occur via direct contact with body fluids. many clusters occurred when people attended the funeral of an infected patient [ , ] . a caseecontrol study showed that household contacts with direct physical contact with the ill patient or cadaver and exposure to body fluids were risk factors for acquiring infections [ ] . ebolavirus can be transmitted directly through broken skin or mucous membranes from the blood, body fluid, and secretions of the infected person, as the virus could be detected in blood, urine, saliva, seminal fluid, breast milk, tears, stool, skin, and swabs from vagina, rectum and conjunctiva [ ] . virus shedding can be prolonged. reverse-transcriptase polymerase chain reaction (rt-pcr) remained positive in the blood for up to days, in the vaginal, rectal and conjunctival swab for up to days, and in the seminal fluid for up to days [ ] . live virus could be isolated from a patient's seminal fluid days after symptom onset. transmission through environmental surfaces is possible. it was shown that live ebolavirus can survive on dried glass or plastic surface for up to days [ ] . studies have shown that lower temperature and higher absolute humidity are associated with evd outbreaks [ ] . animal studies showed that other routes may be possible. reston ebolavirus can be transmitted from pigs to cynomolgus macaques without direct contact, suggesting that ebolavirus can be transmitted from animal reservoirs to humans without direct contact [ ] . studies in rhesus macaques showed that ebolavirus given orally can cause fatal infections [ ] . aerosol transmission in macaques has been documented [ ] , but this route of transmission has not been documented in humans. almost all cases in the current outbreak are related to person-to-person transmission. the effective reproduction numbers for the outbreak were estimated to be . for guinea, . for liberia, . for nigeria, and . for sierra leone [ ] . hospital-acquired infections are common. during the evd outbreak, the index case had transmitted the virus to healthcare workers and hospitalized patients with at least generations of person-to-person transmission [ ] . during the current outbreak, at least healthcare workers were infected, with at least deaths [ ] . in addition, ebolavirus is also transmitted indirectly when the broken skin or mucous membranes come into contact with the contaminated environment or items such as soiled clothing, bed linen, or used needles. unsterilized syringe was associated with the outbreak in zaire [ ] . in one study, the virus could also be found on the doctor's blood-stained glove and the bloody intravenous insertion site, but was not found on the patient's surrounding environment [ ] . laboratory-acquired infections from accidental puncture while handling infected materials have been reported [ , ] . in a detailed analysis of confirmed and probable ebolavirus cases in guinea, liberia, nigeria and sierra leone from december , to september , , the median age was years with an interquartile range from to years. the male to female ratio was : [ ] . the incubation period is usually e days, but can be as short as days and as long as days [ ] . in the current outbreak, the mean incubation period was . days, with % of patients had symptom onset within days. ebolavirus has been found in several animals, including bats, primates (chimpanzee, gorilla), rodents (rats, mice, shrews), duikers (cephalophus species), and pigs [ ] . although ebolavirus-specific antibody can be detected in up to . % of serum samples from dogs in ebolavirus endemic areas [ ] , there have not been any reports on the isolation of ebolavirus or detection of ebolavirus nucleic acid from dog's samples. in some animals, ebolavirus causes epidemic fatal disease. it was estimated that after the ebolavirus outbreak in the drc between and , there were %, % and % reductions in the chimpanzee, gorilla and duiker populations, respectively [ ] . bats have been proposed to be the source of ebolavirus. bats have been known to be the source of several human viruses including severe acute respiratory syndrome-related coronavirus (sars-cov), hendra virus, nipah virus, menangle virus, rabies virus and lyssaviruses [ , ] . ebolavirus was first reported to be found in the fruit bat species hypsignathus monstrosus, epomops franqueti and myonycteris torquata, which were captured during the and outbreak in gabon and the drc [ ] . during the investigation of the outbreak in drc, it was found that the affected area has a large palm plantation where migratory fruit bats settled for food between april and may, and that the first human case ate a freshly killed bat which was bought from a hunter in may [ ] . ebolavirus is not limited to africa. serological study showed that antibodies against zaire and reston ebolavirus could be detected in fruit bats from bangladesh [ ] , while reston ebolavirus could be detected in fruit bats from the philippines [ ] . a study in china showed that up to . % of bats were seropositive for ebolavirus [ ] . the most common bats species with ebolavirus identified in china include rousettus leschenaultia, hipposideros pomona, miniopterus schreibersii, pipistrellus pipistrellus, myotis ricketti, in which other novel viruses have also been identified [ e ]. reston ebolavirus have been found in domestic pigs in the philippines and china [ , ] . antibodies specific against all ebolavirus species have been found in apes of indonesia [ ] . like all filoviruses, ebolavirus is a filamentous enveloped virus with a negative-sense, non-segmented single-stranded genome of about kb, measuring nm in diameter and up to nm in length [ ] . the end of the viral genome consists of a non-coding region, followed by genes (nucleoprotein [ , and then a non-coding region at the end. each gene encodes one protein, except for the gp gene, which encodes three glycoproteins. the full-length gp is produced by rna editing, in which the two reading frames are joined together by slippage of viral polymerase at an editing site, generating an mrna transcript that allows read-through translation of gp. gp contains gp subunit for host cell receptor binding and the gp subunit for cell-virion membrane fusion. the soluble gp (sgp) is generated by an unedited transcript, which is much more abundant than gp [ ] . a third protein, called small soluble gp (ssgp), is produced via rna editing [ ] . gp, vp and vp are associated with membrane, while np, vp , vp , and l protein bind to the viral genome, which are required for viral genome replication and transcription. vp is also required for the assembly of nucleocapsid. the viral life cycle starts when gp attaches to cell surface receptors [ , ] . although ebolavirus can bind to host cell surface dendritic cell (dc)-specific icam -grabbing nonintegrin (sign) (dc-sign), liver and lymph node sign (l-sign) and t cell immunoglobulin and mucin domaincontaining (tim ), it is currently unclear which cell surface receptor is most important. after attachment, viral entry occurs via macropinocytosis and clathrin-mediated endocytosis [ ] . after entry, the virus is then trafficked into endosome. inside the endosome, several factors are required for the fusion of the viral and endosomal membrane to occur, including acidification of the endosome, and priming and triggering of the gp. priming of gp occurs when gp , which is bound to gp , is cleaved into the kda gp by cathepsin l and then to kda by cathepsin b. triggering occurs when the kda gp undergoes conformational change to expose the fusion loop [ ] . another important event in the fusion step is the binding of the endosomal membrane protein, niemann-pick c (npc ), to cleaved gp [ ] . viral genome replication and transcription then take place in the cytoplasm, which require the viral polymerase l protein, vp , vp and np. vp is required for nucleocapsid formation and assembly. viral transcription is also regulated by vp [ ] . the gp, after modification in the golgi, is trafficked to the plasma membrane, where it is associated with other proteins. virus budding and release then occur, and require the matrix protein vp . in addition to the viral life cycle, these viral proteins are also involved in the pathogenesis of the infection. gp can cause destruction of endothelial cells [ , ] . several lines of evidence suggest that the sgp is important in the modulation of host inflammatory response and immune defense. in vitro, sgp can inhibit the neutralizing activity of anti-gp antibody [ ] . sgp also subverts anti-gp immune response by inducing a host antibody that competes for the binding site of anti-gp antibody [ ] . sgp can also interact with neutrophils, although the receptor for this interaction is controversial [ , ] . on the other hand, sgp may limit the virulence of the virus. recombinant ebolavirus without sgp are less cytotoxic than those with sgp [ ] . sgp can protect endothelial cells from tnf-a [ ] . sgp can also bind to gp , but the importance of this finding requires further study [ ] . vp also inhibits the innate immune rig-i signaling, interferon(ifn)-a and ifn-b production, and dendritic cell maturation [ ] . vp is important in the inhibition of ifn signaling [ , ] . it is currently unclear whether the west africa ebolavirus strain possesses unique characteristics that favor its spread among the human populations. one possible reason is the higher mutation rate. it has been shown that the mutation rate in the current outbreak is about twice as high than that in previous outbreaks [ ] . decontamination methods for ebolavirus include heat inactivation at e c for h or at c for min, g-irradiation, chemicals, including formalin and quaternary ammonium ion, and nanoemulsions, which disrupts the membrane [ ] . in most cases, ebolavirus likely enters the body via breaks in the skins or mucous membranes. infection of monocytes, macrophages and dendritic cells helps to disseminate the virus to the lymph nodes via the lymphatics, and to the liver and spleen via the blood. notably, ebolavirus does not infect lymphocytes, although lymphocyte depletion occurs due to apoptosis [ ] . when the infected monocytes, macrophages or dendritic cells move out of the lymph nodes and spleen, the virus can disseminate to other organs [ ] . ebolavirus can also infect endothelial cells, fibroblasts, hepatocytes, adrenal cortical cells, and epithelial cells. since patients with severe disease have higher viral load in blood, uncontrolled viral replication may play an important role in the pathogenesis of severe evd [ ] . macroscopically, there are hemorrhagic lesions on the skin, mucous membranes, and visceral organs at autopsy. microscopic examination reveals necrosis in many organs, including the liver, spleen, kidneys and gonads [ ] . in the liver, there is also evidence of apoptosis, microvesicular steatosis and kupffer cell hyperplasia. councilman bodies, which are apoptotic liver cells that have dislodged from adjacent hepatocytes, may be present. eosinophilic oval or filamentous cytoplasmic inclusions may be present, and they are aggregates of ebolavirus np. examination of the lung shows hemorrhages and diffuse alveolar damage. infection of the adrenal gland has been documented in humans [ ] . adrenal necrosis may be one possible pathogenic mechanisms leading to hypotension. marked coagulopathy is a hallmark of evd. disseminated intravascular coagulation frequently occurs. it is believed that tissue factors secreted from monocytes/macrophages are related to the coagulopathies in macaques [ ] . the level of protein c is reduced during coagulopathy [ ] . protein c is important in inflammatory response. a study in which rnapc and rhapc-treated rhesus macaque had better outcome, had higher levels of genes transcriptionally regulated by ccaat/ enhancer-binding protein alpha, tumor protein , and megakaryoblastic leukemia and myocardin-like protein [ ] . although the virus can infect endothelial cells, vascular lesions are not seen in postmortem tissues, and therefore the severe bleeding is unlikely to be related to the direct destruction of the blood vessels by the ebolavirus. similar to other causes of severe sepsis, cytokine/chemokine dysregulation occurs in patients with severe disease. fatal cases had high levels of mip- b, il- , il- , and il- [ ] . in one study, asymptomatic patients had elevated levels of il- b, il- , tnfa, mcp- , mip- a and mip- b in the plasma [ ] . however, in one study, gene expression levels of cytokines in peripheral blood mononuclear cells from infected patients were not different from that of non-infected patients. the level of plasma nitric oxide is higher in fatal than that of non-fatal cases [ ] . the high levels of nitric oxide may have contributed to lymphocyte apoptosis, tissue and vascular damage, and may be associated with the hemodynamic instability seen in fatal cases. one of the major innate defense mechanisms against viral infection is the ifn pathway. ifn are produced by cells upon viral infection, and induced several proteins, including the ifn-induced transmembrane proteins (ifitms). it has been shown that the type ifns and the ifitm , and to a lesser extent ifitm , restrict the cell entry of ebolavirus [ ] . as mentioned above, the viral proteins vp and vp interfere with the ifn pathway which may in turn dampen the priming effect on the adaptive immune response, thus allowing the virus to replicate to high titers. the importance of humoral and cell-mediated immune response is illustrated by a study comparing survived and fatal cases [ ] . ebolavirus-specific igm and igg were detected in all survivors during the early course of illness, with positive titer detected as early as days after symptom onset. in contrast, only one third and none of fatal cases had detectable igm and igg response, respectively. activation of cytotoxic t cells, as indicated by the upregulation of fasl and perforin mrna expression, was observed at the time of viral clearance for survivors, and the levels of ifng, soluble fas and soluble fasl were low during the recovery phase, suggestive of a regulated cytotoxic t cell response during the recovery phase. for the fatal cases, the levels of ifng, soluble fas and soluble fasl were elevated and increasing before death, suggestive of massive activation of cytotoxic t cells. after natural infection, neutralizing antibodies are produced in some patients. persistent serum-neutralizing activity and igg immunoreactivity for at least years after infection have been found in some survivors [ ] . monoclonal antibodies against gp have been shown to protect non-human primates from lethal infection as both post-exposure prophylaxis [ e ] and treatment [ , ] . the level of anti-gp igg highly correlated with survival in guinea pigs and cynomolgus macaques which were vaccinated by gp expressed in adenovirus or vesicular stomatitis virus vectors [ ] . antibodies are also critical in conferring protection for cynomolgus macaques after vaccination with recombinant vesicular stomatitis virus expressing gp [ ] . vaccine studies in animals have provided clues to the contribution of cell mediated immunity in conferring protection. mice study showed that virus-like particles induced protective immunity only in wild type mice but not in nk-cell depleted mice, therefore suggesting that nk cells are important in protective immunity [ ] . the role of t cells is controversial. while one study showed that cd þ t cells are required for conferring protection [ ] , another study showed that it is not required [ ] . despite a high case-fatality rate, there are many individuals with asymptomatic infections, as evidenced by a high percentage of seropositive individuals. although many factors may determine whether a patient develops symptomatic disease, host genetic differences likely play an important role, as in other infectious diseases [ , ] . mice with different genetic backgrounds had different susceptibility to ebolavirus infection, and possibly related to the variations in the tek gene responsible for coagulation [ ] . evd typically progresses rapidly with multisystem involvements, and in particular coagulopathy leading to severe hemorrhage. during the early stage of illness, the patients usually exhibit an acute onset of non-specific flu-like symptoms, including fever, chills, myalgia, and headache, followed by gastrointestinal symptoms including abdominal pain, nausea, vomiting and diarrhea [ ] . respiratory symptoms, such as cough and sore throat may also occur. a maculopapular rash typically occurs on day e after symptom onset, and is associated with erythema and desquamation. hemorrhagic phenomenon then appears, which can include petechiae or ecchymoses, uncontrolled oozing from venipuncture sites, and mucosal hemorrhages. however, it should be noted that massive hemorrhage occurs in fewer than half of patients and is seldom the cause of death. in the outbreak, unexplained bleeding was reported in only % of patients [ ] . hypovolemia can develop rapidly. as in other causes of severe sepsis, complications including disseminated intravascular coagulopathy and multi-organ failure can occur. death usually occurs between days and after symptom onset. survivors usually improved on day e , when neutralizing antibodies start to develop. in the convalescent phase, myelitis, recurrent hepatitis, psychosis and uveitis may develop [ ] . for pregnant women, there may be an increased risk of severe illness and death. there is also an increased risk of spontaneous abortion and pregnancy-related hemorrhage. in the outbreak in drc, fetal or neonatal loss occurred in all third trimester pregnancies [ ] . in fact, the first case of evd in sierra leone was a pregnant woman with miscarriage [ ] . blood test may show thrombocytopenia, leukopenia, hepatic dysfunction with elevated levels of aspartate aminotransferase more than that of alanine aminotransferase, amylase and d-dimer. hemolysis is severe especially in the acute stage [ ] . blood film may also show atypical lymphocytes [ ] . renal impairment usually appears by the end of the first week. fatal cases have higher viral load in the blood [ , ] . despite a fatal disease in over % of infected patients, some individuals did not develop symptoms. during the evd outbreaks in gabon in , asymptomatic individuals with direct exposure to infected materials were identified [ ] . eleven of these patients developed specific igm and igg response to ebolavirus. furthermore, rt-pcr for ebolavirus was positive in the peripheral blood mononuclear cell samples from of these seropositive individuals. positive-strand rna, the presence of which suggests active replication, was detected in individuals. since high grade viremia occurs in the acute period, the preferred diagnostic test is rt-pcr of the blood. rt-pcr targeting the np can be performed in the serum, plasma, whole blood, or oral fluid [ , ] . rnaemia can be detected on the day of symptom onset with viral loads of about e logs copies per ml. the viral load increases rapidly and reaches to logs on day of symptom onset. the level of rnaemia peaks on about day after symptom onset, and the level of rnaemia is higher in fatal cases than that in survivors [ ] . antigen-capture elisa can also be used on blood samples, but is less sensitive than rt-pcr [ ] . a rapid immunochromatographic assay for the detection of ebolavirus antigen, which claimed to provide result in min, was recently announced by the france's atomic energy commission [ ] . viral culture from the blood using vero e is usually positive in the acute stage, but should not be performed except in biosafety level facilities. viral particles may be seen in the serum under electron microscope, which was used in the confirmation of the first cases in the current outbreak [ ] . other than blood samples and oral fluids, the virus can also be detected in other body fluids, but these are not usually used for diagnosis. serum igm is useful during the convalescent phase, but is not useful in the acute setting. serum igg is not reliable, as one study showed that out of survivors did not have detectable igg levels at the time when viral antigen was no longer detected [ ] . several biomarkers have been proposed to be associated with adverse outcomes. in addition to elevated cytokine/chemokine levels, levels of thrombomodulin and ferritin are also elevated in patients with poor outcome, while the scd l, a protein produced by platelet responsible for repairing damaged endothelium, is higher in survivors [ ] . currently, the cornerstone in the management of patients with evd is supportive care. although this is taken for granted in developed countries, these supportive measures are usually lacking in the most affected areas with poor healthcare infrastructures. aggressive volume and electrolyte management, oral and intravenous nutrition, medications to control fever and gastrointestinal distress, and medications to treat pain, anxiety and agitation are important measures [ ] . coinfections should be actively sought and treated appropriately [ ] . there are currently no licensed antiviral drugs to treat evd. before the outbreak, specific therapy has been used in humans with some success. during the evd outbreak, a male investigator pricked himself while transferring homogenized liver from an infected guinea pig [ ] . six days after the injury, he developed fever, central abdominal pain and nausea. on the same day, he started to receive a -day course of human ifn million units every h administered intramuscularly. the human ifn was prepared by stimulating peripheral lymphocytes with sendai virus in vitro. on day after the injury, he received ml of convalescent sera which was obtained from infected people from zaire, and the viral load was reduced from . guineapig infective units per ml to - guinea-pig infective units per ml. on day after the injury, he received the nd infusion of convalescent sera. he eventually recovered. subsequently in the ebolavirus outbreak in kikwit, of patients who received blood donated from convalescent patients survived [ ] . both convalescent plasma and ifn-b were later tested in rhesus macaques, but only convalescent plasma was found to improve survival [ , ] . in the evd outbreak, convalescent plasma has been given to several patients, but the efficacy of convalescent plasma remains to be determined. in addition to convalescent plasma and ifn-b, several experimental treatments have been shown to improve survival in non-human primates ( table ). the first strategy employs the antiviral effect of neutralizing antibodies, either through direct administration of the antibodies or through active immunization. monoclonal antibody cocktails targeting different sites of the ebolavirus were shown to protect primates [ , , ] . zmapp, a cocktail of monoclonal antibodies that are originally contained in the preparation mb- (consisting of human or human-mouse chimeric mabs c c , h f and c d ), and zmab (consisting of murine mabs m h , m g and m g targeting gp) have been shown to protect rhesus macaques from lethal challenge when given up to days post infection [ ] . post-exposure vaccine, such as the vesicular stomatitis virus-based vaccine, can elicit anti-gp antibodies and improve the survival of rhesus macaques when given e min post infection [ ] . the second strategy is to inhibit the activity of virus proteins. antisense oligonucleotides target the viral l protein and vp proteins, can also improve survival of infected rhesus macaques [ , ] . the third strategy aims to ameliorate the deleterious host immune response. recombinant nematode anticoagulant protein c and recombinant human activated protein c could alleviate the coagulopathy and improve survival in animal models [ , ] . however, the clinical efficacy of recombinant human activated protein c is questioned because a randomized double-blind placebo-controlled study did not show survival benefit in patients with septic shock [ ] . among these experimental treatments, monoclonal antibody cocktail (zmapp) and small interfering rna (tkm-ebola) have been used in patients during the current outbreak [ , ] . both antibody and rna-based therapy might be limited to a particular species, and may become ineffective if there are mutations affecting the related antigenic epitopes or gene targets. the efficacy of these experimental treatments in humans remains to be determined. several drugs currently undergoing clinical trials have antiviral activity against ebolavirus. one of the most promising is nucleotide analog brincidofovir (cmx- ), which is a lipid-conjugated prodrug of cidofovir that is converted intracellularly to cidofovir. brincidofovir is currently undergoing phase iii clinical trials for adenovirus and cytomegalovirus infection. this drug has in vitro activity against ebolavirus [ ] , and has been used as an experimental treatment in the current outbreak [ ] . repurposing of licensed drugs has been considered for the treatment of evd as in other emerging infectious diseases which have no specific antiviral treatment [ e ] ( table ). the ic of clomiphene, chloroquine and imatinib table experimental post-exposure prophylaxis/treatment after lethal ebolavirus challenge in non-human primates. are above the peak serum level in humans, and therefore these are unlikely useful clinically. both toremifene and favipiravir had peak serum levels above the ic , and both of these drugs have shown to improve survival in mouse models [ , ] . toremifene can achieve plasma concentrations of about mm at a high dose of mg/day that are inhibitory in cell culture (ic e mm in vero cells). however the murine model utilizing a high dose of mg/kg initiated at h post infection can only achieve a % survival [ ] . moreover prolonged qtc changes have been reported at a dose of mg once daily [ ] . thus clinical trials should consider dosage adjustment, cardiac and electrolyte monitoring. favipiravir also appears effective in mice model, and has been administered to a patient in france [ ] . although the efficacy of these drugs in humans is uncertain especially when non-human primate treatment data are not available, they may be considered when better options are not available and the benefit-risk ratio is favorable. since fusion of the viral and cellular membrane in the endosome plays an important role in the viral life cycle, several studies have used chemical libraries to screen for molecules which can inhibit processes in the fusion step. using this strategy, molecules that can inhibit cathepsin-l mediated cleavage of gp [ ] and binding of gp and npc [ ] have been identified. the experience of post-exposure prophylaxis in humans mainly comes from laboratory accidents. in , a scientist from the us army medical research institute of infectious diseases (usamriid) suffered from a needlestick injury while working with mouse-adapted variant of zaire ebolavirus [ ] . as post-exposure prophylaxis, he received a liveattenuated recombinant vesicular stomatitis virus expressing gp of zaire ebolavirus h after the accident. the scientist had fever h after receiving the vaccine, but otherwise remained asymptomatic. three phase- clinical trials have been conducted. the first trial used an adenovirus-based vaccine expressing gp, involving subjects in the vaccine group and subjects in the placebo group [ ] . the vaccine group was further divided into a high dose and a low dose group. specific antibody response developed in % for recipients of high dose vaccine. the vaccine was well-tolerated. two vaccine recipients were complicated by the development of antiphospholipid antibody, and one vaccine recipient developed fever > c. in the second trial, two gp (zaire and sudan) dna vaccines were expressed in a vr- expression vector and produced in escherichia coli [ ] . there were subjects in the vaccine group and subjects in the placebo group. specific antibody responses to at least one of the vaccine antigens developed in all vaccine recipients. this second vaccine is also well-tolerated. in the vaccine group, subject developed raised creatine phosphokinase (associated with vigorous exercise) and subject developed herpes zoster. the third trial (vrc study) evaluated a dna vaccine encoding the wild type gp antigens from zaire and sudan ebolavirus which is produced in e. coli [ ] . ten subjects were enrolled. there were no serious adverse events. the vaccine elicited specific antibodies against both gp antigens. at the time of writing, two other vaccines are undergoing phase i clinical trials [ ] . vaccines against ebolavirus consisting of virus-vectors such as adenovirus type , human parainfluenza virus type , vesicular stomatitis virus; virus-like particles with vp , np and gp, and recombinant ebolavirus have been tested in animal models [ ] . the efficacy of these vaccines in humans awaits further studies. current evidence suggests that ebolavirus is transmitted via contact with contaminated body fluid or the contaminated environment, and therefore the practice of contact precautions with appropriate personal protection equipment (ppe) is of utmost importance when handling suspected or confirmed cases of evd. healthcare workers should preferably work in pairs so as to mutually guard against breaks in infection control measures. they are required to put on the ppe in the following sequence, from n respirator, water repellent cap or hood, full length shoe cover or boot, water resistant gown, face shield, and long nitrile gloves. if the patient has hemorrhagic symptoms, double nitrile gloves should be worn. in table licensed drugs with antiviral activity against ebolavirus. view of the high virulence and mortality, patients suspected to have evd should be isolated in airborne isolation room in the developed countries, although who allows cohorted nursing in the designated areas with dedicated instruments, where access should be restricted in the developing countries with limited isolation facilities [ ] . degowning remains the most critical procedure for the healthcare workers. the most contaminated ppe should be removed first, from long nitrite gloves, water resistant gown, full length shoe cover or boot, face shield, water repellent cap or hood, and finally n respirator. hand hygiene with alcohol-based hand rub should be performed in each step of degowning. when the hand is visibly soiled, it should be washed with soap and water. healthcare workers must be well trained and audited for the proper procedure of gowning and degowning. when the suspected or confirmed case of evd dies, the healthcare and mortuary workers are required to wear ppe as described above. the dead body is placed in double bags with leak-proof characteristic of no less than mm thick. absorbent material should be put under the body and placed in the first bag. the surface of each body bag is wiped with , ppm sodium hypochlorite solution. the bags are sealed and labeled with the indication of highly-infectious material (category ) and moved to the mortuary immediately. viewing in funeral parlor, embalming and hygienic preparation are not allowed. the dead body should not be removed from the body bag and should be sent to cremation as soon as possible. since the outbreak was first reported to who on march , , the situation continues to deteriorate, and the consequences can be catastrophic in terms of lost lives but also severe socioeconomic disruption and a high risk of spread to other countries. on august , , who declares the evd outbreak in west africa a "public health emergency of international concern". preparedness and response plan were made available in most of the health authorities all over the world. the aim is to detect the first imported case for early isolation in order to prevent local transmission in the community and healthcare setting. risk assessment in the port health, emergency room, and outpatient clinics for any patient fulfilling both clinical and epidemiological criteria for evd is important. for the clinical definition, patient suffering from a sudden onset of fever with over c, or having at least one of the following signs including inexplicable bleeding, bloody diarrhea, bleeding from gums, bleeding into skin or eye, or hematuria should be alerted, while the epidemiological definition includes close contact with a confirmed or probable case of evd or resided in or history of travel to an affected area or countries within days before onset of symptoms. for healthcare workers working in volunteer medical services or non-government organizations, who have direct contact with patients in the affected areas or countries, should also perform medical surveillance for at least days after leaving the affected areas or countries. they are required to seek medical advice promptly if there are any symptoms of fever, diarrhea, vomiting, rash or bleeding during medical surveillance. one of the major problems with the current outbreak is the panic associated with the disease. many patients with symptom did not seek medical care because of the fear of contracting the disease from the hospital [ ] . therefore, the local governments and health authorities should focus on the health education and give a clear instruction to the person for seeking early medical attention in the unaffected areas of africa. however, when the community transmission of ebolavirus is uncontrolled, implementation of home quarantine for up to days (one incubation period) can be considered. home quarantine measure had been used to control the community spread of sars in beijing, taiwan, singapore, and toronto [ ] . however, the public health staff is expected to face unprecedented challenges in implementing an extensive quarantine policy, as they have a dual role of monitoring compliance and providing support of daily necessities to people in quarantine. the countries next to the affected areas require implementing border control measures to screen for any suspected case of ebolavirus. although these measures may adversely affect the international travel and economy, it may be worthwhile to implement such a strict measure to control this re-emerging infectious disease with high mortality and psychological fear in a timely manner. humans are constantly under the threat of infectious diseases. some emerging infectious diseases have been especially important in human history with significant loss of population, economic disruption and political instability. yersinia pestis caused the black death in europe, killing up to one-third of the population [ ] . the e cholera outbreak after the major earthquake in haiti reminded us that a seemingly easyto-treat and control infection can cause large outbreaks when the infrastructure is damaged [ ] . sars coronavirus, mers coronavirus, and the avian influenza viruses have caused epidemics with major health and economic effects [ e ]. the current west africa evd outbreak is unprecedented in that this is the largest evd outbreak with local transmission outside africa. one of the major differences from previous outbreaks is that it has affected crowded major cities in west africa where the infrastructure has been heavily damaged due to civil wars. the rapid spread is facilitated by the efficient person-to-person transmission due to high viral loads in blood, bodily secretions and the contaminated environment. the large amount of virus particles shed in body fluid makes this virus very contagious, even among healthcare workers who are already equipped with ppe. whole genome study showed that the current west africa ebolavirus strain is phylogenetically distinct from previous outbreak strains, and this current ebolavirus strain has higher mutation rate than previous strains. however, it is currently not known whether this strain is particularly virulent or transmissible. currently, there are major gaps in our understanding of the disease due to the lack of systematic epidemiological, pathological, clinical and virological studies that are taken for granted in developed countries. for example in the pandemics and epidemics caused by coronaviruses and influenza viruses, many studies were conducted quickly within few months of the outbreak, and the results allowed early control of 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virus disease ebola enew challenges, new global response and responsibility efficiency of quarantine during an epidemic of severe acute respiratory syndromeebeijing, china cholera surveillance during the haiti epidemicethe first years the emergence of influenza a h n in human beings years after influenza a h n : a tale of two cities from sars coronavirus to novel animal and human coronaviruses is the discovery of the novel human betacoronavirus c emc/ (hcov-emc) the beginning of another sars-like pandemic severe acute respiratory syndrome coronavirus as an agent of emerging and reemerging infection world health organization. global alert and response. ebola virus disease. disease outbreak news centers for disease c, prevention. ebola viral disease outbreakewest africa single-dose pharmacokinetic study of clomiphene citrate isomers in anovular patients with polycystic ovary disease pharmacokinetic analysis of high-dose toremifene in combination with doxorubicin t- (favipiravir) post-exposure efficacy of oral t- (favipiravir) against inhalational ebola virus infection in a mouse model drugdex system (micromedex . ). truven helath anal bioequivalence study of two imatinib formulations after single-dose administration in healthy korean male volunteers this work was partly supported by the commissioned research grant from the research fund for the control of infectious diseases of the food and health bureau of the hong kong sar and the consultancy service for enhancing laboratory surveillance of emerging infectious disease for the hksar department of health. key: cord- -vgubi k authors: okoi, obasesam; bwawa, tatenda title: how health inequality affect responses to the covid- pandemic in sub-saharan africa date: - - journal: world dev doi: . /j.worlddev. . sha: doc_id: cord_uid: vgubi k the covid- outbreak has infected millions of people across the world, caused hundreds of thousands of deaths, and collapsed national economies. recognizing the importance of handwashing in preventing the spread of covid- , concerns have arisen about the condition of millions of africans who lack access to hygiene facilities and clean water services. this paper compiles evidence from the who-unicef data to show the health disparities that limit the capacity of african countries to effectively address the covid- disease along with recommendations for addressing the challenge. since january , the novel coronavirus (covid- ) outbreak has infected millions of people globally, caused hundreds of thousands of deaths, and collapsed national economies. covid- is a respiratory disease transmitted human-to-human primarily through direct contact with an infected person or via respiratory droplets released as an infected person sneezes, coughs, or talks (offord, ; who, ) . viruses contained in these respiratory droplets can easily infect other people when they land on the nose, eyes, or mouth or are transferred there by people touching their faces with contaminated hands (offord, ) . there are ongoing efforts to understand the pathological features of the disease and develop measures to prevent its community spread. so far, scientists have compiled evidence to explain the human-to-human transmission of covid- (paules et al., ) and how the disease spreads via asymptomatic carriers (chan et al., ) . lu et al. ( ) have examined the potential route of covid- transmission by studying the airflow inside an airconditioned restaurant in guangzhou, china. the study traces the most likely cause of the outbreak to droplet transmission from airconditioned ventilation in which the key factor was the direction of airflow. despite this evidence, ''the mechanism by which asymptomatic carriers could acquire and transmit the coronavirus that causes covid- requires further study" (bai et al., (bai et al., , p. . recognizing the importance of handwashing in preventing the spread of covid- , concerns have arisen about the condition of millions of africans who lack access to hygiene facilities and clean water services. the purpose of this paper is to show the health disparities that limit the capacity of africans to effectively address the spread of the covid- disease using evidence from the who-unicef household data. our analysis reveals the challenging context of mitigating the spread of the covid- pandemic in sub-saharan africa, given the disparities in health and the socioeconomic conditions in which they arise. we present three policy options for preventing the spread of the covid- pandemic in sub-saharan africa. various governments have developed policies to address health inequality and its social determinants (owusu-addo, renzaho & smith, ). academics and practitioners have given considerable attention to efforts aimed at improving overall population health and reducing the burden of diseases as well as eliminating health disparities based on socioeconomic status, race, geography, gender and ethnicity (arcaya, arcaya & subramanian, ; balaj et al., ; devaux, ; graham & kelly, ; hu et al., ; kilbourne et al., ; whitehead, ) . omotoso and koch ( ) contend, however, that despite significant efforts to address the socioeconomic issues that aggravate health inequalities, strikhttps://doi.org/ . /j.worlddev. . - x/Ó elsevier ltd. all rights reserved. ing disparities in ''health status still exists within and among countries" (p. ). we cannot ignore the importance of making hygiene services accessible to vulnerable populations in sub-saharan africa. as the who-unicef data reveals, about million africans have no basic handwashing facility (see fig. ). in the democratic republic of congo, over million people, more than three-quarters of the country's population, have no handwashing facilities. the situation in nigeria, an oil-rich country where nearly million people have no handwashing facilities, is unspeakable. health disparities in nigeria affect the distribution of water and hygiene services among poor populations, which can lead to a disproportionate impact on public health outcomes during a pandemic outbreak such as covid- . ethiopia is another country where the health disparity is appalling, as million people have no handwashing facility (see fig. ). the health disparities in sub-saharan africa are prevalent in small countries such as rwanda, angola, zambia, togo, senegal, chad, liberia, and sierra leone, where more than half the population lack handwashing facilities. for example, million rwandans, million angolans, . zambian, million togolese, . million liberians, . million senegalese, and . million sierra leoneans have no handwashing facilities (see fig. ). in a small and low-income country like liberia with a . million population, . million people, representing percent of the country's population, have no handwashing facilities. equally important is a small country like sao tome and principe with a population of , in which three quarters is urban, yet where about , -nearly half of the country's population-have no handwashing facilities. water scarcity is another public health challenge in sub-saharan africa, where a staggering million population had no access to piped drinking water between and . in alone, about million africans did not have access to piped drinking water (fig. ) . the disparity between the demand for drinking water and its availability has a disproportionate impact on the poor. socioeconomic differences determine which populations have access to water and hygiene services or denied these services. the disparity in handwashing facility coverage across sub-saharan africa paints a disturbing picture of health inequality that reveals the vulnerability of the poor to the covid- pandemic. as abdullahi ( ) notes, poverty is rooted in the deprivation of people's access to necessities such as healthcare and sanitation. therefore, the impact of poverty in countries where existing health inequities may exacerbate the vulnerability of the poor to the covid- pandemic remains a critical challenge. in , the brookings institution released the global poverty projections based on data from the world poverty clock, which shows that africans account for two-thirds of the more than million people across the world living in extreme poverty. the worst affected countries are nigeria ( million); democratic republic of congo ( million); ethiopia ( . million); tanzania ( . million); mozambique ( . million); kenya ( . million); and uganda ( . million) (adebayo, ; kharas, hamel & hofer, ) . the failure of an oil-rich country like nigeria to translate its oil wealth into rising living standards for millions of its citizens weakens prospects for populations living in extreme poverty (okoi, ) . under these conditions, poverty and economic inequality can increase the vulnerability of the poor to the covid- pandemic. as one of the world's most unequal regions regarding income inequality (gandhi, ) , poverty in sub-saharan africa manifests in significant disparities in health status (adeyanju, tubeuf & ensor, ; boutayeb & helmert, ; braveman and tarimo, marmot, ; orach & garimoi, ; wagstaff, ) . because elders are considered the most at-risk population due to pre-existing conditions, economic inequalities that manifest in significant health disparities can increase their vulnerability to covid- . cloos ( ) found a positive relationship between health and the socioeconomic status of elders in barbados. by implication, health inequalities correlate with the social determinants of health (ataguba, akazili & mcintyre, ) , with elders being the most vulnerable. in african countries with severe health disparities arising from socioeconomic factors, the outbreak of covid- can have a devastating impact on poor populations, especially elders. the refugee crisis in africa calls for concern. we cannot ignore the impact of covid- on millions of africans who have been displaced by conflict, terrorism, and persecution. in recent years, south sudan has been the origin of most refugee cases on the continent, which often produce a spillover effect. the influx of south sudanese refugees to neighbouring countries such as uganda, kenya, ethiopia and the democratic republic of congo (drc) impose a humanitarian burden on these countries. the complex humanitarian challenge that displacement poses on the continent aggravates health disparities that render millions of displaced per- sons vulnerable to the covid- disease. we argue, therefore, that the humanitarian challenge in sub-saharan africa is likely to increase the risk of the disease spreading more easily in refugee and displacement camps where millions of people are living in unhealthy conditions. this paper examined the health inequities in sub-saharan africa that expose vulnerable populations to the covid- pandemic. while covid- is transforming our way of life, including our health, in unprecedented ways (lichfield, ) , containing the spread of the disease in societies with dysfunctional health systems raises critical concerns. efforts to contain the spread of the disease would require developing and implementing public health interventions that take into consideration concerns about equity and social justice. the key challenge is how to translate research on the social determinants of health into public health practice (tod & hirst, ) . the research agenda needs to move beyond documenting health inequalities to include efforts to support policy development to reduce inequality and improve healthy living conditions for the most vulnerable populations (masseria, hernández-quevedo & allin, ) . as the world awaits the development and availability of vaccines, several measures can be undertaken at the national and subnational levels to prevent the worst effect of covid- pandemic on poor communities across sub-saharan africa. we propose three policy options for addressing the challenge. the human-to-human spread of the covid- disease is preventable by implementing measures that promote healthy behaviours at the population level in culturally appropriate ways. health promotion must emphasize community-based interventions designed to achieve change in risk behaviour across a population ** (merzel & d'afflitti, ) . such initiatives must focus on engaging with populations at risk to learn about their needs and the type of interventions required to support the population in practicing healthy behaviours such as physical distancing, handwashing, and the wearing of face mask in public. these measures must include organizing information sessions with local volunteers to assess threats and the capacity of community health institutions. there are rising concerns about the lack of access to community health services to support hygienic behaviour. the governmentimposed lockdown measures and the promotion of handwashing behaviour have been counterproductive in african communities where marginalized populations lack access to drinking water, handwashing facilities, and soap due to poverty. as munodawafa, sookram & nganda ( ) noted, access to health services is key to addressing the prevalence of health inequalities in sub-saharan africa. improving the living conditions of marginalized populations must include providing access to water, handwashing facility, and hand sanitizers. governmental actors have responsibilities to prevent the spread of covid- by making these services accessible to populations at risk. pro-poor strategies focused on improving living conditions are key to addressing health inequalities in sub-saharan africa (munodawafa, sookram, & nganda, ) . the implementation of cash transfer measures can mitigate the structural determinants of health, such as income poverty, that limit the capacity of marginalized populations to fight the covid- pandemic. when people have the means to meet their basic needs for food and shelter, they will be encouraged to engage in healthy behaviours such as physical distancing and hygienic practices that will decrease their vulnerability to the covid- disease. three things nigeria must do to end extreme poverty nigeria overtakes india in extreme poverty ranking fig. . drinking water -sub-saharan africa. source: who-unicef data on population with piped and non-piped drinking water socio-economic inequalities in access to maternal and child 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inequalities: concepts, frameworks and policy inequality, gender gaps and economic growth: comparative evidence for sub-saharan africa trends in socioeconomic inequalities in self-assessed health in european countries between and socioeconomic differences in mortality in the antiretroviral therapy era in agincourt, rural south africa, - : a population surveillance analysis the start of a new poverty narrative. brookings institution advancing health disparities research within the health care system: a conceptual framework we're not going back to normal covid- outbreak associated with air conditioning in restaurant achieving health equity: from root causes to fair outcomes social determinants of health inequalities health inequality: what does it mean and how can we measure it? a strategy for addressing the key determinants of health in the african region. brazzaville: who, regional office for africa how covid- is spread the paradox of oil dependency in nigeria assessing changes in social determinants of health inequalities in south africa: a decomposition analysis health equity: challenges in low income countries the impact of cash transfers on social determinants of health and health inequalities in sub-saharan africa: a systematic review coronavirus infections-more than just the common cold health and inequality: applying public health research to policy and practice research on equity, poverty and health outcomes: lessons for the developing world a typology of actions to tackle social inequalities in health water, sanitation, hygiene, and waste management for the covid- virus the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. key: cord- -u s uzp authors: bamgboye, ebun l.; omiye, jesutofunmi a.; afolaranmi, oluwasegun j.; davids, mogamat razeen; tannor, elliot koranteng; wadee, shoyab; niang, abdou; were, anthony; naicker, saraladevi title: covid- pandemic: is africa different? date: - - journal: j natl med assoc doi: . /j.jnma. . . sha: doc_id: cord_uid: u s uzp covid- has now spread to all the continents of the world with the possible exception of antarctica. however, africa appears different when compared with all the other continents. the absence of exponential growth and the low mortality rates contrary to that experienced in other continents, and contrary to the projections for africa by various agencies, including the world health organization (who) has been a puzzle to many. although africa is the second most populous continent with an estimated . % of the world's population, the continent accounts for only % of the total cases and % of the mortality. mortality for the whole of africa remains at a reported , as at august , . the onset of the pandemic was later, the rate of rise has been slower and the severity of illness and case fatality rates have been lower in comparison to other continents. in addition, contrary to what had been documented in other continents, the occurrence of the renal complications in these patients also appeared to be much lower. this report documents the striking differences between the continents and within the continent of africa itself and then attempts to explain the reasons for these differences. it is hoped that information presented in this review will help policymakers in the fight to contain the pandemic, particularly within africa with its resource-constrained health care systems. introduction c ovid- , a novel disease caused by the sars-cov- virus was declared by the world health organization (who) as a public health emergency of international concern on january , and as a global pandemic on the march , . first noted in wuhan in the hubei province of china in december , it has now spread to all the continents except antarctica. every country in the world, with the possible exception of north korea and turkmenistan, has documented confirmed cases with a spiraling increase in covid- related mortality and an excess of overall mortality compared to previous years. although covid- manifests primarily as a respiratory tract infection, there have been many reports of renal involvement, more so in the severe forms of the disease. , patients with chronic kidney disease (ckd) are amongst those at the highest risk for developing severe disease. this is over and above other recognized risk factors like hypertension, diabetes, chronic lung disease, and cancers,which are common comorbidities and often coexist with ckd. patients on maintenance haemodialysis (hd) are at particular risk, given the need to come into dialysis centres for their treatment sessions. the enclosed spaces of most dialysis units with centralized, recycled air-conditioning and the length of time necessary for haemodialysis further compounds this risk. patients with kidney transplants need to use immunosuppressive agents which increases their risk of acquiring the illness and of progression to severe disease. acute kidney injury (aki) is one of the more common complications of severe covid- and studies have reported an incidence as high as % amongst hospitalized patients, with it being one of the major reasons for mortality in these patients. recent reports have also suggested a possible association between high-risk apol genotype, common in peoples of african descent, and the increased risk of kidney disease in covid- . reports of collapsing glomerulopathy associated with covid- in patients of african ancestry who are carriers of apol risk variants have also been described and the name covid- -associated nephropathy (covan) for the condition has been proposed. these challenges are superimposed on nephrology practice in a continent that has limited resources and capacities to deal with renal patients even preceding the ongoing pandemic. africa is the world region with the lowest density of nephrologists at . per million population (pmp), and nine of the ten countries with the lowest nephrologist densities are from the africa region. many countries have no trained nephrologists and many that do, have very low numbers with few dialysis units often restricted to the urban centres. peritoneal dialysis is not widely available as the fluids are not manufactured locally and the cost of importation puts this beyond the reach of most patients as costs are often borne out-of-pocket by the patients themselves. [ ] [ ] [ ] [ ] [ ] against this background, the african association of nephrology (afran), developed covid- guidelines to guide nephrologists in the continent on measures to be taken by nephrology practitioners in the care of our regular patients during this pandemic and also in the management of patients developing the renal complications of covid- . during the discussions leading to the production of the guidelines, local experiences and insights were shared by members of the expert committee from the different countries represented on the committee. these discussions prompted afran to conduct a more formal survey to document the experience of covid- in different member countries. this report also summarizes the results of the survey and reflects on the reasons for some of the apparent differences in the pandemic between african countries and those in other parts of the world. two sets of data were collected for this study. the first included data to allow comparisons between africa and other regions as well as comparisons within africa itself. we also collected data on variables that could explain the apparent differences in covid- case numbers, mortality, and tests in africa, compared to other parts of the world. for all data sets, publicly available data was gathered up until august , . data on covid- cases, mortality, and test was retrieved from the worldometer website (http://www.worldometers.info/coronavirus/), worldometer is a trusted data aggregator site that retrieves timely data from official websites and social media accounts of ministries of health, government institutions, and official press briefings. the african data was augmented with information from the african centres for disease control (http://africacdc.org/covid- /) and official reports from the disease control centres of various african countries. data on environmental variables i.e. humidity, temperature, and uv index was obtained from weather online (https://www.weatheronline.co.uk/), a site that provides global meteorological data. this source has also been used in previous studies on temperature and coronavirus cases. , the human development index (hdi) data was retrieved from the united nations development program (undp) human development report. flights data was accessed from the international civil aviation organization, which publishes civil aviation statistics on air transport. additionally, data on healthcare access and quality index (haqi) was sourced from the lancet global burden of disease study. furthermore, data on population density and diabetes prevalence was accessed from worldometer and the international diabetes federation (idf). , the second set of data was collected via a survey amongst physicians in various countries in africa in the process of developing the afran covid- guidelines. an electronic (google forms) questionnaire was sent out on a whatsapp forum populated by nephrologists from different countries in africa. questions focused on the availability of nephrology resources in the countries of the various respondents and on their experience with managing cases of covid- with particular focus on the renal complications of the disease. case numbers, mortality, number of tests performed, and demographic data were summarized and compared by continents, regions, and countries within the continent of africa. also, we compared all african countries to the top worst-hit covid- countries. scatter plots were used to visualize the data and correlation coefficients were calculated to identify the strengths of the relationships between variables. the data analysis tool on the google forms platform was used to summarize the survey responses. africa accounts for . % of the world's population, but only about % of the total covid- cases diagnosed and % of the related mortality ( figure ). the number of cases per million population (pmp) globally is , , with south america ( pmp), north america ( , ) and europe ( , ) the most affected regions, while africa has a lower rate of pmp ( figure ). the case fatality rates have been . % worldwide, . % in europe, . % in north america, . % in south america and . % in africa. furthermore, as shown in figure , the values also vary considerably within the various countries in the african continent, although this might be related to differences in the number of tests performed (table ) . south africa and egypt have reported the most cases. importantly, these countries are amongst the countries at the top of tests done which is a critical factor in determining the number of confirmed cases. all the countries surveyed employed the rt-pcr method for diagnosis and many have experienced constraints with obtaining the necessary reagents. south africa, morocco, ethiopia and ghana however stand out prominently in terms of the number of tests done thus far. ghana has used pooled samples for screening suspected cases with separate tests done for only the positive pooled samples. the experience shared by african nephrologists has revealed that most of the cases have been completely covid- pandemic: is africa different? asymptomatic or mildly symptomatic, with very few patients requiring intensive care. the first set of patients managed in nigeria were mostly asymptomatic and none required intensive care. this has also reflected in the prevalence of the renal complications of covid- and the need for renal replacement therapy (rrt). the responses from the survey have indicated a paucity of cases requiring rrt, with % of respondents having no cases in their country requiring rrt. countries with more developed healthcare systems like egypt and south africa had a greater number of cases. approximately % of respondents noted that haemodialysis was available as a means of rrt. the survey also confirmed the poor state of nephrology care in the continent with many countries having limited numbers of nephrologists, few dialysis centres and very few dialysis machines. the median number of dialysis centres and nephrologists among the respondents were and respectively. the public health response of several countries consisted of a containment policy involving the isolation of all positively diagnosed cases at isolation centres. unfortunately, quite a number of these isolation centres lacked the capacity to perform dialysis as indicated by % of the survey respondents, with the consequences of avoidable mortality. some centres with limited capacity had only a single dialysis unit. there are regional differences within the continent as regards the severity of cases and the outcomes, with the countries in north africa having the worst outcomes. the case fatality rate is . % for north africa, . % for west africa, . % for south africa, . % for east africa and . % for central africa. south africa and egypt account for % of all african cases and for % of the mortality. these two countries along with nigeria, the third ranked in terms of numbers, are also the three strongest economies on the continent. north africa particularly appears to have the worst statistics in africa, even though their numbers represent % of total cases, they constitute % of mortality. several reasons have been adduced for this unexpected pattern of illness being seen in africa. given that covid- reached countries in africa by importation from asia, europe, and america, the onset of the disease in most countries was much later than was experienced in other continents. of the countries in africa, reported their first case in february, in march, in april, and in may. this of course suggests that many of these countries are still experiencing the early stages of the pandemic. the number of cases in the early stages of the pandemic was directly proportional to the number of international flights into african countries. the busiest international airports in the continent are located in south africa which also has the highest numbers on the continent, followed by egypt which is also second in case numbers ( figure a ). countries with infrequent business and tourism contacts with other continents are those with the lowest numbers ( figure b ). the few countries to buck this trend were countries like kenya and ethiopia whose airports serve as hubs for several countries on the continent and many international travelers pass through their airports and not actually into these countries. many african countries with previous experience of managing other epidemic infectious diseases like ebola, tuberculosis, and lassa fever closed down their airports to international travels much earlier than had been done in other continents. prior to the closure, many commenced disease surveillance activities and contact tracing at the airports, again much earlier than was done in many other countries outside the continent. all of these factors limited the number of cases "seeded" into african countries delaying the outset and the subsequent growth in numbers thereby "flattening the curve" in many of these countries. this is another major potential reason for the relatively lower numbers of cases on the continent. the number of positive cases reported is driven by the number of rt-pcr tests performed. the top five testing countries in the world (as of august , ) were china À million, the usa- million, russia- million, india- million, and the uk- million. in contrast, the top four countries in africa were south africa with . million tests, morocco with . million, ethiopia with , , and ghana with , tests done as at the same date. within the continent, the top testing countries were also the countries with the highest number of cases. many countries have been limited by the costs of these tests and the non-availability of the necessary equipment, reagents, and trained personnel. ghana notably has done many more tests per million of its population by pooling samples, thus testing more patients with each kit deployed. antibody testing in several countries suggests that many cases might have been missed by the paucity of tests carried out in the continent. many of these tests suggest that as much as %- % of the population in some of these countries might have already contracted and recovered from the disease. in fact, preliminary results from a study from the western cape in south africa revealed a seroprevalence of antibodies in % of antenatal screening specimens and routine monitoring blood tests covid- pandemic: is africa different? done for hiv positive ante-natal clinic patients. it is also possible that many deaths attributed to other reasons in the absence of testing might have been due to covid- . the population density in africa is much lower than many of the countries in other continents. the disease spreads quicker and more easily in crowded, enclosed, and noisy spaces. many communities on the continent are rural and widely dispersed, which slows the spread of the virus. the "hotspots" in most countries are the crowded major cities like lagos in nigeria (responsible for over % of cases), johannesburg and cape town in south africa, nairobi in kenya, and cairo in egypt. within these cities, the greatest numbers are seen in crowded communities such as kosofe and alimosho in lagos. the institution of lockdown measures early in the pandemic has also served to limit the spread of the disease. countries like rwanda and senegal which implemented strict and efficient measures were able to limit the spread even better than surrounding countries in their sub-regions. many of these countries, following the economic distress caused by these lockdown measures, have had to relax some of these measures with the consequence of, in some cases, rising numbers. africa is the youngest continent on the planet; the median age of the countries in sub-saharan africa is years. this is in comparison to europe for instance where the median age is years. individuals in europe over the age of years constitute . % of the population, whilst that of sub-saharan africa is %. younger individuals are times less likely to acquire the illness and when they do, they seldom develop severe symptoms or die from the illness. within the continent as well, countries with slightly older populations like egypt and south africa are also the ones with the highest numbers and the greater case fatality rates ( figure ). older individuals are also the ones more likely to have the various co-morbidities that have been associated with severe disease and the risk of mortality. these include obesity, type diabetes, and malignancies. the prevalence of these conditions is greatest in the countries of the maghreb and south africa all of which have the highest case numbers and the worst cfr on the continent (figures and ) . in nigeria, % of patients admitted at the isolation centres had no comorbidities whilst in south africa, % had at least one comorbidity. this could partly explain the larger numbers and higher mortality observed in south africa. the cultural practice of caring for elderly relatives at home as opposed to using care facilities may also be a major factor. in europe and the usa, these care homes were major centres for transmission of covid- with the resultant heightened mortality. age might also be relevant in the vitamin d related factor as younger individuals are more efficient in the production of vitamin d from sunlight and are more likely to be ambulant and exposed to the sun for this to happen. people living near the equator get more uvb light from the sun and thus generally have higher serum vitamin d levels than those living farther away. healthy levels of vitamin d give patients with covid- a survival advantage by helping them avoid the cytokine storm. some preliminary studies have demonstrated that vitamin d status and sun exposure are important factors to consider for reducing the rates of transmission, infection, and severity of illness. , exposure to previous infections there are speculations of the possible relative resistance to the virus with resultant milder presentation and much lower mortality being observed on the continent. there is a hypothesis that exposure to similar coronaviruses in the past may have conferred relative immunity to patients on the continent. coronavirus cross-reactive antibodies may contribute to a low transmission rate and reduced severity of disease associated with sars-cov- through crossneutralization and rapid clearance. the heightened immunity obtained from exposure to previous infections like malaria and other ongoing endemic infections, like tuberculosis and hiv, has been speculated as a possible reason for the milder presentation of the covid- in africa. ongoing vaccination for tuberculosis using the bcg vaccine has also been speculated to be a factor in protecting vaccinated individuals from acquiring the illness and when they do, from the severity of disease and mortality. most countries in africa continue to vaccinate their citizens against pulmonary tuberculosis with bcg, as the disease remains endemic in various countries on the continent. countries in europe with later discontinuation of bcg vaccination also all seem to have relatively fewer cases and milder illness than their surrounding neighbours. although we could not find a correlation with bcg vaccination and the number of coronavirus cases, some studies have shown bcg to be protective against severe cases of the illness. , human development and healthcare quality a correlation has been observed between the human development index (hdi) and the numbers of cases and case fatality rate. countries with higher hdi have higher numbers and worse outcomes ( figure a ). another surrogate of healthcare development, the healthcare access and quality (haq) index showed quite a similar pattern ( figure b ). the pearson correlation coefficients for hdi and haq, against covid- cases pmp were noted to be . and . respectively. some studies have suggested that temperatures in excess of c, ultra-violet rays associated with sunlight and humidity all tend to have negative effects on the survival of the virus. we could not demonstrate this for african countries. however, the rise in numbers in the southern part of the continent currently experiencing their winter season and the relatively lower numbers and mortality in countries closer to the equator with higher temperatures and higher intensity of uv-light might be in keeping with these speculations. despite weaker health care facilities and systems, the growth of cases in africa has defied most predictions and has remained geometric and not exponential. available data and statistics continue to reflect consistently lower numbers than those in other continents except for oceania. the severity of presentation has also remained relatively mild and the anticipated overwhelming of the health systems, including the renal services of the various countries on the continent has not been seen. mortality and case fatality rates have been a fraction of what had been predicted. this is however not a reason to be complacent as for many african countries, these are still early days in the pandemic and a change in the pattern may yet occur as the numbers continue to rise. it has taken six months to reach the first , cases but less than two months to cross the million cases mark on the continent. a novel coronavirus from patients with pneumonia in china, j nejm who director-general's opening remarks at the media briefing on covid- - who coronavirus disease (covid- ) dashboard excess deaths associated with covid- clinical features of patients infected with novel coronavirus in wuhan kidney disease is associated with in-hospital death of patients with covid- collapsing glomerulopathy in a patient with covid- covan is the new hivan: the re-emergence of collapsing glomerulopathy with covid- outcomes in adults and children with end-stage kidney disease requiring dialysis in sub-saharan africa: a systematic review global dialysis perspective: senegal isn global kidney health atlas global nephrology opinion paper workforce: gaps and opportunities toward a sustainable kidney care system the challenges of esrd care in developing economies: sub-saharan african opportunities for significant improvement guidelines for the prevention, detection and management of the renal complications of covid- in africa coronavirus update (live): , , cases and , deaths from covid- virus pandemic -worldometer world weather j world weather online impact of weather conditions on atopic dermatitis prevalence in abuja, nigeria on the global trends and spread of the covid- outbreak: preliminary assessment of the potential relation between locationspecific temperature and uv index healthcare access and quality index based on mortality from causes amenable to personal health care in countries and territories, e : a novel analysis from the global burden of disease study global diabetes data report maverick citizen: spotlight: covid- : high prevalence found in cape town antibody study the possible role of vitamin d in suppressing cytokine storm and associated mortality in covid- patients vitamin d insufficiency is prevalent in severe covid- lessons for covid- immunity from other coronavirus infections bcg vaccine protection from severe coronavirus disease (covid- ) is global bcg vaccination coverage relevant to the progression of sars-cov- pandemic? med hypotheses covid- pandemic: is africa different? key: cord- -hvp ell authors: yazdanbakhsh, maria; kremsner, peter g. title: influenza in africa date: - - journal: plos med doi: . /journal.pmed. sha: doc_id: cord_uid: hvp ell maria yazdanbakhsh and peter kremsner argue that there needs to be better awareness, surveillance, and clinical management of common febrile diseases in africa, especially influenza. whereas in europe and north america most of the influenza cases are reported between december and march, in tropical and subtropical regions such as in brazil [ ] or in hong kong [ ] cases are seen throughout the year. epidemic peaks in the tropical areas mostly occur in between those found in the northern and southern hemispheres. a recent survey over years in brazil showed that annual peaks of influenza cases occurred in association with the rainy seasons [ ] . important reports on spatial and temporal data that describe the global circulation of influenza highlight the fact that there is virtually no data from africa [ , ] . indeed, until recently, the burden of influenza in africa was believed to be negligible. however, sporadic reports from the gambia [ ] , senegal [ ] , congo [ ] , madagascar [ ] , kenya [ ] , ivory coast [ ] , and from gabon [ ] , have indicated that influenza is circulating and may be causing epidemics regularly. the study in gabon recorded extremely high levels of antibodies to influenza a h n virus in schoolchildren [ ] . the haemagglutination inhibition (hi) antibodies to this influenza a virus at titers of , (ranging from to , ) indicated that the virus had been circulating within the community in the recent past. in addition, almost all children, had anti-h n hi titers above , while % showed antibodies to influenza b with hi titers of or above, again highlighting the fact that multiple influenza virus strains are present in the region. the recent swine flu pandemic provides an interesting example. in the who influenza a (h n swine flu) update of may , many countries, but none in africa, reported virus victims [ ] ; whereas two reports appeared in october that showed data on confirmed swine flu cases from south africa [ ] and kenya [ ] , indicating that the virus was circu-lating in africa, but because of the lack of a rigorous surveillance system, it was not reported as readily. clinically, influenza is not distinguishable from most other infectious diseases with fever in the tropics. in this context malaria is of particular interest when considering the african continent. in tropical africa, malaria is an important infectious disease and is still