key: cord-0686687-86ae13vb
authors: Tulchinsky, Theodore H.; Varavikova, Elena A.
title: Chapter 4 Communicable Diseases
date: 2014-12-31
journal: The New Public Health
DOI: 10.1016/b978-0-12-415766-8.00004-5
sha: 8d1ca4b0b4048b0a815b48a9a720dfe8aad3d08e
doc_id: 686687
cord_uid: 86ae13vb

Abstract Sanitation, food control, vaccines, and antibiotics have reduced the toll of communicable diseases, saving millions of lives. Smallpox was eradicated in 1977, and poliomyelitis eradication is close. Measles mortality has reduced drastically yet outbreaks occur where immunization lags. HIV/AIDS emerged in the 1980s, grew into a global pandemic costing millions of lives, and despite progress remains a major global health issue. Malaria and tuberculosis still cause millions of deaths. Influenza pandemics with new, deadly versions continue to appear. Neglected tropical diseases are responding to global donor efforts. Newly emerging diseases move to new regions and became endemic, and deadly localized hemorrhagic fevers threaten to transmit more widely. Rapid mass travel allows infectious diseases in isolated villages to quickly become global threats. New strains of viruses, antibiotic resistance, and microorganisms causing chronic diseases are challenges for infectious disease control requiring continuing political, financial, and scientific support, and much tenacity.

Despite enormous advances in medical sciences and their applications in public health, infectious diseases remain a central challenge for public health in the twenty-first century. Of particular concern are human immunodeficiency virus/ acquired immunodeficiency syndrome (HIV/AIDS), tuberculosis (TB), malaria, severe acute respiratory syndrome (SARS), avian flu, and antibiotic-resistant infections (superbugs), among others. Globalization has facilitated the spread of many infectious agents to all corners of the globe. Mass travel, economic globalization, and climate change, along with accelerating urbanization of human populations, are causing environmental disruption, including global warming. There are and will be more consequences in international transmission of infectious diseases than are now known, in humans and wildlife, as well as domestic animals in the food chain.

This chapter describes communicable and infectious diseases and programs for their prevention, control, elimination, and eradication. Eradication refers to the total elimination of the organism from nature; elimination designates a stop in the circulation of the organism locally; and control means reducing the disease as a public health problem. All of these require a systems approach using available resources, conducting research, and effectively mobilizing environmental measures. This must be carried out in conjunction with strengthening primary care and the overarching health care framework. Rapid transportation and communication make a virus outbreak in any part of the world an international concern, both for health professionals and for the general public. With rapid changes in our understanding of basic sciences, and in vaccine research, production, and associated measures, it is incumbent upon all medical and allied professionals, educators, policy makers, and students entering the field to have a working understanding of the exciting and dynamic advances. Here, the interesting overlap between communicable diseases and non-communicable diseases (NCDs) becomes evident and imperative. Furthermore, it is crucial to be aware of the social environment in which the risk and exposure of vulnerable groups and individuals cause greatly varying degrees of morbidity and mortality in populations.

The material presented in this chapter is intended to provide an introduction to the student or a review for the public health practitioner, with an emphasis on the applied aspects of communicable disease control. The authors have relied for the content of this chapter on several standard references, especially Heymann's Control of Communicable Diseases Manual, 19th edition (2008) , WHO Vaccine Preventable Diseases Monitoring System: 2007 Global Summary, and Jawetz, Melnick and Adelberg's Medical Microbiology, 26th edition (2012) . Regular access to the Centers for Disease Control and Prevention (CDC) publication Morbidity and Mortality Weekly Report (MMWR), the European Union's Eurosurveillance, and the World Health Organization's (WHO's) Weekly Epidemiological Record (WER) provides continuing sources of information on communicable diseases, and these are available free online. ProMed, a highly effective Harvard University-based website, is a frequently updated source of current infectious disease outbreaks around the world. The authors have also relied on electronic sources such as PubMed, the American Academy of Pediatrics, WHO, and United Nations Children's Fund (UNICEF) websites, as well as library-access journals. The references listed will augment the limited discussion possible in this text. A recommended standard reference text is Plotkin, Orenstein, and Offit's Vaccines, 5th edition (2008) .

Each disease has its own characteristic organism and natural history from onset to resolution. Many infectious diseases may remain at a presymptomatic or subclinical stage without progressing to clinical symptoms and signs, but may be transmissible to other people. Even a subclinical disease may cause an immunological effect, producing immunity. The drama of infectious disease is exemplified in the tragic event of the plague in the fourteenth century and its periodic recurrence, as in the epidemic of 1665 in London, described by Daniel Defoe (Box 4.1).

Organized public health emerged out of the sanitation movement of the mid-nineteenth century, which sought to reduce the environmental and social factors in communicable disease (Box 4.2). Traditionally, the prevention and control of communicable diseases have been accomplished by sanitation, safe water and food supply, isolation, and immunization.

The potential for infectious disease to disturb or destroy human life still exists today, especially in low-income countries, but can also pose serious challenges in the highincome countries. This threat may increase as infectious diseases evolve and escape current human-developed control mechanisms. The spread of the plague throughout Europe and Asia in the fourteenth century caused death and social destruction to an estimated one-third to half of the population of Europe, and is long embedded in the folk culture of the western world. The 1918 -1919 influenza pandemic may have affected one-third of the world's population; it was very severe and carried a case fatality rate of over 2.5 percent, particularly hitting young adults, resulting in between 50 and possibly as high as 100 million deaths, and killing more young men than died in World War I (Tautenberger, 2006) .

Other pandemics that have caused massive recurring devastation, such as smallpox, TB, syphilis, measles, cholera, and influenza, show the explosive potential and epidemic nature of infectious diseases. Some of these diseases have been brought under control and some may be eliminated as public health problems; however, new or recurrent communicable diseases continue to emerge. The spread of AIDS since the 1980s, ongoing cholera epidemics in Asia, Africa, and South America, diphtheria in the former Soviet Union in the 1990s, measles in Western Europe in 2010-2012, and diphtheria and pertussis in many western countries in 2011-2013, all remind us why communicable disease control remains one of the major responsibilities of public health.

The miasma theory (i.e., environment-host) and germ theory (microbiological agent-host) were bitterly contested by their proponents in the nineteenth century. Both have contributed to great achievements in the control of communicable disease in the first half of the twentieth century. The emergence of the germ theory in the late nineteenth century led to the sciences of bacteriology and immunology, growing out of the work of Jenner, Pasteur, Koch, Lister, and many others (see Chapter 1). The control of vaccine-preventable diseases (VPDs) has been a boon to humankind, saving countless lives and providing a cornerstone for public health. Despite this, millions of children still die annually from preventable or readily treatable diseases, such as respiratory infections, diarrheal diseases, and measles. Infectious diseases of childhood are still tragically undercontrolled internationally. Infectious diseases also undermine the health of other vulnerable groups in the population, such as the elderly, the socially and economically most disadvantaged, and the chronically ill, thereby playing a major role in the economics of health care.

Great strides have been made in the control of communicable diseases through public health successes in environmental sanitation, safe foods, vaccination, and antibiotics in the USA (Figure 4 .1), as in other industrialized countries. However, the field of infectious disease continues to be dynamic and challenging. Emerging infectious disease threats from new diseases not previously identified, such as HIV and SARS, and new variants of old diseases with resistance to current methods of treatment, together provide great challenges to public health. Increasing resistance to therapeutic agents augments the need for new strategies and coordination between public health and clinical services. Understanding the principles and methods of communicable disease control and eradication is important for all health providers and public health personnel.

An infectious disease may or may not be clinically manifested, and therefore it is possible for a person to carry the disease agent without having clinical illness. Acute infectious diseases are intense or short term, but may have longterm sequelae of great public health importance, such as poststreptococcal glomerulonephritis or rheumatic heart disease. Other infectious diseases are chronic with their own long-term effects, such as HIV infection or peptic ulcers. Infections may have both short-term and long-term morbidity, as with viral hepatitis infections. The importance of infectious disease prevention in a global context is shown in Box 4.3. The stages and context of infectious disease include: A modern example of the recurrence of an infectious disease is measles in 2010-2011 in Europe and continuing in Africa. Diseases once localized to specific parts of the world, such as Dengue, West Nile Fever, Lyme disease, Chikungunya, and Rift Valley Fever (RVF) , are emerging and spreading in locations far from their normal habitat, and in some cases these diseases may become endemic (Box 4.4) ; this means that after importation they may spread locally and become "resident" or endemic and transmit locally. 

Infectious diseases are a leading cause of illness and death throughout the world. The enormous diversity of microbes combined with their ability to evolve and adapt to changing populations, environments, practices, and technologies creates ongoing threats to health continually challenges our ability to prevent and control disease.

In low-income countries, the impact of infectious diseases is often devastating -decreasing survival rates, particularly among children, and impeding opportunities for economic growth and development. In more developed countries, infectious diseases also continue to significant health and economic concerns. In the USA, examples of major infectious disease challenges include human immunodeficiency virus (HIV), which continues to newly infect approximately 50,000 Americans (and millions globally) each year, healthcare-associated infections (HAIs), a leading preventable cause of death, chronic viral infections, causing cancers of the liver and cervix, and drug-resistant pathogens, a major cause of severe and untreatable infections. Additional concerns include the emergence of new diseases such as the novel 2009 H1N1 influenza virus, the resurgence of "old" diseases in new locations, and local and multistate outbreaks of foodborne diseases. Recent examples include a resurgence of local dengue fever in Florida, a resurgence of pertussis in California that sickened infants too young to be vaccinated, and an outbreak of diarrheal disease caused by Salmonella-infected eggs sold throughout the country. These disease problemsendemic, new, and resurgent -cause immense suffering and death and impose enormous financial burdens on society.

CDC's Framework for Preventing Infectious Diseases: Sustaining the Essentials and Innovating for the Future was developed to provide a roadmap for improving our ability to prevent known infectious diseases and to recognize and control rare, highly dangerous, and newly emerging threats, through a strengthened, adaptable, and multi-purpose US public health system.

for the future. Atlanta, GA: CDC; . Available at: http://www.cdc.gov/ oid/framework.html [Accessed 18 January 2013 .

The host-agent-environment triad, discussed in Chapter 2, is fundamental to the success of understanding the transmission of infectious diseases and their control, including wellknown diseases, those changing their patterns, and those newly emerging or escaping current methods of control. Infection occurs when the organism successfully invades the host's body, where it multiplies and produces an illness.

Hosts are people, or other living animals, including birds and arthropods, which provide a place for growth and sustenance to an infectious agent under natural conditions. Some organisms, such as protozoa or helminths, may pass through successive stages of their life cycle in different hosts, but the definitive host is the one in which the organism passes its sexual stage. The 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, such as in socially deprived and undernourished populations or among immunocompromised people who are vulnerable to the spread and development of the disease. A disease may be present in an infected person in a dormant form, such as TB, or a preclinical stage, such as poliomyelitis (polio) or HIV, without clinical paralytic disease in the case of polio or before clinical AIDS appears in the case of 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. Virulence describes the severity of clinical disease and may vary among serotypes or strains of the same agent. 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. Reservoirs may be in people, animals, arthropods, avians, reptiles, 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. A fomite is an inanimate object contaminated with infectious material which may transmit disease, such as improperly sanitized medical equipment.

Contacts are people or animals that have been in some form of association with an infected person, animal, fomite, or environment that may provide a risk for acquiring and transmitting the infective agent. People 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 unapparent infection (a healthy carrier) or may be in the incubation or convalescent stage of the infection.

The emergence of health facility-acquired infections, often from catheters or other invasive devices, has become a major issue in all health systems with multidrug-resistant (MDR) organisms. Infection control and isolation techniques are vital to control such infections, which in individual patients cause overwhelming complications and in multiple patients can spread in epidemic form, such as in nurseries, nursing homes, or even in well-respected hospitals.

Communicable diseases may be classified by a variety of methods: by clinical syndrome, mode of transmission, methods of prevention (e.g., vaccine preventable), or by major organism classification, that is, viral, bacterial, fungal, 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 living cell. The capsid may have a protective lipid-containing envelope. The capsid and envelope facilitate attachment and penetration into host cells, and often contain virulence factors. Inside the host cell, the nucleic acid molecule utilizes cellular proteins and processes for virus replication. Prions -discovered in recent years (Stanley Prusiner, Nobel Prize 1997) -are proteins, which can induce disease. As infectious agents, prions cause a number of degenerative central nervous system (CNS) diseases, including spongiform encephalopathy in livestock (mad cow disease and scrapie in sheep) and humans [variant Creutzfeldt-Jakob Disease (vCJD) ].

Bacteria are unicellular organisms that reproduce sexually or asexually and can exist in an environment with oxygen (aerobic) or in a situation 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 have a nucleus of chromosomal DNA material within a membrane surrounded by cytoplasm, itself usually enclosed by a cellular membrane. Bacteria are classified by morphology and growth conditions, including coloration under Gram stain (Gram-negative or Gram-positive), microscopic morphology, immunological (antigen) or molecular (DNA) markers, or by the diseases they may cause. 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).

Mycoses are infections caused by molds and yeasts. Clinical manifestations of fungal disease range from relatively mild superficial infection to systemic, life-threatening conditions. Immunocompromised individuals are at elevated risk. Cryptococcus, Candida, Aspergillus, and Mucor molds or fungi are among the leading causes of morbidity in HIV-positive patients and among immunosuppressed populations, such as those receiving chemotherapy and radiation for cancer treatment. Pneumocystis jiroveci (formerly P. carinii), once thought to be a protozoan, is now classified a fungus, based on genetic analysis. Common dermatophytic infections, known as tinea, are caused by fungi invading the hair, skin, or nails, and they occur in nearly all living organisms. A case report on contaminated drugs used for treating neurological conditions leading to a fungal meningitis outbreak in the USA in 2012 is reported in Chapter 15, including index case follow-up and epidemic investigation.

Parasitology studies protozoa, helminths, and arthropods that live within, on, or at the expense of a host. Protozoa include oxygen-producing, unicellular organisms such as the flagellates Giardia and Trichomonas, and amoebae such as Entamoeba, in enteric and gynecological disorders. Sporozoa are parasites with complex life cycles in different hosts, such as Cryptosporidium or malarial parasites. Helminths are worms that infest humans, especially in places with poor sanitation and tropical areas. Arthropods, the most numerous of animal species, include lice, fleas, sandflies, blackflies, and ticks, and they serve as important disease vectors. Arthropods can live on the body's surface (ectoparasites) and transmit bacterial, viral, rickettsial, and other diseases. They are also capable of fecal-oral transmission, for instance, in cases of Shigella and Escherichia coli, in or via biological effects within the host such as in malaria. This group constitutes among the most important public health threats globally and their control is a continuing public health challenge.

Transmission of diseases occurs via the spread of an infectious agent from a source or reservoir to a person (Table 4 .1). Direct transmission from one host to another occurs during touching, biting, kissing, sexual intercourse, projection via droplets, as in sneezing, coughing, or spitting, or by entry through the skin. Indirect transmission includes aerosols of long-lasting suspended particles in air; this can be central among passengers on an aircraft being exposed to a TB patient or a measles carrier. Fecal-oral transmission such as foodborne and waterborne can occur easily, as well as by poor hygienic conditions with fomites, such as soiled clothes, handkerchiefs, toys, or other objects. Waterborne and foodborne diseases are still among the most common causes of death, particularly of children in low-income countries with poor infrastructure for water and sewage management. This situation is exacerbated by crowded and unhygienic housing and by the effects of poverty on sanitation, nutrition, and access to health care. Transmission in medical settings is common, yet preventable by hand washing and consistent use of sterile techniques and cleaning procedures. The use of face masks, hand washing, gloves, gowns, and tissues when sneezing are all vital in implementing practices to reduce the spread of hospital-acquired infections and influenza. Promoting these simple measures is of utmost importance as hospital-acquired infections represent a major cause of morbidity and result in extended hospital stay, thus significantly elevating economic costs. Sterile practices among health care and hospital workers should certainly be made a priority. The use of bed nets and vector control for malaria are among the most effective ways of reducing the burden of this highly dangerous disease.

Vectorborne 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 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 Shigella on the legs of a housefly.

Airborne transmission occurs indirectly via infective organisms in small aerosols that may remain suspended for long periods and which easily enter the respiratory tract. Viruses such as influenza, the common cold, and measles can be transmitted in this way. 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), or during delivery (as in gonorrhea) or breastfeeding (e.g., HIV), with transfer of infectious agents from mother to fetus or newborn.

Many types of invasive devices and procedures are used to treat patients in hospitals, long-term care facilities, and surgical centers, and in the community. Healthcare-associated infections (HAIs) are complications with devices including catheters, ventilators, central venous lines causing bloodstream infections, catheter-associated urinary tract infections, and ventilator-associated pneumonia, together accounting for roughly two-thirds of all HAIs, or at surgery sites. Clostridium difficile can cause gastrointestinal infection; patients can be exposed to this bacterium through contaminated surfaces or the spores can be transferred from other people's unclean hands. Methicillin-resistant Staphylococcus aureus (MRSA) is a widespread skin contaminant especially of concern in hospitals. CDC monitors and promotes preventive procedures as these infections are an important threat to patient safety (CDC, 2012) .

Resistance to infectious diseases is related to many host and environmental factors, including age, gender, pregnancy, nutrition, trauma, fatigue, living and socioeconomic conditions, and emotional status. Good nutritional status has a protective effect and bolsters immune competency. Vitamin A supplements reduce complication rates of measles and enteric infections. TB may be present in an individual person whose resistance is sufficient to prevent clinical disease, but the infected person (with or without symptoms) may be a carrier of an organism which can be transmitted to another or cause clinical disease if the person's susceptibility is reduced (Box 4.5).

The body is protected by physical barriers, e.g., skin and stomach acidity, against the entry of foreign organisms. The body also has passive immunity and acquired immunity both cellular and in humoral components of blood. Immunity is the means by which the body recognizes and resists infection resulting from the presence of specific foreign antigens on the surface of bacteria, viruses, fungi, or other toxins, chemicals, drugs or foreign objects, e.g., a splinter, which may be harmful. The immune system recognizes and acts to destroy or contain the dangerous agent. Humoral (blood) immunity is activated by B lymphocytes, which produce antibodies, complement proteins, or cells that act on the microorganism associated with a specific disease, toxin, or foreign body. The body also reacts to infective antigens with cellular responses, including those that directly defend against invading organisms and other cells which produce antibodies. T lymphocytes attack antigens directly and assist with chemicals controlling the immune response (cytokines). Inflammation attracts white cells (macrophages and neutrophils) which act as phagocytes to kill germs and dead or damaged cells. l Infectious agent -a pathogenic organism (e.g., virus, bacterium, rickettsia, fungus, protozoa, helminth, pollen, or chemical) is one capable of producing infection or an infectious disease in humans, animals, and plants.

l Infection -the process of entry, development, and proliferation of an infectious agent in the body tissue of a living organism overcoming the host's defense mechanisms, resulting in a non-apparent or clinically manifest disease.

Immunity can be acquired by response to an organism or its antigenic components which, when introduced into a person's body, produce a natural protective immunity. Passive immunity is temporary, by the passage of preformed antibody from mother to infant via the placenta and breast milk, or by injection of preformed immunoglobulins. Active immunization introduces effective killed or attenuated organisms, or parts of organisms as antigens into the body, which responds by producing antibodies. This enables public health systems to prevent millions of deaths from communicable disease and provides hope for more success in the future as the sciences of microbiology, vaccinology, and public health practice advance.

Surveillance of disease is the continuous scrutiny of all aspects of the occurrence and spread of a 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 elements listed in Box 4.6.

Epidemiological monitoring based on individual and aggregated reports of infectious diseases provide data vital to planning interventions at the community level or for individual patients, 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 another location that will provide a "finger on the pulse" to assess suspicious changes 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 typing, for vaccine planning, production, and distribution. Epidemiological 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 is vital in order to promote involvement and improved quality of data, as well as to allow evaluation of local situations 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 and academic settings for further research and analysis.

Notifiable diseases are those that a physician is legally required to report to state or local public health officials. Notification is mandatory because of the degree of contagiousness, severity, frequency, or other public health importance of these diseases (Table 4 .2). Public health laboratory services provide validation of clinical and epidemiological reports. They also provide 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. Reference laboratories are specialized central facilities usually operated by the public health at higher levels of government (i.e., state or federal). They enable public health authorities to monitor and validate the work of other laboratories and may be assisted by specialized faculties in teaching centers. With newly emerging diseases capable of spreading far from their previously known habitat, and the threats of pandemics such as SARS and, of greater concern, avian influenza, surveillance for human and animal disease is crucial to the societies we live in, including the global society. The first diagnosis of a strange new disease entity may lead to its identification and practical measures to halt its spread. When signs point to anticipated or surprise epidemics and pandemics, and when the real threat of bioterrorism emerges, multisectoral preparation and training are of utmost importance.

Healthcare-associated infections (HAIs) are among the leading communicable and preventable causes of morbidity and mortality throughout the world. Nosocomial infections are those wherein a patient is exposed to and contracts disease while hospitalized or in another care facility. While great strides have been made in hospital sanitation, HAI still occurs in as many as 10 percent of admissions in developed countries. Recent CDC estimates place the number of nosocomial infections in the USA for 2002 at 1.7 million, a higher incidence than any notifiable disease. With a case mortality of nearly 6 percent, HAIs are also among the most deadly. Although progress has been made in HAI prevention, the organisms implicated are becoming resistant to conventional therapy.

MRSA is among the most virulent and treatment-resistant bacteria, now accounting for over 50 percent of wound infections in many hospitals. Rare reports of vancomycin-resistant Staphylococcus aureus (VRSA) cause alarm, proving that antibiotic resistance has transferred from other species. Treatment options for VRSA and vancomycin-resistant Enterococcus species are extremely limited, with major concern that these organisms could spread or become resistant to the few known effective therapies. The increasing number of immunodeficient patients has increased the importance of prevention of nosocomial infections (Box 4.7).

Where standards of infection control are deficient or lacking in both developed and developing countries, hospital patients and staff are vulnerable to serious infection. Of note, TB and hepatitis B exposure is common among health care workers, but preventable through airborne precautions and vaccination, respectively. In developing countries, deadly emerging viruses, such as avian influenza H5N1 and Ebola viruses, infect nursing, medical, and other staff as secondary cases.

A great obstacle in quantifying the impact of HAI is the lack of uniform and clear case definitions, as well as reliance, in most countries, on voluntary reporting by institutions. While many recommendations have been made, notably by the Society for Healthcare Epidemiology of America, no uniform regulations have been established to mandate reporting of HAIs. However, much work has been focused on prevention. Standard Precautions (formerly known as Universal Precautions) are a set of basic practices by which health care workers may reduce the spread of nosocomial infection among patients, visitors, and staff, as well as protect health workers from occupationally acquired disease. These include adequate hand-washing hygiene and use of protective barriers suited to specific risks. Expanded precautions and mandatory use of organism-specific clinical guidelines are necessary procedures in many health care institutions as protective measures.

The 2007 CDC and Healthcare Infection Control Practices Advisory Committee (HICPAC) guidelines provide recommendations applicable to all settings. In 2011 the CDC published evidence-based guidelines for minimum prevention expectations for safe ambulatory care settings. Organizational policy must be established for each institution by an integrated and authoritative department of infection control and epidemiology (CDC Guide to Infection Prevention, 2011) .

In the USA, approximately one out of every 20 hospitalized patients will contract an HAI. Costs of HAI to US hospitals range from US$28.4 to US$45 billion (2007 dollars). With 20 percent of infections preventable, potential cost savings range from an estimated low of US$5.7 to US$6.8 billion annually; with 70 percent of infections preventable, cost savings range from US$25.0 to US$31.5 billion (CDC 2009 and Public Health Reports 2007) .

As illustrated, the cost of nosocomial infections serves as a major consideration in planning health budgets. Reducing the risk of HAIs justifies substantial expenditure for hospital epidemiology and infection control activities. With the diagnosis-related group (DRG) payment system for hospital care (classified by diagnosis rather than by days of stay), the effective manager has a major incentive to minimize the risk of nosocomial infections to improve patient care. Infections can greatly prolong hospital stay, increasing serious complications, patient dissatisfaction, and health care costs.

The US Agency for Healthcare Research and Quality patient safety program initiated a program to reduce central line-associated bloodstream infections (CLABSIs) in newborns. CLABSIs are health care-associated infections of central vein or artery catheters, especially in premature low birth-weight babies. These catheters may be in place for long periods to provide fluids, nutrients, and medications, but they are readily subject to infections that seriously harm or kill infants or adults.

Neonatal intensive care units (NICUs) participating in this project included 100 NICUs in nine states caring for 8400 newborns. The project was to improve the safety of procedures of care of these infants with intravenous bloodstream infections, adopting safe practices and guidelines provided by the CDC. As a result, the program reduced in-hospital infections by 58 percent in less than a year and relied on the program's prevention practice checklists and better communication to prevent an estimated 131 infections and up to 41 deaths and to avoid more than US$2 million in health care costs (AHQR, 2013) .

Patient safety and prevention of infections are longstanding issues in health care, going back to Florence Nightingale at Scutari Hospital in the Crimea, Ignaz Semmelweiss in Vienna, and Joseph Lister in Glasgow in the nineteenth century (see Chapter 1), but they remain vital issues in health care management economics and epidemiology.

An endemic disease is the continuous usual presence of a disease or infectious agent in a given geographic area or population group. Hyperendemic means 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 takes place in a community or region when the occurrence of a number of cases of an illness is in excess of the usual or expected number of cases, or health-related behaviors (e.g., smoking) or events (e.g., road traffic injuries). The number of cases constituting an epidemic varies with the disease. A number of 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. Therefore, it is a public health emergency, as one clinical case may represent as many as 1000 carriers with non-paralytic or subclinical polio. If two to three or more cases of any unusual disease locally are linked in time and place, this may be considered sufficient evidence of transmission and presumed to be an epidemic. Moreover, a pandemic refers to the occurrence of a disease on a wide scale over an expansive area, crossing international boundaries and affecting a large proportion of the world.

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, person and potential common source is 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. It 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 followup (secondary) cases occurred, as well as how the disease was transmitted. Samples are taken from index case patients (e.g., blood, feces, throat swabs) as well as from possible reservoirs (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 sources or risk factors, such as food, water, contact, and environment, and drawing a timeline of cases to define the epidemic curve.

The number of individuals who are ill (the numerator) and the population at risk (the denominator) establish the attack rate; namely, the percentage of sick among those exposed to the common factor or common source. Questions arise to determine 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 biological and epidemiological 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, to document and distribute reports, and to respond to the public's right 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. The term "epidemiological investigation" means a broad review of all evidence related to a topic, not just one epidemic or outbreak. Epidemiological investigations have defined many public health problems. Steps in epidemiological investigation are shown in Box 4.8. Rubella syndrome, Legionnaire's disease, AIDS, Lyme disease, 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 CDC, originally organized in 1946 as the Office for Malaria Control in War Areas, is part of the US Public Health Service. As of 1993, the CDC had a budget of US$1.5 billion, and its 7300 employees included epidemiologists, microbiologists, and many other professionals. By 2007, the CDC budget had reached US$9 billion, employing 8467 individuals. 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. Recently, however, budget reductions have imposed limits of capacity in such areas as overseas work. In 2010, the budget reached nearly US$10.9 billion, and CDC employed over 14,000 people in 2011.

The key increases for 2012 were support for the prevention and control of infectious diseases [HIV/AIDS, other sexually transmitted infections (STIs), global polio eradication, Strategic National Stockpile] and chronic disease prevention and health promotion (CDC, 2011) .

The Epidemic Intelligence Service (EIS) of the CDC in the USA is an excellent model for the organization of the national control of communicable diseases. Clinicians are trained to carry out epidemiological 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 a personal computer program to support field epidemiology, including epidemic investigations (EPI-INFO). It can be accessed and downloaded free of charge from the Internet. 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.

Any unusual increase in disease incidence should be investigated. The intensity and effort of the investigation are dependent on the severity of the disease, the number of people affected, the potential for the disease to spread, and the effectiveness of available countermeasures. The fundamental objective of syndromic surveillance is to identify illness clusters early, before diagnoses are confirmed and reported to public health agencies, and to mobilize a rapid response, thereby reducing morbidity and mortality. Epidemic curves for people with earliest symptom onset and those with severe illness can be depicted graphically.

Public health surveillance systems for early outbreak detection include early warning systems, prodrome surveillance, outbreak detection systems, information system-based sentinel surveillance, biosurveillance systems, health indicator surveillance, and symptom-based surveillance. The term "syndromic surveillance" is generally used and meant for early detection of potentially serious events such as terrorism with biological or chemical agents (Pavlin, 2003; Henning, 2004) . A 2012 epidemiological event of an outbreak of fungal meningitis due to contaminated medication used for back pain relief (see Chapter 15) was detected by an alert clinician and followed by traditional "shoe leather epidemiology" and by syndrome surveillance with rapid conclusions, withdrawal of the offending drug mix, and onsite investigation, followed by legal action (CDC, 2013) .

The CDC's epidemiological data are published in the excellent Morbidity and Mortality Weekly Report (MMWR), which contains articles on diseases of current interest and may be subscribed to as a free resource available from the Internet. The publication includes special summaries of reportable infectious diseases as well as NCDs of epidemiological interest, comprehensive reviews of the literature, and recent investigative work by the CDC and other reputable health organizations. In 1999, MMWR published a review of "Ten great achievements of public health in the United States in the twentieth century", which included control of communicable disease and VPDs, as well as improvements in public health organization, occupational health, maternal and child health, motor vehicle accidents, tobacco control, reduction in cardiovascular disease mortality and motor vehicle deaths and injuries, and fluoridation of community water supplies (see Chapter 2). In 2011, MMWR published a special report on advances in the first decade of the twenty-first century in the USA and one on advances in public health globally.

