key: cord-027859-citynr6c
authors: P. Shetty, Nandini; S. Shetty, Prakash
title: Epidemiology of Disease in the Tropics
date: 2020-06-22
journal: Manson's Tropical Diseases
DOI: 10.1016/b978-1-4160-4470-3.50007-0
sha: 
doc_id: 27859
cord_uid: citynr6c

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. 1 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 1996: 'Fighting disease, fostering development', states that infectious diseases are the world's leading cause of premature death. 2 Infectious diseases account for 45% of deaths in low-income countries (Figure 3 .1) and up to 63% of deaths in children under 4 years of age worldwide. Africa and South-east Asia carry the highest mortality due to infectious diseases (Figure 3 .2). In addition, new and emerging infections pose a rising global threat (Table 3 .1).

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 3 .3).

Acute respiratory infections (ARIs) are the leading cause of death of infectious aetiology, killing more than 4 million people a year, 1.9 million of which constitute children under the age of fi ve. 3 Among the 42 countries of the world that carry 90% of the child mortality burden, 14-24% of the under-5 mortality is due to pneumonia and nearly 70% 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 154 million cases per year. 3 This range of infections, which includes pneumonia in its most serious form, accounts for more than 8% 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 1992 that switching to better fuels could halve the number of pneumonia deaths. 4 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 25-50%. 5 However, implementation of community ARI treatment programmes remains patchy and current rates of children with ARI being taken to a health provider are ~40% in Africa and South Asia. In nearly half of the 81 countries with available data, less than 50% of the children with ARI were taken to an appropriate healthcare provider. 5 

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 2005 (UNAIDS and WHO), 6 the epidemiology of HIV in the tropics varies enormously from place to place (Figure 3 

Latest estimates show some 8.3 million people (2 million adult women) were living with HIV in 2005, including the 1.1 million people who became newly infected in the past year. AIDS claimed some 520 000 lives in 2005. 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 20% 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 5% 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 2003, an estimated 5.1 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 2003 found 14% of commercial sex workers in Karnataka (26% in the city of Mysore) and 19% 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 85% 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 1%, 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 52 000 people were living with HIV in 2004, the vast majority of them young men (aged 20-29 years), of whom approximately 75% were injecting drug users. After peaking at 3% in 1997, national adult HIV prevalence in Cambodia fell by one-third, to 1.9% in 2003. 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 2003, estimated national adult HIV prevalence had dropped to its lowest level ever, approximately 1.5%. However, Thailand's epidemic is far from over; infection levels in the most at-risk populations are much higher: just over 10% of brothel-based female sex workers were HIV-infected in 2003, as were 45% of injecting drug users who attended treatment clinics.

While Cambodia and Thailand in the 1990s 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 1.8% in 2004. 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 1994-1995, and reached 780 in 2004; 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 67 000 people became infected with HIV in 2005. Approximately 510 000 people are living with HIV in this region. An estimated 58 000 adults and children died of AIDS-related conditions in 2005. 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 2004, HIV prevalence of 1.6% was found compared with under 0.3% 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 10% of the world's population, but is home to more than 60% of all people living with HIV -25. 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 15 and 24 years old are at least three times more likely to be HIV-positive than young men (Figure 3 .5). 6 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), 66% reported having one lifetime partner, 79% had abstained from sex at least until the age of 17 (roughly the average age of fi rst sexual encounter in most countries in the world). Yet, 40% 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 5 years of age and accounts for considerable mortality in childhood. Estimates from studies published between 1992 and 2000 show that there was a median of 3.2 episodes of diarrhoea per child-year in developing countries. This indicates little change from previously described incidences. Estimates of mortality revealed that 4.9 children per 1000/year in these countries died as a result of diarrhoeal illness in the fi rst 5 years of life, a decline from the previous estimates of 5.6-3.6 per 1000/year. The decrease was most pronounced in children aged under one year. Despite improving trends in mortality rates, diarrhoea accounted for a median of 21% of all deaths of children aged under 5 years in developing countries, being responsible for 2.5 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. 7 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 6 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. 8 The factors contributing to childhood mortality and morbidity due to diarrhoea are described in Table 3 .2. 8 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 69% decline in diarrhoea deaths after creation of an ORT unit. 9 In May 2002, 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. 10 A total of 53 280 patients, including 22 536 children younger than 60 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. 10 Changing patterns in the epidemiology of diarrhoea have been noted in many studies. In Matlab, Bangladesh, acute watery diarrhoea accounted for 34% of diarrhoea deaths in under-fi ves, while the remaining 66% 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 40% of deaths, and less important in later childhood, being associated with 10% of deaths. 11