thought to be the main cause of febrile episodes in children. however, the threshold of clinical manifestation of malaria is strongly influenced by the endemicity of plasmodium falciparum infection in an area: in very low transmission areas, any microscopically detectable parasitemia would indicate malaria, whereas in regions of high transmission, a certain parasitemia needs to be reached to lead to malaria at least from years of age on. recent, mainly unpublished observations show that there is a considerable drop in malaria incidence [ ] and in p. falciparum prevalence rate [ ] in some african countries. despite this reduction, the old habit of treating every child with fever with antimalarials continues. as fever due to many infectious diseases wanes after a few days without treatment, the belief that medical staff are successfully treating malaria cases lingers on. a recent study in lambarene, gabon, illustrates the extent of the problem and the unresolved conundrum. in and around lambarene all febrile children are still treated with antimalarials, mainly amodiaquine-artesunate [ ] . in a study of , the essay section contains opinion pieces on topics of broad interest to a general medical audience. consecutive children presenting with fever at our research center in lambarene, the results from the thick blood smears indicated that only about % had malaria. recent serological tests have shown that parts of the febrile illnesses in lambarene are due not only to influenza, but also to dengue fever, chikungunya disease, and streptococcal pneumonia [ ] . in addition, in tanzania where malaria is considered to be highly endemic, d'acremont and coworkers refer to recent data indicating that only %- % of under- year-old patients with fever have malarial parasites in rural areas [ ] . thus, in lambarene and perhaps elsewhere in africa, the majority of febrile cases may be unnecessarily exposed to antimalarial drugs, with the well-recognized negative consequences. it is acknowledged that the problem of diagnosing influenza-like illness is already challenging in resource-rich settings apparent from data collected on the ongoing pandemic of influenza a (h n , swine flu). examining symptomatic individuals with recent history of travel to countries where the h n virus was circulating indicated that other respiratory viruses such as rhinovirus, coronavirus, or parainfluenzavirus were responsible for influenza-like illness [ ] . therefore, not surprisingly, yet often ignored, there is simultaneous transmission of different respiratory viruses and bacteria in addition to malaria that lead to febrile illnesses in africa and elsewhere in the tropics. the task of diagnosing and treating febrile illnesses properly in resource-poor tropical settings is daunting. yet, with attention to upgrading clinical research in africa focused on combatting the well known diseases such as aids, tuberculosis, and malaria, we need to start taking a few steps towards implementing programs that deal with influenza-like illness. thus in each of the northern, western, eastern, central, and southern african regions one well-established research center could be identified to act as a surveillance center. already in senegal and south africa such centers exist, but there is a need for identifying new ones in other regions and upgrading and intensifying activities in already existing ones. training should ensure that epidemiological data can be gathered on attack rates, clinical spectrum of illness, and risk factors, while molecular diagnosis of collected samples confirms influenza and identifies the strain/subtypes. in close collaboration with who centers, the behavior of the influenza virus would then be monitored properly on the african continent. contrary to common belief, excellent clinical research centers are developing in africa with good epidemiologists, information technology infrastructure, and laboratory equipment. there is no information on influenza vaccine efficacy in tropical africa. the question of whether the immune system of populations living in tropical african environments would react similarly to a vaccine developed mainly for populations restricted to certain geographical areas of the world needs to be considered. helminthic infections, malaria, and other chronic parasitic infections along with nutritional status lead to altered functioning of the immune system [ ] . not only th responses [ ] but also regulatory t cells are expanded during many parasitic infections [ , ] and are thought to affect responses to unrelated antigens. interestingly, a study of meningococcal vaccination of infants in ghana showed lower titres of mena and menc bactericidal antibodies than in other studies in africa [ ] . in a recent trial in gabon, schoolchildren from a rural and a semi-urban setting were vaccinated with influenza vaccine [ ] . clear immunological differences were seen in response to the vaccine in rural versus semi-urban children. weaker th and pro-inflammatory cytokine responses to influenza virus antigens were seen in vaccinated rural children compared to the semi-urban vacinees. antibody levels following vaccination increased in all, but to a different extent in subjects from rural than in semi-urban areas. the antibody response following vaccination to a-h n and b virus strains were significantly lower in rural compared to urban schoolchildren. the clinical relevance of such findings remains unanswered, even years after studies of mcgregor in the gambia examining influenza-like illness and reporting differences in antibody reactivity in african populations and populations of european descent [ ] . therefore it is important to undertake clinical trials with this vaccine in different regions of africa. the end point in these studies should be the occurrence of influenza cases to assess the efficacy of the vaccine in africa and learn about a threshold for a protective hi titer. taken together, data from sporadic studies suggest that influenza is prevalent in africa and the disease may have considerable impact on morbidity and mortality on the continent. a raised awareness of the presence of common febrile diseases such as influenza is essential for the clinical management of patients. to this end proper surveillance systems should be set up in already existing and well-established clinical research centers to understand the epidemiology of influenza in africa, which in turn may help the processes of decision making regarding influenza vaccination on the continent, which may have a high impact on health in africa. seasonality of influenza in brazil: a traveling wave from the amazon to the subtropics influenza-associated hospitalization in a subtropical city seasonality of influenza in the tropics: a distinct pattern in northeastern brazil global patterns in seasonal activity of influenza a/h n , a/h n , and b from to : viral coexistence and latitudinal gradients the global circulation of seasonal influenza a (h n ) viruses etiology of serious infections in young gambian infants epidemiological and virological influenza survey in dakar, senegal: - influenza virus strains in nairobi, kenya results of two-year surveillance of flu in abidjan cellular and humoral responses to influenza in gabonese children living in rural and semi-urban areas influenza a (h n ) -update interim report on pandemic h n influenza virus infections in south africa introduction and transmission of pandemic influenza a (h n ) virus-kenya mortality rates from malaria in children under fall sharply in countries the limits and intensity of plasmodium falciparum transmission: implications for malaria control and elimination worldwide amodiaquine-artesunate versus amodiaquine for uncomplicated plasmodium falciparum malaria in african children: a randomised, multicentre trial community acquired pneumonia in children in lambarene, gabon time to move from presumptive malaria treatment to laboratory-confirmed diagnosis and treatment in african children with fever a variety of respiratory viruses found in symptomatic travellers returning from countries with ongoing spread of the new influenza a(h n )v virus strain immune regulation by helminth parasites: cellular and molecular mechanisms upregulation of tgf-beta, foxp , and cd +cd + regulatory t cells correlates with more rapid parasite growth in human malaria infection a phase ii, randomized study on an investigational dtpw-hbv/hib-menac conjugate vaccine administered to infants in northern ghana the epidemiology of influenza in a tropical (gambian) environment key: cord- -vm btiue authors: walwyn, david r. title: turning points for sustainability transitions: institutional destabilization, public finance and the techno-economic dynamics of decarbonization in south africa date: - - journal: energy res soc sci doi: . /j.erss. . sha: doc_id: cord_uid: vm btiue existing socio-technical systems tend to be intransigent to change. decarbonisation, on the other hand, is an imperative, leading to an obvious conflict between the need for, and highly effective resistance to, change. moreover, the abandonment of fossil fuel-based technologies in favour of more sustainable alternatives will require substantial reallocation of government’s operational expenditure, particularly in countries like south africa with high per capita greenhouse gas emissions and low per capita income. in this article, it is argued that reallocation will require more than niche experimentation and destabilisation of the present socio-technical regime. based on a study of south africa’s budget processes, it is concluded that change will only occur when four separate pre-conditions converge, namely a rapidly growing environmental problem capable of leading to civil unrest, a supportive and recently developed policy framework, decreasing techno-economic costs for its solution, and strong political support from an effective ministry or minister. turning points for transition, although infrequent, can be reached through strategic attention to these pre-conditions. a modified kingdon multiple streams approach, which introduces the additional dimension of techno-economic feasibility, is proposed as a useful framework for anticipating when and how to act in order to mobilise sufficient public resources for decarbonisation. the decarbonisation of energy and other systems is essential for the transition to a low-carbon future [ ] . many countries have committed to binding targets for greenhouse gas (ghg) emissions, including the attainment of net zero emissions by [ ] . the paris agreement is clear on what countries need to achieve in terms of such emissions, and over what time period these nationally determined contributions (ndcs) must be realised [ ] . however, the costs of decarbonisation have not been similarly specified in the agreement. individual countries are only now beginning to fully understand and quantify what investment will be required to reach the ndcs, and how these funds might be secured. some initial assessments have been reported in the literature [ ] [ ] [ ] [ ] . for the united kingdom, it has been estimated that the plan to reach net zero ghg emissions by will cost $ . trillion or $ , per metric tonne (mt) carbon dioxide equivalent [ ] . a similar value has been estimated for the united states of america, where the cost of replacing fossil fuels in the energy sector is estimated at $ . trillion or $ , per mt carbon dioxide equivalent [ ] . these values can be more easily comprehended by firstly calculating a total cost based on the present carbon emissions, then annualising this cost by assuming that the transition to low-carbon will take place over a -year period ( to ), and finally expressing the annual cost as a proportion of gross domestic product (gdp). the normalised costs of decarbonisation for the united kingdom and the united states of america are estimated at . % and . % of gdp respectively, whereas for south africa the value is about %. the issue of cost will be particularly acute for south africa [ ] . it is an upper middle-income country, heavily dependent on coal as a source of both electricity and liquid fuel [ , ] . decarbonisation of the energy sector will be a formidable undertaking, whose solution is made more difficult not only by the extent of the economic disruption and social dislocation that may result, but also by the constrained resources with which to address the issue [ , ] . a similar conclusion about the limited readiness of south africa for a low-carbon future has been reached by the world economic forum, which has placed the country in the th position out of countries based on the energy transition index [ , ] . already south africa has been criticised for its insufficient progress towards the attainment of the country's ndc targets [ ] . there is concern about its renewable energy programme, including ongoing delays [ ] , a poor outcome relative to the intended targets for economic development [ ] , and general deficiencies in the implementation of off-grid solar home systems [ ] [ ] [ ] . the government has also significantly alleviated the impact of a recently introduced carbon tax, and is failing to adequately resource the realisation of its ndcs [ ] . moreover, the covid- pandemic has caused a massive shock to the economy, reducing tax revenue collection by % and cutting at least % from the gdp [ ] . in short, the south african government appears unwilling and increasingly unable to resource its low-carbon transition. the issue of public sector resource allocation is critical for sustainability transitions. budget decisions within governments have direct and often irredeemable consequences. once such decisions are made, the resultant allocation of funds allows some programmes to be pursued and compels others to be halted. although there are several publications on green financing within south africa, such as its broader challenges and necessary design features [ ] and the role that public financial intermediaries have already played in the country's energy transition [ ] , there have been no specific studies on how to mobilise and reorient government expenditure for sustainability transitions, and particularly the decarbonisation of its energy sector. the unique contribution of this paper is its analysis of budget processes, leading to the proposition that four preconditions should be met before a significant reallocation of government's operational budgets, in support of decarbonisation, can be achieved. notably, in addition to the three factors of problem, policy and politics, which are central to kingdon' s multiple streams approach (msa) and are already welldescribed [ ] , the techno-economic value of the proposed solution must be addressed. the analysis in this paper seeks not only to support its claim for the four streams approach, but also to recommend ways of dislodging lock-in and re-directing government expenditure. the study was exploratory in its approach. it drew on interviews with ex-government officials, examples of previous re-allocations and government documents relating to the budget process. its objective was to identify the causal factors that could lead to profound changes in these budgets, and then to present these factors as preconditions that should be concurrently fulfilled. in its analysis, the study uses a theoretical framework which combines msa [ ] with historical instutionalism [ ] , as explained in the second section. the third section presents the relevant background on south africa's budget processes. the methodology, results, discussion and conclusions follow in sections , , and respectively. kingdon's msa postulates that change happens at single points in time or 'policy windows', when a number of causal chains or streams converge [ , ] . typically, the three streams comprise of the problem itself, a relevant policy framework and the political process through which change can be realised. msa further stresses the importance of policy entrepreneurs, who must attempt to couple the three streams through process of power brokerage and manipulation of problem contexts [ ] . msa specifically acknowledges the complex and chaotic nature of policymaking, and the difficulty of operating within an environment of ambiguity, irrationality and unpredictability [ ] . changes in policy are seen in msa to emerge spontaneously and stochastically, and can be missed by policy entrepreneurs due to the absence of well-developed policy solutions [ ] . msa's emphasis on windows of opportunity and convergence is also a central aspect of historical institutionalism, which refers to windows of opportunity as critical junctures and convergence as a process of conjuncture [ ] . historical institutionalism emerged in the s as a means of conceptualising and theorising how reform takes place at the meso-level, introducing such terms as path dependence and selfreinforcing processes, whose identification are critical to understanding and hence overcoming intransigence to transition and change. it adopts a longitudinal approach, perhaps over several decades, the analysis of which is used to identify the relationships of lock-in and dependence that comprise the socio-technical landscape [ ] . the hierarchies of micro, meso and macro, as developed within historical institutionalism, have become widely accepted and applied in the sustainability transitions literature [ , ] , as exemplified by its adoption of the multi-level perspective (mlp). the latter defines the three levels as the socio-technical landscape, consisting of government policy and inter/national systems, the socio-technical regime and the niche level, the latter including firms and networks of individual actors. although arguably a simplification of the broad diversity of individuals, collectives, organisations and systems, this layered hierarchy is fundamental to an understanding of transition, and how different processes take place within each level. in much of the mlp literature, change is considered to begin through niche innovations and policy experimentation, undertaken by an array of minor actors. the efforts of these actors may eventually become aligned and sufficiently powerful to destabilise an extant socio-technical regime, which has been wellestablished at the meso-level over a long period [ ] . a possible weakness of this model in the context of a developing country is the extent to which agency is possible within a highly resource-constrained political system. indeed, in the wider debate about structure vs agency, it can be argued that individuals and small networks of actors are disempowered by the broader structural context. it is precisely this consideration which makes the use of historical institutionalism, with its focus on the meso-level, as a highly relevant analytical framework for a country such as south africa. although operating as a democracy, it is clear that the societal environment in south africa still acts as a major constraint on the micro-level actors, given the low level of education and human capability [ ] . furthermore, the highly rigid approach of the pre- system of apartheid resulted in an extensive entanglement of the technological systems and the state, creating an almost irreversible degree of lock-in [ ] . in some senses, historical institutionalism is about theories of continuity, providing an explanation for why regimes remain stable, even though they are contested, rather than why they change. in order to address this gap, roberts and geels [ ] supplemented the insights of historical institutionalism with those of mlp as a means to further develop a theory of change. in their analysis of conditions for politically accelerated transition, informed by two case studies in the united kingdom, they argue that conditions for change must include both a weakening of the socio-technical regime, which they refer to as a push factor, and a strengthening of niche actors, which they label as a pull factor. following the insights from historical institutionalism, in which major policy change arises from struggles for power at the meso-level, they conclude that at least one mechanism of change is a macro-or landscape level shock. this severely disrupts the incumbent regimes and allows the emergence of niche actors as a new socio-technical system [ ] . in summary, historical institutionalism has two specific advantages when used to understand sustainability transitions, firstly its focus on meso-level institutions and policy regimes, and secondly the recognition that power struggles between political collectives or groups over scarce resources lie at the centre of politics and are critical to policy change [ , ] . institutional structures and arrangements, typically referred to as a political community or polity, engage in power struggles through the process of politics. in this sense, historical institutionalism is more appropriate in understanding south africa's budget processes and has been used in this study. it is argued that important decisions relating to resource allocation, which have the capacity to alter the course of sociotechnical systems, are the consequence of conjunctures taking place at critical moments. such turning points have a low probability of occurrence, given the dominant approach to policy stability and lock-in. the state can play an important role in transitions, either through exogenous changes at the level of the socio-technical landscape, or by strategic and planned initiatives to change the institutional environment [ ] . it is precisely the issue of the role of the state, and how it can be internally directed, that is the subject of this article. the study considers the separate roles of the executive, the administration and the legislature. the nature of the power balances between these three arms is explored by analysing their relative roles with respect to a core public sector process, namely the allocation of funds from the national fiscus to individual departments. an overview of this process, as it normally takes place, is presented in the next section. the adoption of south africa's new constitution in necessitated a comprehensive reform of the management of public finances, including its budget procedures. the latter were amended in several respects, such as strengthening the link between policy and budget allocations, the introduction of systems to address fragmentation and lack of clarity, and measures to improve transparency and re-establish fiscal stability [ ] . although the new processes were more top-down, the changes improved the alignment between post- priorities and actual public expenditure [ ] . a core feature of the revised budget process was the introduction of the medium-term expenditure framework (mtef), which was intended as the means by which government could ensure budget stability and predictability while allowing changes "at the margin" [ , p ] , thereby managing the "tension between competing policy priorities and budget realities" [ , p ] . the mtef was positioned as a first step in the "wider overhaul of the budgetary process, emphasising transparency, output-driven programme budgeting and political prioritization", that provided the link between the "technical preparation of budgets and the need to reflect political priorities in expenditure plans" [ p ]. its key features include rolling baselines, which are the core budgets for each department and are substantially unchanged within a single mtef, and a contingency reserve, which is intended to cover unforeseen expenditure. a detailed review of the timeline for the budget process is not possible in this article. in summary, the process is initiated by a cabinet lekgotla, which takes place in february to march of each year (see fig. ). at this meeting, the cabinet reviews the macroeconomic and fiscal policies, and the extent of the required budget cuts, or the additional funding that may be available for new priorities. these changes are then incorporated in a set of mtef budget guidelines [ ] , which are issued to the various national departments and provinces. in response to the guidelines, the departments prepare budget proposals, which are then submitted to national treasury, where they are consolidated into an overall budget estimate. based on the alignment between the estimates and the guidelines, national treasury provides feedback and, if necessary, requests revisions from the departments. the adjusted budgets are then assessed in the ministers' committee on the budget (mincombud) technical committee (mtec), which is composed of senior officials from national treasury (nt), the department of planning, monitoring and evaluation (dpme), the department of cooperative governance (dcog) and the department of public service and administration (dpsa). mtec then prepares recommendations for mincombud and cabinet regarding budget allocations in the mtef, taking into account government priorities, funding available, exchange rates, alternative funding sources and the division of revenue amongst the three spheres of government [ ] . once mincombud has approved the budgets, the minister of finance tables the medium-term budget policy statement in the whole process intentionally reinforces a central design principle of the post- reforms, namely the establishment and maintenance of a stable public finance environment, otherwise stated as a predictable expenditures and policies [ ] . one effect of this approach is that it severely limits the available funding for new policies or initiatives and reinforces a pattern of lock-in or pathway dependence within the budget allocations. however, there are two mechanisms through which small amounts of money can be sourced for new policies, if there is sufficient political support. before the estimated income is divided between the different departments and spheres of government, a contingency reserve is 'top-sliced' and retained by national treasury for emergency needs or novel policy instruments. this reserve provides a level of flexibility to the budget allocations, although, as shall be discussed later, it is a small amount relative to the demand for new funding from the various departments. the other mechanism, known as virement, involves the shifting of funds from one subdivision of a budget vote to another. there are a number of restrictions to this practice, including the requirement that it may not exceed % of the total allocation in the source subdivision (from which the funds are taken), that it may not involve the shifting of funds from capital to recurrent expenditure and that it cannot be used to increase remuneration without special approval from national treasury. clearly, expenditure predictability and budget stability are important objectives, especially in respect of financial markets and the cost of borrowing. however, both elements act against the needs of transition or change, particularly where the change has a significant cost or budget implication. the prospects of sufficient allocations for major new policy directions are limited by the mtef and the system weakens the role that government can play in enabling such changes. this imbalance has led to the growing realisation by south africans that reform can only take place in response to external pressure, widespread protest, and even violence. the / student protests regarding "free" higher education are an illustration of this perspective. provoked by a statement from the department of higher education and training (dhet) on transformation in higher education [ ] , the students embarked on nationwide protests, demanding that promises of free education be fulfilled. after a number of incremental changes, president zuma finally announced on december that higher education for the poor and working class students would be free [ ] . the president's decision was taken against the advice of national treasury, especially since it ran counter to the agreed budget processes and mechanisms [ ] . moreover the impact was profound; funding for the national student financial aid scheme (nsfas), the primary vehicle for the implementation of the new policy, a 'mere' r . billion in / , increased to r billion in - [ ] , as shown in fig. . certainly, in respect of this decision, it can be concluded that the executive directed, the administration was out-manoeuvred and the legislature side-lined. the intent that such decisions should be the outcome of evidence-based information and a collective consensus between the three arms, as stipulated by a range of policy documents, was over-ruled. thus, issues of policy conflict and priorities are often resolved through a political process which may relate to the power or influence of key positions within the executive arm of government (cabinet), or to the ability of the operational and legislative arms to determine the expenditure allocations. despite such processes being of critical importance to an understanding of how decisions on resource allocation are made, there is little published research in south africa on this topic. as illustrated by the earlier example of the nsfas, budget re-allocations are possible and do take place. accelerated sustainability transitions, as will be necessary for the timely implementation of the paris agreement, will require significant government investment, especially in new systems of transport and energy. to disregard or overlook these outlays under the pretext of lacking the necessary funds, appears disingenuous. it is a matter of priority and policy, and of avoiding the disrpution of existing, exclusive institutions [ ] . in summary, the analysis of budget processes leads to the following propositions about how change, and in particular realignment to operational budgets in favour of sustainability transitions, could take place. • for change to take place, the problem must be highly visible, a coherent and aligned policy framework must be in place, the solution should be affordable, it must require a political intervention, and failing to act must have severe consequences (such as social unrest). • the dynamics of each aspect are the problem must be accelerating in its severity; the solution must have falling cost implications; the window of change is generally very brief, opened by the sway of politics and rising popular dissent; and the political response must be rapid and effective. • the simultaneous convergence of these four aspects, described as a process of conjuncture resulting in a turning point or critical juncture, is essential for change to take place. in order to explore the validity of these propositions, a research project, involving a series of interviews over an -month period, was designed and initiated. the overall objective of the study, as already noted in the introduction, was to identify the factors that can lead to profound changes in government expenditure, and hence how greater priority can be mobilised for the support of sustainability transitions. further details of the research method are provided in the next section. the research followed a qualitative, inductive and exploratory approach with a purposive sampling strategy [ ] . the population consisted of ex-members of national treasury, and other departments, who had occupied senior positions within government in the recent past, including director-general, deputy director-general and chief director, and had more than years' experience of budget processes in the public sector. approval of the project by the faculty ethics committee was subject to two explicit conditions, namely that only exmembers could be interviewed and the responses had to be anonymised. the latter is a standard requirement and was fulfilled by following the normal procedures. however, the former condition added lengthy delays to the project due to the difficulty in identifying suitable respondents meeting the two criteria of having recently left a senior post in government. altogether, six interviews were completed. the respondents were interviewed using a semi-structured questionnaire in order to understand, primarily, how policy priorities are assessed and balanced within the public sector. the questionnaire was divided into four separate sections, with the first section covering the participant's view on the role of the state with respect to the environment and how this is presently being fulfilled, followed by three sections on the process of budget allocations and determination of funding priorities, the resolution of cases involving competing priorities, and general recommendations on accelerating support for sustainability transitions, respectively. in each case the interviews were recorded, transcribed and then analysed using atlas.ti. the coding structure was developed based on the research questions, with the coding groups covering the core questions of role, examples of policy conflict, the determination of priorities, details of the budget process, moments of change and lessons for sustainability transitions. it is acknowledged that the small sample size limits the external validity or generalisability of the results [ ] . the credibility and exclusivity of the data is, however, robust in that the respondents had all occupied senior positions and accumulated more than fifteen years of experience in budget processes within the public sector. although there were differences in perspectives, mostly there was agreement on the main determinants of the central question that this article seeks to address, namely how to influence such budget processes. as a result, it has been possible to extract a set of useful insights from the data. as mentioned earlier, south africa faces a huge decarbonisation challenge. its electricity sector is the most carbon intensive of all the g countries, it has a bankrupt power utility without resources to finance its normal operations, let alone decarbonisation, and it has a high level of unemployment, which places even more pressure on the imperative for a just transition [ ] . the global decarbonisation imperative will place huge financial pressure on state income. it has been estimated that the cumulative impact on south africa of a low-carbon transition, referred to as the 'transition risk' will be $ billion, which includes the loss of export revenue, and the loss of local markets for coal and liquid fuels [ ] . in addition, south africa will need to invest in new energy infrastructure, the extent of which can be illustrated by considering investment cost normalised for gdp. using data for carbon emissions and gdp data from the world development indicators database [ ] , and assuming that the average investment cost will be $ , per mt of carbon, it is calculated that south africa must source $ billion, or % of the gdp to finance the transition, as shown in fig. . it is clear from this comparison that the cost of decarbonisation will be more acutely experienced by countries with lower gdp and higher carbon emissions. for instance, iran, russia, india and saudi arabia have high relative ghg emissions and can expect a larger cost, normalised to gdp, than other countries. the combined impact of this investment cost and the transition risk, which represent a major challenge to the south african government, has a number of budgetary implications. as will be the case in many countries, the public sector will be required to implement mitigation strategies, such as the retraining of mining sector employees, introduction of new policy instruments to support the renewable energy sector, changes to legislation, interim approaches to reduce the impact of revenue changes on municipalities, measures to build resilience to climate change, programmes in research and development focussed on the necessary diversification of the economy and the remediation of environmental damage from fossil fuel usage. although several departments will be affected by transition risk, this study has looked specifically at the department of environment, forestry and fisheries (deff), which has overall responsibility for environmental management and is represented at executive level by the minister and deputy minister. the department has an annual budget of about $ billion, an amount which has not changed much over the last seven years, and under the medium-term expenditure framework allocations is projected to stay at a similar level in the immediate future (see fig. ). allocations to the department were considered by the interviewees to have grown from a low base, with the department being one of those to have benefitted from the growth in overall government revenue over the period to . opinions as to the adequacy of the present budget in meeting the department's responsibilities were mixed, although it was generally considered that the major constraint was not funding, but capacity to deliver. this sentiment is not echoed by the present minister, who indicated a need to leverage the resources of other sectors in order to ensure that the department could deliver on its present mandate [ ] . the respondents agreed that deff's role is to ensure the protection and preservation of the environment, or in broad terms 'environmental sustainability', and that this role was being fulfilled through the combined actions of regulation and enforcement. however, it was noted by the respondents that the department's efforts can be compromised by the very nature of public policy, which is to represent a broad range of interest groups, and the diversity of government's activities, some of which can impinge on the environment and have direct environmental costs. for instance, the granting of coal mining or fishing licenses was cited as an example of the tension between protection of the environment and economic development. in the case of fishing licenses, the desire to ensure the economic livelihoods of small fishing enterprises was considered to have led to over-harvesting of fish stock, with subsequent depletion, and in some cases collapse, of fish populations. similarly, the granting of additional coal mining licenses as a means of transforming the sector, or the use of pesticides to control malaria, had led to significant degradation of the environment in the affected areas. it can also be argued that environmental protection through restrictions on mining and other resource extraction activities can be justified economically, and that defining sustainability vs. development as a dichotomy is unproductive and misleading. longer term economic development is about environmental sustainability, a perspective which is expressed by the present minister, barbara creecy, who stated [ ] : "what i want to bring to this portfolio is the understanding that caring for the environment, caring about climate change and threats to biodiversity may well be an emotional concern for some people, but -million south africans are directly dependent on our natural resources." it is clear that conflict between the mandate of deff and other departments arise on a regular basis, and that in some cases, the deff is successful in preventing decisions leading to adverse environmental impacts. although no clear pattern emerged from the discussions, the interviewees were questioned about how such tension was managed, and, typically, which areas were prioritised. the results of these questions are presented in the next section. disagreements on government choices are generally resolved through the existing policy framework, which forms the blueprint for government action. however, in ambiguous situations, where proponents of each position can find relevant policies in support of their perspectives, decisions are taken based on the power of coalitions, politics, the charisma of individuals and the strength of lobby groups. such decisions often take place in the executive, which, in the view of one respondent, is a forum with weak environmental representation, given that there is one minister of environmental affairs, but five or six economic ministries, and eight or nine social ministries. in order to ensure a positive result for the environmental portfolio, it is therefore essential that the minister attempts to build an alliance with other ministries and civil society, and is then able to depend on this alliance in supporting a particular issue. as noted by one respondent: [ : ] "a flat-footed environment ministry that refuses to play the politics that is required ain't going to get anywhere." (respondent ) the choice of alliance partners is one of several important components in the construction of such a coalition. it was indicated that likely partners for environmental issues included the security cluster (defence, police, justice) and one or several of the cross-cutting departments (finance; foreign affairs; public service and administration; and planning, monitoring and evaluation). it was noted that the former was often supportive of longer-term perspectives as a means of averting social unrest and inter-nation conflict. apart from being a forum in which the environmental mandate is outnumbered, the executive is also a constitutional body which lacks a referee, particularly if the president does not assume at least some responsibility for non-partisanship. this one-sidedness is especially relevant in decisions relating to the construction of infrastructure or the expansion of one of its public enterprises, where the government acts as both the regulator and the player, and may too easily be able to bend the rules in its favour, or make a trade-off, as described by one respondent: [ : ] government always has to make trade-offs between various sectors and importantly with respect to the environment it is constantly making trade-offs between environmental and economic/social objectives, and really that is its function. so, it is not just a regulator of the environment. in regulating the environment, it balances multiple competing objectives …. i think that is just the hierarchy of decisionmaking that it needs to do (follow). (respondent ) it is not clear how such a hierarchy of decision-making is established, other than that it is political and highly contextual. a propensity for persistent and patient negotiation is an important prerequisite for the minister of environment, forestry and fisheries, especially in pursuing a pro-environment agenda which may be perceived as anti-employment or economic growth. in the next section, the respondents' comments on how such agendas have evolved, and particularly the reasons for any successes, are discussed. during the interviews, several incidents of decisions relating to significant policy changes were discussed, including the implementation of the sugar tax, the introduction of plastic bag regulations, the proposed carbon tax and the reforms on student fees. in the earlier discussion on historical institutionalism, it is argued that such moments of change require, inter alia, strong political support. one important strategy for obtaining this support, which emerged from the discussions, is the inclusion of revenue collection, which predictably secures agreement of arguably the most powerful government department, the department of national treasury. according to the respondents, the ability to extract additional fiscal revenue accounts for the relative ease with which changes such as the sugar tax were introduced, compared to other policy initiatives. the respondents noted, however, that even in the case of additional tax revenue, obtaining consensus from the executive always required a great deal of finesse. the nature of this 'footwork' is central to this study, but inevitably the most elusive aspect to define. it depends on the issue, the context, the personalities, the relevant institutions, the affected sectors, and a number of other factors. it is what distinguishes an effective from an ineffective minister, a progressive from an intransigent or reactionary administration. the respondents noted that in government change generally takes place with difficulty, if at all. the processes and systems are designed to maintain the status quo, perhaps for important reasons. policy stability, particularly macro-economic, is both a desire and a goal in governments, and change, especially when it is driven by narrow political interests outside of established governance processes, can be damaging to countries and economies. such momentum in government action is reflected acutely in budget allocations. the respondents commented that these allocations are mostly unchanged from one year to the next, giving little flexibility to the executive in being able to implement new initiatives. for instance, [ : ] "… every now and then there are some shifts, but those shifts might be fairly significant in the context of one particular department, but i'm not sure that they are significant in the context of an entire sector and usually those shifts are either … i don't think that they are ever more than maybe % of any government's allocation from one year to the next." (respondent ) in other words, there is no new money within treasury and budgets remain substantially unchanged from one year to the next. moreover, the re-allocation of funds from one budget line to another, within the rules of virement, is tightly controlled and requires national treasury approval. individual line managers are able to re-allocate unspent funds within a programme or line item, such as from one project to another, but these changes are relatively minor and cannot be applied to the funding of new initiatives. the challenge for the funding of sustainability transitions is, therefore, to persuade government departments to redirect their existing budgets over time, and mainstream the sustainability development goals in their daily practices. this challenge is recognised by deff as being central to its mandate and it engages regularly with other departments on the need to include such goals with some success. for example, the establishment of the biodiversity centre of excellence by the department of science and technology (now the department of science and innovation), the creation of the green fund and the implementation of the renewable energy independent power producers procurement programme were mentioned by the respondents as resulting from such inter-departmental discussions. there is one important exception to the overall situation of budget stasis, which is the power afforded to the president of south africa. although not explicitly stated in the constitution or the legal system, it appears that the president is able to circumvent the standard budget processes, as happened in the example of the student fees crisis of [ ] . the appropriateness of this use (or abuse) of power was questioned by a respondent: [ : ] "you know if the politicians don't accept the institutional rules of the game, then it is very easy for them to wreck the institutions. … there has to be a basic acceptance, a collective acceptance that this is the rules and this is how you do things. if people don't accept that, they can just wreck institutions very, very easily." (respondent ) in summary, the interviewees concurred on the budget situation as being highly constrained with the opportunity of finding new funding to support sustainability transitions (in pursuance of the sustainability development goals) as being not just remote, but impossible. the redirection of existing funds is the only option, although the budget process is ill-suited to such changes and in general only incremental adjustments over a long period are possible. the implication of these results for sustainability transitions are discussed in the next section. decarbonisation of south africa's energy sector is largely a problem for the state. more than % of the country's carbon emissions derive from the fleet of coal-based power stations owned and operated by the state-owned power utility, eskom [ ] . replacement of these facilities with renewable energy alternatives will require significant new finance. given its present financial circumstances, eskom itself is highly unlikely to be at the forefront of this reinvestment and the reform of the electricity sector. as already noted, the utility is deep in debt, and embroiled in a series of technical and political crises which severely constrain its ability to raise finance from capital markets or the state [ ] . this outlook suggests that much of the investment finance for the energy transition will be provided by the non-government sources. however, government will be required to provide financial support for a range of operational activities, including energy research and development, retraining workers affected by the energy transition, building of capacity to manage energy markets, and incentives to support local manufacture of renewable energy equipment. such funding will be mostly additional to the existing budgets of government departments, and will require either new funding or the re-allocation of budgets from other activities. the likelihood of new funding is minimal. government finances, already stretched to the limit before covid- , are now in a highlyborrowed predicament, with the level of government debt rising to % of gdp in the / financial year [ ] . the re-allocation of monies from other expenditure items within the operational budgets will be an imperative if government funding for decarbonisation and the energy transition is to be made available. the premise of this article has rested on the assumption that high-level decisions for such changes reflect not only the extent of the need to fulfil each department's public mandate, but also the strength or weakness of the interdepartmental power relationships. an understanding of these dynamics is therefore critical to the implementation of emergent and experimental policies within government, such as policies to support decarbonisation, sustainability transitions and the transformation of socio-technical systems. this study has intimated that the budget process affords limited opportunity for negotiations on departmental budgets. however, there are points in the process, referred to as windows of opportunity, when such changes are possible if a number of preconditions have been met. the concept of a window of opportunity is by no means unique. as already outlined, it is shared by both msa and the multi-level perspective; the latter focuses on the two streams of regime destabilisation and niche consolidation, whereas msa requires the conjuncture of problem, policy and politics. the south african context supports both approaches, but identifies the fourth precondition of an affordable solution. conditions in developing countries are frequently resourceconstrained, implying that regime changes lead to extreme changes for the affected parties. as a result, the conflict can be more apparent, the outcomes more divisive and the moments of change take place more unpredictable. in other words, the higher financial stakes determine the nature of the struggle and the resultant change, should it occur. the critical junctures or windows of opportunity are less frequent, more contested, require more significant alignment of interest groups and are characterised as strong conjunctural processes. the pre-conditions for these windows of opportunity are also different. it is argued here that one further stream is required, namely favourable techno-economic value or improvements in the benefit to cost ratio of the potential solution, as exemplified by the introduction of the sugar tax. this amendment to the msa is essential to understand how change can emerge, and hence to engineer or accelerate sustainability transitions. furthermore, each of the four streams needs to be characterised based on its dynamics or rates of change. the four streams are now discussed in more detail. policy changes rarely seem to take place in response to opportunities. politics is a domain that appears to be mainly reactive, and often takes the form of crisis management. given the multiple demands on the public sector, and the huge scale of the issues, this reactiveness is perhaps not surprising. one general precondition for policy change seems to be clear: there must be a shared understanding of a clearly defined problem for such changes to be considered. the mere existence of a problem is also not on its own sufficient; policy windows are more likely to open when the problem is both growing in scope and the rate of growth is accelerating, to the extent that it is mobilising extensive political support outside of government, most notably in civil society with its ability to mobilise civil unrest. the power of civil society to destabilise the landscape depends on the extent of mass mobilisation and public support for a particular issue, and the degree to which this support is able to gain momentum within nation states. government may then act to repress or outlaw civil society protest, as happened repeatedly under apartheid south africa [ ] . the inclusion of regime destabilisation as a necessary step in the processual framework of this model is also part of the msa and also the multi-level perspective. examples of such changes include the occurrence of pandemics, the environmental crisis, the advent of widespread road transport and the rise of wheat mono-culture [ ] . opinions on how to change a dominant regime have been offered by many authors. milton friedman, well known for the development of stabilisation policy, surprisingly had a perspective on how to change a socio-technical regime. he considered that only a crisis produces change, and that the most important pre-condition was to be wellprepared [ , p ix] . this requirement of being well-prepared is partly captured in the theories of policy experimentation and strategic niche management [ , ] . these argue that transition requires initial experimentation with new approaches, some of which may fail, but the successful interventions may eventually gather sufficient momentum to result in changes at the meso level. importantly, there are no clear predictors of success with early experiments, and policy frameworks may themselves not achieve the desired outcomes. it is therefore critical that such interventions be accompanied by a transparent and insightful monitoring and evaluation framework, which can inform whether the policy should be continued, strengthened or withdrawn. the stream of techno-economic value refers to the perceived cost benefit ratio of a public policy or intervention [ ] . such analyses are a legislative requirement within the south africa public service, and are typically framed with questions such as "what is the value for money?" or "what is the cost/benefit ratio?" [ ] . cost/benefit analysis is used as a means of informing budget decisions based on the economic viability or socio-economic benefit of a particular intervention. there are multiple approaches to the analysis, including the use of standard financial techniques such as discounted cash flows, net present values, internal rates of return and payback periods [ ] . mostly, the analysis requires the monetisation of the resultant social welfare and economic benefits of the intervention, the sum of which are then compared to the overall costs. measurement of the net social welfare is complicated by the large variety of possible benefits, the relative value of each intervention and the prediction of its impact. although costs are mostly explicit and relatively straightforward to calculate, the quantification of benefits is subject to assumptions on critical issues such as the contribution of energy to the quality of life, or the magnitude of the social discount factor, or the value of possible externalities (such as an improvement in the quality of the natural environment) which are associated with a particular intervention. some of these limitations can be avoided by applying cost/benefit analysis only as a comparative technique. in this way, the same assumptions apply to all the options being reviewed, and allow for the selection of the most cost-effective alternative amongst a portfolio of analogous projects. a useful example of how the techno-economic value can influence resource allocation decisions is the case of the declining cost of renewable energy technologies. although the cost of electricity from photovoltaic panels and onshore wind turbines was, prior to , generally more expensive than energy obtained from fossil fuels, this situation has now reversed and renewable energy technologies are now consistently cheaper [ ] , due mostly to improved manufacturing efficiencies and greater production capacity within the sector [ ] . the lower levelised cost of energy has been an important influence on the planning of national energy systems and the decisions to incorporate higher levels of renewable technologies within such systems [ ] . as for the problem stream, a positive impact on social welfare is not a sufficient condition; the benefit should have, at least, the prospect of growth. in other words, the potential savings should be increasing, or the cost of implementation should be decreasing, as indicated in the example of renewable energy technologies. accepting the validity of the normative process that policy determines strategy, strategy determines operational plans and operational plans drive budget allocations, it is reasonable to assume that budget allocations match the overall policy framework. however, government as a punctualised actor is in fact not a single entity; it is a loose agglomeration of multiple actors with overlapping but also conflicting policy objectives. for instance, industrial policy may contradict environmental policy, fiscal policy may oppose energy policy, health policy may conflict with trade policy, and defence policy may act against science and technology policy. in terms of decarbonisation, and the likelihood that departments of the environment will be able to secure funds from the national fiscus in support of decarbonisation, it is clear that attention to the politics is critical. for south africa, which faces a million metric tonne per annum decarbonisation challenge with limited ability to raise the necessary resources, this aspect of the environmental campaign will be vital. using the estimated value of $ , per mt carbon dioxide equivalent, the decarbonisation cost for south africa will amount to $ , billion, or % of gdp over a -year period ( to ). in comparison, the decarbonisation costs for the united kingdom will be . % of gdp, as previously indicated in the introduction. south africa, therefore, has limited options in addressing the decarbonisation challenge, other than to consider budget reallocation. the issue of securing resources to support sustainability transitions, and particularly public funding, is also highlighted in the literature on technological innovation systems, where resource mobilisation is identified as one of several critical functions for the establishment of systems to support such transitions [ ] . technological innovation systems as a conceptual model for transition is also a processual framework and in its discussion of resource mobilisation, it is argued that this function needs to be sufficiently covered from the early stages in the development of a new system. identifying resource allocation as an important part of the overall transition process is in itself insufficient in supporting the transition. it is equally important to understand the source of the funds and how they can be secured. public funding is critical in such transitions since the initial stages will be characterised by high levels of risk and limited participation from private funders. however, public budgets are subject to intense competition from other priorities including health, security, education and infrastructure, and the prospects of successfully lobbying for the re-direction of public funds from existing portfolios are severely restricted. this article has argued that such moments do exist, but in resource constrained setting such as south africa, they occur only within narrow windows of opportunity characterised by an escalating problem, the adoption of a recent policy framework, the prospects of an improving benefit to cost ratio, and a willingness to engage in realpolitik. previous studies have concluded with a number of policy recommendations for low-carbon transitions including the need for dynamic policy mixes dealing with demand-and supply-side instruments, a focus on politics in addition to policy, and active steps to phase-out existing technologies in addition to supporting niche-innovation [ ] . the results of this study suggest a number of more specific recommendations for resourceconstrained countries as follows. low-carbon futures are unlikely to be realised without public funding. as is argued in the case of public-funded research and development, such transitions will be subject to market failure and under-investment in the absence of public support. it is therefore important that government establish dedicated funding for sustainability transitions, in the same way that they have created budgets for industrial development or energy infrastructure. developing the structure and rationale for these budgets is an important step towards securing the actual funding. in resource-constrained settings, it will be hugely challenging to secure funds without re-allocation from existing portfolios, the prospects of which are unlikely on a daily basis. however, there will be windows of opportunity or critical junctures, which will arise when there is alignment between an escalating problem, a supporting policy framework and a rising benefit to cost ratio. an appreciation of such moments, and a mechanism for recognising their opening, is an important insight of this study. although leadership and agency are critical, engaging in politics is more that individual action. all actors, but especially politicians and senior public servants, need to enter into relationships with each other, and with civil society, labour and advocacy organisations. in the final decision on budgets, the most important factor may not be the strength of the evidence for the intervention, but the strength of the alliances which are willing to support the re-allocation proposal. conclusion and recommendations in addition to an overall cultural change, transitions to sustainability in south africa, and perhaps other countries, will require new programmes and projects within government. importantly, these programmes will require new funding. however, the prospects for this are severely limited by the present situation of decreasing government revenues and the overall path dependence of budget allocations. the lack of new funding will hinder such transformation and requires the development of new strategies. this research has sought to define the main components of the budget process in south africa and hence develop a strategy to overcome funding limitations for necessary and important operational programmes. it concludes that the conjunction of four streams is key to successful changes in budget allocations, namely a growing problem, preferably accelerating, a recently developed policy framework, a strong techno-economic justification whose prospects likely to become more attractive, and a strengthening political stream consisting of powerful alliances able to drive budget changes through the executive. these conclusions align with the insights of historical institutionalism, which include the supposition that change takes place as a result of contestation, and at the meso 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journeys: theory, findings, research agenda, and policy applied welfare economics: cost-benefit analysis of projects and policies socio-economic impact assessment system guidelines, department of planning monitoring and evaluation renewable energy gathers steam in south africa functions of innovation systems: a new approach for analysing technological change the socio-technical dynamics of low-carbon transitions the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. key: cord- -vipfgvgh authors: sylvester, steven p.; soreng, robert j.; sylvester, mitsy d.p.v.; clark, vincent ralph title: festuca drakensbergensis (poaceae): a common new species in the f. caprina complex from the drakensberg mountain centre of floristic endemism, southern africa, with key and notes on taxa in the complex including the overlooked f. exaristata date: - - journal: phytokeys doi: . /phytokeys. . sha: doc_id: cord_uid: vipfgvgh we present taxonomic notes on the festuca caprina complex from southern africa that includes description and illustration of the new species f. drakensbergensis from the drakensberg mountain centre of floristic endemism of south africa and lesotho. festuca drakensbergensis can be differentiated from f. caprina s.l. by forming lax short tufts with extravaginally-branching tillers and lateral-tending cataphyllous shoots or rhizomes present, basal foliage reaching < ½ the length of the culms, with generally shorter leaves and shorter anthers, . − . (− . ) mm long. the species also differs from the overlooked species f. exaristata – currently known from two collections from lesotho − by its fibrous basal sheaths, usually sharp, keel-like leaf blade midrib, drooping panicle with lightly to densely scabrous pendent panicle branches, longer lemmas, . − . mm long, with awns usually present, . – mm long, ovary apices sparsely to densely hairy and anthers . − . (− . ) mm long. taxonomic notes on the different taxa of the f. caprina complex in southern africa are also provided, including images, key, and lectotypification of f. caprina var. curvula. this research adds a further two endemic species (f. drakensbergensis and f. exaristata) and two endemic varieties (f. caprina var. irrasa and f. caprina var. macra) to the drakensberg mountain centre of floristic endemism. carbutt's ( ) drakensberg mountain centre of floristic diversity and endemism (dmc) includes the only alpine region in mainland africa south of mount kilimanjaro (killick ) , with a km disjunction. the dmc, covering some , km , comprises a montane sub-centre, dominated by c grass species and an alpine sub-centre [the former drakensberg alpine centre of van wyk and smith ( ) and carbutt and edwards ( , ) ] dominated by c grass species (brand et al. ). the dmc is renowned for its high levels of plant diversity and endemism, hosting endemic angiosperm species that account for ca. % of the angiosperm flora; the dmc hosts grass species in genera (carbutt and edwards ) , of which eight species and one genus are endemic (carbutt ) . despite being the dominant ecosystem-forming component of these high elevation grasslands, grasses of the dmc are still relatively poorly studied, with only a few genera receiving attention, for example, anthoxanthum l. (mashau ) ; catabrosa p. beauv. (soreng and fish ) ; poa l. (soreng et al. in prep.) ; trisetopsis röser & a. wölk (e.g. mashau et al. ); pentameris p. beauv. (linder and ellis ) . the genus festuca l. s.l. is a monophyletic lineage with ca. perennials and ca. annuals (beyond those in lolium l.), totalling ca. species (plants of the world online accepted species belonging to the lineage). the genus s.l. is divided into two major clades (minaya et al. ) : the narrow leaf clade (nlc) of festuca s.s., ca. species (syn. [following soreng et al. including the annuals] ctenopsis de not., loliolum v.i. krecz. & bobrov, micropyrum (gaudin) link, narduroides rouy, vulpia c.c.gmel. and wangenheimia moench), and the broad leaf clade (blc), ca. species (perennials, and some annuals in lolium), including drymochloa holub, leucopoa griseb., lojaconoa gand., lolium (syn. micropyropsis romero zarco & cabezudo, schedonorus p. beauv.), patzkea g.h. loos, pseudobromus k. schum. and xanthochloa (krivot.) tzvelev. fish and moeaha ( ) accepted nine species of festuca s.l. (but excluding vulpia and lolium in the narrow traditional sense) as present in the flora of southern africa (fsa) region (comprising botswana, lesotho, namibia, south africa and eswatini a.k.a. swaziland). generic limits of festuca s.l. are still being resolved, particularly in the blc (soreng et al. ) . of the fsa species with dna examined (minaya et al. ) , f. caprina nees and f. vulpioides steud. belong stapf and f. scabra vahl belong to the blc. although it generally holds true, not all nlc and blc taxa have narrow and broad leaves, respectively, for example, f. vulpioides being placed in the nlc (minaya et al. ; identity of voucher specimen not verified by us). festuca dracomontana h.p. linder (predicted to be blc), f. exaristata e.b. alexeev (not accounted for by fish and moeaha , predicted to be nlc) and our new species (predicted to be nlc) have not been tested. festuca s.l. is one of the prominent genera present in the montane-alpine ecotone (ca. - m alt.) and alpine sub-centre (> m alt.) of the dmc (irwin and irwin ) and often dominates, especially in less disturbed areas (sylvester et al. unpubl. data) . one species, f. killickii, is currently considered to be endemic to the dmc (carbutt : table ), although the poorly-known f. dracomontana and f. vulpioides may also be dmc endemics (fish and moeaha ) . of the species of festuca recorded by fish and moeaha ( ) , f. caprina is perhaps the most widespread in the afro-montane/afro-alpine region of white ( ) , stretching from the coastal southern cape of south africa to tanzania (fish and moeaha ) . festuca caprina s.l. has had three varieties described from the fsa region (var. curvula nees, var. irrasa stapf, var. macra stapf ) and was considered to be a complex of species by alexeev ( ) , who recognised two new species for the complex in sub-saharan africa, f. claytonii e.b. alexeev from kenya and f. exaristata e.b. alexeev from the dmc, and raised f. caprina var. macra to species rank. fish and moeaha ( : ) stated that the different varieties of f. caprina accepted in previous treatments were not upheld in their treatment because of "the variability in the species and leaf anatomy, which are constant throughout". although alexeev's ( ) taxonomy and new species were accepted by agrostologists at kew (phillips a, b; clayton et al. onwards) , there is no mention of it in fish and moeaha ( ) or the older treatment of festuca for the fsa region (gibbs russell et al. ) and the checklist of lesotho grasses (kobisi and kose ) , with this error also being replicated in floristic surveys of the dmc (carbutt and edwards , ; carbutt ) . taxa in the f. caprina complex differ from other festuca s.l. taxa in the fsa region by having: basal sheaths entire or splitting into narrow parallel threads (vs. coarsely fibrous in f. costata), glabrous or scabrous (vs. basal ones velvety in f. scabra); ligules < mm long (vs. > mm long in most, apart from f. dracomontana and f. vulpioides); collars non-auriculate (vs. auriculate in f. arundinacea, f. dracomontana and f. vulpioides) ; blades narrow, . - . mm wide in diameter, involute (vs. flat or relatively broad, [ -] - mm wide in diameter, rarely narrower in f. scabra); panicles loose or contracted (vs. very open, candelabrum-shaped, in f. longipes, open in f. africana, f. arundinacea and f. dracomontana) ; spikelets to several flowered (vs. -flowered in f. africana), awns - . mm long (vs. - mm long in f. africana). during extensive field collecting and ecological research by the authors in the dmc area ( m × m plots studied for all vascular plants, of which plots contained festuca species, with collections of festuca made), followed by herbarium research at pre, clear differences were noted between specimens that were treated under f. caprina by fish and moeaha ( ) . these differences included branching patterns in tillers, presence of cataphylls, abaxial leaf blade indumentum and anther size, which are known to be taxonomically informative for distinguishing festuca taxa in other parts of the world (e.g. stančik and peterson ; ospina et al. ) . these clear differences allowed us to distinguish the new species, f. drakensbergensis, and to recognise the varieties f. caprina var. irrasa and f. caprina var. macra. this new species, coupled with the overlooked species, f. exaristata and distinct varieties, f. caprina var. irrasa and var. macra, add a further two endemic species and two endemic varieties to carbutt's ( ) checklist of dmc endemics. the aim of this paper is therefore to: (i) describe and illustrate the new dmc endemic, f. drakensbergensis. (ii) provide taxonomic notes on the distinct varieties of f. caprina present in the dmc and the overlooked species, f. exaristata. (iii) provide a revised key for the f. caprina complex in the fsa region. extensive field collecting was conducted by sps, rjs and mdpvs in the dmc between feb and mar , with specimens belonging to the f. caprina complex collected, which are deposited in the pre, nu and us (pending export permits) herbaria [herbarium acronyms follow thiers ( , continuously updated) ]. herbarium study was also conducted at pre between and mar . while focus was placed on the new field collections of festuca and notes on variations present in our plots containing taxa belonging to the f. caprina complex, many other older pre herbarium specimens were studied than mentioned in the 'selected specimens examined' sections herein, but, due to unforeseen obstructions caused by the cov-id- pandemic, information regarding these specimens was not adequately recorded. type images on jstor global plants (https://plants.jstor.org) were also assessed. we delimit taxa based on distinct discontinuities in morphological characteristics which are deemed to be phylogenetically conserved and taxonomically informative based on previous research (e.g. stančik and peterson ; ospina et al. ) , as well as distinct discontinuities in ecological and morphological characteristics of taxa observed during extensive fieldwork in the dmc area. distinctive characteristics of habit, colouration and ecological preferences, notable between individual plants within and amongst populations in the field, are often difficult to sort out when dealing only with herbarium specimens. in this treatment, glabrous means without pubescence (in the sense of slender, relatively soft hairs, unless otherwise stated). smooth indicates no prickle-hairs with broad bases and/or hooked or pointed apices (i.e. pubescence can occur on a smooth surface and a rough or scabrous surface can be glabrous). leafblade anatomical characteristics were observed in cross-sections from the middle area of selected tiller blades. we collected many silica-dried leaf samples of festuca s.l. for future dna examinations. tillers intravaginal (cataphylls absent, elongated prophylls present at juncture of lateral shoots), lateral tending rhizomes absent; densely tufted and usually forming large tussocks with basal foliage reaching ( −) - + cm tall and often > ½ the length of the culms; sheaths of tillers and basal culm ( -) - cm long; leaf blades of tillers and basal culm ( −) − . + cm long; lowermost lemmas ( . −) − (− ) mm long; fertile anthers ( . −) − mm long (as short as . mm in var. macra, according to alexeev ) diagnosis. differs from festuca caprina s.l. by forming lax short tufts with extravaginally branching tillers and lateral-tending or ascending cataphyllous shoots or lateral-tending rhizomes present, basal foliage reaching < ½ the length of the culms, sheaths of tillers and basal culm ( . -) - (- ) cm long, leaf blades of tillers and basal culm ( -) - (- ) cm long, and anthers . − . (− . ) mm long. differs from festuca exaristata by its basal sheaths fibrous, leaf blade midrib usually sharp, keel-like, sometimes blunt and rounded, panicle branches pendent, lightly to densely scabrous, lowermost lemma (not including awn) . − . mm long, awn usually present, . - mm long, ovary apex sparsely to densely hairy and anthers . − . (− . ) mm long. description. perennial herbs, generally forming lax, short, isolated tufts, with lateral-tending or ascending cataphyllous shoots or lateral-tending rhizomes present, basal foliage ( −) − (− ) cm tall and generally < ½ the length of the culms, with inflorescences largely exerted. tillers extravaginal, with cataphylls present, intravaginal tillers rarely also present (i.e. sylvester et al. ) . culms ( . -) - (- ) cm tall, . - . (- ) mm diam., erect, delicate, cylindrical to slightly compressed, longitudinally striated, glabrous, smooth, with ( ) or visible nodes, uppermost node at ( . -) - (- ) cm from the base, ca. ( / -) / - / (-½) culm height, distance between uppermost node and panicle ( -) - (- ) cm long, distance between uppermost node and second node down ( . -) . - . (- . ) cm long, nodes at the base covered by imbricate leaf sheaths. leaves mostly basal, with or ( ) cauline leaves, culm leaves similar to those of the base and tillers; sheaths of tillers and basal culm ( . -) - (- ) cm long, proximally fused ca. ½ their length, implicate above, usually slightly obliquely truncated at the apex, herbaceous, persistent, becoming sparingly fine fibrous -decaying into longitudinal fibres -in the lower portion with age, brownish or yellowish, glabrous, usually smooth, rarely retrorsely scabrous, with - veins; flagleaf sheaths . - . (- . ) cm long, fused ca. ½ their length; auricles . - . mm long, inconspicuous, obtuse; ligules . - . mm long, membranous, moderately to strongly decurrent with the sheath margins, truncate, briefly ciliolate; flag-leaf ligules . - . mm long; leaf blades of tillers and basal culm ( -) - (- ) cm long, . - . (- ) mm wide as rolled or folded, setaceous, erect-curved to recurved, firm to ± rigid, conduplicate, convolute or involute, rarely flat in upper leaves, elliptical or obo- vate to carinate outline in cross-section, midrib (middle vein) usually sharp, keel-like, sometimes blunt and rounded, abaxial surface glabrous, usually smooth throughout or lightly antrorse-scabridulous towards the apex, adaxial surface scabrous on veins or prickles elongating to become hair-like and appearing shortly hairy, light-to darkgreen, apex obtuse (to acute); upper culm leaf-blades similar to those of lower culm and tillers, but shorter and sometimes expanded; flag-leaf blades ( . -) . - (- . ) cm long, ( -) - (- )% the length of their flag-leaf sheaths, rarely longer. panicles . - (- ) cm long, open to moderately congested, drooping, with ( -) - (- ) spikelets often held unilaterally on lower side of axis; central panicle axis smooth to lightly antrorsely scabrid, with - nodes, usually branch (rarely branches) per node, lowest internode ( . -) - . (- . ) cm long, ca. - % length of whole pani-cle, lowest internode and sometimes upper