An infectious disease is an event affecting an individual; however, it is transmissible to others, and therefore infection control requires both individual and community measures. Control of a disease comprises 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 a halt in the circulation of the organism. Eradication of a disease is the reduction to zero of naturally occurring incidence, 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, including activities ranging from filtration and disinfection of community drinking water to environmental vector control, pasteurization of milk, and immunization programs (Table 4 .3). No less important are organized programs to promote self-protection, case finding, and effective treatment of infections to stop their spread to other susceptible people (e.g., HIV, STIs, TB, and 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. Bactericidal drugs such as penicillin act to kill pathogenic organisms. Traditional medical emphasis on single antibiotics has changed to the use of multiple drug combinations for tuberculosis (TB) 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. Widescale use of antibiotics has led to increasing incidence of resistant organisms. Multidrug resistance constitutes one of the major public health challenges in the twenty-first century.

Antiviral agents (e.g., ribavirin) are important additions to medical treatment potential, as are "cocktails" of antiviral agents for the management of HIV infection, known as highly active antiretroviral treatment (HAART). Prudent antibiotic use requires the attention of clinicians and their teachers as well as the public health community and health care managers, representing the interaction of health issues across a broad spectrum of services.

Organized public health services are responsible for advocating legislation and for regulating and monitoring programs to prevent infectious disease occurrence and transmission. 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 management. It promotes compliance and community support of preventive measures, including personal hygiene and safe handling of water, milk, and food supplies. Health education is the major method of prevention of STIs. Each of the infectious diseases or classifications of infectious diseases has one or more preventive or control 

Vaccination -pre-exposure to protect individuals and the community (herd immunity); post-exposure for individual protection (e.g., for rabies following animal bite, or contact after exposure to measles cases); or immunization of animals to prevent infected meat or milk transfer of disease to humans (e.g., brucellosis) approaches (Table 4 .3). These may involve the coordinated intervention of different disciplines and modalities, including epidemiological monitoring, laboratory confirmation, environmental measures, immunization, and health education, all of which require teamwork and organized collaboration. Remarkable progress has been made in infectious disease control by clinical, public health, and societal measures since 1900 in the industrialized countries, and since the 1970s in the developing world. This progress 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 VPDs. Despite the great advances, major challenges persist, such as TB, STIs, malaria, HIV, child mortality from respiratory infections and diarrheal diseases, an increase in MDR organisms, and the rise of NCDs in low-and medium-income countries.

Vaccines are one of the most important and indispensable tools of public health in the control of infectious diseases, particularly for child health. VPDs are diseases preventable by currently available vaccines (Table 4 .4). The term vaccine is derived from the use of cowpox (vaccinia virus) to stimulate immunity to smallpox, first demonstrated by Jenner in 1796 (see Chapter 1), and is generally used for all immunizing agents.

According to the trend tables published by the CDC's Health United States, 2010, since 2000 there have been no reported cases of polio in the USA. While the table (Table 4 .5) illustrates zero cases for the years prior to 2000, it represents the number of new cases per 100,000 population; the rate is greater than zero but less than 0.005, and there have been too few cases to count. Thus, in 2000 and the years after, no polio cases have been documented, and since 1950, the incidence has continuously declined each year. The success of the polio vaccine is indicative of what can be achieved with the implementation of a comprehensive program.

As discussed above, the body responds to invasion by disease-causing organisms by antigen-antibody reactions and cellular responses. Together, these act to restrain or destroy the disease-causing potential. Strengthening this defense mechanism is possible through immunization. Vaccines are suspensions of live or killed microorganisms or the antigenic portion of those agents presented to a potential host to induce immunity to prevent the specific disease caused by that organism. The preparation of vaccines uses different techniques, as seen in Box 4.9.

The process of immunization (vaccination) increases host resistance to specific microorganisms to prevent them from causing disease. Doing so induces primary and secondary responses in the human or animal body: l Primary response -occurs on first exposure to an antigen. After a lag or latent period of 3-14 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.

l Secondary (booster) response -the response to a second and subsequent exposure to an antigen. This lag period is shorter than the primary response, with the peak being higher and lasting 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. Booster doses of vaccines are used to activate memory cells to strengthen immunity. l Immunological 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.

Thus, immunization protects susceptible individuals from communicable disease by administration of a living modified agent, a subunit of the agent, a suspension of killed organisms, or an inactivated toxin (Box 4.9) to stimulate development of antibodies to that agent. In disease control, individual immunity may also protect another individual. l Herd immunity -occurs when sufficient numbers of people are protected (naturally or by immunization) against a specific infectious disease, reducing circulation of the organism, and thereby lowering the chance of an unprotected person becoming infected. Each pathogen has BOX 4.9 Immunizing Agents and Processes l Live attenuated organisms -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. Examples: polio (Sabin), measles, rubella, mumps, yellow fever, BCG, typhoid, plague. l Inactivated or killed organisms -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. Examples: polio (Salk), influenza, rabies, Japanese encephalitis. l Cellular fractions -usually of a polysaccharide fraction of the cell wall of a disease-causing organism. Examples: pneumococcal pneumonia, meningococcal meningitis. l 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. l Toxoids or antisera -modified toxins are made non-toxic to stimulate formation of an antitoxin. Examples: tetanus, diphtheria, botulism, gas gangrene. l Immune globulins -antibody-containing solutions derived from immunized animals or human blood plasma, used primarily for short-term passive immunization, e.g., rabies, IgG globulin for immunocompromised people. Antitoxin -an antibody derived from serum of animals after stimulation with specific antigens and used to provide passive immunity. Examples: tetanus, snake and scorpion venom. different characteristics of infectivity, and therefore different levels of herd immunity are required to protect the non-immune individual who may not have been immunized or who is immunocompromised, or whose immunity from vaccination may have waned.

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 80 percent 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 95 percent is required in order to achieve local eradication.

Immunization coverage in a community must be monitored 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 people in the target group immunized at a specific age, and the denominator is the number of people in the target cohort who should have been immunized according to the accepted standard: Immunization coverage in the USA is regularly monitored by the National Immunization Survey, a telephonebased questionnaire of households from all 50 states, as well as selected areas at high risk for inadequate levels of vaccination. An initial telephone survey is followed by confirmation, where possible, from documentation from the parents or health care providers. The childhood immunization survey for 2006, for instance, examined children aged 19-35 months. The results reveal 85 percent of US children having received four or more (4+) doses of diphtheria-tetanusacellular pertussis (DTaP), 93 percent with three or more (3+) doses of oral or injected polio vaccine, and 93 percent with three or more (3+) doses of Haemophilus influenzae type b (Hib). Hepatitis B coverage (3+) greatly increased to 93 percent, while institution of pneumococcal (3+) and varicella (1+) vaccination policies has rapidly achieved 87 percent and 89 percent, respectively. Despite these gains, only 77 percent of children received all vaccinations at the recommended ages.

Present technology allows for control or eradication of important infectious diseases that still cause millions of deaths globally each year. Other important infectious diseases are still not subject to vaccine control owing to difficulties in their development. In some cases, a microorganism can mutate with changes. Viruses can undergo antigenic shifts in their molecular structure, 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, and is responsible for frequent epidemics. Antigenic shift is believed to explain the occurrence of new strains of influenza virus, necessitating annual reformulation of the influenza vaccine. New variants of poliovirus strains are similar enough to three main types that immunity to one strain is carried over to the new strain. Molecular epidemiology is a powerful genetic technique used to determine geographic origin, permitting tracking of the spread of infectious organisms and epidemics.

The trend for increasing the number of vaccines included in a "cocktail" of vaccines (i.e., combination of more than one vaccine) has many advantages in lowering costs and reducing the number of visits and injections, thus increasing convenience and compliance by the public. There are virtually no contraindications to the use of multiple antigens simultaneously. Examples of vaccine cocktails include DTaP in combinations with Hib, polio, varicella, or measles-mumps-rubella (MMR) vaccines. The term DTaP is used for the combination which includes acellular pertussis vaccine. It is more expensive but with reduced complications and is used in the USA and other high-income countries (see website material).

Interventions in the form of effective vaccination save millions of lives each year and immunization coverage contributes to the improved health of countless children and adults globally. Vaccination is 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 major diseases such as malaria and HIV. Molecular technology, producing recombinant vaccines, such as those for hepatitis A and B, holds promise for important vaccine breakthroughs in the decades ahead.

The introduction of new vaccines such as for rotavirus and its potential to reduce child morbidity and mortality is an ongoing challenge pertaining to strengthening immunization programs and prioritizing effective strategies. It is especially difficult for low-income countries to meet the vaccine targets and Millennium Development Goals (MDGs), particularly in the area of reducing child mortality.

CDC reports indicate that worldwide, vaccination prevents over 2 million childhood deaths from VPDs each year (2004 estimate). Globally, over 130 million children are born annually, all needing immunization. Annual routine immunization coverage levels included 83 percent of the world's children for three doses of diphtheria-tetanuspertussis vaccine (DTP3) in 2012, as compared with 20% in 1980 and 73% in 2000 respectively); in 2012, 84 percent had a least one dose of a measles-containing vaccine. However, this means that approximately 27 million infants remained unvaccinated. Hepatitis B coverage in 2012 was 79 percent and Hib vaccine coverage 45 percent.

Further data indicate that one in six children is not vaccinated against TB. Globally, 79 percent of infants receive the complete dose of hepatitis B immunizations, and only 45 percent are vaccinated against Hib disease. Thus, the remaining infants are left unprotected from serious diseases (WHO, 2013) .

The negative impact and the problems that ensue owing to these significant gaps in immunization are tremendous. In 2004, approximately 1.4 million children under 5 years old died from the six major VPDs; an additional 1.1 million succumbed to pneumococcal disease and rotavirus and consequently died. The vaccines protecting against these two diseases are available and accessible in the USA but rarely administered in developing countries. While some medical issues may be inevitable (such as genetic disorders), VPDs are preventable; thus, these deaths and serious morbidities could have, and should have, been averted.

Since 1991, polio eradication and measles elimination programs have received significant financial and professional support from the CDC. CDC's annual investment dedicated to global immunization has increased from slightly over US$3 million to US$140 million in 2006. A US federal agency, the CDC has substantially expanded its influence in the area of global immunization. It plays a key role in the establishment and initiation of instrumental vaccine initiatives, such as the Global Immunization Vision and Strategy for 2006-2015 (GIVS) and the Global Alliance for Vaccines and Immunization (GAVI). Moreover, the CDC supports the research, development, and evaluation needed to create new vaccines, particularly those required to protect against HIV, TB, and malaria, the greatest causes of mortality in developing countries.

In the developing countries, immunization averts some 3 million child deaths each year. Internationally, substantial progress was made in controlling VPDs in the 1980s. Towards the end of the 1970s, fewer than 10 percent of children worldwide were receiving immunizations. Collaboration between the WHO, UNICEF and other international bodies allowed for the promotion of the Expanded Programme on Immunization (EPI) and the target of Changes in coverage varied by geographic region, and the overall increase mainly was attributed to improvements in vaccination coverage in the African (+16 percent), Eastern Mediterranean (+12 percent), and Western Pacific (+10 percent) WHO regions.

National DTP3 coverage of at least 90 percent was reported by 122 countries (63 percent), but only 48 (25 percent) reported 80 percent coverage or higher in all districts, and only 55 percent of low-income countries are on track to achieve 90 percent coverage by 2015 (UNICEF, unpublished data, 2010) . During 2007 During -2009 countries (77 percent) had sustained DTP3 coverage of 80 percent or higher. However, coverage in 2009 was less than 80 percent in 36 countries (19 percent), and six countries failed to achieve even 50 percent DTP3 coverage. Globally, 23.2 million children worldwide did not receive three doses of DTP vaccine during the first year of life in 2009; 70 percent live in 10 countries and approximately half live in India (37 percent) and Nigeria (14 percent).

From 2000 to 2012, estimated global measles-containing vaccine (MCV1) coverage increased from 71 to 84 percent, and 136 countries (70 percent) added a second MCV dose to their routine vaccination schedules. Three-dose coverage with hepatitis B vaccine (HepB3) increased from 30 to 79 percent during this period, and three-dose coverage with Hib vaccine (Hib3) increased from 13 to 45 percent.

In countries where Hib vaccine had been introduced, Hib3 coverage was similar to DTP3 coverage; however, an increase in global coverage did not occur because several large countries (e.g., China, India, Indonesia, and Nigeria) had not yet introduced Hib vaccine. Global immunization coverage has increased in all WHO member states (Figures 4.2 and 4.3) .

While the three-dose Hib vaccine reached 90 percent of those residing in the Americas, coverage was much lower in the European Region (44 percent). Even lower and more disappointing was the 24 percent uptake in the African Region of the WHO. A more positive outcome demonstrates international increases in coverage of other vaccines.

Bacille Calmette-Guérin (BCG) uptake rose from 31 to 89 percent and polio with oral poliomyelitis vaccine (OPV, three doses) increased from 24 to 85 percent. Furthermore, tetanus toxoid vaccine coverage among pregnant women rose from 14 to 57 percent. Despite this, recent drops in uptake have taken place in many countries, most notable in Sudan, Myanmar (Burma), and other areas struggling with violent conflicts.

The number of global polio cases has been reduced by more than 99.8 percent since 1988, including the prevention of 5 million cases of paralysis and of more than 250,000 deaths. This reduction in cases is a remarkable achievement of many agencies (WHO, UNICEF, GAVI, AID, CDC, Rotary International, and many others). By 2010, only four countries remain endemic for polio, the 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 Year With technical support from the WHO, UNICEF, CDC, and other partners, global immunization coverage for DTP3 has increased from 20 percent in 1980 to 82 percent in 2009.

The challenge remains to achieve control or eradication of VPDs, thus saving millions more lives. Part of Health for All (HFA) stresses the EPI approach, which includes immunization against diphtheria, pertussis, tetanus, polio, measles, and TB. In 2009, of the 23.2 million children who did not receive three doses of DTP vaccine during the first year of life, 70 percent lived in 10 countries, with approximately half residing in India (37 percent) and Nigeria (14 percent). A further challenge in eradicating VPDs is overcoming the efforts of segments of the population who are averse to immunization due to transitory side-effects or immunization as a perceived cause of other morbidity (Box 4.10).

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 the international eradication of smallpox has been followed with major progress towards the eradication of polio, measles, and other important infectious diseases.

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. Most typically transmitted via respiratory droplets, it has an incubation period of 2-5 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 1980s, an outbreak of diphtheria occurred in the countries of the former Soviet Union among people over the age of 15. It reached epidemic proportions in the 1990s, with 140,000 cases (1991) (1992) (1993) (1994) (1995) , and 1100 deaths in 1994 in Russia alone. This indicates a failure of the vaccination program in several respects: it used only three doses of DTP or DTaP for infants, no boosters were given at school age or subsequently, the efficacy of diphtheria vaccine may have been low, and coverage was below 80 percent. Efforts to control the epidemic included mass vaccination campaigns for people over 3 years of age with a single dose of DT (diphtheria and tetanus) and increasing coverage of routine DTP vaccines to four doses by the age of 2 years. The epidemic and its control measures have led to improved coverage with DT for those over 18 years, and 93 percent coverage among children aged 12-23 months. By 2010 coverage in Russia reached 97-98 percent.

The WHO recommends three doses of DTP in the first year of life and a booster at primary school entry, as well as at enrollment at college, military, or other organized settings. This is considered by many to be insufficient to produce long-lasting immunity. The USA and other industrialized countries use a four-dose schedule and recommend periodic boosters with DT for adults.

Pertussis is an acute bacterial disease of the respiratory tract caused by the bacillus Bordetella pertussis. After an initial cold-like (catarrhal) stage, the patient develops a severe cough which comes in spasms (paroxysms). The disease can last for 1-2 months. The paroxysms can become violent and may be followed by a characteristic crowing or highpitched inspiratory whooping sound, followed by expulsion of tenacious clear sputum, often followed by vomiting. In poorly immunized populations and malnourished people, pneumonia often follows, and death is common.

Pertussis declined dramatically in the industrialized countries as a result of widespread coverage with DTP. However, because the pertussis component of early vaccines caused rare reactions, many physicians and parents avoided its use, instead opting for DT alone and leaving children susceptible to infection. During the 1970s in the UK, many physicians recommended against vaccination with DTP. As a result, pertussis incidence increased, with substantial mortality rates. This led to a reappraisal of the immunization program, with institution of incentive payments to general practitioners for completion of vaccination schedules. As a result of these 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 Year Coverage (%) measures, vaccination coverage, with resulting pertussis control, improved dramatically in the UK. A new acellular vaccine is now in 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.

The new vaccine is used in the USA and other industrialized countries, and forms part of the US recommended vaccination schedule. Although most Western European countries are advanced in the use of vaccines, there is no Europe-wide equivalent of the CDC-recommended immunization schedule for the region, which will be coming up for discussion in European Union (EU) health forums. The CDC reports that estimates of childhood vaccination coverage in the USA with at least doses of pertussis-containing vaccine have exceeded 90 percent since 1993. However, reported pertussis cases increased from a historic low of 1010 cases in 1976 to 11,647 in 2003, with a substantial increase in reported cases among adolescents, who become susceptible to pertussis approximately 6-10 years after their childhood vaccination. This increase is attributed to waning immunity and lack of booster doses. Although vaccination is recognized as one of the 10 great achievements of public health of the twentieth century, ever since its origins with Jenner's work in 1796, anti-vaccination movements have been active in opposing this indispensible, life-saving tool. This was highlighted in the mid-nineteenth century by anti-vaccination leagues.

Opposition centered on provocative fears of the inefficiency of vaccines, their side-effects, or the principle that the state is interfering with individual freedoms by promoting or mandating vaccination. Opposition was in part promoted by doctors who made good fees from variolation, i.e., passing actual smallpox to young children to give immunity, a dangerous procedure. In Britain and the USA various acts mandating smallpox vaccination in the nineteenth century were bitterly opposed, and modifications of laws allowed for conscientious objectors to opt out of the required immunization.

In the late twentieth century this took on a new form when objections to pertussis vaccine became frequent on the grounds of common side-effects. This reduced compliance with DTP vaccination in the UK, and in consequence, an upsurge in pertussis cases was seen in 2011-2012 in babies of young mothers who themselves may not have been immunized as children.

In 1998, an infamous controversy provoked by a Dr Andrew Wakefield in the UK created a storm of opposition toward the MMR vaccine owing to an alleged causative connection with autism. This alleged association was published in the prestigious medical journal The Lancet. The study was later refuted and ultimately proven fraudulent. Wakefield lost his UK medical license for serious misconduct (General Medical Council Great Britain 2010). His fictitious findings and fraudulent sci ence allegedly motivated for economic gains from legal actions against MMR pro ducers did great harm to vital immunization coverage (BMJ editorial, 2011) . Despite legal action against Wakefield, considerable damage was done to public opinion, and compliance with MMR vaccination reduced in the UK; it gradually recovered from low 80 percent to over 90 percent. The Lancet eventually retracted the paper in 2010, 12 years after initial publication.

A measles epidemic in Europe in 2010-2012 and its subsequent spread to North and South America show the fragility of the immunization system globally even in the advanced countries. Opposition to vaccination is still a major obstacle in achieving the full benefits of vaccines in the USA and other countries. Opposition has hindered efforts to eradicate poliomyelitis in Nigeria and in Pakistan owing to beliefs in some uneducated regions that the vaccine is meant to sterilize girls. Other controversies lurk around the adoption of human papillomavirus vaccine on the grounds that immunization of girls with HPV will encourage early sexual activity.

The H1N1 influenza pandemic of 2009 showed the extent of public concern or apathy to vaccination when the uptake of a vaccine made freely available to avert an international crisis was largely ignored by the general public in most countries. Furthermore, the vaccine was refused by some medical and nursing personnel, a population at high risk of contracting the infection during a pandemic, and thus at risk of transmitting the disease to other patients as well as their own families and contacts.

Vaccination is a pillar of modern public health, saving millions of lives and with potential for millions more to be saved, as medical sciences bring more vaccines into general use. Public apathy and unrelenting opposition by anti-vaccinationists are substantial obstacles to the wider prevention of diseases. Health promotion is crucial to increase support for vaccination by the general public, in order to control very important diseases. New vaccines for HIV, malaria, Helicobacter pylori, sexually transmitted diseases, and cancers will provide both opportunities and challenges for public health to disseminate its message widely.

2003, but pertussis remains endemic and careful protection is required to prevent disease and deaths from pertussis.

Pertussis continues to be a public health threat and recurs wherever there is inadequate immunization in infancy. In addition, recent epidemics have been noted in adults who have lost childhood immunity. While the disease generally follows a milder course in healthy adults, concerns have been raised over adults serving as reservoirs for infection of children and immunocompromised individuals. To eliminate this risk, pertussis booster vaccination is recommended during adolescence and once again in adulthood and also during pregnancy to protect the newborn until routine infant immunization offers full protection. Outbreaks in schools, kindergartens, and hospitals require booster TdaP doses of vaccine.

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 3-21 days, it causes an acute condition of painful muscular contractions. Unless there is modern medical care available, patients are at risk of high case fatality rates of 30-90 percent (highest in infants and elderly people).

Antitetanus serum (ATS) was discovered in 1890, and during World War I, ATS contributed to saving the lives of many thousands of wounded soldiers. Tetanus toxoid was developed in 1993. Owing to the organism's universal presence in the environment, it 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 every decade.

Newborns are infected by tetanus spores (tetanus neonatorum) where unsanitary conditions or practices are present. Infections 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 practices and the use of medically supervised birth centers for delivery also contribute to the reduction of the incidence of tetanus neonatorum.

Elimination of tetanus neonatorum was made a health target by the World Summit of Children in 1990. In that year, the number of deaths from neonatal tetanus was reported by the WHO as 25,293 infants worldwide, declining to 8376 in 2006 (112 countries reporting). Immunization of pregnant women increased from under 20 percent in 1984 to 69 percent in 2006. In 2008, maternal and neonatal tetanus (MNT) still occurred in 46 countries; however, progress continues and at the end of 2010, the goal for elimination had not been reached by 39 countries. The WHO reported the approximate number of cases for 2008 to be an estimated 59,000 newborn deaths caused by MNT (a 92 percent reduction from the late 1980s).

Tetanus cases have declined dramatically in the USA, but the disease still occurs, mainly among older adults. According to the CDC, during 1990-2001 a total of 534 cases of tetanus were reported; 301 (56 percent) cases occurred among adults aged 19-64 years and 201 (38 percent) among adults aged 65 years or older. Data from a national population-based serosurvey indicated that the prevalence of immunity to tetanus was over 80 percent among adults aged 20-39 years; however, this declined with increasing age. These figures support current recommendations to give booster doses of tetanus (with diphtheria) vaccine for adolescents and adults every 10 years.

Poliovirus infection may be asymptomatic or cause an acute non-specific febrile illness. It may reach more severe forms of aseptic meningitis and acute flaccid paralysis (AFP) with long-term residual paralysis or death during the acute phase. Polio 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 1940s and 1950s, engendering widespread fear and panic and thousands of clinical cases of "infantile paralysis".

Growth of the poliovirus in tissue culture, by John Enders and colleagues in 1949, led to the development and widescale testing of the first inactivated (killed) polio vaccine by Jonas Salk in the mid-1950s. This achievement and the largest clinical trial ever conducted up to that point helped to build great hopes and outstanding success in the control of this much feared disease, making Salk a national and global hero. Albert Sabin's development of the live attenuated OPV, licensed in 1960, added a major new dimension to polio control owing to its effectiveness, low cost, and ease of administration. The two vaccines in their more modern forms, enhanced strength inactivated poliomyelitis vaccine (eIPV), and triple oral poliomyelitis vaccine (TOPV), have been used in different settings with great success.

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 people in the sewage gives a booster effect in the community. Immunization using OPV, in both routine practice and on national immunization days (NIDs), has proven effective in dramatically reducing polio and circulation of the wild virus in many parts of the world. Use of the 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 one case per 520,000 with initial doses, and one case per over 12 million with subsequent doses. Approximately eight to 10 cases of VAPP occurred annually in the USA during the 1990s following the elimination of natural transmission. The CDC changed its recommendations to inactivated polio vaccine (IPV) use in 1999, out of concern that the risk of VAPP would outweigh the risk of local wild polio from imported cases. Many developed countries have followed suit. While this eliminates the risk for VAPP, concerns have been raised that herd immunity may be reduced owing to the shorter memory and lower intestinal immunity noted with IPV use.

Controversy as to the relative advantages of each vaccine continues. The OPV program of mass repeated vaccination in the control of polio in the Americas established the primacy of OPV in practical public health, and the momentum to eradicate polio is building. OPV requires multiple doses to achieve protective antibody levels. Where there are many enteroviruses in the environment, interference in the uptake of OPV may result in cases of paralytic polio among people who have received three or even four doses of adequate OPV. The use of IPV as initial protection eliminates this problem. During the 1970s and 1980s, a combined approach bolstering IPV immunity with OPV boosters showed promise in Gaza and Israel, where natural poliovirus was eradicated. Although the sequential use of IPV and OPV was adopted in the routine infant immunization program in the USA in 1997, since 2000 programs have used IPV alone. IPV has been adopted as the exclusive polio vaccine in most of the industrialized countries, while developing countries continue to rely on the less costly and easier to administer OPV. Mop-up campaigns using monovalent OPV (type 1) in still endemic areas.

There are concerns that exclusive use of either vaccine alone will not lead to the desired goal of eradication of polio. In 1988, the global polio eradication initiative was launched and progress since then has been impressive. Global coverage of infants with three doses of OPV reached 85 percent in 2005 compared with 83 percent in 1995 (UNICEF). During this period, OPV coverage increased in the African Region of the WHO from 51 percent in 2000 to 75-80 percent (2006) , but since then has fallen slightly. NIDs are conducted in many countries throughout the world, achieving coverage of over 400 million children annually. Mop-up operations to reinforce coverage of children in still endemic areas are proceeding, along with increased emphasis on AFP monitoring. The number of global polio cases has been reduced by more than 99.8 percent from 1988 to 2009, including the prevention of five million cases of paralysis and more than 250,000 deaths.

With continued national and international emphasis, and the support of the WHO, Rotary International, UNICEF, GAVI, and donor countries, there is real prospect of a world without polio. India had no cases in 2011-2012, while Nigeria, Pakistan, and Afghanistan continue to have endemic wild poliovirus cases. In 2012, a total of 223 polio cases were reported from five countries: Afghanistan, Chad, Niger, Nigeria, and Pakistan. In 2013 (up to 5/11/2013) 328 polio cases were reported from: Afghanistan, Cameroon, Ethiopia, Kenya, Nigeria, Pakistan, Somalia, and Syrian Arab Republic. The end of polio eradication is in sight, but great care must be taken in the end-stage strategy of continued vaccination in the decade ahead at least. In 2012, the murder of polio workers by radical Islamic Taliban fighters in Pakistan cast a pall over the program, but the vaccination program continues and will succeed (WHO Polio Eradication Initiative, 2013).

WHO has a policy to promote conversion from OPV to IPV-only policies. This needs to be reconsidered. In 2013 routine sewage monitoring in Israel revealed widely dispersed WPV was detected in 87 of 220 samples from 79 sites at 26 locations of southern and central parts of the country. There were no clinical cases in the population with 95 percent IPV immunization coverage but 42 healthy WPV1 carriers were found (4.4% of those sampled). In contrast, the West Bank and Gaza with a combined IPV-OPV immunization program since 1978 and over 95 percent coverage and no cases since 1992 had in 2013 sewage sampling identified only 4 positive samples of WPV1. This constitutes a "natural experiment" comparing two adjacent interacting jurisdictions: one with a combined OPV and IPV and one with IVP comparing the effectiveness of the two systems for preventing entry of WPV into an area. This experience should be considered of great importance in determining appropriate end-stage policy for the global polio eradication strategy. IVP alone is insufficient protection against spread of WPV from an unknown source even to well immunized and high level sanitation countries. A combined OPV/IPV policy is recommended .

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 cases (99 to 1). Measles has a characteristic clinical presentation with fever, rhinorrhea, white spots (Koplik spots) on the membranes of the mouth, and a red blotchy rash appearing on day 3-7, lasting for 4-7 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 3000-5000 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 it remains a major childhood infectious disease today.

Single-dose immunization failed to meet control or eradication requirements even in the most developed parts of the world. A live vaccine, licensed in 1963, was later replaced by a more effective and heat-stable vaccine, but still with a primary vaccination failure rate (i.e., fails to produce protective antibodies) of 4-8 percent, and secondary failure rate (i.e., produces antibodies but protection is lost over time) of 4 percent. A two-dose policy incorporates a booster dose, usually at school age, in addition to maximum feasible infant coverage of children in the 9-15 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 vaccine and a resulting increase in 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. Figure 4 .4 illustrates the annual number of reported measles cases in the USA and, most notably, the dramatic drop in cases following the introduction of the first measles vaccine in 1963.

The CDC declares that domestic transmission in the USA has been interrupted and that most localized outbreaks were traceable to imported cases. South America and the Caribbean countries are now considered free from indigenous measles, based on their successful use of NIDs, although a large epidemic occurred in 1999 in Brazil. Eradication of measles is feasible in the second decade of this century, if a two-dose policy is used and sustained with high priority globally, supplemented by catch-up campaigns for older children and young adults, and outbreak control.