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 600 000 deaths each year are associated with this infection. More than 125 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 3-5 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 G1P [8] 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. 12

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 1 (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 10-100 shigella organisms to produce dysentery, a low infectious dose, whereas 1 million to 10 million organisms may need to be swallowed to cause cholera. During the late 1960s, Shiga's bacillus was responsible for a series of devastating epidemics of dysentery in Latin America, Asia and Africa. In 1967, it was detected in the Mexican-Guatemalan border area and spread into much of Central America. An estimated half a million cases, with 20 000 deaths, were reported in the region between 1967 and 1971. In some villages the case fatality rate was as high as 15%; 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. 13 Serious epidemics due to the multiple-drug resistant S. dysenteriae type 1 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. 13 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. 14 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. 15 Worldwide attention was focused on South Africa, when in October 2006 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 536 TB patients at the Church of Scotland Hospital, which serves a rural area with high HIV rates, some 221 were found to have multi-drug resistance and of these, 53 were diagnosed with XDR-TB. Some 52 of these patients died, most within 25 days of diagnosis. Of the 53 patients, 44 had been tested for HIV and all 44 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, 10 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. 14 million Africans who die from malaria each year, most are children under 5 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 1.3% in economic growth for those countries with the highest burden. 16 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 3.7) . 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 40 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. 16 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. 16 Resistance of P. falciparum to chloroquine is now common in practically all malariaendemic countries of Africa (Figure 3.7) , 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. 16 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. 17 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. 16 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 5 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. 18

Although substantial progress has been made in reducing measles deaths globally, in 2000 measles was estimated to be the fi fth leading cause of mortality worldwide for children aged <5 years. Measles deaths occur disproportionately in Africa and South-east Asia. In 2000, the African Region of WHO, with 10% of the world's population, accounted for 41% of estimated measles cases and 58% of measles deaths; the South-east Asia region, with 25% of the world's population and 28% of measles cases, accounted for 26% 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 2000 occurred in countries eligible to receive fi nancial support from the Global Alliance for Vaccines and Immunization's Vaccine Fund (WHO, unpublished data 2003). 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. 19, 20 

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 10-20%. 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 90% of 15-year-olds have serological evidence of infection with HBV. Intermediate levels of infection (2-7%) 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 60% of cases of hepatocellular carcinoma and 80% of cases of cirrhosis of the liver. 21 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. 22

Tetanus is a vaccine-preventable disease that causes a total of 309 000 deaths annually. Of particular concern is maternal and neonatal tetanus (MNT), which can be prevented through immunization of the mother in pregnancy. In 2000, neonatal tetanus alone was responsible for an estimated 200 000 deaths. In addition, an estimated 15 000-30 000 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 57 priority countries, 90% of the neonatal tetanus deaths occur in 27 countries. UNICEF spearheaded the effort to eliminate MNT by the year 2005, with the support of numerous partners. MNT elimination is defi ned as less than one case of neonatal tetanus per 1000 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 2005, 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). 23 

By the end of 2007 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. 24 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 500 000 to 1 million deaths annually and cause a global disease burden equivalent to that of HIV-AIDS. WHO estimates that at least 1 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 25 . 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. 25

Since 1991, 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 3.8) . 26 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  3. 3). 26 International travel and commerce have made it possible for pathogens to be quickly transported from one side of the globe to the other (Figure 3.9) . 26 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 1976 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 50-90% 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 100 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 2500 million people -two-fi fths of the world's population -are now at risk from dengue. WHO currently estimates there may be 50 million cases of dengue infection worldwide every year.