internodes and panicle branches often sinuous-wavy; panicle branches capillaceous, generally pendent and drooping, lowermost patent to pendent, upper ± appressed to central axis, glabrous, antrorsely scabrous to scaberulous on angles or rarely smooth; lowermost primary panicle branch ( -) . - cm long, with ( -) - (- ) spikelets; pedicels . - (- ) mm long, shorter than their spikelets, slightly thickened at their apices, glabrous, antrorsely scabrous to scaberulous on angles or rarely smooth. spikelets (not including awns) ( . -) - (- . ) mm long, laterally compressed, elliptic, green or usually purplish; florets to ( ) fertile and usually apical and ± rudimentary, sterile, lowermost fertile floret largest, with upper fertile florets gradually reducing in size; glumes unequal, lower ca. ½- / (- / ) length and ca. / -½ width of upper glume, narrowly scarious on the margins, usually darker purple compared to the lemmas, glabrous, keels distally scaberulous for ¼- / their length or smooth throughout, surfaces smooth throughout or sometimes sparsely scaberulous towards apex, margins usually with scattered hooks on edges in distal ½(- / ), (acute or) acuminate; lower glumes . - (- . ) mm long, . - . mm wide at base in cross section, reaching to - % length of proximal lemma, linear-lanceolate, -veined; upper glumes . - (- . ) mm long, . - . mm wide at base in cross section, reaching to - % length of proximal lemma, ovate-lanceolate, -veined; rachillas up to ca. . - . mm long, slightly dorsally compressed, glabrous, smooth, lightly scabrous towards apex or densely scabrous throughout; calluses somewhat thick, annulated, angled downward, rugose or smooth, sometimes lightly scabrous; lemmas (lowermost lemma not including awn) . - . mm long, . - . mm wide at broadest point in cross section, ovate-lanceolate, herbaceous with narrowly scarious margins, glabrous, proximally smooth or sparsely to densely scabrous, especially towards the margins, distally sparsely to densely scabrous, especially towards the apex and margins, moderately to densely granulose with clear bead-like raised silica cells appearing like 'granules' throughout or these absent towards apex and margins, margins scabrous throughout or in the distal / - / , green or usually greenish-purple at the margins and towards the apex, -veined, apices acute and tapering into a short awn, sometimes slightly bilobate with awn emerging from between the minute lobes or very rarely muticous, awn . - mm long, straight, scabrous; paleas (lowermost) . - . mm long, subequalling to usually equalling the lemma or slightly surpassing the lemma apex by up to . mm, herbaceous with scarious margins, slightly to deeply bidentate, keels scabrous in distal ( / -)½- / or rarely throughout, between keels smooth, moderately to densely granulose with clear bead-like raised silica cells appearing like 'granules', margins scabrous in distal ¼- / . flowers proximally perfect with uppermost usually sterile; anthers in number, . − . (− . ) mm long, linear, dull yellow; ovaries ca. . − mm long, apex sparsely to densely pubescent; lodicules . - . mm long, bilobed with lobes ca. - mm long, both lobes +/-same size or lateral lobes to . mm shorter, glabrous, margins entire and smooth or sometimes fimbriate, acute. caryopses ca. . - . mm long, ca. - . mm shorter than lemma and palea, adhering to palea and lemma, narrowly elliptic to slightly narrow-obovate, deeply sulcate, hilum linear, - % length of caryopsis, endosperm hard. anatomy-outline elliptical or obovate to carinate with angled arms, ca. vascular bundles all positioned in the centre of the blade and at the same level, ca. grooves, ca. ribs; the central rib is located in the central area of the blade. abaxial surface with straight edges forming angles associated with the vascular bundles, ribs angular, composed of sclerenchyma block and found opposite all vascular bundles, smooth, macro-hairs absent, margins composed of sclerenchyma block. adaxial surface markedly irregular, with rounded ribs situated opposite all vascular bundles, lacking scleren-chyma block, prickles present and densely covering the entire surface, sometimes more prevalent on the ribs, usually extending and appearing hispid (fig. e, f) . distribution and habitat. endemic to the high-elevation dmc of south africa and lesotho (carbutt ) . in south africa, the species is known from the eastern cape and kwazulu-natal provinces, with it also possibly occurring in the free state province, although no specimens have as yet been verified. festuca drakensbergensis is a common constituent of both moderately grazed and little disturbed afro-alpine vegetation (viz. carbutt's 'austro-alpine region'), and less often in afro-montane vegetation, of the dmc, ca. - + m alt. the species is found in grassland, wetland and short afro-alpine shrubland dominated by species in the genera chrysocoma l., erica tourn. ex l., eumorphia dc. and helichrysum mill. these habitats correspondent with mucina and rutherford's ( ) ukhahlamba basalt grassland (gd ), lesotho highland basalt grassland (gd ), drakensberg afro-alpine heathland (gd ) and lesotho mires (azf ). festuca drakensbergensis is rarely dominant and generally occurs in low abundance amongst the larger f. caprina var. macra or amongst other forbs or low shrubs. of the m × m plots studied for all vascular plants across the afro-alpine dmc (sylvester et al. unpubl . data), f. drakensbergensis was encountered in usually low abundance ( . - [- ]% of overall plot cover) in plots, highlighting its high frequency and ubiquity in these landscapes. preliminary conservation status. the overall extent of occurrence of f. drakensbergensis is relatively large compared to many dmc endemics, perhaps % (or , km i.e. above m) of the total dmc area of ca. , km . given that it is a common species without any specific habitat niche, the total population is likely well above , mature individuals. however, given the tremendous pressure that the dmc is under from communal rangeland activities -especially in lesotho (global mechanism of the unccd , ) -it is possibly at medium-to long-term risk from land degradation through overgrazing. initial observations suggest that the species does have resilience, being recorded in areas disturbed by grazing and burning as well as in areas of limited disturbance. there might, however, be competition from shrubland following overgrazing (e.g. chrysocoma ciliata l., selago melliodora hilliard, eumorphia spp. and helichrysum spp.). future projections of global climate change are also of concern for high-elevation species in southern africa (bentley et al. ) . accordingly, we propose the iucn conservation status of near threatened (nt) until further population studies can be undertaken. etymology. the species epithet refers to the drakensberg mountain centre (dmc) of south africa and lesotho (carbutt ) , where this species forms a common component of the afro-alpine vegetation. notes. the character of extravaginal branching is not always easy to distinguish and certain specimens of f. caprina s.l. found growing in moss may have what appear to be rhizomes although these are, in fact, pseudostolons. however, f. caprina var. caprina and var. macra plants are usually much larger, with culms ( −) − + cm tall, basal foliage ( −) - + cm tall, generally (> ½) > ¾ to surpassing the length of the culms, with leaf-blades of tillers and basal culm ( -) - . + cm long, often > cm long, basal sheaths entire, erect panicles with greenish or purplish spikelets on ascending branches, lower lemma often larger, ( . −) − (− ) mm long, and anthers > mm long (vs. culms ( . -) - (- ) cm tall, basal foliage ( −) − (− ) cm tall, leafblades of tillers and basal culm ( -) - (- ) cm long, basal sheaths fibrous, drooping panicles with purplish spikelets on pendent branches, lower lemma . - . , anthers . − . (− . ) mm long in f. drakensbergensis) ( table ) . festuca caprina var. irrasa specimens can sometimes superficially resemble f. drakensbergensis by having shorter basal foliage reaching < ½ length of the culms, with smooth blades and fibrous basal sheaths (table ) . however, in these cases, f. caprina var. irrasa can be distinguished by its intravaginally branched tillers which lack cataphylls, erect panicles with ascending branches, short-hispid or long-scabrous lemmas and paleas that often measure > mm long, and anthers > mm long (vs. extravaginally branched tillers with cataphylls present, drooping panicles with pendent branches, lemmas and paleas glabrous, scabrous, . − . mm long, and anthers < . mm long in f. drakensbergensis). festuca exaristata also bears extravaginally branched cataphyllous tillers or lateraltending rhizomes, with plants forming short isolated tufts. the holotype of f. exaristata is very short, with basal foliage not reaching past cm tall, and bears superficial resemblance to certain shorter specimens of f. drakensbergensis, for example, sylvester et al. . the protologue of f. exaristata mentions culms to cm tall and leaf blades to cm long, which must refer to the one paratype, du toit (k), which has not been seen by us, showing that the species would also superficially match larger versions of f. drakensbergensis. however, f. exaristata differs by its entire, lustrous basal sheaths, blunt, rounded leaf-blade midribs, erect sub-spike-like panicles, smooth panicle branches, shorter lemmas − . mm long which lack awns, glabrous ovary apex and anthers . − . mm long (vs. basal sheaths smooth or rarely retrorsely scabrous, fibrous, leaf blade midrib usually sharp, keel-like, sometimes blunt and rounded, panicles drooping, panicle branches lightly to densely scabrous, lowermost lemma (not including awn) . − mm long, awn rarely absent, usually . - mm long, ovary apex sparsely to densely hairy, anthers . − . (− . ) mm long in f. drakensbergensis). although rarely some characters overlap between f. drakensbergensis and f. exaristata, the combination of characters found in f. exaristata is never found in specimens of f. drakensbergensis. some specimens (e.g. sylvester et al. ) growing in wetlands with limited grazing were substantially larger than normal, with culms to cm tall and inflorescences to cm long. alexeev ( ) , had entire, often lustrous, basal sheaths apart from var. irrasa, which were obviously fibrous. the protologue mentions basal sheaths to be fibrous and, as such, alexeev ( ) may have made an error in his choice of lectotype. nevertheless, as only the type material of var. irrasa, which was designated by stapf ( ) , has fibrous basal sheaths, this also raises questions over the accuracy of the description in the protologue for var. caprina. if we treat f. caprina var. caprina based on the k lectotype and isolectotype designated by alexeev ( ) then var. caprina should be considered as having entire basal sheaths that do not split into fibres. oddly, the inflorescences of all var. caprina specimens studied had a distinct butter-like smell upon the opening of specimen press papers, which then quickly dissipated. this odour was barely to sometimes slightly susceptible in specimens of f. caprina var. macra or var. irrasa or f. drakensbergensis. it remains to be seen whether this character is diagnostic and what phytochemical compounds are involved. festuca caprina var. caprina is more common at lower elevations in the drakensberg mountain centre (carbutt ) and surrounding mountainous habitats of southern africa and extends from southern africa to tanzania. the species appears to prefer more mesic afro-alpine and afro-montane grasslands and is outcompeted by f. caprina var. macra in the drier summit area of the high escarpment in the dmc. of the m × m plots studied for all vascular plants across the afro-alpine dmc (sylvester et al. unpubl. data) , f. caprina var. caprina was rarely encountered, being found in only plots from the eastern cape and free state. the species was usually encountered in lower elevation afro-montane transitioning to afro-alpine grasslands at ca. − m alt. or exceptionally at higher elevations to m alt. in damper shaded sites, highlighting its very low frequency and commonality in the high-elevation xeric afro-alpine zone of the dmc. festuca caprina var. curvula is also herein lectotypified. in the protologue, nees von esenbeck ( : ) only cited a single drége s.n. collection from monte los-tafel- berg, ft ( m alt.), which is assumed to be the same type locality as var. caprina that was found in los-tafelberg of the eastern cape province, near queenstown. nees von esenbeck ( : ) labelled var. caprina and var. curvula 'a' and 'b', respectively, with the s-g- right hand plant chosen as lectotype based on this matching the protologue information and being the only specimen sheet amongst the original material to be annotated with an 'a' and 'b' in nees von esenbeck's cursive handwriting. the right-hand plant annotated with 'b' fitted the protologue description of var. curvula, with nees differentiating the variety based on its shorter height, curved blades and subsecund panicle branches with few purplish spikelets. one specimen amongst the original material, d.f. drége .e. ? (p ), also had 'curvula' written on the label but limited locality information aside from 'plantes du cap' and is here considered a syntype of var. curvula as it also fits the description given in the protologue. while the differentiating characters of f. caprina var. curvula are also found in f. drakensbergensis, we deduce that var. curvula is a slight variation from the norm in f. caprina as neither the type specimens designated herein, nor any of the other original material from the type locality, can be attributed to f. drakensbergensis based on their lacking extravaginal branching and cataphyllous shoots as well as having entire lustrous basal sheaths. notes. festuca caprina var. irrasa may indeed be distinct and warrant elevating to species level. it differs from the other intravaginally branched taxa in the complex (f. caprina var. caprina and f. caprina var. macra) by the obviously fibrous basal sheaths and usually short-hispid or long-scabrous (prickles hair-like) lemmas, paleas and rachillas. the character of lemma, palea and rachilla pubescence sometimes varies with hispid hairs sometimes only found at the apex of some lemmas in the inflorescence. the panicle branches and pedicels are also usually densely short-hispid or long-scabrous with hooks elongating to become almost hair-like, a character not seen in the other members of the f. caprina complex, although this character also appears to vary. the variation may be due to introgressive hybridisation or lateral gene transfer between taxa, which possibly occur frequently in grasses (kellogg ; hibdige et al. ; tkach et al. ). this could be exemplified by how one specimen (sylvester et al. ) that was collected close to both var. macra (sylvester et al. ) and var. irrasa (sylvester et al. ) had inflorescence characteristics of var. irrasa, but antrorsely scabrous abaxial leaf-blade surfaces like var. macra. further work is needed to clarify the circumscription and taxonomic position of var. irrasa. festuca drakensbergensis, described herein, also usually has fibrous basal sheaths and, although not as conspicuous as f. caprina var. irrasa, can be readily distinguished based on its extravaginal tiller branching, presence of rhizomes and smaller anther size, amongst other characters. festuca caprina var. irrasa is endemic to the dmc of southern africa, being found in lesotho and the south african eastern cape and kwazulu-natal provinces and possibly the free state province (although no specimens have been verified by us). the species appears to be more common in the kwazulu-natal province. during our ecological plot-based study across the afro-alpine dmc (sylvester et al. unpubl. data) , f. caprina var. irrasa was only encountered as locally abundant ([ . -] - % of m × m plot cover) populations in the damper southern sites of the dmc, i.e. sehlabathebe national park (lesotho) and barclays pass (eastern cape, south africa). the species was found in only plots ranging from the lower elevation afro-montane to afro-alpine grassland transition at ca. m alt. to wet afro-alpine tussock grasslands at ca. m alt. alexeev ( alexeev ( : notes. alexeev ( ) raised var, macra to species level and differentiated it from f. caprina based on: a) sheaths of old leaves not falling apart into parallel thin threads (vs. falling apart (shredded) into parallel thin threads in f. caprina, although this is now considered erroneous; see comments under f. caprina above); b) leaf blades more or less glaucous (vs. green in f. caprina); c) abaxial leaf-blade surfaces scabrous (vs. smooth or scaberulous in f. caprina); d) adaxial leaf-blade surfaces shortly hairy (vs. scabrous or shortly hairy in f. caprina); e) lemmas . − mm long (vs. − [ ] mm long in f. caprina); f ) awns . − . mm long (vs. [ . ] − m long in f. caprina); g) anthers . − . mm long (vs. [ −] . − mm long in f. caprina); h) spikelets straw-coloured-violet (vs. violetgreen, rarely green in f. caprina). however, only the holotype of f. caprina var. macra was seen by alexeev, as well as original material (from which a lectotype was selected) and a limited number of other specimens of f. caprina var. caprina at the k herbarium. upon study of numerous specimens that belong to f. caprina var. caprina and var. macra during extensive fieldwork in the dmc and herbarium study at pre, it became apparent that the above-mentioned differentiating characters overlap. both f. caprina var. caprina and f. caprina var. macra share most characteristics, such as intravaginal tillers forming dense, often large, tussocks, with entire, often lustrous, basal sheaths, narrow involute blades and similar inflorescence and spikelet morphology, with anthers usually > mm long. the f. caprina var. macra holotype is on the shorter side with regards most inflorescence characters when compared with f. caprina var. caprina, with shorter spikelets, lemmas, awns and anthers according to the protologue. nevertheless, most of these characters have also been found in specimens of f. caprina var. caprina, with variability in lengths of the spikelet parts possibly being related to ecological conditions, including seasonal variations in rainfall (c. mashau, pers. comm.) . the anther length of . mm, mentioned in the protologue for f. macra (alexeev : table ), is shorter than any specimen of f. caprina var. macra studied by us, with it being plausible that the var. macra holotype could be somewhat intermediate between f. drakensbergensis and f. caprina var. macra in its broader sense, with similar plausible hybrids with a mixture of characters sometimes found in the dmc (see below). indumentum of the adaxial leaf-blade surface was also found to vary between scabrous, long-scabrous with prickles becoming elongated and hair-like and shortly hispid in all the taxa of the f. caprina complex from southern africa, with this character seen to have no diagnostic value. festuca caprina var. macra was not included in the treatment of southern african grasses by fish and moeaha ( ) , who chose not to uphold any of the varieties of f. caprina stating that the species was too variable. nevertheless, we consider f. caprina var. macra to be distinct from var. caprina based on the character of notably antrorsely scabrous abaxial leaf-blade surfaces that is not known outside of the dmc, with all other f. caprina specimens across their range being smooth or exceptionally scaberulous towards their apices. specimens with notably scabrous leaf blades were also found to be geographically and ecologically distinct during fieldwork in the dmc, these being predominantly found in drier alpine areas of the dmc, while var. caprina was found in more mesic environments often at lower elevations in the montane belt. plants of the world online ( ), plantlist ( ) , the world checklist of selected plant families ( ) and grassbase (clayton et al. onwards) currently accept f. macra as a distinct species. while we currently disagree with this assessment, more exhaustive research may result in var. macra being raised to subspecies level, with certain characters still needing to be assessed such as lemma micromorphology, which has been proven to be taxonomically informative in festuca (ortúñez and cano-ruiz ) . festuca caprina var. macra is often dominant in less-disturbed afro-alpine grasslands of the dmc (carbutt ), being found in lesotho and the eastern cape, free state, kwazulu-natal provinces of south africa. of the m × m plots stud-ied throughout the dmc, were occupied and often dominated ([ . -] - % of overall plot cover) by f. caprina var. macra (sylvester et al. unpubl. data) , with a total of collections of the species being made. it is more palatable than merxmuellera conert species and so is less common in grazed areas (sylvester and soreng, pers. obs.) . festuca obturbans st.-yves and its allies f. gilbertiana alexeev ex s.m. phillipps and f. macrophylla a. rich., described from afro-alpine vegetation of kenya or ethiopia, also bear superficial similarity to f. caprina var. macra in their intravaginally branched large tussocks with entire basal sheaths and fine, involute and usually scabrid leaf blades (alexeev ; phillips a,b) . these also share similar inflorescence characteristics with f. caprina var. macra, such as relatively-narrow panicles with spikelets loosely arranged on short ascending branches, and spikelets with similar glume, lemma and anther sizes (alexeev ; phillips a,b) . these can be differentiated by their leaf blade cross sections showing sclerenchyma girders bridging both sides of the vascular bundles or, at least, the larger ones (vs. sclerenchyma only present on the abaxial blade ribs in f. caprina var. macra). festuca gilbertiana can be further differentiated by its smooth leaf blades, culms - cm tall, and sparse racemose inflorescence (vs. leaf blades scabrous, culms ( -) - (- +) cm tall, inflorescence usually a large loosely-contracted panicle in f. caprina var. macra). festuca obturbans can be further differentiated by having sheaths open to almost their base and ovary apices glabrous (vs. sheaths closed for ca. ½ their length, ovary apices sparsely to densely pubescent in f. caprina var. macra). two specimens found near the tiffindell ski resort of the eastern cape, south africa (sylvester et al. b) and bokong nature reserve, lesotho (sylvester et al. b) , bore characteristics of f. caprina var. macra, which was collected alongside them (sylvester et al. a, c) , such as tussock-forming habit with intravaginal branching and entire basal sheaths not splitting into fibres. however, they differed by their smooth abaxial leaf blade surfaces, placing them closer to f. caprina var. caprina, unawned lemmas, which is unusual for both var. caprina and var. macra, and short spikelets with lowermost lemmas . − . mm long anthers measuring ca. . − . mm long, placing them closer to f. drakensbergensis. as f. drakensbergensis was also collected at the same localities (e.g. sylvester et al. , b) , it is plausible that these could be hybrids between f. caprina var. macra and f. drakensbergensis. more study, including further collections, is required to ascertain the identity of these specimens. selected specimens examined. lesotho. afriski area, in valley adjoining and northwest of the valley of the afriski resort, on the north side of the a highway, . s, . e, m alt., dry upper slopes above valley, feb , s.p. sylvester et al. (nu, pre, us) ; afriski resort, in valley just west of the resort centre, . s, . e, m alt., relatively undisturbed damp afro-alpine grassland, feb , s.p. sylvester et al. (pre, us) ; bokong nature reserve, ca. m north from the information centre, . s, . e, m alt., afro-alpine grassland dominated by lachnagrostis barbuligera var. barbuligera with moderately-controlled grazing and burning, mar , notes. this species was not included in the treatments to southern african grasses (gibbs russell et al. ; fish and moeaha ) , nor in the checklist to lesotho grasses (kobisi and kose ) , but is accepted in plants of the world online ( ), plantlist ( ) , the world checklist of selected plant families ( ), grassbase (clayton et al. onwards) and tropicos ( ) . it is known from just two collections; the type from sani pass, bordering lesotho and the kwazulu-natal province of south africa, and a paratype from letsing la letsie of the matatiele province of lesotho. exploration by the authors in the sani pass area failed to discover further specimens although, at the time of visiting, the authors were not searching in particular for f. exaristata and did not cover all the habitats present. the holotype label states 'above the sani pass' probably referring to the mountain slopes and ridge immediately above the sani pass, which were not explored by us. our exploration largely focused on the valley bottom, which experienced very heavy grazing, with it being possible that the species may have been grazed out in these areas. as the species exhibits certain characters of both f. caprina s.l. and f. drakensbergensis, as well as other characters not found on any of these (e.g. glabrous ovaries, shorter unawned lemmas), there is also the possibility that the species is a hybrid which failed to survive into subsequent gen- erations. however, the paratype, which was not seen by us, but was collected in , years after and ca. km southwest of the type collection, raises doubt over this. alexeev ( ) distinguished this species from f. macra (= f. caprina var. macra) and f. caprina in part by: a) leaf blade mid-vein blunt and rounded; b) panicle branches smooth; c) lemmas − . mm long; d) lemmas unawned; e) ovary apex glabrous; f ) anthers . − . mm long. it can be further differentiated from f. caprina var. irrasa by the basal sheaths being entire, and from f. caprina var. macra by the leaf blade abaxial surfaces being smooth. furthermore, although not mentioned by alexeev ( ) , the type material appears to have extravaginal branching, with cataphyllous laterally-tending shoots present, differentiating this from the intravaginally branched f. caprina s.l. the species does bear some resemblance to f. drakensbergensis (see notes under f. drakensbergensis). lesotho highland basalt grassland" with clear elements of "drakensberg afroalpine heathland" with erica and helichrysum shrubs dominating the landscape afro-alpine vegetation with ericaceous shrubs dominating the landscape, heavy grazing afro-alpine vegetation with ericaceous shrubs dominating the landscape, heavy grazing afro-alpine grassland, windy ridge, grazed sani pass area, ca. m east of sani mountain lodge, . s, . e, m alt., short afro-alpine grassland, frequently to heavily grazed s, . e, m alt., wet afro-alpine tussock grassland, soil damp, under dripping crag, heavily grazed, close to livestock paths s, . e, m alt., wet afro-alpine tussock grassland, soil damp, under dripping crag, heavily grazed, close to livestock paths eastern cape: between carlisleshoekspruit pass and tiffindell ski area, . s, . e, m alt., afro-alpine grassland eastern cape: tiffindell ski area, next to ski lift, . s, . e, m alt., afro-alpine grassland, annually burnt, appears to be seeded with exotic species afro-alpine grassland amphitheatre, slopes near the tugela waterfall, . s, . e, m alt afro-alpine grassland new narrow-leaved festuca (poaceae) members from tropical and south africa range contraction to a higher elevation: the likely future of the montane vegetation in south africa and lesotho the alpine flora on inselberg summits in the maloti the drakensberg mountain centre: a necessary revision of southern africa's high-elevation centre of plant endemism the flora of the drakensberg alpine centre the endemic and near-endemic angiosperms of the drakensberg alpine centre onwards) grassbase-the online world grass flora identification guide to southern african grasses: an identification manual with keys, descriptions and distributions. strelizia global mechanism of the unccd ( ) land degradation neutrality target setting in the kingdom of lesotho phylogenetic relatedness, co-occurrence, and rhizomes increase lateral gene transfer among grasses a field guide to the natal drakensberg the families and genera of vascular plants biogeography and ecology of southern africa. w. junk, the hague a checklist of lesotho grasses a revision of pentaschistis (arundineae: poaceae) a synopsis of anthoxanthum (poaceae: pooideae: poeae) in southern africa and description of a new subspecies two new species of helictotrichon (pooideae: aveneae) from south africa contrasting dispersal histories of broad-and fine-leaved temperate loliinae grasses: range expansion, founder events, and the roles of distance and barriers the vegetation of south africa, lesotho and swaziland. strelitzia . south african national biodiversity institute nees von esenbeck cgd ( ) florae africae australioris illustrationes monographicae epidermal micromorphology of the genus festuca l. subgenus festuca (poaceae) multivariate analysis and taxonomic delimitation within the festuca setifolia complex (poaceae) and a new species from the central andes a new species of festuca (gramineae) from ethiopia poaceae (gramineae) catabrosa versus colpodium (poaceae: poeae) in southern africa, with a key to these genera and their species in africa a worldwide phylogenetic classification of the poaceae (gramineae) ii: an update and a comparison of two classifications prep.) new records and key to poa (pooideae: poaceae) from the flora of southern africa region, and notes on taxa including a diclinous breeding system in poa binata a revision of festuca (poaceae: loliinae) in south american páramos pontederiaceae to gramineae index herbariorum: a global directory of public herbaria and associated staff phylogenetic lineages and the role of hybridization as driving force of evolution in grass supertribe poodae regions of floristic endemism in southern africa the history of the afromontane archipelago and the scientific need for its conservation we wish to gratefully thank nanjing forestry university (china) and the university of the free state: afromontane research unit (south africa) for financial and logistical support; konstantin romaschenko for providing crucial russian translations; caroline mashau, lyn fish and pre staff for access to the pre herbarium, discussions of taxa and supplying collecting paper; anthony mapaura for assistance as a co-collector during fieldwork in the eastern cape region; nicky and mark mcleod and afriski for logistical assistance in lesotho; ralph and nadine clark for providing an operations base in south africa (including during lockdown); and carmen acedo and mary namaganda for suggestions which improved the manuscript. we also wish to extend grateful thanks to the permitting authorities and landowners for the relevant permits and permissions to undertake the fieldwork: key: cord- -kw c fgk authors: oboh, mary aigbiremo; omoleke, semeeh akinwale; ajibola, olumide; manneh, jarra; kanteh, abdoulie; sesay, abdul-karim; amambua-ngwa, alfred title: translation of genomic epidemiology of infectious pathogens: enhancing african genomics hubs for outbreaks date: - - journal: int j infect dis doi: . /j.ijid. . . sha: doc_id: cord_uid: kw c fgk background: deadly emerging infectious pathogens place unprecedented challenge on health systems and economies, especially across africa where health care infrastructures are weak, and poverty rates remain high. genomic technologies have been vital in enhancing the understanding and development of intervention approaches against these, such as ebola, and recently the novel coronavirus disease (covid- ). discussion: africa has contributed a limited number of sars-cov- genomes to the global pool in growing open access repositories. to bridge this gap, the africa centre for disease control and prevention (acdc) is coordinating initiatives across the continent to establish genomic hubs in selected well-resourced african centres of excellence. this will allow for standardisation, efficient and rapid data generation and curation. however, the strategy to ensure capacity for high-throughput genomics at selected genomics hubs should not overshadow the deployment of portable, field-friendly and technically less demanding genomics technologies in all affected countries. this will enhance small scale local genomic surveillance in outbreaks, leaving validation and large-scale approaches at central genomic hubs. conclusion: the acdc needs to scale-up its campaign for government support across african union countries to ensure sustainable financing of its strategy for increased pathogen genomic intelligence and other interventions in current and inevitable future epidemics in africa. deadly emerging infectious pathogens place unprecedented challenge on health systems and economies, especially across africa where health care infrastructures are weak, and poverty rates remain high. genomic technologies have been vital in enhancing the understanding and development of intervention approaches against these, such as ebola, and recently the novel coronavirus disease . africa has contributed a limited number of sars-cov- genomes to the global pool in growing open access repositories. to bridge this gap, the africa centre for disease control and prevention (acdc) is coordinating initiatives across the continent to establish genomic hubs in selected well-resourced african centres of excellence. this will allow for standardisation, efficient and rapid data generation and curation. however, the strategy to ensure capacity for high-throughput genomics at selected genomics hubs should not overshadow the deployment of portable, field-friendly and technically less demanding genomics technologies in all affected countries. this will enhance small scale local genomic surveillance in outbreaks, leaving validation and large-scale approaches at central genomic hubs. the acdc needs to scale-up its campaign for government support across african union countries to ensure sustainable financing of its strategy for increased pathogen genomic intelligence and other interventions in current and inevitable future epidemics in africa. covid- , africa, gisaid, acdc, genomic hubs. the novel coronavirus disease (covid- ), a viral outbreak caused by the severe acute respiratory syndrome-coronavirus (sars-cov- ), began in wuhan, china in december and was declared a public health emergency of international concern on the th january j o u r n a l p r e -p r o o f integrate this into our decision making processes on managing covid- outbreak within the continent. this set back is primarily due to limited skillset and infrastructure deficiencies (devex ) . till date, only sars-cov- genome sequences from african countries are represented out of a total of , whole-genome sequences uploaded in gisaid (gisaid ); an online database for the rapid sharing of most viral genomes, clinical and epidemiological data. africa has recorded approximately , cases and close to , deaths from covid- (who a). this significantly outnumber the available african sars-cov- genomes, putting the continent at disadvantage in global genetic epidemiology studies of sars-cov- and consideration in design of vaccines that would provide broad potency against all virus strains circulating in the continent. the above narrative could be different if each country appreciated the need for genetic data and deliberately empower at least one molecular laboratory involved in covid- detection and diagnostics with sequencing technologies. the transition to sequencing viral genomes could adopt cost-effective, easily deployable and portable sequencing platforms with less restricted access to reagents and readily available protocol sharing global networks. it is evident that during an epidemic or a pandemic, most countries close their land borders and airspace to restrict movement and curb the spread of the infectious pathogen. therefore, if viral sequencing platforms are not available in-country, they would have to rely on shipping samples to other laboratories in order to generate sequences. this makes real-time contribution to the global sequences challenging and unrealistic. therefore, while acdc aims for a coordinated, centralised approach for high throughput next-generation sequencing using platforms such as the next-seq and hi-seq, consideration for generation of moderate quality data using miseq, capillary electrophoresis and nanopore technology should be prioritised. this model has been tested in the united kingdom with reported success stories (genomicsengland ). lack of concerted financial commitment, skilled personnel and advanced infrastructure are top amongst the many hurdles facing biomedical science research in africa (omoleke et al. ; gilbert et al. ) . unlike in the global north, capacities are heterogeneous with wide differences between most sub-saharan african countries and south africa for example. moreover, research activities are hardly coordinated across borders, disallowing meaningful continental approaches. this is largely driven by lack of political will and buy-in by various african center for disease control. besides data generating platforms, there is also an acute shortage of expertise in genetic and genomic data analysis and interpretation for translation into public health interventions. this lack of trained human capacity has resulted in heavy reliance on research collaborators and donor funding from the global north for limited quality and valid data outputs. hence, the benefit of using genetic epidemiology data in real-time to inform policy is currently largely unrealistic. the acdc has taken up a continental, coordinated perspective to define strategies that will address some of the challenges impeding derivation of full benefit from currently available technologies that facilitate interventions against sars-cov- and future emerging pathogens (acdc ). the big picture is the setting up of centralised genomics laboratory hubs, coordinated by the pathogen genomics intelligence institute (acdc ). the main goal is to strengthen and link health systems with these institutions for effective surveillance, detection, tracking and monitoring outbreaks before they occur across the continent. to substantiate their effort, illumina, one of the leading genomics companies, has donated $ . million in equipment, software, and reagents to the region through the acdc (devex ). of already establish centres such as the european and american cdcs to put in place regulation and structures that will facilitate and sustaine cross-border collaborative platforms for more robust epidemic preparedness, readiness and response across the continent in the near future. despite the efforts of africa cdc towards centralised genomic hubs, a situation analysis of continental needs and priority areas in epidemic preparedness and genomic intelligence is required. the current state of institutions, infrastructure and human resources for data generation, management and analysis need urgent attention. in the event of epidemics such as covid- , genomic data generation for real-time decision making could be enhanced by the adoption and decentralised application of small, portable, easily operated experimental tools such as oxford nanopore technology-minion sequencer, illumina miniseq or the bgi-dnbseq across all countries. these easily deployable, user-friendly field-based technologies were very instrumental in the sequencing of the ebola virus (ebov) during the last outbreak in west and central africa (arias et al. ; hoenen et al. ; quick et al. ) . data generated were useful in strategizing and ensuring the efficacy of interventions, including tracking and stopping the spread of ebov and to evaluate vaccine efficacy. already established genomics hubs strategically located in the four geographic regions (west, east, south and north) of the continent could collate samples from each country for validation and high throughput production of data since they have the requisite technical expertise and infrastructure. in this regard, standardised operating procedures, quality-assured operations, and data curation strategy can be assured and disseminated as well. this can provide the benchmark for future comparative data analysis. to build on its current gains, the acdc should engage in a massive campaign for stronger political commitment from member states in funding genomics as a tool for surveillance and monitoring disease outbreaks. better engagement approaches will enable government buyand ensure the financial strength and sustainability of established genomics institutions towards rapid containment of emerging infectious disease epidemics. union rolls out partnership to accelerate covid- testing rapid outbreak sequencing of ebola virus in sierra leone identifies transmission chains linked to sporadic cases strengthening africa ' s ability to ' decode ' the coronavirus the , genomes project protocol v preparedness and vulnerability of african countries against importations of covid- : a modelling study nanopore sequencing as a rapidly deployable ebola outbreak tool genomic characterisation and epidemiology of novel coronavirus: implications for virus origins and receptor binding quagmire of epidemic disease outbreaks reporting in nigeria real-time, portable genome sequencing for ebola surveillance the cost and cost trajectory of whole-genome analysis guiding treatment of patients with advanced cancers who ramps up preparedness for novel coronavirus in the african region who. statement on the second meeting of the international health regulations ( ) emergency committee regarding the outbreak of novel coronavirus a novel coronavirus from patients with pneumonia in china this perspective idea came from the genomics platform weekly laboratory updates discussion for which mao is grateful. the authors declare that they have no competing financial interest or personal relationship that could have impacted their position. this perspective did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. the work did not involve human subjects. key: cord- -nc v s authors: margolin, emmanuel; burgers, wendy a.; sturrock, edward d.; mendelson, marc; chapman, rosamund; douglass, nicola; williamson, anna-lise; rybicki, edward p. title: prospects for sars-cov- diagnostics, therapeutics and vaccines in africa date: - - journal: nat rev microbiol doi: . /s - - - sha: doc_id: cord_uid: nc v s the emergence of severe acute respiratory syndrome coronavirus (sars-cov- ) has resulted in a global pandemic, prompting unprecedented efforts to contain the virus. many developed countries have implemented widespread testing and have rapidly mobilized research programmes to develop vaccines and therapeutics. however, these approaches may be impractical in africa, where the infrastructure for testing is poorly developed and owing to the limited manufacturing capacity to produce pharmaceuticals. furthermore, a large burden of hiv- and tuberculosis in africa could exacerbate the severity of infection and may affect vaccine immunogenicity. this review discusses global efforts to develop diagnostics, therapeutics and vaccines, with these considerations in mind. we also highlight vaccine and diagnostic production platforms that are being developed in africa and that could be translated into clinical development through appropriate partnerships for manufacture. coronaviruses are ubiquitous rna viruses that are responsible for endemic infections in humans and other animals, and sporadic outbreaks of potentially fatal respiratory disease in humans. four human coronaviruses, namely hcov- e, hcov-oc , hcov-nl and hcov-hku , circulate in the human population, causing the common cold, with some causing potentially life-threatening disease in infants, young children, older individuals and individuals who are immunocompromised . in the recent past, two additional coronaviruses have crossed the species barrier from other animals to infect humans. these are severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov), which emerged in and , respectively , . in december , a novel betacoronavirus, subsequently named sars-cov- , was implicated in an outbreak of respiratory disease in wuhan, china . the first cases to be reported presented as atypical pneumonia and were traced to the huanan seafood wholesale market, although cases without any association with the market, and predating the putative index cases, were subsequently recognized. following these first reports, community transmission rapidly ensued, culminating in a global pandemic , . the virus is speculated to have originated in bats and possibly to have passed through another host before infecting humans, but an intermediate host or intermediate hosts have yet to be defined. this remains the subject of considerable debate, and recent work suggests that the host receptor-binding motif of sars-cov- was acquired through recombination with a pangolin coronavirus [ ] [ ] [ ] , but further work is needed to establish the origin of the virus. infection with sars-cov- in humans manifests as coronavirus disease- (covid- ) , a spectrum of disease that ranges from asymptomatic infection to acute respiratory distress syndrome with multisystem involvement. older individuals and individuals with co-morbidities are at greatest risk . in individuals who are symptomatic, fever and cough are most commonly reported, although sore throat, shortness of breath, fatigue, anosmia, dysgeusia and gastrointestinal involvement are also frequently observed , . extrapulmonary manifestations of covid- are being increasingly recognized. among adults with preexisting diabetes mellitus, diabetic ketoacidosis may be a common complication and is associated with a poor prognosis , . according to the international diabetes federation, africa has an estimated . million adults aged between and years living with diabetes and is the region with the highest proportion of undiagnosed diabetes . neurological and neuropsychiatric complications have also been recognized as presenting or complicating factors . children generally have a milder course of disease and are more likely to be asymptomatic, although recent reports have described hyperinflammatory shock in children who were previously asymptomatic that seems similar to kawasaki disease [ ] [ ] [ ] . further studies are required to determine the prevalence of this phenomenon and to define the immunological the first documented cases in a disease outbreak. a rare condition associated with inflammation in blood vessels that most commonly presents in children under years of age. drivers of the illness. however, the contrasting presentation of covid- in children and adults suggests that the immune responses of children and adults to sars-cov- may be different. the virus continued to spread globally, prompting the implementation of radical travel restrictions and social distancing measures . at the time of writing this article, the virus has resulted in over million confirmed infections and has claimed the lives of over , people . as of august , there have been over . million confirmed cases of covid- in africa, with , deaths reported (africa cdc) there is concern that the pandemic may pose an even greater risk to countries in africa owing to their weak health-care infrastructure, large burden of co-infections, including hiv- and tuberculosis, and ongoing outbreaks of emerging and re-emerging infections such as ebola virus (democratic republic of congo) and lassa haemorrhagic fever (nigeria) that will divert much-needed resources away from the fight against covid- (ref. ) ( fig. ). differences in global population demographics and health status are also likely to affect the severity of the pandemic in different regions and are a major concern in africa ( fig. ). in addition to the health-care infrastructure, the general infrastructure throughout africa is also highly variable, and thus access to appropriate medical care is an important determinant of covid- disease outcome. the number of hospital beds in a population of , individuals varies from as low as in mali to in libya. however, libya is an exception for the region, and many central and west african countries are at the lower end of this range and generally report fewer than beds per , individuals. this is in stark contrast to other developed countries such as germany and the usa, where and . beds per , individuals are available, respectively. a similar trend is also seen for the number of doctors per , individuals. in more than african countries, less than doctor is available (per , individuals), whereas germany and the usa report and doctors (per , individuals), respectively . concerns have been raised regarding the impact of the pandemic on other diseases and access to essential medicines . for example, according to a newspaper article, the ministry of health in zimbabwe reported a % increase in malaria infections compared with (ref. ). many african countries lack the capacity to implement widespread testing, including the identification of asymptomatic and mild infections that are major drivers of the pandemic . although it is difficult to determine the number of tests conducted in many africa countries, the publicly available data clearly highlight the limited testing capacity on the continent. south africa is currently conducting the largest number of tests per , individuals ( . / , individuals), whereas many other countries, including ethiopia, nigeria, zimbabwe, tunisia, senegal and rwanda, perform fewer than . tests/ , individuals. this is markedly less than in the usa ( . / , individuals), the uk ( . / , individuals), italy ( . / , individuals) or germany ( . / , individuals) . similar infrastructure limitations constrain the development of prophylactic vaccines and therapeutic interventions, which results in a concerning reliance on developed countries. another important consideration in the response to the pandemic in africa will be to limit the impact of the virus on vulnerable economies where prolonged lockdowns may not be feasible. the first case of covid- in africa was reported in egypt on february ; subsequently, infections - ) pandemic. this is worsened by the high burden of infectious diseases, which may worsen disease outcome and compete for the available resources. a further challenge is the dire economic consequences of prolonged lockdowns in countries with weak economies. www.nature.com/nrmicro have been documented in other african countries, with south africa reporting the highest number of cases . interestingly, in spite of the obvious challenges in combatting the growing pandemic, african countries have observed a delay in the exponential growth trajectory that has been described by countries in the developed world . this may be partly attributable to lower testing capacity in the region and the impact of implementing lockdowns in the early phase of the pandemic. the warmer climate has also been proposed to influence the spread of covid- , which could explain the delayed pandemic in africa compared with the rest of the world, although this is largely speculative (box ). the transition into winter in southern africa has been accompanied by an increase in sars-cov- infections, further complicated by seasonal influenza and limited influenza vaccine availability. in this review, we discuss the global efforts to develop diagnostic tests and therapeutic options to treat covid- , as well as the vaccine platforms for immunization, with a focus on the opportunities and challenges for africa. the diagnosis of sars-cov- poses a major challenge owing to the prevalence of asymptomatic infections, pre-symptomatic infections with high viral loads in the upper airways (probably at peak infectivity) and the range of non-specific symptoms that manifest in individuals who are symptomatic , . widespread testing is therefore critical to identify infected individuals who are asymptomatic, pre-symptomatic and symptomatic, and to enable contact tracing and isolation . whereas this has been highly successful in countries such as germany and south korea, it is not generally possible in most african countries where the infrastructure is weak. indeed, in countries such as south africa, where widespread community testing was attempted, this has resulted in a very large backlog of tests and delays of weeks for returning test results, which are then rendered meaningless for quarantining of cases and containment . in many african countries, testing is only available for severe cases of presumed covid- , and self-isolation is recommended for less severe cases. therefore, reported cases and true prevalence do not equate. accordingly, the capacity provided by academic laboratories and pharmaceutical companies is being leveraged to increase testing capacity further, as has been necessary even in developed countries . diagnosis of acute infection is by pcr with reverse transcription of respiratory tract specimens, which is generally performed in central laboratories with specialized equipment . scale-up of testing is a major challenge for countries in africa, owing to laboratory infrastructure, costs and availability of test reagents that are largely imported and currently stretched global supply chains. a recently launched, continent-wide initiative, population demographics and prevalence of known co-morbidities for each of the six world health organization regions. although africa reports a lower average age compared with other regions, the burden of infectious disease is disproportionately high. both hiv and tuberculosis are associated with an increase in coronavirus disease- (covid- ) disease severity, and their prevalence in africa will increase the risk of fatal infection for a large number of people. there is also a large proportion of individuals in africa with raised blood pressure, which is a known risk factor for severe disease. other known co-morbidities, including raised cholesterol, raised glucose and obesity, are less prevalent in africa compared with the other reported regions. raised blood pressure (systolic blood pressure ≥ mm/hg or diastolic blood pressure ≥ mmhg), raised fasting blood glucose levels (≥ mmol/l or taking medication), raised total cholesterol levels (≥ mmol/l) and body mass index (bmi) > are reflected as age-standardized estimates. all data shown reflect the latest available data from the world health data platform (global health observatory). the number of people living with hiv- /aids (in millions) reflects the population of individuals who were infected in , tuberculosis cases shown reflect the number of incident cases in and malaria cases reflect the estimated number of cases in . nature reviews | microbiology the africa medical supplies platform, seeks to leverage collective purchasing for procurement of testing supplies, personal protective equipment, medical equipment and even, potentially, future vaccines . in addition, repurposing of rapid, automated molecular diagnostics platforms such as genexpert® (cepheid), which is widely used for the diagnosis of tuberculosis in south africa, has the potential to decentralize and accelerate testing in certain countries, including using mobile testing centres, although test kits are also in limited supply. however, this has to be understood in the light of the potential for unintended consequences on the management of tuberculosis, with fewer diagnostic platforms being available as a result of increased sars-cov- testing. testing for tuberculosis in south africa has reportedly decreased by % during the lockdown period and, concurrently, the weekly average of microbiologically confirmed tuberculosis cases decreased by % (ref. ). recently, a rapid method of heating samples prior to quantitative pcr with reverse transcription has shown promise to improve the turnaround time for testing and bypasses the need to order rna extraction reagents or kits . furthermore, a rapid crispr-cas -based test has also been developed to diagnose infection from respiratory sample-derived rna . the test yields a result within h and is less reliant on sophisticated laboratory infrastructure and test reagents that are in limited supply. implementing this test in africa could be a useful way of expanding the current testing capacity and could offer a faster turnaround time for high-priority cases. serology-based testing approaches have been proposed, but the delay between infection and the development of detectable antibodies (within days) renders this approach impractical for the diagnosis of acute infection , . nonetheless, these tests are critical for seroprevalence studies and to identify appropriate donors for convalescent sera, and potentially for the isolation of monoclonal antibodies that can be developed as therapeutics. serology studies are also crucial for understanding the longevity of the antibody response after infection, with the key caveat that it is not known whether humoral responses are a correlate of immunity against the virus. in addition, preliminary data suggest that not all individuals who are infected may seroconvert , and early evidence is emerging that antibody levels may wane rapidly during the convalescent phase . several serological assays have already been developed, and binding antibodies against the spike and nucleocapsid proteins are both indicative of past sars-cov- infection , . many of these assays are also commercially available, but their specificity and sensitivities seem to be variable . a major outstanding question is which antigen, or region of the antigen, is most appropriate for serology testing. most assays have favoured the spike glycoprotein for the detection of an immune response against the virus, although it is worth noting that the nucleocapsid is the most abundant viral antigen . recent work has suggested that the receptor-binding domain alone may be sufficient to detect antibody responses to sars-cov- , and given that it is not conserved between coronaviruses, its use may limit cross-reactivity arising from other coronavirus infections . nonetheless, a nucleocapsid-based elisa (enzyme-linked immunosorbent assay) may be the easiest to implement in an african context as the antigen could easily be produced locally at low cost. nucleocapsid could be produced in escherichia coli, pichia pastoris or even in plants, as has been reported for the nucleocapsid proteins of three bunyaviruses, two of which were used successfully in validated assays [ ] [ ] [ ] . moreover, the biovac institute in south africa has the capacity for bacterial fermentation and the required infrastructure for downstream processing, and a new plant-based production facility (cape bio pharms) is currently generating s protein derivatives as reagents. although the spike glycoprotein is heavily glycosylated and needs to be expressed in a more complex expression host to ensure appropriate post-translational modifications, both mammalian cells and plants would be suitable to produce both spike and nucleocapsid, and novel approaches to enhance recombinant glycoprotein production in plants have also been developed in south africa . given the optimistic development timeline of - months before any vaccines could be available for widespread use, it is clear that these efforts will not box | potential impact of climate on sars-cov- dissemination the comparatively low incidence of coronavirus disease- (covid- ) in africa has raised the possibility that climate could influence the spread of severe acute respiratory syndrome coronavirus (sars-cov- ). there is some circumstantial evidence describing a possible association between higher temperatures and lower severity of covid- to support this hypothesis; however, outbreaks in malaysia, hong kong, australia and south africa seem to be inconsistent with this theory as large numbers of infections have been reported despite higher temperatures [ ] [ ] [ ] . the influence of climate could potentially account for the severity of the pandemic in central china and northern italy, where winter may have been particularly conducive to the spread of the virus . these cold conditions are reminiscent of the environment in which sars-cov first emerged in china in november (ref. ). although these observations are compelling, it is noteworthy that many of these studies have yet to undergo formal peer review, and the accuracy of species distribution models is constrained by variability in global testing capacity . for example, infections in many african countries are expected to be an underestimate that reflects the lower number of tests conducted. it is also acknowledged that numerous other variables could influence the spread of the virus and may confound interpretations of the impact of climate. these variables may include variation in population density and age distribution, timely lockdown measures, adherence to social distancing protocols or even childhood vaccination with mycobacterium bovis bacille calmette-guérin as examples . the impact of differing behaviour, with increased social mixing, in the winter months also cannot be discounted . as with many respiratory pathogens, both middle east respiratory syndrome (mers-cov) and sars-cov exhibit decreased viability in the laboratory following exposure to increasing temperature and humidity , . similar observations have also been reported for influenza virus and respiratory syncytial virus, for which the incidence of infection is highest under cold and dry conditions, which results in seasonal cycles of infection , . a similar seasonality has also been observed for other endemic human coronaviruses, which led to the speculation that sars-cov- may also conform to a seasonal cycle of infection . however, although all four endemic human coronaviruses (hcov- e, hcov-oc , hcov-nl and hcov-hku ) exhibit a marked winter seasonality , the pathogenic human coronaviruses (mers-cov and sars-cov) do not conform to such a defined infection cycle. for example, mers-cov generally occurs mostly during summer months in the middle east despite temperatures often exceeding °c . by contrast, the highest incidence of sars-cov was reported during the winter months, although the outbreak continued to spread throughout spring in hong kong , . therefore, more research is needed to define the impact of climate on the spread of sars-cov- . a diagnostic test that measures the presence of antibodies in blood to determine exposure to pathogens or to diagnosis autoimmune diseases. sera obtained from individuals who have recovered from an infectious disease and contain antibodies against the pathogen. www.nature.com/nrmicro affect the first wave of the pandemic . more importantly, the lack of manufacturing capacity in africa and the global demand for immunization against the virus will further delay the availability of vaccines in the region. repurposing existing drugs presents a feasible short-term strategy to manage the pandemic, especially given that some of the drug candidates are already available and have an established safety profile in humans . these drugs would face lower regulatory barriers for approval and, in addition to being used for treating active infections, may have potential to be used as prophylactics for individuals at high risk, such as health-care workers or those who have been in contact with documented cases of infection. currently, two treatments have been shown to have an effect on the outcome of covid- . the broad-spectrum antiviral drug remdesivir has been shown to shorten the recovery time in adults admitted to hospital with severe covid- in a publication of preliminary results from a double-blind, randomized, placebo-controlled trial in the usa . however, remdesivir did not reduce mortality. by contrast, initial data from the recent recovery trial in the uk suggest that daily oral or intravenous doses of dexamethasone ( mg for days) reduced mortality by one-fifth in hospitalized patients with proven covid- requiring oxygen therapy, and that mortality was reduced by one-third in patients who needed mechanical ventilation . it had no effect on patients hospitalized with covid- who were not requiring oxygen. the reductions in mortality were seen in patients whose symptoms started > days before receipt of the drug. the fact that a commonly used corticosteroid could reduce mortality in this trial is promising, as numerous other corticosteroids such as prednisolone and hydrocortisone (which were options in the recovery trial in pregnant women) are equally available, and some of them are manufactured in africa, which means that access may be less of an issue than for other more novel medicines. more commonly available medicines have been, and some continue to be, used in investigational treatments for covid- . the commonly available antimalarials chloroquine and hydroxychloroquine were among the first to be investigated. initial studies were small and underpowered, and some combined hydroxychloroquine with azithromycin and some proved highly controversial in relation to their conduct, leading to retraction . one of the arms of the recovery trial included hydroxychloroquine, and on june the independent data monitoring committee review of the data concluded that there was no beneficial effect of hydroxychloroquine in patients hospitalized with covid- (ref. ). shortly after, the world health organization (who) announced that recruitment for the hydroxychloroquine arm of the solidarity trial was being stopped , . all experimental treatments should either be introduced into properly conducted clinical trials or, if a country decides to use such a medicine outside a trial, then it should be controlled according to the who's monitored emergency use of unregistered interventions (meuri) framework, whereby it can be ethically appropriate to offer individuals investigational interventions on an emergency basis, in the context of an outbreak characterized by high mortality . large-scale adaptive studies such as the recovery and solidarity trials continue, and such trials will reduce the time taken for randomized clinical trials . several african countries, including south africa, burkina faso and senegal, are in the process of joining the solidarity study. similarly, small studies are ongoing in several countries, looking at the utility of convalescent plasma from patients who recently recovered from covid- as potential prophylaxis or treatment . the need for randomized control trials using this treatment modality has been stressed . unlike other investigational medicines, convalescent plasma can be readily produced, even in low and middle-income countries, through the national blood transfusion service, making it an attractive option for study. however, scaling production for use is the rate-limiting step for this intervention. preliminary studies identified monoclonal antibodies with the ability to neutralize sars-cov- , which may also be important candidates for both treatment and prophylaxis, although similar issues with manufacture are a challenge , . there is increasing recognition that pathophysiology of severe covid- includes an appreciable component of hyperactivation of inflammatory responses, manifesting as a cytokine storm and secondary haemophagocytic lymphocytic histiocytosis. in addition to the findings relating to dexamethasone detailed above, various immune-modulating drugs have been proposed as treatment options for covid- . the il- inhibitors tocilizumab (actemra; roche) and sarilumab (kevzara; sanofi and regeneron), which are used to treat arthritis, are already being used in patients with covid- (nct ) . their mechanism of action involves the prevention and the inhibition of the overactive inflammatory responses in the lungs. both drugs have entered phase iii clinical trials for sars-cov- . a late-stage clinical trial with another il- inhibitor, siltuximab (sylvant; eusa), started in italy in mid-march (nct ). anti-inflammatory drugs used in combination with an antiviral drug such as remdesivir may increase the potential of the drug to improve disease outcome . genentech has recently initiated a phase iii trial (remdecta) to study the efficacy and safety of tocilizumab and remdesivir in patients hospitalized with severe covid- pneumonia (nct ). additionally, the covacta study (nct ) will evaluate tocilizumab and standard of care versus standard of care alone in a similar cohort . patients who have chronic medical conditions may be at higher risk for serious illness from covid- , including those with pulmonary fibrosis . the antifibrotic drug pirfenidone (genentech) has already entered a study to evaluate its efficacy and safety (nct ). recombinant angiotensin-converting enzyme (ace ; apn ) that lacks the transmembrane region of the protein was developed by apeiron biologics for the treatment of acute lung injury and pulmonary artery hypertension. the soluble ace has the potential to reduce lung injury by activating the anti-fibrotic and a disproportionately large cytokine response that promotes inflammation and is harmful to the host. nature reviews | microbiology anti-inflammatory angiotensin ( - )-mas receptor axis of the renin-angiotensin-aldosterone system, and by acting as a decoy and preventing infection by binding to the sars-cov- virus and inactivating it. apn is being tested in a phase i trial in china, and approval has been secured to carry out phase ii trials in austria, germany and denmark (nct ). currently, there are no targeted therapies for covid- . however, numerous drug discovery programmes are in progress, and a recent study reported a structure-based drug design strategy, as well as virtual and high-throughput screening to identify lead compounds that bind to the main protease of the virus (m pro ; also known as cl pro ) . the active site of the protease is highly conserved among coronaviruses, making a strong case for pursuing an m pro -targeting drug. the organoselenium drug ebselen, which is an anti-inflammatory and antioxidant, showed high affinity for m pro and showed promising antiviral activity (concentration that gives half-maximal response ec = . μm). thus, the presented approach may greatly accelerate the discovery of drug leads with potential in the clinic. the drug discovery and development centre (h d) based at the university of cape town is the only fully integrated drug discovery centre in africa that has taken a drug into a phase ii clinical trial. the centre has very strong collaborations with the pharmaceutical industry and mmv, a leading product development partnership, as well as the infrastructure and expertise to find potential therapies against covid- . h d has assembled chemical libraries for its malaria and tuberculosis projects that could be screened to identify possible drug leads against sars-cov- ; however, this will require additional resources and funding because the centre is contractually focused on antimalarial and anti-tuberculosis drug development. the infrastructure for large-scale, high-volume vaccine manufacturing is largely absent in africa, and the rapidly escalating covid- pandemic highlights the urgent need for capital investment in the region to lessen reliance on developed countries. the few facilities that are available are specialized, and are not well-suited to produce vaccines for sars-cov- (table ) . it is also anticipated that it would take a minimum of months to build a suitable manufacturing plant under ideal conditions, and therefore to contribute to the global covid- vaccine initiative, african developers will need to outsource large-scale manufacturing in the short term. the african vaccine manufacturing initiative, which aims to develop local manufacturing capacity in africa, has established a working group and is actively engaged with key stakeholders to meet the local need for a vaccine. innovative biotech (nigeria) has already partnered with medigen (usa) and merck (germany) to apply their insect cell production platform to producing virus-like particles with the intention of initiating a clinical trial in nigeria. similarly, the ethiopian public health institute (ephi) is planning to partner with techinvention (india) to produce the sars-cov- spike protein in a yeast-based fermentation system, although limited details are available (personal communication, s. agwale, ceo of innovative biotech). last, biovac (south africa) has modern facilities at a modest scale and has initiated a feasibility study for a large-scale facility with an annual minimum production capacity of million vaccine doses for covid- and future pandemic vaccines, as well as vaccines for routine immunization use (personal communication, p. tippoo, head of science and innovation, biovac). given the global demand for a covid- vaccine, it is likely that even when a suitable candidate is approved for human use, there will be a considerable delay before it is available in africa. this is not unprecedentedduring the h n influenza pandemic, a global shortage of influenza vaccines resulted in limited supplies being provided for countries in the region, and, in fact, the vaccines only became generally available after (ref. ). this unfortunate, but entirely plausible, scenario may necessitate prioritizing high-risk groups, such as health-care workers and older individuals, to receive the first sars-cov- vaccines to reach africa. more than vaccine candidates are currently in preclinical development around the world, and vaccines are already being tested in clinical trials , (table ) . these vaccines are mostly focused on eliciting immunity against the spike glycoprotein, although other viral antigens may also have a role in vaccine-mediated protection (box ). the speed of clinical deployment of these vaccines is unprecedented, but there are concerns regarding the longevity of immune responses and the potential although the rapid progress to clinical testing is encouraging, it is still too early to determine whether they will confer immunity against sars-cov- infection or whether they will ameliorate the disease course following infection. the only peer-reviewed report of a sars-cov- vaccine in clinical trial to date is for cansino biologics' ad -ncov vaccine, which recently completed phase i testing. encouragingly, the vaccine elicited both binding antibodies and antigen-specific t cells, although, disappointingly, only % of volunteers developed neutralizing antibodies in the low ( × viral particles) and medium ( × viral particles) dose regimens. however, % of the high-dose group ( . × viral particles) developed neutralizing antibodies. perhaps unsurprisingly, the high-dose group also reported a higher incidence of adverse effects following vaccination and only the low and intermediate doses will be pursued in phase ii trials . despite the absence of suitable facilities for current good manufacturing practice (cgmp)-compliant vaccine or therapeutics manufacturing in most of africa, considerable expertise in preclinical vaccine development is also available in academic institutes, and vaccines could be manufactured on contract for clinical trials as was the case for the south african aids vaccine initiative . accordingly, groups at the university of cape town (south africa), the national research centre (egypt) and the kenya aids vaccine initiative (kavi) have all confirmed that early-stage research on sars-cov- vaccine development is underway -although further details have not been disclosed . important considerations for these vaccines will be the cost, their safety in individuals who box | sars-cov- virus structure and targets for vaccine development severe acute respiratory syndrome coronavirus (sars-cov- ) comprises pleomorphic virions, ranging from to nm in diameter, with prominent glycoprotein spike proteins projecting from the virus surface . the virion also contains the membrane, envelope and nucleocapsid proteins, which encapsulate the viral genome and accessory proteins (see the figure, left). the spike protein is a glycosylated type fusion protein that mediates infection by binding the host membrane-anchored angiotensin-converting enzyme (ace ) . the glycoprotein is organized into extracellular (s ) and membrane-spanning (s ) subunits, which mediate receptor binding and membrane fusion, respectively (not shown). binding of the spike protein to ace results in a conformational change that enables the dissociation of the s subunit and the insertion of the fusion peptide into the host membrane . the spike glycoprotein is the primary target of vaccine development, based on the premise that neutralizing antibodies against spike will prevent viral entry into susceptible cells (see the figure, right). this is supported by preclinical immunogenicity studies, for the related middle east respiratory syndrome coronavirus (mers-cov) and sars-cov, for which immunization with spike-based vaccines elicited protective antibody responses , . more recently, neutralizing antibodies against the sars-cov- spike have been reported in natural infection; these are readily elicited and frequently target the receptor-binding domain in s (ref. ). the potential role of cell-mediated immunity in coronavirus vaccines generally has not been as well explored. it is reasonable to expect that cellular immune responses would contribute to viral clearance and ameliorate the severity of the disease, as well as support the development of antibody responses. accordingly, robust and durable cellular responses have been observed against the spike, membrane, envelope and nucleocapsid proteins in patients who recovered from sars coronavirus infection [ ] [ ] [ ] . ultimately, both cell-mediated and humoral responses are desirable in a vaccine, especially given the observation that cellular responses are longer lived than antibodies following infection with sars coronaviruses , . mhc, major histocompatibility complex. humoral immunity: • neutralizing antibodies prevent interaction of spike with ace • antibody effector functions can contribute to viral clearance • b cell memory for durable immunity genetic immunization with plasmid dna is perhaps the easiest vaccine modality to develop for clinical trials as the manufacturing process is well established, the incumbent costs are low compared with other platforms and multiple clinical trials have shown their safety. technological advances have also substantially reduced the time from identifying the viral sequence to initiating immunizations in humans . accordingly, dna vaccines have been advanced into the clinic in response to several emerging pathogens, including mers-cov, and inovio pharmaceuticals (usa) have