Measles eradication is one of the central targets on the global public health community agenda, with emphasis placed on reducing mortality and then on gradual eradication of the disease (Box 4.11). The relationship between measles vaccination and cases is shown in Figure 4 .4. In 2010, there were 139,300 measles deaths worldwide, which translates to almost 380 deaths daily, or 15 deaths per hour. Europe has experienced large waves of measles in the 1990s and especially between 2010 and 2012. Globally, measles vaccination led to a reduction of 74 percent in measles mortality between 2000 and 2010. From January to November 2012, France, Italy, Romania, Spain, and the UK accounted for 87 per cent of all reported cases, and there were no measles-related deaths, but seven cases were complicated by acute measles encephalitis. This was lower than the 2011 level, but measles transmission continues across Western and Central Europe. Much of the measles epidemic in Europe is school related, occurring among the underimmunized age group 10-16 years. England reports an estimated 330,000 underimmunized children in this age group (Ramsay, 2013). The trend of confirmed measles cases in England from 2009 to 2013 is shown in Figure 4 .5.

In 2000, 72 percent of the world population received the first dose of measles-containing vaccine. Ten years later, total coverage increased to 85 percent. In 2000, measles incidence (cases per million population) amounted to 838 in the African Region of the WHO. In 2010, measles incidence 1954 1956 1958 1960 1962 1964 1966 1968 1970 1972 1974 1976 1978 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 dropped to 238 (per million population), thus representing a 72 percent decline in this period. Furthermore, in the African Region, 90 percent of children under the age of five mostly die from complications such as severe diarrhea, pneumonia, and encephalitis. Over 95 percent of deaths occur in low-income countries with weak health systems. In 2011, large outbreaks were reported by the Democratic Republic of the Congo (DRC) with over 103,000 cases, Nigeria with 17,428 cases, Zambia with 5397 cases, and Ethiopia with 2902 cases. The WHO regional office in DRC reported 1100 measles-associated deaths in 2011 in that country.

International transmission of the virus in carriers has led to importation and subsequent epidemics even in countries thought to have achieved local eradication. This is exemplified by outbreaks in 2006-2008 in the UK, Switzerland (2250 cases), Austria, France, Italy, and other countries. Israel had an epidemic of over 1200 cases in 2007-2008 following an imported case. In July 2008, the Health Protection Agency in the UK declared measles to be endemic for the first time in 14 years, owing to a decade of poor coverage with the measles vaccine. The USA had an annual average of 64 cases during

Measles is a highly infectious viral disease that was responsible for the death of nearly 2 million children globally per year in the 1960s, before the advent of measles vaccine. Gradual adoption of the measles vaccine and growing coverage worldwide reduced global mortality to fewer than 200,000 deaths by 2010. Measles vaccination has been one of the success stories of public health; however, the picture is still mixed, and hopes for measles eradication have been put off until 2015.

Measles vaccine is one of the most immunogenic and safest of all the available vaccines. Two doses, with over 95 percent coverage, and catch-up of older teens and young adults is required in order to ensure full coverage, long-lasting individual protection, and herd immunity. The two-dose policy was adopted late in many countries; therefore, it took time for the circulation of the virus to appear to be under control. While measles cases and deaths were drastically reduced, large pockets of susceptible populations remained vulnerable.

Between 1989 and 1991, measles in the USA resulted in more than 100 deaths, with over 55,000 cases reported. This was followed by a return of subacute sclerosing panencephalitis (SSPE), a rare but fatal neurological complication of measles in children -a condition which had largely disappeared after the vaccine became widely used (CDC, MMWR, 2011) .

In the 1990s in the USA and in 2000 in the Americas as a whole, measles was declared to have been eliminated. However, importation of the virus continued at low levels.

Late in the first decade of the twenty-first century, a number of large-scale outbreaks of measles occurred in countries that had not experienced the disease for many years, as a result of laxity and resistance to immunization. Complacency among parents, and medical and public health practitioners allowed outbreaks to continue due to a weak response to targeted and large-scale strategic immunization efforts.

A decline in coverage with the MMR vaccine in the UK in the late 1990s resulted from widespread publicity and concern over a fraudulent and disproven allegation of an association with autism (the "Wakefield effect"). This led to a reduction in MMR coverage in the UK and large-scale outbreaks, with a return to endemicity of the disease as the virus circulated, finding susceptible children who had not been not immunized and causing disease even among adequately immunized children.

Many children were left unimmunized and, consequently, unprotected, as a result of parents' fears of complications of the MMR vaccine. Other children who were not immunized included those with chronic diseases such as HIV and leukemia, many of whom are unable to receive the vaccine owing to an increased risk of potential complications. Thus, a lack of appropriate levels of herd immunity left these people vulnerable. Unimmunized infants, older children, and young adults are also susceptible to contracting this highly contagious disease.

In sub-Saharan Africa, vaccination with one dose of a measles-containing vaccine reached 83 percent in 2009. In 2011, Nigeria reported 30,000 cases with 122 deaths; the Democratic Republic of the Congo reported 16,000 cases and 107 deaths between January and February 2011 alone. In 2012 and 2013, measles epidemics have been occurring throughout the UK including England, Wales, and Scotland. In the first quarter of 2013, 587 cases of measles were reported in England, mostly in the north-west and north-east regions, among infants before immunization age and among 7-16-year-olds.

Control, elimination, and potential eradication of the disease will require more years of intense effort to raise basic coverage with two doses of the vaccine as well as catch-up campaigns. New strategies are needed to influence global public perception of the vital importance of immunization and its safety. The current WHO target is to achieve measles eradication by 2015. In 2012, the WHO launched a new initiative combining measles and rubella vaccination with three doses of measles-containing vaccine, and promoted MMR so that rubella and mumps and their complications can also be eliminated. In 2010-2012, there was a widespread epidemic of over 50,000 reported cases. The largest burden of disease fell on Western Europe, with the WHO European Region reporting 26,025 cases up to October 2011. In 2012, 115 measles outbreaks were reported from 36 countries with many thousands of cases in France, the UK, Germany, Bulgaria, Italy, and Switzerland, as well as Africa and Asia. Following this string of measles epidemics, the virus has spread outside the region, leading to hundreds of imported and secondary spread cases in the USA and Canada.

A dramatic drop occurred in US measles cases following the introduction of the first measles vaccine in 1963. The WHO has promoted measles vaccination in campaigns combined with other life-saving interventions such as bed nets to protect against malaria, deworming medicine, and vitamin A supplements to make use of the contact occasion to reduce child death rates, in keeping with the MDGs between 1990 and 2015. Elimination of measles as a public health problem, and even eradication, are feasible goals in the second decade of this century. This combination of interventions is critical in attaining the MDG target of reducing child mortality by 2015. The MDGs are a crucial and sometimes underrecognized issue, but this topic deserves to be one of the highest professional and political priorities of international and national donor and public health agencies, as well as national governments.

The WHO strategy of partnership with national governments and non-governmental organizations (NGOs) such as the Measles Initiative, GAVI, and others, includes: The number of countries implementing a two-dose policy has increased sharply from 97 (50 percent) to 141 (73 percent) in 2011, while coverage with MCV1 increased from 72 to 84 percent. The reported incidence rates declined by 65 percent from 146 to 52 per million population; deaths declined 71 percent from 548,000 to 158,000.

With a goal of eradicating measles by 2015, the European Region of the WHO undertook a study to review progress towards the goal. Low vaccination rates occur among hardto-reach population groups, including migrants (employed but not citizens) and members of particular ethnic groups. Across Europe there is inadequate information to monitor vaccination coverage in these groups. The results of the study show that achieving measles eradication requires the collective efforts of policy makers and health providers.

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 12 and 25 days. Orchitis, or inflammation of the testicles, occurs in 20-30 percent of postpubertal males and oophoritis, or inflammation of the ovaries, in 5 percent of postpubertal females. Sterility is an extremely rare result of mumps. CNS involvement can occur in the form of aseptic meningitis, almost always without sequelae. Encephalitis is reported in 1-2 per 10,000 cases with an overall case fatality rate of 0.01 percent. Pancreatitis, neuritis, nerve deafness, mastitis, nephritis, thyroiditis, and pericarditis, although rare, may occur. Most people born before 1957 are immune to the disease, because of the nearly universal exposure to the disease prior to that year.

The live attenuated vaccine introduced in the USA in 1967 is available as a single vaccine or in combination with measles and rubella as the MMR vaccine. It provides longlasting immunity in 95 percent of cases. Mumps vaccine is now recommended in a two-dose policy with the first dose of MMR given between 12 and 15 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 USA, Sweden, the Netherlands, Canada, Israel, and other countries. The incidence of mumps overall has declined rapidly over the years, with routine MMR vaccine in two doses as the main recommended routine; however, it still remains a threat.

During 2004-2005, the UK experienced a nationwide epidemic of mumps, which peaked during 2005 when over 56,000 cases were reported in England and Wales, mostly in people aged 15-24 years, and most of whom had not been eligible for routine mumps vaccination. were hospitalized in Crete and Greece, and almost all were young tourists from Britain. The disease spread among the Greek population as well, in which six cases were reported. Outbreaks in the Netherlands and Canada in the 2006-2008 period were linked to fundamentalist Christian religious groups that refused immunization on religious grounds.

Many countries in Europe still do not use MMR or a two-dose policy; therefore, they are vulnerable to mumps along with rubella outbreaks. MMR vaccination should be adopted as an international standard, with two doses for all children and catch-up for school-age children. Local eradication of this disease is important and should be part of a basic international immunization program. This is an ongoing challenge in the European Region, which lacks a harmonized immunization program.

Rubella (German measles) is generally a mild viral disease with lymphadenopathy and a diffuse, raised red rash. Lowgrade fever, malaise, coryza, and lymphadenopathy characterize the prodromal period. The incubation period typically lasts for 16-18 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 (Box 4.12).

Congenital rubella syndrome (CRS) occurs with single or multiple congenital anomalies including deafness, cataracts, microophthalmia, congenital glaucoma, microcephaly, meningoencephalitis, congenital heart defects, and others. Insulin-dependent diabetes is suspected as a late sequela of congenital rubella. Each case of CRS is estimated to cost some US$250,000 in health care during the patient's lifetime.

Moderate and severe cases are recognizable at birth, but mild cases may not be detected for months or years after birth. The WHO estimates that in 1996, CRS occurred in 22,000 babies in Africa, 46,000 in South-East Asia, and 13,000 in the Western Pacific Region, and that similar rates were occurring in 2008, since few of the countries in these regions have introduced rubella vaccine.

Prior to the availability of the attenuated live rubella vaccine in 1969, the disease was universally endemic, with epidemics or peak incidence every 6-9 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 and colleges, and among military personnel.

A sharp reduction in rubella cases was seen in the USA following introduction of the vaccine in 1970; however, rates increased in 1978, following rubella epidemics in 1976-1978. A further reduction in cases was followed by a sharp upswing of rubella and CRS in [1988] [1989] [1990] . An outbreak of rubella among the Amish in the USA, who refuse immunization on religious grounds, resulted in seven cases of CRS in 1991. It is now thought that vaccination of sufficient numbers in the USA reduced circulation of the virus and protected the most vulnerable groups in the population. Most industrialized countries adopted MMR in the 1990s and, subsequently, a two-dose policy. Rubella and CRS incidence dropped dramatically. Controversy in the UK in the early 2000s led to reduced MMR usage and an increase in cases of measles and rubella (see Box 4.11). This was subsequently improved by providing incentive payments for general practitioners, with 100 percent age-specific immunization coverage.

Some parts of Europe failed to adopt MMR vaccine use and have suffered recurrent outbreaks of these diseases. A number of outbreaks were reported in 2005-2007. Poland reported 7946 cases of rubella in 2005 (20.8 per 100,000 population), an increase of 64 percent compared to 2004. MMR was added to the routine immunization schedule at the end of 2003. In 2003, Italy approved a national plan for the elimination of measles and congenital rubella, with the aim of reducing and maintaining the incidence of CRS to less than one case per 100,000 live births by 2007.

Despite the common program recommended by the European Region of the WHO, childhood immunization programs vary widely across the EU and within some countries where regional autonomy for immunization is permitted. Coverage with a first dose of a measles-containing vaccine was 82 percent in the UK, 84 percent in Ireland, 87 percent in France, and 88 percent in Belgium in 2005, all well below herd immunity levels required for measles control (Venice Project 2007). This leaves each country to develop its own program, without guidelines for countries in transition from the socialist period, operating with high coverage rates. Thus, it allows for obsolescent immunization practices which only very slowly adopt current best practices from western standards. Many countries have not yet adopted MMR. The WHO declares the eradication of measles and rubella to be of higher priority than mumps and, furthermore, suggests that the combination MMR vaccine be used.

In the past, the immunization policy for rubella in some countries was to vaccinate schoolgirls at the age of 12 and women after pregnancy to provide protection throughout 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 people. Women of reproductive age should be tested to confirm immunity prior to pregnancy and receive the immunization if not already immune. Should a woman become infected during pregnancy, termination of the pregnancy is no longer recommended; rather, the infection 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 and critical. Its inclusion in a modern immunization program is fully justified. Elimination of CRS should be one of the primary goals of a program for prevention of VPDs in developed and developing countries. Adoption of MMR and the two-dose policy will gradually lead to the eradication of rubella and rubella syndrome.

In 1942, Norman Gregg, an Australian ophthalmologist, observed an epidemic of cases of congenital cataract in newborns and other birth defects associated with a history of rubella in the mother, during the first trimester of pregnancy. Subsequent investigation demonstrated that intrauterine death, spontaneous abortion, and birth defects including congenital heart disease and deafness occur commonly when rubella occurs early in pregnancy.

For this discovery, Gregg was knighted in 1953 and received many other honors. With the later development of rubella vaccine, its inclusion in MMR vaccine with measles and mumps, and its widespread use around the world, this cause of birth defects has been gradually reduced. The WHO in 2012 made rubella part of its disease eradication program, together with measles, to prevent rubella syndrome globally.

Since the WHO recommended the universal use of rubella vaccine in childhood, immunization coverage has become more widespread: it increased from 83 countries in 1996 to 130 of the 193 WHO member states in 2009. Rubella-containing vaccines (RCVs) are used in national immunization schedules in two of 46 countries in the African Region, all 35 in the Region of the Americas, four of 11 countries in South-East Asia, all 53 in the European Region, 15 of 21 in the Eastern Mediterranean Region, and 21 of 27 countries in the Western Pacific Region (WHO WER, 2010).

Viral hepatitis is a group of diseases of increasing public health importance owing to its large-scale worldwide prevalence, its serious consequences, and our increasing ability to take preventive action. Viral hepatic infectious diseases each have specific etiological, clinical, epidemiological, serological, and pathological characteristics. They have important short-and long-term sequelae. Vaccine development is of high priority for their control and ultimate eradication. Beginning in 2009, CDC requires US-reported cases of acute and chronic viral hepatitis to meet Council of State and Territorial Epidemiologists (CSTE)-defined clinical and laboratory criteria. The first official World Hepatitis Day was held on 28 July 2011.

Hepatitis A virus (HAV) is mainly transmitted by the fecaloral route. Clinical severity varies from a mild illness of 1-2 weeks to a debilitating illness persisting for several months. The norm is complete recovery within 9 weeks, but a fulminating or even fatal hepatitis can occur. Severity of the disease worsens with increasing age. HAV is endemic worldwide.

Improving sanitation lowers childhood exposure to HAV, but infection among adults typically leads to more severe clinical symptoms. It is now prevalent particularly in people from industrialized countries who are exposed to environments characterized by poor hygiene or contaminated food products. HAV also occurs among young adults when traveling to areas where the disease is endemic. Common source outbreaks occur in school-age 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. Short-term risk of infection for people exposed to HAV may be reduced with prompt administration of HAV immune globulin. Hepatitis A vaccine is now recommended for all children over 12 months of age, as well as for people traveling to endemic areas or at increased risk of exposure or morbidity. CDC reports that 33 percent of the US population were ever infected with HAV, but there is no chronic carrier state. HAV immunization is being adopted for routine prevention programs in some countries, including the USA; it is used for pre-exposure prevention; however, immune globulin is still used for postexposure protection. As the costs of the vaccine begin to fall, its widespread routine use may be recommended.

Hepatitis B virus (HBV) was once 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. In contrast to HAV, it is not typically spread by the fecal-oral route.

HBV is endemic worldwide and is especially prevalent in developing countries. Carrier status with persistent viremia is estimated by CDC to be 1.25 million in the USA, with 4.9 percent of the population ever infected. Carrier rates are 5-8 percent in sub-Saharan Africa but between 8 and 15 percent of babies become infected in some parts of the world, thus routine immunization is recommended. Carriers have detectable levels of HBsAg, the surface antigen (i.e., Australian antigen), in their blood. In 2006, an estimated 27 percent of newborns worldwide received a dose of hepatitis B vaccine and 69 percent of the 2008 birth cohort had three doses of hepatitis B vaccine. By 2011, the hepatitis B vaccine was an integral part of national immunization programs in 179 countries (WHO, 2013). Transmission from mother to child and between children by unsafe injections is common, as is infection via sexual contact. It is crucial for the following high-risk groups in developed countries to be immunized: health care workers, intravenous drug users, men who have sex with men, people 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 carriers of HBV. HBV may also be spread in a health system by use of inadequately sterilized reusable syringes, as has occurred in China and the former Soviet Union. Transmission is reduced by screening blood and blood products for HBsAg. Strict technique for handling blood and body fluids in health care settings is absolutely essential and greatly reduces the risk of transmission.

HBV is clinically recognizable in less than 10 percent of infected children but is apparent in 30-50 percent 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, through 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.

HBV is considered to be the cause of 60 percent of primary cancer of the liver in the world and the most common carcinogen, second to cigarette smoking. The WHO estimates that more than 2 billion people alive today have been infected with HBV. It is also estimated that 350 million people are chronic carriers of HBV, with an estimated 1-1.5 million deaths per year from cirrhosis or primary liver cancer. This makes control of hepatitis B 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 donations that are detected as positive. 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 in prison or at work, such as in health care facilities, as well as sex workers and adults in group settings. HBV immunization has been included in the WHO's EPI-plus expanded program of immunization. In 1992, the World Health Assembly (WHA) passed a resolution to recommend global vaccination against hepatitis B, then used in 31 countries. By 2011, 179 countries had adopted this vaccine in their national infant immunization programs, and 93 member states have introduced the hepatitis B birth dose, protecting millions of children from chronic infection with HBV (WHO, 2013).

First identified in 1989, and previously known as non-A, non-B hepatitis, hepatitis C has an insidious onset characterized by jaundice, fatigue, abdominal pain, nausea, and vomiting. Hepatitis C virus (HCV) may cause mild to moderate illness; however, chronicity is common, progressing to cirrhosis and liver failure. The WHO estimates that 150 million people are chronically infected with HCV and 3-4 million are newly infected globally each year. More than 350,000 people die from hepatitis C-related liver diseases every year.

High rates of HCV are reported in Egypt (22 percent of the population), and more than 3 percent of the population in China and Pakistan are infected. The WHO reports identify contaminated equipment in the administration of injections as a primary factor in transmission (WHO, 2010) . The CDC estimates that 3.2 million Americans are chronically infected with HCV, with an estimated 12,000-15,000 resulting deaths per annum (CDC, 2012) . Furthermore, HCV is the main cause of illness necessitating liver transplants.

The virus is transmitted most commonly in blood products, but also among injecting drug users; 90 percent of intravenous drug users (IVDUs) were HCV positive in a Vancouver study in 1998. HCV also poses 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 and antiviral treatment of blood products. For IVDUs, needle-exchange programs and hygiene education are of value. In 1998, the WHO declared hepatitis C a major public health crisis, stressing that this "silent epidemic" is being neglected and that screening of blood products is vital to reduce transmission of this disease, as for HIV.

HCV is a major cause of liver cirrhosis, end-stage liver disease, and hepatocellular carcinoma. The virus is primarily transmitted parenterally. No vaccine is available at present, but research is currently under way to find this "holy grail". The genetic diversity of the virus makes it difficult to find the correct antigen for effective antibody production, so the virus evades the host immune response and, in turn, poses a serious challenge for developing an effective vaccine. The incidence reported in the CDC is estimated to be about half of number of true new infections with hepatitis C, which often has mild symptoms (Figure 4 .7).

Significant advances have been made in the treatment of chronic HCV infection. The combination of pegylated interferon and ribavirin, used since 2001, has been enhanced by the addition of one of two new drugs -boceprevir or telaprevir -with improved results over the previous two-drug therapy, including for those who had been previously treated and failed to clear the virus. Treatment is expensive and carries significant adverse effects, with symptoms of weakness and depression, but the new triple combination reduces the duration of treatment and improves success rates.

Treatment is needed in most cases of hepatitis C carrier status and is needed if there are signs of liver damage to prevent HCV-associated cirrhosis and liver cancer. Prevention of transmission is primarily addressed towards intravenous drug users but screening is recommended for adults including those in the 45-plus age groups. Current research is showing improved methods of multi drug treatment with improved success rates and possibility of eliminating interferon with a reduction in costs and far fewer side-effects as early as during 2013. Developing countries have high levels of this infection but limited resources to control it until a vaccine is developed.

Hepatitis D virus (HDV), also known as delta hepatitis, may be self-limiting or progress to chronic hepatitis. It is caused by a virus-like particle which requires HBV to reproduce. HDV 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. This virus has been the source of epidemics and is endemic in South America and Africa, as well as among drug users. Prevention is achieved by measures similar to those for HBV. Management of 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 virus (HEV) has an epidemiological and clinical course similar to that of HAV, with an incubation period of 15-64 days. There is no evidence of a chronic form of HEV. One striking characteristic of HEV is the high mortality rate among pregnant women. Infections typically result via waterborne epidemics, or as sporadic cases in areas with poor hygiene, spread via the fecal-oral route. In disaster situations with crowding and poor sanitary conditions, HEV presents a major hazard. Prevention is by safe management of water supplies and sanitation. Treatment is supportive and aimed at the symptoms; passive immunization is not helpful and no vaccine is currently available.

The Hib bacterium causes meningitis, pneumonia, and other serious infections in children. Before the introduction of effective vaccines, as many as one in 200 children developed invasive Hib infection. Two-thirds of these developed Hib meningitis, with a case fatality rate of 2-5 percent. Long-term sequelae such as hearing impairment and neurological deficits occurred in 15-30 percent of survivors.

The first licensed Hib vaccine (1985) was based on capsular material from the bacterium. Extensive clinical trials conducted in Finland demonstrated a high degree of efficacy, but less impressive results were in seen in postmarketing efficacy studies. By 1989, a conjugate vaccine based on an additional protein cell capsular factor capable of enhancing the immunological response was introduced. Several conjugate vaccines are now available.

Since the introduction of Hib vaccine into the US recommended immunization schedule, bacterial meningitis cases were dramatically reduced by 55 percent; however, this may have also been an effect of the widening use of pneumococcal pneumonia vaccine. In recent years, the number of cases of Hib infection has increased in adults, especially in elderly or immunocompromised people.

The conjugate vaccines are now combined with DTaP as their schedule is simultaneous with that of DTaP. Hib vaccine has been found to be cost-effective, despite its costing as much as all the basic vaccines combined (i.e., DTP, OPV, MMR, and HBV vaccine). For this reason, its use thus far has been mainly limited to industrialized countries, although it is spreading to many developing countries with support from GAVI. As of 2009, Hib vaccine had been introduced into routine vaccination in 169 countries (WHO Global Advisory Committee on Vaccine Safety, 2013).

The vaccine is a valuable addition to the immunological armamentarium. It has shown dramatic results in local eradication of this serious early childhood infection in a number of European countries and a sharp reduction in the USA. The price of the vaccine has also fallen dramatically since the mid-1990s.

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 1-5 days. It is generally mild and self-limiting, with recovery in 2-7 days. However, in certain population groups, such as young children, and elderly and chronically ill people, infection can lead to severe sequelae. Gastrointestinal symptoms commonly occur in children. During epidemics, 2 0 1 0 2 0 0 8 2 0 0 6 2 0 0 4 2 0 0 2 2 0 0 0 1 9 9 8 1 9 9 6 1 9 9 4 1 9 9 2 1 9 9 0 1 9 8 8 1 9 8 6 mortality rates from respiratory diseases increase because of the large numbers of people affected, although the case fatality rates are generally low.

Over the past century or so, influenza pandemics have occurred in 1889, 1918, 1957, 1968, and 2009 , while epidemics have presented themselves as annual events. The influenza pandemic of 1918 caused millions of deaths among young adults, by some estimates killing more than had died in World War I: the pandemic killed nearly 50 million people worldwide and was characterized by an atypical mortality curve. Influenza typically affects the very old and the very young. The principal group suffering from the 1918 pandemic was young men between the ages of 30 and 60 years, many in army training camps, as well as in the general population. Fear of recurrence of this pandemic led the CDC to launch a massive immunization program in the USA in 1976 to prevent swine flu (the virus was a strain antigenically similar to that of the 1918 pandemic influenza) from spreading from an isolated outbreak in an army camp. The effort was stopped after millions of people were immunized with an urgently produced vaccine when serious reactions occurred (Guillain-Barré syndrome, a type of paralysis) and when no further cases of swine flu were seen. This example demonstrates the difficulty in extrapolating scenarios from a historical experience.

In the 2009 pandemic H1N1 outbreak, the per capita risk factor for hospitalization was highest among children aged under 5 years. The highest risk of death was in the age group 50 and over. Following the pandemic, the WHO defined standards for reporting fatal influenza-related cases. A similar approach has been developed for severe respiratory infections. Assessing the problems with this pandemic, it became evident that many countries lack surveillance systems to monitor outbreaks over an extended period. Respiratory illness is the second leading cause of death in many low-and middle-income countries, and thus justifies directing sufficient resources towards management and prevention. Current best practices for universal immunization annually for influenza for all age groups have been shown to reduce serious complications, death, and the high costs of medical care. It is especially important for health workers and other caregivers (teachers, kindergarten workers, and others whose work entails meeting the public) to have upto-date influenza vaccination. If there are shortages of vaccine, efforts should focus on those listed in Box 4.13. As shown in Box 4.14, vaccination is especially important to prevent influenza during pregnancy.

A CDC report in 2012 indicated that nearly one-third of surveyed health workers were not immunized for influenza because of concern over the vaccine's efficacy and sideeffects and doubts as to whether it was needed (MMWR, 2012) . Unvaccinated health workers put their patients and their families at risk. Current recommendations are for annual influenza vaccination for all people aged 6 months or older and all health care providers. Other groups, such as immunosuppressed patients and those receiving chronic aspirin therapy, should obtain medical advice regarding influenza risk and vaccination. People with allergy to previous flu shot, eggs, or other vaccine components, or with a history or risk for Guillain-Barré syndrome, may not be candidates for vaccination and should obtain medical advice.

In recent years, concern has again risen surrounding the likelihood of virulent influenza pandemics. Particularly noteworthy is the influenza A H5N1 strain, known as avian influenza. The WHO reports that from 2003 to July 2013, the number of confirmed human cases was 633 with 377 deaths. Although relatively few human-to-human transmissions have been documented, the first such transmission was reported in July/August 2013, and this virus has rapidly spread among wild and domestic bird populations throughout Asia and much of the world. People exposed to and in contact with infected birds or poultry are at risk for severe disease, with over 60 percent case mortality. A minor mutation or genetic conjugation with a known human strain could result in a virus as deadly and contagious as the swine flu of 1918. It is estimated that up to 1.9 million people in the USA could die if such an outbreak occurs. Extensive international plans have been developed for intervention should a virulent influenza pandemic occur. These include several vaccines with specificity to known virus strains. As many of the most devastating global communicable disease emergencies of recent centuries have been associated with highly pathogenic respiratory viruses, health systems and emergency plans must be prepared in case of a pandemic. Active surveillance using sentinel chicken flocks now under observation for West Nile Fever could be used to provide early warning of the entry of the bird-borne disease into a specific region. This, in turn, could help to trigger the activation of response mechanisms.

Each year, epidemiological 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 (abrupt major change), are associated with widespread epidemics and pandemics. Type B undergoes antigenic drift (small changes over time) 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 70-80 percent 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.

Avian (H5N1) influenza is a threat to the world's population because of its potential to become a pandemic on the scale of the 1917-1918 influenza epidemic. It is a birdborne zoonotic disease, so far affecting fowl such as chickens and turkeys contacted by infected wild fowl. Sensitive and robust surveillance measures are required to detect any evidence that the virus has changed and acquired the ability to be transmittable between humans. Surveillance is largely passive in relying on reports of infected wild and domestic fowl and, most importantly, human cases. The major concern is to detect human-to-human transmission, which would threaten to transform this disease into a local, regional, and world pandemic in a matter of months.

International efforts to improve national and local capacities in surveillance and response to this threat are vital to review the scale of the threat should the leap from animal-to-human to human-to-human transmission occur. An integral part of the pandemic planning response in the UK was established in 2005 with the National H5 Laboratory Network, capable of rapidly and accurately identifying potential human H5N1 infections in all regions of the UK and the Republic of Ireland.

The CDC relies on seven systems for national influenza surveillance, four of which operate year-round: the WHO and the National Respiratory and Enteric Virus Surveillance System (NREVSS) collaborating laboratory systems; the US Influenza Sentinel Provider Surveillance System; the 122 Cities Mortality Reporting System; and a national surveillance system that records pediatric deaths associated with laboratory-confirmed influenza.

The H1N1 pandemic control efforts (2009) led by the WHO had broad support from national governments, but there was widespread skepticism and apathy among health care providers and the general public. Response rates to immunization were low even among first responders and hospital personnel. There is a lingering controversy regarding alleged overreaction and conflicts of interests; however, preparation for potential pandemics was advanced. More attention must be paid to public information campaigns in the event of future pandemic threats as well as for annual seasonal influenza.