In 2001 alone, there were more than 609 000 reported cases of dengue in the Americas, of which 15 000 cases were DHF. This is greater than double the number of dengue cases which were recorded in the same region in 1995. Not only is the number of cases increasing as the disease is spreading to new areas, but explosive outbreaks are occurring. In 2001, Brazil reported over 390 000 cases including more than 670 cases of DHF. During epidemics of dengue, attack rates among the susceptible are often 40-50%, but may reach 80-90%. An estimated 500 000 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 20%. With modern intensive supportive therapy, such rates can be reduced to less than 1%. 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. 28

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 1997 and early 1998, RVF occurred over vast areas, producing disease in livestock and causing haemorrhagic fever and death among the human population. As of December 2006, WHO fi gures indicate that the outbreak continues to affect the north western provinces of Kenya. In September 2000 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 1998. A total of 1087 suspected cases were identifi ed, of which 121 (11%) persons died. Of the 1087, 815 (75%) cases reported exposure to sick animals, handling an abortus or slaughtering animals in the week before onset of illness. 29

The vibrio responsible for the seventh pandemic, now in progress, is known as V. cholerae O1, biotype El Tor. According to the WHO, it continues to spread in Angola and Sudan; more than 40 000 cases have been documented with over 1500 deaths: a case fatality rate of 3.5-4%. Cholera (biotype El Tor) broke out explosively in Peru in 1991, after an absence of 100 years, and spread rapidly in Central and South America, with recurrent epidemics in 1992 and 1993. From the onset of the epidemic in January 1991 to 1 September 1994, a total of 1 041 422 cases and 9642 deaths (overall case fatality rate 0.9%) were reported from countries in the Western Hemisphere to the Pan American Health Organization.

In December 1992, a large epidemic of a new strain of cholera V. cholerae 0139 began in South India, and spread rapidly through the subcontinent (Figure 3.10) . 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 O139 has been reported from 11 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. 30

In early 1999, 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 1999, 257 cases of febrile encephalitis were reported to the Malaysian Ministry of Health, including 100 deaths. Laboratory results from 65 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 890 000 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. 31 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). 32 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 99% homology with human SARS-CoV. 32 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 20-25% 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. 32

In May 1997, a 3-year-old boy in Hong Kong contracted an infl uenza-like illness, was treated with salicylates, and died 12 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/156/97 (H5N1), which was very closely related to isolate A/Chicken/Hong Kong/258/97 (H5N1). The latter virus was considered representative of those responsible for severe outbreaks of disease on three rural chicken farms in Hong Kong during March 1997, 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 17, of which fi ve were fatal; the case fatality rates were 18% in children and 57% in adults older than 17 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 1997, veterinary authorities began to slaughter all (1.6 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 H5N1 to date seem not to have transmitted on further. Therefore, although the case fatality rate for human infection remains high (around 57% for cases reported to WHO), it seems that H5N1 avian viruses remain poorly adapted to humans. 33 Global prevalence studies (Figure 3 .11) indicate that Indonesia is currently the most active site of bird to human H5N1 transmission in the Asia Pacifi c region, and a large number of human cases have been detected here in 2005-06. China and Cambodia have also reported human cases in 2006. 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 2006. 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 H5N1 infection. If that virus had pandemic potential then a pandemic arising from Africa must be considered a possibility. 33

Non-infectious diseases take an enormous toll on lives and health worldwide. Non-communicable diseases (NCDs) account for nearly 60% 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 1998 alone, NCDs were estimated to have contributed to 31.7 million deaths globally and 43% of the global burden of disease. 34 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, 35 particularly those in rapid transition like China and India (Table 3 .4). According to these estimates at least 40% of all deaths in the tropical developing countries are attributable to NCDs, while in industrialized countries NCDs account for 75% 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 1998, of the total number of deaths attributable to NCDs 77% occurred in developing countries, and of the disease burden they represent 85% was borne by low-and middle-income countries. 34 It has now been projected that, by 2020, NCDs will account for almost three-quarters of all deaths worldwide, and that 71% of deaths due to ischaemic heart disease (IHD), 75% of deaths due to stroke, and 70% of deaths due to diabetes will occur in developing countries 36 and the number of people in the developing world with diabetes is expected to increase by more than 2.5-fold, from 84 million in 1995 to 228 million in 2025. 37 On a global basis, 60% 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 38 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: 1 • 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. 39 

The world we live in is constantly changing. In the past 25 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 10% 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.

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