already completed recruiting participants to initiate a phase i trial with a candidate dna vaccine against sars-cov- (nct ) . recent preclinical data demonstrated that the vaccine elicited neutralizing antibodies in both mice and guinea pigs, and an unrelated study reported that immunization with a dna vaccine protected against viral challenge in macaques , . genetic immunization is well-suited to clinical development for africa, and candidate vaccines could be manufactured to cgmp standards using one of the contract manufacturers offering this service. however, there are no licensed human vaccines based on this platform, and the current delivery methods are not suitable for large-scale immunization. host-restricted viral vectors are another promising vector platform for immunization in africa . replication-deficient chimpanzee adenovirus-based vaccines have shown promise for several emerging viruses, and given their simian origin, they circumvent concerns for vector-specific immunity as was observed when using human adenoviral vectors for immunization . a single dose of a mers-cov- vaccine using this platform was reported to elicit protective immunity in non-human primates . more recently, a single immunization with chadox encoding the sars-cov- spike protected against pneumonia and lowered viral loads in both bronchoalveolar lavage and respiratory tract samples in macaques following challenge . this effect was observed in the absence of high titres of neutralizing antibodies and the impact of the vaccine was to ameliorate severe disease rather than to prevent infection. although it is disappointing that the vaccine did not confer sterilizing immunity in monkeys, it is noteworthy that the monkeys only received a single immunization and that the inoculum used for challenge was high. it should be noted that the high-challenge inoculum was conceived to determine whether immunization resulted in vaccine-mediated enhancement of infection, and that there was no evidence to suggest that this would be a concern . this is the vaccine being pursued by the university of oxford in collaboration with astrazeneca that is now in phase ii testing. a clinical trial for this vaccine has recently been initiated in johannesburg (south africa), and this is the first vaccine for sars-cov- to be tested in africa. the manufacturing cost of chadox would be far less than for a subunit vaccine and, moreover, no adjuvant is needed for immunization. poxvirus-based vectors are similarly attractive: they elicit strong humoral and cellular immune responses, can be manufactured at low cost and are stable in the absence of a sustained cold chain , . in addition, they can accommodate larger genetic insertions, which could be exploited to encode multiple sars-cov- genes (such as the spike, nucleocapsid, membrane and envelope antigens) and could potentially produce virus-like particles. suitable examples of candidate poxvirus vectors include the attenuated orthopoxviruses modified vaccinia ankara (mva) and nyvac , the avipoxviruses canarypox virus (alvac) and fowlpox virus (fwpv) , and the capripoxvirus lumpy skin disease virus (lsdv) . mva is the most widely explored of these vectors. having been attenuated by more than passages in chick embryo fibroblast cells, mva has a well established safety record, including in individuals who are immunocompromised, and has recently been approved as a vaccine against smallpox , . nyvac was engineered by the purposeful deletion of genes involved in host range and pathogenicity; it causes no disseminated disease in immunodeficient mice, like mva, and is unable to replicate in humans . several mva-vectored vaccines of particular relevance to africa have shown promise in clinical trials, usually in prime-boost regimens together with other vectors such as dna or adenovirus. these include vaccines against hiv- (ref. ), mycobacterium tuberculosis and box | immunological challenges for sars-cov- vaccine development two concerns have been raised that could undermine the vaccines against severe acute respiratory syndrome coronavirus (sars-cov- ) in clinical testing: the longevity of immunity, and the potential for adverse effects following sars-cov- infection in immunized volunteers. the durability of antibody responses has implications for vaccine development, as immunization may need to induce stronger immunity than natural infection. this concern is partly due to observations of waning neutralizing antibody titres after sars coronavirus infection, and a lack of knowledge regarding the potential for sars-cov- re-infection [ ] [ ] [ ] . encouragingly, preliminary data suggest that rhesus macaques may be resistant to challenge with sars-cov- after clearing the primary infection . the duration of this protection remains unclear, as do the correlates of immunity. low neutralizing antibody titres were recently reported in % of patients who recovered from mild infection with sars-cov- , which suggests that cellular responses may have an important role in viral clearance. however, it is plausible that neutralizing antibody titres correlate with disease severity and merely reflect the extent of antigenic stimulation . another concern is vaccine-induced enhancement of infection. this can manifest as either antibody-dependent enhancement or cell-mediated inflammatory responses that result in pathology following exposure to the virus. accordingly, type t helper cell-mediated lung pathology with eosinophilic infiltrates has been observed in vaccinated and challenged animals for both middle east respiratory syndrome coronavirus (mers-cov) and sars-cov [ ] [ ] [ ] . the potential impact of antibodydependent enhancement in the context of coronavirus vaccines has not been as well defined, although the phenomenon has been described for a monoclonal antibody targeting the mers coronavirus spike glycoprotein . preliminary data suggest that antibody-dependent enhancement may account for the severity of covid- in some cases, where previous exposure to other coronaviruses may have elicited responses that enhanced infection, although this remains to be determined . www.nature.com/nrmicro ebola virus . lsd, a notifiable disease of cattle worldwide, is prevalent in most african countries, and the live-attenuated neethling vaccine strain is widely used to control the disease on the continent . lsdv is being developed both as a multivalent cattle vaccine vector , and as a host-restricted hiv- vaccine vector . it has been shown to have no adverse effects in immunodeficient mice, and although this vector could not be used in countries free of lsdv, it has potential as a human vaccine in sub-saharan africa . together with mva and nyvac, the avipoxvirus vectors alvac (attenuated canarypox virus) and fwpv are probably more realistic targets for rapid clinical development, as they have also undergone testing in humans, and alvac is already licensed for several veterinary applications plant-based vaccine protein production is an emerging technology that is well-suited to resource-limited areas given the capacity of the system for rapidly scalable production, the low manufacturing costs and the less sophisticated infrastructure requirements than mammalian expression systems . the platform is well established to produce diverse classes of recombinant proteins, and recent advances in expression technologies and molecular engineering have also enabled improvements in glycoprotein production in plants , . encouragingly, a preliminary pilot study suggests that these appro aches can be applied to produce the sars-cov- spike in nicotiana benthamiana plants, warranting further testing of the recombinant antigen in preclinical vaccine immunogenicity models . three leading plant biotechnology companies, medicago inc. (canada), ibio inc. (usa) and kentucky bioprocessing inc. (usa), have already announced the successful production of candidate virus-like particle vaccines against sars-cov- . although plant-based manufacturing of recombinant protein antigens may be the most suitable solution for africa, it may also pose a challenge for manufacturing. the major advantages of plant-based vaccine production for sars-cov- in africa are the lower costs and the potential for rapid production scale-up to accommodate the large demand for a vaccine. this is best demonstrated in the context of influenza vaccine development, as a fully formulated virus-like particle vaccine was produced within weeks following release of the viral sequence . this rapid development timeline supported the production of million doses of the vaccine within month . however, despite the costs to establish a gmp-compliant plant-based manufacturing facility being considerably less than those for the equivalent mammalian platform (for example, us$ - million versus us$ - million, respectively), they are not insignificant, and the capital investment required has been prohibitive for africa . furthermore, there are few suitable contract manufacturing organizations worldwide, and these are already invested in their own sars-cov- vaccine development programmes. several recent preliminary data have suggested a possible correlation between bacille calmette-guérin (bcg) vaccination and lower prevalence and mortality due to covid- (refs [ ] [ ] [ ] [ ] ). the bcg vaccine is one of the most widely used vaccines worldwide and has been used to vaccinate against tuberculosis for nearly years. the vaccine comprises a live, attenuated form of mycobacterium bovis, which provides protection against disseminated forms of tuberculosis in infants but gives variable protection against pulmonary tuberculosis in adults , . non-specific cross-protection against other pathogens, including those causing respiratory tract infections, has also been documented . this effect may be attributable to altered expression of host cytokines and pattern-recognition receptors, as well as the reprogramming of different cellular metabolic pathways that, in turn, increases the innate immune response to other pathogens , . however, potential correlation between bcg vaccination and covid- severity should be interpreted with caution. first, it is unlikely that bcg vaccination at birth will still provide non-specific cross-protection against viral pathogens in older individuals. second, the correlation could be influenced by numerous unknown confounding factors, including variation in testing between countries, which leads to differences in the recorded case numbers; differences in average population age, ethnic and genetic backgrounds; the stage of the pandemic in each country; and different approaches to mitigating the spread of the disease in different countries. numerous clinical trials are presently underway to determine whether bcg vaccination reduces the incidence and severity of covid- in health-care workers and older individuals (supplementary table) . a trial has also started in egypt (nct ), where disease severity and mortality in patients with covid- will be compared between those with positive and negative tuberculin tests. in brazil, the bcg vaccine will be given to patients with covid- as a therapeutic vaccine to evaluate the impact on the rate of elimination of sars-cov- , the clinical evolution of covid- and the seroconversion rate and titres of anti-sars-cov- antibodies. as the bcg vaccine has been administered to most neonates in south africa and france until recently, these trials will also investigate the effect of revaccination with the bcg vaccine. in addition, a new modified version of bcg, namely vpm , which expresses listeriolysin instead of urease c, will be tested in health-care workers and older individuals in germany . securing a reliable supply of bcg vaccine doses could be a challenge in africa if re-immunization shows promise, as there is limited manufacturing capacity for the vaccine on the continent. historically, shortages of the vaccines were documented in % of countries on the continent between and (ref. ). this was largely due tuberculosis diagnostic tests that involve the intradermal injection of bacterial antigens to determine whether the recipient mounts an immune response at the site of injection. nature reviews | microbiology to lack of supply, but the limited availability of financing, procurement shortcomings and ineffective vaccine management also contributed to the shortage. the low price for a bcg vaccine and limited investment has also reduced the incentive for manufacturers to redesign and improve production processes in the region. from to , the -tokyo bcg strain was produced at the state vaccine institute in cape town, south africa; however, this was discontinued as the cost of importing the vaccine was lower than that of local manufacture. the potential impact of co-infections africa shoulders a considerable burden of co-infections. although hiv- and tuberculosis may be the most important infections when considering potentially enhanced covid- disease severity, the high incidence of malaria and helminth infections as well as multiple ongoing outbreaks of ebola virus disease, lassa fever, cholera, measles, yellow fever, hepatitis e and chikungunya virus all represent infections with unknown interactions with sars-cov- . the high prevalence of hiv- and tuberculosis in sub-saharan africa presents an important but largely unknown challenge for the continent with regard to covid- . the urgent question that needs answering is whether individuals with hiv- , or those with past or current tuberculosis, have a higher risk of infection or greater morbidity and mortality from covid- . of the . million people living with hiv- globally, . million live in sub-saharan africa, and it is estimated that % are accessing antiretroviral therapy and % are virally suppressed . although individuals who are immunocompetent with well-controlled hiv- infections may be at no greater risk for covid- , there remains a considerable number of individuals with low cd counts and uncontrolled hiv- viraemia who may be at risk of severe disease. to date, there have been two published reports of concurrent covid- and hiv- infection , . although the cohort was an extremely limited group of patients predominantly established on antiretroviral therapy, the pattern of clinical disease did not differ from that observed in the general population, but more research is needed to confirm this result. the severity of other respiratory infections concomitant with hiv- may provide some clues: although the immunopathogenesis of sars-cov- is probably distinct in several aspects from influenza viruses, there are some shared clinical features. hiv- infection is associated with a greater susceptibility to influenza virus infection, increased severity of influenza-related disease and poorer prognosis in patients who are severely immunocompromised . a large south african study observed an eightfold higher incidence of influenza virus infection and a fourfold greater risk of death in the case of hiv- co-infection . paradoxically, there is also evidence that lower inflammatory responses in individuals who are immunocompetent and infected with hiv- may lead to milder influenza-related disease . in addition to altering the clinical course of disease, hiv- infections may result in poorer antibody responses that may lead to prolonged viral shedding, thereby influencing disease transmission . tuberculosis, a disease that causes chronic lung damage, may also present a challenge in the covid- era. there were approximately . million new cases of tuberculosis in africa in (ref. ). in a south african study of patients who were hospitalized for severe respiratory illness, those with influenza virus infection together with laboratory-confirmed tuberculosis had a . -fold greater risk of death . hiv- largely drives the tuberculosis epidemic in sub-saharan africa, and the 'triple-hit' of hiv- , tuberculosis and sars-cov- infection is consequently of considerable concern. a preliminary study suggests that hiv- infection increases the risk of mortality from covid- by . -fold, and this increased risk seemed to be independent of suppressed hiv- viral load due to antiretroviral therapy. individuals with current tuberculosis had a . -fold greater risk of death . these figures represent a modest increased risk compared with older age and co-morbidities such as diabetes in the same population, which suggests that hiv- and tuberculosis may not be considered major risk factors for covid- . although this would be considered good news, further studies are awaited to confirm these initial observations. the two main potential issues for using sars-cov- vaccines in individuals infected with hiv- are safety and efficacy. however, potential safety issues are likely to be restricted to use of certain vaccine modalities, such as live-attenuated or replicating vaccines, in individuals who are highly immunosuppressed. when considering vaccine efficacy, the magnitude and durability of immunity in individuals infected with hiv- for both vaccination against and natural infection with sars-cov- is unknown. to date, there are no reports describing immune responses to sars-cov- in individuals infected with hiv- . it is possible that individuals with hiv- may have incomplete immune reconstitution and impaired immunity that may influence vaccine safety and efficacy, even if they are receiving antiretroviral therapy, owing to persistent immune activation and incomplete recovery of t cell and b cell immunity , . suboptimal neutralizing antibody responses have been described following immunization against influenza virus or other pathogens in individuals infected with hiv- (ref. ). weaker antibody responses and lower influenza virus-specific memory b cell responses in individuals infected with hiv- were directly related to cd counts . it will be important to test candidate vaccines for their ability to generate immune responses in a range of high-risk groups, including patients with hiv- . several strategies may improve the magnitude and durability of vaccine responses in individuals infected with hiv- , such as higher doses, booster immunizations and/or the use of adjuvants . substantive data on the clinical and immunological interaction of hiv- , tuberculosis and covid- will emerge from africa in time for improved strategies to guide clinical management of patients who are co-infected and the vaccine regimens. finally, an important additional point to note is the indirect effects of covid- on health in africa within the setting of a high burden of infectious diseases. the who estimates that the disruption in vaccination due to www.nature.com/nrmicro disruption in supply could put million infants at risk of contracting vaccine-preventable diseases . several countries have reported reduced uptake of tuberculosis testing, and patients failing to collect tuberculosis medication or antiretroviral therapy owing to overwhelmed health-care systems, lockdown interventions and public fear of contracting covid- (ref. ). mitigating these interruptions in prevention, diagnosis and treatment, and ensuring that essential health services continue, will ultimately lower the overall impact of the covid- pandemic in africa. the ongoing covid- pandemic presents an unprecedented global humanitarian and medical challenge. although this has prompted unparalleled progress in the development of vaccines and therapeutics in many countries, it has also highlighted the vulnerability of resource-limited countries in africa. not only do these countries have limited testing capacity but the infrastructure to manufacture tests, vaccines and therapeutic drugs is largely absent, and few clinical trials are underway on the continent to combat sars-cov- . clearly, there is an urgent need for capacity development and the available resources should focus on solutions that are specific to the needs of the continent. for example, there is an urgent need to inexpensively manufacture viral antigens for serological testing: this will determine the seroprevalence of the virus where pcr-based testing is not available for mild infections. therapeutics development should focus on repurposing existing drugs, or using convalescent plasma that can rapidly be used to treat infection and could be prioritized for individuals who are at high risk. appropriate manufacturing partnerships need to be established to produce vaccines that could be tested and licensed on the continent, to limit reliance on global initiatives that may be overwhelmed by the global demand for a vaccine. in fact, this may present an opportunity for governments to finally invest in much-needed cgmp-compliant vaccine manufacturing facilities. although the situation is unquestionably dire, africa has an important 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protection in mice and induces increased eosinophilic proinflammatory pulmonary response upon challenge molecular mechanism for antibodydependent enhancement of coronavirus entry medical countermeasures analysis of -ncov and vaccine risks for antibody-dependent enhancement (ade) the authors acknowledge support from the south african medical research council with funds received from the south african department of science and technology, core funding from the wellcome trust ( /z/ /z) and funding from the south african research chairs initiative of the department of science and technology and national research foundation (grant number ). the authors contributed equally to all aspects of the article. the authors declare no competing interests. nature reviews microbiology thanks m. baylis, g. dougan, s. jiang and l. f. p. ng for their contribution to the peer review of this work. springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. supplementary information is available for this paper at https://doi.org/ . /s - - - . key: cord- -aapg af authors: tambo, ernest; tang, shenglan; ai, lin; zhou, xiao-nong title: the value of china-africa health development initiatives in strengthening “one health” strategy date: - - journal: global health journal doi: . /s - ( ) - sha: doc_id: cord_uid: aapg af implementing national to community-based “one health” strategy for human, animal and environmental challenges and migrating-led consequences offer great opportunities, and its value of sustained development and wellbeing is an imperative. “one health” strategy in policy commitment, partnership and financial investment are much needed in advocacy, contextual health human-animal and environmental development. therefore, appropriate and evidence-based handling and management strategies in moving forward universal health coverage and sustainable development goals (sdgs) are essential components to the china-africa health development initiatives. it is necessary to understand how to strengthen robust and sustainable “one health” approach implementation in national and regional public health and disaster risk reduction programs. understanding the foundation of “one health” strategy in china-africa public health cooperation is crucial in fostering health systems preparedness and smart response against emerging and re-emerging threats and epidemics. building the value of china-africa “one health” strategy partnerships, frameworks and capacity development and implementation through leveraging on current and innovative china-africa health initiatives, but also, mobilizing efforts on climatic changes and disasters mitigation and lifestyle adaptations strategies against emerging and current infectious diseases threats are essential to establish epidemic surveillance-response system under the concept of global collaborative coordination and lasting financing mechanisms. further strengthen local infrastructure and workforce capacity, participatory accountability and transparency on “one health” approach will benefit to set up infectious diseases of poverty projects, and effective monitoring and evaluation systems in achieving african union agenda and sdgs targets both in africa and china. the china-africa partnership is one of the most important geopolitical and economic relationships of the st century that has ushered a new era of investment in mutual health development [ ] . china has become the world's second-largest economy and offered africa various based on win-win cooperation. traditionally, china is willing to work together with africa to achieve mutual benefits by taking advantage of its status as assistanceprovider in tackling infectious diseases of poverty [ , ] . furthermore, since africa is home to seven of world's ten fastest growing economies, chinese investments in the health sector in the continent can produce substantial financial gains and generate invaluable public health commodities and other goods that are much needed [ , ] . the need for an african centre for disease control and prevention (cdc) was recognized at the african union special summit on hiv and aids, tb and malaria held in abuja, nigeria, in july . the africa cdc has launched year with the establishment of an african surveillance and response unit, which will include an emergency operations center and exchanges on china's national disease surveillance and reporting system [ ] . currently, africa continent is experiencing a rapid economic growth, with a gross domestic product (gdp) of $ . trillion usd in and is estimated to increase to $ . trillion usd by . health-care spending rose from $ . billion usd in to $ billion usd in across african countries [ ] [ ] [ ] . the fact that sub-saharan africa accounts for % of the world's population and % of the global burden of infectious diseases caused by poverty, millions of people could be lifted out of poverty through bilateral trade and cooperation between china and africa. increasing and robust new commitments of outbreak and accounts for about % of all deaths recorded (a total of suspected cases, confirmed cases and deaths recorded since disease onset in august . in , us cdc estimated the yearly number of lf cases to be between , to , resulting in about , deaths across west africa. lf is endemic in most parts of west africa with sporadic cases occurring in other african countries every year. studies have predicted approximately % of liberia and sierra leone, % of nigeria, and % of benin to be at risk of lf through spatial analysis. in nigeria, approximately cases and deaths have been reported from to date. due to a paucity of data, the actual number of cases in other west african countries to date is still unknown. however, seroprevalence studies in the past have shown a prevalence of lassa igg antibodies in % to % of the general population in sierra leone and in guinea, and as high as % to % among inhabitants of tropical rain forest and % to % in hospital staff of gueckedou and lola prefectures in guinea. direct transmission from rodent to humans mainly occurs through inhalation of primary aerosols from infected rodent urine, ingestion of food contaminated with rodent excreta or by direct contact with broken skin. regional and nosocomial outbreaks of lf are commonplace in lf endemic countries and played a major role in recent outbreak. in nigeria, the lf outbreak has been estimated to have an overall case fatality rate of % and % in confirmed cases; the impact on healthcare workers due to inadequately equipped, weak preventive measure for hospital associated infections (hai) and well trained staff and facilities with poor laboratory and clinical management practices were the main reasons for a dearth of data. while there is no known vaccine for lf, early supportive care and treatment with ribavirin. prevention efforts include isolation of cases, implementing infection control measures such as barrier nursing supplies, rodent control and practicing adequate food hygiene (storing grain and other foodstuffs in rodent-proof containers) and personal hygiene. although treatment for lf is available, early diagnosis, prevention and prompt management of infection are necessary (table ) . these growing public health emergencies and challenges prompted a memorandum on building the africa cdc that was signed by the african union with two parties are including chinese and us govemrnents. this cooperation exploring ways of further cooperation and lessons learning from china's national disease surveillance and reporting system model [ , ] . based on a unified and integrated plan, china and us government are willing to leverage their respective strengths to support the african union in building this system, which will be the first regional disease surveillance system on the african continent from the ebola crisis. it is important to strengthen disease surveillance and monitoring efforts at the regional level in providing technical expertise and response coordination in future health emergencies, address complex health challenges, and build needed capacity responses, responsible for disease surveillance, investigations, analysis, and reporting trends and anomalies. this is a landmark event in african ownership of improving health across the continent. the us cdc looks forward to engaging in this partnership for many years to come to advance public health across africa and global health security [ , ] results from the first and second china-africa ministerial health development forum held in beijing, china and cape town, south africa in and , respectively, showed that china-africa health development partnership had entered a new collaborative paradigm with great global health opportunities [ , , ] . chinese and african health ministers have adopted a declaration to increase access to facilities, medication, health workers and training, linking chinese scholars with those in africa into shared responsibility and global solidarity [ ] . importantly, china-africa collaboration in health development will use "one health" approach to set the collaborative priorities, such as developing innovative information and communication technology for health, building regional surveillance systems, improving the core capacities of international health regulations and enhancing the using regulation of traditional medicines, etc [ , , ] . the significance of africa-china cooperation health development initiative milestone was the broad consensus mou aimed to support the establishment of africa cdc signed on april , as part of the agreement and of the pledge made at the summit that was held under focac in johannesburg, south africa december [ ] . this laudable mutual commitment was realized through the full operationalisation of the africa cdc in early supported by the chinese government, including providing infrastructure construction, equipment, information system, expertise, and professional training, etc. as well fostering continuous strengthening african states public health prevention and control system under the chinese supports are also provided through comprehensively capacity building (e.g., staff, postdocs and students) and providing technical assistance and technology transfering to africa cdc sub-regional centres. the benefits of the translation of the immense mutual public health priority aligns "africa union health vision " in the fields of infectious diseases of poverty surveillance and elimination, emergency preparedness timely response to early alert and risk communication capabilities against public health emergencies and disaster crises events. previously, china has already provided two million us dollars cash aid for the africa cdc in terms of capacity building and the on-site chinese experts visit for the regional collaboration with other partners' support [ ] . africa cdc has now developed a five year strategic plan to improve surveillance, emergency response, prevention and resilience against infectious diseases threats and outbreaks, man-made and natural disasters, antimicrobial resistance and chronic diseases public health events of regional and international concerns. africa cdc focus on strategic priority areas and innovative programs aiming at improving evidence-based decision making and practice in event-based capacity development for surveillance, disease prediction, and improved functional clinical and public health laboratory networks and actions in minimizing health inequalities, and promoting quality care delivery, public health emergency preparedness and response best practices in achieving regional [ , , ] . africa cdc collaborating sub-regional centres in five countries provides an opportunity for effective collaboration, integration and coordination in harnessing existing public health assets, epidemiological surveillance, strengthening existing networks of quality laboratories for early detection and response. infectious public health preparedness and emegergency response cannot deliver effectively if we do not implement "one health and biosecurity" approach bringing human, animal and environmental health. building evidence-based and adequate capacity building need to support integrated "one health" surveillance, laboratory systems and networks, emergency preparedness and response, and public health research for evidence-based heath programing and ample resource allocation. greater commitment to strengthen local and regional operationalization of integrated disease surveillance and response, public health systems and core capacities have been documented to critically address public health emergencies, biosecurity and disaster risk across the continent. national and regional public health emergencies, biosecurity surveillance, preparedness, rapid response, and recovery policy and strategies are robust and sustainable assets for socioeconomic transformation in line with africa health strategy ( - ), the africa union agenda and in attaining sdgs [ , , , ] . firstly, developing innovative information and communication technology for health will provide opportunities to avert thousands of deaths and disability by improving access to good-quality essential drugs, by increasing coverage of vaccines immunization and use of other pharmaceutical and medical commodities nationwide [ , , ] . in addition, leveraging on the unique "one health" approach to transform health care and health policy and to prioritize collaborative programs can be extended from infectious diseases to maternal and child health and health disparity in the poorest populations in africa [ , [ ] [ ] [ ] . secondly, building regional surveillance systems is another way to enhance the local health system. the importance of implementing a local and national "one health" policy and programs holds tremendous prospects, such as co-tackling the epidemiological and environmental challenges, and accelerating in the transition from control to elimination of infectious diseases under china-africa collaboration [ , ] . furthermore, it has potential to revolutionize national health systems, policies and strategic priorities and the patterns in health financing and resources allocation of african countries that require careful understanding of the local context of diverse stressors and drivers [ , ] . these will continue to dominate the performance and effectiveness of "one health" in threats and epidemics prevention strategies and policies on healthcare and health outcomes. thus, assessing health impact especially how greenhouse gas and ozone emissions, rising temperature and environmental pollution resulted in climate change impacts to health ecosystem, such as population movement, animal trading and ecology of vectorborne disease and ill health, aging, chronic disease, drug use and domestic violence, inequity and poverty [ ] . thirdly, improving the core capacities of international health regulations is the sustained efforts to improve the human welfare. for example, china's response impacting the global health fund (e.g., malaria, hiv/aids, schistosomiasis, ebola, influenza, tb, hepatitis, etc.) has shown robust global health leadership engagement [ , , ] . the leadership reflected in the strategic mobilization and investment of resources fostering more easily accessible, availability and cost effectiveness of prevention and treatment interventions to resources limited countries including african countries [ ] . the growing mutual china-africa win-win collaboration spans to technical expertise, technology transfer and capacity development using scientific and advanced methods to tackle the disease, and have enhanced their commitment to respect the dignity of the people such as chinese ebola outbreak emergency response in west africa. fourthly, enhancing the use and management of traditional medicines could improve the community involvement in health care and extend the trade among countries. so far, trade between china and africa is projected to reach $ million usd a year by . increasingly, embracing "one health" strategy to increase universal coverage of healthcare is significant as sharing china's rich expertise and lessons learnt in strengthening health systems and tackling public health burden both in china and africa communities. thus, africa has the opportunity to improve capacity of community health workers to reach remotes rural communities living beyond the margins of traditional health care systems [ , ] . therefore, china's advancements in research and development, technical and scientific capacity transferring can support african next generation of proactive scientists to develop more sensitive simplified diagnostic tools and reduce the costs of laboratory diagnosis and medical equipment. furthermore, research and development (r&d) is needed in examining the biological mechanisms of stressors or risk factors exposure and health effects, assessing evidence-based mitigation or adaptation interventions and benefits [ , , ] . innovative solutions and breakthroughs in human-animal-environment fields would not only enable africa to meet its own growing needs, but also support integrating health systems, including strengthening the capacities of laboratory diagnostics and medical care, as well as establishing the china-africa platforms that could generate evidence-based low-cost, available and easy-to-use health packages and solutions for the reduction of public health burden. the present paper has analyzed the values of implementing national to regional "one health" strategy for dealing with human, animal and environment related public health threats, diseases outbreaks emergencies and disaster risk challenges, and promote healthy mitigation measures and resilient management approaches in advancing targeted local, national and global health agenda. also, understanding how to develop, package and implement evidence-based and sustainable "one health" approach needs partnerships and investment for strategic priorities and resource mobilization. in addition, it also needs better financing mechanisms and participatory coordination in building capacity and technical assistance, monitoring, performance and effectiveness metrics evaluation for one health indicators. understanding the foundation of "one health" strategy in china-africa public health needs and challenges although significant progress has been made in improving health and safety of vulnerable population in low and middle-income countries (lmics), there is growing unprecedented public health emergencies crises due to natural disasters (such as disease outbreaks, floods, climate change, droughts and mud-/land-sliding) and man-made disasters including armed conflict and resulting forced refugees and displaced populations in lmics and mainly in africa as well as china. these have been resulting in significant direct and indirect health impacts including limited access to food, clean water, medicines, pre-existing mental health and other health services. conflict-affected countries have not achieved a single millennium development goal and have significantly higher maternal and infant mortality rates compared to stable and peaceful countries. natural disasters affect nearly million people each year, with a disproportionate effect on populations and environment. there is also limited quantity of highquality and integrated research to build evidence "one health" approach response. for example, recent emerging zika virus is known to be circulating in latin america, america, africa, asia-pacific and middle east regions due to climate change and rapid urbanization, intense regional and global travel and trade impact on zika virus risk transmission and documented congenital complications on fetal and maternal health. efforts to strengthen regional and global public health emergencies surveillance and preparedness should be maintained in order to better characterize the intensity of aedes and culex vectorial capacity, asymptomatic or syndromic viral circulation and geographical infection spread, epidemiology and laboratory monitoring of zika virus related complications in vulnerable settings. we found that most existing and emerging infectious diseases of poverty and chronic diseases public health programs are based more on top-down and anecdotal experiences rather than accurate research in fostering an integrated humananimal and environment or "one health" community practice in most vulnerable settings in africa and china (table ) . "one health" approach was officially adopted by international organizations and scholarly bodies in in response to the growing global human-animal and environment inter-dependence challenges and issues including climate change which needed new approaches. in such, "one health" broader interconnections understanding offers tremendous advantages and manifold benefits in tackling emerging zoonotic diseases and chronic diseases to disaster risk consequences, but also in improving safety health of people and animals, and safeguarding environment against pollutants and pollution. it aims to enhance across disciplinary and interagencies assessment complex including human-animal health systems vis-a-vis environmental and climatic determinants of health, development of contextual health or disease detection and surveillance-response systems, data sharing and communication; partnerships and mutual learning for positive transformation and behavioral changes outcomes. hence, strengthening firmer foundation in building evidence-based integrated healthy approach decision making, health programming and actions plans implementation, training and research practice to community-based programs ownership, shared values and experiences in integrated cost effective and beneficial china-africa "one health" strategy initiatives for mutual wellbeing and economic prosperity. prioritizing "one health" approach in emerging and current infectious diseases public health emergencies and disaster risk reduction is essential in attaining the regional africa union and global health agenda promises and benefits. it requires promoting and implementing evidence-based, effective and sustainable national "one health" strategy advocacy and mitigation strategies in most africa countries and worldwide [ ] [ ] [ ] . strengthening evidence-based, consistent and reliable community, national and regional 'one health' and biosecurity people's medical publishing house co., ltd. partnerships, leadership, road maps commitment, approaches and strategies is a crucial for zoonotic diseases threats and outbreaks public health emergencies and other disasters risks humanitarian crises. integration "one health" principles and frameworks in health and relating multisectorial units or agencies planning and actions plans in generating comprehensive, consistent and real time knowledge and information in guiding evidence-based decision-making policy and participatory commitment and investment [ , , ] . articulated interest and reliance of all stakeholders will cover communities and public articulated actions in preparedness and response to climate changes, infectious and zoonotic threat and epidemics public health burden has provided [ , , ] . the extent and nature of "one health" approach through political engagement and funding is critical in advancing community social mobilization and awareness on "one health" strategy integration in public health systems and primary health care. the needs and value is prerequisite in sustainable public emergencies and disaster risk reduction priorities, preparedness, preventive and control programs and activities. while, providing the enabling health-animal and environment interface biosecurity and protection of legislative and technical assistance support to policy makers, planners and implementers including the local vulnerable communities in transforming contextual positive knowledge, behavioural and attitudes changes [ , ] . understanding the climate change, global migration and country-specific complexities of emerging and current infectious diseases of poverty is needed in tackle operational programs challenges and bottlenecks, improved sustained control into elimination. for example national immunization programs hesitancy and resistance issues, such as misconceptions and mistrust or fear, weak coverage and non-adherence, persistent resurgence of zoonotic threats and emerging epidemics, continue to place a huge toll of maternal and child health morbidity and mortality on burden and coupled with the rising trend of chronic diseases related inequities and poverty vicious cycle [ , , , , ] . building china-africa "one health" strategy partnerships, frameworks and capacity development china's global health approach is an unique and distinctive path. this approach based on contextual policies and realities-based on their history, driveninter sectoral and multidisciplinary government related ministries strengthen health systems in different african countries [ , , , , ] . there is a steadily growth in depth and strength of china's global engagement and collective participation in fostering global health agenda through china-africa health development strategies. event-based preparedness and transparent support management and technical assistance on transferable chinese lessons in infectious diseases elimination and eradication including measles, filariasis, schistosomiasis, malaria, sars and ebola, etc. for example, the china-tanzania pilot project of community-based and integrated malaria control strategy and applications funded by china-uk partnership aimed at assessing the feasibility and transferability of chinese malaria skills in strengthening malaria health education, awareness knowledge and access to vector control interventions (e.g., rdt, llin, acts) to reduce the risk of malaria infection in tanzania [ , ] . moreover, in the absence of specific ebola infection treatment, the partners or organizations, including african governments, who, the gavi alliance and "ebola ça suffit ring vaccination trial consortium" should accelerate on joint consensus for the adoption and "expanded access" to proven efficacious and safe rvsv-zebov vaccine ring ebola immunization strategy implementation to boost immune response and protect vulnerable populations and global travelers from potential ebola outbreaks [ , , ] . china-africa mutual and comprehensive partnership in health and pharmaceutical has been encouraging and promoting the use of community-based health services; and increasing government investment in public health interventions [ , , ] . china has been very supportive on african countries' efforts in building medical facilities and health service. for example, in , the chinese government constructed medical facilities and provided batches of medical equipments and supplies to african countries. chinese enterprises and nongovernmental organizations have helped african people get quality medical services by means of building and running hospitals, investing in pharmaceutical factories and localizing medicine production in improving health management and well-being, including maternal and child health, and emerging pandemic threat programs, etc. moreover, chinese medical assistance to africa has been sustained and operative win-win mutual support tailored to local settings, which could enhance research priorities in dynamic mapping of vectors and infectious diseases transmission with interaction of human-animal-environment, and provide evidence-based strategies in national or regional diseases control programmes and effective response packages [ , , [ ] [ ] [ ] . good progress remains in developing and implementing these policies and strategies coupled with shared lessons learnt and experiences against unprecedented infectious diseases public health emergencies and rising non-communicable diseases (ncds) challenges, such as obesity, cardiac arrest and stroke, hypertension, diabetes, cancer, kidney disorders and mental health, etc. there is a shortage of qualified health professionals at grassroots health facilities. it is also shortage in accessing to basic health control and elimination packages and service delivery including vaccine preventable diseases immunization programs coverage inadequacies in most rural and remote settings across africa compared to china, insufficient public and private sector funding to r&d on safety and effective vaccines or drugs against most emerging coupled with unattended public health diseases threats and epidemics impact preparedness, and strategies mutually gains and economic benefits [ ] . remarkable results and outcomes have been documented from chinese medical assistance in of african countries, ranging from health workers, implementers and policy-makers. capacity development and skills acquisition were achieved in over health-related training courses to , health implementers and health workers since . chinese medical teams friendship and health cooperation, including construction of ophthalmic center where more than , free cataract surgeries were completed in four african countries and construction of more than six other chinese medical hospitals in the last decades [ , , ] . it is also worth noting the robust and efficient participation and contribution of twenty-seven chinese provinces, autonomous regions and municipalities with accumulated more than , chinese medical workers in medical centers since , and currently over , medical workers are working in african countries. continuous support in building medical facilities, africa cdc reference laboratories per excellence and health service capacity has been appraised in embarking on assessing public health emergencies needs, risk factors and determinants in understanding the perception, knowledge, attitude and practice in evidence-based promotion of integrated "one health" approach and biosecurity decision-making approach. this also provide priority and targets, methodologies and programs through effective indicators surveillance and monitoring. for examples, chinese government dispatched over medical facilities and over batches of comprehensive medical equipment for early diagnostics and prompt treatment or response, and supplies across africa since [ , ] . chinese partnerships with local firms and communities have helped medical services delivery to remote and rural vulnerable populations through joint activities in building and running hospitals, investing in improving and scaling up localized production in pharmaceutical and biotechnologies industries in africa. in addition, we also recorded the establishment of more than clinics of standard traditional chinese medicine (tcm) integrated to africa traditional medicine (atm) [ , ] . in achieving universal coverage and healthcare for all, upgrading china-africa mutual health development cooperation and collaboration through independent and joint institutional research project and capacity development in health services delivery and in promoting science and technology capabilities, joint projects and activities have been increasingly developed and implemented. these projects and activities aim at tackling the persistent and growing burden of infectious diseases of poverty, maternal and child morbidity and mortality, and responding timely to the global health concerns and emergency response called on emerging threats and epidemics in the continent. some examples of the landmark achievements include the china-zanzibar and china-tanzania projects on sharing chinese lessons and experiences in infectious diseases to support schistosomiasis and malaria prevention and control in african countries respectively, as well as chinese maternal-child heath safety and children nutrition, dissemination and transfer experiences in ghana [ , , ] . furthermore, china-comoros support to national malaria elimination that led to interruption of transmission and reducing in malaria mortality to zero in the last eight years in comoros [ , , ] . likewise, understanding strategic public health financing and human resources systems capacity is necessary in promoting uptake and efficiency of chinese global health initiatives and innovations in strengthening healthcare delivery system and quality outcomes in lmics including africa, asia-pacific, middle east and latin american countries. strikingly again, during the west africa ebola outbreaks in - , the chinese assistance in response valued at $ million usd and more than , experienced medical professionals were deployed in the frontline affected and neighboring communities to combat and contain the rapid spread of the ebola virus epidemics [ ] . in addition to the mobile biosafety laboratory, china also built permanent and well-equipped public biosafety laboratory in seirra leone and dr congo to improve the national capacity to detect, prevent and respond to future threats and epidemics. over batches of public health, clinical medicine and laboratory experts were dispatched in african countries in scaling up public healthcare delivery capacity and training of health workers and communities in risk assessment, communication, and response measures in effective ebola, malaria, schistosomiasis prevention and containment, amongst other shared responsibility and mutual commitment [ , , , , [ ] [ ] [ ] . future expansion of china-africa health development initiatives offers immense opportunities in increasing mutual benefits and growth to both continents' several domains not only limited to health, technology and trade. the scale and sustainability of existing and forthcoming programs and plan of actions will require aligning of national priorities and defining contextual performance and effectiveness indicators, but also mutual respect and trust, accountability and transparency with good governance and proactive stewardship. it is imperative that efforts should also be made in strengthening evidence-based translation to the benefits of vulnerable populations and global community through sharing of lessons learnt and care knowledge experiences and information for all generations in combating infectious diseases and rising burden of noncommunicable diseases. fostering health systems preparedness and smart response against emerging and re-emerging threats and epidemics chinese and african rapid economic growth and the importance of strengthening the local and national public health laboratory systems in both continents have been recognized in tackling the rising healthcare needs, challenges and issues [ , , ] . globalization of travel and trade is ever increasing local, national and global emerging and re-emerging infectious diseases threats and their impacts on human and animal health. resolving the persistent and unprecedented rising of emerging and reemerging epidemics, and new priorities of ebola, zika, hiv/aids, tuberculosis, malaria and neglected tropical diseases (ntds) requires collaborative and mutual cooperation with governments, bilateral and multilateral initiatives, including boosting private-public partnerships, regional and international organizations in achieving the global health security threat and agenda [ , , , , ] . for example, china has dispatched more than , medical experts to resist west africa ebola epidemics through contributions to coordinated international emergency response efforts that helped to contain ebola virus transmission dynamics and spread that retrieved lives of over , people [ , , ] . similarly, zika virus belongs to the family flaviviridae, genus flavivirus, and includes africa subtype and asia subtype. it is a mosquitoborne virus primarily transmitted by aedes aegypti mosquitoes, sexual transmission; blood transmission and mother-to-fetus transmission have been also reported. zika virus can go through blood-brain barrier and infect central nervous system. symptoms are generally mild and self-limited, but recent evidence suggests a possible association between maternal zika virus infection and adverse fetal outcomes, such as congenital microcephaly, as well as a possible association with guillain-barré syndrome. in absence of safe vaccine or effective antiviral zika medication for prevention and control zika virus infection, early laboratorial diagnosis includes nucleic acid detection, serological test, and isolation of virus and epidemiology and clinical risk assessment and syndromic surveillance is crucial [ , , ] . nevertheless, there remains a need to build a platform with function of effective surveillance, recovery, preparedness, consultation and communication, and to share surveillance based on the principle of sincerity, real time problem-solving and results-giving, and good faith towards collaborative global health solutions [ , [ ] [ ] [ ] . fostering surveillance capacity in laboratory, clinical, veterinary and allied health sciences in the africa continent are critical to overcoming the growing burden of diseases and ensuring a healthy future of its citizens [ , ] . meeting the urgent growing healthcare needs in africa requires strategic and technical approaches in the development and integration of sound and harmonized regulatory systems for diagnostic products, new drugs and vaccine r&d. while reinforcing the national and international public health laboratories networks are able to improve collaborative and participative early disease detection, early warning and surveillance research in guiding proactive vigilance and smart response activities. effective good governance and leadership coordination of sustainable strategies on emerging outbreak preparedness and response capacity is necessary towards the transformation from traditional to modernized digital laboratory systems in timely and effective quality service delivery. however, the need for laboratories quality improvements and accreditation of methods, tools and programs are critical in upholding the gains preparedness, and emergency response in various infectious diseases programs and strategies should be supported through both national and international initiatives. bilateral and multilateral cooperation with the world bank, un and who, global fund to fight aids, tuberculosis and malaria, worthy philanthropic individuals and organizations efforts can enable country to be ready and capable of early detection, prognosis, prevention, and smart response or management in any detrimental natural or man-made epidemics eventuality, while facing operational challenges and setting new research priorities [ , , , ] , for contextual "one health and biosecurity" programs, are also need to be supported with appropriate regulations and guidelines. there is an urgent need to invest in basic and operational research on climatic, ecological and evolutionary changes for understanding and forecasting persistent and future emerging threats dynamics and epidemics. timely evidence-based translation into policy programs and interventions is imperative to defeat the budding threat and burden through coordinate robust actions and better stakeholders leadership in response advocacy and mitigation in line with the paris climate change declaration in december, [ , ] . fostering integrated approaches with cuttingedge inter-sectoral and trans-disciplinary partnership is also needed evidence-based nationwide scaling up contextual surveillance and response capacity. moreover, with improvement of targeted strategies to deal with emerging outbreaks and infectious diseases of poverty elimination, understanding human-animal interface with increasing urbanization, globalization of trade and travel are necessary. hence, china-africa "one health" strategy sustainable implementation and alignment with local and national priorities hold great promises. integrating collaborative human-animal-environmental projects and programs have substantial prospects in increasing local and national food production and global food security [ , ] . this is critical in averting or reducing the persistent malnutrition, under-nutrition and related health complications and diseases (e.g. malnutrition linked kwashiorkor or rickets, obesity, typhoid, diarrhea, dysentery) resulted in children and youth developmental retardation, poor educational performance, poor quality of life and living including high daly and low qaly short life expectancy, worsening the vicious cycle of poverty and premature death documented in africa countries [ , , , , ] . similar high public health challenges and burden in africa were recorded in china before s, mainly in chinese rural communities circumventing with the implementation of the chinese rural cooperative medical insurance schemes. however, more investment is still needed in achieving food autosufficient and balanced food and nutrition/diet for all in both continents [ ] . developing and integrating climate changes resilience , mitigation and adaptation measures in allied health programs is vital in protection, conservation and management of the adverse socio-demographic, ecological, health and economic effects of greenhouse gas emissions and changes consequences, and in securing the future benefits of green and eco-friendly environment. the value of china-africa "one health" strategy implementation financial support from governments and various levels, advocacy and social mobilization to develop supportive community environment for infectious and emerging zoonoses threats and epidemics in population-based public health control and elimination interventions is imperative through implementation of evidence based and cost-effective "one health" surveillance and response strategy, in order to integrate human, animal, and environmental landscape, continue health education promotion, improve awareness and quality public health service delivery performance and effectiveness metrics across africa. enhanced disease surveillance response, community capacity development and strain capacity can provide significant opportunities in health education and promotion, shared responsibility, positive behavior changes and best practices by different health facilities, training health practitioners of diagnosis, treatment and rehabilitation services. identification of local and national health needs and evidence-based effectiveness of "one health" solutions are urgently needed to improve appropriate and sustainable resource development policies and strategic programs across africa. such new partnership initiatives linked to china belt and silk initiative action plan should attract more indigenous and international partners and stakeholders, more qualified multidisciplinary professionals to work, communicate and share experiences and lessons collectively. building local and national trans-disciplinary and trans-sectoral research teams towards improved understanding the genetic and molecular mechanisms of invasive pest and drug resistance, and control of complex disease systems and in strengthening continuous improvements of human, animal, ecosystem health and well-being [ ] [ ] [ ] [ ] . robust evidence in comprehensive control for multiple risk factors including health guidance on diet, fitness activity and promoting individual and community self-management model is important to services by general practitioners and mainly in translational research directed toward sustainable development activities and global environmental health. to support integrated veterinary, medical and ecosystem education, and to provide more professional career development opportunities, the governments need to continuously increase its investment in public health intervention programs and financial support to health insurance schemes. increased funding from both central and local governments needs to be directed to the underdeveloped regions and poorer rural areas to support global and national programes on infectious diseases of poverty and sustain control and elimination agenda for emerging epidemics tackle maternal and child health challenges, improve ncds mitigation interventions, and set up better health insurance schemes. in addition, it is equally important to strengthen monitoring of the use for public health interventions. "one health and biosafety" systems research projects development and implementation are also urgently needed in improving training programs and educational empowerment in guiding human-animal health and environment programming and technical assistance. addressing the existing and unprecedented public health emergencies or disaster risks requires optimizing the "one health and biosecurity" targets and interventions which will benefit indicators metrics monitoring in routine public health programs and humanitarian emergencies crises response [ , ] . there is need to promoting "one health and biosecurity" youths voices in healthy and ecofriendly "one health" community advocacy, engagement and participation. strengthening and sustaining "one health and biosecurity" strategy will improve the cost-effectiveness surveillance and communication interventions through continuous awareness, and knowledge improvements for the overall china-africa and global health security benefits [ , , , ] . robust and sustainable leadership commitment and investment is needed in integration of "one health" and global health security. advocacy and mitigation programs is needed in china-africa health development initiatives. to establish public emergencies indicators and metrics for early and timely community engagement and effective risk communication, following actions need to be handled to achieve sdgs and global health agenda: ( ) community-based partnerships and programs ownership, ( ) assessment for evidence based "one health", ( ) identification of the various stressors or risk factors, ( ) programmatic and proactive development and implementation of appropriate and sustainable "one health", ( ) resource mobilization mechanisms and solutions based on animal-humanenvironment interface challenges and impacts surveillance, preparedness, and timely collective response to public health threats and humanitarian emergency crises. china-africa health development initiatives: benefits and implications for shaping innovative and evidenceinformed national health policies and programs in subsaharan african countries enhancing collaboration between china and african countries for schistosomiasis control china-africa cooperation initiatives in malaria control and elimination establishing the africa centres for disease control and prevention: responding to africa's health threats tackling the challenges to health equity in china china's distinctive engagement in global health implementing a one health approach to emerging infectious disease: reflections on the sociopolitical, ethical and legal dimensions one health: an opportunity for an interprofessional approach to healthcare new orientation for china's health assistance to africa elimination of tropical disease through surveillance and response global implications of china's healthcare reform rift valley fever epidemic in niger near border with mali. the lancet inf diseases deciphering emerging zika and dengue viral epidemics: implications for global maternal-child health burden joint china-us call for employing a transdisciplinary approach to emerging infectious diseases china harvard africa network (chan) team. china, africa, and us academia join hands to advance global health china-africa cooperation initiatives in malaria control and elimination global health security: the wider lessons from the west african ebola virus disease epidemic one health: the hong kong experience with avian influenza genetic diversity and evolutionary dynamics of ebola virus in sierra leone building international genomics collaboration for global health security china's role as a global health donor in africa: what can we learn from studying under reported resource flows? the ebola threat: china's response to the west african epidemic and national development of prevention and control policies and infrastructure china's distinctive engagement in global health china takes an active role in combating an ebola outbreak: on-site observations and reflections from a chinese healthcare provider schistosomiasis control: experiences and lessons from china a strategy to control transmission of schistosoma japonicum in china schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people at risk surveillance-response systems: the key to elimination of tropical diseases rebuilding transformation strategies in post-ebola epidemics in africa evidence on public health interventions in humanitarian crises thanks to nipd, china cdc, shanghai, and universite des montagnes for the enabling environment to complete this review. data are freely available and accessible. the authors have no conflict of interests. not applicable. key: cord- -dtdsd j authors: buonsenso, danilo; cinicola, bianca; raffaelli, francesca; sollena, pietro; iodice, francesco title: social consequences of covid- in a low resource setting in sierra leone, west africa date: - - journal: int j infect dis doi: . /j.ijid. . . sha: doc_id: cord_uid: dtdsd j economical and psychological consequences of the lockdown in low-resource setting in rural africa are unknown. we drafted a survey in order to address the social impact of covid- lockdown on a rural village in sierra leone. the survey developed by the study group and translated in the local language, distributed to the householders of the village on april (th) and responses collected on april (th), when sierra leone was on day of lockdown. the questions aimed to assess in the community the following items: age group, main activities before lockdown, change in income and ability to feed the family during lockdown, anxiety during lockdown. householders ( % of bureh town) replied. all, expect one, declared a - % ( . %) to - % ( . %) reduction of weekly income compared with the pre-lockdown period, declaring difficulties in providing food for the family members ( %), and anxiety ( %). our analyses showed that people lost their jobs and have difficulties in providing food for their families. liberia were closed; on april rd a three-day lockdown started and eventually on april th, due to the local escalation in reported cases, a -day lockdown was released, with the possibility of extension according to the epidemiological development. despite these restrictions, on april th, confirmed cases were reported, people put in quarantine but still zero deaths related j o u r n a l p r e -p r o o f to covid- were documented. economical and psychological consequences of the lockdown in low resources setting in rural africa are worrying the experts of global health (el-sadr et al. ), but are still unknown and their early analysis will allow corrective interventions or preventive measures to support fragile areas to minimize the impact on the population. we drafted a survey in order to urgently address the social impact of covid- lockdown on the rural village of bureh town, sierra leone, west africa (figure ) and quickly implement corrective measures. it was developed in english by the lead author, reviewed by the research team and translated in the local language by the headman and the authors of this study. the headman represent the chief of rural areas in sub-saharan west africa, being comparable as a mayor of city in high resource countries. the survey had been deliberately made simple so that everyone could respond regardless of schooling and included questions on age of the respondents, number of people and age groups of people living in the house, work situation and weekly income before and after the lockdown. the administered survey was composed with a descriptive purpose and composed of detailed questions aimed to assess the following items in the community: age group, main activities before lockdown, change in income and ability to feed the family during lockdown, anxiety during lockdown (supplementary material). the survey was a clinical/demographic one with descriptive aims. (table ) , representing a total of bureh town citizens ( children under ; aged between and ; aged between and ; aged between and , aged between and ; aged more than years). all people were dependent from the local stream to collect water, where the younger groups of the family go every morning for this issue. people were involved in local jobs such as: fishing ( , . %), tourism ( , . %), marketing ( . %), schoolteacher ( , . %), others ( , . %) while ( . %) declared not to have a job before the lockdown. all householders, expect one, declared a - % ( householders, . %) to - % ( householders, . %) reduction of weekly income compared with the pre-lockdown period, declaring difficulties in providing food for the family members in % of respondents, due to lack of economic resources related to the reduced income and activities related to the lockdown; . % of respondents declared to be very worried about economic fallout from the lockdown with % of householders declaring a mild-moderate anxiety. our analyses, even if just focused on a small village, showed a profound indirect impact of sars-cov- spread in sierra leone. considering the rapid worldwide diffusion of covid- dramatic health impacts (of note only one ventilator is available for the whole population of sierra leone). lockdown seemed to be the only measure to delay contagion but this decision was not without consequences for people, especially those living in fishing and touristic areas of the country. in our survey, all people but one declared a % to % reduction of weekly income with consequences in the ability to provide food for the family members, thus confirming results by other studies (dyer ) . most of the respondents considered themselves worried j o u r n a l p r e -p r o o f about the situation with a mild percentage of the population living in a mild-anxiety state. in fact, the households provided the response on day eleven since first lockdown was declared, meaning that local touristic activities, as well as minor markets, were already affected, with economic consequences for local workers, by more than seven days. these results are probably due to the fact that, differently from governments of high-income countries, community members were not supported by the administrations. for example, in the european union and the united states, the government pushed the economy providing billions of euros/dollars to support those families that lost jobs or whose income was severely affected by the reduced business. the findings of our survey confirm the fear of severe consequences of the spread of sars-cov- in sub-saharan africa and the need for special surveillance tools(el zowalaty and järhult ). although kapata et al.