Pneumococcal diseases, which are caused by Streptococcus pneumoniae, include pneumonia, meningitis, and otitis media. Together these constitute the world's leading cause of vaccine-preventable child mortality, as over 1 million children die from pneumococcal diseases each year. The 23

Preventing influenza during pregnancy is an important part of prenatal care. Influenza can cause severe illness among pregnant women, placing them at high risk owing to changes to the immune system, lungs, and heart during pregnancy. Pregnant women suffered excess mortality in previous influenza pandemics, such as in 1918, 1957, and 2009. To protect her health, as well as that of her unborn baby, a pregnant woman is strongly advised to receive an influenza vaccine, regardless of the trimester. The CDC Advisory Committee on Immunization Practices as well as the American College of Obstetricians and Gynecologists support this recommendation. The inactivated influenza vaccine has proven to be safe, with no adverse effects in pregnant women or their infants. The vaccine is not designed for infants aged < 6 months, so maternal immunity is key to protecting newborns.

CDC surveyed vaccination uptake among pregnant women in the USA during the 2011-2012 influenza season. Of 1660 survey participants, only 47 percent had received influenza vaccination; 9.9 percent before, 36.5 percent during, and < 1 percent after pregnancy. Health care and public health professionals play a key role in educating women on the importance of the vaccine and to increase influenza vaccine uptake. capsular types of pneumococci selected out of 83 known types of the organism for the conjugate vaccine (PPV23) are responsible for 88 percent of pneumococcal pneumonia cases and 10-25 percent of all pneumonia cases in the USA.

This vaccine has been found to be cost-effective for highrisk groups, including people with chronic disease, HIV carriers, patients whose spleens have been 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. In addition, sevenvalent conjugate vaccines (PCV7 and PCV13) are now recommended for routine childhood immunization for children under 2 years of age, the highest risk age group for pneumococcal disease mortality. The WHO and CDC recommend PCV7 routinely for children under 2 years old and PPV23 for adults over 65 years of age. Moreover, others at risk for respiratory disease or pneumococcal infection should be vaccinated with PCV23. Pneumococcal conjugate vaccine is now recommended for routine childhood immunization in the USA and globally by the WHO. By 2010, pneumococcal conjugate vaccine was in routine use for childhood vaccination in 55 countries covering 42 percent of the world's child population. It is now also recommended for routine use among elderly and chronically ill people.

Varicella is an acute, generalized viral disease caused by the varicella zoster virus (VZV). Despite varicella's reputation as an innocuous disease of childhood, patients can become quite ill. A mild fever and characteristic generalized red rash last 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 2 days of delivery are at increased risk, with a case fatality rate of up to 30 percent.

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 elderly people. It can, however, occur in immunocompromised children (especially those on cancer chemotherapy), AIDS patients, and others. Some 15 percent of a population will experience herpes zoster during their lifetime. Reye's syndrome is an increasingly rare but serious complication of varicella or influenza type b. It occurs in children and affects the liver and CNS. Congenital varicella syndrome with birth defects similar to CRS has been identified, emphasizing the importance of effective immunization against VZV. Varicella vaccine is now recommended for routine immunization at 12-18 months of age in the USA, with catch-up for nonimmunized children and adults, especially non-pregnant women of childbearing age. To maintain immunity in adolescence and adulthood, booster vaccinations after 13 years of age and again after 50 years of age are effective in those who have no history of VZV infection or evidence of immunity. Varicella vaccine is likely to be added to a "cocktail vaccine" containing DTP, polio (IPV), and Hib.

Meningococcal meningitis, caused by the bacterium Neisseria meningitides, is characterized by headache, fever, neck stiffness, delirium, coma, and/or convulsions. The incubation period is 2-10 days. It has a case fatality rate of 5-15 percent if treated early and adequately, but rises to 50 percent 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 college student populations. In 1997, meningococcal meningitis spread widely in the "meningitis belt" in Central Africa. In the 2009 epidemic season, 14 African countries implementing enhanced surveillance reported 88,199 suspected cases, including 5352 deaths, the largest number since an epidemic in 1996.

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, Y, and W-135 are available. Their use is effective in epidemic control and prevention in institutions and among military recruits, especially for A and C serogroups. Recommendations are to immunize using the tetravalent meningococcal conjugate vaccine (MCV4) during the preadolescent years, so that immunity is established before residential education or military service.

Vaccine preventable diseases (VPDs) are still among the leading causes of death in developing countries; many mid-level developing or transition countries are not using the full potential of vaccines currently available to protect their children. VPDs are a fundamental aspect of public health not only because of the success achieved in saving millions of lives, but in the enormous potential for future developments that may make equally valuable contributions to the length and quality of life. Despite this, the potential of even currently available vaccines is not yet fully realized and traditional practices mean that many countries are slow to adopt the newer vaccines and their great life-saving capacity. Table 4 .6 shows the number of deaths from VPDs in relation to level of DTP vaccine coverage, classified by WHO region.

Vaccination is one of the key modalities of primary prevention and one of the principal cornerstones of public health. 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 95 percent or higher coverage at appropriate times, including infants, schoolchildren, and adults. Immunization policy should be adapted from current international standards applying the best available program to national circumstances and financial capacities. Public health personnel with expertise in VPD control are needed to advise ministries of health and the practicing pediatric community on current issues in vaccination. Furthermore, they are needed to monitor the implementation and evolution of control programs. Controversies and changing views are common to immunization policy, and therefore discussions must be conducted on a continuing basis. Policy should be under continuing review by a government-appointed national immunization advisory committee, including professionals from public health, academia, immunology, laboratory sciences, economics, and relevant clinical fields.

The WHO and UNICEF monitor global mortality from vaccine-preventable deaths and vaccination coverage as well as the introduction of new vaccines in routine immunization programs by countries around the world. Table 4 .7 shows features of progress and remaining challenges in the prevention of VPDs.

Complacency is dangerous in vaccination program implementation. In 2000, the CDC declared measles eliminated in the USA. But in 2011, 222 Americans contracted the disease, the most cases the government health agency had seen in 15 years (CDC MMWR 2012). Measles is one of the most contagious VPDs. Most of the cases between 2010 and 2012 were among people who had not been vaccinated, but a significant number had received one or even two doses of measles-containing vaccine. Cases in North and South America have occurred after importation among people traveling in Europe or visitors from Europe, where there have been very large epidemics. France reported 14,966 measles cases in 2011 and six deaths. The UK has an ongoing epidemic of measles which often affects babies too young to receive the vaccine, who are vulnerable to severe cases. Measles is a highly infectious and dangerous disease with important complications, including pneumonia, encephalitis, and even death. Infants before the age of routine vaccination, people with compromised immune systems, including the elderly and those with HIV or types of cancer, are at risk. Mumps has also seen a resurgence in the USA, although the circumstances surrounding the spike differ from measles. Diphtheria and pertussis are "back in town". An undercurrent of anti-vaccinationism is quite common and ready to spring open in response to any willful unfounded damaging reports, as generated by an antipertussis movement in the 1980s in the UK and elsewhere, and in the aftermath of the 1998 MMR "Wakefield effect" alleging a causal relationship between MMR vaccine and autism (see Box 4.11). The latter was proven to be fraudulent, yet damaging, and an overreaction to charges of mercury poisoning due to the use of thiomersal as a preservative. The latter caused a switch in vaccine production to single-dose vials which carry a large increase in costs, making vaccines even less affordable in low-income countries.

Because of an increase in anti-vaccination attitudes many mothers are avoiding or delaying immunization, putting their children and others at risk. The US state of Washington is considering making the "opt-out clauses" for mandatory vaccination for school entry more stringent by requiring written statements from parents and their doctors. Opposition to immunization is widespread on the Internet among a generation who never experienced the horrors of children dying from pertussis, diphtheria, and measles, and being crippled by polio. Public health has a responsibility to work steadily with communities and advocacy groups to change the climate of public opinion towards vaccination.

The schedule shown in Table 4 .8 reveals the recommended and optimal ages for routine administration of currently licensed immunizations in the USA, targeted for children from birth until the age of 6 years. Doses not administered at the suggested age should be given at a subsequent doctor's visit, when indicated. The 2011 immunization schedule, which has been approved by the Advisory Committee on Immunization Practices, the American Academy of Pediatrics, and the American Academy of Family Physicians, also outlines a range of ages to administer specific vaccines for certain high-risk groups.

Vaccine supply should be adequate and continuous. Supplies should be ordered from known manufacturers meeting international standards of good practice. All batches should be tested for safety and efficacy before being released for use. There should be a sufficient 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 patient-oriented and community-oriented approaches.

Ongoing education and training on current immunization practices are needed. Incentive payments by ensuring agency or managed care systems promote complete, ontime coverage. All clinical encounters should be used to screen, immunize, and educate parents and 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 people having a history of mild to moderate local reactions, convulsions, or a 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 cases of interference between vaccine antigens.

Accurate, complete recording with computerization of records and automatic reminders helps to promote compliance, as does co-scheduling of immunization appointments with other services. Adverse events should be reported promptly, accurately, and thoroughly. A tracking system should operate with reminders of upcoming or overdue immunizations; various forms of communication such as mail, telephone, and home visits should be implemented, especially for high-risk families. Semiannual audits should be carried out to assess coverage and review patient records in the population served to determine the percentage of children covered by their 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. For example, Manitoba, Canada, established the population-based electronic Manitoba Immunization Monitoring System (MIMS) in 1988 for all Manitobans registered with the government public health insurance program. Routine immunizations provided by physicians and public health staff are included. Infants are registered at birth and the family is contacted to initiate immunization. Reminder letters are distributed through the public health offices. There is active follow-up of children to ensure completion of immunization according to the recommended schedule (MIMS Annual Report, 2011).

All health care providers should be trained in the 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 carried out by physicians in private practice, as in the USA, coverage is determined by periodic surveys.

Inspection of vaccines for safety, purity, potency, and standards is part of the public health regulatory function. Vaccines are defined as biological products and are therefore subject to regulation by national health authorities. In the USA, 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 specific federal agency empowered to carry out this regulatory function is the Center for Drugs and Biologics of the Federal Food and Drug Administration.

In the past, litigation regarding adverse effects of vaccines has led to inflation of legal costs as well as efforts to limit court settlements. The US federal government enacted the Child Vaccine Injury Act of 1988, establishing the National Vaccine Injury Compensation Program (NVICP). This legislation requires providers to document vaccines administered and to report on complications or reactions. It was intended to pay benefits to people 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 providers 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 Hib, HAV, HBV, human papillomavirus (HPV), influenza, meningococcal, pneumococcal, rotavirus, and VZV vaccines, and DTaP/TdaP, MMR, OPV, and IPV.

Adverse effects are documented through the US federal Vaccine Adverse Event Reporting System (VAERS). Created in 1990, it is a national passive reporting system that receives statements on side-effects and adverse events related to US licensed vaccines. Data obtained from VAERS are used to determine patient risk factors, assess increases in known adverse events, and identify new or rare harmful effects. An estimated 30,000 VAERS reports are filed per year, of which 10-15 percent are identified as serious. This degree of classification refers to a patient who received the vaccine and experienced permanent disability, hospitalization, a fatal illness, or death. Reports may be made by anyone, including health practitioners, manufacturers, and vaccine recipients and their guardians. Important information is obtained, but the data are limited so that determining whether the vaccine truly caused an adverse effect cannot be established from a VAERS report. A compensation system was established in the USA in 1988 for injury suffered as a result of vaccines. It includes a compensation system for such injuries as well as ensuring adequate supplies of recommended vaccines (HRSA National Vaccine Compensation Administration Program, 2012).

Newly recommended vaccines for children and adolescents have nearly doubled in number since 2000, and the cost of fully vaccinating a child has increased dramatically in the past decade. Funding of the extensive recommended schedule is a problem in all countries where this is provided as a public health service or where it is covered by health insurance. In the USA, with a lack of health insurance for some 15 percent of the population and low levels of coverage for another 15 percent, lack of coverage for immunization poses a significant problem. Many of the poorest children are covered under the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC); however, many in the working poor population lack access. Providing universal coverage for children remains to be resolved and is crucial to meeting the international standards of developed nations; it is an issue of debate in current political struggles for national health insurance in the USA.

The development of vaccines, from Jenner in the eighteenth century to the advent of recombinant hepatitis B vaccine in 1987, stands as one of the pillars of public health and, consequently, vaccines have saved innumerable lives. A giant in the field of vaccinology was Maurice Hillman who, between 1944 and 1995, was the outstanding scientific leader in the development of most of the basic vaccines in use today (Box 4.15) .

Vaccines for viral infections in humans for HIV, respiratory syncytial virus, Epstein-Barr virus, dengue fever, and hantavirus are the subjects of intense research with genetic approaches using recombinant techniques. The potential for the future of vaccines will be greatly influenced by scientific advances in genetic and molecular technology. Moreover, there is potential for the development of vaccines attached to bacteria or protein in plants, which may be given in combination against an increasing range of organisms and toxins.

Recombinant DNA technology has revolutionized basic and biomedical research since the 1970s. 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 that 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 the production of new whole-cell or subunit vaccines that are safe and inexpensive, and produce more 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 enormous sums of money and years of research on new products, are more inclined to work on vaccines that will bring great financial rewards for the company and are critical to the local health care community. This has led to less effort being expended on developing vaccines for diseases such as malaria, which affect primarily the developing world. Industry plays a crucial role in continued progress in the field. Therefore, principles and guidelines must be created to establish incentives for research, development, and application of vaccine technology from a global perspective.

Advances in science have opened an entirely new front in public health with prevention of major chronic diseases by infection control. These advances include vaccines to prevent HPV (the major cause of cervical cancer) and hepatitis B, as well as control of peptic ulcer diseases caused by the nearly universally present Helicobacter pylori, a major cause of cancer of the stomach. Making links between infectious and chronic diseases has been one of the major His role in their development included the laboratory work, as well as scientific and administrative leadership, with fundamental breakthroughs leading to development of over 40 experimental and licensed animal and human vaccines. He characterized antigens and isolated them, and performed the basic and process research and the clinical studies, all the way through the manufacturing process.

In 1944 Hilleman's contributions in the fields of virology, epidemiology, immunology, cancer research, and vaccinology led to many professional awards for lifetime achievement. Despite this, he never received a much deserved Nobel Prize or reached the level of the public or professional recognition given to Pasteur, Salk, or Sabin.

Maurice Hilleman's work led to more human and animal vaccines than any other scientist. His work saved tens of millions of lives, extending human life expectancy, improving economies, and changing the world. advances in public health and clinical medicine over the past several decades, as shown in Table 4 .9, which uses data from a CDC review of infectious disease control in 2011.

Control and eradication of infectious diseases is of national and international concern, particularly with diseases that may be used in bioterrorism or spread quickly on a worldwide basis, requiring strengthened biosafety, biosecurity, and readiness for outbreaks of dangerous and emerging pathogens. The Global Outbreak Alert and Response Network (GOARN) (Box 4.16), coordinated by the WHO on behalf of member countries, is a technical collaboration of existing institutions and networks to pool human and technical resources for rapid identification, confirmation, and response to disease outbreaks of international importance. GOARN provides an operational framework to link expertise and skills needed to keep the international community constantly alert to the threat of outbreaks and ready to respond.

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 the diseases have been abandoned owing to practical difficulties with current technology as well as management, funding, and human resource limitations. Diseases that have been under discussion for eradication have included TB, measles, and polio; some tropical diseases, such as malaria, leprosy, onchocerciasis, filariasis, and dracunculiasis; and some non-infectious conditions of public health importance. In the past, eradication has encompassed multiple definitions, such as extinction of a disease pathogen, the achievement of a situation in which no further cases of a disease occur anywhere, or control of an infection whereby transmission has ceased in a specified area. The definitions in Box 4.17 were delineated by WHO consultant Walter Dowdle in a 1999 MMWR report, The principles of disease elimination and eradication. Although developed in reference to infectious disease, the definitions describing control and elimination are relevant to non-infectious diseases as well.

Reducing epidemics of infectious diseases, through control in selected areas or target groups, contributes to the ultimate goal of eradication of the disease. Local elimination 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 address the importation of carriers and changing epidemiological patterns. 

Smallpox is characterized as 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 (c. 320 CE), and inoculation against the disease was practiced there from the eleventh century CE. 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, with 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 1721 (see Chapter 1), it was commonly practiced as a lucrative medical specialty during the eighteenth century. In the 1720s, variolation was also introduced into the American colonies, Russia, and subsequently Sweden and Denmark.

Despite all efforts, in the early eighteenth century, smallpox was a leading cause of death in all age groups. Towards the end of the eighteenth century, an estimated 400,000 people 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 1774, a cattle breeder in Partners meeting in Geneva in April 2000 brought together representatives of technical institutions, organizations, and networks in global epidemic surveillance and response, to discuss "Global Outbreak Alert and Response". Participants identified the need for a global network, building on new and existing partnerships, to strengthen biosafety and biosecurity to deal with global threats of epidemic-prone and emerging diseases. A steering committee of network partners is guiding development of the network.

WHO Geneva coordinates the international outbreak response of the Network as part of its Global Alert and Response operations. Protocols for network structure, operations, and communications have been developed to improve coordination between partners. The Network focuses technical and operational resources from scientific institutions in member states, medical and surveillance initiatives, regional technical networks, networks of laboratories, United Nations organizations (e.g., UNICEF, UNHCR), the Red Cross (International Committee of the Red Cross, International Federation of Red Cross and Red Crescent Societies and national societies), international humanitarian non-governmental organizations (e.g., Médecins sans Frontières, International Rescue Committee, Merlin, and Epicentre), and other technical institutions, networks, and organizations with capacity to contribute to international outbreak alerts and responses.

Agreed standards to international epidemic responses were developed as guiding principles for International Outbreak Alert and Response and operational protocols. These help to standardize epidemiological, laboratory, clinical management, research, communications, logistics support, security, evacuation, and communications systems. The guiding principles aim to improve the coordination of international assistance in support of local efforts by partners in the Network.

Emerging infectious diseases have been a growing concern of the global public health community for generations, but awareness and action have grown since the 1990s with more and more examples of the movement of diseases and their vectors to locations other than their natural habitat. Rift Valley fever (RVF) is one such disease which has moved to wider locations as environmental conditions permit. RVF could reach the USA via livestock, much as the Schmallenberg virus has recently reached European farm animals. International cooperation is vital to anticipate and attempt to halt the spread of such diseases, which can do very great damage to population health.

Examples Yorkshire, England, inoculated his wife and two children with cowpox to protect them during a smallpox epidemic. In 1796, Edward Jenner, an English rural 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 1). Vaccination, or at the time, the deliberate inoculation of cowpox material, was slow to be adopted universally, but by 1801, over 100,000 people in England had been vaccinated. Vaccination gathered support in the nineteenth century in military establishments and in some countries that adopted it universally. Opposition to vaccination remained strong for nearly a century based on religious grounds and observed failures of vaccination to give lifelong immunity, and because it was seen as an infringement by 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 believed that 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 1958, the Soviet Union proposed a program to the WHA to eradicate smallpox internationally, and subsequently donated 140 million doses of vaccine per year as part of the 250 million needed to promote vaccination of at least 80 percent of the world population. In 1967, the WHO adopted a target for the eradication of smallpox. The program 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 people, the aim of the mass vaccination phase was 80 percent coverage.

Increasing vaccination coverage in developing countries reduced the disease to periodic and increasingly localized outbreaks. In 1967, 33 countries were considered endemic for smallpox, and another 11 experienced importation of cases. By 1970, the number of endemic countries fell to 17, and by 1973 only six 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 five per 100,000. The program then moved into the consolidation phase, with emphasis on the 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 1920s, there was wide variation in sources of the smallpox vaccine. In the 1930s, 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 1950s made a heat-stable vaccine that could be effective in tropical field conditions in developing countries. The invention of the bifurcated needle (by Rubin in 1961) allowed for easier and more widespread vaccination by less 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 1977 the last case of smallpox was identified in Somalia, and in 1980 the WHO declared the disease eradicated. No subsequent cases have been found except for several associated with a laboratory accident in the UK in 1978. The cost of the smallpox eradication program was US$112 million or US$8 million per year. Globally, savings from vaccination were estimated to be in the order of tens of billions of US dollars of direct savings. Malaria is estimated to cost sub-Saharan African countries US$100 billion worth of lost annual gross domestic product (GDP), much of which can be saved by low-cost interventions such

l Control -reduction of disease incidence, prevalence, morbidity, or mortality to a locally acceptable level as a result of deliberate efforts; continued intervention measures are required to maintain reduction. Example: diarrheal diseases. l Elimination of disease -reduction to zero of the incidence of a specified disease in a defined geographic area as a result of deliberate efforts; continued intervention measures are required. Example: neonatal tetanus. l Elimination of infections -reduction to zero of the incidence of infection caused by a specific agent in a defined geographic area as a result of deliberate efforts; continued measures to prevent re-establishment of transmission are required. Example: measles, poliomyelitis. as insecticide-impregnated bed nets and vector control, and, it is hoped, with vaccines now in development.

The WHA recommended destruction of the last two remaining stocks of the smallpox virus in Atlanta, Georgia (USA) and Moscow (Russia) in 1999. This was delayed in 1999 owing to concern that illegal stocks may be held by some states or terrorists for potential use as weapons of mass destruction. Destruction of the stocks was also postponed owing to concern regarding the appearance of monkeypox, and a wish to use the virus for further research. Today, virus stocks are handled only in select laboratories with high security. In addition, emergency plans have been developed, including the immunization of key health workers to limit the extent of a bioterror-engendered epidemic.

Given the success in eradicating smallpox, the WHO in 1988 established a target for the eradication of polio. Although polio epidemics continue, largely in countries with limited access to public health services, the burden of disease worldwide has been greatly reduced. At the initiation of the polio eradication campaign, 350,000 cases of childhood paralysis were attributed to polio in 125 countries. By 2009, this number was reduced to 1604 cases. Thus, since 1988, the number of polio cases has fallen by over 99 percent. Only three countries have never achieved wild-poliovirus interruption, and remain endemic for polio: Afghanistan, Nigeria, and Pakistan. However, in 2009-2010, 23 countries that were previously polio free were reinfected, including Angola, Chad, and DRC. Support from member countries and international organizations and agencies such as UNI-CEF, GAVI, the Gates Foundation, and Rotary International has led to wide-scale increases in immunization coverage throughout the world. The WHO promotes use of OPV as part of routine infant immunization on National Immunization Days (NIDs) or supplementary immunization activities (SIAs). This strategy has been successful in the Americas, Europe, and China, but several countries remain problematic. In 2011, India experienced far fewer cases than in 2010 as a result of a massive commitment to supplementary immunization activities (SIAs) and a slow improvement in basic immunization coverage in key problematic states where polio remains endemic at low levels.

Eradication of wild polio will require flexibility in vaccination strategies and may necessitate the combined approach, using OPV (Sabin, attenuated live vaccine) and IPV (Salk, inactivated polio vaccine), as adopted in the USA between 1997 and 2000 to prevent vaccine-associated clinical cases (i.e., VAPP). The USA has since switched to an IPV-only vaccination policy, which has been adopted by most of the industrialized countries but is impractical for developing nations because of high cost and less than needed immunization coverage.

Currently, IPV is largely used only in countries where interruption of wild poliovirus has occurred, but lower intestinal immunity from IPV may be a risk for imported polio. 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. Polio made a resurgence in 2004 in Nigeria, and in 2005 in a number of countries previously thought to be under control. The use of OPV has been put in doubt by recent decisions in the industrialized countries to follow the US example of IPV only. The developing countries will need to rely on OPV in the coming years because of the high cost and limited supply of IPV.

Eradication of malaria was thought to be possible in the 1950s when major gains were seen in malaria control by aggressive environmental control, with case finding and management. However, poorly sustained vector control, banning of DDT, and lack of development of an effective vaccine have been major obstacles. Malaria control suffered serious setbacks because of a failure of political resolve and continuity needed in the support for necessary programs.

In the 1950s great progress was made largely using dichlorodiphenyltrichloroethane (DDT) in eliminating malaria in the Caribbean, the Balkans, and many countries in the Pacific Region. However, widespread use of DDT as an agricultural pesticide reduced its effectiveness as resistance developed in mosquito populations. A movement against the use of DDT was stimulated by the publication of Silent Spring by Rachel Carson in 1962, which raised concerns over the environmental and long-term effects of the large-scale use of DDT. In 1972, DDT was banned in the USA, and subsequently for agricultural use worldwide.

Malaria control efforts were not sustained in many countries, and a dreadful comeback of the disease occurred in Africa and Asia in the 1980s. The emergence of mosquitoes resistant to insecticides, and strains of the parasite resistant to antimalarial drugs have made control even more difficult, expensive, and cumbersome.

Renewed efforts in malaria control required new approaches with case finding and treatment as well as vector control. The 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 1990s. The CHWs investigate suspect cases by taking clinical histories and blood smears. A presumptive diagnosis is made clinically or by local examination of blood smears. Therapy is instituted rapidly and the patient is followed up. Quality control monitoring shows high levels of accuracy in the reading of slides compared to professional laboratories.

The total ban on DDT is now seen as an overreaction to legitimate concerns over its persistence in nature. Banning of its widespread use by international convention had a critically disabling effect on national malaria control programs, contributing to a relaxation of efforts to control the disease and its comeback on a massive scale in those countries least able to adapt with the few and expensive alternative insecticides. In 2006, nearly 30 years after DDT was phased out for indoor spraying to protect residents from malaria, the WHO announced that DDT would once again play a key role in household spraying to fight the disease. DDT remains a key element for vector control, a vital aspect of malaria control.

In 2010, there were an estimated 219 million cases of malaria (uncertainty range of 154-289 million) globally, with some 660,000 deaths (490-836,000). Malaria mortality rates have fallen by more than 25 percent globally since 2000, and by 33 percent in the WHO African Region. Most deaths occur among children in Africa (WHO, World Malaria Report 2011 and Malaria fact sheet no. 94, January 2013).

DDT for malaria control through indoor spraying of homes is once again widely used in endemic areas. Since 2006, the WHO has recommended the use of insecticideimpregnated bed nets and limited uses of DDT for internal residual spraying to protect homes and reduce the risk of infection to children. Vector control by removing still water sites, particularly near residences, is a crucial part of malaria control, along with early case finding, bed nets, and multidrug treatment.

The WHO's rollback malaria program has set ambitious targets for the reduction of malaria deaths by the year 2015. Real progress has been made in international donor and national governmental support, in the widespread use of insecticide-impregnated bed nets and indoor residual spraying, as well as outdoor vector control by reducing still waters where mosquito vectors breed, the clinical management of cases, and early diagnosis and treatment with effective combination therapy. In 2010, there were just under 700,000 deaths from malaria, mainly among children and mostly located in sub-Saharan Africa. The WHO has launched the "T3: Test. Treat. Track" initiative, urging endemic countries and stakeholders to scale up diagnostic testing, treatment, and surveillance for malaria. The potential for increased control of malaria has been demonstrated by a complex of factors that depend on international donor funding, which will be problematic in times of recession.

Before the development of the measles vaccine, this disease affected most children, causing an estimated 2 million deaths globally and tens of thousands of cases of blindness. In the late 1970s, widening use of the successful measles vaccine, with local elimination of the disease in the Americas and Europe, brought measles deaths down to 535,000 in 2000 and to 240,000 in 2010. Rubella remains a threat to pregnancies, with 100,000 children born with CRS yearly. Measles combined with rubella and mumps vaccine if given in two doses can protect children and adults from these highly contagious diseases. Controversial claims against the MMR vaccine, which were later proven to be fraudulent, promoted a loss of confidence in measles vaccination in the UK and other countries.

Optimism over the potential for the eradication of measles led to an initial target date of 2010 being set, which was later moved to 2015. Measles eradication was set back owing to low levels of immunization coverage in many developing countries and breakthrough epidemics occurring in the USA, Canada, and many other countries during the 1980s and early 1990s. Despite this, regional eradication was achieved combining the two-dose policy with catch-up campaigns for older children or on NIDs, as demonstrated in the Caribbean countries. In the years 2010-2012, largescale epidemics were spreading across Western Europe, with export of cases by travelers and visitors to the Americas and elsewhere.

In 2012, the WHO launched Strategic Plan 2012-2020 to promote measles and rubella elimination, applying lessons learned from polio eradication and from the measles experience to date. This needs to be strengthened by routine immunization of children with two doses of measles-and rubella-containing vaccines, plus supplemental campaigns to reach out to the immunized, backed by improved epidemiological monitoring and laboratory capacity surveillance capacity along with improved supply-and cold-chain efforts. This program has support from many international, national, and charitable organization donor agencies with successful experience in controlling VPDs.

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 eradication of candidate diseases. Its goals were to identify specific barriers to the eradication of these diseases that might be surmountable, and thus promote eradication efforts. Selecting diseases for eradication is not purely a professional issue of resources such as vaccines and human resources, organization, and financing. It is also a matter of political will and perception of the burden of disease, and thus triggers many controversies. The CDC has published criteria for the selection of disease for eradication, as shown in Box 4.18.

NCDs are also included in the discussion of eradicability, but this is oriented towards elimination as public health problems with specified targets, such as eliminating iodine deficiency conditions together with measuring urinary iodine levels in surveys of schoolchildren and pregnant women. In many developing countries, with the support of international organizations and donors, mass immunization days are held to reach those who did not receive the routine vaccinations of childhood. These immunizations are often coupled with micronutrient supplements such as vitamin A, iron, zinc, and in some cases multivitamins as drops or sprinkles to be added to regular foods.

The subject of eradication versus control of infectious diseases is of central public health importance as technology expands the armamentarium of immunization and vector control into the twenty-first century (Table 4 .10). 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.

Health targets in the field of infectious disease control for the twenty-first century, selected by the WHO, include the following for control or eradication: Table 4 .11 shows the causes, impact, and strategies for control of neglected tropical diseases (NTDs) as defined by a 2013 report of the US Institute of Medicine based on Hotez et al. (2009) .