(kapata et al. ) gave a positive answer to the question "is africa prepared and equipped to deal with yet another outbreak of a highly infectious disease -covid- ?", our data suggest that community members is economically and then psychologically suffering from this situation. certainly, substantial progresses has been made in africa since the - ebola outbreak (delamou et al. ) , with lessons learned from previous and ongoing outbreaks (largent ; omoleke et al. preparedness and response to pediatric covid- in european emergency departments: a survey of the repem and peruki networks public health impact of the - ebola outbreak in west africa: seizing opportunities for the future building resilience against biological hazards and pandemics: covid- and its implications for the sendai framework covid- : africa records over cases as lockdowns take hold africa in the path of covid- from sars to covid- : a previously unknown sars-cov- virus of pandemic potential infecting humans -call for a one health approach. one health is africa prepared for tackling the covid- (sars-cov- ) epidemic. lessons from past outbreaks, ongoing pan-african public health efforts, and implications for the future ebola and fda: reviewing the response to the outbreak, to find lessons for the future ebola viral disease in west africa: a threat to global health, economy and political stability a novel coronavirus from patients with pneumonia in china we are thankful to the local operators of bureh village: ismail jaber, matilda yamba, prince williams, memunatu n kallon, nee turay. we are also grateful to all our colleagues that j o u r n a l p r e -p r o o f key: cord- -b ufs y authors: ebigbo, alanna; karstensen, john gásdal; bhat, purnima; ijoma, uchenna; osuagwu, chukwuemeka; desalegn, hailemichael; oyeleke, ganiyat k.; gebru, rezene b.; guy, claire; antonelli, giulio; vilmann, peter; aabakken, lars; hassan, cesare title: impact of the covid- pandemic on gastrointestinal endoscopy in africa date: - - journal: endosc int open doi: . /a- - sha: doc_id: cord_uid: b ufs y background and study aims as with all other fields of medical practice, gastrointestinal endoscopy has been impacted by the covid- pandemic. however, data on the impact of the pandemic in africa, especially sub-saharan africa are lacking. methods a web-based survey was conducted by the international working group of the european society for gastrointestinal endoscopy and the world endoscopy organization to determine the impact and effects the covid- pandemic has had on endoscopists in african countries. results thirty-one gastroenterologists from countries in north, central, and sub-saharan africa responded to the survey. the majority of respondents reduced their endoscopy volume considerably. personal protective equipment including ffp- masks were available in almost all participating centers. pre-endoscopy screening was performed as well. conclusion the covid- pandemic has had a substantial impact on gastrointestinal endoscopy in most african countries; however, the impact may not have been as devastating as expected. background and study aims as with all other fields of medical practice, gastrointestinal endoscopy has been impacted by the covid- pandemic. however, data on the impact of the pandemic in africa, especially sub-saharan africa are lacking. methods a web-based survey was conducted by the international working group of the european society for gastrointestinal endoscopy and the world endoscopy organization to determine the impact and effects the covid- pandemic has had on endoscopists in african countries. results thirty-one gastroenterologists from countries in north, central, and sub-saharan africa responded to the survey. the majority of respondents reduced their endoscopy volume considerably. personal protective equipment including ffp- masks were available in almost all participating centers. pre-endoscopy screening was performed as well. conclusion the covid- pandemic has had a substantial impact on gastrointestinal endoscopy in most african countries; however, the impact may not have been as devastating as expected. in central and sub-saharan africa, disease epidemics have been easily spread and sustained, primarily due to socioeconomic, regulatory, and demographic factors [ ] . weak and poorly resourced health-care systems in african countries have led to concerns about the possible devastating effects that a rapidly spreading coronavirus could have in these countries [ ] [ ] [ ] . at the time of writing, the world health organization has reported , cases of covid- and , deaths in africa [ ] . nevertheless, many african countries have made quick and timely efforts to prepare their medical systems for the pandemic [ ] . also, the experience of many african countries with past epidemics, including the ebola virus disease epidemic of , may prove advantageous in the current situation. in addition to this, infrastructure from previous global initiatives in dealing with hiv, malaria, and tuberculosis could also have a positive effect in facing the current pandemic [ ] . as with all other fields of medical practice, the covid- pandemic has impacted gastrointestinal endoscopy, especially with regards to triage and prioritization of patients and procedures, cleaning and disinfection of equipment as well as protection of health care workers (hcw) [ , ] . a survey from northern italy showed a dramatic burden of the pandemic on endoscopy units [ ] . however, data on the effects of the pandemic on gastrointestinal endoscopy in central and sub-saharan africa (ssa) are lacking. possible underreporting of disease burden, unavailability of test kits, and scarcity of personal protective equipment (ppe) may have had a greater impact on endoscopy practice in ssa than in other parts of the world. in this study, we report the results of an africa-wide survey of the impact of the covid- pandemic on endoscopy practice in central africa and ssa. the survey was developed by the international affairs working group (iawg) of the european society of gastrointestinal endoscopy (esge) and the world endoscopy organization (weo) and conducted between the and may, . to acquire information on the impact of the covid- pandemic in ssa including changes in endoscopic activity, availability of ppe, use of pre-endoscopic screening measures, and capacity of endoscopy units in general, a web-based survey with questions (appendix ) was distributed to gastroenterology and endoscopy centres across northern and central africa and ssa. survey participants included personal contacts and members of national societies with close-working relationships to the esge and weo [ ] [ ] [ ] . overall, responses were received from different african countries. to provide context on the results, we have included the current per-country world health organization (who) covid- situation report (▶ table ) [ ] . detailed results of the individual questions are reported in appendix , and the main results are summarized below. fifty-three percent of participants perform fewer than endoscopic procedures, % between and , and % more than endoscopic procedures per year. the majority of participants ( %) had not performed an endoscopy on a patient with confirmed or suspected covid- but % of participants were working in medical institutions that took care of patients with covid- . however, more than % of participants felt that covid- was underreported or underdiagnosed in their countries. where an emergency endoscopy was performed on a patient with covid- ( %), the indication was upper gastrointestinal bleeding. overall, % of participants reduced their endoscopy case volume by % to %, % by % to %, % by % to %, while % had no reduction in case load (▶ fig. ). ninety-four percent of participants changed their triage protocol during the pandemic. in reducing endoscopy volume, the majority of participants performed only emergency and urgent procedure but % continued all procedures including elective endoscopy throughout the pandemic. sixty-nine percent of participants cancelled % to % of all procedures, while % did not cancel or postpone endoscopic examinations (▶ fig. ). eight-sev-▶ patients with covid- represent a potential disease transmission risk to the hospital staff, endoscopy staff, and other patients, which requires specific risk management practice. one such practice is prescreening, which involves assessment of a patient's infectiousness risk prior to arrival at the hospital, admission or undergoing a procedure. while % of respondents used no prescreening measures, % prescreened their patients prior to endoscopy. questions and history-taking as well as temperature check were the predominant prescreening procedures prior to endoscopy. only % of respondents used viral polymerase chain reaction (pcr) testing as a prescreening measure (▶ fig. ). during the pandemic, ppe regulations changed in % of respondents' centers. eighty-two percent of participants answered that ppe changed for all patients, irrespective of confirmation or suspicion of covid- . n masks and long-sleeved, water-resistant gowns were the most limited ppe during the pandemic even though % of participants used n masks for endoscopy in their centers (▶ fig. ) for % of respondents, a negative-pressure room was not available for examination of covid- patients while % had a specifically dedicated room for examination of confirmed or suspected covid- cases. in %, family members were not allowed access into the endoscopy unit. only % of respondents changed their disinfection and cleaning protocol as a result of the pandemic. furthermore, % changed the personal protection procedures for cleaning personnel. changes described by the respondents included: . regular hand hygiene/washing with soap. . cleaning and disinfecting endoscopy rooms between each procedure. . extending disinfection time for endoscopy equipment and endoscopy rooms. . routinely using surgical face masks and two pairs of gloves for cleaning and disinfection of endoscopes. . using complete ppe for cleaning and disinfection of endoscopes. in consideration of low prevalence rates for covid- patients, % of participants are now considering changing back to normal and % have a specific return-to-normal strategy. most return strategies involve continuation of prescreening procedures for risk-stratification as well as performing all endoscopy procedures in the future with surgical masks irrespective of covid- risk. ssa experiences major infectious disease outbreaks on a regular basis that threaten public health, with the who regularly reporting regional outbreaks of ebola, river blindness, and malaria among others [ ] . in the face of this, the preparedness for covid- with its potential to rapidly spread and devastate a resource-deprived population in ssa is of particular concern. in this paper, we presented data on the effects and impact of the covid- pandemic on the practice of gastrointestinal endoscopy in northern, central, and sub-saharan africa. the prevalence of covid- in most parts of africa [ ] seems to be lower than the rates reported in europe and the united states; however, more than three-quarters of participants agreed that covid- may be underreported or underdiagnosed in their countries. nevertheless, a considerable burden on gastrointestinal endoscopy with reduction or cancellation of procedures in almost all participating centers was observed. most cancelled procedures were postponed indefinitely or for at least weeks while procedures still being performed were limited to urgent indications or emergencies. only two survey participants had examined patients with covid- in an emergency situation. this is in contrast to the results of a survey from italy in which about half of all endoscopy units were directly involved in emergent or urgent procedures in covid- cases [ ] . however, this may not have been the case in other parts of the world that did not experience the same extremely sharp rise in incidence of covid- cases within a short period of time. in comparison, we have included the survey results from three other centers in australia, denmark, and germany in appendix . an interesting aspect of the survey is the impact the pandemic had on use and availability of ppe as well as reuse strategies implemented by participating centers. as was the case in europe and the united states, n /ffp- masks were the ppe for which shortages, scarcity, and reuse strategies were most commonly described. nevertheless, all forms of ppe including n masks were available in most centers (▶ fig. ). at least from the results of this survey, there does not seem to be much of a difference between the availability of ppe for gastrointestinal endoscopy in africa and in other parts of the world. however, this must be interpreted in context of endoscopy case volume and covid- prevalence rates in most centers in central and sub-saharan africa. with regards to prescreening, again there seems to be no difference from other parts of the world in which viral pcr testing is not done routinely while temperature checks as well as pre-endoscopy risk-stratification are commonly recommended [ , ] . finally, return strategies are now being planned by more than half of the participating centers in africa, again similar to approaches in europe. the main limitation of this survey is the relatively low overall response rate received, which may limit the generalizability of the data. however, the limitation is relativized by the adequate number and distribution of countries that participated in the survey. the results of this africa-wide survey have shown that the covid- pandemic has had a substantial impact on gastrointestinal endoscopy in most african countries; however, due to the low prevalence rate and the low case-volume in most centers, and possibly also the local experience with communicable diseases, the short-and intermediate-term impact may not have been as devastating as expected. early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia the socio-economic implications of the coronavirus pandemic (covid- ): a review covid- in africa: care and protection for frontline healthcare workers africa in the path of covid- covid- ʼs final frontier: the central africa region is sub-saharan africa prepared for covid- covid- : perspectives and reflections from africa covid- threatens health systems in sub-saharan africa: the eye of the crocodile covid- : situation update for the who african region keeping covid- at bay in africa gastrointestinal endoscopy during covid- pandemic covid- ) outbreak: what the department of endoscopy should know endoscopy units and the covid- outbreak: a multi-center experience from italy esophageal stenting for benign and malignant disease: european society of gastrointestinal endoscopy (esge) cascade guideline partnership with african countries: european society of gastrointestinal endoscopy (esge) -position statement nonvariceal upper gastrointestinal hemorrhage: european society of gastrointestinal endoscopy (esge) cascade guideline world health organization. the african region health report: the health of the people esge and esgena position statement on gastrointestinal endoscopy and the covid- pandemic esge would like to thank all survey participants for their valuable responses to the survey. the authors declare that they have no conflict of interest. key: cord- -lepsuyns authors: braimoh, ademola title: building resilient food systems in africa date: - - journal: nan doi: . /j.oneear. . . sha: doc_id: cord_uid: lepsuyns climate change constitutes a significant threat to food security and poverty reduction in africa, and the food system is severely off target in meeting development goals. policy response should focus on investing in agricultural public goods, scaling up digital solutions, and developing innovative finance mechanisms to enhance resilience. food security is a major development challenge in africa. demand for food has been growing rapidly and will continue to do so in the conceivable future, exceeding % per year through . population growth at the rate of about % per year, per capita income growth and urbanization, and changing consumer preference toward processed foods and more nutritious and higher calorie foods are the major drivers of demand. today, africa is a net food importer, at an annual cost of $ billion. and as climate change progresses, food security concerns only grow. adapting africa's food system to climate change will be crucial if it is to achieve food security and lift people out of poverty. about million of africa's population ( %) are undernourished, and the number could increase to million by if appropriate adaptation measures are not taken. crop productivity declines by % for every degree of warming above historical levels. from devastating droughts in southern africa and west africa to cyclones and intense flooding in east africa, extreme weather is putting millions of africans at risk of food insecurity. at the same time, climate change is predicted to reduce the income of people in the bottom % by more than % by , further constraining their ability to respond to climate shocks and adapt to climate change. this only grows more worrying in light of the coronavirus pandemic that is highly disrupting the food market and exacerbating food price inflation. climate impacts will continue to deepen existing vulnerabilities and low capacities, leading to poverty, fragility, conflict, and violence. for africa to be prepared for this troubling and uncertain future, it is vital that resilience is built into its food systems. in response to the climate and food security challenges, members of the african union met at malabo in june . the resulting ''malabo declaration'' provides the direction for africa's agriculture transformation for the period - , within the framework of the comprehensive africa agriculture development programme (caadp). among its goals were pledges to enhance investment finance in agriculture, boost intra-african trade in agricultural commodities and services, end hunger, and halve poverty. it also explicitly aims to enhance the resilience of livelihoods and production systems to climate variability. however, the biennial review of progress indicated that africa's food system is severely off track. while out of reporting african union member states improved their overall agricultural transformation scores compared to , only four countries surpassed the benchmark. similar trends are seen throughout the report, with few countries on track to meet specific targets. however, there are exceptions. boosting intra-african trade in agricultural commodities and services is on track in countries. regional trade helps to maintain farm gate prices and safeguard farmers' incomes while serving as an important buffer to offset production shortfalls in a country and helping to stabilize food prices for consumers. in addition, countries are on track for increasing the total area of land under irrigation. however, this is only million hectares, less than % of africa's poten-tially irrigable lands. only countries are on track in implementing policies to enhance resilience to climate variability, indicating more needs to be done in meeting this goal. creating momentum for resilience current progress toward achieving the malabo declaration's targets reveals the pressing need to accelerate progress toward food systems' resilience in africa. but it also reminds us that africa has vast agricultural potential. throughout africa, there exists over million hectares of uncultivated land that can be brought to productive use in climate-smart ways. the expansion of irrigation can help intensify the use of farm labor by facilitating year-round cultivation, improving crop response to fertilizers and improved seeds, and promoting the adoption of higher-value crops such as fruits and vegetables. developing the agricultural sector is also a pathway toward reducing poverty. on average, growth in agriculture is two to three times more effective in reducing poverty than the same amount of gdp growth elsewhere in the economy. africa's food and beverage markets are expected to top $ trillion in value by compared to usa's $ billion in . african agriculture is also energized by entrepreneurial youth and an engaged private sector that is taking note of its potential. young africans are making agriculture a viable business, creating opportunities for farmers as well as themselves. if africa is to build a resilient food system and lift agricultural workers out of poverty, it is essential that this potential is unlocked. for agriculture in africa to not only persist but to flourish in an uncertain future, improved policy responses are crucial. african governments need to strengthen enabling environment through improved policies and investments in agricultural public goods, scale up digital solutions for agriculture, and develop innovative financing schemes through public-private partnerships. foster policies for enabling climate action the starting point for a more enduring agricultural transformation in africa is to implement policies that enable effective climate action. such policies are needed across a wide variety of domains, including agricultural research and extension, market information systems, and development and maintenance of rural roads. policies must also eliminate agricultural, trade, and macroeconomic regulations that reduce farmers' incomes, which could increase agricultural output by . %. investments in international and agricultural research can result in the development of varieties that are tolerant to harsh conditions. publicly financed agricultural research should focus on emerging problems faced by farmers, designing inclusive knowledge management systems to strengthen farmers' knowledge of climate-smart agricultural practices, facilitate sharing of improved techniques, and support the integration of indigenous knowledge systems with modern science. doubling agricultural research spending could increase agricultural output by . %- . %. doubling irrigated land area can increase agricultural output by . %, while public spending to increase average schooling level of agricultural labor force to years will increase output by . %. better policies are also needed to improve land governance to ensure equitable access to land. small and commercial farmers must also have access to input and credit and product markets, and receive similar prices for their products, and policies should create the opportunities for rural labor force to migrate to access rural employment. technologies for collecting, storing, analyzing, and sharing information digitally, including mobile phones and the internet, have great potential to improve efficiency, equity, and environmental sustainability of the food system. from videobased agricultural advice to the internet of things-enabled climate-smart irrigation tools to agroweather advisories that provide personally relevant information on weather and impending disasters and help farmers capitalize on changing conditions, digital solutions could be a game-changer in boosting agricultural productivity and resilience in a sustainable way in africa. the technologies enable actors within the food system to make informed decisions, improve productivity and incomes, and achieve better nutrition, health, and resilience outcomes. furthermore, digital technologies can be applied for agriculture e-commerce, thereby helping to match buyers with sellers, shorten agricultural value chains, provide access to new markets, reduce transaction costs, and create new business opportunities for actors within the food system. in addition, digital agriculture can successfully leverage africa's youth bulge. about to million youth enter the workforce each year, but only . million jobs are created, leaving several million youths unemployed. rural youth are well-placed to benefit from jobs created by digital agricultural innovation since they are more likely to own mobile phones. however, increasing the adoption of digital technologies in the food system will require expanding mobile internet coverage, currently at % of the population, and promoting the availability of relevant digital applications tailored to different actors within the food system. as network coverage increases, so do potential users of digital solutions, which increases the incentives for digital solution providers to develop relevant applications. additionally, farmers and aggregators require the knowledge and skills to use digital technologies. for example, farmers must know that a certain technology exists, believe it will solve a problem, and then learn how to apply the technology. to encourage adoption more broadly, digital technologies should be user friendly and require low-level skills and literacy for its use, for example, with interactive voice response functionality. for current and new generations to make use of digital technology and engage profitably in agriculture, they need entrepreneurial programs that provide a package of services to overcome the multiple constraints they face. these services include trainings, access to land, inputs, finance and markets, and mentoring. producer organizations, nongovernmental organizations, and social enterprises can be instrumental in designing and delivering effective entrepreneurship programs. another strategic approach is to upgrade skills in agriculture universities and training institutes by revamping training curriculum to include the application of information and communications technology (ict) tools, as well as improved techniques of food storage and processing, and the application of renewable energy in agricultural value chains. develop innovative financing instruments the agricultural financing gap in many african countries surpasses government budgets and available donor funding. to maximize finance, it is important to leverage private sector resources and minimize the burden of public debt. innovative financing leverages all sources of financing to support agricultural growth and resilience, crowding in private investment to optimize the use of scarce public resources. sources of private finance for the food system are growing and includes farmers' own-savings, local and international banks, microfinance institutions, value chains actors, impact investors, development finance institutions, private sector foundations, and agricultural investment funds. because the agricultural sector is prone to considerable production, market, and enabling environment risks, blended finance can be used to support high-impact projects where perceived risk is higher than actual risk. this is especially true for new projects with which investors are unfamiliar. high levels of direct public participation in markets leave little space for private sector activities in the agricultural sector in many african countries. public sector dominance needs to be reduced, and public sources instead need to be used to increase the flows of capital to enhance resilience in africa. this should focus on enhancing farmers' access to tailored and demand-driven financial services, building the capacity of financial institutions to manage exposure to specific agricultural risks, and supporting financial institutions in reducing transaction costs. it should be noted, however, that reduced public sector dominance is not a sufficient condition to increase productivity and commentary resilience; there is still a crucial need for public resources to finance essential agricultural public goods and services as discussed above. food system resilience is an unfinished agenda in africa, compounded by the coronavirus pandemic. several countries are lagging in terms of efforts to meet food security, poverty reduction, and climate change goals. african governments need to improve the enabling environment for the food system to thrive by increasing investments in agricultural public goods, supporting smallholders to benefit from digital revolution, and developing innovative financing instruments through public-private partnerships. these measures could do much to transform african agriculture, increase food security, reduce extreme poverty, and boost shared prosperity in the region. a meta-analysis of crop yield under climate change and adaptation unbreakable: building the resilience of the poor in the face of natural disasters second biennial review report of the african union commission on the implementation of the malabo declaration on accelerated agricultural growth and transformation for shared prosperity and improved livelihoods (african union the (evolving) role of agriculture in poverty reduction: an empirical perspective growing africa: unlocking the potential of agribusiness resources, policies, and agricultural productivity in sub-saharan africa future of food: harnessing digital technologies to improve food system outcomes jobs for youth in africa: catalyzing youth opportunity across africa mobile industry impact report: sustainable development goals (gsma) future of food: shaping the food system to deliver jobs future of food: maximizing finance for development in agricultural value chains making climate finance work in agriculture key: cord- - qj rrgd authors: lvov, dimitry konstantinovich; shchelkanov, mikhail yurievich; alkhovsky, sergey vladimirovich; deryabin, petr grigorievich title: single-stranded rna viruses date: - - journal: zoonotic viruses in northern eurasia doi: . /b - - - - . - sha: doc_id: cord_uid: qj rrgd in this chapter, we describe zoonotic viruses that were isolated in northern eurasia and that belong to the different families of viruses with a single-stranded rna (ssrna) genome. the family includes viruses with a segmented negative-sense ssrna genome (families bunyaviridae and orthomyxoviridae) and viruses with a positive-sense ssrna genome (families togaviridae and flaviviridae). among them are viruses associated with sporadic cases or outbreaks of human disease, such as hemorrhagic fever with renal syndrome (viruses of the genus hantavirus), crimean–congo hemorrhagic fever (cchfv, nairovirus), california encephalitis (inkv, tahv, and khatv; orthobunyavirus), sandfly fever (sfcv and sfnv, phlebovirus), tick-borne encephalitis (tbev, flavivirus), omsk hemorrhagic fever (ohfv, flavivirus), west nile fever (wnv, flavivirus), sindbis fever (sinv, alphavirus) chikungunya fever (chikv, alphavirus) and others. other viruses described in the chapter can cause epizootics in wild or domestic animals: geta virus (getv, alphavirus), influenza a virus (influenzavirus a), bhanja virus (bhav, phlebovirus) and more. the chapter also discusses both ecological peculiarities that promote the circulation of these viruses in natural foci and factors influencing the occurrence of epidemic and epizootic outbreaks single-stranded rna viruses the bunyaviridae family was named after the prototypical bunyamwera virus (bunv) isolated in from mosquitoes (aedes spp.) in bunyamwera, uganda. currently, the bunyaviridae family includes four genera of animal viruses (orthobunyavirus, phlebovirus, nairovirus, and hantavirus) and one genus (tospovirus) of plant viruses. bunyavirus virions are spherical in shape (size, about À nm) and have an outer lipid bilayer with the viral envelope glycoproteins gn and gc exposed on the surface. the genome consists of three segments of single-stranded, negative-sense rna with a total length from , to , nt. depending on the size, the segments are designated l (large), m (medium), and s (small). the viral proteins are synthesized on the mrna that is produced during replication and that is complementary to the genomic rna. the length of segments varies for different genera, but in general, they have a common structure. the l-segment, whose length is from , nt (phlebovirus) to , nt (nairovirus) , has a single open reading frame (orf) encoding rna-dependent rna polymerase (rdrp). the m-segment of all of the genera also has a single orf, which encodes a polyprotein precursor of envelope glycoproteins gn and gc. the length of the m-segment ranges from , nt for some of the phleboviruses to , À , nt for the nairoviruses. the mature glycoproteins gn and gc of the bunyaviruses are derived during complex endoproteolytic events leading to cleavage of the polyprotein precursor by cellular proteases. the s-segment of the bunyaviruses encodes a nucleocapsid protein. additional nonstructural (nss) protein is encoded by the s-segment of viruses of the phlebovirus, tospovirus, and orthobunyavirus genera. , the bunyaviruses are widely distributed in the world and are one of the most numerous known zoonotic viruses. most of the zoonotic bunyaviruses are transmitted to animal or humans by bloodsucking arthropod vectors, usually mosquitoes or ticks. viruses of the hantavirus genus are the exception, being transmitted mainly by aerosol formed from virus-laden urine, feces, or saliva of infected rodents or insectivores that are their natural hosts. À the genus hantavirus consists of those bunyaviruses of vertebrates which do not have the ability to replicate in an arthropod's cell and which are transmitted by respiratory route through the formation of aerosols from urine or feces containing the virus. the morphology of the virion and the genome structure of the hantaviruses are common to all bunyaviruses. the size of the negative-sense ssrna genome of the prototypical hantaan virus (htnv) is , nt for the l-segment, , nt for the m-segment, and , nt for the s-segment (figure . ). in nature, hantaviruses persist asymptomatically in rodents and insectivores, with each type of hantavirus associated predominantly with one host species. the phylogenetic relationships of hantaviruses enable virologists to divide them into three lineages, which correspond in general to their main hosts. in the s-segment of some hantaviruses carried by arvicolinae and sigmodontinae rodents, there is an additional orf-encoded nonstructural protein nss. but nss is absent in the hantaviruses of the murinae rodents. À history. hemorrhagic fever with renal syndrome (hfrs) was originally described as a separate nosological category (called "endemic (epidemic) hemorrhagic nephroso-nephritis" at that time) by anatoly smorodintsev (figure . ) during À in the far east. later, japanese scientists described hfrs in northeastern china as "songo fever" and swedish scientists as "epidemic nephropathy"; a similar disease was described in in china. the abbreviation "hfrs" was suggested by mikhail chumakov (figure korea. hantaviruses. the hantaviruses are members of the hantavirus genus of the bunyaviridae family. the first serotype, -htnv, included strains isolated from mouselike rodents (muridae) in south korea, china, and the southern part of the russian far east (primorsky krai). À the second serotype, puumala virus (puuv), was isolated from hamsterlike rodents (cricetidae), mainly the bank vole (myodes glareolus) in finland and then in other european countries and the western part of russia, as well we from maximowicz's vole (microtus maximoviczii) in the far east). À the third serotype, seoul virus (seov), was isolated from brown rats (rattus norvegicus), black rats (rattus rattus), and laboratory albino rats (rattus norvegicus f. domestica) in south korea and elsewhere, including the united states. , the fourth serotype, dobravaÀbelgrade virus (dobv), was isolated from the striped field mouse (apodemus agrarius) in slovenia and yugoslavia. the fifth serotype, sin nombre virus (snv), literally "nameless virus" in spanish, was isolated from the meadow vole (microtus pennsylvanicus). in addition to the main serotypes, other serotypes are known today, including in eurasia: amur virus (amrv), isolated from asiatic forest mice (apodemus peninsulae) in the far east of russia and in china ; tula virus (tulv), from common voles (microtus arvalis) in central russia , ; khabarovsk virus (khav), from from reed voles (microtus fortis) and siberian brown lemmings (lemmus sibiricus) in the far east ; thottapalayam virus (tpmv), from asian musk shrews (suncus murinus) in india ; thailand virus (thaiv), from bandicoots (bandicota indica) in thailand ; and a newfound hantavirus, from chinese mole shrews (anourosorex squamipes) in vietnam. virion and genome. the size of the negative-sense ssrna genome of the prototypical htnv is , nt for the l-segment, , nt for the m-segment, and , nt for the s-segment (figures . and . ). epizootiology. rodents (order rodentia) are the main natural reservoir of hantaviruses. nevertheless, strains have been isolated from birds in the far east and from bats in china. infection in rodents is asymptomatic, but the virus is expelled with saliva, urine, and excrement, most intensively during the first month after inoculation. (during this period, virus antigen can be detected in the lungs.) the evolution of hantaviruses is closely related to that of its rodent host (figure . ). , , at least species of rodents (rodentia), species of lagomorphs (order lagomorpha), species of insectivores (order insectivora), species of predators (order carnivora), and species of artiodactyls (order artiodactyla) are known to take part in hantavirus circulation on the territory of northern eurasia. , , the main species of rodents, which are the hosts of hantaviruses in russia, are presented in table . . the infection rate of mouselike rodents and insectivores lies within the limits . . %. hantavirus antigens have been detected in birds as well: the oriental turtle dove (streptopelia orientalis), coal tit (parus ater), marsh tit (parus palustris), daurian redstart (phoenicurus auroreus), nuthatch (sitta europaea), black-faced bunting (emberiza spodocephala elegans), eurasian jay (garrulus glandarius), hazel grouse (tetrastes bonasia), pheasant (phasianus colchicus), ural owl (strix uralensis), green-backed heron (butorides striatus), and grey heron (ardea cinerea). hantavirus (magboi virus, or mgbv) was isolated in from the hairy slit-faced bat (nycteris hispida) in africa (sierra leone), but the role of bats in the circulation of hemorrhagic fever with renal syndrome virus (hfrsv) is yet to be investigated in detail. in western siberia, the main natural reservoir of hfrsv is rodents of the hamsterlike (cricetidae) family-in particular, bank voles (myodes glareolus), with a susceptibility up to %; red-backed voles (myodes rutilus), susceptibility %; and, in the north, siberian brown lemmings (lemmus sibiricus), %. the infection rate of other rodents and insectivores is about . À . %. , in eastern siberia, the maximum susceptibility is demonstrated in grey red-backed voles (myodes rufocanus), %; house mice (mus musculus), %; water voles (arvicola terrestris), %; and tundra voles (microtus oeconomus), %. in the far east, hfrsv was revealed to circulate among field mice (apodemus agrarius) with a susceptibility of about %; asiatic forest mice (a. peninsulae), susceptibility %; reed voles (microtus fortis), À %; grey redbacked voles (myodes rufocanus), %; and other rodents (rodentia), . À . %. , , epidemiology. hfrsv infection starts by aerogenic penetration of the virus during the inhalation of waste products (saliva, urine, excrement) of latently infected animals. an alimentary pathway (with contaminated food and water) of the infection is also possible. , , , , hfrs is distributed over eurasia (russia, belarus, ukraine, moldova, the baltic countries, the czech republic, slovakia, bulgaria, romania, serbia, slovenia, england, france, germany, belgium, hungary, denmark, fennoscandia, kazakhstan, georgia, azerbaijan, china, north and south korea, japan), as well as american and african countries. , , during À , in of regions in russia, , cases of hfrs were registered (table . ). annual morbidity of hfrs in russia is in the range from , to , cases ( . À . %) and is decreasing. about % of cases take place in european forest landscapes. puuv associated with the bank vole (myodes glareolus) provokes about % of hfrs cases in russia (especially in bashkortostan, udmurtia, mari el, tatarstan, the chuvash republic, orenburg, ulyanovsk, and the penza region). , morbidity in the urban population is higher ( %) than in the rural one. the peak of the disease occurs during julyÀoctober in forests and in gardens and kitchens closely situated to the forests. , À dobv associated mainly with field mice (apodemus agrarius) and small forest mice (a. uralensis) is of leading epidemiological significance in the central and southwestern sectors of the european part of russia (the voronezh, lipetsk, orel, and belgorod regions), as well as in georgia. , , , puuv and tulv are associated with the common vole (microtus arvalis) and the bank vole (myodes glareolus) and are also distributed over this territory. , , a similar situation is observed in other regions of the central federal district: in the moscow, yaroslavl, ryazan, tver, kaluga, vladimir, ivanov, kostroma, smolensk regions. hfrs morbidity in the moscow region is associated with puuv, the infection rate of which is À % among bank voles (myodes glareolus), À % in the common vole (microtus arvalis), % in major's pine vole (microtus majori), and in À % other rodent species. in krasnodar krai, the black sea field mouse (apodemus ponticus) and major's pine vole (microtus majori) play the main role in human morbidity. , human morbidity in the european part of russia is registered beginning at a relatively low level in marchÀapril, decreasing to yet a lower level in mayÀaugust, increasing in septemberÀnovember, and then increasing again during decemberÀjanuary. the hyperendemic territory is the southwestern ural region (especially the bashkortostan republic and the chelyabinsk and orenburg regions), the volga-vyatka economic region (especially the udmurt republic), the chuvash republic, and the tatarstan, mari el, samara, penza, saratov, and ulyanovsk regions. , the main human morbidity occurs among those À years old (chiefly men). in russia, hfrs represents a significant part of all naturalfoci zoonotic diseases. the immune layer to hfrsv in the european part of russia is a mean . %; in the bashkortostan republic, it reaches up to % (mean, %). the immune layer among the populations of western and eastern siberia is about % for the entire region, . % in krasnoyarsk krai, . % in the irkutsk region, . % in the omsk region, and . % in the tyumen region. , the far east provides about % of all hfrs cases in russia. the highest morbidity was revealed in khabarovsk krai, primorsky krai, and the amur region. in khabarovsk krai and primorsky krai, las in china and japan, -htnv is associated with grey red-backed voles (myodes rufocanus). , , , the morbidity of seov (the third serotype) associated with the synanthropic brown rat (rattus norvegicus) and black rat (r. rattus) was examed in both the far east and the european part of russia. the researchers found that seov provoked hfrs more often among the urban population, whereas htnv did so more often among the rural population, of primorsky krai. morbidity in the far east has a small uptick in mayÀjuly and reaches its main peak in novemberÀdecember. the immune stratum in the far east is about % (ranging from . % in the amur region to . % in primorsky krai). , pathogenesis. capillary damage is the basis of hfrs pathogenesis. in the first part of the disease, toxicoallergic phenomena predominate, caused by viral infection of the walls of vegetative centers, venules, and arterioles. lesions on the sympathetic nodes of the neck are followed by hyperemia of the face and neck. irritation of the vagus nerve leads to bradycardia and a fall in arterial pressure. damage to the vascular permeability is accompanied by hemorrhages in mucous membranes and the skin. the cause of death is cardiovascular insufficiency, massive hemorrhages into the vital organs, plasmorrhea into the tissues, collapse, shock, swelled lungs, spontaneous rupture of the kidneys, a hypertrophied brain, and paralysis of the vegetative centers. , clinical features. the incubation period is À days. hfrs starts with fever, headache, muscular pain, dizziness, nausea, vomiting, hyperemia of the face and neck, bradycardia, and a fall in arterial pressure. abnormalities of the central nervous system (cns) in the form of block, excitement, hallucinations, meningeal signs, and visual impairments often occur. hemorrhagic syndrome becomes apparent as plasmorrhea into the tissues, together with microthrombosis; exanthema; petechial skin rash; nasal, pulmonary, and uterine bleeding: vomiting blood, hematuria, and visceral bleeding. in some cases, pasternatsky syndrome, pain in the kidneys, oliguria, and albuminuria become morphologically apparent as interstitial and tubular nephritis. the duration of fever is À days. two-wave temperature dynamics is possible. , analyses of , cases of hfrs etiologically linked with puuv in sweden during À found . % mortality in the first three months of the disease. , defense immunity remains for at least years. , diagnostics. laboratory diagnostics are based on the fluorescent antibody method (fam), enzyme-linked immunosorbent assay (elisa), and reverse transcription polymerase chain reaction (rt-pcr) testing. the virus can be isolated with the use of vero e (green monkey kidney cell line), bs (diploid human embryo lung cell line), a- (human lung carcinoma cell line), or rlc (rat lung tissue primary cell culture). , control and prophylaxis. treatment of hfrs can be symptomatic, pathogenetic, or etiotropic (or any combination thereof). during the fever period, early hospitalization, disintoxical therapy, and strengthening of the walls of vessels are necessary. during the oliguria period, transfusion with desalinated human albumin, hemodes, a % glucose solution, and an isotonic nacl solution (under the control of the emitted volume of urine) are given. in case of shock, antishock therapy is applied, and hemodialysis is prescribed for kidney insufficiency. , vaccination is the most effective approach to the prophylaxis of hfrs. the efficacy of vaccination was demonstrated in china and in north and south korea. nevertheless, it must be mentioned that vaccines in these countries are produced from htnv and seov stains and do not defend against puuv infection, which is the main etiological agent of hfrs in the european part of russia (where % of all russian morbidity occurs) . for a long time, anti-hfrs vaccine was difficult to produce because there were no sensitive cell lines to accumulate hantavirus. however, the recent adaptation of puuv and dobv to the certified vero e cell line affords an opportunity to produce candidate vaccines against hfrs. experimental series of "combi-hfrs-vac" vaccine have passed compliance tests for medical immunoglobulin preparations for use in humans. , , the genus nairovirus includes the ticktransmitted bunyaviruses, whose genome is the largest in the family bunyaviridae. the size of l-segments of the dugbe virus (dugv), a prototypical species of the nairoviruses, is , nt. the m-and s-segments are , and , nt, respectively (figure . ) . as with other bunyaviruses, the l-segment of the nairoviruses encodes an rdrp, the m-segment encodes a polyprotein precursor of the envelope glycoproteins gn and gc, and the s-segment encodes the nucleocapsid (n) protein. , the genus nairovirus was established on the basis of antigenic relationships among viruses of the six antigenic groups of arthropod-borne viruses: the crimeanÀcongo hemorrhagic fever (cchf), nairobi sheep disease (nsd), qalyub (qyb), sakhalin (sak), dera ghazi khan (dgk), and hughes (hugv) groups. À subsequently, a seventh, thiafora (tfa), group was assigned to the genus. , currently, about viruses are assigned to the genus nairovirus, now united in the aforementioned seven groups. sequence analysis of previously unclassified bunyaviruses revealed that the nairoviruses actually number much more than . three additional groups of nairoviruses-issyk-kul (isk), artashat (artsv), and tamdy (tam)-were established on the basis of phylogenetic analysis (table . ). cchfv belongs to the nairovirus genus of the bunyaviridae family and is the etiological agent of crimeanÀcongo hemorrhagic fever (cchf). history. cchf was first mentioned as "hunibini" and "hongirifta" by tajik physician abu-ibrahim djurdjani in the twelfth century. the viral nature of cchf was originally established in during an expedition to crimea headed by mikhail chumakov at the time of an outbreak. À the modern history of cchfv investigation starts in june with an epidemic of the disease in the northwestern steppe part of the crimean peninsula. more than severe cases of the disease broke out, all exhibiting hemorrhagic syndrome, known in that time as "severe infectious capillary toxicosis." mikhail chumakov headed an expedition to the region, and much research revealed that the disease is transmitted by hyalomma plumbeum (marginatum) ticks of the ixodidae family. the disease in , the historical hodzha strain was isolated from a patient with hemorrhagic fever in uzbekistan, as was a set of strains from h. marginatum larvae and nymphs in the astrakhan region, near the caspian sea. , in , the similarity between the etiological agent of crimean hemorrhagic fever and that of congo virus, isolated from a patient in in zaire (congo), was demonstrated, so the virus was renamed cchfv. , genome and taxonomy. like the genomes of all nairoviruses, that of cchfv consists of three segments of negative ssrna: a signed small (s) ( , nt) segment, a medium (m) ( , nt), and a large (l) ( , nt) segment. each segment has a single orf that encodes the nucleocapsid protein (n, aa, s-segment), a polyprotein precursor of envelope glycoproteins gn and gc ( , aa, m-segment), and rdrp ( , aa, l-segment). genetic diversity among cchfv strains may reach % nt and % aa differences for m-segment sequences, a reflection of pressure on the immune system and adaptation to various ecologic zones with different prevalences of hyalomma tick species. the s-and l-segments are more conservative: the level of divergence of s-segment sequences is % nt and % aa, and that for l-segment sequences is % nt and % aa. phylogenetic analysis based on sequence data comparisons of s-segments shows that cchfv isolates from different regions can be clustered into seven phylogeographic groups: west african isolates (group i), as well as isolates from central africa (uganda and the democratic republic of the congo) (group ii); south africa and west africa (group iii); the middle east and asia (group iv) (the asian strain can be divided to two distinct subgroups: asia (iva) and asia (ivb)); europe and turkey (group v); and greece (group vi), a separate group detached from the rest of europe (figure . ) . À in general, the genotypic structure defined on basis of the s-segment analysis is correlated strictly with geography. cases of isolation of strains not typical for a given territory were attributed to possible transmission of the virus by infected ticks carried by migratory birds. the tree topology based on the l-segment comparison is, on the whole, similar to that generated on the basis of the s-segment. exceptions are the viruses from senegal, which represent a separate lineage in the s-segment analysis, and those clustered within group iii in the l-segment analysis. similarly, the division of group iv into group iva (asia ) and ivb (asia ) is not clear (figures . and . ) . in russia, most of the strains of cchfv that were isolated were isolated in the country's southern regions (astrakhan, volgograd, and stavropol districts). phylogenetic analysis showed that all of them are closely related to european and turkish strains (group v). À epizootiology. up to today, cchfv has been found to circulate in countries in europe, africa, and asia. , À cchfv was isolated from at least species of mainly ixodidae ticks, but their roles in maintaining virus circulation are different (tables . and . ). the main significance for cchfv reservation and transmission belongs to ticks of the hyalomma genus: h. marginatum in the south of he european part of russia, h. anatolicum and h. detritum in the middle east and asia, and h. asiaticumin kazakhstan. according to our data, the viral load among imagoes of h. marginatum in the astrakhan region in À was . %; among nymphs, the load was . %. the presence of transphase and transovarial transmission of cchfv provides a reservation for viruses during the interepidemic period. three hostsfor larvae (ground birds, mainly corvidae; table . isolation of cchfv from ixodidae ticks mouselike rodents; and hares), nymphs (also ground birds, mouselike rodents, and hares), and imagoes (large mammals-mainly cattle, sheep, and camels)-provide a variety of ecological links of cchfv to vertebrates. , À in nigeria, cchfv was isolated from midges (culicoides sp.) the distribution of h. marginatum is limited by the isotherm of effective temperatures such that sum (Σ t $ c ) , c, or days with mean temperature $ c per year. so, the northern boundary of the distribution of cchfv in the south of the european part of russia lies in the dry steppe subzone. in russia and south africa, cchfv is often isolated from hares. , cchfv was isolated from hedgehogs (atelerix spiculus) in nigeria. hares and mouselike rodents play the main role in cchfv circulation. , , viremia in birds is not sufficient for vector transmission (although specific antibodies appear); nevertheless, ground birds are an important element of cchfv transmission because they are the hosts for the preimaginal phases of h. marginatum development. , , during field investigations of chatkalsky ridge in kirgizia, nymphs and larvae of h. marginatum dominated among field-collected materials from birds. the highest number of ticks was found on rollers (coracias garrulus), crested larks (galerida cristata), tree sparrows (passer montanus), and blackbilled magpies (pica pica). in the astrakhan region, rooks (corvus frugilegus) are the main hosts for h. marginatum preimaginal phases. during migrations, birds can take part in dispersing preimago ticks that carry the virus. for example, in spain in , cchfv of african origin (probably introduced by migrating birds) was isolated from h. lusitanicum. european birds overwintering in africa were also found to harbor ticks that carried the virus. cchfv infection rates found as the result of an investigation of , domestic animal sera are presented in table . . domestic animals are one of the main reservoirs of cchfv among vertebrates. viremia ( . À . (log ld )/ mcl) sufficient for the infection of ticks was detected À days after experimental inoculation of sheep. viremia after up to days post inoculation was detected in small gophers (citellus pygmaeus), long-eared hedgehogs (hemiechinus auritus), and wood mice (apodemus sylvaticus). experimental infection was revealed only in nymphs, and that is why hares and corvidae birds-the main hosts for nymphs-play the chief role in cchfv circulation. astrakhan volgograd dagestan rostov stavropol krasnodar total , of ixodidae (at first, h. marginatum) ticks in this region as the result of climatic changes. during À , , cases of cchf were recorded in russia, including in stavropol krai, in the rostov region, in the kalmyk republic, in the astrakhan region, in the volgograd region, in the dagestan republic, in the ingush republic, and in the karachaevoÀcherkesskaya republic (table . ). in , cases of cchf were recorded on the territory of the southern federal district and the north caucasian federal district (table . , figure . ). the absence of any recorded cases of cchf in krasnodar krai could be explained by a lack of attention to cchf diagnostics. a decrease in the proportion of severe clinical forms with hemorrhagic syndrome occurred after . the drop could have been due to the introduction of high-grade express diagnostics methods into clinical practice and an intensification in seeking out and diagnosing those suspected of having cchf. at the same time, the disease extended its incidence into the new territories of the volgograd region, with nosocomial cchf cases recorded there once again. pathogenesis. pathogenesis is defined by lesions of the vascular and nervous systems. , , clinical features. the incubation period after transmissive cchfv inoculation (as the result of a tick bite) is À days, whereas that after contact inoculation is À days. the difference is due to a much higher quantity of virus entering the system during contacts inoculation. , , cchf starts rapidly, with the temperature increasing to À c and the appearance of fever, skin hyperemia in the top half of the trunk, headache, lumbar pain, abdominal and epigastric pains, generalized arthralgia, conjunctivitis, pharingitis, and diarrhea. about % of cases have two obvious waves of increasing temperature, with the temperature decreasing in À days after the end of the incubation period. petechial rash appears in the majority of all cchf patients in À days after the incubation period and is a marker of the second increasing-temperature wave. hemorrhagic diathesis with nasal bleeding (in two-thirds of cases), bloody vomiting, blood in the sputum, and hematuria, all starting À days after the end of incubation period, are characteristic in % of cases. the duration of the hemorrhagic period is À days. meningitis symptoms and signs of psychosis (depression, sleepiness, lassitude, photophobia) could develop as well. lethality is À % for transmissive inoculation and up to % for contact inoculation. nevertheless, lethality is decreasing as the result of the introduction of modern testing systems and treatment with ribavirin. the convalescent period is about a month. , , , e.v. leshchinskaya has suggested the following clinical classification of cchf: (i) severe form with hemorrhagic syndrome ( .a. without band bleeding; .b. with band bleeding); (ii) without hemorrhagic syndrome ( .a. medium-severe form; .b. light form). , diagnostics. diagnosis is based on the detection of both specific antibodies via elisa (igm after days post disease progression and igg) and virus rna via rt-pcr testing (earlier than days post disease progression). , both tests must be conducted for a definitive diagnosis of cchf to be made. during the first week of infection with cchf, positive results via rt-pcr are obtained in % of cases; during the second week, the percentage is %. during the second week of the disease, positive results in igm via elisa are obtained in % of cases; during the third week, the percentage of positive reults in igg via elisa is %. À control and prophylaxis. ribavirin is the most effective drug prescribed today. , À ribavirin is used for days after symptoms first appear: , mg ( capsules) or mg/kg for the first time, then mg times a day if the weight of the patient is more than kg or mg times a day if the weight of the patient is is less than kg). the duration of treatment is À days. ribavirin must not be used by pregnant women, except when the disease is considerd life threatening. vaccine development is currently just in the experimental stages, À so prophylaxis involves early detection of sick humans and the prevention of further contact infections. nonspecific prophylaxis includes the eradication of ixodidae ticks on livestock and acaricide treatment of locations inhabited by domestic animals. in pastures with large numbers of ixodidae ticks, animals have to be led into box stalls and the humans leading them there must use special suits. history. artashat virus (artsv, strain leiv- ar) was originally isolated from ornithodoros alactagalis ticks (family argasidae) collected in the burrows of a small five-toed jerboa (allactaga elater) near arevashat village ( absence of antigenic relationships with any known viruses, it was referred to as an "unclassified bunyavirus." À taxonomy. three strains of artsv were sequenced. a full-length genome comparison revealed that artsv has À % nt similarity to other nairoviruses. phylogenetic analysis revealed that the virus is a new species in the nairovirus genus and forms a distinct genetic lineage on the nairovirus tree, which was constructed for all three segments of the genome (figures . À . ) . the phylogeny of the nairoviruses is based mainly on analyses of the partial sequence of the conservative catalytic core domain of rdrp. , the similarity of this domain of artsv to other nairoviruses is À % nt and À % aa. the phylogenetic tree constructed by the maximum-likelihood method on the basis of the amino acid alignment of the rdrp catalytic core domain of nairoviruses confirms the topology of artsv on a newly formed genetic lineage (figures . À . ). the nairoviruses on the tree can be divided into two main phylogenetic groups. the first group includes the nairoviruses, which are transmitted predominantly by ixodids: the crimeanÀcongo hemorrhagic fever group (hyalomma and haemaphysalis, as well as dermacentor, rhipicephalus, and ixodes), the dugbe group (mainly amblyomma, but also hyalomma, rhipicephalus, and haemaphysalis), the sakhalin group (ixodes), and the tamdy group (hyalomma). the first group also includes erve virus (ervev), whose vectors are unknown. , the second phylogenetic lineage includes the nairoviruses from the hughes, issyk-kul, dera ghazi khan, and qalyub groups, whose vectors are argasids: argas and ornithodoros. the tree topology of artsv shows that the virus is in the lineage of the nairoviruses transmitted predominantly by ixodidae ticks, although all isolations of artsv were obtained from the argasidae ticks o. alactagalis and o. verrucosus (table . ). it can be assumed that the adaptation of artsv to argasids is the result of the the narrow ecologic niche occupied by those ticks, which are ticks of the subgenera theriodoros and pavlovskyella. note that, although ervev, a european nairovirus, is phylogenetically close to the nairovirus transmitted by ixodids, the association of ervev with ixodes spp. ticks has not been established in endemic areas (southern europe). ervev has been isolated from shrews (crocidura russula). arthropod vectors. the adaptation of viruses to argasidae ticks facilitates the possibility of survival of viral populations in winter at low temperatures and in dry periods. the ability of argasids to fast (up to years and more), the long life cycle of these ticks (up to À years), and their polyphagia and ecological plasticity determine the stability of the natural foci of arboviruses transmitted by argasids. these foci are confined mainly to the arid regions of the southern part of the temperate and subtropical zones. , , the northern border of the range of argasids coincides with isolines denoting a frost-free period of À days per year and an average daily temperature above c for no less than À days per year. tick species from the subgenera theriodoros (ornithodoros alactagalis, o. nereensis) and pavlovskyella (o. papillipes, o. verrucosus, o. cholodkovskiy, o. tartakovskiy) are associated mainly with burrows of rodents. this ecological peculiarity narrows the possibility of the spread of viruses that are adapted to ticks from the theriodoros and pavlovskyella subgenera. it also applies to artsv associated with burrowÀ shelter biomes and found only in transcaucasia. history. caspiy virus (casv, prototypical strain leiv- az) was originally isolated from the blood of a sick herring gull (larus argentatus) caught on gil island in the baku archipelago, off the western coast of azerbaijan in the caspian sea ( n, e; figure . ) in . À on the basis of electron microscopy, casv was classified as a member of the bunyaviridae family, but antigenic relationships with known bunyaviruses have not been found. thus, casv was categorized into the unclassified bunyaviruses. , À at the same time, and in the same place, three strains of casv were isolated from ornithodoros capensis (family argasidae) ticks taxonomy. the genome of the prototypical strain leiv- az of casv was sequenced, and it has been shown that casv is a member of the hugv group of the nairovirus genus. the s-segment of casv is about , nt in length and has a single orf that encodes the nucleocapsid protein (n, aa). the second start codon, in position , is located in the n-protein orf of casv. the identity of the amino acid sequence of the n-protein of casv with those of other nairoviruses is only %, on average. the cleavage site for caspase- (d evd ) that has been found in the n-protein of cchfv is absent in casv. cleavage of n by caspase- is required for effective replication of cchfv. note that caspase cleavage sites in the nucleocapsid protein are also necessary for replication of human influenza a viruses. the m-segment of casv, like that of the other nairoviruses, has a single orf-encoded polyprotein precursor of the envelope glycoproteins gn and gc. the length of the gn/gc precursor of casv is , aa. according to the results of an analysis of polyprotein in the program signalp server . , the first aa constitute the signal peptide that is cleaved on the ssa/sy site. the cleavage site between pre-gn and pre-gc is in position (vsg/ik). these data are confirmed by the location of transmembrane domains in mature proteins gn and gc that was defined with the use of the program tmhmm server . . six potential sites of n-glycosylation are predicted in the mature gn protein of casv, only one in the gc protein. in general, the level of identity of polyprotein in casv is À % aa with that of other members of the nairovirus genus (table . ). the l-segment of casv has an orf ( , aa) that encodes the viral enzyme rdrp, which is the most conservative viral protein. the similarity of the rdrp of casv to that of other nairoviruses for which complete genome sequences were available is . À . % aa. phylogenetic analysis based on the predicted full-length amino acid sequences revealed that casv is equidistant from other nairoviruses, and forms a distinct branch, on the trees (figures . À . ). for many nairoviruses, only short sequences of the catalytic core domain of rdrp are available in genbank. this domain of rdrp is very conservative and relevant to phylogenetic analysis. , , the highest level of similarity ( % aa) that the rdrp core domain of casv has is with the same sequences in viruses of hug. on the dendrogram, constructed on the basis of a comparison of rdrp core domains, casv is located on the branch of the hug group (figures . À . ). note that viruses of this group (as well as casv) have been isolated from ornithodoros (carios) ticks that are associated with seabirds on the coasts and islands of the world's oceans. , thus, the phylogenetic relationship of casv with hug group viruses reflects the ecological features of those coasts and islands. arthropod vectors. ornithodoros capensis ticks inhabit the coasts and islands of the atlantic, indian, and pacific oceans from the southern part of the temperate zone to the equator, as well as some large inland ponds. , , o. capensis ticks feed on many bird species, mainly those of the order charadriiformes: gulls (family laridae) and terns (sturnidae), but also cormorants (phalacrocoracidae) and pelicans (pelecanidae). , these argasid ticks have a life cycle made up of six to eight stages: egg, larva, three to five stages of nymphs, and imago. according to laboratory study, the cycle is from to days and so can be completed during a single breeding season. these ecological peculiarities provide stability to the natural foci of the viruses, which are adapted to the o. capensis tick viruses and their transcontinental transfer by migrating birds. vertebrate host. in , during the collection of field material on islands in the baku archipelago, an epizootic among herring gulls was observed. the first strain of casv was isolated from sick birds. migrations in search of food, including migration between the western and eastern coasts of the caspian sea, result in a sharing of the argasids and viruses ranging over the area. history. the prototypical strain leiv- uz of the chim virus (chimv) was isolated from ornithodoros tartakovskyi ticks collected in july in the burrows of great gerbils (rhombomys opimus) in the vicinity of the town of chim in the kashkadarinsky region of uzbekistan) ( n, e; figure . ). À isolation of chimv was carried out during monitoring of these arboviruses' foci on the territory of central asia and kazakhstan. chimv was investigated through serological testing with viruses from different families and with unclassified viruses isolated earlier in the ussr. because no antigenic relationships of chimv were (and still have not been) found, chimv was assigned to the category of unclassified viruses. , later, four strains of chimv were isolated from the ticks o. tartakovskyi, o. papillipes, and rhipicephalus turanicus (rhipicephalinae) respectively collected in the burrows of great gerbils in the kashkadarya, bukhara, and syrdarya districts of uzbekistan in À . , three strains of chimv also were isolated from hyalomma asiaticum (hyalomminae) ticks and from the livers of great gerbils, which were collected in the floodplains of the or river and karatal river (dzheskazgan district, kazakhstan) in april (figure . ). , taxonomy. the genome of the prototypical strain leiv- uz of chimv was sequenced, and, on the basis of sequence analysis, the virus was classified as a novel member of the nairovirus genus. phylogenetic analysis based on a partial sequence of a catalytic center of rdrp placed chimv on the genetic branch of the qybv group. , the amino acid sequence of this domain of chimv has an % identity with qybv, geran virus (gerv), and bandia virus (bdav), the other members of the qybv group. À all these data are consistent with the fact that viruses of the qybv group, as well as chimv, have an environmental connection to ticks of the ornithodoros genus and to the burrows of rodents. qybv has repeatedly been isolated from o. erraticus ticks, collected in burrows of the african grass rat (arvicanthis niloticus) in the nile valley and the nile delta in egypt. to date, only short sequences of the rdrp of qybv are available in genbank, but recently we gave a genetic characterization of gerv, isolated in transcaucasia and, apparently, closely related to qybv. the full-length amino acid comparison of chimv with gerv showed that their nucleocapsid proteins n (s-segment) have only a . % identity. the similarity of complete amino acid sequences of rdrp (l-segment) is . %. the similarity of the polyprotein precursor of gn/gc is . %. the proteins of chimv have . À . % aa (n-protein), . À . % aa (gn/gc precursor), and . À . % aa (rdrp) identities with their counterpart proteins in other nairoviruses. among these nairoviruses, chimv has the highest level of similarity with iskv, which is associated with bats in central asia (figures . À . ) . arthropod vectors. most isolations of chimv were obtained from ornithodoros tartakovskyi ticks. these ticks are common in the irano-turanian and mountain provinces of asia (kazakhstan, the central asian republics, northeastern iran, and china (xinjiang)). the western border of the area in question is the eastern shore of the caspian sea ( À e), the eastern border is in xinjiang ( e) , and the northern border is À n. the typical biotopes that o. tartakovskyi ticks inhabit are the foothills of dry steppes with loess soils. the ticks also inhabit meadow steppes and deserts (floodplain terraces and canals). o. tartakovskyi ticks prefer burrows of small diameter (inhabited by rodents, including jerboas, ground squirrels, small predators, and hedgehogs, as well as by turtles and birds). synanthropic biotopes are rarely inhabited. vertebrate hosts. the great gerbil (family muridae, subfamily gerbillinae, genus rhombomys) is distributed from the shores of the caspian sea on the plains of central asia and southern kazakhstan, to the deserts of central asia, iran, and afghanistan, and on eastward to northern china and inner mongolia. great gerbils are typical inhabitants of sandy deserts and form a colony with complex multistory burrows that have a large number of entranceways and egresses (up to À ). these burrows are a specific biotope that exists for many decades, and they maintain natural foci (in particular, of plague) in arid areas. , animal infection. the significance of chimv in the pathology of humans is unknown. antibodies to chimv have been found in camels ( . %) in the kashkadarya region in uzbekistan. this finding shows the ability of chimv to infect camels, as does qybv, but additional studies are necessary to clarify the pathogenicity of chimv in humans and cattle. history. grnv (strain leiv- az) was isolated from ornithodoros verrucosus (family argasidae, subfamily ornithodorinae) ticks collected in a burrow of red-tailed gerbils (meriones (cricetidae) erythrurus) near geran station, goranboy district, azerbaijan; figure . ). serological methods have failed to identify grnv, but the virus has been sequenced and classified into the nairovirus genus (family bunyaviridae). taxonomy. the genome of grnv was sequenced by a next-generation sequencing approach. full-length genome analysis revealed that the genetic similarity of grnv to other known nairoviruses is, on average, À % aa for the nucleocapsid protein (n, s-segment), À % aa for the polyprotein precursor of the proteins gn and gc (m-segment), and . À . % aa for rdrp (l-segment). the highest level of similarity all three proteins of grnv have is to that of chimv ( . À . % aa identity) and that of iskv ( . À . % aa identity). , further analysis based on a comparison of partial sequences of the conservative core domain of rdrp of the nairoviruses showed that grnv and chimv were most closely related to qybv, which is the prototypical virus of the group of the same name. the nucleotide sequence of the rdrp core domain of grnv has . % nt and . % aa identities with the counterpart sequence of qybv. the data obtained allow grnv to be classified as a virus of the qybv group (figures . À . ). the phylogenetic relationship between grnv and qybv corresponds to their similar ecological characteristics. qybv was first isolated in by r. taylor and h. dressler from argasid ornithodoros erraticus ticks collected in a rodent burrow in the nile river delta near qalyub village, egypt ( n, e). À complementbinding antibodies to qybv were found in humans ( . %), camels, donkeys, pigs, buffalos, dogs, and rodents. , the antigenic group of qalyub, a group that includes qybv and antigenic-related bdav, is one of the prototypical groups of the nairovirus genus. , previously, qybv had been repeatedly isolated from o. erraticum collected in the burrows of rodents (arvicanthis) in africa. the second member of the qybv group, bdav, was isolated from o. sonari (a member of the o. erraticus group) collected in the burrows of rodents (mainly mastomys) in senegal. , the isolation of gerv, which is closely related to qybv, is the first confirmation of the circulation of qybv group viruses in transcaucasia. arthropod vectors. the area of distribution of o. verrucosus ticks covers the southern part of moldova as well as ukraine and the caucasus region, and is limited by n latitude. the area includes the southern part of russia (the krasnodar and stavropol regions), the northern and eastern foothills of dagestan, the foothills and lowland hills of georgia, the valleys of the hrazdan river in armenia, the foothills of the lesser caucasus mountains in azerbaijan, and the gobustan plateau and the absheron peninsula, also in azerbaijan. o. verrucosus ticks inhabit shelter biotopesin particular, the burrows of red-tailed gerbils (meriones (cricetidae) erythrurus), animals that are common in central asia, southern kazakhstan, and eastern transcaucasia. redtailed gerbils tends to inhabit desert and semidesert landscapes. their burrows are deep and may have À entranceways and egresses. history. iskv (prototypic strain, leiv- k) was originally isolated from a pool of internal organs (liver, spleen, brain) of nyctalus noctula bats, and their ticks (argas (carios) vespertilionis) were collected near issyk-kul lake in kyrgyzstan in (figure . ). , subsequently, iskv was isolated from other bat species of the vespertionidae family (vespertilio serotinus, vespertilio pipistrellus, myotis blythii, rhinolophus ferrumequinum), and from birds, in different regions of kyrgyzstan and tajikistan. À two strains were isolated from anopheles hyrcanus mosquitoes and culicoides schultzei biting midges, respectively (figure . , table . ). , , complement-fixation testing showed that iskv is closely related or identical to the keterah virus, which was isolated from scotophilus temminckii bats and a. pusillus ticks in malaysia in . , a strain that has a close, one-sided antigenic relationship to iskv, leiv- taj (named garm virus), was isolated from a common redstart (phoenicurus phoenicurus) caught in the village of garm, tajikistan, morphological studies by electron microscopy characterized iskv as a member of the bunyaviridae family, and because no antigenic relation to any known viruses was found, it was assigned to the unclassified bunyaviruses. taxonomy. the genome of the prototypical strain of iskv, leiv- k, was sequenced, and, on the basis of sequence analysis, the virus was classified into the nairovirus genus. like the genomes of other nairoviruses, that of iskv consists of three segments of rna (in negative polarity), each of which has a single orf-encoded nucleocapsid protein (n, aa, s-segment), a polyprotein precursor of the envelope glycoproteins gn and gc ( , aa, m-segment), and a rdrp ( , aa, l-segment). a pairwise comparison of the full-length nucleotide and deduced amino acid sequences of the iskv orfs with those of other nairoviruses revealed . À . % nt ( . À . % aa), . À . % nt ( . À . % aa), and . À . % nt ( . À . % aa) identity for rdrp, the precursor of gn and gc, and the n protein, respectively (table . ) . phylogenetic analysis carried out for the fulllength amino acid sequences by the maximumlikelihood nearest-neighbor method showed that iskv occupies a new and distinct branch on the phylogenetic trees relevant to all three nairovirus proteins (rdrp, gn/gc, and n) (figures . À . ) . for the many known nairoviruses (i.e., qybv, dgkv, and hugv, as well as for a new nairovirus that was found in european bats by a metagenomics approach), there are only partial sequences of the conservative catalytic core domain of rdrp. , , the level of identity for this domain of iskv with other nairoviruses ranged from . À . % for the nucleotide sequence and . À . % for the amino acid sequence (table . ). the iskv rdrp core domain has the highest level of identity with qybv ( . % nt and . % aa). the phylogenetic tree constructed on the basis of the amino acid alignment of the rdrp core domain of nairoviruses confirms the topology of iskv on a new genetic branch of the nairoviruses (figures . À . ) . arthropod vectors. most isolates of iskv were obtained from argas vespertilionis ticks, and we can assume that these ticks are the main natural reservoir of the virus. the range of ticks of the a. vespertilionis group covers territory in central asia, africa, oceania, and australia ( figure . ) . vertebrate hosts. the natural vertebrate hosts of iskv are apparently bats-specifically, the genera nyctalus, vespertilio, rhinolophus, and myotis (family vespertilionidae). these bats are common in the temperate and subtropical zones of europe, asia, and north africa, and widespread iskv transmission and the appearance of an emergency are possible in all of their territories. human pathology. the first case of issyk-kul fever was registered in tajikistan in august when a staff member became ill after catching bats during surveillance for arbovirus. iskv was isolated from his blood on the second the disease occurs with fever ( À c), headache ( %), dizziness ( %), hyperemia of the throat ( %), cough ( %), and nausea ( %). the outcome is generally favorable, and no deaths have been registered. most of the cases were associated with the presence of bats in the attic of the residence. the primary route of human infection was apparently by argasid ticks, but respiratory or alimentary routes (via the feces and urine of bats) could not be excluded. furthermore, a laboratory experiment showed that iskv can be transmitted by aedes caspius mosquitoes. the percentage of the population immune to iskv in the southern part of tajikistan is . %. in kyrgyzstan, antibodies to iskv have been found in . À . % of the human population. the highest percentage ( %) with antibodies to iskv was found in the southeastern part of turkmenistan. history. uzun-agach virus (uzav), strain leiv-kaz , was isolated from the liver of a myotis blythii oxygnathus (order chiroptera, family vespertilionidae) bat caught in the vicinity of the village of uzun-agach, alma-ata district, kazakhstan, during the virological sounding of territory in central asia and kazakhstan in (figure . ). À on the basis of virion morphology, uzav was classified into the bunyaviridae family. no serological study of uzav was ever conducted, but the place of uzav isolation, uzun-agach, is close to where iskv was originally isolated, namely, near issyk-kul lake, and the source of both viruses is the same: bats. , taxonomy. the full-length genome of uzav was sequenced, and, on the basis of phylogenetic analysis, the virus was classified into the nairovirus genus. the genome of uzav, like those of other nairoviruses, consists of three segments of ssrna with negative polarity. the l-segment encodes rdrp ( , aa), the m-segment encodes a polyprotein precursor of the envelope glycoprotein gn and gc ( , aa), and the s-segment encodes the nucleocapsid protein n ( aa). a pairwise comparison of the sequence of the uzav genome with those of other nairoviruses showed that the virus is related most closely to iskv. full-length sequences of the l-and m-segments of uzav have, respectively, . % nt and . % nt identities with those of iskv. amino acid sequences of rdrp (s-segment) of uzav