Many of these campaigns have already successfully achieved their interim goals. Primary targets for eradication, such as polio and measles, have proven problematic and may require changes in immunization tactics, but are achievable by 2020. Progress in the control of leprosy, onchocerciasis, filariasis, and dracunculiasis has been impressive. The coming years hold hope for breakthroughs and elimination of many preventable diseases.

In 2005, the Department for Control of Neglected Tropical Diseases was established at the WHO headquarters. Eradication is defined as the interruption of transmission worldwide and zero cases in each country to be certified as free of disease, as is the case for dracunculiasis (guinea worm) in many countries.

A WHO review and roadmap for achieving goals in NTDs noted progress made in reducing the NTDs up to 2009, with preventive chemotherapy for schistosomiasis, soil-transmitted helminths, lymphatic filariasis, onchocerciasis, and trachoma. Most progress has been made for onchocerciasis, with chemotherapy reaching nearly 60 percent of the population in need by 2009. Filariasis chemoprophylaxis reached nearly 42 percent of the population in need in 2007, but declined subsequently. For trachoma, schistosomiasis, and helminthiasis the level of coverage with chemotherapy was low (reaching 13, 8.3, and 31 percent, respectively). Progress in the adoption of intensified disease management has been uneven.

Yaws chemotherapy was made much easier when oral azithromycin was found to be as effective as injected benzathine penicillin, since it can be administered by CHWs and reach the population in need much more readily. Onchocerciasis eradication efforts in 2002 concluded that most probable elimination of the disease could be achieved in the WHO Region of the Americas, but not yet in the African Region given the existing tools. Achievements to date should be

l Scientific feasibility l Epidemiological vulnerability: existence of non-human reservoir, ease of spread, natural cyclic decline in prevalence, naturally induced immunity, ease of diagnosis, duration of any relapse potential l Effective practical intervention available: vaccine or other primary preventive or curative treatment, and means of eliminating vector. Intervention should be safe, inexpensive, long-lasting, and easily used in the field l Demonstrated feasibility of elimination in specific locations: documented elimination from island or other geographic unit l Political will/popular support l Perceived burden of the disease: morbidity, mortality, disability, extent, other effects, true burden may not be perceived, the reverse of benefits expected to accrue from eradication, and costs of care in developed and developing countries l Expected cost of eradication, particularly in relation to perceived burden of disease preserved and built upon by continued cooperative efforts of the WHO, World Bank, United Nations Development Programme (UNDP), and others. The struggle to eliminate and potentially eradicate important diseases, such as was achieved with smallpox, will require many years of strong political and funding support as well as a strong cadre of a public health workforce with new scientific breakthroughs (such as malaria and HIV vaccines). The movement, even when only partially successful, is saving millions of lives and improving the quality of life for many.

TB is caused by a group of organisms including 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 people with pulmonary or laryngeal TB through coughing, sneezing, talking, or singing. The initial infection may go unnoticed, but tuberculin sensitivity appears within a few weeks. About 95 percent of those infected enter a latent phase with a lifelong risk of reactivation. Approximately 5 percent 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 2 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. TB affects people in their adult working years, with 80-90 percent of cases in people between the ages of 15 and 49. Its devastating effects on the workforce and economic development contribute to a high cost-effectiveness for TB control. Nearly one-third of the world's population is infected with TB. In 2010, there were over 8.8 million incident cases, and nearly 1.1 million deaths and an additional 0.35 million deaths among HIV-positive people. During 2005, new cases of TB included 3 million in South-East Asia and 2.5 million in Africa, where HIV disease has become the leading comorbidity and risk for TB mortality. Approximately 13 percent of TB cases occur among HIV-positive individuals. Throughout the period between 1990 and 1999, the WHO estimates that there were 88 million new cases of TB, of which 8 million cases were in association with HIV infection. During the 1990s, an estimated 30 million people died of TB, including 2.9 million with HIV infection.

TB has also increased in the USA 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 epidemiological 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 multidrug-resistant strains (MDR), as well as homelessness, rising prison populations, poverty, and other deleterious social conditions. Directly observed therapy is an important recent breakthrough, making more effective use of the available technology, and this strategy will certainly play a major role in TB control in the twenty-first century.

The 2008 Global Tuberculosis Control Report noted 9. A new and dangerous period for TB resurgence has resulted from parallel epidemiological events, specifically the advent of HIV infection and the occurrence of MDR-TB. MDR-TB refers to organisms resistant at least to both isoniazid and rifampin, two mainstays of TB treatment. MDR-TB can have a case fatality rate as high as 70 percent. Since HIV reduces cellular immunity, people with latent TB have a high risk of activation of the disease. It is estimated that HIV-negative people have a 5-10 percent lifetime risk of contracting TB; HIV-positive people have a risk of 10 percent per year of developing clinical TB (Box 4.19) .

The incidence of TB in the USA decreased steadily until 1985, increased in 1990, and since the early 1990s has been continuously declining (Figure 4.8) . From 1986 to 1992, there was an excess of 51,600 cases over the expected rate if the previous decline in case incidence had continued. This sudden rise in TB was largely due to the HIV/AIDS epidemic and the emergence of MDR-TB, as well as a greater concentration among immigrants from areas of higher TB incidence, drug abusers, homeless people, and those with limited access to health care. This is particularly true in New York City, where MDR-TB has appeared in outbreaks among prison inmates and hospital staff. Since 2000, the majority of cases have been among people born outside the USA. Although case rates have declined in all age groups, the burden of disease is highest among older people.

The resurgence of TB cases peaked in 1992, but since then the number of cases reported annually has declined by 58 percent (to 2009). The incidence of TB in the USA has been reduced because of strong TB control programs that promptly identified people with TB and ensured completion of appropriate therapy. Aggressive staff training, outreach, and case management approaches were vital to this success. Rising rates among recent immigrants, the continued challenge of HIV/AIDS, and coincidental transmission of hepatitis A, B, and C among drug users and marginal population groups demonstrate a need for continued support for TB. Primary multidrug resistance increased from 1.1 percent of reported cases in 2009 to 1.2 percent in 2010.

Bacille Calmette-Guérin (BCG) is an attenuated strain of the tubercle bacillus developed in the early 1920s at the Pasteur Institute in Paris. It was and still is used widely as a vaccination to prevent TB, especially in high-incidence areas. It induces tuberculin sensitivity or an antigen-antibody reaction in which the antibodies produced may be somewhat protective against the tubercle bacillus in 90 percent of vaccinees. There are now several strains of BCG. Although 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 5. In some developed, low-incidence countries, it is used selectively rather than routinely. It may also be used in asymptomatic HIV-positive people or other high-risk groups.

The BCG vaccine for TB remains controversial. While used widely internationally, in the USA 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 BCG is used. Studies showing equivocal benefit of BCG in preventing TB have added to the dispute and uncertainty. While those in the field in the USA continue to oppose the use of BCG, internationally it is still felt to be of benefit in preventing TB, primarily in children. Currently, the WHO recommends the use of a single dose of BCG as close to birth as possible as part of the EPI. However, there is concern that BCG given to immunocompromised people can be dangerous.

A 1994 meta-analysis of the literature on BCG, carried out by the Technology Assessment Group at Harvard School of Public Health, concluded that BCG vaccine significantly reduces the risk of TB, by 50 percent on average. Protection is observed across many populations, study designs, and forms of TB. Age at vaccination does not affect the efficacy of BCG. Protection against TB 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.

Limitations of current chemotherapy and the only available vaccine, BCG, in the fight against TB make the continued search for new vaccines and therapeutics vital, possibly aided by new methods in the design of vaccines and drugs. However, the struggle is now best fought using the directly observed treatment, short-course (DOTS) strategy, improved diagnostic methods, and poverty alleviation and nutritional improvements in vulnerable population groups.

DOTS is a case management strategy adopted in 1993 by the WHO to improve the effectiveness of compliance with treatment of TB and reduce the increasing global burden of the disease, especially in developing countries, but also in vulnerable population groups in developed countries. The five elements of the DOTS strategy are sustainable government commitment, quality assurance of sputum microscopy, standardized short-course treatment (including DOTS), regular supply of drugs, and establishment of reporting and recording systems (Box 4.20). The strategy of DOTS uses CHWs to visit the patient, and observe him or her taking the various medications, providing incentive, support, and moral coercion to complete the needed 6-8 month therapy. DOTS has been shown to cure up to 95 percent of cases, at a cost of as little as US$11 over the period of treatment per patient. It is one of the few hopes of containing the current TB pandemic.

The goal of this approach is to reduce TB morbidity and mortality and the chance of M. tuberculosis developing resistance to primary treatment drugs. Target goals of TB control adopted in 1991 by the WHA include at least a 70 percent detection rate of the estimated incidence of sputum smearpositive pulmonary tuberculosis (PTB+) and a cure rate of 85 percent or higher for newly detected PTB+ cases. The 85 percent or higher cure rate was adopted on the basis of accumulated experience in Africa and certain districts of China.

Performance indicators surrounding the DOTS program use the proportion detected of PTB+, which is the most infectious form of TB. PTB+ is associated with high mortality and is the most effective form of TB to use for bacteriological monitoring of treatment progress. The proportion of newly detected PTB+ cases among the total number of adults with PTB reflects the proper application of diagnostic criteria. In countries with a medium or high TB burden, when necessary laboratory resources are available and sputum smears for microscopy are administered to TB patients, PTB+ accounts for more than 50 percent of all TB cases and over 65 percent of new PTB cases in adults. Achieving a high (i.e., ≥ 85 percent) cure rate for PTB+ is a critical priority for TB control programs. Failure to achieve this rate results in continued infectiousness and possible development of MDR-TB, characterized by resistance to at least isoniazid and rifampin.

Even under adverse conditions, DOTS produces excellent results. It is one of the most cost-effective health

DOTS remains at the heart of the Stop TB Strategy. The following are crucial components of a national TB program as an internationally recommended strategy for TB control that has been recognized as a highly efficient and cost-effective strategy. DOTS comprises five components: 1. Political commitment with increased and sustained financing -legislation, planning, human resources, training.

Case detection through quality-assured bacteriologystrengthening TB laboratories, drug resistance surveillance.

-TB treatment and program management guidelines, International Standards of TB Care (ISTC), PPM, Practical Approach to Lung Health (PAL), community-patient involvement. 4. An effective drug supply and management systemavailability of TB drugs, TB drug management, Global Drug Facility (GDF), Green Light Committee; regular, uninterrupted supply of high-quality anti-TB drugs. 5. Monitoring and evaluation system and impact measurement.

interventions combining public health and clinical medical approaches. It proves most efficacious among patients in poor self-care settings, such as homeless people, drug users, and those with AIDS. In 2006, the WHO rededicated itself to TB control with the "Stop TB Strategy" for control of TB 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 shortterm chemotherapy in well-managed programs of DOTS, emphasizing strict compliance with therapy for infectious cases with a goal of an 85 percent cure rate. The primary goals of the Stop TB Strategy are to reduce TB incidence and mortality by 50 percent by 2015, relative to 1990 rates, and to eliminate TB as a public health problem by 2050.

TB control remains feasible with current medical and public health methods. Deterioration in its control should not lead to despair and passivity. The recent trend towards successful control by DOTS, despite the growing problem of MDR-TB, suggests that control and gradual reduction can be achieved by an activist, community outreach approach. In 2006, the WHO reaffirmed TB control as one of its major priorities, expressing grave concern that the MDR organism, now widespread 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. Extremely drug-resistant tuberculosis (XDR-TB) has become a central concern in addressing the current TB epidemic and is part of a WHO-led strategy in this field.

To manage a high and increasing burden of TB in Kazakhstan, in 1998 the Ministry of Health adopted and implemented a new National Tuberculosis Program, the objectives and target goals of which are in accord with the DOTS strategy. Primary health care physicians and TB specialists have received training in case detection, and laboratories have been equipped with binocular microscopes. Unfavorable treatment outcomes for new TB+ cases were associated with alcohol abuse, homelessness, previous incarceration, unemployment, being male, and urban residence.

The epidemic curve peaked in 1998 and has since been in continuous decline. Treatment of MDR-TB is costly and complex, but has become an essential part of international TB work. The standardized mortality rates from TB for Kazakhstan, the Commonwealth of Independent States, the Central Asian Republics (Uzbekistan, etc.), the old EU countries and the new EU (Eastern European) countries are shown in Figure 4 .9.

Acute infectious diseases caused by group A streptococci include streptococcal sore throat, scarlet fever, puerperal fever, septicemia, erysipelas, cellulitis, mastoiditis, otitis media, pneumonia, peritonsillitis (quinsy), wound infections, toxic shock syndrome, and fasciitis, the "flesh-eating bacteria". Streptococcus pyogenes group A includes some 80 serologically distinct types which vary in geographic location and clinical significance. Transmission is by droplet, person-to-person direct contact, or food infected by carriers. Important complications from a public health point of view include acute rheumatic fever and acute glomerulonephritis, as well as skin infections and pneumonia. Acute rheumatic fever (ARF) is a complication of Streptococcus A infection that has virtually disappeared from industrialized countries as a result of improved standards of living and antibiotic therapy. Mortality rates from rheumatic fever and rheumatic heart disease have declined steadily over the past three decades, largely due to the increased availability and use of antibiotics. In developing nations and lower socioeconomic areas where rheumatic fever is more prevalent, ARF is a major cause of death and disability in children and adolescents. Moreover, outbreaks were recorded in the USA in 1985, and an increasing number of cases has been seen since 1990. 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. It 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.

Group B streptococci (GBS) are related organisms. They commonly colonize the reproductive tract of women of reproductive age, and are the leading cause of meningitis in newborn infants. As with other strains of beta-hemolytic streptococci, treatment with penicillin (or appropriate therapy for allergic patients) is effective. Women should be screened for GBS at 35-37 weeks of pregnancy and treated during labor and delivery. If screening tests are unavailable, the risk of infection is high, thus recommendations are to treat prophylactically.

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 USA for large sectors of the population, along with crowding and possibly poor access to medical care due to a lack of or inadequate health insurance.

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 public information are needed to ensure rapid and effective care to prevent chronic and costly conditions.

Zoonoses are infectious diseases transmissible from vertebrate animals to humans. Common examples of zoonoses of public health importance in non-industrialized countries include brucellosis and rabies. In industrialized countries, salmonellosis, mad cow disease, and influenza have reinforced the importance of relationships between animal and human health. Strong cooperation between public health and veterinary public health authorities is required to monitor and to prevent such diseases. Zoonoses have been described and recognized over many centuries. They involve several types of agents: bacteria, parasites, viruses, and unconventional agents. Bacterial organisms transmitted by animals include salmonellosis and campylobacteriosis, anthrax, brucellosis, E. coli, leptospirosis, plague, shigellosis, and tularemia.

Viruses transmitted by animals include rabies, which is a disease of carnivores and bats mainly transmissible to humans by bites. Almost all people severely exposed to rabid animals will die if not treated. An estimated 55,000 people, predominantly children, die of this disease in the world every year. Control measures focus on immunization of domestic animals and household pets. Infected dog-bite transmission is responsible for most human deaths.

Other viral zoonoses include avian influenza, Crimean-Congo hemorrhagic fever, Ebola, and RVF. Bovine spongiform encephalopathy (BSE) is thought to be the cause of variant Creutzfeldt-Jakob disease (vCJD), which is a neurological disease different from CJD, leading to death in humans.

Other important zoonoses are brucellosis and echinococcosis/hydatidosis. The class of zoonoses still represents significant and often neglected public health threats, affecting hundreds of thousands of people, particularly in developing countries. Schmallenberg virus, which affects cattle, is moving into new countries in Europe (for example, it was recently imported from France into Poland), indicating once again that disease agent transmission is a potent issue in public health affecting animals. This is of great economic importance in itself but in time it can also affect humans. Despite the heavy burden they represent and their potential to transfer to human diseases, many zoonotic diseases are preventable with professional veterinary public health measures, which are an essential part of general public health.

Brucellosis is a disease occurring in cattle (Brucella abortus), dogs (B. canis), goats and sheep (B. melitensis), and pigs (B. suis). Humans are affected mainly through ingestion of contaminated milk products, by contact, or by 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. Transmission can occur as a result of contact with tissues, blood, urine, vaginal discharges; however, brucellosis is predominantly spread 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 2 percent, but disability is common and can be pronounced.

The disease is primarily seen in Mediterranean countries, the Middle East, India, central Asia, and Central and South America. Brucellosis occurs primarily as an occupational disease of people working with and in contact with tissues, blood, and urine of infected animals, especially goats and sheep. It is an occupational hazard for farmers, veterinarians, packing house workers, butchers, tanners, and laboratory workers. It is also transmitted to consumers of unpasteurized milk from infected animals. Because animal vectors include wild animals, eradication of the disease 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. Epidemiological investigation may help to 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 all serve as important actions to prevent 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 a 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 the disease, including foxes, wolves, bats, skunks, and raccoons; these wild animals may infect domestic animals such as dogs, cats, and farm animals. Animal bites break the skin or mucous membrane, thus allowing entry of the virus from the infected saliva into the bloodstream. The incubation period of the virus is 2-8 weeks; it can be as long as several years or as short as 5 days. Accordingly, postexposure preventive treatment is a public health emergency.

The clinical disease often begins with a feeling of apprehension, headache, and pyrexia, followed by muscle spasms, acute encephalitis, and death. Both fear of water ("hydrophobia") and fear of swallowing are characteristics of the disease. Rabies is almost always fatal within a week of onset of symptoms. There is no effective treatment, thus control relies on vaccination of animals, rapid prophylaxis of exposed people, and prevention of contact with biting and scratching animals. The disease is estimated to cause 30,000 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 pre-exposure prophylaxis for groups at risk (e.g., veterinarians, zoo workers) and postexposure immune globulin and vaccine administration for people 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 3 months of age and revaccinated according to veterinary instructions.

Prevention in wild animals to reduce the reservoir is successful in achieving local eradication in settings where re-entry from neighboring settings is limited. Since 1978, 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 under way since 1989. The number of rabies cases in these affected areas has declined by some 70 percent. Switzerland is now virtually rabies free because of this vaccination program. However, the WHO Collaborating Centre for Rabies Surveillance and Research reports that rabies cases in 2012 increased by more than 300, to a total of 6185 cases, mainly due to the large increase in cases in Poland.

The potential exists for local eradication, especially on islands or in partially restricted areas with limited possibilities for wild animal entry. Livestock need not be routinely immunized against rabies, except in high-risk areas. In regions in which bats are major reservoirs of the disease, as in the USA, eradication is not currently feasible (WHO Collaborating Center for Rabies Surveillance and Research, 2012).

Salmonella, discussed later in this chapter under the classification of diarrheal diseases, is one of the most common infectious diseases among animals. It is easily spread to humans via poultry, meat, eggs, and dairy products. Transmission may also occur from contact with infected animals, particularly reptile pets. Specific antigenic types are associated with foodborne transmission to humans, causing generalized illness and gastroenteritis. The severity of the disease varies widely, and salmonella can be devastating among vulnerable populations, such as young children and elderly or immunocompromised people. Epidemiological investigation of common food source outbreaks may uncover hazardous food handling practices. Laboratory confirmation or serotypes help in monitoring the disease. Prevention is achieved 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 herbivorous animals and its spores contaminate soil worldwide. It predominantly affects humans exposed in occupational settings. Transmission is cutaneous by contact, gastrointestinal by ingestion, or respiratory by inhalation. In recent decades it has gained attention as a highly potent agent for germ warfare or terrorism, as in Iraq in 1997. In 2001, anthrax was used as a bioterror agent against the USA. Twenty-two people were infected, with a 50 percent case mortality rate.

Although most B. anthracis strains are susceptible to common antibiotics, concern over the possible existence of weaponized, antibiotic-resistant anthrax has prompted extensive planning to counter the possibility of terrorist or other attacks. Limited supplies of vaccine are available; however, in the absence of an epidemic, its use is only justified for veterinarians, key public health workers, soldiers, and laboratory personnel with a higher risk of exposure.

Creutzfeldt-Jakob Disease (CJD) is a rare degenerative disease of the CNS linked to consumption of beef from cattle infected with BSE. It is transmitted by prion proteins in animal feed prepared from contaminated animal material and in transplanted organs. This disease was identified in the UK linked to infected cattle. This noteworthy case led to a 1997 ban on British beef in many parts of the world as well as the slaughter of large numbers of potentially contaminated animals. Between 2000 and 2011, the UK accumulated a total of 175 reported cases of vCJD, and there were 49 in other countries, but few cases of the disease have been reported since 2000. This disease is still under study with surveillance and follow-up by veterinary services among cattle, and under public health watch for human cases.

The tapeworm causing diphyllobothriasis (Diphyllobothrium latum) is widespread in North American freshwater fish, passing from crustacean to fish to humans by consumption of raw freshwater fish. It is especially common among Inuit peoples and may be asymptomatic or cause severe general and abdominal disorders. Food hygiene (freezing and cooking of meat) is recommended; treatment is by anthelmintics.

Leptospiroses are a group of zoonotic bacterial diseases found worldwide in rats, raccoons, and domestic animals. They affect farmers, sewer workers, dairy and abattoir workers, veterinarians, military personnel, and miners with transmission via exposure to or ingestion of urinecontaminated water or tissues of infected animals. Disease 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.

Vectorborne 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 conditions; mosquitoes thrive in warm, wet weather, and are suppressed by cold weather; and 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 1902). 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 is approximately 12-30 days, depending on the specific Plasmodium involved. Some strains of P. vivax may have a protracted incubation period of 8-10 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 10 percent. An untreated attack may last for 18 months. Other forms of malaria may present as a nonspecific fever. Relapse of P. ovale malaria may occur up to 5 years after initial infection; malaria may persist in chronic form for up to 50 years.

Malaria control advanced during the 1940s to 1960s through improved chloroquine treatment and the 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, case finding, and treatment were reduced. Moreover, the world saw an increase in drug resistance, thus this disease is now recognized as a central public health problem globally. The need for a vaccine for malaria control is now more apparent than ever.

Globally, 225 million people are infected with malaria each year. Of the hundreds of thousands of deaths resulting from malaria, more than two-thirds are concentrated in sub-Saharan Africa, and a large proportion strike children. Up to 50 percent of health expenditures are attributed to treatment of malaria patients. Large areas, particularly in forest or savannah regions with high rainfall, are holoendemic; this means that nearly all individuals residing in the region are infected. At 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 11 percent of all disability-adjusted life years (DALYs) lost per year in sub-Saharan Africa are from malaria, which places a heavy economic burden on a country's health system.

In the Americas, the number of cases detected has risen every year since 1974, and the WHO estimated there to have been 2.2-2.5 million cases in 1991. The nine most endemic countries in the Americas achieved a 60 percent reduction in malaria mortality between 1994 and 1997. In 2002, CDC reported that of the 1337 malaria cases in the USA, all but five were imported, i.e., acquired in malariaendemic countries.

Malaria kills more nearly 800,000 people annually and infects 200-300 million (WHO, 2011) Sub-Saharan Africa is by far the hardest hit region, with approximately 90 percent of the deaths. Among the most vulnerable and afflicted are children: a child dies from malaria every 45 seconds. An enormous burden causing unspeakable harm, malaria is responsible for approximately 20 percent of all child mortality in Africa. Moreover, there is an increase in strains resistant to the major available drugs and of mosquitoes resistant to the insecticides in use.

Vector control, case finding, and treatment remain the mainstay of control. Use of insecticide-impregnated bed nets and curtains, residual house spraying, and strengthened vector control activities are important, as are early diagnosis and carefully monitored treatment with evaluating for resistance. Control of malaria will ultimately depend on a safe, effective, and inexpensive vaccine (Box 4.21). Attempts to develop a malaria vaccine have been unsuccessful to date owing to the large number of genetic types of P. falciparum even in localized areas. Twenty-three prospective

The World Health Organization has indicated that it could recommend the first malaria vaccine, RTS,S/AS01 Plasmodium falciparum vaccine, for use in some African countries as early as 2015; the full phase III trial results will be available in 2014. The vaccine has been developed by a public-private partnership primarily for use in infants and young children in sub-Saharan Africa. It is a hybrid construct of the hepatitis B surface antigen fused with a recombinant antigen derived from part of the malaria circum-sporozoite protein. This is the protein coat of the sporozoite, the parasite stage inoculated by the feeding anopheline mosquito; it then invades liver cells and multiplies there before entering the bloodstream. Many other potential malaria vaccines are in various stages of development, but the RTS,S/AS01 vaccine is closer to registration and potential deployment than the others (White, 2011).

Great improvements have been achieved using existing methods of vector and transmission control prevention such as insecticide treated bed nets, use of DDT for targeted use in indoor spraying, reduction of still water breeding sites for carrier mosquitoes, seasonal chemo-prevention and arstesunate for severe cases to reduce mortality (White, 2011) .

In 2013, GlaxoSmithKline in the UK is seeking approval of a vaccine which has shown encouraging results and safety in a large field trial in Africa with 25% reduction in infant malaria cases in Phase III clinical trials.

A safe, effective, and affordable malaria vaccine will have an enormous impact on the world. As the tenacious scientists, researchers, and investigators persist, the rest of the world anticipates the day this vaccine is announced: it will be like the day the first man landed on the moon. The WHO is optimistic that a safe and effective new vaccine is within sight. 

P. falciparum vaccines are currently in clinical trials, with some reported effectiveness. Research into 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. Because of increasing drug resistance, research on malaria has concentrated on the pharmacological aspects of the disease. Effective control of malaria will require both new drugs for resistant infections and primary prevention through vector control. Larvicides are used with some success, including bacteria which destroy larvae and genetic modification of mosquitoes to reduce their fertility, with hopes for eventual vaccine development.

In 1998, the WHO initiated a campaign to "Roll Back Malaria" and maintain the dream of eradication in the future; malaria is included in MDG6 and Rollback Malaria for the period 2006-2015. Effective low-technology interventions include community-based case finding, early treatment with good-quality insecticides, and vector control. The use of CHWs and widespread provision of insecticideimpregnated bed nets in endemic areas has shown promising results. Between 2008 and 2010 insecticide-treated nets protected 578 million people (10 percent of the at-risk population). DDT was banned in many countries; however, it is recommended by the WHO for limited uses such as inhouse spraying but not for wide environmental insecticide use. Local control and even eradication can be achieved with currently available technology. This requires the integration of public health and clinical approaches with strong political commitment internationally and nationally in the affected countries. After decades of work in many centers, in 2013 there are hopeful signs of an effective vaccine for malaria emerging, but this will take more years of research and clinical trials to become an effective instrument for control of this still deadly disease.

The Rickettsiae are obligate parasites; they can only replicate in living cells, but otherwise they have characteristics of bacteria. They represent a class 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 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 before the advent of antibiotics.

This group of diseases exists in nature in ways that make them impossible to eradicate; however, clinical diagnosis, host protection, and vector control can help to reduce the burden of disease and control any outbreaks that may occur.

Public education regarding self-protection, appropriate clothing, tick removal, and localized control measures such as spraying and habitat modification are effective.

Epidemic typhus, first identified in 1836, is due to Rickettsia prowazekii. Spread primarily by the body louse, typhus was the cause of an estimated 3 million deaths, especially during war and famine, in Poland and the Soviet Union from 1915 to 1922. Untreated, the fatality rate ranges from 5 to 40 percent. 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, antimosquito measures, judicious use of pesticides such as DDT and lindane, bed nets, vector control, and protective clothing. 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 represented a serious health problem for US armed forces in the Pacific during World War II. It is spread by Rickettsia tsutsugamushi and has a wide variation in case fatality according to region, organism, and age of the patient.

Rocky Mountain spotted fever is a well-known and deadly 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 antitick spraying of sheep, cows, and goats helps to protect exposed workers. Protective clothing and regular removal of body ticks help to protect exposed people.

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. Transmission also occurs through 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 mouth parts.

These viruses cause acute CNS infections (meningoencephalitis), myocarditis, or undifferentiated viral illnesses with polyarthritis and rashes, or severe hemorrhagic febrile illnesses. The most important of the arbovirus diseases are yellow fever, dengue, and a wide group of encephalitic diseases, such as eastern and western equine encephalitides, Japanese encephalitis, Murray Valley encephalitis, and another group which includes West Nile fever, and others with exotic names like Rift Valley fever, Chikungunya, African swine fever, Crimean-Congo hemorrhagic fever, Powassan virus, Ppataci fever, and many others. Arbovirus diseases are often asymptomatic in vertebrates but may be severe in humans.

Over 250 antigenetically distinct arboviruses are associated with disease in humans, varying from benign fevers of short duration to severe hemorrhagic fevers. Each has a characteristic historic and geographic location, and vectorspecific clinical and virological characteristics. They can spread globally via travelers and become endemic in new regions, as ecological conditions and mass travel enable disease transfer and endemicity in newly suitable environments with increased vector presence, such as the appropriate mosquito population.

They are of international public health importance because of the potential for spread via natural phenomena and modern rapid transportation of vectors and people incubating or ill with the disease, with potential for further spreading at the point of destination. Key preventive measures include vector control to reduce mosquito breeding, mosquito nets, and individual protection with protective clothing and the use of insect repellents against mosquitoes and ticks.

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 Valley encephalitides. Japanese encephalitis is caused by a mosquito-borne arbovirus found in Asia and is associated with ricegrowing areas. It is characterized by headache, fever, convulsions, and paralysis, with fatality rates in severe cases as high as 60 percent. A currently available vaccine is used routinely in endemic areas (Japan, Korea, Thailand, India, and Taiwan) and for people traveling to infected areas. Tick-borne arboviruses causing encephalitis include the Powassan virus, which occurs sporadically in the USA and Canada. Tick-borne encephalitis is endemic in Eastern Europe, Scandinavia, and the former Soviet Union.

West Nile Virus (WNV) was first discovered in Uganda in 1937 and in the Nile Delta in 1953. Outbreaks subsequently occurred in the 1990s in Algeria and in Romania, and in Israel in 1997. Prior to 1997, the virus was not recognized as pathogenic for birds; however, scientists' understanding of the disease changed, as during this time in Israel, birds of various species died from a more virulent strain of the virus; these infected birds showed signs of paralysis and encephalitis.

WNV is a potentially severe disease typically spread by the bites of infected mosquitoes, which become infected by feeding on birds that carry the virus. Culex pipiens mosquitoes are recognized as the primary vectors of the virus. The virus remains in mosquito populations via vertical transmission, or transmission from adults to eggs; birds remain the reservoir hosts of WNV. Thus, the virus survives in nature through a mosquito-bird-mosquito cycle. Humans are at risk of acquiring the virus though the bite of infected mosquitoes. WNV can also rarely be spread through organ transplants, blood transfusions, breastfeeding and pregnancy.

WNV may cause deadly neurological disease in humans, although 80 percent of those infected with the virus show no symptoms at all. Despite this, there is no way to determine whether a person will develop an illness or not. Up to 20 percent of those who are infected will develop West Nile fever and show symptoms such as headache, body ache, nausea, swollen lymph nodes, and skin rash. The duration of these symptoms ranges from a few days to many weeks. A much smaller proportion (approximately one out of 150) of individuals infected with WNV represent a subset of people whose condition will advance, causing them to become severely ill. Corresponding symptoms include high fever, stiff neck, disorientation, coma, tremors, convulsions, loss of vision, numbness, and paralysis. The neurological effects may become permanent. Most commonly, symptoms begin to affect people approximately 3-14 days following the bite of an infected mosquito.

The disease has become endemic in many regions of the world (Box 4.22) and no WNV vaccine currently exists for humans. There is no specific treatment for WNV infection. The mild symptoms experienced by patients will pass by themselves, but patients experiencing the more severe symptoms and neuroinvasive WNV typically need to be hospitalized. Treatment is supportive and includes administration of intravenous fluids, respiratory assistance, and prevention of further infections. Individuals over the age of 50 incur the highest risk of WNV complications and death. Moreover, chronic kidney disease may occur in convalescent patients.

Many of the control measures revolve around vector control, which includes draining still waters where mosquitoes can breed, spraying with antimosquito compounds, and repairing window and door screens. Furthermore, it is very important that people use mosquito repellents and wear long sleeves and long pants (trousers) outdoors, particularly at dusk and dawn, when mosquitoes are most active. Laboratory confirmation is by serological testing. Monitoring the serology of dead birds or horses which are frequently infected via the mosquito vector may give the first indication of local appearance of the disease. In addition, the use of strategically located sentinel chicken flocks has been very effective in determining the geographic distribution of WNV and predicting local risks for infection. When birds test positive in a new area, health care providers are alerted to the signs and symptoms of WNV, increasing the effectiveness of surveillance, early intervention, and prevention. This highly successful model may potentially be applied to other zoonotic diseases.

Chikungunya fever is a disease caused by a virus (alphavirus, in the family Togaviridae) spread by the bite of infected mosquitoes. Chikungunya fever has no specific treatment and care is symptomatic but the disease is not usually fatal. It is mainly located in over 40 countries in Africa, India, and South-East Asia, causing a severe dengue-like illness that is mostly nonfatal. Insect repellents, appropriate clothing, and staying in areas with screens are standard protective measures.

The disease has spread to Europe with outbreaks in France and later Italy following importation from India by a single traveler. This disease is common in former French colonies (e.g., Réunion) and it has become common in parts of France along with its major vectors Aedes aegypti and A. albopictus.

Because of outbreaks of Chikungunya fever such as that in Italy in 2007, with over 197 cases, and in France in 2010, with 76 suspected cases reported and 32 confirmed by laboratory analysis, two of which were indigenous cases, concerns have been raised that it may become endemic in Europe, especially with climatic warming and laxity in mosquito control measures.

Rift Valley fever (RVF) is a hemorrhagic fever whose virus (Phlebotomus genus, Bunyaviridae family) is spread by mosquitoes and other insect vectors. The virus mainly affects ruminant animals (e.g., cattle, sheep, and goats), resulting in hemorrhage, abortion, and death: it causes universal abortion in ewes and a high percentage of death in lambs. It also affects humans who have been in direct contact with the meat or blood of affected animals. RVF virus causes a generalized illness in humans, and can advance to encephalitis, hemorrhage, retinitis and retinal hemorrhage leading to partial or total blindness, and death (1-2 percent).

The virus's normal habitat is in the Rift Valley of East Africa, often spreading to southern Africa, depending on climatic conditions. The primary reservoir and vector is the Aedes mosquito. RVF was first identified in Kenya, near the great Syrian-African rift which stretches from South-East Africa to the Nile valley and the Red Sea, along the Arava and Jordan valleys, up to the Bekah Valley in Lebanon and Syria.

The disease has been known since the 1930s as a health hazard for cattle and sheep. Veterinary services were well developed in British Rhodesia and South Africa. An effective veterinary vaccine was produced to protect domestic animals. A vaccine for humans was developed by the US Army at Fort Dietrich for biological warfare defense, but in limited supply.

West Nile Virus (WNV) is a potentially fatal neurological infection transmitted to people as well as horses and other mammals by infected mosquitoes and maintained in nature by transmission by birds through mosquitoes. The disease was first identified in the West Nile region of Uganda in 1937 and is now considered endemic in Africa, the Middle East, North America, Europe including Russia, the Mediterranean and Middle Eastern countries, and Australasia. Most cases are subclinical or with mild flu-like symptoms and rash. The virus is also reported in parts of Europe, e.g., north-eastern Italy and Serbia (37 cases with three deaths). Greece, Israel, Romania, Russia, and the USA represent countries which have experienced the largest outbreaks.

West Nile fever was first seen in the USA in 1999 in New York City. US populations are seeing a major resurgence of the virus, as the number of infected individuals has increased sharply, particularly in August 2012. The USA has now seen animal and human cases in nearly every state.

In 2012 CDC reported the USA to be "in the midst of one of the largest West Nile virus outbreaks ever seen in the United States". As of 11 December 2012, WNV was reported in 48 states, with 5387 cases including 243 deaths. Most cases (80 percent) were reported in 13 states, but onethird of cases were concentrated in Texas. In 2013, there were 2,059 reported cases (to 29 October) in the USA, of which 49 percent were neuroinvasive, mostly in the north east coast, the Midwest, California and Texas.

The time and place of outbreaks are affected by weather, the flight pattern of birds that sustain the virus, the number of mosquitoes that spread the virus, and human behavior. Atypically mild winters and hot summers experienced by many states may promote conditions for the spread of the virus to humans. International transportation of the WNV by bird vectors has led to importation and establishment of vectorborne pathogens outside their usual habitat. This is a serious global threat which may worsen as climatic changes favor vector proliferation.

An unusual spread of RVF northward to the Sudan and along the Aswan Dam reservoir to Egypt in 1977-1978 caused hundreds of thousands of animal deaths, as well as 18,000 human cases and 598 deaths. RVF appeared again in Egypt in 1993. This disease is suspected to have been one of the 10 plagues of Egypt leading to the exodus of the Children of Israel from Egypt during pharaonic-biblical times.

Preventive measures taken in Israel to prevent entry of RVF included the immunization of 1.5 million domestic animals, from dairy cattle to Bedouin sheep and goat flocks in Israel, the West Bank, Gaza, and the Sinai Peninsula, to create a cordon sanitaire of protected animals. Laboratories were prepared to identify any suspected animal or human cases. Public health and veterinary staff of the Ministry of Agriculture were given training and guidelines to handle a public health emergency alert situation, lest the RVF virus become established in the country and endanger animals and humans alike, with possible spread throughout the region and into Europe.

In 1997, an outbreak of RVF occurred in Kenya, initially thought to be anthrax, with hundreds of cases and dozens of deaths, related to an 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.

RVF has reappeared in the Middle East in Yemen and Saudi Arabia since 2000 and may have become endemic in the region. Box 4.23 summarizes unexpected RVF outbreaks in Mauritania in 2010 and 2012.

Renewed interest in RVF stems from its movement away from traditional habitats to the Middle East and potentially to Europe. This disease is of great economic importance because of its potential impact on animal husbandry. It is also a threat to human public health and its spread to new pastures in Africa and Europe may accelerate with changing climatic conditions. Imported suspected cases have been reported in France, in a tourist to Zimbabwe, and in French soldiers returning from duty in Chad.

RVF has recently reappeared in East Africa, including Sudan, the Nile Valley, and countries near the Indian Ocean. RVF is very active and sensitive to climate and other environmental as well as socioeconomic changes, such as occurred with the Nasser Dam in the 1970s. Ecological changes and growing human populations with increased demand for meat promote greater movements of livestock, controlled and uncontrolled. This increases the risk of spread of RVF in the Mediterranean basin, Central Europe, and the Middle East (Chevalier et al., 2010) , as has occurred with other arboviruses. This provides an incentive for intensive research into the vaccinology of RVF virus (Dar et al., 2013) . RVF was in the past considered a potentially seriously disruptive biological warfare agent. The potential methods and effects of deliberate or inadvertent introduction of RVF into the USA via international movement of livestock or as a terrorist act come under the watchful eye of the CDC and security agencies (Hartley et al., 2011) .

Arboviruses can also cause hemorrhagic fevers, which are acute febrile illnesses. They are characterized by extensive

On 4 October 2012, the Mauritanian Ministry of Health announced an outbreak of Rift Valley fever (RVF). The first (index) case was identified in mid-September, and 1 month later 24 cases, including 13 deaths, were reported. By the end of October, the number of RVF cases had risen to 34 and 17 deaths in six regions of the country. Laboratory tests on human and human samples with enzyme-linked immunosorbent assay and polymerase chain reaction at the National Veterinary Research Laboratory confirmed that RVF virus was circulating in various regions.

Mauritania had a previous unanticipated outbreak in September and October 2010, after exceptional amounts of rainfall. The formation of large ponds resulted in oases in the Saharan region of Adrar. Atypical growth of vegetation drew in shepherds from distant regions, and provided optimal conditions for mosquito growth in masses, mostly Culex and Anopheles. In the weeks following the heavy rainfall, major outbreaks of both malaria and RVF occurred in many oases.

The first documented case in livestock was an infected camel. A herdsman slaughtered the animal and ate the uncooked meat, sharing it with others. A few days later, those who had consumed the camel meat had severe intestinal and hemorrhagic symptoms and died. Laboratory tests confirmed RVF virus.

By the end of 2010, 63 human cases including 13 deaths due to RVF had been confirmed, although the true RVF morbidity and mortality was likely to be much higher in these remote regions with unrecorded cases and deaths.

RVF outbreaks have long afflicted regions in Kenya, where the virus is endemic, and have moved to new regions further north, including Sudan, Egypt (1976 -1977 , and more recently Yemen, Aden, and Saudi Arabia (2000) . Camels and small rodents are thought to have served a crucial role in transmission of RVF from northern Sudan to southern Egypt in 1977.

hemorrhagic phenomena (internal and external), liver damage, shock, and often high mortality rates. The potential for international transmission is high.

Similar to a number of other infectious diseases examined in this chapter, yellow fever is transmitted via infected mosquitoes. It is characterized as an acute viral disease of short duration and varying severity with jaundice, hence the name "yellow" fever. The mosquito is the chief vector of yellow fever, which transmits the virus from host to host, typically from monkeys to humans.

Once the virus is transmitted to a human, it typically incubates for 3-6 days. Subsequently, the infection can follow one of two pathways. It can enter an acute phase, in which typical symptoms include fever, muscle pain, backache, headache, and nausea. For the majority of patients, their condition improves and these symptoms are gone a few days later.

The other possible route the infection can take represents a more toxic phase; generally 15 percent of patients infected with the yellow fever virus enter this phase as well. Multiple body systems are affected, the high fever reappears, and the patient is suddenly struck with jaundice, severe abdominal pain, and vomiting. As the disease advances, bleeding from the mouth, nose, eyes, or stomach may occur. Kidney function may weaken, causing an emergency situation. Approximately 50 percent of patients who experience this toxic phase die within 10-14 days; the other 50 percent recuperate without suffering from major organ damage.

The case fatality rate is 5 percent in endemic areas, but may be as high as 50 percent in non-endemic areas and during epidemics. It has caused major epidemics in the Americas in the past, but was successfully controlled by elimination of the vector, A. aegypti. As no specific treatment for yellow fever currently exists, supportive care is effective in treating dehydration and fever. While this form of care can be successful in improving the condition of severely ill patients, it is unlikely to be available in poor, low-resource regions.

Undoubtedly, vaccination is the most significant, effective preventive measure against yellow fever. To effectively prevent outbreaks in affected areas, experts agree that vaccination uptake must reach at least 60-80 percent of the population at risk. To improve vaccination rates throughout endemic areas, preventive vaccination can be implemented via routine infant immunizations as well as one-off mass campaigns. Also recommended for those traveling to infected areas, the live attenuated yellow fever vaccine is regarded as safe and affordable. One single dose offers protection from yellow fever for 30-35 years, and perhaps for life. Other important preventive measures include mosquito control and epidemic preparedness, which refers to rapid detection and blood tests for yellow fever capable of being carried out at a national laboratory. Furthermore, determining the mode of transmission and vector control of yellow fever played a major role in the development of public health (see Chapter 1). The WHO reports that annually there are 200,000 cases of yellow fever, resulting in 30,000 deaths globally. Originally imported to the Americas from Africa, yellow fever is endemic in 45 countries in Africa and Latin America. In Africa, over 500 million individuals reside in 32 endemic countries.

Other populations are at risk in 13 countries in Latin America; Ecuador, Brazil, Bolivia, Columbia, and Peru represent the countries at highest risk of yellow fever. Cases of yellow fever have been increasing over the past two decades owing to declining population immunity to infection in conjunction with environmental factors such as deforestation, urbanization, and global travel.

Dengue fever is a serious influenza-like illness, capable of advancing and leading to a fatal complication called severe dengue (formerly referred to as dengue hemorrhagic fever). An acute sudden-onset viral disease, dengue is transmitted by Aedes mosquitoes; humans contract the disease via bites of infected female mosquitoes. Unlike most other mosquitoes, A. aegypti feeds during the day: early morning and evening time before sunset account for its peak biting times. Dengue surveillance shows that dengue is occurring more frequently, mostly in tropical and subtropical climates (Box 4.24), with a dramatic increase globally as shown in Figure 4 .10.

Dengue fever is characterized by 3-5 days of high fever, intense headache, myalgia, arthralgia, nausea, vomiting, and rash. Severe dengue is a lethal complication that may develop as a result of dengue fever. It may occur due to any of the following conditions: fluid accumulation, plasma leakage, respiratory problems, severe bleeding, or organ impairment. Warning signs that a person has developed severe dengue include continuous vomiting, rapid breathing, severe abdominal pain, bleeding gums, and the presence of blood in vomit. According to the WHO, these warning signs arise 3-7 days after the initial symptoms and they coincide with a reduction in fever. Medical treatment with fluid replacement infusions is essential to avoid further illness and death, as the next 1-2 days of this period can be fatal. To date, no particular treatment for dengue exists; however, for severe dengue the supportive medical treatment can drastically reduce mortality rates from over 20 percent to below 1 percent.

Scientists have recognized four particular, closely associated serotypes of the virus that lead to dengue. Thus, patients recovering from an infection by one serotype acquire a lifelong immunity protecting against that specific one. Nevertheless, following recovery, immunity against the other three serotypes is incomplete and temporary. Further infections by more than one serotype raise a patient's risk of acquiring severe dengue. Similar to other vectorborne diseases, prevention of dengue relies on human behavioral practices that limit contact with mosquitoes. These measures include disposing of solid waste appropriately, consistently cleaning water storage containers, and using household protective measures such as window screens, vaporizers, and insecticides. Epidemics of dengue fever can be explosive; however, as mentioned, adequate treatment can greatly reduce the number of deaths.

Lassa fever is an acute viral hemorrhagic fever caused by the Lassa virus, first isolated in Lassa, Nigeria, in 1969. It is widely distributed in West Africa and is responsible for 200,000-400,000 cases and 5000 deaths annually. It is spread by direct contact with blood, urine, or secretions of infected rodents as well as by direct person-to-person contact in hospital and laboratory settings. The disease is characterized by a persistent or spiking fever for 2-4 weeks, and may include severe hypotension, shock, and hemorrhaging. The case fatality rate is 15 percent. A global network of WHO Collaborating Centers in many parts of the world works together and with WHO member states to investigate and manage outbreaks (WHO, 2012).

Marburg disease is a rare viral disease causing a hemorrhagic fever. It was discovered in 1967 in an epidemic in Marburg, Germany, and Serbia, following exposure to African green Dengue is a mosquito-borne virus that is now endemic in over 100 countries, with a significant increase in the global incidence in recent decades. Found mostly in tropical and subtropical climates, dengue predominantly affects urban and semi-urban regions. Severe dengue was seen in the USA in the nineteenth century: in Charleston, South Carolina, in 1828; Savannah, Georgia, in 1850; and 16,000 cases in Austin, Texas, in 1885; further outbreaks occurred in the 1920s, and "breakbone fever", as it was called, affected almost 10 percent of the population of Miami, Florida, in the 1940s. After World War II, mosquito control with DDT reduced outbreaks in the USA.

Dengue virus is thought to have transferred from monkeys to humans hundreds of years ago, but remained localized geographically until it emerged as a worldwide problem in the 1950s, probably as a result of mass movement of goods and people with mosquitoes, when epidemics were seen in the Philippines and Thailand. From the 1980s, large numbers of cases began to appear in the Caribbean and Latin America, following declines in vector control programs from the 1970s. Dengue is now a global public health problem in Asia, the Pacific, the Americas, and Caribbean countries. Severe dengue represents a major cause of hospitalization, morbidity, and mortality, particularly among children living in these regions.

The WHO reports that more than 2.5 billion individuals, or 40 percent of the global population, are currently at risk for developing dengue fever. Estimates suggest that 50-100 million cases of dengue occur annually worldwide. The substantial increase in global evidence is illustrated in Figure 4 .10. Dengue stands as the world's most significant mosquito-borne viral disease. Incidence is currently 30 times higher than that of 50 years ago. Furthermore, prior to 1970, severe dengue epidemics occurred in only nine countries. In 2012, dengue was endemic in over 100 countries in Africa, the Americas, and the Eastern Mediterranean; however, South-East Asian and Western Pacific countries are most dramatically affected.

Dengue thrives in tropical and subtropical areas of developing countries owing to environmental conditions that promote mosquito multiplication and viral transmission by Aedes aegypti. Conditions in which mosquitoes flourish include rapid population growth, movement between rural and urban regions, and water being stored in containers close to homes owing to poor infrastructure with insufficient or inconsistent water supply. A high volume of solid waste also contributes to mosquito concentration and reproduction, as neglected and discarded objects contain water which serves as a larval habitat and breeding ground.

In addition to the increase in incidence and spread of endemic countries, the WHO warns of the potential for explosive outbreaks. There is now risk of potential dengue fever outbreaks occurring in Europe, as local transmission was officially detected in both Croatia and France in 2010. Moreover, imported cases have been recorded in three more countries in Europe. Most dengue cases in the USA were acquired abroad, but outbreaks have been reported in Florida, Texas, Puerto Rico, Alaska, and Hawaii in recent years. As a result of the rapid spread of the disease, the WHO has created a central data management system, DengueNet, as a standardized epidemiological system that can effectively monitor dengue.

Approximately half a million patients infected with severe dengue fever require hospitalization annually and an estimated 2.5 percent of those infected do not survive. Globalization, international commercial trade, the rise in air travel, and in many high-risk areas the lack of efficient vector control methods, all play major roles in the global burden of dengue and severe dengue. The global resurgence of dengue and the development of hyperendemicity in many regions reflect a level of concern that necessitates action and makes this disease a major public health challenge. In 2013, Thailand reported 7033 cases and five deaths in the first 5 weeks of the year: fives time higher than during the same period in 2012. monkeys, with 32 cases and seven deaths among laboratory workers and their families and caregivers. It has a sudden onset of generalized illness, malaise, fever, myalgia, headache, diarrhea, vomiting, rash, and hemorrhage. Person-toperson transmission occurs via blood, secretions, organs, and semen. Confirmed cases have been identified in a number of countries in Africa. The virus is carried by the fruit bat, which is widely distributed globally. Case fatality rates vary between 23 and 90 percent. Treatment is symptomatic support, and prevention is mainly focused on guidelines for the safety of health workers in African hospitals to prevent transfer of the disease to health workers.

Ebola is a virus that leads to severe viral hemorrhagic fever outbreaks, characterized by a particularly high case fatality rate of up to 90 percent. It is described by the WHO as "one of the most virulent viral diseases known to humankind". As an acute viral infection, Ebola hemorrhagic fever (EHF) typically leads to a sudden onset of fever, weakness, and extreme muscle pain and headache. Subsequent major symptoms include vomiting, diarrhea, and complications pertaining to liver and kidney functions, often with both internal and external bleeding. Laboratory results indicate low levels of white blood cells and platelets and elevated liver enzyme levels.

Ebola virus initially affects humans through contact with wild animals, specifically their secretions, organs, and blood. Fruit bats originating from the Pteropodidae family are recognized as the natural host of the virus; specifically in Africa, infections have occurred through contact with infected chimpanzees, gorillas, monkeys, fruit bats, forest antelopes, and porcupines. Typically, contact with these animals, which have been found dead or infected in the rainforest, leads to further transmission. The infection subsequently enters a community through human-to-human transmission. Humans are capable of transmitting the virus to others when it is present in body fluids, i.e., blood and secretions. The incubation period ranges from 2 to 21 days and the case fatality varies depending on the outbreak, from 25 to 90 percent. A common route of transmission is through health workers treating Ebola patients; this carries a high risk if proper control measures are not taken and sufficient barrier nursing procedures not followed. Moreover, widespread African practices of the washing and displaying of dead bodies facilitate the spread of this deadly hemorrhagic fever. This can be exemplified through burial ceremonies in which mourners have direct contact with a dead body.

Since the virus was discovered, an estimated 1850 cases with more than 1200 deaths have occurred (Box 4.25). While there is no treatment or vaccine for this virus, it is crucial that patients receive intensive supportive care, as many are severely dehydrated and require oral rehydration or intravenous fluids. Prevention is critical and should be implemented through various measures, such as routine disinfection of monkey farms; detergents such as sodium hypochlorite are capable of inactivating Ebola virus. Prevention of the virus in humans should revolve around educating community members on the risk factors of acquiring the infection as well as protective methods, such as the use of gloves. This is absolutely imperative to all, but especially for health care workers, laboratory workers, and those caring for ill patients at home. Educational messages must be spread to populations afflicted by Ebola, providing information about the disease itself as well as methods to control an outbreak. Measures include practicing timely and safe burials of community members who have died from Ebola. This disease is considered highly dangerous unless outbreaks are effectively controlled. Once identified, an Ebola epidemic becomes an international emergency; public health workers 1955-1959 1960-1969 1970-1979 1980-1989 1990-1999 2000-2007 from across the world are involved in control and intervention through WHO-and CDC-directed projects.

Lyme disease is characterized by the presence of a rash, as well as musculoskeletal, neurological, and cardiovascular symptoms. Confirmation is by laboratory investigation. It is the most common vectorborne disease in the USA. It primarily affects children in the 5-14-year age group and adults aged 35-55. Lyme disease is preventable by avoiding contact with ticks and by applying insect repellent. Lyme disease infects some 24,000 Americans per year but the true incidence may be three times higher or more. Risk is highest in the north-east, north-central, and mid-Atlantic regions (Box 4.26). Although localized in 13 states, Lyme disease ranked sixth on a list of the leading US nationally notifiable diseases in 2011. Several US manufacturers have developed vaccines but these are not used owing to concerns about adverse event reporting and tracking.

NTDs are a group of 17 parasitic diseases high rates of associated mortality and morbidity mostly in tropical countries. WHO estimates they affect nearly 1 billion persons in 77 countries, and CDC estimates that NTDs kill an estimated 534,000 people worldwide annually, mainly in 149 countries and territories with high burdens of years of life lost due to premature disability and death. Innovative and Intensified Disease Management (IDM) involves surveillance, capacity building, advocacy and research (Table 4 .11). In 2012, the NTD goals and commitments of the London Declaration on Neglected Tropical Diseases was agreed to by key public and private stakeholders.

Medically important parasites are animals that live in, take nourishment from, and thrive in the body of a host; which may or may not harm the host, but never bring benefit. They include unicellular organisms such as protozoa (malaria, Giardia, amebiasis, and Cryptosporidium), and helminths (worms), which are categorized as nematodes, cestodes, and trematodes (Box 4.27).

Central Africa, particularly those close to tropical rainforests. EHF cases were first documented in 1976 in two concurrent outbreaks, one occurring in Sudan and the other in the Democratic Republic of the Congo (DRC). Both were characterized as major and devastating outbreaks. Of the 284 cases in the Sudan outbreak, 151 deaths occurred, representing a case fatality rate of 53 percent. Even more disastrously, in the outbreak occurring in DRC, 318 fell ill and 280 died, a case fatality rate of 88 percent.

The nature of these outbreaks is not the same, as they were caused by two different virus subtypes. In total, there are five recognized Ebola virus subtypes; each has been named based upon the area in which it was initially identified in an Ebola outbreak.

Uganda experienced an outbreak in 2007 of a new strain of EHF (Bundibugyo) with a lower case fatality rate (17 of 43 cases or a 40 percent case fatality rate). In August 2012 an outbreak of EHF occurred in Kibaale district with 24 probable and confirmed cases, including 16 deaths. Of the total, 10 cases were confirmed through the Uganda Virus Research Institute in Entebbe. Some suspect cases had negative laboratory results, so 43 individuals were treated symptomatically then released from the isolation facility. They received counseling by psychosocial teams with guidance on reintroduction to the community. Even patients confirmed negative for the EHF virus need counseling to mitigate fears, diminish stigma, and improve their acceptance back into society. All contacts of probable and confirmed cases are monitored and evaluated daily for 21 days. Red Cross volunteers and village health teams created social mobilization teams, visiting households in the most afflicted regions of the district and communicating health awareness messages. As a precaution, countries neighboring Uganda are working to improve surveillance of the Ebola virus.

Another Ebola outbreak in DRC began on 3 September 2012, with 28 cases including 14 deaths in the Haut-Uele district, in Orientale Province. Of these, eight were confirmed, six considered probable, and the remaining 14 are suspect cases. Fatal cases in one of the two affected health zones include three health care providers. As of 24 September 2012, the number of documented Ebola cases in DRC has increased to 51; of these, 19 were laboratory confirmed and 32 probable cases; of the total, 20 cases were fatal.

Epidemiologists and logisticians from the WHO Regional Office for Africa as well as from WHO headquarters and from the CDC assisted the Ministry of Health in the outbreak response, social mobilization, active case finding, contact tracing, improved surveillance and monitoring, and case management with strengthened infection control.

The recent and simultaneous outbreaks in Uganda and DRC are considered to be epidemiologically unrelated and no specific travel warnings have been issued. However, the lower case fatality rates seen recently may leave more survivors to transmit this alarming disease. 

Box 4.28 discusses NTDs and their presence in the USA, predominantly among impoverished populations. Moreover, parasitic diseases such as malaria are among the most common causes of illness and death in the world. Milder illnesses such as giardiasis and trichomoniasis cause widespread morbidity. Intestinal infestations with worms may cause severe complications, although they commonly cause chronic low-grade symptomatology and iron-deficiency anemia. Deworming every 6 months has become an effective part of the Expanded Programme of Immunization (EPI-plus) along with vitamin A supplementation and insecticide-impregnated bed nets for children. The paradigm shift in global approaches to control of diseases originating at the animal-human interface requires strong support from highly professional veterinary public health.

Echinococcus granulosus, a small tapeworm commonly found in dogs. 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, CNS, or bones. Cysts, which may grow up to 10 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 USA and Canada. The human disease 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 away 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 USA. 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 longterm 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. Taenia solium is especially deadly; delay in diagnosis and treatment may lead to severe disease, including neurological cysticercosis. In developing countries, infection is associated with pork consumption, while in the USA, several epidemics have occurred from eating carnivorous game animals such as mountain lions and bears. Freezing or cooking meat, especially that of pigs and carnivorous mammals, is essential to destroy the tapeworm. Fish tapeworm (Diphyllobothrium latum) is common in populations living primarily on uncooked fish, such as Inuit, Eastern European, and Scandinavian. 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 fecal-oral transmission of the eggs. The disease is usually asymptomatic. Similarly, dwarf tapeworm (Hymenolepis nana) is transmitted through fecal-oral contamination from person to person, or via contaminated food or water. Rat tapeworm (Hymenolepis diminuta) also mostly affects young children.

In the mid-1970s, a mother of two young boys who were recently diagnosed with arthritis in the town of Old 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. Her findings 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 Ixodes ticks were shown to be the vector. Cases respond well to antibiotic therapy.

Lyme disease has been identified in many parts of North America, Europe, the former Soviet Union, China, and Japan. Personal protection by clothing and insect repellent applications to protect from tick bites, especially in forest areas, and environmental modification are important to limit spread of the disease.

WHO reports that at least 1 billion people suffer from one or more of the 17 major diseases which affect the poorest, most vulnerable people mainly in tropical and subtropical areas of the world. Some diseases affect individuals throughout their lives, causing a high degree of morbidity, social stigmati zation and abuse. The diseases include: Buruli ulcer, cysticercosis, dracunculiasis (guinea-worm disease), foodborne trematode infec tions (such as fascioliasis), hydatidosis, leishmaniasis, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helmin thiasis, trachoma, trypanosomiasis, and vectorborne 

Onchocerciasis, known as river blindness, is caused by a parasitic worm capable of producing millions of larvae which move through the body causing intense itching, debilitation, and eventually blindness. The disease is spread via the bites of blackflies belonging to the genus Simulium; the blackflies transmit the larva from infected individuals to those uninfected.