and iskv have . % aa similarity. the similarity of the amino acid sequences of the precursor of gn and gc for uzav and iskv is . % aa. a comparison of the s-segments of uzav and iskv revealed that they are almost identical ( . %). thus, we can conclude that uzav is a reassortant virus that got an s-segment from iskv. phylogenetic analysis based on l-and m-segments placed uzav in the lineage of iskv (figures . À . ). , vertebrate hosts. the vertebrate host of uzav is apparently bats, but because only a single isolation was obtained, this assertion is speculative. the finding that uzav is a reassortant virus closely related to iskv suggests that uzav occupies the same ecological niche as iskv and therefore is associated with bats and their argasid ticks. myotis blythii oxygnathus, the bat from which uzav was isolated, is common in the southern parts of the russian plain and in western siberia, caucasia, kazakhstan, southern europe, northern africa, middle and central asia, iran, and iraq. bats are important natural reservoir of emerging viruses. À iskv and uzav are the first nairoviruses that appear to be associated with bats. sakhalin virus (sakv) has been isolated from ixodes (ceratixodes) uriae (family ixodidae, subfamily ixodinae) ticks, which are obligate parasites of auks (family alcidae). the prototypical strain of sakv (leiv- c) was isolated in from i. uriae ticks collected in a colony of the common murre (uria aalge) on tyuleniy island near the southeastern coast of sakhalin island in the sea of okhotsk ( n, e; figure . ). À subsequently, strains of sakv were isolated from i. uriae ticks on tyuleniy island and iona island in the sea of okhotsk, the commander islands in the barents sea, and the southeastern coast of the chukotka peninsula in the bering strait (table . ). À on the basis of virion morphology, sakv has been classified into the bunyaviridae family. sakv was the first of the eponymous viruses, which together have formed a basis for the nairovirus genus. paramushir virus (pmrv), prototypical strain, leiv- , a virus of the sakv group, was originally isolated from ixodes signatus ticks collected in in a colony of cormorants (phalacrocorax pelagicus) on paramushir island (in the kuril islands) ( n, e; figure . ). , later (in À ), strains of pmrv were isolated from i. uriae ticks, collected in the nests of auks (family alcidae) on tyuleniy island in the sea of okhotsk and on the commander islands in the bering sea (table . ). À at least five nairoviruses are included in the sakv group. , , À avalon virus (avav), which was isolated from engorged imagoes and nymphs of i. uriae collected in l. argentatus nests on great island, newfoundland, , in , is apparently identical to pmrv. , several strains of avav were isolated in in cap sizun, brittany, france. clo mor virus (cmv) was isolated in from nymphal i. uriae ticks collected in a uria aalge colony of clo mor, cape wrath, scotland. cmv was found to be closely related to sakv in a complementfixation test. two strains of cmv were isolated from i. uriae collected in seabird colonies on lundy island (england) and the shiant isles (scotland) ( table . ) . , rukutama virus (rukv) (strain leiv- s), which previously had been included in the sakv group, is now classified into the uukuniemi virus (uukv) group in the phlebovirus genus. , taxonomy. complete genomes of sakv (strain leiv- c) and pmrv (leiv- k) were sequenced. also, partial sequences of rdrp of tillamook virus (tillv, identical to sakv), isolated from i. uriae ticks on the pacific coast (oregon) of the united states, are available (table . ). a full-length genome comparison showed that sakh and pmrv respectively share . % nt and . % aa identities in rdrp (l-segment), . % nt and . % aa in the precursor of gn and gc (m-segment), and . % nt and . % aa in the nucleocapsid protein (s-segment). sakv n-protein ranges from % (casv, hugv) to % (cchfv) similarity to other nairoviruses. the similarity of rdrp and the precursor of gn and gc proteins of sakv to other nairoviruses ranges from . % (casv, hugv) to . % (cchfv), respectively, and from . % (ervev, tfav) to . % (nsdv, dugv), respectively. arthropod vectors. it has been shown that the infection rate of infected ixodes uriae imagoes is times higher than of the species' nymphs and times higher than that of the larval stage. transovarial transfer of sakv has been found to be %. the infection rates of male and female ticks are approximately the same. the hypostome of male i. uriae ticks is vestigial; therefore, they cannot be infected by breeding on infected birds. the infection rate of i. uriae imagoes is at least times higher than that of i. signatus imagoes. À , , some other species of ixodes ticks are parasites of seabirds and may be an additional reservoir of sakv. i. auritulus and i. zealandicus ticks are distributed from alaska to cape horn in south and north america. laboratory experiments have demonstrated that aedes aegypti and culex pipiens molestus mosquitoes can be infected by sakv as they suck blood. the virus was found in mosquitoes on , , and days after infection in titers . , . , and . log (ld )/ μl, respectively. however, it was shown that infected mosquitoes could not transmit the virus to mice through a bite. , vertebrate hosts. ixodes uriae ticks and their host, the common murre (uria aalge), are a natural reservoir of sakv. pelagic cormorants (phalacrocorax pelagicus) and their obligate parasites (i. signatus) likely have only an additional influence. antibodies to sakv have been found in the common murre (u. aalge), pelagic cormorants (p. pelagicus), fulmars (fulmarus glacialis), tufted puffins (lunda cirrhata), and black-legged kittiwakes (rissa tridactyla) in the far east. À , a serological examination of birds via an indirect complement-fixation test revealed that the northern boundary of the range of sakv is the commander islands, where antibodies have been found in . % of birds. the southernmost place where antibodies have been detected ( . % birds) is kunashir island in the kuril islands. antibodies were found most often (in . À . % of birds) in the central part of the basin of the sea of okhotsk (on sakhalin island, tyuleniy island, and iona island). antibodies were also found in the red-necked phalarope (phalaropus lobatus), sanderling (calidris alba), the long-toed stint (c. subminuta) (up to . % of the population), fulmars (f. glacialis) ( . %), leach's petrels (oceanodroma leucorhoa), tufted puffins (l. cirrhata) ( . %), the common murre (u. aalge) ( . %), japanese , , neutralizing antibodies to avav, a virus closely related to pmrv, have been found in . % of puffins (fratercula arctica), petrels (calonectris leucomelas), and herring gulls (larus argentatus) in canada. , findings of antibodies to sakv in seabirds carrying out their annual seasonal migration to the southern hemisphere suggest the possibility of transcontinental transfer of the virus to the southern hemisphere. the closely related taggert virus (tagv) was isolated from ixodes uriae ticks in penguin colonies on macquarie island, a phenomenon that may indicate a transfer of viruses by birds and their ticks between the northern and southern hemispheres. human infection. three human cases of cervical adenopathy associated with avav were described in france. serological examination of farmers in cap sizun, brittany, france, found only % of the population positive. history. tamv (prototypal strain, leiv- uz) was originally isolated from hyalomma asiaticum asiaticum (family ixodidae, subfamily hyalomminae) ticks collected from sheep in the arid landscape near the town of tamdybulak subsequently strains of tamv were isolated in uzbekistan, À turkmenistan, À kyrgyzstan, , kazakhstan, , , armenia, , and azerbaijan , À in À (table . ) . most of the strains were obtained from h. asiaticum ticks, but several were isolated from birds, mammalians (including bats), and sick humans. on the basis of virion morphology, tamv has been classified into the bunyaviridae family. serological studies by complement-fixation and neutralization tests revealed no antigenic relationships of tamv with any known viruses. taxonomy. three strains of tamv isolated in uzbekistan (leiv- uz), armenia (leiv- ar), and azerbaijan (leiv- az) were completely sequenced. phylogenetic analysis of the full-length sequences showed that tamv is a novel member of the nairovirus genus, forming a distinct phylogenetic lineage (figures . À . ). the similarity of the amino acid sequence of tamv rdrp (l-segment) with those of other nairoviruses is % aa, on average. the similarity of the rdrp of tamv with that of the nairoviruses associated predominantly with ixodid ticks (cchfv, hazara virus (hazv), and dugv) is higher ( % aa) than that with viruses associated with argasid ticks (iskv and casv) ( % aa). the similarity of the tamv polyprotein precursor of cn and gc with that of other nairoviruses is less than % aa. the similarity of the amino acid sequence of the nucleocapsid protein (s-segment) of tamv is % aa with ixodid nairoviruses and % aa with argasid nairoviruses. phylogenetic analysis of the catalytic core domain of the rdrp of the nairoviruses confirms that tamv forms a novel group in the nairovirus genus (figures . À . ). genetic diversity among the three sequenced strains of tamv is low. the prototypic strain leiv- uz, isolated in central asia, has % nt identity in the l-segment with leiv- az from transcaucasia. the l-segment of the strain leiv- ar has . % nt and . % aa identity with the l-segment of leiv- uz. the similarity of the m-segment of leiv- uz with those of leiv- az and leiv- ar is % nt and % aa, respectively. the similarity of the s-segment among the three strains is À % nt. arthropod vectors. h. asiaticum ticks are apparently a main reservoir of tamv. more than half ( %) of tamv isolations were obtained from h. asiaticum asiaticum ticks, % from h. asiaticum, % from h. anatolicum, % from h. marginatum, % from rhipicephalus turanicus, and % from haemaphysalis concinna. the infection rates of male and female ticks in endemic territory were : and : , respectively. the infection rate of h. asiaticum nymphs was times lower. , , , furthermore, tamv was isolated from larvae of h. asiaticum, which were hatched from eggs in the laboratory, indicating transovarial transmission of the virus. h. asiaticum asiaticum ticks are the most xerophilous subspecies of the hyalomma genus (ixodinae subfamily), a characteristic that allows tamv to be distributed over the karakum desert in turkmenistan, the moinkum desert in kazakhstan, and the central part of the kyzyl kum desert in kazakhstan and uzbekistan. . animal hosts. the larvae of h. asiaticum feed on ruminants, hoofed animals, small predators, hedgehogs, birds, and reptilians. one of the major hosts of h. asiaticum preimagoes is the great gerbil (rhombomys opimus). wild animals, as well as sheep and camels, are the hosts for h. asiaticum imagoes and may be involved in the circulation of tamv (table . ). human pathology. sporadic cases of the disease associated with tamv was registered in kyrgyzstan in october , when tamv was isolated from the blood of a patient with fever ( c), headache, arthralgia, and weakness. h. asiaticum asiaticum ticks rarely attack humans, and no outbreaks of tamv fever have been registered; however, human infection by h. asiaticum ticks is still possible concinna (ixodidae, haemaphysalinae) during À . , according to preliminary information, burv is not able to agglutinate erythrocytes of birds and mammals and has no antigenic relationships with arboviruses from different groups of the togaviridae, taxonomy. the genome of burv was sequenced, and the virus was classified into the nairovirus genus, family bunyaviridae. the genome consists of three segments: an l-segment (orf, , nt; encodes rdrp); an m-segment (orf, , nt; encodes a polyprotein precursor of the envelope proteins gn and gc); and an s-segment (orf, , nt; encodes the nucleocapsid protein n). , a comparison of rdrp sequences of burv with those of other nairoviruses demonstrated that the virus is distantly related to tamv ( % aa similarity). the similarity of the rdrp catalytic core domain of burv to that of tamv is % aa, compared with about % aa for viruses in other phylogenetic groups. the level of similarity for the nucleotides sequences of this part of the rdrp of burv is % nt with those of tamv and À % nt with those of other viruses (figure . ). the m-segment of burv has a long orf and encodes a polyprotein precursor of the envelope glycoproteins gn and gc. the size of the polyprotein precursor is , aa. the mature gn and gc proteins of nairoviruses are formed by complex processes involving cellular peptidases. by the netnglyc . server, potential glycosylation sites were predicted, with only within mature gn or gc proteins. , the level of similarity of the amino acid precursor of gn and gc in burv is % with that of tamv and no more than % with viruses of other phylogenetic groups. phylogenetic analyses based on a comparison of the full-length polyprotein precursor demonstrated the position of burv on the tamv branch and was consistent with the rdrp data ( figure . ). the s-segment of nairoviruses encodes a nucleocapsid protein (n). , the size of the burv nucleocapsid protein is aa, corresponding to the average size of the n protein of other nairoviruses ( À aa). the level of similarity of the amino acid sequence of burv n protein with that of tamv is %, and that with the amino acid sequences of other nairoviruses is À %. phylogenetic analyses of burv n protein are represented in figure . . the phylogenetic position of burv is on the tamv branch, despite the virus's having the lowest level of similarity of the n protein compared with that of other virus proteins. arthropod vectors. as mentioned earlier, six strains of burv were isolated from the ticks haemaphysalis punctata (five strains) and haem. concinna (one strain) in À . the rate of infected ticks was . À . %. burv is associated with haem. punctata and haem. concinna ticks in pasture biocenoses. the virus is phylogenetically close to tamv, which is also associated with ixodes ticks in pasture and desert biocenoses. the orthobunyavirus genome consist of three segments of single-stranded negative-sense rna designated as large (l), medium (m), and small (s) (figure . ). the l-segment of the prototypical bunv ( , nt in length) encodes the viral rdrp. the m-segment ( , nt) encodes two surface glycoproteins (gn and gc) and a nonstructural protein (nsm). , the s-segment ( nt) encodes the nucleocapsid protein (n) and a nonstructural protein (nss). the nss protein is considered a pathogenic factor for vertebrates, because it may act as an antagonist of interferon, which is involved in blocking the host's innate immune responses. À , to olyka virus, isolated in from an. maculipennis mosquitoes collected in western ukraine; À and to chittoor virus, isolated in from an. barbirostris mosquitoes collected in brahmanpally, chittoor district, andhra pradesh state, india. the african ngari virus (nriv) is reassortant between batv and bunv. , in russia, batv was repeatedly isolated in different regions (figure . ). anadyr virus (anadv), strain leiv- , was isolated by s.d. lvov from a pool of aedes mosquitoes collected in september in a swamp tundra landscape near the village of ukraine, and russia are members of the european group. two strains of batv-leiv-ast - - and leiv-ast - - -isolated in russia were completely sequenced and placed into the cluster of the european strains. within this group, they are phylogenetically close to strain , isolated in the volgograd region in from anopheles messeae (maculipennis) mosquitoes, for which the partial nucleotide sequences of the l-and m-segments are known. between the strains leiv-ast - - and leiv-ast - - , there is very high level of nucleotide and amino acid identity of three segments of the genome: . / . % (l-segment/rdrp), . / . % (m-segment/ polyprotein predecessor), and . / . % (s-segment/nucleocapsid). the levels of nucleotide identity of strain with these strains on partial sequences of l-and m-segments are . / . % and / %, respectively; that is, for the m-segment, all available nucleotide polymorphisms are synonymous. the lowest observed genetic differences and the temporal and geographical proximities of the various strains of these viruses suggest a common origin as different isolates of the same strain of batv circulating in the southern part of russia. phylogenetic analysis of anadv (strain leiv- ) revealed its similarity to batv. the l-segment of anadv is from . % to . % identical with those of the different batv strains (figure . , table . ). the identity of the l-segment of anadv with the l-segments of other viruses of the bunyamwera group is . % (bunv), . % (cvv), and . % (tenv). the amino acid and is about . % with tenv and cvv. the amino acid similarity of the nucleocapside protein is . % with that of batv from uganda. phylogenetic analysis of the nucleotide sequences of the s-, m-, and l-segments conducted with the use of a maximum-likelihood algorithm placed anadv (leiv- ) on a distinct branch of the dendrogram that considers it a new representative of the bunyamwera group. arthropod vectors. batv has been reported in sudan, africa. the distribution of batv in southeastern asia includes malaysia, india, sri lanka, thailand, cambodia, and japan, , while in europe batv is distributed over austria, germany, yugoslavia, moldova, ukraine, belarus, and other countries. , À in central europe, batv was isolated from anopheles claviger, an. maculipennis (an. messeae), coquillettidia richiardii, aedes (ochlerotatus) punctor, and ae. communis. , , a wide distribution of batv in different landscape belts of the european part of russia, as well as in siberia and the far east, was demonstrated: in the temperate belt the main source of batv isolation was the zoophilic anopheles genus, whereas in high latitudes (tundra, northern taiga) it was the aedes genus. , À in the european part of russia, batv has been isolated in the northern (komi republic), middle (vologda region), and southern (leningrad, yaroslavl, and vladimir regions; , , , , in the southern hyperendemic regions of russia, the main vector of batv is an. messeae. according to our data, the infection rate of an. messeae in the middle belt of the volga delta (astrakhan region) reaches . % (approximately infected mosquito out of ). because this species of mosquito attacks mainly domestic animals, it serves as a biological barrier, reducing risk of infection to humas. in the northern areas (the subarctic, the northern taiga), batv circulation is due mainly to aedes mosquitoes: ae. communis complex and ae. punctor. under experimental conditions, batv was isolated from hibernating females of an. messeae. hibernation is one of the mechanisms by which batv survives during the winter. , vertebrate hosts. in anthropogenic biocenoses of the southern regions of russia, domestic animals are the main vertebrate reservoir, because they (especially cattle) are the main hosts for an. messeae. batv-neutralizing antibodies were found in india among rodents (mus cervicolor ( . %), rattus exulans ( . %), rattus rattus ( . %), bandicota indica ( . %)) and bats (cynopterus sphinx) ( . %). , this indicator is significantly higher in india among domestic animals: goats ( . %), camels ( %), cows ( . %), and buffalos ( . %). in finland, anti-batv antibodies occasionally were found among cows ( . %), but not among reindeers. the chittoor strain is associated with mild illness, but is pathogenic to sheep and goats. batv was isolated from birds: crows (corvus corone), coots (fulica atra), and grey partridges (perdix perdix). persistent avian infection was established experimentally with reactivation of viremia by cortisone six months after the acute infection period. an investigation of , sera of domestic animals in russia during À revealed anti-batv antibodies among these animals significantly more often than among people (table . ). the largest immune layer was found in populations of horses (up to %), cattle ( À %), sheep (up to %), and camels in forestÀsteppe, semidesert, and desert landscape belts. in contrast to the situation in finland, antibodies were found in reindeer sera in a tundra landscape belt of the chukotka peninsula. no examinations of vertebrates in natural biocenoses were conducted. epidemiology. epidemic outbreaks and sporadic cases caused by batv, as well as outbreaks of hemorrhagic infection caused by ngari virus, have been reported. , , , , to date, no cases of laboratory infection are known. according to a serological examination of , people in the endemic regions of russia, about À % withstand batv infection in an asymptomatic form. the highest infection rate was established in forestÀsteppe and steppe belts. (however, as a rule, the rate is higher for domestic animals than humans.) some northern areas in russia became hyperendemic for no apparent reason. , , pathogenesis. no pathogenetic mechanism during batv infection in humans has yet been described in detail. there are experimental data, however, on batv infection in primates: green monkeys (chlorocebus sabaeus) were found to be carriers of the virus days after inoculation (the observation period); the virus was pantropic, destroying small vessels and producing vasculitis and perivascular focal lymphohistiocytic infiltrates. clinical features. the disease etiologically linked with batv proceeds mainly as influenzalike disease complicated by meningitis, malaise, myalgia, and anorexia. , , , , at the same time, ngari virus (reassortant between batv and bunv) infection in east africa appears as outbreaks of hemorrhagic fever. diseases associated withtheclosely related ilev in africa and madagascar also proceed with hemorrhagic phenomena and with lethal outcomes. , diagnostics. a highly specific test based on rt-pcr has been developed, as have elisa tests for the detection of specific anti-batv igm and igg. genome and taxonomy. the genome of the ce group of viruses consists of three segments of ssrna with negative polarity. the l-segment of lacv, a prototypical virus of the group, is , nt in length, the m-and s-segments , and nt, respectively. as in other bunyaviruses, the l-segment encodes rdrp, the m-segment a polyprotein precursor of the envelope glycoproteins gn and gc, and the s-segment nucleocapsid protein (n). two nonstructural proteins are found in infected cells: nss, which encodes by adding an orf in the s-segment; and nsm, which forms during the maturation of the gn and gc proteins from the precursor. , but viruses of the ce serocomplex were isolated from ae. albopictus (a known vector for at least arboviruses), which was imported from southeastern asia and spread into states of the united states. , transovarial transmission was established in ae. vexans and cs. annulata. overwintering of tahv was documented in cx. modestus and cs. annulata females. mosquito species have been defined and classified only partially in connection with the huge volume of this laborious work. the majority of strains were isolated from pools of mosquitoes belonging to different species. of strains that were isolated ( strain was isolated from a wild population of the common house mouse, mus musculus), only were isolated from strictly defined species (table . ). the other strains were isolated from aedes mosquitoes of unidentified species: % of strains were from ae. communis, % from the mixed pools, in which ae. communis prevailed. strains were isolated from other species significantly less often. only one strain was isolated from anopheles maculipennis (an. messeae) and culiseta alaskaensis. the dynamics of the seasonal infection rate of mosquitoes was investigated for two years on the model of the northern part of the russian plain and the eastern part of fennoscandia. in tundra, the epizootic period begins with the second decade of july and proceeds to the beginning of august, when the activity of mosquitoes comes to an end. in forest tundra, the epizootic period begins with the first decade of july and proceeds for . months; in the northern taiga, this period lasts at least months (julyÀaugust); in the middle and southern taiga, the first strains began to be isolated in the second decade of june. the mosquito infection rate increases significantly in the third decade of july and reaches a maximum in the middle to end of august, when the total number of mosquitoes decreases. , the data collected testify to an almost universal distribution of ce serocomplex viruses in all landscape belts, except the arctic, in all six physicogeographical lands examined in the north of russia, located on a territory of more than million km . the infection rate of mosquitoes increases (р , . ) in moving from the subarctic (tundra) ( . . %) to the landscape belt of the middle taiga ( . . %). this indicator in tundra and in the forest tundra is close to that in the southern taiga of the russian plain ( . %), in north america ( . %), and in the forest steppes of the russian plain ( . À . %). in the steppe belt of the russian plain, the infection rate of mosquitoes appeared to be the smallest ( . %). in the leaf forests of the russian plain ( . %) and of the former czechoslovakia ( . %), the infection rate of mosquitoes is comparable to that for landscape belts of the northern and middle taiga. to date, at least s ce serocomplex virus strains were isolated from mosquitoes in the central and southern parts of the russian plain. among them, strains were isolated from the blood and spinal fluid of patients, and strains from the internal parts of rodents ( from the bank vole, myodes glareolus; and from the wood mouse, apodemus sylvaticus). the infection rate of mosquitoes depends on the landscape belt and the particular season in which field material was collected. the rate decreases, as a rule, from the north to the south. data indicating an absence of viruses in semideserts can be explained by an insufficient quantity of mosquitoes collected, but in wet subtropical zones in azerbaijan ce serocomplex viruses were isolated from anopheles hyrcanus. in the southern taiga belt and mixed forests, the infection rate of mosquitoes was defined to be from the third week of may to the second week of august and two peaks were noted: at the end of june (the emergence of the first generation of aedes mosquitoes) and at the end of july to the beginning of august (the emergence of the second generation of aedes mosquitoes). in the majority of the southern belts, the infection rate was registered from the second week of june until the end of august with a small peak in the first week of august caused by the emergence of the second generation of aedes mosquitoes and by the peak of activity of culex, coquillettidia, and anopheles mosquitoes. in steppe and forestÀsteppe belts, ce serocomplex viruses were isolated from mosquitoes collected in the rostov and orenburg regions, as well as in the foothills of the caucasus mountains (krasnodar krai). most of the strains were obtained from aedes mosquitoes, which play the leading role in virus circulation. in these regions, anopheles mosquitoes join the virus population maintenance (three strains were isolated), being ecologically connected with agricultural animals and, because of that connection, playing an important role as an indicator species in anthropogenic biocenoses. in the center and south of the russian plain, there is a mix of populations of inkv, tahv, khtv. , vertebrate hosts. the principal vertebrate hosts of tahv in europe are lagomorpha (hares (lepus europaeus), rabbits (oryctolagus cuniculus), hedgehogs (erinaceus roumanicus), and rodents (rodentia)). experimental viremia has been established in lagomorphs, hedgehogs, ground squirrels (citellus citellus), muskrats (ondatra zibethicus), squirrels (sciurus vulgaris), martens (martes foina), polecats (putorius eversmanni), foxes (vulpes vulpes), badgers (meles meles), bats (vespertilio murinus), piglets, and puppies. , , , in total, strains of ce serocomplex viruses were isolated within all landscape belts of all physicogeographical lands (figure . , table . ). according to our data, the susceptibility of mosquitoes increased from the tundra to the northern and middle taiga; however, the highest indicators were noted to be in the forestÀsteppe and the steppe of western siberia (in altai krai). identification of these strains revealed at least three viruses of the ce complex: strains of tahv, of inkv, and strains of khtv. in all landscape belts east of the yenisei river (central and northeast siberia and the physicogeographical lands bordering the north pacific ocean), only khtv strains have been isolated. west of the yenisei river, inkv strains predominated in the tundra and the forestÀtundra of western siberia, whereas khtv prevailed in other landscapes located to the south. in the eastern part of fennoscandia and in the north of the russian plain, inkv and khtv strains were isolated in about equal proportions. the pattern of distribution of tahv, inkv, and khtv over northern eurasia suggests that the emergence of the ancestor of ce serocomplex viruses probably is connected to oligocene chineseÀmanchurian fauna of the deciduous forests of eastern siberia evolving into okhotsk fauna during the upper tertiary period. the okhotsk fauna, in its turn, extended in early glacial times to the north, the west, and partially to the east in tundra through ancient beringia and on into north america. the ancestral virus could then penetrate into north america together with this fauna and gradually extend in the southern direction, in the process laying the foundation for the appearance of some other viruses of the ce serocomplex now circulating mainly in north america. mercurator, nigripes, excrucians . maculipennis b . total a one strain was isolated from the genus culiseta. b one strain was isolated from the genus anopheles. the introduction of the virus population to the western hemisphere probably occurred through two pathways around the central siberian plateau: (i) through the tundra lying to the north of the plateau and (ii) through southern taiga and forestÀsteppe territories. these pathways can explain the modern predominance of khtv in the forestÀsteppe belt of siberia and in a taiga belt west of the yenisei river. in moving to other ecological systems further to the west, khtv could have been transformed partially to inkv and tahv. the inkv population penetrated into the western part of the eurasian subarctic through the taiga belt and occupied that part of eurasia, whereas tahv proceeded into the deciduous forests of europe, where it now prevails. epidemiology. cev is endemic in the united states in california, new mexico, texas, the southwestern part of virginia, tennessee, and kentucky. , sporadic morbidity with cns lesions occurs in those states, but the main morbidity is linked to lacv, which is endemic in states, predominantly the u.s. census bureauÀdefined east north central states (ohio, wisconsin, minnesota, iowa, and indiana), where morbidity reaches . À . %. cases of lacv-associated encephalitis are within the distribution of the main vector-aedes triseriatus-eastward from the rocky mountains. during the last few decades, natural foci in west virginia, north carolina, and tennessee, with sporadic cases occurring in louisiana, alabama, georgia, and florida, joined with previously known ones in wisconsin, illinois, minnesota, indiana, and ohio. thus, having traversed the distance from southeastern asia to north america, ae. triseriatus is now part of the north american virus circulation. the clinical picture varies from an acute fever syndrome (in some cases with pharyngitis and other symptoms of acute respiratory disease) to encephalitis. lethality is about . %. from to cases occur annually. generally, the virus attacks children age and under ( %), a phenomenon that may be explained by the existence of a layer of immunity in up to % of adults. jcv (in the united states and canada) and sshv (in the northern part of the united states and in canada) are associated with sporadic cases of fever and encephalitis. domestic dogs are susceptible to lacv, which provokes encephalitis. , , , the role of deer in virus circulation has been established as well. horizontal and vertical transmission of viruses provides an active circulation of the virus, a high rate of infection in mosquitoes, and stability of natural foci under the relatively rough conditions of the central and northern parts of the temperate climatic belt. all three viruses (inkv, khtv, and tahv) of the ce serocomplex distributed in eurasia have significance in human pathology. , these viruses were found in czechoslovakia in , , austria in , finland in , , romania in , norway in , the former ussr(in transcaucasia) in , and elsewhere in the european and asian parts of russia. , , , , , , À in europe, human disease associated with tahv presents as an influenzalike illness mainly in children with sudden-onset fever, headache, malaise, conjunctivitis, pharingitis, myalgia, nausea, gastrointestinal symptoms, anorexia, and (seldom) meningitis and other signs of cns lesions. , , À the circulation of ce serocomplex viruses was established in china, where they provoke human diseases with encephalitis as well as acute respiratory disease, pneumonia, and acute arthritis. in north america (the united states and canada), lacv is the most important of these viruses, but sshv also is associated with human disease. between and in the united states, , cases of ce were reported. , so, ce serocomplex viruses have circumpolar distribution. in russia, these viruses are found from subarctic to desert climes ( figure . , table . ). , according to our summary data for , sera, the number of people with specific antibodies to ce serocomplex viruses in the tundra and forestÀtundra belts ( . %) is significantly lower than the number in the north and middle taiga belts ( % and %, respectively). these data correlate with the infection rate of mosquitoes in those landscape belts. , results obtained from serological investigation of the human population correlate with those obtained from virological investigation of the mosquitoes (figure . ). the maximum immune layer of the healthy population is registered in the southern taiga. in the landscape and geographical zones located south of that landscape, a gradual decrease in this indicator takes place. specific antibodies to inkv are seen everywhere that this virus circulates. in forest-Àsteppes, specific antibodies to tahv and inkv are marked out with an identical frequency. in semideserts, anti-tahv antibodies are found twice as often as anti-inkv ones. the small number of strains isolated in these natural zones precludes establishing a relationship between the circulation of viruses and an immune layer of the population. active circulation of ce serocomplex viruses on the territory of russia results in regular registration of the diseases caused by these viruses. more than % of all seasonal fevers are etiologically linked to such viruses, and in some natural zones (the southern taiga and the mixed forests), this indicator increases to À %. in mixed forests, the main etiological role most often belongs to inkv ( . %), and in semideserts (astrakhan region) to tahv ( . %). the diseases caused by ce serocomplex viruses in the center and south of the russian plain start appearing during the middle of may and reach a maximum in almost equal titers of specific antibodies to more than one virus were revealed in patients ( . %) in a neutralization test. , , diseases were registered from may to september: in may, cases ( . %); in june, ( . %); in july, ( . %); in august, ( . %); and in september, ( . %). the seasonal dynamics in all landscape zones were identical: the maximum number of diseases is noted in julyÀaugust. diseases were registered everywhere in the form of sporadic cases and small outbreaks, but more often in the taiga and the deciduous forests of the european part of russia and western siberia. most patients were À years old, with those up to years making up . % of all people infected. pathogenesis. a systematic destruction of small vessels, together with the development of vasculitis and perivascular focal lymphohistiocytic infiltrates, underlies the pathogenesis of the diseases caused by ce serocomplex viruses. lesions in the lungs, brain, liver, and kidneys are the most frequent complications. , clinical features. the incubation period lasts from to days, but in some cases is only days. three main forms of disease linked with ce serocomplex viruses have been proposed: (i) influenzalike; (ii) with primary compromise of the bronchiopulmonary system; (iii) neuroinfectious, which proceeds with a syndrome of serous meningitis and encephalomeningitis. analysis of the clinical picture of cases examined showed that . % of cases proceeded without signs of cns lesion, . % with a syndrome of acute neuroinfection, and . % with radiologically uncovered signs of changes in the bronchiÀlung system. a comparison of clinical forms and etiologic agents showed that inkv and tahv often cause disease without cns lesions ( . % and . %, respectively) and that inkv plays the leading role in acute neuroinfection ( . %). the etiological role of khtv was established in cases without cns symptoms of lesions. eighty-three patients had an influenzalike form of the disease etiologically linked to ce serocomplex viruses. the incubation period was À days. the disease began abruptly, with a high temperature that reached a maximum of À c in . % of patients on the first day. the duration of the fever was . . days. one of the main symptoms was an intensive headache ( . . days in duration) that developed in the first few hours and was often accompanied by dizziness, nausea ( . %), and vomiting ( . %). , À a survey of patients revealed infection of the sclera ( . . %), hyperemia of the face and the neck ( . . %), and, in some cases ( . %), a spotty and papular rash on the skin of the trunk and the extremities. violations of the upper respiratory airways were characterized by hyperemia of the mucous membranes of the fauces ( . . %)and congestion of the nose and a dry, short cough ( . . %). with regard to the lungs, . . % of patients exhibited rigid breathing a dry, rattling cough during auscultation, and a strengthening of the bronchovascular picture on roentgenograms. among cns symptoms, the most common were a decrease in appetite, a stomachache without accurate localization and with liquid stool, and a small increase in the size of the liver with a short-term increase in aminotransferase activity in the blood. inflammatory changes in the bronchiÀlung system (bronchitis and pneumonia) occurred as well. in all cases in which it appeared, pneumonia had a focal character with full the etiological role of different ce serocomplex viruses has been established in % of cases with acute diseases of the nervous system (serous meningitis, encephalomeningitis, arachnoiditis, acute encephalomyelitis, and seronegative tick-borne encephalitis (tbe)): inkv ( . . %), tahv ( . . %), and unidentified ( . . %). the age of patients with cns lesions was from to years, with the majority ( . %) from age to . serous meningitis was observed in patients who arrived at the hospital a mean . days after symptoms appeared. the disease began abruptly. the majority ( . %) of patients complained of a high temperature that reached a maximum the first day, the duration of the fever was . . days, with a critical ( . %) or steplike ( . %) decrease. headache was noted in % of patients and was accompanied by dizziness in %. vomiting developed on the first ( . %) or the second ( . %) day and continued in . % of patients. meningeal signs appeared in . % of patients but were weak and dissociated in most cases, with only . % of patients exhibiting rigidity of the occipital muscles. the duration of the meningeal signs was . . days. the cells of the spinal fluid (investigated on the . th . day of the disease) was lymphocytic, mostly reaching three digits and up to cells ( . %); the protein concentration was reduced ( . . g/l) in . % of cases but was within the normal range ( . . g/l) in other cases. in . % of patients exhibiting acute neuroinfection symptoms of bronchitis and focal pneumonia, their condition was confirmed radiologically. encephalomeningitis caused by inkv was characterized by an abrupt beginning and fast development of focal symptomatology (ataxy, horizontal nystagmus, and discoordination) against a background of common infectious and meningeal syndromes, including inflammatory changes to the spinal fluid. , À the variability of the clinical picture of the diseases caused by ce serocomplex viruses and its similarity-especially at early stagesto that of other infections suggest the necessity of carrying out differential clinical diagnostics with a number of diseases. the influenzalike form needs to be differentiated, first of all, from influenza, especially in the presence of symptoms of neurotoxicity, as well as from other acute respiratory diseases (parainfluenza, adenoviral and respiratoryÀsyncytial diseases), pneumonia (including a mycoplasma and chlamydia etiology), and enteroviral diseases. the main epidemiological features and clinical symptoms that lend themselves to carrying out differential clinical diagnostics for the influenzalike diseases described here are presented in table . . note that considerable difficulties arise in implementing differential clinical diagnostics of the diseases that proceed with acute neuroinfection syndrome (serous meningitis, encephalomeningitis), especially when those diseases occur in the same season (tables . and . ). , , the main criteria in differential clinical diagnostics of the disease etiologically linked with ce serocomplex viruses are as follows (see tables . and . ): acute onset; high short-term fever ( À days, on average) reaching a maximum on the first day and decreasing critically at the end of the feverish period; and intensive headache, nausea, vomiting, and weakness. also observed are insignificant catarrhal phenomena (nose congestion, rare dry cough) or their complete absence. a radiograph of the chest reveals signs of bronchitis and focal pneumonia with poor clinical symptomatology. an examination of the liver shows that its size, as well as its aminotransferase activity, has increased. changes in urine, such as albuminuria and, in some cases, cylindruria, are frequently reported. finally, symptoms relating to the vegetative nervous system (hyperemia of the face and the neck, subconjunctival hemorrhage, bradycardia, and persistent tachycardia) can be observed, as can both cns lesions in the form of serous meningitis and encephalomeningitis in combination with compromise of the bronciopulmonary system, liver, and kidneys. diagnostics. specific diagnostics of the diseases etiologically linked with ce serocomplex viruses could be based on virological testing (using sensitive biological models of newborn mice or cell lines to isolate the strains) or on serological testing. in the presence of the sera taken from patients during the acute period of the disease (the first À days) and in À weeks, the best method of retrospective inspection is a neutralization test. a hemagglutination inhibition test is considerably less sensitive. both complement-binding reactions and diffuse precipitation in agar have no diagnostic value today. for serological reactions, it is necessary to utilize hktv, tahv, and inkv antigens simultaneously. (in reference labs, sshv antigen should be used as well.) a quadruple (or greater) increase in the titers of specific antibodies or the detection of specific antibodies in the second serological test in their absence in the first test are diagnostic criteria. elisa for igg indication and monoclonal antibody capture elisa (mac-elisa) for igm indication provide good diagnostic opportunities. control and prophylaxis. supervision of morbidity and of the activity of natural foci linked with ce serocomplex viruses offers the following instructions: (i) monitor the patient clinically and the disease epidemiologically. (ii) provide well-timed diagnostics and seroepidemiological investigations. (iii) track the number and specific structure of mosquito vectors and possible vertebrate hosts. history. khurdun virus (khurv), strain leiv-ast - (deposition certificate n , . . , in the russian state collection of viruses), was isolated from a pool of internal parts of the coot (fulica atra; order gruiformes, family rallidae), collected august , , in natural biomes in the western part of the volga river delta, in khurdun tract, ikryaninsky district, astrakhan region. later, nine more strains of khurv were isolated from f. atra and the cormorant phalacrocorax pygmaeus; order pelecaniformes: family phalacrocoracidae) in À (figure . ). at least six viruses associated with birds have been shown to circulate in the volga river estuary. , khurv has not been identified by any serological method, including sera against viruses of the flaviviridae, togaviridae, bunyaviridae, and orthomyxoviridae families. taxonomy. the genome of khurv was sequenced, and phylogenetic analysis revealed that it is a new representative of the orthobunyavirus genus (figures . À . ). the genome consists of three segments of ssrna with negative polarity-an l-segment ( , nt), an m-segment ( , nt), and an s-segment ( nt)-and has only À % identity with those of other orthobunyaviruses. the terminal -and -sequences of khurv genome segments, determined by rapid amplification of cdna ends, are canonical for the orthobunyavirus ( -ucaucacaug and cgtgtgatga- ). the l-segment of khurv has a single orf ( , nt) that encodes rdrp ( , aa). the similarity of khurv rdrp with those of the orthobunyaviruses is %, on average. the similarity of the conservative polymerase domain iii (a, В, c, d, and e motifs) in rdrp reaches % (in bunv). the М-segment of khurv is shorter than those of the orthobunyaviruses ( , nt vs. , nt for bunv). the М-segment of khurv has a single orf ( , nt), which encodes a polyprotein precursor ( aa) of the envelope glycoproteins gn and gc. apparently, the m-segment of khurv does not contain a nonstructural protein nsm, which is common in most of the orthobunyaviruses. , the putative cleavage site between gn and gc of khurv was found in position / aa (asa/en). this site corresponds to the cleavage site between nsm/gc of the orthobunyaviruses and the conservative amino acid a/Е (vaa/ee in bunv). the size of the gn protein of khurv is the same as that of the other orthobunyaviruses, aa. the similarity of khurv gn is À % aa, on average, to that of the other orthobunyaviruses ( . % aa to bunv). the size of the gc protein of khurv, aa, is shorter than that of the other orthobunyaviruses (cf. aa for the gc protein of bunv). the c-part (approx. aa) of the gc protein, which includes the conservative domain g (pfam ), has about % aa similarity to the c-part in the other orthobunyaviruses, whereas the n-part (approximately aa) has no similarity to that of any proteins in the genbank database. the s-segment of khurv is nt in length and encodes a nucleocapsid protein ( aa). the similarity of the n protein to that of the orthobunyaviruses is À aa%. most orthobunyaviruses have an additional orf that encodes arthropod vectors. there are no known arthropod vectors of khurv; the virus has been isolated only from birds. more than , aedes, culex, and anopheles mosquitoes were examined during the survival period for arboviruses in this region, and no khurv isolations were obtained. the family ceratopogonidae of biting midges is a potential vector of khurv, but these insects have not been surveyed. vertebrate hosts. all isolations of khurv were obtained from birds. nine strains of the virus were isolated from coots (fulica atra). (one hundred seventeen birds were examined and were found to have an infection rate of . %.) one strain was isolated from the pygmy cormorant (phalacrocorax pygmaeus). (two hundred eighty-nine cormorants, mostly ph. carbo, were examined and were found to have an infection rate of . %.) the phlebovirus genus comprises about viruses that are divided into two main groups based on their ecological, antigenic, and genomic properties: mosquito-borne viruses and tick-borne viruses. , the genome of the phleboviruses consists of three segments of ssrna with negative polarity: l (about , nt), m (about , À , nt), and s (about , nt) (figure . ). in general, the structure of the genome is the same for mosquito-borne and tick-borne phleboviruses, but the m-segment is shorter in tick-borne viruses and it does not encode the nonstructural protein nsm. phylogenetically, the phleboviruses can be divided into two branches in accordance with their ecological features. the tick-borne phleboviruses comprise viruses of the uukuniemi group, the bhanja group, and the two novel related viruses severe fever with thrombocytopenia syndrome virus (sftsv) and heartland virus (hrtv), which form separate clusters and are unassigned to any group (figures . À . ). the uukv serogroup currently comprises viruses, but the status of some of them may be revised with the accumulation of more genomic and serological data. history. bhanja virus (bhav) was originally isolated from haemaphysalis intermedia ticks that were collected from a paralyzed goat in the town of bhanjanagar in the ganjam district in the state of odisha, india, in and was assigned to the unclassified bunyaviruses. in europe, the first isolation of bhav was obtained from adult haem. punctata ticks collected in italy ( ) and then in croatia and bulgaria. , , palma virus (palv), a virus closely related to bhav, was isolated from haem. punctata ticks in portugal. two viruses-kismayo virus (kisv) and forécariah virus (forv)-antigenically related to bhav were isolated in africa. , these viruses have been merged into the bhanja group on the basis of their serological cross-reactions. , in transcaucasia, bhav (strain leiv- az) was isolated from ixodidae ticks rhipicephalus bursa collected from cows in ismailli district, azerbaijan, in ( figure . ). closely related to bhav, razv (strain leiv- arm) was isolated from ixodid ticks dermacentor marginatus collected from sheep near the village of solak in the razdan district of armenia ( figure . ). , serological methods (detection of antibodies in animals and humans) have shown that bhav circulates in many mediterranean countries, the middle east, asia, and africa. , taxonomy. viruses of the bhav group are not antigenically related to any of the other bunyaviruses, but they were assigned to the phlebovirus genus on the basis of a genetic analysis of their full-length genome sequences. , , weak antigenic relationships were found between bhav and sftsv, a novel phlebovirus isolated in china. , , sftsv, in its turn, is antigenically related to viruses of the uukuniemi group. the genomes of certain viruses of the the m-segment of bhav ( , nt) encodes a polyprotein precursor ( , aa) of the envelope glycoproteins gn and gc. like the m-segments of other tick-borne phleboviruses, that of bhav has no nsm proteins that are common to mosquitoes-borne phleboviruses. the predicted cleavage site between gn and gc proteins has been found by signal ip software (http://www.cbs.dtu.dk/services) to be in position / of the polyprotein precursor (motif mhmalc/cdesrl). a dipeptide cd in the cleavage site is also typical for sftsv and hrtv, which were associated with human disease in china and the united states, respectively. , , other phleboviruses, including uukv and rvfv, contain a dipeptide cs in this position. the s-segment ( , nt) of bhav has two orfs (n and nss proteins) disposed in opposite orientations (an ambisense expression strategy) and separated by an intergenic spacer ( nt) . the similarity of the nucleocapsid vertebrate hosts. the ungulates, including domestic cows, sheep, and goats, are apparently involved in the circulation of bhav. usually, bhav infection in adult animals is asymptomatic, but it is pathogenic to young ones (lamb, calf, suckling mouse), causing fever and meningoencephalitis. , À experimental infection of rhesus monkeys by bhav induced encephalitis. several strains of bhav were isolated from the four-toed hedgehog (atelerix albiventris) and the striped ground squirrel (xerus erythropus) in africa. antibodies have been detected in dogs, roe deer (capreolus capreolus), and wild boars (sus scrofa). human pathology. bhav infection in human is mainly asymptomatic, but several cases of fever and meningoencephalitis caused by bhav have been described. À history. gissar virus (gsrv) was isolated from argas reflexus ticks collected in a dovecote in the town of of gissar in tajikistan ( n, taxonomy. the genome of gsrv (strain leiv- taj) has been sequenced. phylogenetic analysis shows that gsrv is a member of the phlebovirus genus of the uukuniemi group (figures . À . ). gsrv is closely related to grand arbaud virus (gav), which was isolated from a pool of argas reflexus ticks collected in a dovecote near gageron in arles in the rhô ne river delta in the camargue region of france in . gav is classified as virus belonging to the uukuniemi group. the identity of the nucleotide and amino acid sequences of gsrv and gav is % nt for the s-segment ( % aa for the nucleocapsid protein), % nt for the m-segment ( % aa for the polyprotein precursor of gn/gc), and % nt for the l-segment ( . % aa for rdrp). arthropod vectors. regardless of their geographical distribution, gsrv and gav occupy a narrow ecological niche associated with ticks (argas reflexus) and birds (most likely, pigeons (columbidae)). in laboratory experiments, gsrv reproduced in a. reflexus ticks in days with titers up to . log (ld )/ mcl. the distribution of argas reflexus ticks is limited between n on the north and n on the south. the a. reflexus metamorphosis cycle is about three years. the ticks inhabit pigeons' habitats, which are also used by other birds, such as swallows and swifts. a. reflexus larvae were found in europe on a rock swallow (ptyonoprogne rupestris), in egypt on a little owl (athene noctua), in israel on a rock dove (columba livia) and a fan-tailed raven (corvus rhipidurus), and in crimea on the western jackdaw (corvus monedula). the mass reproduction of mites in a dovecote has a negative impact on pigeons' bereeding behavior. worse, at night the ticks can go down to the living space and bite people if the dovecote is built into a house. vertebrate hosts. the main vertebrates involved in the circulation of gsrv are apparently birds, particularly the columbidae. in laboratory experiments, gsrv was isolated from the blood of small doves (streptopelia senegalensis) , , , and days after infection. the virus titer in the blood was . À . log (ld )/ mcl, on average. serological examination of birds in tajikistan found antibodies to gsrv % of doves (columba livia). history. khasan virus (khav) was isolated from haemaphysalis longicornis ticks collected from spotted deer (cervus nippon) in in the forest in khasan district in the south of primorsky krai, russia (figure . ). morphologic studies showed that khav belongs to the bunyaviridae family. the virion of khav has structural elements (filaments up to nm) that are typical for uukv, but no antigenic relationships between khav and uukv (as well as zaliv terpeniya virus, ztv) have been found. , in a complement-fixation test, khav did not react with serum used in the identification of certain bunyaviruses, so it was categorized in with the unclassified bunyaviruses. taxonomy. the genome of khav (strain leiv-prm ) was sequenced, and the virus was classified into the phlebovirus genus of the bunyaviridae family. the genome of khav consists of three segments of ssrna whose size and orf structure correspond to the size and orf structure of the other tick-borne phleboviruses. a full-length pairwise comparison of l-segments revealed a . % nt identity between khav and uukv and . % between khav and rvfv. the predicted amino acid sequence of rdrp of khav has . % and . % aa identities with uukv and rvfv, respectively. as in other tick-borne phleboviruses, the m-segment of khav does not contain any nsm protein. the similarity between the m-segments of khav and uukv is . % nt, and that between the polyprotein precursors of khav and uukv is . % aa. the s-segment of khav has % nt ( . % aa for the n-protein) identity, on average, with that of the uukuniemi group viruses and % nt ( . % aa), on average, with the mosquitoborne phleboviruses. on phylogenetic trees constructed on the basis of the alignment of full-length genome segments, khav forms a distinct branch external to the uukuniemi group viruses (figures . À . ). at least viruses with unsettled taxonomy are included in the uukuniemi group. some of them can be considered variants of the species uukv, manawa virus (mwav), precarious point virus (ppv), and gav. two tick-borne phleboviruses, sftsv and hrtv, are more closely related to the bhanja group than the uukuniemi group. , arthropod vectors. only a single isolation of khav was ever obtained, and the ecology of the virus has not been studied. haemaphysalis longicornis ticks, from which khav was isolated, are distributed in the far east of russia, the northeastern part of china, the northern islands of japan, korea, fiji, new zealand, and australia. haem. longicornis ticks also are the main vector of sftsv (oterwise called huaiyangshan virus, hysv), which caused a large outbreak of febrile illness with a high mortality rate ( %) in in china. vertebrate hosts. the principal vertebrate host of khav is unknown. khav was isolated from ticks collected on deer. haemaphysalis longicornis ticks are repeatedly found on cows, goats, horses, sheep, badgers, and dogs. history. the sandfly fever virus group includes naples and sicilian subtypes. epidemics of the comparatively mild acute febrile disease of short duration brought on by these viruses in countries bordering the mediterranean have been known since the napoleonic wars. the same disease was common among newly arrived austrian soldiers on the dalmatian coast each summer. experiments conducted by an austrian military commission proved that the disease was caused by a filterable agent in the blood of patients and that the sandfly phlebotomus papatasi can serve as a vector to transmit the disease. during world war ii, epidemics occurred among troops in the mediterranean and two antigenically distinct strains were isolated from the blood of patients in in sicily and naples. these strains have been designated the sandfly fever sicilian virus (sfsv) and sandfly fever naples virus (sfnv), with prototype virus tosv. , dr. a. sabin gave a clinical description of the disease and demonstrated that immunity developed to one type of virus does not protect from infection caused by the other type. later, several viruses related to sfnv (anhanga (anhv), bujaru (bujv), candiru (cduv), chagres (chgv), icoaraci (icov), itaporanga (itpv), and punta toro (ptv)) were isolated from humans and rodents in south america. , , to date, viruses related to tosv have been found in all regions of the world, including the palearctic, neotropical, ethiopian, and oriental zoogeographical regions. the prototype strain of tosv was isolated from phlebotomus papatasi sandflies in in monte argentario in central italy. two viruses antigenically related to tosv-karimabad virus (karv) and salehabad virus (salv)-were isolated from phlebotomus flies collected in near karimabad village and salehabad village, respectively, in iran. , several related viruses were isolated in the mediterranean: sandfly fever cyprus virus (sfcv; adria virus (adrv, salehabad-like), isolated in saloniki (alternatively, thessaloniki), greece; and massilia virus, isolated near marseilles, france. epidemic outbreaks of sandfly fever whose agents could not be typified occurred in some central asian countries and in crimea during and after world war ii and in turkmenistan after the devastating earthquake of . antibodies to sfsv, sfnv, and karv were found in the blood of humans in tajikistan, azerbaijan, and moldova. antibodies were also found in wild animals in turkmenistan: the great gerbil (rhombomys opimus), the long-clawed ground squirrel (spermophilopsis leptodactylus), and the hedgehog (erinaceus auritus). three strains of sfnv and two strains of sfsv were isolated in À from the blood of patients in afghanistan. , taxonomy. the genome of tosv consists of three segments of negative-polarity ssrna: l-segment ( , nt in length), m-segment ( , nt) and s-segment ( , nt). phylogenetic analysis revealed that viruses of the sfnv complex are divided into five genetic clades that differ in their geographical distribution: (i) from africa (saint floris virus and gordil virus (gorv)); (ii) from the western mediterranean (punique virus (punv), granada virus (grv), and massilia virus); (iii) tosv; (iv) viruses from italy, cyprus, egypt, and india; (v) strains from serbia and tehran virus. distribution. sfnv and sfsv are distributed over those areas of the southern parts of europe and asia, and over those areas of africa, which are within the range of the vector. , À tosv is distributed over italy; spain; portugal; the south of france; slovenia; greece, including the ionian islands: cyprus; sicily; and turkey. , , À both the naples and sicilian strains were isolated from the blood of patients with febrile illness in the vicinity of aurangabad, maharashtra state, in northern india. sandfly virus fever also circulates in western india, as well as in pakistan. the cocirculation of two tosv genotypes was uncovered in the southeast of france. , , a case of disease associated with tosv befell a tourist returning from elba to switzerland in , and another struck an american tourist returning from sicily the same year. tosv from france is genetically different from that in spain. , , , periodic outbreaks of sandfly fever occurred in the first half of the twentieth century in some central asian republics, transcaucasia, moldova, and ukraine. arthropod vectors. the primary vector of sfnv and sfsv is phlebotomus papatasi; for tosv, the primary vectors are ph. perniciosus and ph. perfiliewi. the viruses can be transmitted by the transovarial route and therefore may not require amplification in wild vertebrate hosts. the infection rate of sandflies can reach : . the active period of phlebotomus in the southern part of europe lasts from may to september. sandflies are peridomestic; the immature stages feed on organic matter in soil and do not require water, but are sensitive to desiccation and therefore are often found in association with humid rodent burrows. vertebrate hosts. the main vertebrates involved in the circulation of sfnv are rodents, particularly the great gerbil (rhombomys opimus) and the long-clawed ground squirrel (spermophilopsis leptodactylus), as well as a hedgehog (erinaceus auritus). the great gerbil is distributed over areas ranging from near the caspian sea to the arid plains and deserts of central asia. the northern border of the animal's distribution is from the . family bunyaviridae mouth of the ural river on northward to the aral karakum and betpak-dala deserts, to the southern coast of lake balkhash, and thence to northern china and inner mongolia. the habitats of rh. opimus are sandy and clayey deserts. tosv was isolated from the brain of the bat pipistrellus kuhlii. animal and human pathology. sandfly virus fever does not cause disease in domestic or wild animals. the hosts of phlebotomus sandflies are usually rodents, which may develop antibodies. over human experimental volunteers were infected at the time of world war ii. , the incubation period is between and days, and the onset of fever and headache in those patients was sudden. nausea, anorexia, vomiting, photophobia, pain in the eyes, and backache were common and were followed by a period of convalescence with weakness, sometimes diarrhea, and usually leucopenia. viremia was present h before and h after the onset of fever. tosv was established as the cause of one-third of previously undiagnosed human aseptic meningitis and encephalitis cases examined in central italy. sfcv was associated with a large outbreak in the ionian islands of greece. adrv is associated with serious illness with tonic muscle spasms, convulsions, difficulty urinating, and temporary loss of sight. human disease frequently goes unrecognized by local health-care workers. studies of antibodies in people indicate that the most infections occur in children. when large numbers of unimmunized adults are introduced into an endemic area, the incidence of disease can be high. human exposure to sandflies can be reduced by repellents, air-conditioning, and screens on windows. because sandflies have a flight range of not more than m, human habitats can be constructed at a distance from potential domestic sandflies' breeding places, such as chicken houses and quarters for other farm animals. history. uukv was originally isolated from ixodes ricinus ticks collected in from cows in southeastern finland. , antigenically similar isolates (strains leiv- az and leiv- az) have been obtained from blackbirds (turdus merula) and i. ricinus ticks collected in the foothills of the talysh mountains in the southeast of azerbaijan in and , respectively. À uukv is distributed in the mid-and southern boreal zones of fennoscandia and adjacent areas of the russian plain. twelve strains of uukv were isolated from i. ricinus ticks (the infection rate was . %), and one strain from aedes communis mosquitoes, in landscapes in the mideastern region of fennoscandia. , three strains were isolated from i. persulcatus ticks collected in belozersky district, vologda region, russia, in . , uukv was also isolated from the mosquitoes ae. flavescens and ae. punctor in the west of ukraine, as well as at the border between poland and belarus. , twenty-eight strains of uukv were isolated from i. ricinus ticks collected in lithuania and estonia in À . , , À uukv was isolated as well from birds and i. ricinus ticks in western ukraine and belarus. , , in central europe, uukv was found in the czech republic, slovakia, and poland. À the prototypical strain leiv- c of ztv was isolated from ixodes uriae ticks collected in in a colony of common murres (uria aalge) in tyuleniy island in zaliv terpeniya bay in the sea of okhotsk). , in accordance with the results of electron microscopy, ztv was assigned to the bunyaviridae family. complement-fixation testing revealed that ztv is most closely related to uukv, but the two viruses are easily distinguishable in a neutralization test. , more than strains of ztv were isolated from i. uriae ticks collected in colonies of seabirds on the shelf and islands of the sea of okhotsk, the bering sea, and the barents sea (table . , figure . ). , , , two strains of ztv were isolated from i. signatus ticks collected on ariy kamen island in the commander islands, but their infection rate was less than : , (, . %). a similar virus was found in norway. one strain of ztv (leiv- az) was isolated from the mosquito culex modestus collected in in a colony of herons (genus ardea) in the district of kyzylagach in the southeastern part of azerbaijan (figure . ). natural foci of ztv and uukv associated with bloodsucking mosquitoes (subfamily culicinae) are found in continental areas in the european part of russia, particularly murmansk region. taxonomy. the viruses of the phlebovirus genus can be divided into two main ecological groups: those transmitted by bloodsucking mosquitoes (subfamily culicinae) and midges (subfamily phlebotominae), together called mosquito borne, and those transmitted by ticks (tick borne). uukv is a prototypical virus of the uukuniemi antigenic group, which includes at least related tick-borne phleboviruses (figures . À . ). the genome of uukv consists of three segments of ssrna: an l-segment , nt long, an m-segment , nt long, and an s-segment , nt long. the m-segment of uukv, and indeed, that of all tick-borne phleboviruses, is shorter than the m-segment of mosquito-borne phleboviruses, owing to the absence of the nonstructural protein nsm, which is common in the mosquitoborne phleboviruses. originally, ztv was described as a virus closely related to uukv. a full-length sequence comparison showed that the similarity of ztv to uukv is . % nt identity of the l-segment ( . % aa of rdrp) and . % nt identity of the m-segment ( . % aa). arthropod vectors. most isolations of uukv and ztv were obtained from ixodes ricinus and i. uriae ticks, respectively. the infection rates of nymphs and larvae of i. uriae are and times lower, respectively, than that of the imago. these rates indicate a high frequency ( À %) of transovarial transmission of ztv. , probably, ztv has a more pronounced ability to replicate in mosquitoes that are active in the subarctic climate zone (tundra landscapes) in july through the first half of august at temperatures sufficient for the accumulation of virus in the salivary glands. islands. in the murmansk region, which lies to the north of the european part of russia, antibodies were found in % of common murres (u. aalge), % of black-legged kittiwakes (rissa tridactyla), and % of voles (microtus oeconomus). , apparently, ruminants could be infected by mosquitoes or by eating fallen birds. on the north coast of the kola peninsula, antibodies were found in % of thick-billed murres (u. lomvia), in % of blacklegged kittiwakes, and in % of voles. , in central and eastern europe, a number of vertebrate hosts are involved in the circulation of uukv: forest rodents (myodes glareolus, apodemus flavicollis) and terrestrial passerine birds-the blackbird (turdus merula), pale trush (t. pallidus), ring ouzel (t. torquatus), european robin (erithacus rubecula), hedge sparrow (prunella modularis), wheatear (oenanthe oenanthe), european starling (sturnus vulgaris), carrion crow (corvus corone), magpie (pica pica), brambling (fringilla montifringilla), hawfinch (coccothraustes coccothraustes), yellow bunting (emberiza sulphurata), turtle dove (streptopelia turtur), and ringnecked pheasant (phasianus colchicus). , À viremia and long-term persistence of the virus were demonstrated in experimentally infected birds of many species. specific antibodies were detected in cows and reptiles. human pathology. an association was revealed between uukv and different forms of disease, including neuropathy. , a serological survey of , people in lithuania concluded that antibodies existed in . À . % of the population. human antibodies to uukv were detected in less than % of the human population in central europe À and À % in belarus. the people living in the tundra landscape had antibodies to ztv in . % of cases, while in the forest no such antibodies were detected (via a neutralization reaction). (table . ). in previous studies, rukv was mistakenly included in the sakhalin serogroup in the nairovirus genus. taxonomy. the genome of komv (strain leiv- ) and rukv (strain leiv- ) were completely sequenced, and the two viruses were classified into the phlebovirus genus. , a full-length comparison showed that the genetic similarity between komv and rukv is . À . % nt. among other tick-borne phleboviruses, komv and rukv are most closely related to mwav, which was isolated from argas abdussalami ticks in in pakistan. the similarities of the genomes of komv and rukv to that of mwav are . % nt for the l-segment ( . % aa for rdrp), . % nt of the m-segment ( % aa for the polyprotein precursor), and . % nt for the s-segment ( . % aa for the n-protein). in phylogenetic trees, komv and rukv were placed into the uukuniemi group (figures . À . ). the ecology and area of distribution of komv and rukv are the same as those of ztv, which is closely related to uukv. several strains of ztv isolated on the commander islands were sequenced, and no reassortants of ztv with komv were found. , arthropod vectors. all isolations of komv and rukv were obtained from ixodes uriae ticks, the obligate parasite of alcidae birds. the commander islands are located on the border of the temperate and subarctic climatic zones, and many different viruses belonging to the bunyaviridae (ztv, sakv, pmrv), flaviviridae (tyuleniy virus, tyuv), and reoviridae (okhv) families have been isolated from i. uriae ticks collected from birds living in colonies there. À note that the komv infection rate of the i. uriae ticks in the commander islands is times less than the ztv ( : ) and tyuv (family flaviviridae, genus flavivirus) infection rates of the same ticks. vertebrate hosts. the main vertebrate host of komv and rukv is apparently alcidae birds, especially the common murre (uria aalge), but their involvement in the circulation of komv and rukv has not been studied sufficiently. human pathology. uukv group viruses, in general, do not play a role in human infectious pathology, although serological studies have detected antibodies to various viruses of this group in people. the flaviviridae family (from the latin flavus, "yellow," as well as from yellow fever virus (yfv)) includes three genera: flavivirus, pestivirus, and hepacivirus. the flaviviridae are small ( À nm) enveloped viruses. the genome is represented by ssrna the flavivirus genus includes more than viruses classified into antigenic groups. , the flavivirus virion is spherical ( nm) and consists of a nucleocapsid ( nm) and a lipid bilayer envelope covering it. the lipid envelope contains two transmembrane glycoproteins: m (matrix protein, kd) and e (envelope protein, kd). the genome of the flaviviruses is a single molecule of rna about , nt in length and capped on the terminus. the genomic rna encodes a long orf of a polyprotein precursor flanked by and untranslated regions. mature viral proteins are produced during a complex process of proteolytic cleavage of the polyprotein precursor by cellular and viral proteases. structural proteins (core, m, and e) occupy one-third of the rna (the n part of the polyprotein) on the part of the genome, followed by nonstructural proteins (ns -ns b) (figure . ). , most of the flaviviruses are arboviruses; that is, they can be transmitted to vertebrate hosts by bloodsucking arthropod vectors (figure . ). approximately % of known flaviviruses are transmitted by mosquitoes, about % by ticks. the arthropod vectors of some flaviviruses are unknown. there is also a group of flaviviruses that infect only insects and not vertebrates. some flaviviruses (e.g., west nile virus, wnv) have ecological plasticity and can be transmitted either by mosquitoes or by ticks. flaviviruses are distributed over all continents, with mosquito-borne viruses found mainly in regions with an equatorial and tropical climate and tick-borne viruses found mostly in regions with a temperate climate zone. many flaviviruses are associated with birds, which can transfer them during the birds' seasonal migration. flaviviruses belongs to natural foci zoonoses. certain flaviviruses, such as yfv, dengue virus (denv), and west nile virus (wnv), pose a serious threat to humans. À history. the first hint that omsk hemorrhagic fever (ohf) was etiologically linked figure . ) an area with a wide network of lakes. about cases with two lethal outcomes ("atypical tularemia" and "atypical leptospirosis") were investigated (without the expedition produced prodigious results: the prototype strain ohfv/kubrin was isolated from the blood of one patient; the mechanism of transmission of the virus by the ixodidae tick dermacentor reticulatus was established; the epidemiological and clinical features of ohf, as well as its pathogenesis and pathomorphology, were described; and inactivated vaccine from mouse brain was developed and prepared for epidemiological trials. later, the role of another species of ixodidae ticks (d. marginatus) as an ohfv vector was revealed. , taxonomy. ohfv belongs to the phylogenetic branch of the mammalian tick-borne virus group (figure . ). the ohfv genome has a length of , nt, and its organization is common to the flaviviruses. two genotypes of ohfv are known today: prototypical strains for the first one are ohfv/kubrin and ohfv/bogolubovska, which have an extremely small genetic distance between them; the prototypical strain for the second genotype is ohfv/uve. À only six nucleotide substitutions, which encode four amino acids, have been found in the entire genome. three of four amino acid changes were located in the envelope glycoprotein e. phylogenetic analysis based on a comparison of partial sequences of the e gene available in genbank showed that ohfv isolates can be divided to three genetic lineages (figure . ). the genetic diversity among strains of different lineage is up to . %. arthropod vectors. the natural foci of ohfv are found in the forestÀsteppe landscape zone of western siberia, an area with numerous bogs and a wide network of lakes within the omsk, novosibirsk, kurgan, and tyumen regions (figure . ). the natural foci border the area of distribution of tbev, and the two virus's natural foci are intermingled. À the principal ixodidae tick vectors for ohfv are dermacentor pictus (in the northern forestÀsteppe subzone) and d. marginatus (in the southern forestÀsteppe subzone). , , the infection rate of d. pictus in epidemic years reaches %, in interepidemic years . À . %. the main host for preimago phases of d. pictus is the narrow-headed vole (microtus gregalis). this species of rodent is host to À % of d. pictus nymphs and larvaein the northern forestÀsteppe subzone. in À , when the number of microtus gregalis voles fell significantly, there was a concomitant decrease in the number of d. pictus ticks in the center of an epidemic zone that was accompanied by a sharp decrease in the infection rate of ticks and an attenuation of the meadow natural foci of ohfv. in some of those years, however, a high number of ixodes apronophorus, all phases of which feed on the water vole (arvicola terrestris), become involved in the virus's circulation on a par with d. pictus ticks. ar. terrestris makes fodder migrations in juneÀaugust from damp locales (where their infection takes place) to coastal meadows (where peak activity of the larvae and nymphs of d. pictus is observed during those months). small animals living in those meadows become infected as they feed on the d. pictus larvae and nymphs. in damp locales, i. apronophorus could infect muskrats. also, d. marginatus, whose optimum zone lies in a steppe landscape belt, plays some (though largely insignificant) role in the lake areas of the southern forestÀsteppe subzone. during epizootic and epidemic activity of ohf natural foci, gamasidae ticks, as well as aquatic organisms belonging to the hydracarinae, take part in ohfv circulation. their involvement is confirmed by the identity of isolated strains with those isolated from muskrats and sick humans. experiments with experimentally and spontaneously ohfvinfected gamasidae ticks testify to the ability of longitudinal (more than six months) virus preservation. vertebrate hosts. the principal vertebrate host of ohfv, which is able to directly infect humans, is the muskrat (ondatra zibethicus). this species was introduced into western siberia from canada in . their population density reached a modern-day high in the s. close interactions among o. zibethicus and local populations of arvicola terrestris emerged. ar. terrestris has periods of rapid population growth followed by epizootics of tularemia, leptospirosis, and ohfv. muskrats suffered these epizootics together with other local species of rodents: microtus oeconomus, m. gregalis, myodes rutilus, apodemus agrarius, and ar. terrestris. the ofv infection rate among muskrats is about % in both the autumnÀwinter and the springÀsummer periods. latent infection was established in all rodents except the muskrat. ohfv was detected in birds and in mosquitoes, but the role of these two animals in virus circulation is not clear. À epidemiology. ohfv is transmitted both by ixodidae tick bites and as the result of direct contact with infected muskrats, their flesh, and fresh fells. , ohf morbidity during À reached . À . %. then there was a gradual decrease down to single cases. most ohf cases ( . %) were detected in the lake forestÀsteppe, in the south of the forestÀsteppe landscape zone, which occupies . % of the territory where . % of country people in the omsk region live. the northern forestÀsteppe landscape zone is the youngest landscape of western siberia, having evolved in place of the former southern taiga landscape zone. , in the south of western siberia, the following territorial zones can be marked out: (i) the . family flaviviridae preferred territory of tick-borne encephalitis virus (tbev) (the southern taiga); (ii) intermediate territory (the boundary of the southern taiga with the northern forestÀsteppe); (iii) the preferred territory of ohfv (the northern and southern forestÀ steppe); and (iv) the territory of sporadic cases of ohf (part of the southern forestÀsteppe and steppe). , in the first zone, more than % of all cases of tbe in western siberia are registered and only single ohf cases are found; in the second zone, % each of cases of tbe and ohf; in the third zone, % of tbe and % of ohf; and in the fourth zone, % of tbe and single cases of ohf. the seasonal incidence of ohf distinctly correlates with the activity of the principal ixodidae tick vectors. cases (a few) of ohf acquired by direct contact with muskrats occur mainly during the season in which the animals are hunted, in octoberÀjanuary. in the springÀ summer season, ohf cases occur chiefly in rural areas. the age of patients ranges from to years, but cases occur mainly among middle-aged persons ( À years old). in the autumnÀwinter period, ohf occurs mainly among muskrats trappers ( %), adult members of their families ( %), and children ( %). it appears that all patients infected directly from muskrats develop symptomatic illness. seroprevalence ranges from to % in populations of endemic regions. , , in the last decade of the twentieth century, an increase in ohf natural foci activity took place in the tyumen ( ), omsk ( , À ), novosibirsk ( À ; regular epidemic activity took place on the territory of only four administrative districts), and kurgan ( ) regions. in the absolute majority of laboratoryconfirmed cases, the nontransmissive pathway (direct contact with muskrats) of the infection dominated. pathogenesis is determined first of all by the destruction of capillaries, the vegetative nervous system, and the adrenal glands. , clinical features. the incubation period of ohfv is À days long. the disease begins abruptly, with fever, head and muscular pain, hyperemia, and injection in the sclera. the body temperature increases up to À c and stays that way for À days, then decreases a little and critically falls on the th to th day after symptoms appear. from the first days of the illness, there are diapedetic bleedings, especially in the nose. recovery is usually complete, without any residual phenomena; lethal outcomes are possible, but are rare. , À control and prophylaxis. ohfv survives up to days in lake water. water can be contaminated by urine and feces of the infected muskrats or some other rodents. the water pathway in human infection has been discussed in the literature. , prevention of the infection depends on the use of protective respirators and rubber gloves in processing muskrat pelts and on personal protective measures against tick bites. tbe vaccine offers a high degree of protection against ohf. , cases of laboratory-acquired ohf have been reported in unvaccinated persons, and tbe vaccine is recommended for laboratory personnel working with either virus. interferon and its inductors have shown a high efficiency in preventing ohf in experiments using animal models. the genome of powv is a about , nt in length. the virus comprises two genetic lineages, formed by powv (lineage i) and the closely related deer tick virus (dtv, lineage ii) (figure . ). phylogenetic analysis based on partial sequences of the e gene showed that the population of powv in russia has a low genetic diversity. the strains of powv isolated in russia have a high genetic similarity to the strains of lineage i isolated in north america. a full-length genome comparison revealed that far eastern isolates (leiv- prm, spassk- , and nadezdinsk- ) have a . % identity with strain powv/lb from canada (figure . ) . arthropod vectors. powv was isolated from ixodidae ticks collected in the russian far east and in the u.s. states of california, colorado, connecticut, massachusetts, south dakota, and west virginia. serological investigations of wild mammals indicate that powv also circulates in the canadian provinces of alberta, british columbia, and nova scotia. , À in north american natural foci, powv was isolated from ixodes cookei, i. spinipalpus, i. marxi, and dermacentor andersoni ticks. , , in the far east, known vectors of powv are haemaphysalis longicornis, haem. concinna, haem. japonica, d. silvarum, and i. persulcatus ticks. , , , transphase and transovarial transmission of powv in ixodidae ticks has been established. vertebrate hosts. in north america, powv was isolated from wild mammals: the woodchuck (mormota monax, the main reservoir), american red squirrel (tamiasciurus hudsonicus), deer mouse (peromiscus maniculatus), red fox (vulpes fulva), eastern gray squirrel (sciurus carolinensis), north american porcupine (erethizon dorsatum), striped skunk (mephitis mephitis), raccoon (procyon lotor), long-tailed weasel (mustela frenata), and gray fox (urocyon cinereoargenteus). , , infection of wild vertebrates most often is inapparent. , in the south of the russian far east (in primorsky krai), powv was isolated from aquatic birds: the common teal (anas crecca) and the mallard (anas platyrhynchos). , , , epidemiology. human infections of powv were reported in canada (ontario and quebec), the united states (new york and pennsylvania), and russia (primorsky krai). , , nevertheless, human infection rarely develops. clinical features. the clinical picture of developing meningitis and encephalomeningitis includes high temperature, dryness in the gullet, drowsiness, headache, disorientation, convulsions, vomiting, difficulty breathing, coma, and paralysis, with % lethality in the severe phase of the disease. autopsy has revealed widespread perivascular and focal parenchymatous infiltration. in % of recoveries, consequent damage to the cns develops, which could lead to death in À years. , control and prophylaxis. the vaccine against tbev is not effective against powv. history. in À , the russian military medical doctorÀneuropathologist a.g. panov, together with his colleagues a.n. shapoval and d.a. krasnov, described a neuroinfection with a high level of mortality in the far east. this neuroinfection later was called "springÀ summer encephalitis." , during field expeditions in À , the historical strain tbev/ sofjin was isolated from the brain of a patient with encephalitis who died in khabarovsk krai (figure . ) . in that period, the main vector of tbev-ixodes persulcatus tickswas established, epidemiological peculiarities of tbe were studied, and the first anti-tbev vaccine was developed on the basis of intracerebrally infected mouse brain and was successfully used in medical practice. complex expeditions were undertaken by a number of prominent virologists (l.a. zilber (figure . strain tbev/leiv- kaz (the former aav) was isolated from ixodes persulcatus in the low-mountain part of southeastern kazakhstan (alma-ata region) in . preliminary investigation revealed a one-sided antigenic relation between aav and powv. aav was associated with human cases of meningitis. specific antibodies to aav were found among ground squirrels (citellus fulvus), agricultural animals, and humans. later, the aav genome was sequenced (genbank id: kj ). a full-length genome comparison showed that aav has the highest similarity ( . % nt and . % aa identities) to the tbev/ chita- , tbev/irkutsk- , tbev/aino, and tbev/vasilchenko strains belonging to the siberian genotype (figure . ) . recent genetic studies of tbev revealed two additional genotypes of this virus on the territory of eastern siberia (irkutsk region): for the first one, only a single strain is known today; for the latter, there are five strains in mongolia. thus, tbev has a high level of genetic diversity in northern eurasia. tbev-sib genotype dominates in europe, western siberia, and eastern siberia, tbev-fe in the far east. , the tbev-fe genotype, which was widely distributed in siberia and northeastern europe, is now being displaced by tbev-sib. tbev-fe strains are often pathogenic to laboratory mice, whereas tbev-sib frequently provokes severe and lethal disease. local populations of all genotypes of tbev could be stable for a long time. distribution. tbev is distributed within the areas of distribution of its main vectors: ixodes persulcatus and i. ricinus ticks (figure . -see details in the detailed work of e.i. korenberg norway; À in the rest of europe, the czech republic, , slovakia, , , bulgaria, hungary, , poland, , croatia, latvia, lithuania, estonia, , denmark, germany, À austria, slovenia, france, italy, , and spain (table . ); and in asia, the russian far east and siberia, , , japan (hokkaido), north and south korea, , china, mongolia, kazakhstan, and kyrgyzstan. arthropod vectors. natural tbev infection has been observed in species of ixodidae ticks. the principal arthropod vectors for tbev in russia are the ixodidae ticks ixodes persulcatus (in the far east, siberia, and the north of the european part of the country) and i. ricinus (in the south of the european part) (figure . ). the northern boundary of i. persulcatus and i. ricinus lies within the limits of an effective temperature sum isoline of about , À , c (the middle taiga landscape belt). the most suitable climatic conditions for these ticks are within the south taiga. imago tick activity begins in the third d decade of april and reaches a maximum in the second and third decades of may or in the first and second decades of june, with activity beginning to decrease in the third decade of june. this time frame correlates with morbidity dynamics having an -to -day lag (figure . ). the ecological links of tbev during its circulation in natural foci are extremely diverse as the result of wide distribution of this virus (figures . and . ). ixodidae ticks, mainly i. persulcatus, are the natural reservoir of tbev and the core of natural foci. , , , from the very beginning of the tick's larval stage, a suctional, tarlike liquid appears around the hypostome and becomes rosin. , the quantity of virus in this rosin plug is comparable to that in the tick's body ( À pfu/mcl). the place of suction on the body of the host is significant for the development of infection; for example, suction in the axillary hollow results in the highest lethality ( . %, . times more in comparison to suction in the neck and in the head. ticks become infected as they suck blood from a vertebrate host with a level of viremia that is equal to or higher than the threshold required for infection. ticks can also become infected from an uninfected vertebrate host as they suck blood together with infected ticks. , transovarial and transphase transmission of tbev has been described in the literature; nevertheless, the effectiveness of vertical transmission of tbev is low. (about % of progeny turn out to be infected). , the sexual pathway of tbev transmission from male to female is quite effective (about %). À the aggressiveness and activity of tbev-infected ixodidae ticks increases with the tbev titer in their bodies. , infected ticks have been found on the clothing of figure . trends in the incidence of tbe in russia, by month (as a percentage of the amount of disease for the year, according to long-term data). humans at a fequency À times higher than uninfected ticks have been found. , , tbev has been isolated from the mosquitoes anopheles hyrcanus in kyrgyzstan and aedes sp. in western siberia. the strain tbev/malyshevo was isolated from aedes vexans nipponii mosquitoes collected in on the coast of petropavlovskoe lake in khabarovsk krai in the russian far east ( ʹn, ʹe ). À a preliminary investigation concluded that this strain belonged to negishi (negv) virus, and later the possibility was discussed that the strain belonged to a separate, malyshevo virus. then, phylogenetic analysis using a next-generation sequencing approach revealed that malyshevo is a strain of tbev and is closely related to tbev strains isolated in the far east: tbev/ , tbev/ spassk- , tbev/primorye- . tbev has been isolated many times fromticks and fleas of the superfamily gamasoidea living in nests of rodents and birds (table . ), even during the winter period. , , À vertebrate hosts. hosts for the preimago stage of ixodidae ticks-asian chipmunks (tamias sibiricus), shrews (members of the soricidae family), bank voles (myodes glareolus), field voles (microtus agrestis), mountain hares (lepus timidus), and species of birds (table . )-have great significance in tbev circulation. , , , , , , , persistent tbev infection in bank voles and field voles has been found during the winter period. infection among vertebrates occurs mainly by tick bites. in rare instances, alimentary transmission of tbev through milk containing viruses is possible. , epidemiology. there are two basic modes of human infection by tbev: (i) as the result of being bitten by infected ixodidae ticks (the main mode); and (ii) as the result of consuming infected raw goat, sheep, and cow meat, milk, or dairy products (mainly in natural foci linked to ixodes ricinus). , , the latter pathway of tbev distribution often involves whole families. as much as % of cases in belarus have been alimentary. tbev can persist in milk at c for more than min, and some of the viruses can remain viable even after pasteurization at c for min. nor is tbev inactivated after h at c and ph . . many laboratory infection cases (usually by aerosol) have been described. several hundred cases are recorded in europe (table . ) and in russia (table . ) each year, with considerable interannual variation. , , À the highest level of tbe morbidity is registered in the baltic states (latvia, . À . per , population); lithuania, . À . ; and estonia, . À . ) and in slovenia ( . À . ) and the czech republic ( . À . ). in neighboring austria, where the vaccination rate is higher, the index is lower ( . À . ). seasonal tbe morbidity in russia is connected with seasonal activity of the ixodidae tick vectors (figure . ) . the risk of infection depends upon the frequency of tick bites, which is different for populations living in the different landscape belts. results of an investigation of almost , people demonstrate that the highest risk is for the population living in the southern taiga belt, where about % of adults were found to have tick bites during one epidemic season (table . in rural localities of the southern taiga belt, about half of schoolchildren and about % of adults have antibodies to tbev. for comparison, only À % of adult citizens of kemerovo, a city of about half a million in western siberia, and À % of citizens of moscow have antibodies specific to tbev (table . ) . a mathematical model for evaluating the infection rate and the probability of developing the disease as a function of the density of the tick population, its infection rate and biting activity, and the level of the immune human layer was developed by d.k. lvov and coauthors. À the same approach, which is also suitable for other arboviral infections, was used for landscape-epidemiological zoning of tbev natural foci in altai krai in the southern part of western siberia: more than , residents living in the different landscape belts on a territory about , km were tested by serological methods (figure . ) . the tests produced a good fit between calculated and registered morbidity data (table . ) . pathogenesis. tbe can be realized in several pathogenetic variants. an inapparent clinical form is characterized by short-term localization of tbev in lymph nodes and immune cells, as well as by extranervous reproduction without viremia. infection is terminated by the development of stable immunity. about % of cases of infection are inapparent. clinical fever is expressed as a common infectious process, but both the central and the peripheral nervous system are involved in the pathology. neuroinfection is characterized by lesion of the envelope and substance of the spinal cord and cns. clinical features. the incubation period ranges from to days, but usually is À days. the onset of illness in typical cases is abrupt and with a headache. the temperature clinical symptoms of tbe, as well as the severity of the disease, are at least partially determined by biological properties of the virus. there are two main clinical forms of tbe: the far eastern variety, associated with far eastern and siberian strains of the virus, and the european variety (also known as western biphasic meningoencephalitis or biphasic milk fever), associated chiefly with european strains. human disease of the first type is usually clinically more severe in the acute phase, but is associated with a lower rate of chronic cns sequelae. the first phase starts with sudden fever, flulike symptoms (pronounced headache, weakness, nausea, myalgia, arthralgia), and conjunctivitis. the second phase appears after À days of apparent recovery, but then the cns is affected (meningoencephalitis appears), accompanied with fever, retrobulbar pain, photophobia, stiff neck, sleeping disorders, excessive sweating, drowsiness, tremors, nystagmus, meningeal signs, ataxia, pareses of the extremities, dizziness, confusion, psychic instability, excitability, anxiety, disorientation, and/or memory loss. tbev produces diffuse degenerative changes in neurons, perivascular lymphocytic infiltration, and damage to purkinje cells in the cns. mortality ranges from % (tbev-eur), to % (tbev-sib), to À % (tbev-fe). convalescence is prolonged, and neurological and psychotic sequelae often include paresis and atrophic paralysis of the neck and shoulders. , , a chronic form of the disease occasionally combines with a progressive course (called kozhevnikov's epilepsy), in which progressive neuritis of the shoulder plexus, multiple sclerosis, and progressive muscle atrophy often develop. , the chronic form is registered in À % of all tbe cases and is said to be the result of virusÀimmunity interactions. many authors have noted a decreasing number of severe tbe cases. diagnostics. laboratory diagnosis of tbe involves both serological (elisa, hemagglutination inhibition test (hit), neutralization testing) and virological methods (virus isolation using a biological model of intracerebrally inoculated newborn mice, À g mice, cell culture), as well as highly sensitive rt-pcr and real-time rt-pcr. control and prophylaxis. specific and nonspecific prophylaxis tools are highly efficient if they are utilized correctly. personal safety includes protection against ticks. vaccination against tbev has a long history of success. mass vaccination of populations in the endemic territory is necessary. a full course of vaccination provides % safety. all vaccines produced in russia are effective in the entire area of distribution of tbev, independently of the strain used to prepare the vaccine. vaccination has reduced tbe morbidity down to single cases in austria, the czech republic, and slovakia. single cases of tbev among vaccinated persons need to be investigated because possible causes are personal peculiarities of the immune system and errors in the control of vaccine production. the presence of brain tissue in vaccines produced on the basis of intracerebrally inoculated newborn mice was a source of danger for a long time: demyelinating encephalitis could develop. this danger was eliminated after vaccines were developed which used tbev strains that reproduced in cell cultures. in the s, cell culture vaccines against tbev were developed by e.n. levkovich history. japanese encephalitis virus (jev) was originally isolated by h. hayashi in from a patient who died with encephalitis and then, again, in from a patient who died with a fever in tokyo. , before that, however, japanese encephalitis (je) epidemics was documented in japan in and onward as "ioshiwara cold." in the south of the russian far east, strains of jev were known since the end of the s (figure . ). je played a role in the historical events of world war ii. american military personnel massed on okinawa and preparing to invade japan were demoralized by an outbreak of encephalitis among the indigenous people. a fictionalized account of the risk from je for american soldiers during world war ii underscores the military risk. taxonomy. phylogenetic studies indicated that jev isolates be divided into five genotypes, the distributions of which overlapped (figure . ). genotypes i, ii, and iii are most prevalent and are spread throughout asia (japan, china, india, korea, malaysia, and vietnam), the far east of russia, and northern australia. genotypes iv and v are rarer and were isolated in indonesia and india, respectively. genotypes i and iii are found mostly in temperate zones, whereas genotypes ii and iv predominate in tropical zones. À genetic diversity between strains of the different genotypes ranges from . % to . %. arthropod vectors. jev circulation in the equatorial and subequatorial climatic zones is year-round and is seasonal in the tropical, subtropical, and temperate belts, with a peak at the end of summer and the beginning of fall. jev is brought from the equatorial and tropical climatic belts to the subtropical and temperate belt during the spring migration of birds. about species of mosquitoes are able to transmit jev; nevertheless, only some of them are effective vectors. the main vector in japan, the philippines, the korean peninsula, china, the indochinese peninsula (except malaysia), indonesia, sri lanka, india, and nepal is epidemics usually develop after plentiful precipitation and a long rise in environmental temperatures until they are no less than c (but within the range À c). for a long time, the main vector for jev in the south of primorsky krai in russia was culex tritaeniorhynchus. in the s, as a result of both improvements in agriculture and meteorological changes, this species of mosquitoes consisted about % of all field collections. in subsequent years, however, their numbers abruptly declined, and by the s the species represented only . À . % of all mosquitoes collected. cx. pipiens is an accessory vector, and aedes togoi transmits jev in seashore areas. jev was also isolated in from ae. vexans. , vertebrate hosts. aquatic and semiaquatic birds (especially herons) have the main significance in the natural cycle of jev circulation. regular transfer of jev in migratory birds from endemic territories with year-round circulation of the virus to regions of the southern part of the temperate climatic belt (in particular, the southern part of primorsky krai, to the south from lake khanka ) is likely. jev transfer over hundreds of kilometers by infected mosquitoes is possible as well, especially in areas with a monsoonal climate (e.g., in australia through the torres strait À ). birds transfer jev from natural to synantropic biocenoses, where, thanks to culex tritaeniorhynchus mosquitoes willingly attacking wild birds, pigs, persons, synantropic birds, and domestic animals (chiefly pigs), these all join into jev circulation. infection in pigs could be inapparent, or it could be clinically expressed with encephalitis and a lethal outcome. the level of viremia in infected pigs is enough to infect mosquitoes. such epizootics among pigs are, in effect, amplifiers for jev, serving as prerequisites for the development of epidemics, first of all among people living in the countryside, but then among city dwellers as well. antibodies to jev specifically were revealed among wild boars ( %), raccoons ( %), and dogs ( %). in the south of china, jev was isolated from both leschenault's rousette (rousettus leschnaulti), a species of fruit bat, and the little tube-nosed bat (murina aurata), and anti-jev antibodies were identified in the blood of those animals. jev preservation in bats could be one of the mechanisms of the year-round circulation of the virus in its natural foci, with activation in the spring and subsequent replication and spreading in the summer and autumn. in natural foci, birds are the principal vertebrate hosts contributing to transmission of the virus; in synantropic foci, pigs are the most important vertebrate hosts. , jev has been isolated from the grey-headed bunting (emberiza fucata), great cormorant (phalacrocorax carbo), japanese thrush (turdus cardis), azure-winged magpie (cyanopica cyana), japanese wagtail (motacilla grandis), barn swallow (hirundo rustica), and night heron (nicticorax nicticorax). natural foci are situated in meadows. of late, culex tritaeniorhynchus has become more abundant in connection with intensive rice cultivation, portending the possibility of increased jev circulation and epidemics. , epidemiology. all the territory of japan, except for northern part of hokkaido, is endemic, but most diseases are registered near islands in a closed sea, as well as in tokyo and adjacent prefectures. before , outbreaks of je emerged in japan practically every year, with , À , patients seen. later, morbidity began to decrease to tens of cases per year. in the a and s, morbidity fell to the level of single cases per year. the main cause of the decrease was a significant drop in the population of the main jev vector-culex tritaeniorhynchus mosquitoes-as the result of a reduction in the acreage of rice fields as well as water pollution in places of mosquito habitation. in addition, the program of mass vaccination carried out annually among children of school age and a change in the structure of pork farms lessening the availability of pigs played a significant role in the falloff in the mosquito population. je is a serious problem in countries of southeast asia and oceania. during the last few years, more than , cases per year were registered, with about % lethality. morbidity increases annually in bangladesh, indonesia, laos, myanmar, north korea, and pakistan. , in addition, , the occurrence of an epidemic in southeastern asian countries is becoming more and more likely because those countries are now seeking to increase their production of rice. the greatest risk of je is said to be in china, nepal, sri lanka, thailand, laos, and vietnam. je is of the highest importance among all kinds of endemic encephalitis, potentially threatening nearly % of the population of our planet. the disease especially affects military contingents, as it did the american army during the concentration of armies in okinawa and the soviet army during the battle of lake khasan (also called the changkufeng incident) in the south of primorsky krai. precursors of jev circulated in indonesia and then evolved into six genotypes. genotype iii is widespread in a moderate climatic belt and often provokes epidemic outbreaks in eastern and southeastern asia. genotype i originated in indonesia, circulated in thailand and cambodia in the s and in south korea and japan in the s, and has now completely replaced genotype iii. genotype i got into japan in two ways: from southeastern asia and from mainland china. , two island territoriesthe philippines and taiwan, in both of which genotype iii circulates-were free of genotype i-and the philippines remains free-but the genotype appeared in taiwan in . the evolution of jev led to the emergence of two new subclusters in À ; the two together have replaced genotype iii. until recently, the qinghai-tibet plateau, in china, was free of jev, but in august the virus was isolated from culex tritaeniorhynchus mosquitoes there. during an epidemic in septemberÀnovember , genotype i circulated in japan. in nepal, on the northern border of india, je has been known since , after which outbreaks were observed annually. jev circulates in the north of australia as well. , je claimed morbidity in the south of the russian far east (in primorsky krai) in during an expedition headed by p.g. sergiev and i.i. rogosin. epidemics of jev broke out in the region in , , and . more than cases were recognized between and , with % reported in the extreme south of primorsky krai. the northern extent of this area is limited by the southern part of the ussuri lowland (about À n, À e). enzootic jev circulation without human morbidity has been documented, with the seroprevalence of residents estimated at about À %. , , , je cases occur mainly in augustÀseptember (but also when heavy rains are combined with high temperatures from april to september: $ c in april, $ c in june, $ c in august, and $ c in september). clinical features. the clinical picture of je varies from asymptomatic and easy feverish forms to an encephalitis syndrome. the ratio of clinical to asymptomatic forms is from : to : , , although the ratio in india in the s and s was from : to : . À the start of the disease is sudden, with fever ( %), headache, vomiting ( %), and symptoms of cns destruction (most often, hemiplegia and articulation lesions)-in % of cases, and at the height of the illness in % of cases. about one-third of patients with cns lesions recover completely. lethal outcomes are preceded by unconsciousness and then coma ( À % of the total number of patients). death comes in two-thirds of cases during the first week, in one-fourth during the second week, and in the rest of the cases in one month, from the onset of symptoms. after the disease, residual phenomena in the form of paralysis and mental issues are quite often observed. , control and prophylaxis. inactivated vaccines are used to immunize people, , , , À live vaccines to immunize pigs and horses. vaccination and protection of pigs from mosquito attack and protection of humans from mosquitoes (through the use of repellents, mosquito nets, bed curtains, etc.) are recommended during epidemics among people. mass vaccination has been carried out successfully in japan, south korea, china, and india. , , , À live vaccine manufactured on the basis of the chinese strain sa À is is given in china, south korea, and other countries in government programs aimed at expanding immunization of children. the complete genomes of tyuv and kamv (genbank id: kf and kf , respectively) were presented in a article in the journal of medical entomology, and it was established that kamv was a new virus within the tyuv group of the flavivirus genus. virion and genome. tyuv is a prototypical virus of the tyuleniy antigenic complex. the viruses of that complex belong to the ecological group of seabird tick-borne flaviviruses, which forms a distinct branch on the phylogenetic tree. four species are known in the tyuleniy antigenic complex: tyuv (in russia and the united states), meav (in europe), srev (in oceania) and kamv (in russia). the genetic similarity between the seabird tick-borne flaviviruses and the mammalian tick-borne flaviviruses is about % nt. a full-length genome comparison showed that the similarity among the four viruses in the tyuleniy antigenic complex is % nt and % aa, on average. tyuv leiv- c, isolated in the russian far east, has % nt and % aa identities with tyuv isolated on the pacific coast of the united states. kama virus (strain leiv-tat ) has % nt identity with the other viruses of the tyuleniy antigenic complex (meav, srev, tyuv). the similarity of the polyprotein precursor of kamv is % aa with each of tyuv and srev, % aa with meav. arthropod vectors. tyuv is distributed over the basins of the sea of okhotsk and the bering and barents seas. the infection rate of ixodes uriae in the pacific part of the virus's distribution is . times greater than in the atlantic part (table . ). , À outside of northern eurasia, tyuv is distributed over the west coasts of the united states (chiefly in oregon) and canada. , the infection rate of nymphs and larvae of i. uriae is one-twentieth to one-half the infection rate of the imago. the infection rates of i. uriae females and males (the males have only a rudimentary hypostome and do not feed) are practically the same. these data testify to the transphase and transovarial transmission of tyuv. (the efficiency of this type of transmission is about %.) attempts to isolate tyuv from i. signatus ticks were unsuccessful. the presence of antibodies to tyuv among local cows and indigenous people of the commander islands , indicates the possible role of sanguivorous mosquitoes (e.g., aedes communis, ae. punctor, and ae. excrucians) in infection. mosquitoes could also take part in virus circulation: their infection rate from the end of july to the beginning of august reaches . % in nesting colonies of seabirds and . % on the seacoast. experimental infection of tyuv on the model of aedes aegypti demonstrated the presence of the virus À days after inoculation, with . À . lg ld / mcl on days À ; . À . lg ld / mcl on days À ; and . lg ld / mcl on day . the transmission of tyuv during the feeding of infected mosquitoes on mice was established À days after infection of the mosquitoes. in culex pipiens molestus, tyuv was detected À days (the period of observation) after infection, with . À . lg ld / mcl. vertebrate hosts. migratory seabirds play a role in the exchange of tyuv group flaviviruses between the northern and southern hemispheres. , investigation with the help of indirect complement-binding reactions of sera samples from , birds collected in the far east revealed that the maximum tyuv infection rate takes place in brü nnich's guillemots (uria lomvia), common murres (u. aalge), and tufted puffins (fratercula cirrhata). lower rates were seen in pelagic cormorants (phalacrocorax pelagicus), redfaced cormorants (ph. urile), glaucous-winged gulls (larus glaucescens), kittiwakes (rissa tridactyla), northern fulmars (fulmarus glacialis), and sandpipers (scolopacidae). , , , , , the presence of specific anti-tyuv antibodies among sandpipers-red-necked phalaropes , , considering the annual migrations of these birds, tyuv can be found within the i. uriae area of distribution in nesting colonies of puffins. about % of adult and % of juvenile northern fur seals (callorhinus ursinus) on the commander islands have specific anti-tyuv antibodies, implying that these animals are involved in the circulation of that virus. a tyuv strain was isolated from the arctic ground squirrel (citellus (urocitellus) parryii) on the southeastern coast of the chukotka peninsula ( n, e). this event is one more argument for virus splash into the continent, with rodents included in virus circulation. in the tundra of the kola peninsula seacoast, antibodies specific to tyuv were detected among cattle ( . %) as well as red-necked phalaropes (phalaropus lobatus), snow buntings (plectrophenax nivalis), ruffs (philomachus pugnax), and rodents: tundra voles (microtus oeconomus). thus, in the atlantic part of its distribution, tyuv also tends to penetrate into the continent. experimental infection of kittiwakes (rissa tridactyla), herring gulls (larus argentatus), and brü nnich's guillemots (uria lomvia) was followed by the development of clinical features with cns lesions and lethal outcomes. epidemiology. the indigenous population in the far eastern part of tyuv distribution has specific anti-tyuv antibodies: . % in tundra on the coast of the chukotka peninsular, . % in forestÀtundra on the coasts of the sea of okhotsk and the bering sea, . % -in taiga on sakhalin island, and . % in tundra on the coast of the kola peninsula. the development of fever in humans visiting nesting colonies of seabirds on the coast of the barents sea has been described in the literature. ecological peculiarities of tyuv and kamv distribution. penetration of tyuv from the northern to the southern hemisphere is carried out by about species of birds, mostly turnstones (arenaria interpres), that nest in the north of asia and overwinter in australia and new zealand. wedge-tailed shearwaters (puffinus pacificus) nest in the southern hemisphere and carry out an annual migration along the coasts of the pacific ocean up to northern eurasia and north america. , close genetic relations found between tyuv and kamv have not been explained yet because information is lacking about ecological links between alcidae birds in the north and bank swallows in the central part of the russian plain. nontheless, the closeness demonstrates an ancient link between the flaviviruses and ixodidae ticks-obligatory parasites of colonial and burrow-shelter birds not only on the ocean coast, but also on the continental part of the distribution of those viruses. , , , , meav and srev, which are genetically close to tyuv, , could be intermediate evolutionary branches between tick-borne viruses of seabirds and later mammalian viruses transmitted by ticks. , the main vector of tyuv in subarctic regions-ixodes uriae, adapted to seabirds-is replaced by the ornithodoros capensis complex or argas spp. in the subtropics and tropics. , the northern boundary of the argas genus distribution is limited by a july isotherm of À c and of the ornithodoros genus by À c in europe and À c in asia. the vector of kamv-the i. lividus tick-has transpaleoarctic distribution, from the british isles in the west to japan in the east and from n down to s. this species of tick has an extrazonal distribution in the diggings of bank swallows (riparia riparia) made in the soft ground of steeps along the banks of rivers and lakes in taiga, leaf forest, forestÀsteppe and . family flaviviridae steppe climatic belts. i. lividus ticks are typical parasites of-burrow-shelter birds and relate strictly to the life cycle of the host: after the appearance of birds in the nesting areas in may, larvae begin to feed. in june, nymphs feed on the nestlings; female imagoes also feed on the nestlings, but male imagoes do not. given the presence of kamv-a virus closely related to tyuv-in the central part of the russian plain, it is worthwhile, and even necessary, to carry out a wider search for tyuv analogues on the continental part of northern eurasia. history. dengue fever (denf), etiologically linked to dengue virus (denv) (family flaviviridae, genus flavivirus), has been known in asia, africa, and america since the end of the eighteenth century. , wide epidemics of denf appeared in southeastern asia after world war ii. according to who data, denf morbidity, including imported cases, has been detected in more than countries of asia, africa, and europe. more than . billion people on earth are under the threat of denf. about million people fall victim to denf annually. american armies sustained heavy losses as the result of denf during world war ii, as well as during À in vietnam, the philippines, somalia, and haiti. simultaneous outbreaks of denf and chikungunya fever often occur. the virus etiology of denf and its transmission by mosquitoes was established by p.m. ashburn and c.f. craig in experiments using volunteers at the beginning of the twentieth century. denv- was isolated in from the blood of patients with fever on the hawaiian islands, denv- in from the blood of patients with fever on new guinea, denv- in from the blood of patients with fever in the philippines, and denv- in from the blood of patient with fever during epidemics in manila. taxonomy. four different serotypes of denv form a distinct phylogenetic lineage on the mosquito-borne flavivirus lineage (figure . ). genetic variation among different strains suggested that denv be divided into distinct genetic clusters considered as genotypes. the genetic diversity of denv is best exemplified in denv- , the different strains of which are divided into four genotypes: asian , asian , american/asian and so-called cosmopolitan. denv- strains are divided into five genotypes (iÀv), and denv- strains form three genotypes. in general, a particular genotype is linked to specific geographical regions and that genotype may be used in describing imported cases of denv infection. arthropod vectors. denf belongs to natural-foci diseases. its vectors are anthropophilic species of mosquitoes: aedes aegypti and ae. albopictus in synantropic natural foci. humans are the only vertebrate hosts in synantropic natural foci, whereas wild mammals are involved in virus circulation in sylvatic natural foci. vectors in equatorial africa are ae. furcifer, ae. vittatus, ae. tailori, and ae. luteocephalus. vertebrate hosts. in southastern asia, the vertebrate hosts of denv are macaques (genus macaca) and surilis (genus presbytis) living in the rain forests of equatorial climatic belts; the main vector is aedes niveus; a circulation of denv-{ , , } has been identified. natural foci of denv were also found in the eastern part of equatorial africa, in senegal and nigeria. the vertebrate hosts are patas monkeys (erythrocebus patas); wild strains are considered possible precursors of epidemic ones. among humans, wild strains provoke slight clinical forms of dengue fever. À epidemiology. denf has an epidemic character involving tens of thousands of people in southeastern asia, oceania, the caribbean basin, central and south america, and africa. the transmission pathway is a mosquito bite, mainly by members of the aedes genus. these mosquitoes are able to transmit denv in À days after feeding on a sick person. about À % of the human population falls victim to denf during epidemics. denv continues to circulate actively and to provoke wide epidemics. for example, all four types of denv exist in sri lanka, with new clades replacing old ones, accompanied by a severe clinical picture. , in the s, a new wave of denf epidemics began to develop in sri lanka, india, pakistan, and central and south america. , these epidemics were linked mainly to the relatively new denv- , but to denv- and denv- as well. in some cases-for instance, in myanmar and china -all four types of denv circulated simultaneously. clinical features. the incubation period is À days. the start of the disease is quick, with fever and with frontal and retroorbital headache. lymphadenopathia, rash in macule and papule forms (not always), leukopenia, skin hyperesthesia, changes in taste, loss of appetite, and muscle and joint pains gradually develop. then, after À days of normal body temperature, the second wave of fever develops, accompanied by a measleslike rash. the palms and soles are rash free. severe cns complications have been described to arise in endemic regions (e.g., brazil). the hemorrhagic clinical form of denf, with shock and a high level of lethality (especially among children), was originally seen in the philippines in . later, this clinical form was registered in india, malaysia, singapore, indonesia, vietnam, cambodia, and sri lanka, as well as on islands in the pacific. according to who data, more than . million patients had hemorrhagic denf from to , with , lethal outcomes. starting from , hemorrhagic denf has become the main cause of hospitalization and deaths among children in the countries of southeastern asia. the hemorrhagic form of denf usually develops after a secondary infection by a type of denv different from the primary one. the primary type of denv is not neutralized, but fragments antigen binding (fab)associated enhancement of the infection occurs. for example, in french polynesia in , two years after epidemics of denv- , an outbreak etiologically linked to denv- emerged and hemorrhagic denf was detected among children À months and À years old. five symptoms are characteristic of the hemorrhagic clinical form of dengue: high temperature, rash, hemorrhagia, hepatomegalia, and insults to the circulatory system. thrombocytopenia with blood condensation also occurs. hemorrhagic denf can be without shock or can precede it. shock develops in À days of the disease, wheninsults to the circulatory system appear: the skin becomes cold, sticky, and cyanochroic; the pulse rate increases; and drowsiness appears. in the absence of antishock actions, patients die within À h. the severity of the disease depends on a number of factors: the infection titer in the blood, the type of denv, its biological properties, and more. À imported cases of dengue. there is a high risk of denv infection for visitors to endemic regions, with consequent penetration of the virus into nonendemic regions. , denf has occurred in spain in the past (e.g., in cádiz in ). several tens of human cases are introduced into the country each year from equatorial and subequatorial regions. denv- and denv- caused a huge outbreak in greece in augustÀseptember of both and : in those periods, about , of , inhabitants of athens and piraeus contracted denf, including hemorrhagic forms and about , lethal outcomes. penetrations of denv also took place in the netherlands in À and in japan, france, northern italy, and germany in . during À in russia, among patients with fever from the risk group that visited tropicalÀequatorial countries, cases of denf were identified with the help of serological investigation ( cases arrived from indonesia; from thailand; each from vietnam and india; each from venezuela and the dominican republic; and each from sri lanka, malaysia, singapore, sierra leone, and costa rica). À in in russia, cases of denf were identified in moscow, in st. petersburg, and imported strains of denv were isolated. the risk of denf for europe has appeared again with the introduction of aedes albopictus and ae. aegypti mosquitoes in the countries of the mediterranean and black sea basins. stable populations of both these species were found on the southeastern coast of the black sea (in krasnodar krai, russia, as well as in abkhazia). À control and prophylaxis. the main approach to prophylaxis is to struggle against mosquito vectors. during the s and s, a program against ae. aegypti mosquitoes that was unprecedented in terms of scale and expense was conducted in america, but it was stopped in ; as a result, in the number of ae. aegypti mosquitoes was estimated to be same as that before the program began. the struggle against mosquito vectors in singapore turned out to be more successful, but still did not prevent denf morbidity. investigations into four-component vaccines are far from completion today. , express methods of denf diagnostics are used in airports. who issues a reference guide for the diagnosis, treatment, prophylaxis, and control of denf. (table . , figure . ). further serological investigations with the help of hit revealed that sokv belongs to the flaviviridae family, and with the help of complement-fixation testing (but not neutralization testing), to the entebbe bat serogroup. À a prototypical strain of this serogroup was isolated from a kenyan big-eared free-tailed bat (tadarida lobata) collected near entebbe, uganda, in july . taxonomy. the genome of sokv was sequenced, and genome analysis showed that the virus is related most closely ( % nt and % aa identities) to entebbe bat virus (entv). sokv has about % nt and % aa identities with other flaviviruses, except viruses of the rio bravo (rbv) and modoc (modv) groups (, % similarity). no arthropod vector of entv and sokv has been established; however, phylogenetic analysis based on a full-length genome comparison placed sokv and entv together on a distinct branch of mosquito-borne flaviviruses related to yfv and sepik virus (sepv) (figure . ) . arthropod vectors. according to serological data, domestic animals do not take part significantly in sokv circulation, although antibodies to sokv were detected among cows and sheep. isolation of sokv from birds that were known not to have made contact with obligatory parasites of bats, as well as the presence of positive sera from humans and domestic animals, suggest the participation of mosquitoes in sokv circulation. transmission of the virus by bats could be carried out by argas vespertilionis and ixodes vespertilionis. À vertebrate hosts. more than flaviviruses were isolated from bats (order chiroptera); about half are unique to these mammals. ; and yokose virus (yokv). the insectivorous bats vespertilio pipistrellus, from which sokv was isolated, belong to the evening bats family (vespertilionidae), which is active during the evening and at night. their daylight shelters are situated mostly in house garrets. v. pipistrellus is distributed over europe, the mediterranean, the caucasus region, and central asia. a part of the population overwinters in africa, where infection by local viruses (e.g., bbv, dbv, entv) could occur. experimental infection of sparrows (passer montanus) resulted in sokv being detected in internal parts of infected birds on the th and th days after inoculation. epidemiology. there are no laboratoryconfirmed human cases of sokv infection. nevertheless, the proximity of sokv hosts (bats) to human habitats, as well as the presence of encephalitis and hemorrhagic fever agents among the flaviviruses, suggest that sokv may be dangerous to humans. complement-binding specific anti-sokv antibodies were detected among humans in kyrgyzstan and turkmenistan ( . % and . %, respectively), testifying to recent infection events. À , , , , , À history. wnv (family flaviviridae, genus flavivirus), theetiological agent of west nile fever (wnf), was first isolated during research on yfv in from the blood of a native of uganda who was suffering a mild fever. the strain isolated, b , belongs to genetic lineage ii. (see "taxonomy" next.) strain eg , isolated from the sera of a child without clinical signs in egypt, is the prototype for african genetic lineage i, widely used for investigations. wnv belongs to the jev group, has the broadest antigenic properties, and, on theoretical grounds, appears to be the most ancient member of the flavivirus genus. lowpassaged wnv strains are known by many investigators to be common causes of laboratory infection, apparent or inapparent. taxonomy. phylogenetic analysis revealed that different geographic isolates of wnv could be grouped into two major genetic lineages (figure . ). lineage i includes strains from africa, southern and eastern europe, india, and the middle east. lineage ii includes isolates from west, central, and east africa, as well as madagascar. lineage can be subdivided into three clades: clade a consists of strains from europe, africa, the united states, and israel. the topotypic isolates of wnv in australia-kunjin virus (kunv)belong to clade b, and clade c is formed by isolates from india. subsequently, two genetically divergent rabensburg strains- À (isolated in the czech republic) and leiv-krnd - (isolated in russia)-were proposed to form novel lineages iii and iv, respectively. À a fifth lineage was formed by strains from india. phylogenetic analyses based on complete genomic sequences revealed that the various lineages differed from each other by À %. a putative novel sixth lineage has been detected in spain in , but only a partial sequence of the ns gene of this isolate is available in genbank. world distribution. the distribution of wnv in northern eurasia, and indeed, in the whole world, covers vast territories within the equatorial, tropical, and temperate (the southern part) climatic belts in africa, europe, asia, australia, and north america (the last starting from ). in africa, it is very difficult to find a country or landscape in which wnv has not been detected by either a virological or serological approach. the isolation of this virus from a wide array of species of birds, mosquitoes, ixodidae and argasidae ticks, and domestic animals as well as humans testifies to the ecological plasticity of the virus and therefore to its ability to adapt to different ecological conditions. two genetic lineages circulate in africa: the first, which dominates, and the second. sporadic morbidity and epidemic outbreaks permanently take place in a number of african countries, especially the republic of south africa, where a wide outbreak with at least , human cases occurred in after an active period of rain. according to a report from the pasteur institute, during the last À years alone, epidemic outbreaks were registered in algeria (in , with more than cases and deaths, and in , with cases), in tunisia (during À , with cases), morocco (in and ; the epidemic reached both humans and horses), in senegal (in ), and in kenya (in ). new centers of infection continue to be arise in africa-for example, in in morocco, where morbidity among people and horses was observed and . % of birds had specific anti-wnv antibodies, and in in the republic of south africa, where there were a number of lethal outcomes. the wide distribution of wnv in africa and its circulation among populations of the majority of the continent's species of local and migrating birds indicates that the virus is able to penetrate to southern europe and western siberia through the birds' migration pathways. most of the birds nesting in or migrating through the volga delta overwinter in africa. thus, africa is the main source of penetration of wnv genotypes i and ii into southern europe and western siberia. in asia, a peculiar third genotype of wnv appears to be circulating in the indian subcontinent. a prototypical strain of wnv genotype was isolated from xculex vishnui mosquitoes in southeastern india, and human morbidity was identified in india, pakistan, and israel. taking into account the fact that most of the birds from western siberia and many from eastern siberia overwinter in india and other countries of southern asia, there is a high probability that wnv genotype has penetrated into siberia. also in asia, both epidemics and sporadic cases etiologically linked with the first genotype of wnv have arisen regularly in israel since at least . one such outbreak was observed in À . surveillance in south korea does not indicate any wnv circulation in that country. in australia and oceania, the kunjin variant of the first genotype of wnv appears to be circulating. À kunv could be introduced into northern eurasia (in eastern siberia and the far east) by migrating birds overwintering in southeastern asia and australia. , in , an outbreak among horses in new south wales, australia, was identified. in central europe, for a long time only two strains of wnv were known: one isolated in from aedes cantans in in western slovakia and the other isolated from ae. vexans, ae. cinereus, and culex pipiens in in the czech republic, near the austrian border. anti-wnv antibodies were identified in the czech republic among . À . % of birds, including crows, daws, turtle doves, common kestrels, ducks, coots, and thrushes. later, two strains of the so-called rabensburg genotype of wnv were isolated from cx. pipiens in and in the czech republic. À the strain belonging to the second lineage of wnv was isolated from a goshawk in hungary. in in tuscany, italy, usutu virus (usuv), which is closely related to wnv, was isolated during an epizootic episode among birds, especially thrushes (turdus merula), and then, again, in in austria. later, this virus was found in hungary, switzerland, and germany. practically all of the southern european countries are endemic for wnv. , especially tragic events unfolded in romania, where there was an epidemic in julyÀoctober with a peak at the end of august to the beginning of september in the southeastern part of the country, downstream of the danube river. six administrative units and bucharest were affected, among other jurisdictions. human morbidity reached . %, and patients with cns insult were hospitalized. the number of patients with fever was at least times more, and the number of infected individuals À times more. the outbreak, which dragged on until , testifies to the development of a city epidemic form of wnf. the virus belonged to the first genotype of wnv and probably was brought to romania by birds from africa. wnv distribution in europe indicates an especially high risk of a wvf outbreak in deltas of the large rivers-the rhô ne in france and the danube in romania-through which the main migratory paths of birds overwintering in africa lie. in the recent past, wnv has been active in europe in italy, , greece, , spain, poland, the czech republic, , and france. infected mosquitoes were imported into great britain from the united states by airplane travel. as for north america, before that continent was free of wnv. penetration of wnv into america most likely happened by infected mosquitoes in the holds of ships from ports in the mediterranean sea or black sea. fifty-six cases of human wnf were revealed in new york city and its surroundings at the end of julyÀseptember , with a peak in the second half of august. seven cases ( . %) had a lethal outcome. the virus was found in culex sp. and aedes vexans mosquitoes caught in septemberÀoctober in new york city and in the states of new jersey and connecticut. positive results were obtained by rt-pcr during an investigation of brain tissues of dead birds: crows, seagulls, storks, herons, ducks, cuckoos, pigeons, jays, robins, hawks, and eagles. the genomes of the strains that were isolated were found to belong to the first genotype and were close to the strains isolated in in romania and in in israel. in , wnv was registered in the united states, probably translocated there by migrating birds or by infected mosquitoes inhabiting the holds of visiting ships. wnv was found in by À , practically all the territory of the united states, southern canada, and latin america became endemic with high morbidity and mortality. the greatest morbidity in the united states was found in the states of northdakota, south dakota, and nebraska. , the number of diseased individuals reached , À , cases in separate years. during À in the united states, more than , wnf cases were identified, with more than ( %) succumbing to the disease. the economic damage was estimated in billions of dollars. , today, wnv continues to circulate in the united states. , morbidity grew in the states of louisiana and mississippi after hurricane katrina. in montana, the infection rate of people living in close proximity to a colony of pelicans (pelecanus erythrorhynchos) is five times higher than in other regions of the state. in a sea park in texas, grampuses (orcinus orca) contracted encephalitis and died, and previous episodes of polyencephalomyelitis were revealed among seals (phoca vitulina). also in texas, three new genetic clades of wnv were found, testifying to rapid evolution of the virus on the american continent. in , an epidemic arose again, accompanied by a large number of lethal outcomes. in texas, a state of emergency was declared. northern eurasia. in northern eurasia, on the basis of the results of multiple investigations, the distribution of wnv includes moldova, ukraine, belarus, armenia, azerbaijan, georgia, kazakhstan, tajikistan, kyrgyzstan, uzbekistan, turkmenistan, the south of the european part of russia (the desert, semidesert, steppe, and forestÀsteppe landscape belts), and western siberia. , , the first data on wnv isolation were obtained from hyalomma marginatum ticks collected in the astrakhan region in . data were also obtained in azerbaijan from a blackbird (turdus merula) and a european nuthatch (sitta europaea) and, later, from a herring gull (larus argentatus) and argasidae ticks (ornithodoros coniceps) parasitizing it. wnf morbidity is now a permanent feature in the astrakhan region, kazakhstan, central asian countries (republics of the former ussr), ukraine, and azerbaijan. virological, entomological, zoologicoornithological, and epidemiological investigations of wnv in the astrakhan region and the kalmyk republic were conducted especially actively. , , À virus activity in the volga river delta was found at least as far as years ago. , , but interactions between wnv, on the one hand, and animal and vector populations, on the other, were not investigated in detail as well as genetic characteristics of the virus; indeed, the latter began to be studied well only during the first decade of twenty-first century, when suckling mice and vero-e cell culture were used to isolate the virus and serological investigations were employed to detect viral rna (neutralization testing, elisa, hit) and to sequence genes (rt-pcr). wnv endemic territories in southern russia were known from the moment the virus was isolated in the astrakhan region in . (the number of cases confirmed by elisa in the southof the european part of russia is presented in table . .) sporadic cases with a moderate clinical picture and minor outbreaks were observed in the area practically annually, as well as in other southern regions of the former soviet union. the immune structure to wnv among humans in the ussr was also known, with the most immunity occurring in the south of russia, mainly the astrakhan region (figure . , table . ). all this familiarity with wnf is why an outbreak in in volgograd was not exactly unexpected, even though it originally was identified by regional experts as an enterovirus infection. still, laboratory-confirmed wnf cases reached more than that year, and according to our estimations, the number of infected patients exceeded , (table . ) . mortality (about %) was also unusually high. large deltas of european rivers such as the rhô ne, danube, and volga rivers are known to be transit hubs for migrating birds and places of introduction of viruses linked with birds. the main natural focus in russia is the volga delta. the volga delta and contiguous territories around the northern caspian basin have been endemic for wnf for many years (tables . À . ) , and other arboviruses have been ecologically linked with aquatic and semiaquatic birds frequenting the region. ninety percent of these species of birds overwinter on the african continent. up to , birds pass over the region daily during their seasonal migrations via the volga delta main line of the eastern europe migratory route. (see figure . .) the problem is that the volga delta is the place from which viruses are introduced into anthropogenic biocenoses in close vicinity to human habitation. one consequence of this scenario was epidemic outbreaks in the astrakhan and volgograd regions in À . the volga delta consists of three basic belts, each with its own unique ecosystem features (figure . ) . the lower volga delta borders the caspian sea and is characterized by extensive exposed spaces with water. the water depth usually does not exceed . À . m, a situation that is highly conducive to the mass propagation of mosquitoes and one that also provides nesting opportunities for aquatic and semiaquatic birds. near where it empties into the caspian sea, the volga bed turns significantly to the west, so the western part of the delta, including both the reed bed of the northwestern caspian coast (up to lagan in the kalmyk republic) and some flooded islands, is more extensive than the central and eastern parts. the extreme eastern part of the delta lies in kazakhstan. a number of hunters and fishermen could be infected in the lower delta of the volga. the middle volga delta is more distant from the sea, has powerful currents, and consists of shallow lake ecosystems with reeds and shrubs. water ecosystems adjoin semidesert ones. within the limits of this zone, wild biocenoses combine with anthropogenic areas around a number of settlements, whose inhabitants keep cattle, sheep, and camels. wnf is widely registered among the native population. the upper volga delta adjoins the volgaÀ akhtuba lowlands and semideserts. large cities, including astrakhan, are located within the limits of this zone. some species of wild birds that are common in the middle delta also occur in this zone, coming into close contact with domestic animals and synanthropic birds. analysis of retrospective data collected before revealed that the main locus of native-population morbidity by wnf is in the volga delta (table . ). viruses could be introduced into the northern part of the volgaÀakhtuba lowland up to volgograd and maybe even higher. thus, in the future it will be necessary to control the introduction of the virus into the volgaÀakhtuba lowland from astrakhan to volgograd. arid landscapes occupying contiguous terrian to the west of the volgaÀakhtuba system and the volga delta are situated within the boundaries of the caspian seaÀturanian basin physicogeographical area (figure . ) . every year at the end of july, a group of specialists from the d.i. ivanovsky institute of virology in moscow has traveled to the astrakhan region and the kalmyk republic to organize and conduct a joint scientific expedition with local centers of sanitaryÀepidemiological inspection for ecologo-virological monitoring of the northwestern caspian region (figures . À . ) . the main goal of the expedition is to contain the ecological and epidemiological situation after suppression of wnv circulation in the previous epidemiological season as the result of a combination of natural factors. the plan for the collection of field material took into account the results of previous expeditions, when key milestones and marker species of mosquitoes and wild and domestic animals were identified. in particular, the researchers planned to investigate the role of the ixodidae tick hyalomma marginatum (figure . ) in wnv and other arbovirus circulation in anthropogenic and wild biotopes. both federal and local heads of various services, as well as virologists, epidemiologists, veterinarians, hunters, and frontier guards, were supplied with materials containing evaluations of ecologo-virological monitoring of their respective territories in the previous epidemiological season. practical recommendations were given for prophylaxis of wnf, cchf, and other arboviral diseases. field materials-bloodsucking mosquitoes, ixodidae ticks, internals (blood, serum, liver, spleen, and brain) of wild birds and mammals, and sera from donors and domestic animalswere collected on the territory of the astrakhan region and the kalmyk republic from the end of july to the beginning of august À within the boundaries of the volga delta, the volgaÀakhtuba valley, and adjacent arid landscapes. field materials were collected in the biotopes of the west volga coast and the east akhtuba coast, including internal waterÀmeadows of the upper and lower volgaÀakhtuba zones, hydromorphic and adjacent meadowÀsteppe biotopes of the upper and meddle belts of the volga, the volga avandelta, the territory of the sarpa lakes, and the east side of ergeny (see figures . À . ). during À , the expedition collected , bloodsucking mosquitoes (of the order diptera and family culicidae: genera culex, aedes, coquillettidia, and anopheles); , ixodidae ticks (of the taxon acari and family ixodidae: genera hyalomma, rhipicephalus, and dermacentor), mainly h. marginatum; internal parts of , birds and hares (lepus europaeus); sera from , human donors ( , in the astrakhan region and , in the kalmyk republic); and sera from , domestic animals ( , in the astrakhan region and , in the kalmyk republic) (figure . ). the field materials that were collected were stored and transported to the d.i. ivanovsky institute of virology in liquid nitrogen in dewars, in accordance with all requirements for the handling and transport of infectious samples. internal parts of , wild birds were investigated by virological methods (table . ). twelve wnv strains (tables . and . ) were isolated. according to the bioprobe method used, the total wnv infection rate among wild birds is about . %, with the highest level ( . %) reached in the middle and rt-pcr testing for any indication of wnv rna was carried out on samples of internal parts collected from wild mammals on the territory of the northwestern caspian region. positive results are presented in tables . detected in anopheles messeae ( . %), a common visitor to houses with domestic animals in anthropogenic biocenoses, as well as in an. hyrcanus ( . %) in rushes in natural biocenoses. as is illustrated in figure . , the highest intensity of wnv circulation takes place among sanguivorous mosquito populations in anthropogenic biocenoses on the territory of the volga delta (figure . ). rt-pcr testing was carried out for the detection of wnv rna in , samples of hyalomma marginatum ticks (taxon acari, wnf cases began to be registered starting in june , with the maximum reached in august (figure . ) . durint the first three . % of patients in the latter group had intracranial hypertension syndrome. there were two cases of severe disease: a -year-old patient with seromeningitis and an -year-old child with neurotoxic syndrome during the acute period. all of the cases had a favorable result: no lethal cases were registered. sera from , farm animals collected in the astrakhan region during À were tested by hit and neutralization testing in order to detect specific anti-wnv antibodies. in addition, hit-positive sera underwent neutralization testing. anti-wnv antibodies were found by hit in all species investigated: horses (mean positive result for the entire observation period, . %; coincidence with neutralization testing, . %), cattle ( . %; . %), camels ( . %; . %), pigs ( . %; cattle are the main host of anopheles messeae, and cowsheds offer favorable conditions for the mosquitoes to reproduce. cattle-specific antigens could often be found in the intestines of culex pipiens females (but not an. messeae females), which inhabitat damp basements. town utilities adjoin with farm utilities in all settlements of the astrakhan region, so cattle are the hosts both for an. messeae and for cx. pipiens. both species of mosquitoes are active vectors of wnv in anthropogenic biocenoses. horses were the only species of farm animals with clinically expressed wnf. in contrast to cattle, whose pastures are situated close to human settlements, horses browse far from settlements, often grazing in natural biocenoses. a significant portion of horse livestock in the astrakhan region are of the kushum breed, bred for meat and racing, and browse freely all year. pedigree horses (don, akhaltekinsky and arabian race horses) are kept in bloodstock farms in a stall, or they browse locally. draft horses are kept in settlements. horse-specific antigens have been found in the intestines of replete females of all mosquitoes species (except for culiseta annulata, which are relatively fewer). the total ( À ) distribution of hitpositive horses increases from the upper volgaÀakhtuba to the lower, with the highest number found in the middle belt of the volga delta (where the epicenter of the natural foci is located). pigs are the animals closest to human settlements, so pig-specific antigens are often found in the intestines of replete females of the anthropogenic mosquito species anopheles messeae and culex pipiens. pigs are kept in individual yards or on pig farms. the latter are situated far from human settlements. as they are in cattle housing, an. messeae are the main mosquito species on the pig farm; nevertheless, all mosquitoes collected here by probe were negative for wnv. in , we collected sera on the pig farms, and all probes were hit negative. in , we collected sera both on pig farms and in individual yards. sheep are the most numerous species of farm animal in the astrakhan region. sheep pastures are in the dry steppe, where conditions are favorable for the ixodidae tick hyalomma marginatum. only a couple of species of mosquito could live in the saltish, dry steppe il'mens: aedes caspius and cx. modestus. the latter is an active vector for wnv. a stable and low level of infection rate among sheep (about %) reflects the low level of intensity of wnv circulation in arid landscapes of the astrakhan region. kalmyk racing camels inhabit more arid landscapes than sheep inhabit; consequently, one might expect a lower level of seropositive camels. however, hit often demonstrates a high percentage of positive results: . % in and . % in . so, we instead collected sera from camels during À in semiwild pastures, and the percentage of seropositive results decreased. the coincidence between the results of hit testing and neutralization testing is presented in table . . horses are the best marker of wnv circulation, because they have the largest percentage of hit-positive results and the greatest coincidence between hit and nt results. kushum race horses are the most significant marker. monitoring the infection rates among farm animals will be continued, taking into account the relationships and phenomena described. it has been found that wnv can remain viable during interepidemiological periods in overwintering imagoes of sanguivorous mosquitoes (e.g., anopheles messeae, culex pipiens and culiseta annulata) as well as overwintering imagoes of the ixodidae tick hyalomma marginatum. the scheme of wnv circulation on the territory of the northwestern caspian region is presented in figure . . after the À outbreak of wnf in four administrative units in southern russia, a significant outbreak with more than cases arose in the summer and autumn of . the disease spread up to km to the north and northeast from an earlier known endemic area and now includes an additional two administrative units (tables . the orthomyxoviridae includes six genera of enveloped viruses with a segmented, negative-polarity ssrna genome. the genome of the orthomyxoviruses consists of six (thogotovirus and quaranjavirus), seven (influenza c virus), or eight (influenza a virus, influenza b virus and isavirus) segments. , all orthomyxoviruses encode three enzymes formed of viral rdrp: pb (figure . ) , pb , and pa. these proteins are about % similar among viruses of different genera. common structural proteins are np, associated with genomic rna; matrix protein; and two envelope proteins: hemagglutinin, or ha (possesses hemagglutinating activity) and neuraminidase, or na (also called sialidase) in the influenza viruses. viruses of the thogotovirus and quaranjavirus genera are transmitted by arthropod vectors, predominantly ixodidae and argasidae ticks, respectively. viruses of the influenza a virus, influenza b virus and influenza c virus genera are important human pathogens transmitted by a respiratory route. genus isavirus has only one species: infectious salmon anemia virus, which strikes fish in the salmonidae family. genus influenza a virus has just one named species: influenza a virus, represented by numerous antigenic and genetic subtypes. the genome of influenza a virus consists of segments of ssrna that encode or more proteins. À influenza a viruses are divided into distinct subtypes based on the antigenic and genetic properties of their ha and na proteins. sixteen subtypes of ha (ha À ) and subtypes of na (na À ) have been found worldwide in aquatic birds. two additional subtypes of ha (ha and ha ) and na (na and na ) are seen in new world bats. , , h and ha form a clade distinctly history. influenza as a human disease was originally described in b.c. by hippocrates (figure . ) in his book epidemics, but the "father of medicine" did not consider influenza to be an infectious disease. instead, the famous english physician thomas sydenham (figure . ) was the first who suggested the infectious nature of the disease. , the term "influenza" has been around since the first half of eighteenth century and derives from the italian "influenza di freddo" ("influence of the cold") or from spanish "influencia de las estrellas" ("influence of the stars"), the latter reflecting the contemporaneous belief in astrological reasons for the emergence of disease. up to the nineteenth century, the archaic terms "catarrhus epidemicus," "cephalgia contagiosa," "febris catarrhalis" and "febris comatose" had wide currency. the english word "grippe" (related to the russian "грипп") is related to the german "greifen" ("to catch hold") and derived from the french "gripper" ("to catch hold," "paralyze"); the word gained currency at the beginning of nineteenth century. (cf., e.g., the passage from volume , chapter of tolstoy's famous novel war and peace: "she was, as she said, suffering from la grippe; grippe being then a new word in st. petersburg, used only by the elite."). before the nineteenth century, influenza a epidemics were described only qualitatively. subtypes of the etiological agent were retrospectively revealed for the À epidemic (h n ), the À epidemic (h n ), and the À pandemic (h n , the so-called spanish flu) À -retrospectively only because influenza a virus wasn't found until by richard shope (figure . ) on the model of swine (sus scrofa) flu. , human flu was found two years later , by a group of english scientists: wilson smith (figure . ), christopher andrewes (figure . ) and patrick laidlaw (figure . ) . during the pandemic of À , it was suggested that the etiological agent of influenza a was the socalled afanasievÀpfeiffer bacillus," À named after the russian bacteriologist mikhail afanasiev (figure . ) and the german bacteriologist richard pfeiffer (figure . )-the modern haemophilus influenzae bacillus. , three