Leading to visual impairment and debilitating skin disease, onchocerciasis is primarily located in sub-Saharan Africa and in Latin America. By December 2009, over 112,000 million individuals in Africa were at risk for onchocerciasis. Approximately 70 percent of this population lives in only five of the 24 countries in which this disease is endemic: Nigeria, DRC, Cameroon, Ethiopia, and Sudan. Earlier the same year, 73.7 percent of the population at risk received ivermectin treatments and, consequently, it is estimated that the burden of this disease has dropped significantly. 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 1974 and is sponsored by four international agencies: the Food and Agriculture Organization (FAO), UNDP, World Bank, and WHO. It covers 11 countries in sub-Saharan Africa, focusing on control of the blackfly by destroying its larvae, mainly via insecticides sprayed from the air. The Vision 2020 program of the WHO aims for control of river blindness by the year 2020. The program has been successful in protecting some 30 million people and helping 1.5 million infected people to recover from this disease.

The WHO estimates that the program prevented 500,000 cases of blindness by 2000 and has freed 25 million hectares of land for resettlement and cultivation. The program cost US$570 million. This investment is considered by the World Bank to have a return of 16-28 percent in terms of largescale land reuse and improved output of the population.

A WHO program, the African Program for Onchocerciasis Control (APOC), established in 1996, includes ivermectin and selective vector control efforts by spraying for the blackfly. This program involves 30 countries in Africa and six in a similar program in South America. APOC has utilized rapid epidemiological mapping techniques to determine populations at risk, and thus provide community-directed treatment. Mapping strategies allow experts to understand levels of endemicity of each area. Moreover, while onchocerciasis is unlikely to be eliminated from Africa in the foreseeable future, emphasis on interrupting transmission of the disease is vital and certainly making progress.

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 (60 cm) nematode roundworm, Dracuculiasis medenisis; it typically affects the lower extremities, causing pain and disability. This disease is an infestation of the body via contaminated drinking water that contains the larvae of the parasite.

The parasite grows and mates in the intestine and over a year after infection, begins to emerge from the body via painful skin lesions. Most commonly, the victim bathes in stagnant waters to soothe the pain of the lesion. As a result, the worm, which may be up to 90 cm in length, emerges from the ulcer and releases new larvae to the water source. The larvae are ingested by water fleas which then can transmit the disease to new victims who drink the contaminated water.

Prevention is based on improving the safety of water supplies and preventing contamination by infected people. Education of people in endemic areas cautions individuals not to enter water sources. Promotion of filtering drinking water to reduce transmission is also essential. Insecticides remove the crustaceans and chlorine kills the larvae and crustaceans, which prologue larval infectivity. Box 4.29 discusses progress towards eradicating dracunciliasis.

Schistosomiasis 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 74 countries in Africa, South America, the Caribbean, and Asia. There

Public health continues to face the problems of parasitic diseases in the developing world but, increasingly, parasitic diseases are being recognized in industrialized countries as well. Giardiasis and Cryptosporidium infections in water and other outbreaks have occurred in the USA.

The First National Summit on Neglected Infections of Poverty in the USA held in Washington DC in 2009 was attended by public health experts, public policy leaders, and government officials. A follow-up workshop on the "neglected infections of poverty" (NIPs) and neglected tropical diseases (NTDs) was held in Washington in 2010.

Globally, there is no common definition of NTDs. NIPs, which include a range of NTDs, occur among poor groups living in wealthy countries such as the USA and Canada, and in Europe. In the USA, these are found in areas of the Mississippi Delta, post-Katrina Louisiana, along the border of Mexico, and in the Appalachians. These are largely made up of minority groups including African Americans, Hispanics, and Native Americans. The major US NTDs include dengue fever, toxocariasis, and Chagas disease.

There are an estimated 300,000 cases of Chagas in the USA with 30,000-45,000 cardiomyopathy cases and 63-315 congenital infections annually (Bern and Montgomery, 2009 ). The disability-adjusted life years (DALYs) associated with these NTDs in the USA are similar to those of HIV/ AIDS, malaria, or tuberculosis in low-and middle-income countries.

NIPs and NTDs have a low profile and status in public health priority, often with poor statistics, but are well known in the public health community. Surveillance and monitoring to provide more precise data on morbidity, mortality, and transmission rates need strengthening. NIPs and NTDs are frequently unrecognized or misdiagnosed in the USA often because the people do not or cannot seek health care or the health care providers have not had training in these diseases. Led by Congressman Hank Johnson Jr, Georgia introduced legislation, the Neglected Infections of Impoverished Americans Act 2010 (HR 5896), for the Department of Health and Human Services to collect additional information on these "neglected" diseases.

are an estimated 200 million people infected worldwide and more than 600 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 and pyelonephritis, with a high risk for bladder cancer, the ninth most common cause of cancer deaths globally.

A recently identified species, Schistosoma intercalatum, is genetically unique, but thought to cause both intestinal and genitourinary disease. Schistosoma intercalatum is largely identified in inhabitants and immigrants from western Africa. Infection by all schistosomes 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 which 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 serological 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 people, treatment of infected people, destruction of snails, and health education in affected areas. People 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 Dracunculiasis was traditionally endemic in the 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 some African countries (Gambia and Guinea).

Worldwide prevalence was reduced from 12 million cases in 1980 to 3 million in 1990 and 3,190 cases in 2009 with 187 countries certified as free of the disease by WHO. India's reported cases fell from 17,000 in 1987 to 900 in 1992, and the country was free from transmission in 1997. Similarly, formerly high-prevalence countries such as Kenya reported no cases in 1997. Major progress can be attributed to the World Health Organization's (WHO's) forceful promotion of eradicating dracunculiasis. In 1986 the World Health Assembly called for the elimination of dracunculiasis; at that time there were an estimated 3.5 million cases of the debilitating disease in 21 countries in Africa and Asia.

A Guinea Worm Eradication program was initiated leading to a great reduction in cases. Several target dates were set and not reached. However, the campaign was strengthened by strong support from non-governmental organizations (NGOs), and increasing cooperation from the governments of affected countries. Ghana was declared Guinea worm free in 2011. In 2012, the remaining countries with cases were South Sudan, Mali, Ethiopia, and Chad. The WHO reported 396 cases in 2012, from the beginning of the year to 30 June 2012, compared with 807 cases for the same period in 2011. A total of 1058 cases was documented for whole of 2011, a significant improvement from 2010 with 1797 cases. Transmission has been limited to four countries in 2011, compared with 20 countries in 1990.

As there is no vaccine or curative treatment, control of this formidable disease relies entirely on people screening water for household use and as well as case finding. Prevention is key and emphasis must be on education and change in human behavior, including preventing people from bathing in drinking water sources and strongly promoting the filtration of water from the source before use. The WHO, UNICEF, the Carter Center, the US Centers for Disease Control and Prevention, the Gates Foundation, and the UK government have all collaborated with affected countries in joint efforts to prevent and contain this disease.

The WHO International Commission for the Certification of Dracunculiasis Eradication sends teams to previously endemic countries to assess their progress. The great advances made to date suggest that with continuing political support in affected countries, eradication of dracunculiasis may be achieved in the coming few years. The success of this massive international effort to eradicate dracunculiasis relies on education and on village health workers, who are the backbone of the program. This is seen in evaluation measures demonstrating a marked reductions in cases where village health workers have been mobilized. Some experts believe that dracunculiasis eradication may be achieved before polio eradication, despite polio's two remarkably successful vaccines and massive global efforts. Extraordinary success can be achieved through the power of organized health promotion, supported by the affected nations, international agencies, and NGO participation. may last from weeks to more than a year. Diagnosis is by biopsy, culture, and serological 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 5-24 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 USSR, the Middle East, Latin America, and sub-Saharan Africa. Some 90 percent of visceral leishmaniasis occurs in six countries: India, Bangladesh, Sudan, South Sudan, Ethiopia, and Brazil. It usually occurs as scattered cases among infants, children, and adolescents. Cutaneous leishmaniasis is more widespread and may be increasing with global climate change. Transmission is by the bite of the infected sandfly, with an incubation period of 2-4 months. There is no vaccine, but specific treatment is effective and environmental control measures, such as the use of antimalarial insecticides, reduce the disease prevalence. In localities where the dog population has been reduced, the disease is less prevalent. Estimates of deaths vary between 20,000 and 40,000 per year (Alvar, 2012).

Sleeping sickness is a fatal degenerative neurological disease caused by Trypanosoma brucei, transmitted by the tsetse fly, primarily in the African savannahs, affecting cattle and humans. Subspecies are known to cause both acute and chronic forms of sleeping sickness. Some 55 million people are at risk in sub-Saharan Africa. Between 1998 and 2004, renewed surveillance and control reduced the incidence of African trypanosomiasis from 38,000 to approximately 18,000. Prevention depends on vector control and effective treatment of human cases. A dramatic reduction has occurred since 2004 (17,600 cases), with 9878 cases in 2009. The drop below 10,000 is a first time achievement in 50 years.

Chagas disease is a chronic vector-and blood transfusionborne parasitic disease (Trypanosoma cruzi) which causes significant disability and death. Globally, some 10 million people are infected with T. cruzi, the protozoan parasite that leads to Chagas disease. The majority of infected individuals reside in Latin America. The WHO estimates that 7-8 million people worldwide are infected with Chagas disease, with approximately 10,000 deaths (2008).

Once found mainly in Latin America, in recent decades increasing cases have been identified in the USA, Canada, and other continents including some European and Western Pacific countries. These cases can be explained by migration and mobility patterns between populations in Latin America and the rest of the world. Thus, the demographics of this disease have changed and its presence has expanded to other continents.

The disease manifests itself in two phases. Within the first, acute phase, parasites circulate throughout the blood. Typically symptoms are mild, but may consist of fever, muscle pain, trouble breathing, and enlarged lymph glands. By phase two, characterized as the chronic phase, parasites have traveled through the body and, by this time, are hidden in the heart and digestive muscle. About 30 percent of affected people develop severe heart disease. After years have passed, heart failure or sudden death may occur as a result of the deterioration of the heart muscle.

While vaccine development is not likely owing to the ability of trypanosome antigens to cause autoimmunity and rapid immunological drift of the organism, two drugs have been developed which show effectiveness in limiting early chronic disease. Brazil achieved elimination of transmission in 1998 in , after Uruguay (1996 and Venezuela (1997) , and followed by Argentina (1999) . While the initial WHO elimination goal by 2010 proved unfeasible, efforts continue to dramatically reduce the incidence of T. cruzi infection.

Control is difficult, but vector control by ecological and insecticide measures is the most effective measure of reducing the animal host and vector insect population in its habitat. Other measures emphasize educating those residing in high-risk areas in prevention by clothing, bed nets, and repellents. Chemotherapy is utilized for case management. Blood screening to prevent transmission via transfusion or transplantation is also vital.

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.

Entamoeba histolytica infection sometimes results in invasive abdominal infestation, severe liver disease, and death.

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 is the basis for control.

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 50 percent of the population. Children aged 3-8 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 (oxyuriasis) is common worldwide in all socioeconomic classes; however, it is more widespread among people living in crowded and unsanitary conditions. The Enterobius vermicularis infestation of the intestine may be asymptomatic 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 fecal-oral 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. Likewise, mass treatment is indicated in high-prevalence communities.

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 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 rats to humans. Control of rats has reduced the flea population; however, during war and disasters, rat and flea populations may thrive. Scabies, which is caused by a mite, is common worldwide and 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 immediate attention in school health and public health policy.

Legionnaire's disease (legionnellosis) is an acute bacterial disease caused by Legionnellae, a Gram-negative group of bacilli, with 35 species and many serological groups. The first documented case was reported in the USA in 1947, and the first disease outbreak was reported in the USA in 1976 among participants of a veterans' convention in Philadelphia. General malaise, anorexia, myalgia, and headache are followed by fever, cough, abdominal pain, and diarrhea. Pneumonia followed by respiratory failure may ensue. The case fatality rate can be as high as 40 percent of hospitalized cases. A milder, non-pneumonic 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 jacuzzi baths. The disease has been reported worldwide. Significant epidemics have occurred on cruise ships, where insufficient air-conditioning sanitation and an older, more susceptible clientele are a dangerous combination. Prevention requires the cleaning of water towers and cooling systems, including whirlpool spas. Hyperchlorination of water systems and the replacement of filters are 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 19,000 leprosaria in the year 1300. The disease was largely wiped out during the Black Death in the fourteenth century, but maintained 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 9 months and 20 years (average of 4-8 years). Rifampin and other medications allow the patient to become non-infectious in a short time, thus 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. The increase has been associated with improved case finding. BCG may be useful in reducing tuberculoid leprosy among contacts. Investigation of contacts over 5 years is recommended.

The disease has been eliminated from 119 out of 122 countries in which leprosy was previously recognized and perceived as a public health problem in 1985. In the last two decades over 14 million people suffering from leprosy have been cured.

Despite this progress, leprosy is still present in 11 countries in South-East Asia (including India), in sub-Saharan Africa, the Middle East (Sudan, Egypt, and Iran), and in some parts of Latin America (namely Mexico and Colombia), with isolated cases in the USA. However, world prevalence has declined from 10.5 million cases in 1980, through 5.5 million in 1990, to fewer than 300,000 in 2005 declining to 228,474 cases in 2010 and increasing slightly to 232,857 cases in 2012 (WER, 2013) .

The WHO aimed to eliminate leprosy as a public health problem by 2000, defined as prevalence of fewer than one per 10,000 population, or fewer than 300,000 cases. The goal was met and this achievement has served as a major historic event in public health. Extensive use of MDT has contributed to a marked reduction in leprosy. In addition, the implementation of national and subnational campaigns in endemic countries has strengthened the control of leprosy. Emphasis is increasingly placed on incorporating primary leprosy medical services into existing general health services; this approach has successfully simplified diagnosis and treatment of the disease. The goals for 2011-2015 are to continue reducing the disease burden of leprosy where the disease is still endemic. This is achievable with early diagnosis and treatment with MDT. Numbers of new cases of the disease have declined (Figure 4.11) , but it remains a serious problem in some countries; those with the largest burden of new cases of leprosy in 2010 were India (126,800), Brazil (34, 894), and Indonesia (17, 012) . 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 CDC, 2013) . This class of infections represents a substantial global cause of infertility, acute illness and disability, as well as further medical and psychological issues to many. Moreover, many STIs detrimentally affect pregnancy, leading to spontaneous abortions, stillbirths, or preterm deliveries. They can cause neonatal infections and, depending on the infection, may result in blindness, chronic respiratory disease, or herpes encephalitis. Accordingly, the public health and social consequences are devastating in many countries. Women, specifically adolescents, are most vulnerable to STIs. Many cases are asymptomatic, thus easing transmission of the disease. Populations residing in urban regions, people in low socioeconomic groups, and those involved in prostitution and drug use represent the highest risk of infection.

Since STIs, especially in women, may be asymptomatic, it is common for severe sequelae to occur before patients seek care. Infection by one STI increases the risk of infection by other diseases in this group. Prompt diagnosis and treatment can have enormous benefits for infant health and the overall health of a population. Coverage of services that prevent mother-to-child transmission of infections reached 45 percent in 2008; a major factor in saving infants' lives, UNAIDS estimates that transmission can be reduced by 30-35 percent, compared to a reduction of 1-2 percent without preventive services. Globally, an estimated 200,000 infant HIV infections were averted over a 12 year period, between 1996 and 2008 (Figure 4 .12).

Syphilis is caused by the spirochete Treponema pallidum. After an incubation period of 10-90 days (mean of 21 days), primary syphilis develops as a painless ulcer or chancre on the penis, cervix, nose, mouth, or anus, lasting 4-6 weeks. The patient may first present with secondary syphilis 6-8 weeks (up to 12 weeks) after infection with a general rash and malaise, fever, hair loss, arthritis, and jaundice. These symptoms spontaneously disappear within weeks or up to 12 months later. Tertiary syphilis may appear 5-20 years after initial infection. Complications of tertiary syphilis include catastrophic cardiovascular and CNS 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 is caused by the bacterium Neisseria gonorrhoeae. Worldwide, an estimated 62 million people are infected with gonorrhea annually. The incubation period is 1-14 days, and gonorrhea is often associated with concurrent chlamydia infection. In women, gonorrhea 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, gonorrhea causes urethral discharge and painful urination. Treatment with antibiotics ends infectivity, but untreated cases can remain infectious for months. Drug resistance to penicillin, tetracycline, and quinolones has emerged in many countries, thus 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 (see Chapter 1).

While the control of STIs is an integral part of public health, work in this field must be carried out appropriately and delicately. This philosophy was certainly not applied to a study into STIs conducted in Guatemala (described in Box 4.30); on the contrary, study participants experienced a gross violation of human rights and ethical standards. Refer to Chapter 15 for more ethics in the framework of public health.

Chancroid is an infection caused by Haemophilus ducreyi. In women, chancroid may cause a painful, irregular ulcer near the vagina, resulting in pain during intercourse, urination, and defecation; however, it may be asymptomatic. In men it causes a painful, irregular ulcer on the penis. The incubation period is usually 3-5 days, but may last up to 14 days. An individual is infectious as long as there are ulcers, usually 1-3 months. Treatment is by erythromycin or azithromycin.

Herpes simplex is caused by herpes simplex virus types 1 and 2 and has an incubation period of 2-12 days. Genital herpes causes painful blisters around the mouth, vagina, penis, or anus. The genital lesions are infectious for 7-12 days. Among severe cases, herpes may lead to CNS meningoencephalitis infection. It can be transmitted to newborns during vaginal delivery, causing infection, encephalitis, and death. Caesarean delivery is therefore necessary when a mother is infected. Antiviral drugs are used in treatment, orally, topically, or intravenously. In 2003 the first systematic review was undertaken to establish the estimated global incidence and prevalence of herpes simplex virus (HSV) type 2. The 2003 estimated global prevalence among 15-49-year-olds was 535.5 million (16 percent of the world's population). In the same year, the estimated number of new HSV type 2 infections was 23.6 million.

Researchers indicate challenges associated with inadequate availability of data; however, they have recognized some general trends. For instance, there are more cases of HSV type 2 among women than men. Among the 535.5 million cases affecting 15-49-year-olds, women comprise approximately 315 million cases, and men the remaining 221 million infections. An additional trend is that the number of infected individuals directly increases with age. Data on prevalence rates of HSV type 2 in the USA indicate that 40-60 million individuals are infected. The estimated annual incidence is 1.2 million infections; the prevalence rate specifically among the 30-40-year-old age group is approximately 30 percent. Moreover, there is now plenty of evidence indicating that HSV type 2 is a major cofactor of HIV infection.

Chlamydia, caused by Chlamydia trachomatis, is the second most common STI after HPV in the USA. The reported incidence increased to nearly 2.9 million in 2008. Despite this, underreporting is a major problem and actual incidence is estimated at more than twice the figure reported. In women, it usually presents asymptomatically, 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 7-21 days and the infectious period is unknown. Treatment for chlamydia is doxycycline, azithromycin, or erythromycin. Because cotransmission with gonorrhea is extremely common, CDC recommends treatment for both diseases when either is confirmed. Chlamydia infection, not necessarily venereal in transmission, may be transmitted to the newborns of infected mothers.

In the past, Chlamydia pneumoniae has been suspected as a possible cause of or contributor to coronary heart disease. This correlation has been under much investigation, leading to the following findings. Chlamydia (C. pneumoniae) infection is known to be a widespread chronic risk factor for coronary artery disease. Intra-arterial infection, among other contributing etiologies, contributes to plaque formation, thromboembolic occlusion of arteries, and myocardial infarction. While antibiotic treatment of chlamydia as a preventive measure for heart disease has not been used, this could potentially reduce the burden of the leading worldwide cause of death at a relatively low cost.

The WHO reports that Chlamydia trachomatis causes more cases of STIs than any other bacterial pathogen, thus it represents a worldwide public health challenge, exacerbated by the infection's silent, asymptomatic nature among many, leading to an ease and unawareness of transmission, affecting both men and women. Vaccine development is underway.

Informed consent, ethical standards, and regulation compliance may seem mindless, tedious, and perfunctory to some; to others, they may determine life or death, health, or illness. In the shameful medical experiment discussed below, US medical researchers conducted unscrupulous research victimizing their Guatemalan study participants.

Between 1946 and 1948, American researchers from the US Public Health Service conducted a study in Guatemala on 1300 prisoners, commercial sex workers, psychiatric patients, and soldiers. The group and local employees carried out experiments in which they deliberately infected these populations with sexually transmitted diseases (STDs). Consent was not obtained and the researchers made great effort to keep these acts a secret. Secrecy was critical in order to receive funding from senior authorities, who clearly should have never allowed these experiments to be carried out.

Funded by the US National Institutes of Health, the aim of the study was to determine new methods of preventing STDs, such as gonorrhea, syphilis, and chancroid. The researchers infected female sex workers with gonorrhea or syphilis; they subsequently allowed them to engage in unprotected sex with the other populations of their study, namely soldiers or prisoners. Consequently, some of these men contracted the STDs. The doctors then chose to directly inoculate the soldiers, inmates, and psychiatric patients, by injecting gonorrhea into the subjects' urethras; syphilis was transmitted both via skin injections and by exposing the penis to infectious agents.

Analysis of their own internal communications revealed that a few years before the Guatemalan experiment, the medical researchers attained informed consent prior to conducting research on prisoners in Terre Haute, Indiana. The researchers were fully aware of their obligation to obtain informed consent, but undertook the study with a conscious decision to skip this fundamental step, resulting in serious harm and immense humiliation.

Trachoma, an infectious disease of the eye, is currently responsible for approximately 3 percent of blindness in the world. Although not classified as an STI, it is placed in this section because its causative organism is Chlamydia trachomatis, the same as a bacterium that causes chlamydia, one of the most common STIs. The organism is transmitted through contact with eye discharge of an infected individual, typically by use of household items such as handkerchiefs and washcloths; the bacterium can is also transmitted by flies that have landed on the eyes or nose of someone infected. If this infection is not treated and further trachoma infections occur, it can cause major scarring in the inside of the eyelid. As a result, the eyelid may turn inward and, consequently, the eyelashes can scratch the cornea. This becomes painful and disabling as the permanent corneal damage can result in irreversible blindness.

Trachoma is recognized as the top cause of preventable blindness due to an infection. It is most easily transmitted in regions with insufficient access to water and inadequate sanitation. Affecting the most marginalized populations, trachoma is common in poor rural areas of Central America, Brazil, Africa, parts of Asia, and some countries in the Eastern Mediterranean. The WHO estimates that approximately 2.2 million people are visually impaired as a result of trachoma, and 1.2 million cases have advanced to blindness. Once considered endemic in most countries, more recent reports indicate trachoma endemicity in 57 countries. Hygiene, vector control, and treatment with antibiotic eye ointments or simple surgery for scarring of eyelids and inturned eyelashes are important in preventing blindness. Moreover, a new drug, azithromycin, is effective in curing the disease. The WHO is promoting a program dedicated to the global elimination of trachoma in endemic areas by 2020. The comprehensive intervention, known as SAFE, focuses on four major elements: surgery (to correct advanced stages), antibiotics, facial cleanliness, and environmental improvements pertaining to water and sanitation.

Trichomoniasis is caused by the protozoan parasite Trichomonas vaginalis. The incubation period is 4-20 days (mean 7 days). 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 or itching or irritation inside the penis. Treatment is by a single dose of antibiotics, metronidazole or tinidazole, taken orally. These antibiotics can cure trichomoniasis; without treatment, the disease may persist and remain infectious for years. CDC reports that in the USA approximately 3.7 million people are infected with trichomoniasis; however, only 30 percent develop symptoms of the infection. It is possible for those infected but experiencing no symptoms to transmit the infection to others. Moreover, approximately one in five people become reinfected within 3 months after taking the antibiotics.

HPV, endemic throughout the world, is now known as the leading cause of cervical neoplasia and cancer of the cervix. Silent among many people, the majority of HPV infections cause no symptoms. Despite this, genital HPV infections that are persistent can lead to the development of cervical cancer. Nearly all cases of cervical cancer (99 percent) are associated with a genital HPV infection, which represents the most prevalent viral infection affecting the reproductive tract. HPV includes many types associated with venereal warts (condylomas).

Scientists have identified over 40 types of HPV that infect the genital area in males and females. Among 90 percent of cases, the body's immune system manages to clear HPV naturally, within 2 years. Despite this, there is no way of determining which HPV cases will lead to cancer, genital warts, or other medical problems. Screening tests are integral in preventing cervical cancer or detecting it early. They include the HPV test, which detects the virus that can cause cervical cell changes, and the Papanicolaou (Pap) smear, which detects precancerous lesions as well as cell changes on the cervix.

An effective vaccine against the most common carcinogenic strains is now available and recommended for young women to prevent cervical cancer, a breakthrough of enormous importance as this is one of the leading causes of cancer mortality in women. HPV vaccines are administered in three doses over a period of 6 months. Although originally developed for females, an HPV vaccine has also been created to protect males from the most common types of the virus.

The prevention of cervical cancer by vaccination and Pap smear screening is a major advance in public health, along with the prevention of liver cancer by hepatitis B immunization. Circumcision is now recommended by the WHO for primary prevention of transmission of HPV (see Chapters 5 and 6).

In areas where a full range of diagnostic services is lacking, a "syndromic approach" is recommended for the control of STIs. 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 people who might not return for follow-up. Moreover, it may place them in a noninfective stage so that even without follow-up care, they will not transmit the disease. STI incidence per 100,000 population from 1950 to 2009 is shown in Table 4 .14. The decline in syphilis and gonorrhea from 1950 to 1990 was followed by a leveling or slow decline in the 2001-2009 period, while the increase in chlamydia is probably due to greater awareness and diagnosis.

Screening in prenatal and family planning clinics, prison medical services, and clinics serving sex workers, homosexuals, or other potential risk groups will detect subclinical cases of various STIs. Treatment can be carried out inexpensively and immediately. For instance, the screening test for syphilis costs US$0.10 and the treatment with benzathine penicillin injection costs about US$0.40. Partner notification is a controversial issue, but may be needed to identify contacts who may be the source of transmission to others.

Control of STIs through a syndrome approach based on primary care providers is being promoted by the WHO. Health education directed towards high-risk target groups and marginalized populations is essential. Providing easy and cost-free access to acceptable, non-threatening 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 a reduced risk of other STIs. Training medical care providers in STI awareness should be stressed in undergraduate and continuing educational efforts, including personal protection as caregivers.

HIV/AIDS has captured world attention since it was first identified in the early 1980s. HIV is a retrovirus that infects various cells of the immune system, and also affects the CNS. Two types have been identified: HIV1, worldwide in distribution; and the less pathogenic HIV2, 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 1-3 months.

Within several weeks to months of the infection, many people develop an acute self-limiting flu-like syndrome. They may then be free from any signs or symptoms for months to more than 10 years. Onset of illness is usually insidious with non-specific symptoms, including sweats, diarrhea, weight loss, and fatigue. AIDS represents the later clinical stage of HIV infection. According to the revised CDC case definition (1993), AIDS involves any one or more of the following: low CD4 count, severe systemic 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.

This pandemic presented lessons of public health and hygiene that had been forgotten in a smug confidence and reliance on antimicrobial therapy and vaccines that were assumed to be capable of defeating all infectious diseases. Regrettably this is not the case, and the HIV/AIDS experience showed the price of negligence in infectious disease control of STIs. With no vaccine yet on the horizon, the prospects for this disease are grim and its spread certain until an effective vaccine can be developed. However, the pattern of mortality in the USA is shown in Figure 4 .13 from CDC, indicating modest success in the changing potential for prolonging survival, improving quality of life, and reducing transmission. Active public health measures include education on AIDS prevention and condom promotion, and effective medical care based on antiretroviral therapy (ART). Other measures include promoting early diagnosis and treatment for TB, with special attention to MDR-TB, and other opportunistic infections, as well as nutritional supplementation and general care, which are also gaining ground as preventive measures in sub-Saharan Africa. The graph in Figure 4 .13 shows important trends in AIDS diagnosis and prevalence in the USA over several years. The numbers of both AIDS diagnoses and deaths have fallen significantly, beginning around 1993 and 1995. When examining the number of Americans living with HIV infection or an AIDS diagnosis, the graph shows a gradual increase beginning in the early to mid-1990s. While the HIV prevalence is higher than ever before, this echoes a trend that can be described as a higher number of new infections than number of people who die of HIV/AIDS yearly. Thus, effective medical care and ART have contributed immensely to allowing those infected with HIV to live longer. Likewise, ART has allowed for decreased mortality due to HIV/AIDS.

According to the CDC, in the USA, by the end of 2008, nearly 1.2 million adults and adolescents were living with HIV. When compared to the estimate for 2006, this figure signifies a 7 percent increase. Another important trend discovered by researchers is that the majority of those infected with HIV did not transmit the virus to others in recent years. Experts estimate that in the USA in 2006, of every 100 people living with HIV, there were five transmissions. Thus, at least 95 percent of HIV-positive people did not transmit the virus to otherwise healthy individuals that year. This represents a significant (89 percent) decline in the approximate rate of HIV transmission since the mid-1980s. The reduction in transmission is likely to be attributable to successful preventive measures, improved testing, and highly effective treatment.

AIDS was first recognized clinically in 1981 in Los Angeles and New York (Box 4.31). By mid-1982 it was considered an epidemic in those and other US cities. It was primarily seen among men who have sex with men and recipients of blood products. After initial errors, testing of blood and blood products became standard and 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 activity, and maternal-fetal transmission becoming major sources of infection. Comorbidity with other STIs apparently increases HIV infectivity and, furthermore, may have helped to convert the epidemiology to a greater degree of heterosexual transmission. The disease grew exponentially in the USA but the incidence of new cases has declined since 1993. AIDS represents a major public health problem in most developed and developing countries, reaching catastrophic proportions in some sub-Saharan African countries, affecting up to 30 percent or more of some populations.