influenza a pandemics were described after the discovery of the etiological agent: the avian flu has been known under the name "lombardian disease" since the beginning of the nineteenth century. À in , the italian veterinarian edoardo perroncito (figure . ) described a highly contagious disease (previously named "exsudative typhus of chickens") among chickens, with % lethality in the vicinity of turin. the terms "classic fowl plague" and "bird pest" came into wide use in , when a large epizootic outbreak in tyrol province, italy, did away with the population of farm birds there. the term "braunschweig disease" was used to identify an analogous disease among guinea fowls in europe. in , the italian scientists eugenio centanni and ezio savonuzzi demonstrated that the etiological agent of classic fowl plague is a filtrated substance. nevertheless, classic fowl plague wasn't identified as influenza a virus until , by werner shäfer (figure . ) on the example of the historical strain a/chicken/brescia/ / (h n ). , w.b. becker was the first who identified influenza a virus among wild birds when he subtypes of influenza a virus in northern eurasia. at present, we know that numerous avian influenza viruses are abundant in the bird populations of northern eurasia. however, until the end of the s, these data were absent. at that time in the former ussr, avian influenza a virus was being isolated only from poultry. one of the first avian viruses isolated in the ussr-a/duck/ukraine/ / -was destined to play an important role in the development of the theory of influenza virus evolution. in À , a group of researchers in the ukrainian soviet republic isolated several influenza virus strains from ducklings affected with sinusitis. the first three strains were isolated in in crimea and in the kharkov astrakhan region volgograd region institute of virology in moscow. as early as , the duck strains ya- , b- , z- , and c- were analyzed with respect to their antigenic specificity by hit and were found to be antigenically distinct from the human h and h viruses. after the appearance of the h pandemic virus in , some of the ukrainian duck strains were shown to be antigenically , moreover, hit testing also showed that the b- and bv strains of the virus reacted with human sera, including those collected in À and in À . on the basis of this phenomenon, the authors suggested that an avian virus similar to the strains b- and bv was the precursor of the human pandemic strain and that this antigenic variant had appeared in humans several times in the past. formerly known as ya- , strain a/ duck/ukraine/ / was shown to belong to the h n subtype, whereas a/duck/ ukraine/ / was identified as h n and a/duck/ukraine/ / as h n . the highly pathogenic h n and h n strains were isolated from chickens in the moscow region. , several virus strains producing enteritis in chickens were isolated in and in in chicken farms and identified as h n strains, , , an unusual antigenic formula for a pathogenic virus affecting poultry. six h n isolates were obtained in a chicken farm in kamchatka from chickens affected with rhinitis, conjunctivitis, and laryngotracheitis. , in , isolates identified as h n viruses were isolated from sick chickens and ducks in the russian federation and uzbekistan in the former ussr. in , h n strains were isolated in the western part of the ukrainian soviet republic from the lungs of ducklings affected with pneumonia. the isolation was the only one of an h influenza virus in the ussr (lvov dk, unpublished data). in , a large-scale series of virus isolations from wild birds, combined with some serological studies, was initiated as a part of the coordinated program of the national committee on the studies of viruses ecologically linked to birds together with the virus ecology center of the d.i. ivanovsky institute of virology. by the end of the s, the pattern of circulation of avian viruses in the territory of the ussr was identified. , , , in the ensuing years, the pattern of the influenza a virus subtypes (including h and h ) circulating in northern eurasia was amplified (figure . ). blood sera collected in the spring and autumn of near lake khanka and peter the great bay (both in primorsky krai) from birds-mainly mallards (anas platyrhynchos), common teals (an. crecca), baikal teals (an. formosa), garganeys (an. querquedula), falcated ducks (an. falcata), pintails (an. acuta), grey herons (ardea cinerea), coots (fulica atra), black guillemots (cepphus grylle) and blacktailed gulls (larus crassirostris)-were hittested against h , h , h , h , h , and h avian influenza viruses. no antibodies were found in the sera of grey herons and coots, nor were any found against h in any species. antibodies against all the other subtypes tested were encountered occasionally in the sera of gulls, black guillemots, and ducks. in some species, such as teals, falcated ducks, and black guillemots, antibodies against several subtypes were detected. in , sera were collected from gulls, cormorants, murres, and tufted puffins in the commander islands. antibodies against h , h , h , and h viruses were detected. in À , sera from gulls, cormorants, and murres were collected in the kamchatka, sakhalin, and magadan regions and antibodies to h , h , h , h , h , and h viruses were detected. antibodies against h , h , h , h , and h were identified in sera taken from arctic terns (sterna paradisaea), black-throated loons (gavia arctica), mallards (anas platyrhynchos), common teals (anas crecca), tufted ducks (aythya fuligula), greylag geese (anser anser), skuas (stercorarius sp.), and a blue whistling thrush (myophonus caeruleus) collected in the white sea basin in the estuary of the pechora river in the arkhangelsk region of russia in À . the serologic studies suggested a wide range of avian influenza viruses circulating in wild birds in northern eurasia. this suggestion was confirmed and extended by the isolation of virus strains from other wild birds. many avian species proved to be hosts of h viruses. a virus belonging to the h n subtype was isolated in from a tern in the southern part of the caspian sea basin. in , an h n strain was isolated from a common teal (anas crecca) in the russian republic of buryatia in eastern siberia. several h n viruses were isolated in kazakhstan in from waterfowl, including the common teal (an. crecca), garganey (an. querquedula), shoveler (spatula clypeata), and coot (fulica atra), as well as in from tree sparrows (passer montanus) and hooded crows (corvus cornix). in , an h n virus was isolated from a hawfinch (c. coccothraustes) in mongolia. in the same year, an h n strain was isolated from a black-headed gull (larus ridibundus) on an island in the northern part of the caspian sea. the avian viruses belonging to the h subtype seem not to be abundant in russia. in fact, for a long time the only virological evidence of the presence of this subtype in russia was the isolation of an h n virus in from a pintail (anas acuta) in primorsky krai. however, serological data suggested that h viruses circulated in wild birds not only in primorsky krai, but also in other regions of the far east, including the commander islands as well as the kamchatka, sakhalin, and magadan regions. , avian influenza a viruses belonging to the h subtype are widespread in northern eurasia. an h n virus was isolated from a common murre (uria aalge) in on sakhalin island, and another h n strain was isolated in from a pintail (anas acuta) in primorsky krai. two h n strains were isolated in in the ukrainian soviet republic from unusual hosts for avian viruses: the white wagtail (motacilla alba) and the european turtle dove (streptopelia turtur). h n strains were also isolated from grey crows (corvus cornix) in in the volga basin and from a shelducks (tadorna ferruginea) in in kazakhstan. an h n virus was isolated from a tree sparrow (p. montanus) in in the ukrainian soviet republic. in À , h n and h n viruses were isolated from ducks and herons in khabarovsk krai. one of the viruses closely resembled a strain isolated a year later in central asia. this resemblance demonstrated that h n viruses circulated in regions fairly distant from one another. in À , h n viruses were isolated in khabarovsk krai from wild ducks (anas sp.), tufted puffins (fratercula cirrhata), and horned puffins (f. corniculata) and in the arkhangelsk region in the pechora river estuary (white sea basin) from arctic terns (sterna paradisaea) and black-throated loons (gavia arctica). in , h n strains were isolated in the republic of buryatia from a mallard (an. platyrhynchos) and a pintail (an. acuta), as well as in khabarovsk krai from the common murre (u. aalge) and from black-headed gulls (larus ridibundus). avian viruses of the h subtype were isolated in À mostly in a narrow belt stretching from the lower volga, through kazakhstan, and on to the south of eastern siberia. several h n strains were isolated in from slender-billed gulls (chroicocephalus genei) in the volga delta and from great black-headed gulls (ichthyaetus ichthyaetus) on the islands in the northern part of caspian sea. in , h n virus was isolated from the black tern (chlidonias niger) in central kazakhstan. in the republic of buryatia, h n strains were isolated in from the common goldeneye (bucephala clangula). isolations of h influenza viruses from wild birds were scarce. in , several h n strains were isolated from terns (common terns and little terns) and a slender-billed gull in the volga river delta. a detailed description of the penetration of the h n strain of of highly pathogenic avian influenza (hpai) a into northern eurasia and its further dissemination is presented shortly. the strains belonging to the h subtype seem not to be abundant, but their geographic distribution is wide. an h n strain was isolated in from the arctic tern (sterna paradisaea) in the arkhangelsk region (white sea basin). one h n strain was isolated in from the pintail (anas acuta) in primorsky krai, and an h n strain was isolated from the common tern (s. hirundo) in in the caspian sea basin. in , two h n strains were isolated on kunashir island (the southernmost of the kuril islands) and four were isolated on sakhalin island. an h n strain was isolated in from a sandpiper (a member of the scolopacidae family) in the arkhangelsk region of russia. one strain of h n was isolated in in the republic of buryatia, and one strain in in mongolia. an h n strain was isolated from a mallard (anas platyrhynchos) in primorsky krai in and in khabarovsk krai in . over h n strains were isolated from a wide array of bird species near alakol lake in east central kazakhstan in . the strains were isolated from several species of ducks (anas sp.), from shorebirds (members of the order charadriiformes), to passerine birds (members of the order passeriformes), to coots (fulica atra), plovers (members of the family charadriidae, subfamily charadriinae), and chukars (alectoris chukar). this situation is a rare case of an isolation of closely related viruses from an extremely wide array of avian species. the viruses identified as h n strains were isolated in from the arctic tern (sterna paradisaea) and the red-throated diver (gavia stellata) in the estuary of the pechora river in the northern part of european russia. several h n strains were isolated from the common teal (anas crecca), the european widgeon (an. penelope), and the european golden plover (pluvialis apricaria) in in eastern siberia. in , h n strains were isolated from mallards, a pintail, and european widgeons south of issyk-kul lake in kyrgyzstan. two strains of h n were isolated from wild ducks (subfamily anatinae) in kyrgyzstan. the results of virus isolation and serological studies in the territory of the ussr in À suggested a wide circulation of avian influenza viruses in wild birds and enabled researchers to construct a map of avian influenza viruses encountered in different regions of northern eurasia. the general pattern of distribution of influenza virus subtypes in wild birds was fairly evident by the end of the decade. virus isolation was continued in the ensuing years, and it brought . single-stranded rna viruses several major results. isolations were performed mostly in the central and southern parts of european russia, in western and eastern siberia, and in the russian far east. overall, , strains were isolated from wild birds in russia in À (table . ). about samples were taken yearly from to birds in each geographic region. the mean percentage of successful isolations ranged from . % to . %. over % of the isolates were h viruses (h n , h n , h n , and h n ) isolated mostly from gulls and shorebirds in the northern part of the caspian sea. the viruses of the h subtype (over % of the total number of isolates) were isolated in several regions. many strains isolated in À from great black-headed gulls (ichthyaetus ichthyaetus), herring gulls (larus argentatus) and caspian terns (hydroprogne caspia) on the island of maly zhemchuzhny in the northern part of the caspian sea were not identified at the time of isolation with respect to the subtype of their ha. as it turned out, the strains belonged to the subtype h , was first described in , and in the mysterious caspian isolates were identified as h n , h n , and h n . to characterize the h subtype molecularly and antigenically, the complete nucleotide sequence of the ha of the strain a/great black-headed gull/astrakhan/ / was used for comparison with the has of two american strains isolated from a gull and a pilot whale. virus isolation studies in the northern caspian basin were continued in the s and s. materials were collected from wild birds in the area of the northern coast of the caspian sea (including maly zhemchuzhny island) from the delta of the terek river in the north caucasus region to the emba river in western kazakhstan. most of the strains that were isolated belonged to the h subtype, including h n , h n , h n , and h n isolates; besides these strains, only single isolates belonging to the h n , h n , h n , and h n subtypes were isolated. , in , a new, previously unrecognized, subtype of influenza virus h ha was described on the basis of the characterization of two strains isolated in from mallards (anas platyrhynchos) in the ural river delta. the h n and h n subtypes were isolated from mallards and gulls in astrakhan. a partial sequencing revealed that ns gene of the h strains isolated from the gulls was closely related to the ns gene of h and h strains isolated previously from gulls and terns in the caspian sea basin and to the h n strain isolated in the russian far east. the ns gene of an h n strain isolated from a mallard was much more distantly related to the ns gene of the viruses isolated from gulls. the results suggest that reassortment events play a significant role in the evolution of h viruses, with the ns gene being an important determinant of the range of the host. a large-scale isolation of avian influenza viruses from fecal samples was performed in À in eastern siberia and the far east by a group that included both russian and japanese researchers. scientific contacts between russian and japanese researchers of avian influenza a virus were ongoing during the eighth russianÀjapanese consultations at a conference titled "protection of migratory wild birds in the asiaÀpacific region" held at the russian ministry of natural resources in moscow april À , . at the conference, the d.i. ivanovsky institute of virology took the initiative to renew the international meetings on medical ornithology at the level of experts of asiaÀpacific countries that had been taking place regularly during the and s. as a result, the first international meeting for medical ornithology in the asiaÀpacific region was held in tokyo, japan, on june , . the meeting was devoted to the topic of hpai h n distribution in asia. a second meeting was conducted in moscow at the d.i. ivanovsky institute of virology march À , (figure . ) . in the summer of in a valley in the sayan mountains in southeastern siberia, the strains h n , h n , h n , h n , and h n were isolated. the h n and h n strains were isolated from ruddy shelducks (tadorna ferruginea) and common redshanks (tringa totanus), the h n strains from common pochards (aythya ferina), and the h n strains from northern shovelers (anas clypeata) and great crested grebes (podiceps cristatus). the h n strains were isolated from all of the aforementioned species, as well as from teals, ducks, and terns. in À , the subtypes h n , h n , h n , h n , h n , h n , h n , h n , and h n were isolated in the same region; , samples were taken from bird species. a strain isolated from the muskrat (ondatra zibethicus) in in the republic of buryatia was identified as an h n virus closely resembling the h n strains isolated from ducks in the same year and the same region. the has of the h strains (including the muskrat strain) isolated in buryatia formed a separate group of the eurasianÀaustralian branch in the phylogenetic tree of h ha (figure . ). they had a c-terminal proline residue in their ha subunit, in contrast to the serine residue of most eurasian strains. the ha genes of the h n isolates turned out to have cleavage peptides lrnvpqretr/gl identical to the ones of the low-pathogenic strains isolated from ducks in hong kong and malaysia. in contrast, the has of h and h strains isolated from teals in and from mallards in near lake chany in novosibirsk region western siberia, were related to the has of the european h and h strains. , interestingly, the has of the h strains were closely related to the ha of a/duck/ukraine/ / (h n ). however, unlike the has of h and h , the has of h strains isolated in the same area in from mallards resembled the has of h strains isolated in in japan from mallards (anas platyrhynchos). in , influenza a virus strains belonging to a rare subtype h n were isolated in mongolia from the great cormorant (phalacrocorax carbo), white wagtail (motacilla alba), and magpie (pica pica). penetration of hpai h n into northern eurasia: reasons and consequences. during longitudinal wide-scale monitoring of influenza a viruses among wild bird populations in northern eurasia, several h n and h n strains were isolated in and in the caspian sea basin. , more recently, in À , strains belonging to the same subtypes were isolated in siberia, and their features proved to be relevant to h virus circulation. onn the one hand, the has of the strains isolated from teals in in primorsky krai, as well as the has of strains isolated from a mallard in lake chany in western siberia in , were shown to be closely related to has of h strains isolated in in italy from poultry. , on the other hand, the ha of the h n strain isolated from a wild duck as early as in altai krai in southwest siberia was closely related to the ha of a/duck/malaysia/f - / (figure . ). the ha of the altai ( ) and lake chany ( ) viruses had a monobasic ha Àha cleavage site, and, accordingly, it had a low-pathogenic avian influenza (lpai) phenotype. , , , besides the amino acid sequence of the ha, the sequences of other genes of the h viruses isolated in russia proved to be relevant. the np genes of the h n and h n strains isolated in primorsky krai in formed a separate cluster in the phylogenetic tree, together with the np genes of the h n strains isolated from common shelducks (tadorna ferruginea) and common pochards (aythya ferina) in the republic of buryatia in , the h n strain isolated from the northern pintail (anas acuta) in primorsky krai in , and the , however, they were very distantly related to the np genes of h n , h n , and h n strains isolated from poultry and humans in southeast asia in À and to the np genes of h n viruses isolated from wild ducks in the caspian sea basin in the european russia in . by contrast, unlike the np genes, ns genes of the strains from primorsky krai were closely related to the ns genes of the h n and h n viruses isolated in southeastern asia in À , as well as to the ns genes of an h n virus isolated in the caspian sea basin in (figure . ) . , an abundance of influenza a subtypes in the avian populations of northern eurasia provides excellent conditions for gene exchange. the extent of the exchange is demonstrated by the relatedness of different genes of the russian isolates to the genes of european strains, on the one hand, and south asia isolates, on the other. , , , the exchange is to a certain extent restricted by host specificity, but this restriction is not rigid, and the virus genes frequently traverse interspecies barriers. avian migration routes crossing russian territory are an important factor in the gene flow. the extensive intra-and interspecies contacts in the natural habitats of wild birds in russia stimulate rapid virus evolution and the appearance of new variants through reassortment events and, presumably, through the postreassortment adjustment of genes, thereby restoring the functional intergenic match. , another factor may be the occurrence of avian influenza viruses in lake water, first registered in in eastern siberia. this phenomenon might provide a means for the temporal as well as territorial transfer of genes, as suggested by the recent detection of influenza thus, the sequencing data suggest that there exists an extensive exchange of genes of the avian influenza viruses circulating in europe, siberia, and southeast asia along the avian migration routes connecting europe, through the russian territory, with southeastern asia, the cradle of potentially pandemic reassortant viruses. after the highly pathogenic h n viruses began disseminating from southeastern our second prediction was that overwintering migrating birds could transmit the hpai virus into northern eurasia during their spring migration. we discussed two possible routes by which the birds might introduce the virus: the dzungarian (indianÀasian) migration route and the asianÀpacific route. preparing for these two possibilities, we increased our surveillance in the southern part of western siberia (through the russian foundation for basic research project -а - ) and in primorski krai (through the international scienceÀtechnical center project ) in the spring of . in april of , a wide epizootic outbreak emerged at kukunor lake (also called qinghai lake) in qinghai province, china, and from this location the virus could spread through the dzungarian gate, which links the northwestern mountain ranges of tibet with the western siberian lowland. our second prediction was confirmed as well, when hpai h n first appeared in northern eurasia, in western siberia (novosibirsk region, russia) in the summer of (figure . ). although the official start of the epizootic among poultry was dated july , (table . ), that one occurred among wild birds about weeks before was retrospectively established. the outbreak spread quickly and caused over % lethality among poultry. the virus isolations in the area were performed independently by two groups of researchers. a number of strains were isolated in zdvinsky district, novosibirsk region, by a group of researchers from the d.i. ivanovsky institute of virology in moscow. the materials for isolation (cloacal and tracheal swabs, pools of internal organs, and blood) were taken from dead, sick, and healthy birds at the farm where the epizootic occurred and from wild birds in the vicinity. , three strains were isolated from dead chickens (gallus gallus domesticus), two strains from sick or dead ducks (anas platyrhynchos domesticus), and one strain from a healthy great crested grebe (podiceps cristatus). all of the strains were deposited into the russian state collection of viruses functioning under the auspices of the d.i. ivanovsky institute of virology ( several features of the primary structure of virus proteins, such as lys residue in pb and glu residue in ns , characteristic of highly virulent variants of h n viruses, correlated with the high pathogenicity of the novosibirsk isolates. a deletion in the na gene in amino acid positions À indicated that the strains belonged to the genotype z, which dominated in in southeastern asia. the other group of strains was isolated by a team of researchers from the state research center of virology and biotechnology vector (also known as the vector institute) in koltsovo, novosibirsk region. two strains were isolated from chickens and one strain from a turkey in the village of suzdalka, dovolnoe district, in july . the viruses were isolated from homogenates guangdong province, china. the viruses were highly pathogenic to chickens in a laboratory test. our third prediction was that the virus would move with the migrating birds to their overwintering locations. as it turned out, coincident with this prediction, epizootic outbreaks occurred along the main migration routse in the urals, the russian plain, europe, africa, central asia, and india figure . ), indicating the distribution of the virus through the eastern european flyway of birds (figure . ), connecting western siberia, the russian plain, eastern europe, the middle east, and africa. our fourth prediction was that the virus would return in birds migrating from their overwintering places to northern eurasia in the spring of , with a widening of the epizootic. dramatic events occurred june À , , at uvs-nuur lake, which is situated on the boundary between the great lakes depression of mongolia and the tyva republic of russia (figure . ). an estimated , -plus birds died in the russian part of this lake, which is only about % of the total area of the lake. the species most affected was the great crested grebe (podiceps cristatus); as also affected were coots (fulica atra) and cormorants (phalacrocorax carbo). terns and gulls were involved in the epizootic to a significantly less extent. the absence of poultry farms in the vicinity of uvs-nuur lake precluded outbreaks among poultry. the tyva strains appeared to be the beginning of a new genetic lineage in the qinghaiÀsiberian genotype . . the lineage was designated as a tyvaÀsiberian subgroup (figure . ) that was isolated not only in siberia, but also in europe. it is believed (table . ) from dead and sick poultry, and all the isolates were identified as hpai h n (table . ) with a high level of sequence similarity to the qinghaiÀsuberian genotype . (figure . ) . this outcome implied a common source of infection for all the local outbreaks ( figure . ) , and subsequent epidemiologic investigation demonstrated a link to live-bird markets in moscow, where the affected farmers had purchased poultry several days before. a complete genome analysis of the prototype a/ chicken/moscow/ / revealed group of strains is shown with the use of braces: designations common to all strains in the given group are shown outside the braces; the variable part of the designations is cited inside the braces; the asterisk "*" means "any designation." only mutations that are found in all the strains of the given group are listed in the table. b bold font indicates substitutions with respect to hpai/h n / . consensus; the frame -substitutions unique to northern eurasian strains (tables À )-that is, they did not occur among northern eurasian strains previously; the frame with grey background -substitutions unique to all hpai/h n / . genotypes (strains isolated in both northern eurasia and other places); {kc-substitution that takes place in the strains of the given epizootic outbreak only; {£c-substitution that takes place in the strains of both the given and later or previous epizootic outbreaks. valley ecosystem in the north or south caucasus in the winter of and was introduced into the live-bird market through contaminated poultry cages or contaminated grain. in september , an outbreak was detected in the northeastern part of the basin of the sea of azov on a chicken farm called "lebyazhje-chepiginskaya" in the krasnodar region of russia (figure . ) . the virus isolates-a/ chicken/krasnodar/ / from poultry and a/cygnus cygnus/krasnodar/ / from a sick whooper swan (cygnus cygnus) found in a "liman" (shallow gulf) near the farm-were closely related to each other (they had two synonymous nucleotide substitutions in pb , two synonymous in pb , one nonsynonymous in m , two nonsynonymous in na, and one nonsynonymous in ns ) and belonged to the iranÀnorth caucasian subgroup of qinghaiÀsiberian genotype . (figure . ). the isolated strains contained unique amino acid substitutions with respect to a qinghaiÀsiberian consensus in pb , pa, ha, na, and ns , suggesting that regional variants were continuing to emerge. in december , a poultry farm called "gulyai-borisovskaya" in the rostov region became infected (figure . ) . unfortunately, the infection was not reported in time, and infected poultry manure was spread on adjacent fields, where wild terrestrial birds could be infected. this exposure is thought to have contributed to the infection of a number of species. including rooks (corvus frugilegus), jackdaws (corvus monedula), rock doves (columba livia), common starlings (sturnus vulgaris), tree sparrows (passer montanus), house sparrows (passer domesticus), and more. surveillance of these species by rt-pcr detected h virus in % of pigeons and crows, in around % of starlings, and in % of tree sparrows, all without clinical features. these results were confirmed by viruses isolated from wild birds and poultry (table . ). birds whose infection was confirmed by rt-pcr and virus isolation seemed reluctant to move and had ruffled feathers. on necropsy, the birds were observed to have had conjunctivitis; hemorrhages on the lower extremities and in muscle, adipose, intestine, mesentery, and brain tissue; and changes in the structure of the pancreas and liver. wide involvement of wild terrestrial birds in virus circulation, presumably from the exposure to infected chicken manure, distinguished this outbreak from others. genome analysis ( the qinghaiÀsiberian clade includes viruses that have infected and caused severe disease and mortality in humans, but currently they do not appear to be transmitted efficiently in humans. upon analyzing representative viruses in our collection for their potential to replicate in mammals, we found that isolated strains replicated effectively in mammalian cell culture lines bhk- , lech, vero e , mdck, and spev. , , pb has consensus k that promotes virulence in mammalian cells. on the basis of the amino acid sequence of ha receptor-binding sites of qinghaiÀsiberian isolates containing e , q , and g , its affinity of qinghai siberian isolates for α - À sialic acids was predicted. however, a double mutation q- l and g- s or just a single mutation e- d could switch ha receptor-binding affinity from avian to human receptors. all the qinghaiÀsiberian isolates are sensitive to amantadine, rimantadine, and oseltamivir, as has been confirmed by both direct biological experiments in vitro the first overwintering area could be the source for the iranÀnorth caucasian subgroup, the second for the tyvaÀsiberian subgroup. returning to their nesting areas in northern eurasia in the spring of , wild birds afforded a mixed virus population the opportunity to spread (figure . ) . , , , , , a decrease in the potential of isolated strains to reproduce in vitro (figure . ) is more evident in poultry (tcid . À . t) than in to wild birds (tcid although hpai h n has penetrated into northern eurasia through the dzungarian flyway of wild birds, this fact did not exclude the possibility of the virus transferring through other flyways -(e.g., through the far eastÀpacific flyway). indeed, in april with wild waterfowl. one initial theory of the introduction of the virus to poultry was from the birds' exposure to hunted ducks, but the direct interaction of wild birds with poultry seems more likely. the isolates (see table . ) from dead chickens and the common teal (anas crecca) collected in the vicinity of epizootic farms were identical and indicated a direct role of migrating birds in the introduction of the virus. the teal, which appeared to be the most likely source of infection of poultry, had no obvious behavior changes but did have hemorrhagic lesions in the intestines on necropsy. it is interesting to underline the fact that common teals were the source of isolation of h (figure . ) . , fortunately, both clades ( . and . . . ) of hpai h n that had penetrated into northern eurasia had low epidemic potential because their receptor specificity did not switch from α À -to α À -sialoside affinity, a fact that was revealed by the primary structure of the ha receptor-binding region and direct testing in sialoside-based experiments in vitro. , thus, we discuss the epizootic event provoked by hpai h n in northern eurasia during À as a model of an emer-gingÀreemerging situation in need of permanent ecologo-virological monitoring. influenza a viruses among mammals. the circulation of influenza a viruses among swine (order artiodactyla: family suidae, genus sus) was originally established in by richard shope (figure . ): his investigations not only established the viral etiology of swine flu and isolated the first historical strain a/swine/iowa/ / (h n ), but also serologically demonstrated the close relation between human infection agents and those of swine. shope's findings gave rise to a number of isolations of swine respiratory disease agents. many of these agents later turned out not to be influenza a virus; for example, "kö be porcine influenza virus," isolated in germany; "infectious pneumonia of pigs;" , "beveridgeÀbetts virus" (more often, these pathogens belonged to chlamydia sp.); and "hemagglutinating virus of japan," , which initially was named "influenza d virus" and was later identified as sendai virus (sev) (family paramyxoviridae, genus respirovirus). nevertheless, a number of strains isolated at the end of s in korea (strain oti), and in the s and s in lithuania (prototype a/swine/kaunas/ / ), estonia, poland, and russia were identified as influenza a (h n ) virus. also, in the middle of twentieth century, influenza a strains closely related to a/ swine/iowa/ / (h n ) were isolated in czechoslovakia , and hungary. finally, after the beginning of the "asian flu" pandemic in , swine influenza a (h n ) virus strains were isolated initially in china and later in czechoslovakia the principal peculiarity of pigs is the presence of both α À -sialosides (typical of human cells) and α À -sialosides (typical of avian cells) on the surface of respiratory tract cells. this feature permits both human (or adapted swine) and bird influenza a virus strains to circulate simultaneously, giving rise to conditions favorable to the reassortment and emergence of virus variants with suddenly appearing new properties. , À avian influenza a virus strains have been demonstrated to initiate productive infection in swine under experimental conditions. , À the great number of reassortment forms of influenza a viruses isolated from swine constitute evidence of the extremely high reassortment potential of the swine viral population. thus, a/swine/england/ / , isolated from nasal swabs of sick pigs in great britain in , belongs to the unique h n subtype, which was formed by the reassortment of a/ussr/ / (h n ) (the source of pb , pb , pa, ha, np, and ns segments) and a/equine/prague/ / (h n ) (the source of na and m segments). the most evident illustration of the reassortment potential of swine populations is the emergence of the pandemic "swine flu" h n pdm in as the result of the reassortment of two swine genotypes of the h n subtype: the "american swine genotype" (the source of pb , pb , pa, ha, np, and ns segments) and the "european swine genotype" (the source of na and m segments) (figure . ). À using different receptor-mimicking sialosides (table . ), we investigated the evolution of receptor specificity in influenza a (h n ) pdm virus during pandemic and postpandemic epidemiological seasons. different types of sialoside specificity spectra are presented in figure . . to compare α À -and α À -sialoside specificities, we introduced the special parameter w / , which is the ratio of the optical density for flat α À -sialosides ( sl and sln) to the optical density for flat α À -sialosides ( sl and sln): if w / is , (w / , . ), then α À -specificity dominates. in contrast, if w / . . , then α À -specificity dominates. (strains with w / % . have approximately equal α À -and α À specificities.) the sialoside specificity of the first pandemic strains isolated in our study, a/california/ / (h n ) pdm , demonstrates dual affinity to both α À -and α - -sialosides (figure . ) . therefore, such strains might be able to effect swineÀhuman and humanÀhuman transmission, and their pathogenicity is higher than that of seasonal influenza viruses (w / % pigs could be the source of influenza a virus not only in humans, but also in synantropic animals. s. agapov published an article on the pathogenic properties of influenza a virus specimens isolated from brown rats (rattus norvegicus) in pigsties. experimental infection of swine influenza a virus strains in rodentsmice (subfamily murinae) and hamsters (subfamily cricetinae)-has been described in a number of publications. , , , À rodents have become a widely used laboratory model for influenza a virus. productive infection in laboratory mice (order rodentia: family muridae, genus mus) was revealed in a pioneer publication of w. smith (figure . ), c. andrewes (figure . ) and p. laidlaw (figure . ). adapted to mice, influenza a virus strains are widely used to investigate infectious process, pathology, and the efficiency of antivirals. , À in , the strain influenza a/muskrat/ buryatia/ / (h n ) was isolated from muskrat (ondatra zibethicus) hunted in the selenga river delta, near where it empties into lake baikal. despite mountain relief along the lake coast, the delta represents a sandbank wedge overgrown with low reeds where the conditions are conducive to a mass nesting of ducks and a high density of population of muskrats. as a result, there is a high level of interaction between the populations of aquatic birds and muskrats. in particular, a/muskrat/buryatia/ / (h n ) has the highest homology with a/pochard/buryatia/ / (h n ). the strain from muskrat turned out to be virulent to mice without any preliminary adaptation, like the majority of h strains from siberian ducks. it was suggested that virulence was promoted by an r g mutation in ha. , the russian state collection of viruses contains the influenza a/sciurus vulgaris/ su- sln -su- -sialyllactose: -su-neu acα - galβ - glcβ primorje/ / strain with an undetermined subtype isolated from a red squirrel (sciurus vulgaris). weasels (order carnivora: family mustelidae) are another sensitive group of hosts for influenza a viruses. the sensitivity of the domestic ferret (mustela putorius furo), an albino form of the forest polecat (mustela putorius), to the virus was explored even in the earliest scientific publications devoted to influenza a virus. , today, ferrets are the best animal model of influenza a virus infection. in particular, sera of infected ferrets (as well as infected rats) are widely utilized for influenza a virus subtype identification. in , japanese scientists demonstrated that the epidemic strain a/kumamoto/ / (h n ) was able to provoke disease in the european mink (mustela lutreola), and perhaps it was this virus that caused a respiratory disease epizootic on japanese fur farms during À . in À , during an epizootic among minks in sweden, six strains of influenza a (h n ) virus (prototype a/ mink/sweden/e / ) were isolated and turned out to have an avian origin. in , an influenza a/stone marten/germany/r / (h n ) strain was isolated from the internals of a stone marten (martes foina) that was found dead in a place where there was mass mortality of birds in germany. , the circulation of influenza a virus among cats (order carnivora: family felidae) was originally established in by the japanese virologists j. nakamura and t. iwasa: strain a/cat/fusan/ / (known as "chiba virus") turned out to be an avian strain of the h n subtype. in , c.k. paniker and c.m. nair described the successful experimental infection of adult cats and eight-monthold kittens by a/hong kong/ / (h n ), of the "hong kong flu" pandemic strain. a number of h n strains from felidae members-tigers (panthera tigris), À leopards (p. pardus), and domestic cats (felis catus) À -were described after . the first experiment involving the infection of dogs (order carnivora: family this strain had an avian origin, but provoked lethal pneumonia in dogs. it is noteworthy that influenza a virus can be isolated from nasal swabs of dogs during inapparent infection, so this virus might be more widely distributed among dogs than is usually considered. influenza a virus is often the cause of pericarditis in dogs. the circulation of influenza a viruses among horses (order perissodactyla: family equidae, genus equus) was originally explored in by a group of czechoslovakian scientists headed by bella tumova (figure . ). in that year, a widespread epizootic emerged among horses (equus ferus caballus) and the historical strain a/equine/prague/ / was isolated. a subtype of this strain was given an initial designation h eq n eq and later was identified as h n (but, for a long time, veterinarians designated this subtype as equine influenza type ). later, influenza a (h n ) strains were isolated in other european countries and the united states. during the "asiatic flu" pandemic of À , a number of strains of influenza a (h n ) were isolated from sick horses in the moscow region of the former ussr hungary. , it was shown that these strains were significantly different from a/equine/ prague/ / (h n ), belonged to the h n subtype, and had a human origin. equine influenza a type was originally found in in miami, florida, in the united states, when the prototypical strain a/equine/ miami/ was isolated and designated as subtype h eq n eq . later, this subtype was identified as h n and was multiply isolated À in both north and south america. in the former ussr, influenza a (h n ) virus strains were isolated from horses in the ukrainian soviet republic during a widespread epizootic in in the vicinity of kiev. the russian state collection of viruses contains the influenza a/equine/mongolia/ / (h n ) strain, which originates from birds and over came the interspecies barrier to penetrate into the equine population. the circulation of influenza a virus among camels (suborder tylopoda: family camelidae, genus camelus) was originally established by d. k. lvov (figure . ) in . in december , an epizootic of "contagious cough" among bactrian camels (camelus bactrianus) emerged in mongolia. thirteen strains were isolated from nasal swabs; , tajikistan, and the ukrainian soviet republic in the former ussr. the circulation of influenza a viruses among cattle has been confirmed by multiple serological data. , À the first isolation of influenza a strain from sick sheep (ovis aries) (order artiodactyla: family bovidae, subfamily caprinae) was carried out in by a group of hungarian scientists under the direction of g. takatsy during an epizootic among farm animals. , the strain a/sheep/hungary/b / (h n ) isolated by takatsy was later utilized by j.l. mcqueen and f.m. davenport for experimental infection in lambs, but they observed no clinical symptoms. the circulation of influenza a viruses among deer (order artiodactyla: family cervidae) was originally established by t.v. pysina and d.k. lvov when they isolated the a/rangifer tarandus/chukotka/ / (h n ) strain from slowed reindeer (rangifer tarandus) in the chukotka peninsula. the russian state collection of viruses in the d.i. ivanovsky institute of virology contains the strains a/ deer/primorje/ / (h n ), isolated from red deer (cervus elaphus) in primorsky krai, and a/rangifer tarandus/yamal/ / (h n ), isolated from reindeer (r. tarandus) on the coast of the barents sea. specific antibodies towards influenza a (h n ) and a (h n ) were detected in the sera of red deer (c. elaphus) and elks (alces alces) in the north of germany. , s.q. li established the presence of about a % immune layer toward influenza a (h n ) and a (h n ) among cervidae in the northeastern provinces of china. the strain influenza a/whale/pacific ocean/ / (h n ) (or, alternatively, a/ whale/po/ / ) from a whale belonging to the balaenopteridae family (order cetacea, suborder mysticeti) and bagged in the south pacific ocean was isolated by a group of soviet virologists under the direction of d.k. lvov (figure . ) in . this strain turned out to be reassortant between human and avian virus variants. two strains of influenza a virus were isolated by a group of american virologists under the direction of r. webster (figure . ) from slowed long-finned pilot whales (globicephala melaena) near portland, maine, in the united states in : a/whale/maine/ / (h n ) (from periapical lymph nodes in the lungs) and a/whale/maine/ b/ (h n ) (from the lungs). further molecular genetic investigation, carried out by a russianÀamerican group of scientists, revealed that influenza a variants in gulls (family laridae) were the source of these strains. a number of influenza a virus strains were isolated on the coast of north america: h n , h n , and h n . , thus, one could expect to find influenza a viruses among seals in northern eurasia as well. pathogenesis. epithelial cells of mucous membranes are the main targets of influenza a viruses. degeneration, necrosis, and further apoptosis, followed by tearing away of the epithelial cell layer take place as a result of the infection. nevertheless, the main element of influenza a virusÀinduced pathogenesis is lesions on the system of vessels; the lesions emerge as the result of the toxic effect of the virus, an effect that includes the multiple formation of active oxygen forms. the latter provoke the generation of hydroperoxides, which interact with lipids and phospholipids of the cell wall to oxidize their peroxide, thereby hindering transport across the cell membrane. À a subsequent increase in the permeability of vessels, the fragility of their walls, and a violation of the body's microcirculation result in hemorrhagic manifestations, from nasal bleeding to hemorrhagic hypostasis of the lungs and hemorrhages in the substance of the brain. , frustration of the circulation, in turn, defeats the nervous system. the pathomorphological picture is characterized by the existence of lymphomonocytic infiltrates around small and average-size veins, hyperplasia of glial elements, and a focal demyelinization that testifies to the toxic and allergic nature of the pathological process in the cns during influenza. , , the most significant factors involved in cell tropism of the influenza a virus are the receptor assembly on the surface of the potential target cell and the ability of cell proteases to cleave ha into two subunits (ha and ha ) followed by fusion peptide rescue. À for example, for avian influenza a virus variants, there is an obvious threshold in the virulence level: so-called lpai and hpai. hpai strains strike vascular endothelial and perivascular parenchymal cells as well as the cardiovascular system, quickly reproduce high titers in practically all internal organs, and cause systemic disease leading to death of a bird À days after infection. lpai strains, to the contrary, reproduce in low titers, have a narrow tropism toward mucous in the digestive and respiratory tracts (figure . ), and cause enteritis or rhinitis with low mortality. (however, bird diseases connected with lpai also cause significant damage to agriculture and can break the interspecies barrier, resulting in diseases that are dangerous to people). wild aquatic and semiaquatic birds, which are natural reservoirs of influenza a viruses, can have inapparent disease during either lpai or hpai infection. , , , , , À , , , À the ability of ha to be cleaved by proteases depends on the amino acid composition of the proteolytic cleavage site: lpai strains contain only one or two positively charged basic amino acids (k or r), whereas hpai strains have an enriched amount of basic amino acids. , , , , , , À nevertheless, pandemic strains with extremely high virulence in humans have only single basic amino acids within the limits of the proteolytic cleavage site (table . ). still, it is noteworthy that lpai could provoke human disease as well. except for the amino acid composition of the proteolytic cleavage site of ha, the efficiency of the cleavage process depends on glycosylation of ha in the vicinity of this site. , amino acid substitutions that switch virus tropisms from avian to mammalian cells in different influenza a virus proteins have been described: e k, , , , the classic diagnostic approach is to isolate the virus with the use of sensitive biological models (ferrets, developing chicken embryoa, and cell lines). influenza a virus infection could be retrospectively detected by hit or neutralization testing, but the most effective diagnostic methods are rt-pcr and biological microchips. control and prophylaxis. vaccination, together with the forced slaughter of livestock. is the most effective and accessible approach to influenza a prophylaxis among domestic animals. each country chooses its own strategy for combining these methods. for example, in russia only livestock in small and individual farms is to be vaccinated whereas birds in poultry farms are not vaccinated, but are killed if either hpai or lpai is detected. the genome of the quaranjaviruses consists of six segments of negative ssrna. segments À encode the proteins of a replicative polymerase complex (polymerase basic protein , or pb ; polymerase acidic protein, or pa; and polymerase basic protein , or pb , respectively). the pb protein (polymerase basic protein, rdrp) is one of the most conservative proteins of all viruses with a segmented rna genome. the amino acid sequence similarity of the pb protein among the viruses of different genera in the orthomyxoviridae family is À %, on average, but the similarity of the functional domains of rdrp (pre-a, a, b, c, d, and e motifs) is À % (figure . ) . the envelope glycoprotein gp (ha, segment ) of the quaranjaviruses has a very low similarity to the homologous protein (ha, segment ) of influenza viruses. however, it has some similarities tgo the surface glycoprotein of the baculoviruses. the amino acid sequences of thogotovirus genus members have about % identity with qrfv and tlkv. two other segments of the genome (segments and ) of the quaranjaviruses encode two proteins whose function is unknown. these proteins are probably structural proteins, which act as nucleocapsid (n) and matrix protein (m), respectively, but currently their function is not well known. other viruses of the quaranjavirus genus have been found in south africa, nigeria, egypt, iran, afghanistan, and oceania. the quaranjaviruses are associated with argasidae ticks (argas arboreus, a. vulgaris, ornithodoros capensis), which are obligate parasites of birds. tlkv has been classified into the quaranfil group of the orthomyxoviridae family on the basis of its antigenic reactions. À taxonomy. like the other members of the quaranjavirus genus, tlkv has a genome that consists of six ssrna segments. the pb protein amino acid sequence of tlkv has % and % identities with qrfv and jav, respectively (table . ). the similarity of the pb and pa proteins of tlkv to those of orf virus (orfv) is %, on average. the envelope glycoprotein (gp, segment ) of the quaranjaviruses has very low similarity to the homologous protein (ha) of influenza viruses. however, it has some similarities to the surface glycoprotein of the baculoviruses. the similarity of the gp of tlkv to that of qrfv is % nt and % aa (table . ). segment of tlkv has one orf and encodes a protein with unknown function ( aa). its similarity to the same protein of qrfv is % aa. segment encodes a protein aa long, which has no homology with any of the virus's proteins that are deposited in the database genbank. the similarity of this protein in tlkv and the same protein in qrfv is %. figures . and . show the results of phylogenetic analysis based on a comparison of pb and the envelope protein (gp and ha, respectively). on the phylogenetic trees, tlkv is grouped with qrfv and jav within the quaranjavirus genus. arthropod vectors. natural foci of tlkv associated with argas vulgaris ticks in kyrgyzstan are located below the northern border of the area of distribution of argasidae ticks ( % on). this boundary coincides with the line of a frost-free period of À days a year and an average daily temperature above for no less than À days per year. the ability of these ticks to withstand prolonged starvation (up to years), as well as their long life cycle ( À years), polyphagia, and ability to transfer viruses transovarially, provides stability of the virus's natural foci. À , À animal hosts. tlkv was isolated from argasidae ticks collected in the nesting burrows of birds. complement-fixation testing of the birds from these colonies revealed that qrfv have been found in . % of the human population. the genus thogotovirus currently includes four viruses: thogoto virus (thov), dhori virus (dhov), araguari virus (argv), and jos virus (josv). , the viruses of thogotovirus are arboviruses, transmitted mainly by ixodidae ticks; therefore, the genus had previously been called orthoacarivirus, to emphasize these viruses' association with ixodids (taxon acari: order parasitiformes, family ixodidae). thov was originally isolated from the ticks rhipicephalus (boophilus) decoloratus and rh. evertsii collected from cattle in thogoto forest, nairobi, kenya, in . subsequently, it was isolated from human, cows, camels, and ticks in many countries in africa. , the genome of the thogotoviruses consists of six segments of negative-polarity ssrna that encode seven proteins. (segment encodes two forms of matrix protein.) , the most conservative proteins of the replicative complex (pb , pb , pa) of thogotoviruses have À % identity with those of the influenza a virus genus. history. dhori virus (dhov) was originally isolated from hyalomma dromedarii ticks collected from camels in india. dhov has also been isolated in egypt, portugal, russia, and transcaucasia. À in russia, several strains of dhov were isolated from h. plumbeum ticks, anopheles hyrcanus mosquitoes, and lepus europaeus hares, all in the volga river estuary. , one strain of dhov was isolated from the cormorant phalacrocorax carbo in maly zhemchuzhnyi island in the caspian sea ( n, e; figures . and . ). the prototypical strain of batken virus (bknv), leiv-k , was isolated from hyalomma marginatum ticks collected from sheep near the town of batken in kyrgyzstan in april . other strains of bknv were isolated from a mixed pool of aedes caspius and culex hortensis mosquitoes in kyrgyzstan and from ornithodoros lahorensis and dermacentor marginatus ticks in transcaucasia. antigenic studies showed that bknv is closely related to dhov, but differs from it. taxonomy. the similarity of the structural homologous proteins of the thogotoviruses (thov, dhov, argv, and josv) ranges from % (m-protein, segment ) to % (np, segment ). the envelope protein ha (segment ) has À % identity, on average. the similarity of the nonstructural proteins (pb , pb , and pa) ranges from % to %. bknv has a high similarity to dhov. the proteins are % (pb , pa, np, m) and % (pb ) identical. the similarity of the envelope protein ha of bknv to that of dhov is %, a percentage that explains the antigenic differences between these two closely related viruses. because the homology of the other structural and nonstructural proteins of bknv and dhov is À %, it can be concluded that bknv is a variant of dhov, typical to central asia and transcaucasia. a phylogenetic analysis based on a comparison of the pb and ha proteins is presented in figures . and . . arthropod vectors. apparently, the main arthropod vector of dhov and bknv is hyalomma sp. ticks-in particular, h. marginatum. dhov has also been isolated from h. dromedarii, dermacentor marginatus, and ornithodoros lahorensis ticks. rare isolations of dhov and bknv from mosquitoes (anopheles hyrcanus, aedes caspius, and culex hortensis) suggest that they play some role in the circulation of these viruses. vertebrate hosts. antibodies to dhov were found in % of camels, % of horses, and % of goats in the indian state of gujarat, where the virus was first isolated. antibodies to bknv were found in . % of sheep and . % of cattle in kyrgyzstan. two strains of dhov were isolated from a hare (lepus europaeus) and a cormorant (phalacrocorax carbo) in natural foci of the virus. , the bird, from which dhov was isolated on maly zhemchuzhnyi island, was ill with respiratory failure, inability to fly, and loss of coordination (figure . c) . human disease. several cases of disease caused by dhov have been registered. the disease occurred with fever, encephalitis ( %), headache, and weakness. antibodies to dhov were found in À % of the population in the volga river delta (in the south of russia) and in . % in the south of portugal. antibodies to bknv were found in the sera of . % of the human population of kyrgyzstan. five cases of laboratory infection were identified. the togaviridae family consists of two genera (alphavirus and rubivirus) of enveloped rna viruses. the virion of the togaviruses ( nm) contains a core particle ( nm) formed by a capsid protein and comprising a single-stranded, positive-sense genomic rna , À , nt long. the lipid bilayer contains the heterodimers of two surface glycoproteins e and e , which form an icosahedral surface of the virion. the genomic rna has a cap structure at the -and poly-a tail at the -end, as well as two orfs encoding nonstructural and structural proteins. the nonstructural proteins are encoded by the -orf (which occupies two-thirds of the genome), whereas the structural proteins are encoded by the subgenomic -orf. most viruses of the alphavirus genus are arboviruses and can replicate in either a vertebrate host and or an invertebrate vector. , the rubivirus genus consists of one species-rubella virus-that is transmitted by aerosol and is the causative agent of disease known as rubella. , the genome of the alphaviruses is a singlestranded rna with positive polarity about , nt in length. the viral rna has a cap at the -end and a poly-a tail at the -end. a large part of the genome of the alphaviruses (about two-thirds, beginning from one-third into the genome and extending to the -end) encodes nonstructural proteins that form the viral replicative complex nsp , nsp , nsp , and nsp ). structural proteins (core, e , e , k, and e ) are translated from subgenomic rna ( s rna), which is formed in the process of replicating the virus and corresponds to the other one-third of the genome (figure . ). the alphaviruses can infect a wide range of vertebrates. most of the alphaviruses are arboviruses and are associated with mosquitoes (genera culex, culiseta, aedes, coquillettidia, and haemogogus) and birds, the latter of which can transfer viruses during migration. À other vertebrate hosts of the alphaviruses are ruminants, reptiles, amphibians, and fish. , the alphaviruses are divided into antigenic complexes. among the alphaviruses are dangerous pathogens of humans or animals, such as eastern equine encephalitis virus (eeev), western equine encephalitis virus (weev), sindbis virus (sinv), chikungunya virus (chikv), and others. history. chikv (family togaviridae, genus alphavirus, semliki forest group) is the etiological agent of a fever that is mortally dangerous to humans. this disease is accompanied by joint and muscle pains (right up to complete immobilization of the patient) and a two-wave course of the fever, together with a macu-larÀpapular rash emergency (usually during the second wave). the etymology of the name "chikungunya" is {chee-kungunyalac, which, in the makonde local language, means "doubled up," owing to the severe joint pains. chikv was originally isolated by r.w. ross from the serum of a patient with fever during the decoding of an epidemic outbreak in tanzania in februaryÀmarch . À the close relation of chikv to mayaro virus (mayv), from the semliki forest group, was demonstrated in by serological methods. , distribution. chikv was also isolated in cambodia in southeastern asia in , in hindustan in , , and in the eastern part of new guinea in . the basic area over which chikv is distributed (table . taxonomy. chikv belongs to the togaviridae family, alphavirus genus, semliki forest group. on the basis of comparative analysis of the e gene, chikv was classified into three genotypes: a (asian), cesa (centre, east, and south african), and wa (west african) , À (table . vertebrate hosts. rodents, bats, and monkeys are the natural reservoir of chikv. , À , there is substantial evidence, that, in africa, wild primates play an important role in the natural transmission cycle, but it is not clear whether infection in primates is incidental to or necessary for the maintenance of the virus. in uganda, chikv was frequently isolated from aedes africanus mosquitoes, which preferto feed on monkeys in the forest canopy. specific anti-chikv antibodies were found among chimpanzees (pan troglodytes) in equatorial and savanna forests in the democratic republic of the congo (kinshasa) and in savannas in southern africa. antibodies were found over a wide area in vervet monkeys (cercopithecus aethiops) and baboons (pipio ursinus), and in both species the virus could circulate in the blood for two to three days at high concentrations without evidence of illness. so, wild animals could play an important role as amplifying hosts. chikv was isolated in dakar , senegal, from bats, which developed viremia after experimental infection. but in india, inoculation of the virus into two species of fruiteating bats was followed by low virulence. , antibodies were found among donkeys, bats, and wild rodents in africa and among domestic animals in asia. , inoculation of african strains into cattle, sheep, goats, and horses failed to produce viremia. apart from chickens, adult fowl and several species of wild birds did not develop viremia after experimental infection. but experimental infection of vervet monkeys and baboons led to high viremia (up to log pfu/ml) during six days, which is sufficient for the infection of mosquitoes. arthropod vectors. chikv is transmitted by bloodsucking mosquitoes. the main vectors for this virus during epidemics are aedes aegypti and ae. albopictus in urban regions and mosquitoes from the aedes, culex, and coquillettidia genera in rural landscapes. , À , chikv has been multiply isolated from ae. africanus, ae. luteocephalus, ae. furciferÀtaylori, cx. fatigans, and coq. fuscopenatta, all of which could preserve the virus and realize virus circulation in natural foci. , , epidemiology. a high level of viremia in humans (up to log pfu/ml) makes it possible for mosquitoes to transmit chikv from human to human -a plausible reason that large epidemic outbreaks have been known in big cities of southern and southeastern asia since the s. , , À beginning in the middle of the s, epidemiological processes linked to chikv have intensified (table . ), although this fact could be explained by improvements in laboratory diagnostics: previously, chikungunya fever was often confused with dengue. in any event, chikvprovoked lethality has increased, in some cases up to . %). , increases in the frequency of imported chikungunya fever cases seen at the beginning of the twenty-first century (table . ) are most dangerous, especially when the possibility of chikv penetration into local mosquito populations is taken into account. since , imported cases of chikungunya fever have become more frequent in europe (italy, , , , spain, france, , , belgium, switzerland, germany, the czech republic, norway ); the americas (canada, the united states, , brazil ); eastern asia (hong kong, south korea, japan , ); and australia. outbreaks in brazilian cities emerged with infections from aedes aegypti, whereas in rural regions aedes albopictus was the vector, introduced from southeastern asia, including japan. imported cases of chikungunya fever in russia. a -year-old patient arrived in russia september , , and suddenly fell ill, with a body temperature of . c. antipyretic drugs were not effective. early in the morning on september , , the patient was delivered to a moscow infection hospital with a diagnosis of "fever with unknown etiology." the fever had mid-level severity, and the patient complained of shivering, headache, and asthenia. hyperemia of the conjunctivae, papularÀhemorrhagic rash on the abdomen, and cruses were found. a medical radiolograph (figure . ) of the lungs of the patient revealed decreased clarity at the back of the lung field and diffuse reticular pneumosclerosis in the right lower lobe pyramid, as well as local changes with expressed peribronchial and perivascular alterations. a round shadow was detected near (i.e., peribronchially to) the intermediate bronchus. the roots were intensified. the heart was enlarged at the left. thus, the medical radiography portrait was consistent with rightside pneumonia with lymphadenopathy. several peculiarities of the case were the bareness of clinical symptoms (pneumonia was diagnosed only via medical radiography), a rapid progression of changes in the lungs, and the absence of inflammation markers in the peripheral blood. three days later, positive dynamics were detected: the basal parts of the right lung were restored to their previous level of clarity, although the shadow indicating a hypertrophic lymph node and right root broadening remained. bioprobes (blood swabs and nasopharyngeal swabs) were delivered to the d.i. ivanovsky institute of virology. the absence of influenza a and b viruses was established by rt-pcr. the strain chikv/leiv-moscow/ / was isolated with the use of intracerebrally inoculated newborn mice and was identified with the help of a completegenome (genbank id: kf ) nextgeneration sequence approach. phylogenetic analysis (figure . , table . ) revealed that the chikv/leiv-moscow/ / strain belonged to an asian genotype. this strain was deposited into the russian state collection of viruses (deposition certificate n with a priority of november , ). serological methods revealed eight cases of imported chikungunya fever that had previously been described in russia: from indonesia, singapore, india, the island of réunion, and the maldives islands. the chikv/leiv-moscow/ / strain was found to belong to the a-genotype, whereas most of the cases imported into europe belong to the cesa genotype, reflecting the "bridge" role of russia between europe and asia. the modern-day intensification of both international links and transport flows among countries increases the probability of imported cases of infection emerging. the penetration of aedes aegypti and aedes albopictus to the russian black sea coast , , suggests the emergence of seasonal outbreaks in the dynamically developing greater sochi region as well. history. getah virus (getv) was originally isolated in western malaysia from culex gelidus and cx. tritaeniorhynchus mosquitoes. À this virus is widespread in southeastern asia and in australia. À the first isolation of getv in northern eurasia was carried out by m.p. the genome of getv is , nt long. the strains of getv, circulating in different geographical regions of northeastern and southeastern asia, have a high level of similarity. À a pairwise comparison of complete genome sequences revealed that isolates from malaysia, south korea, china, mongolia, japan, and russia have À % nt identities, suggesting that the rate of getv evolution is low. phylogenetic analysis of the e gene ( figure . ) is not conducive to dividing the getv strains into distinct clusters. analyses of numerous strains isolated in japan showed that genetic differences were determined by the time of isolation more than the place of isolation. an analysis of strains of getv isolated in different regions of russia revealed their high degree of similarity, but still, they could be divided into three groups on the basis of minimal differences. the first group comprises strains from tundra and for-estÀtundra in the magadan region and the sakhaÀyakutia republic in the north of asia. the second group encompasses strains from leaf-bearing forests of khabarovsk krai. the third group consists of isolates from forestÀsteppe and steppe landscape belts of khabarovsk krai, the republic of buryatia, and mongolia. , distribution. according to our data, , , À getv is distributed over eastern siberia and north pacific physicogeographical lands (figure . ) . the most intensive virus circulation was revealed in the steppe landscape belt of mongolia, as well as in the mixed forests of khabarovsk krai and in the northern taiga of the magadan region and the sakhaÀyakutia republic. getv circulation intensity is significantly lower in tundra and forestÀtundra landscapes, a phenomenon that could be explained by the temperature there. getv is the only member of the alphavirus genus whose distribution extends to the rough climatic conditions of the high latitudes of northern eurasia. , getv has penetrated to the north of asia from the overwintering places of birds, which regularly migrate by the east asian flyway , (figure . ) . the distribution of the virus in the north coincides with that of aedes mosquitoes, which are the effective vector of getv. getv and closely related viruses are known outside of northern eurasia in japan, various countries in southeastern asia, and australia. À , , À human infection. the pathogenicity of getv to humans has not yet been described. nevertheless, the antigenically close rrv has been associated with large epidemic outbreaks of polyarthritis in australia and sarawak. , vertebrate animal infection. symptomatic and subclinical infections of animals were reported in in japan, where there was a large outbreak involving racehorses. , among the clinical features seen were fever, rash on various parts of the body, and edema on the hind legs. virus isolates were more similar to the prototypical malaysian strain than to the japanese sagiyama strain. getv has been implicated in illness and abortion or stillbirths in pigs. , disease among horses was described in india. infection in cattle is usually subclinical. arthropod vectors. getv has been isolated from culex gelidus, cx. tritaeniorhynchus (malaysia, cambodia, china), cx. bitaeniorhynchus, anopheles amictus (australia), cx. vishnui (philippines); the sagiyama subtype of getv was isolated from cx. tritaeniorhynchus and aedes vexans, as well as from pigs with fever, in japan. , although their natural transmission cycle is not known in details, mosquitoes acquire getv mainly while feeding on domestic mammals and fowl. there may also be a jungle cycle involving wild vertebrates. the bebaru subtype was isolated from culex lophoceratomyia and aedes spp. mosquitoes collected in mangrove swamp forests of western malaysia. the main vectors in russia (i.e., in northern eurasia) are aedes nigripes, ae. communis, ae. impiger, ae. punctor, and ae. excrucians. , kfv was first noted in the summer of in the central and southwestern parts of fennoscandia, including russia, finland, sweden, and southern norway (figure . ). the prototypical strain leiv- a of kyzv was first isolated from culex modestus mosquitoes collected in a colony of ardeidae birds (herons) in kyzylagach reservation, located on the coast of kyzylagach bay in the caspian sea ( n, e; figure . ). taxonomy. on the basis of a comparison of a partial sequence of the e gene, isolates of sinv can be divided into five genotypes (figure . ). genotype i includes viruses from europe and africa, genotype ii isolates from australia and oceania, and genotype iii viruses from india and the philippines. together with the chinese strain sinv xj- , kyzv was assigned to genotype iv. genotype v consists of only the strain m from new zealand. the strains of genotype i form two subclusters, one of which comprises sinvs from northern europe and sub-saharan africa and the second of which consists of strains from the mediterranean region (southern europe, northern africa, and the middle east). the genetic distance between the viruses of the different genotypes of sinv (e.g., between the european and australian isolates) is not more than % nt (table . ). at the same time, sinvs isolated in the same geographic region are characterized by a high degree of similarity (figure . ) . thus, sinv strains isolated in russia, germany, sweden(ockv), and finland have about % similarity (table . ). , , , babanki virus, which is from cameroon, has % similarity to the european strains of sinv. despite the high degree of similarity among the different genotypes of sinv, known cases of human disease are caused only by strains of the europeanÀafrican subcluster of genotype i (karelian fever, a disease of ockelbo, a disease of babanki). kyzv has a high similarity ( %) to the chinese isolate sinv xj- , isolated from anopheles sp. mosquitoes in the xinjiang uighur autonomous region in the northwest of china. the divergence of kyzv and xj- from the european isolates of sinv is % nt and % aa of the entire genome sequence (table . ). the geographic isolation of kyzv and xj- and their genetic divergence from the european and australian isolates suggest that kyzv is a variant of sinv that is typical to central asia. distribution. sinv has been isolated in many regions of southern europe, the middle east, africa, southeastern asia, the philippines, and australia. , , the african continent is almost all endemic for sinv: strains are known from egypt, the republic of south africa, uganda, the central african republic, sudan, nigeria, and zimbabwe. as for asia, there are strains from turkey, india, malaysia, and the philippines. in australia, sinv strains were multiply isolated in the north of the continent. in europe, sinv has been isolated in sicily (italy) and slovenia. on the territory of the former ussr, sinv strains were multiply isolated in belarus, ukraine, azerbaijan, tajikistan, and western siberia (in the areas around the central region of the ob river valley). À . vertebrate hosts. the main vertebrate hosts of sinv are different species of birds, predominantly of the orders passeriformes, pelecaniformes, ciconiiformes, and anseriformes. sinv infection in birds can chronic, allowing them to transfer the virus during their seasonal migration. À migratory birds play an important role in the wide distribution of this virus. sinv has been known to persist for as much as two months after experimental infection. sinv strains have been multiply isolated from aquatic and semiaquatic birds in the delta of the nile river in egypt, from the white wagtail (motacilla alba) and the common hill myna (gracula religiosa) in india, and from the reed warbler (acrocephalus scirpuceus) in the western part of slovakia. in zimbabwe, sinv has been isolated from insectivorous bats of the rhinolophidae and hipposideridae families. occasionally, sinv has been isolated from rodents and amphibians. on the territory of the former soviet union, sinv was originally isolated from a yellow herons (ardeola ralloides) caught out of a bird colony in the southeastern part of azerbaijan in . serological methods have revealed sinv circulation in the astrakhan region among aquatic and semiaquatic birds, especially those of the orders pelecaniformes ( %), ciconiiformes ( %), and anseriformes ( %). neutralizing antibodies to sinv were found in coots (fulica atra) ( . %) from natural foci of the middle belt of the volga river delta. in the kuban river delta in krasnodar krai, specific anti-sinv antibodies were found among eight species of aquatic and semiaquatic birds, most frequently mallards (anas platyrhynchos) and purple herons (ardea purpurea). in belarus, anti-sinv antibodies were detected in % of birds in the summer and in . % in the fall. antibodies to sinv have been detected among farm animals (table . cattle ( . %) and horses ( . %) in the middle belt of the volga river delta. arthropod vectors. sinv is closely associated with ornithophilic mosquitoes. in egypt, this virus was isolated from culex univittatus, cx. antennatus, and anopheles pharoensis; in uganda, from coquillettidia spp.; in sarawak, (malaysia), from cx. bitaeniorhynchus; in australia, from cx. annulirostris, aedes normanensis, and ae. vigilax; in india, from coq. fuscopennata; in sudan, from cx. quinquefasciatus; and in europe, from cx. pipiens, cx. torrentium, culiseta morsitans, coq. richiardii, ochlerotatus communis, oc. excrucians, ae. cinereus, and an. hyrcanus. , according to our data, in the volga river delta sinv is transferred by culex pipiens in anthropogenic biocenoses and by anopheles hyrcanus and coquillettidia richiardii in natural ones. in the natural foci of the middle belt of the volga delta, strain can be isolated from approximately , an. hyrcanus or , coq. richiardii mosquitoes; in the low belt of the delta the ratio is in about in a power less, and in anthropogenic biocenoses it is strain per , cx. pipiens mosquitoes. sinv strains from gamasidae ticks (ornithonyssus bacoti) in india and from ixodidae ticks (hyalomma marginatum) in sicily (italy) are known. productive experimental infections were described in the argasidae ticks ornithodoros savignyi and argas persicus (although infected ticks did not transmit the virus during feeding). most likely, ticks do not play an important role in sinv circulation or as a reservoir for this virus. human pathology. sinv causes acute fever in humans but has a favorable outcome. antibodies to sinv are widely detected in human sera (table . ), although in eastern siberia and the far east cross-reactions with getv (another member of the semliki forest serogroup) can take place. the start of the disease is sudden. clinical symptoms include fever, muscle and joint pain, and rash. severe progressive arthritis of large joints could develop several years after the disease and could lead to disability. this pathology appears in À % of citizens of endemic territories. outbreaks of sindbis fever in egypt and israel emerged at the same time as west nile fever; hence, it is necessary to distinguish these infections in the laboratory. a neurotropic virus isolated from aedes mosquitoes caught in the semliki forest virus taxonomy: classification and nomenclature of viruses: 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