HIV-related deaths were the eighth leading cause of all deaths in 1993 in the USA, the leading cause among men Globally, deaths from AIDS totaled 2.8 million in 2005, with an estimated 11.7 million people having died from this pandemic up to 1997. In 2005, there were an estimated 4.1 million new cases. HIV/AIDS is the fourth largest killer in the world, and the leading cause of death in sub-Saharan Africa. However, owing to implementation of coordinated control programs, it is believed that the pandemic expansion peaked in the late 1990s. The WHO aims to reverse the increase in HIV infection by 2015. With increased attention, training, funding, and resources, this may be possible. Globally in 2008, deaths totaled 1.8 million and new cases 2.6 million. Moreover, there were 33.3 million (2.5 million children) living with AIDS. The 2008 Report on Global AIDS Estimates indicates that globally, in 2007 there were approximately 15 million orphans due to AIDS. In this study, orphans are defined as children between the ages of 0 and 17 who have lost one or both parents to AIDS. Of the 15 million orphans worldwide, 11.6 million live in sub-Saharan Africa. These figures can be compared with those of 2001, in which globally, there were an estimated 8 million orphans due to AIDS. Of these, 6.5 million reside in sub-Saharan Africa.

The declining incidence of new cases in industrialized nations 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 facets of public health management of the AIDS crisis. In developed countries, highly active antiretroviral therapy (HAART) has been successful in substantially reducing disease advancement to AIDS. Thus, this form of treatment has converted HIV/AIDS from a fatal illness to a fairly manageable chronic disease. While Over 30 million people globally, including an estimated 1.1 million Americans, have died from AIDS since 1981. UNAIDS estimated that the epidemic peaked in 1996 at 3.5 million new infections, and deaths peaked at 2.2 million in 2004, even though more than half of those who need treatment do not receive it.

The 2008 Nobel Prize for Medicine was awarded to Luc Montagne and Francoise Barre-Sinoussi from the Pasteur Institute for the discovery of HIV. In total, 33 million people were living with HIV in 2008, but death rates were dropping. Since then, AIDS has receded from public view but new case rates are still climbing, mainly among men who have sex with men, but still over 30 percent of new infections are acquired heterosexually. HIV vaccine studies are showing promise and there is growing optimism that an effective vaccine will be developed.

this is, of course, a favorable outcome, HIV treatment does not come without major challenges. It typically consists of a cocktail of multiple drugs, and it functions as a lifelong therapy. Adherence is crucial for treatment be effective, for increased virological control, and in preventing drug resistance. Regimens are complex and many patients experience serious side-effects. A central challenge associated with treatment is access and availability to marginalized populations, particularly in poor, less developed countries.

In 1987, the first phase I trial of an HIV vaccine was carried out in the USA. Phase II and III trials have also been conducted, and while plenty of research is dedicated to this potential form of prevention, scientists have not been successful in developing a safe, effective, and affordable HIV vaccine. 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 90 percent of people living with HIV/AIDS are in developing countries, where transmission largely occurs through heterosexual contact. Every day, more than 8500 people, including 1000 children, are infected. In Thailand, one person in 50 is now infected. In sub-Saharan Africa more than one in 40 is infected, and in some cities as many as one in three people carry the virus. Estimations of new infections per year in sub-Saharan Africa range from 1 to 2 million people, while in Asia there are 1.2-3.5 million new infected people per year. Lessons are still being learned from the AIDS pandemic. Furthermore, the prevalence of those living with the HIV is three times that of 1990. Between 2003 and 2008, there was a 10-fold increase in access to antiviral drugs among low-and middle-income countries. The explosive spread of this infection, from an estimated 100,000 people in 1980 to an anticipated 40 million people HIV infected, shows that the world is still vulnerable to pandemics of emerging infectious diseases. Enormous movements of tourists, businesspeople, truck drivers, migrants, soldiers, and refugees promote the spread of such diseases. Widespread sexual exchange, transfusion of blood products, and illicit drug use can 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.

The HIV pandemic has spread throughout the world. However, there is the somewhat hopeful indication that the rate of increase has slowed in the USA. This may be a reflection of a number of factors including higher levels of self-protective behavior, the most susceptible population groups having already been affected, and the spread into the general population at a slower rate. The slowdown may yet be only a lull in the storm, as heterosexual contact becomes a more important mode of transmission and male-to-male transmission is increasing, especially among black homosexual Americans.

The 2013 UNAIDS reports major progress in control of the world pandemic of HIV/AIDS, in part due to designation of the Millennium Development Goal 6 of halting and reversing the spread of AIDS and providing ART treatment for all those who need it. An estimated 2.5 million people became HIV positive in 2011, with 25 countries showing a drop in new HIV infections of 50 percent or more; half of this reduction was among newborns as a result of antiretroviral treatment of HIV-positive mothers during pregnancy. In 2011, over 8 million people were receiving ART management for HIV, an increase of over 60 percent from 2009, and this includes an increase in the number of people receiving ART in low-and medium-income countries. However, 7 million who need ART do not receive it, and new HIV infection rates are rising in the Middle East, North Africa, Eastern Europe, and Central Asia.

Combinations of several drugs from among a number of antiretroviral medications are showing promise in suppressing HIV in infected people. At a current annual price of nearly US$20,000 per patient, these sums are well beyond the capacity of most developing countries. The development of methods for measuring the HIV viral load has 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, and transmission to newborns has been reduced by recent therapeutic advances, specifically prevention of mother-to-child transmission (PMTCT). Safe-sex practices and condom use may have helped in reducing heterosexual transmission. Further advances in therapy and preventive measures based on a vaccine are expected over the next decade.

The HIV/AIDS pandemic is one of the great public health challenges of the twenty-first century for a myriad of reasons. It is a complex disease involving strong cultural elements, and challenging factors include its international spread, its sexual and other modes of transmission, the associated stigma, its devastating and costly clinical effects, and its impact on parallel diseases such as TB, respiratory infections, and cancer. The cost of care for the AIDS patient can be exceedingly high. Programs needing strengthening include home care with home health aides or CHWs to encourage compliance with treatment, along with adequate nutrition and self-care, as well as mutual help among HIV carriers and AIDS patients. Adding to the complexity, difficult ethical issues associated with AIDS arise. Important matters needing support include improved screening of pregnant women and newborns; partner notification, reporting, and contact tracing; and financing the cost of care. The AIDS pandemic is not by any means over or "under control", but progress has been made and there is hope for the "magic bullet" of an effective and inexpensive vaccine.

Diarrheal diseases are the leading cause of child mortality in the world. They are caused by a wide variety of bacteria, parasites, and viruses (Table 4 .15) infecting the intestinal tract. They cause secretion of fluids and dissolved 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 the use of oral rehydration therapy (ORT), an inexpensive and simple method of intervention easily used by a non-medical primary care worker and by the mother of the child as a home intervention. In 1983, diarrheal diseases were the cause of almost 4 million child deaths, but by 1996 this figure had declined to 2.4 million, largely owing to the increased use of ORT.

Diarrheal diseases are transmitted by water, food, and directly from person to person via fecal-oral contamination. Diarrheal diseases occur in epidemic levels in situations of food poisoning or contaminated water sources; they 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. A dangerous practice, 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 2000 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 rarely affect disease progression and may lead to increased carrier rates and produce resistant strains; therefore, only symptomatic and supportive treatment is recommended, except in systemic and life-threatening cases.

Salmonella typhi causes typhoid fever and according to the WHO kills some 500,000 people per year, while seriously affecting millions of others. While treatable by ampicillin and fluid replacement, the antibiotics are becoming less effective. Two vaccines are currently available and are used in high-risk areas.

Shigella are a group of bacteria that are pathogenic in humans. The infectious dose of Shigella is among the lowest of all pathogens; fewer than 10 organisms are sufficient to cause disease within 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 40 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. Flies can transmit the organism, and in non-refrigerated foods the organism may multiply to an infectious dose. Control is in hygienic practices and in the safe handling of water and food. Shigella is a common cause of waterborne disease outbreaks where water supplies are contaminated and not treated adequately. Shigella bacteria can contaminate community water sources, local surface water, and recreational waters such as streams and swimming pools, via human, animal, or sewage sources, causing large waterborne disease outbreaks.

Escherichia coli bacteria are common fecal contaminants of inadequately prepared and cooked food. Particularly virulent strains such as O157:H17 can cause explosive outbreaks of severe (enterohemorrhagic) diarrheal disease with a hemolytic-uremic syndrome and death, as occurred in Japan in 1998 with cases and deaths due to a foodborne epidemic. Sporadic, but significant epidemics occur often, mostly in developed countries where food processing and transport are common. Other milder strains cause traveler's diarrhea and nursery infections. Inadequately cooked hamburgers, 

Cholera is an acute bacterial enteric disease caused by Vibrio cholerae. It is characterized as causing sudden-onset, profuse, painless watery stools, occasional vomiting, and if untreated, rapid dehydration, circulatory collapse, and death. Similar disease may be caused by other "cholerogenic" species of Vibrio. Asymptomatic infection or carrier status, and mild cases are common. In severe, untreated cases, mortality is over 50 percent, but with adequate treatment, mortality is under 1 percent. Diagnosis is based on clinical signs, epidemiology, serology, and bacteriological confirmation by culture. The two types of cholera are the classic and el Tor (with Inaba and Ogawa serotypes).

In 1991, 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 4.32). Since 1991, epidemics in South America, south Asia, and Iraq have caused hundreds of thousands of cases and, consequently, thousands of deaths. Haiti experienced its first outbreak of cholera in decades following the 2010 earthquake.

According to the WHO, the number of documented cases of cholera continues to increase. In 2011 alone, nearly 590,000 cases were reported from 58 countries, including some of the most severe cases and over 7800 deaths. Experts understand that these figures do not represent the actual cases and deaths. As a result of limitations in surveillance in conjunction with concern over potential trade and travel sanctions, many more cases have been unaccounted for and undocumented. Furthermore, discrepancies occur owing to inconsistencies in case definitions and a lack of agreed upon vocabulary. A more accurate depiction of the burden of cholera is 3-5 million cases, with 100,000-120,000 deaths per year.

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. Crucial treatment is prompt fluid therapy with electrolytes in large volume to replace all fluid loss with ORT. Using this form of treatment can successfully treat up to 80 percent of cholera cases. Tetracycline shortens the duration of the disease, and chemoprophylaxis for contacts following stool samples may help in reducing its spread. A vaccine is available; however, it has no value in the prevention of outbreaks.

Cholera and its burden on a country provide meaningful information, as this disease serves as a chief indicator of inadequate social development. It persists as a major public health challenge in developing countries that lack fundamental infrastructure capable of providing clean, safe water. Owing to unsanitary living conditions, these populations and communities are at high risk of major cholera outbreaks as well as other diarrheal diseases.

Viral gastroenteritis can occur in sporadic or epidemic forms in infants, children, and adults. Some viruses, such as the BOX 4.32 Cholera Pandemics in South America, 1991 -1998 , and Haiti, 2010 In the 1980s, 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 US Environmental Protection Agency (EPA) and the US Public Health Service. In January 1991, a Chinese freighter arrived in Lima, Peru, and dumped bilge (sewage) in the harbor, apparently contaminating local shellfish. Raw shellfish is a popular local delicacy (ceviche) and is associated with cases of cholera seen in local hospitals.

Contamination of local water supplies from sewage resulted in an exponential increase in cases, and by the end of 1992, the Pan American Health Organization (PAHO) reported an epidemic of 391,000 cases and 4002 deaths. The epidemic spread to 21 countries, and in 1992 there were a further 339,000 cases and 2321 deaths spreading over much of South America, continuing in 1999.

In the USA, 102 cases of cholera were reported in 1992; of these, 75 cases and one death were among passengers of an airplane flying from South America to Los Angeles in which contaminated seafood was served. In 1993, 91 cases of cholera were reported in the USA, though unrelated to international travel. These occurred mostly among people consuming shellfish from the Gulf coast with a strain of cholera similar to the South American strain, also possibly introduced in a ship's ballast. Cholera organisms are reported in harbor waters in other parts of the USA.

Haiti has experienced recurring cholera epidemics following overwhelming damage and loss of life in an earthquake. This event killed over 220,000 people and led to the displacement of 1.3 million people, with enormous damage to an already poor sanitary infrastructure. The cholera epidemics that occurred in 2010 and 2012 caused a reported 635,980 cases and 7912 deaths. rotaviruses and enteric adenoviruses, affect mainly infants and young children; they may be severe enough to require 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, characterized by 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 immunological 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 the age of 5. Most children in developing countries experience this disease by the age of 4 years, with the majority of cases occurring between 6 and 24 months. In developing countries, rotaviruses are estimated to cause over 1 million 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. ORT is the key treatment.

Rotavirus represents the most common trigger of severe diarrheal disease affecting infants and young children worldwide. It is estimated that this class of viruses causes 527,000 deaths annually; over 85 percent of these deaths occur in low-resource countries in Africa and Asia. Each year over 2 million of these infants and children require hospitalization and supportive care to combat severe dehydration.

A live attenuated vaccine was approved by the FDA in 1998 and adopted in the 1999 US recommended routine vaccination programs for infants. In 2009 the WHO recommended rotavirus vaccine be included in all national immunization programs. There is strong evidence of herd immunity, as fewer children and adults are hospitalized following the introduction of infant vaccination. The vaccine for rotavirus is considered the single form of prevention recognized as having the strongest impact on reducing new, severe cases. In the USA the burden of rotavirus disease as a cause of hospitalization is greater than previously known. Furthermore, rotavirus as a cause of hospitalization for gastroenteritis has declined significantly over the years since the introduction of the vaccine (Figure 4 .14).

Adenoviruses, Norwalk, and a variety of other viruses (including astrovirus, calcivirus, and other groups) cause sporadic acute gastroenteritis worldwide, mostly in outbreaks. Spread occurs via the fecal-oral route, often in hospital or other communal settings, with secondary spread among family contacts. Foodborne and waterborne transmission are both likely, and can represent serious problems 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. It is usually asymptomatic, but is 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 or duodenal fluid, or in intestinal mucosa from a biopsy. This disease is prevalent worldwide and affects mostly children. Like many other diarrheal diseases, it is spread in areas of poor sanitation, in preschool settings and swimming pools. Giardiasis 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 USA in the 1980s and 1990s, as the protozoa are not readily inactivated by chlorine; rather, adequate filtration before chlorination is required. 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 parvum is a parasitic infection of the gastrointestinal tract in humans, small and large mammals, and other 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 people with AIDS, it can be a serious problem. The disease is most common in children under 2 years of age and those in close contact with them; it is also common among homosexual men. Diagnosis is by identification of the Cryptosporidium organism cysts in stools. The disease is present worldwide. In Europe and the USA, the organism has been found in 1-4.5 percent of individuals sampled. Spread is common by person-to-person contact via fecal-oral contamination, especially in such settings as day-care centers. Raw milk as well as waterborne outbreaks have also been identified in recent years. A large waterborne disease outbreak due to Cryptosporidium occurred in Milwaukee in 1986, as described in Chapter 9. Management is by rehydration and prevention is achieved by careful hygiene in food handling and water safety.

Helicobacter pylori, first identified in 1982, is a bacterium causally linked to gastrointestinal ulcers and gastritis, contributing to high rates of chronic peptic ulcer disease and to gastric cancer (Chapter 5). It is an important example of the causative link between infection and a group of chronic diseases. The discoverers of this link were Robin Warren and Barry Marshal in Australia, later rewarded with the Nobel Prize in Medicine in 2005. The diagnosis and management of chronic peptic ulcer revolutionized medical and surgical practices with a simple cure for this disease group. It had enormous implications for prevention of cancer of the stomach and chronic peptic ulcers, which filled medical and surgical wards of hospitals until the 1990s at great cost and consumed large amounts of medical resources.

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 ORT.

ORT is considered by UNICEF and WHO to have resulted in the saving of 1 million lives each year in the 1990s. Proper management of an episode of diarrhea by ORT (Table 4 .16), 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 1990 called for a reduction in child deaths from diarrheal diseases by one-third and malnutrition by one-half, with emphasis on the widest possible availability of, education in, 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 supported by the widest possible publicity to raise awareness among parents.

ORT is an essential public health modality in developed countries as well as in developing countries. Although diarrheal disease does not cause death as frequently in developed countries, it represents a significant factor in infant and child health. Even under the most optimal conditions, it 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); however, it is an excellent form of secondary prevention, by preventing complications from diarrhea. Accordingly, it 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 USA. A form of ORT, marketed as "sports drinks", is used in sports where athletes lose large quantities 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 and 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 falter in growth and development. Supportive measures may be needed following as well as during the episode. These involve 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, is important for routine infant and child care, and more so for conditions affecting total nutrition such as diarrheal diseases.

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 elderly and chronically ill people. They are also the major cause of morbidity in infants in developed countries, causing much anxiety to parents even in areas with adequate 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 and mortality, and the considerable expenses of health care.

ARIs are due to a broad range of viral and bacterial infections. Secondary bacterial infections progress to pneumonia with mortality rates of 10-20 percent. 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, such as tracheobronchitis, bronchitis, bronchiolitis, and pneumonia. ARIs are frequently associated with VPDs, including measles, varicella, and influenza. They are caused by a large number of viruses, producing a wide spectrum of acute respiratory illnesses. 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 due to absence from work.

Bacterial agents causing upper respiratory tract infection include group A Streptococcus, Mycoplasma pneumoniae, 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 83 known types of this organism, distinguished by capsule characteristics; 23 account for 88 percent of pneumococcal infections in the USA. An excellent polyvalent vaccine based on these types is available for high-risk groups such as elderly people, immunodeficient patients, and people with chronic heart, lung, liver, or blood disorders, or diabetes.

Opportunistic infections attack the chronically ill, especially those with compromised immune systems, often with life-threatening ARIs. Mycoplasma (primary atypical pneumonia) is a lower respiratory tract infection which sometimes progresses to pneumonia. TB and Pneumocystis jiroveci are especially problematic for AIDS patients. Other organisms causing pneumonia include Chlamydia pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, E. coli, Staphylococcus, rickettsia (Q fever), and Legionella. Parasitic infestation of the lungs may occur with nematodes (e.g., ascariasis). Fungal infections of the lungs 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 in controlling 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 USA and Russia than in other industrialized countries. The continuing gap in mortality rates between white and African American children in the USA 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 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 political and public awareness. Furthermore, it is too expensive for developing countries. This vaccine is recommended for infants in the USA and many industrial nations and recommended by the WHO for developing countries, but has yet to be widely applied in the latter. 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 caregivers is currently the only feasible way to reduce the still enormous burden of morbidity and mortality from ARIs among young and elderly people.

As in other fields of public health, there are wide variations or inequities between and within countries pertaining to the control of communicable diseases. The differences between the industrialized countries and the developing countries are enormous. The gaps are not only in coverage, but also in the content of the immunization programs. For instance, adoption of Hib vaccine is increasing; however, the decade-long gap from availability to widespread global usage results in many preventable deaths. Similarly, the lag in adoption of pneumococcal pneumonia and rotavirus vaccines will prolong the time it takes to achieve the MDGs of reducing child mortality in very many countries.

Even in the European Region, there are wide differences between groups of countries, as seen in Figure 4 .15 comparing standardized mortality rates (3-year moving averages) for infectious and parasitic disease between long-standing members of the EU (such as France, Germany, and the UK) with the new members (since 2004, such as Hungary, Poland, and other countries of Eastern Europe), those of the Commonwealth of Independent States (e.g., Ukraine and Russia), and finally the Central Asian Republics (e.g., Kazakhstan, Uzbekistan, and Tajikistan). The trends show low and stable rates in the countries of Western and Eastern Europe, high and falling rates in Central Asia, but high and rising rates in the key countries of the former Soviet Union. While there may be artifacts of reporting, the trends are thought to be accurate, and are likely to be related to many factors such as water and food safety, obsolescent immunization programs, TB and HIV control, and a myriad of other determinants. Comparisons within countries also reveal social and regional disparities, which constitute failings of public health systems. Inexcusably and unreasonably wide gaps indicate that communicable diseases must remain a key part of the modern public health agenda. The European Region, which includes all of these groups of countries such as the EU, does not have a standard or harmonized immunization schedule; thus, each country follows its own patterns. Western European countries are generally up to date with the content of their immunization programs and with high coverage, but this is not uniformly so even in this group, and certainly not in the European Region as a whole. The countries of the former Soviet Union are gradually updating their immunization schedules but remain largely at least a decade behind. The WHO's advisory committee system on immunization has been updating its recommendations rapidly in recent years for hepatitis B, and more recently Hib and pneumococcal pneumonia, and adopting of the two-dose policy of MMR vaccination. As new vaccines become available transitional and developing countries will need support to expand their programs of immunization, a key part of the drive to attain the MDGs of reduced child mortality and control of infectious diseases (malaria, HIV, and others).

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 long-standing availability of an effective and inexpensive vaccine, the persistence of measles as a major killer of 1 million children per year represents a failure in effective use of both the vaccine and the health system. The resurgence of TB and malaria has led to new strategies, such as managed or directly observed care, with CHWs ensuring compliance needed to render the patient non-infectious to others and, similarly, to reduce the pool of carriers of the disease.

Successes achieved in reducing polio, measles, dracunculiasis, onchocerciasis, and other diseases to the level of local or global eradication have 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. ORT is one of the most cost-effective methods of preventing excess mortality from ordinary diarrheal diseases, yet it is not utilized on a 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 the application of epidemiological 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. CHW programs can greatly enhance TB, malaria, and STI control; or in AIDS care, promote prevention and appropriate treatment.

The link between infectious disease and non-communicable disease (NCDs) has become a major new development of public health in the past several decades. Vaccines for hepatitis B and HPV to prevent cancer of the liver and of the cervix will save countless lives. The discovery of H. pylori as the cause of chronic peptic ulcer disease and gastric cancer provided an easily diagnosed and treated infection which will also save many lives and reduce hospitalization for diseases that formerly filled the medical and surgical wards of hospitals. The potential for new discoveries of infectious and genetic factors in disease is augmented by a growing understanding of the importance of social and economic factors in all diseases. The advent of health promotion awareness became evident when the HIV/AIDS pandemic struck, for which there were no medical answers except palliative care, but human behavior was the vital link to management and remains so even since excellent medical treatments have become available.

In the industrialized and mid-level developing countries, epidemiological and demographic shifts have created new challenges in infectious disease control. The 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 pulmonary 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 subject of communicable disease as one of its key issues in protecting individual and population health. Methods of intervention include classic public health through sanitation, safe water and foods, immunization, and well beyond that into nutrition, education, case finding, treatment, and changing human behavior. The knowledge, attitudes, beliefs, and practices of policy makers, health care providers, and parents are as important in the success of communicable disease control as the technology available and methods of financing health systems. Together, these encompass the broad programmatic approach of the New Public Health to the control of communicable diseases.

In a world of rapid international transport and contact between populations, systems are needed to monitor the potentially explosive spread of pathogens that may be transferred from their normal habitat. The potential for the international spread of new or re-emerged, reinvigorated infectious diseases constitutes a threat to humankind akin to ecological and other anthropogenic disasters.

The eradication of smallpox has paved the way for the eradication of polio, 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 immunological revolution into the twentyfirst century.

As the triumphs of control or elimination of infectious diseases of children continue, the scourge of HIV infection continues, with distressingly slow progress in the development of an effective vaccine or cure for the disease it engenders. Partly as a result of 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 dangerous in that MDR-TB 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, and public health workers.

The burden of infectious diseases has appeared to recede as the predominant public health problem in the developed countries. Despite this, new challenges of emerging infectious diseases have come to the fore in public health, and communicable disease remains a dominating problem in the developing countries. With increases in longevity and the 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 elderly and chronically ill people are 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 challenges include applying a comprehensive approach and managing resources to define and reach achievable targets in communicable disease control.

Control of communicable diseases is one of the fundamental pillars of public health. The new capacities of vaccines and other methods of control develop slowly, and the advent of effective vaccines for HIV, malaria, and TB will bring untold benefit to the global community. The challenges of natural dispersion of communicable disease can be made more threatening because of the advent of bioterrorism and the emergence of new diseases or the spread of those previously localized in a less mobile, less globalized world. The challenges, the potential for harm, and the benefits that can be achieved in this aspect of public health are enormous.

For an abstract, guidance for student review and expected competencies as well as an extended bibliography, please see companion website at http://booksite.elsevier.com/ 9780124157668

Note: The figures listed for syphilis include all three stages of the disease as well as congenital syphilis. Rates are cases per 100,000 population, rounded. Prior to 1994, Chlamydia was not notifiable

Year FIGURE 4.13 AIDS diagnosis and cases and estimated number of people aged ≥ 13 years

Isolation of Vibrio cholerae O1 from oysters -Mobile Bay

Estimated reduction in US hospitalizations

Reduction in acute gastroenteritis hospitalizations among US children after introduction of rotavirus vaccine: analysis of hospital discharge data from 18 US states

Leishmaniasis worldwide and global estimates of its incidence

When is a disease eradicable? 100 years of lessons learned

An estimate of the burden of Chagas disease in the United States

Leprosy: Global status

Evolution of epidemic investigations and field epidemiology during the MMWR era at CDC

Jawetz, Melnick and Adelberg's medical microbiology

Guinea worm disease eradication

International Task Force for Disease Eradication

Ten great public health achievements -United States

150th anniversary of John Snow and the pump handle

A CDC framework for preventing infectious diseases: sustaining the essentials and innovating for the future

Achievements in public health, 1900-1999: control of infectious diseases

Achievements in public health, 1900-1999: impact of vaccines universally recommended for children -United States, 1990-1998. MMWR

Chikungunya fever

Emerging infectious diseases national summit on neglected infections of poverty in the United States

Centers for Disease Control and Prevention. Health disparities and inequality report

HIV in the United States: an overview

Human papillomavirus (HPV), signs and symptoms

Impact of the sequential IPV/OPV schedule on vaccination coverage -United States

Measles -United States

Multistate fungal meningitis outbreak investigation

Pertussis (whooping cough) outbreaks

Progress toward global eradication of dracunculiasis

Public health then and now: celebrating 50 years of MMWR at CDC. MMWR

Recommended immunization schedule for persons age 0 through 18 years -United States

Sexually transmitted diseases treatment guidelines 2010. MMWR

Ten great public health achievements -United States

Ten great public health achievements -worldwide

Vaccines & immunizations Glossary/acronyms

Viral hepatitis statistics & surveillance

West Nile virus, statistics, surveillance, and control: West Nile virus (WNV) human infections reported to ArboNET, by state

Immunization schedules: Birth-18 Years & "Catch-up" Immunization Schedules United States, 2013: Details For Health Care Professionals

Recommended Immunization Schedule for Persons Aged 0 Through 18 Years -United States

Rift Valley fever -a threat for Europe?

History of anti-vaccination movements

Vaccines: vaccine development and licensing events

Vaccines: the history of Lyme disease

Rift Valley fever and a new paradigm of research and development for zoonotic disease control

The principles of disease elimination and eradication

EuroCJD surveillance data: vCJD cases worldwide 28

Influenza pandemics: past, present and future challenges

Dr Andrew Jeremy WAKEFIELD Determination on Serious Professional Misconduct (SPM) and sanction

Global Polio Eradication Initiative

Poliomyelitis control in Israel, the West Bank and Gaza Strip 1948-1993: changing strategies with the goal of eradication in an endemic area

Government of Manitoba, 2011. Health. Manitoba Immunization Monitoring System (MIMS)

National Center for Foreign Animal and Zoonotic Disease Defense Advisory Group. Potential effects of Rift Valley fever in the United States

Control of communicable diseases manual, nineteenth ed

Global health: disease eradication

The causes and impacts of neglected tropical and zoonotic diseases: opportunities for integrated intervention strategies

Uniting to combat neglected tropical diseases. Ending the neglect and reaching 2020 goals

Ethical failures and history lessons: the US Public Health Service research studies in Tuskegee and Guatemala. Public Health Rev. 34. epub ahead of print

AMP zeros in on continued net distribution in malaria-endemic countries 31

Training the global public health workforce through applied epidemiology training programs: CDC's experience

Helicobacter pylori infection

Measles control in developing and developed countries: the case for a two-dose policy

Polio lessons 2013: Israel, the West Bank, and Gaza

Polio lessons 2013: Israel, the West Bank, and Gaza

Global fact sheet

Demand for male circumcision rises in a bid to prevent HIV

World Health Organization, Chagas disease (American trypanosomiasis)

World Health Organization

Controlling rubella and preventing congenital rubella syndrome -global progress

First WHO report on neglected tropical diseases: working to overcome the global impact of neglected tropical diseases

World Health Organization. Cumulative number of confirmed human cases for avian influenza A(H5N1) reported to WHO

World Health Organization

Ebola haemorrhagic fever. Fact sheet no

Global Advisory Committee on Vaccine Safety, report of meeting

Global Alert and Response (GAR): Ebola in Uganda -update

Global Alert and Response (GAR): Hepatitis C. Available at

World Health Organization

Immunization coverage. Fact sheet no

Sexually transmitted diseases. Chlamydia trachomatis

World Health Organization

Global leprosy: update on the 2012 situation

World Health Organization

World Health Organization, MDG 6: combat HIV/AIDS, malaria, and other diseases

World Health Organization/UNICEF. WHO vaccine-preventable disease monitoring system, 2013 global summary

Measles. Fact sheet no. 286

World Health Organization. Viral hepatitis statistics and surveillance

Meeting of the International Task Force for Disease Eradication

New and underutilized vaccines: Rotavirus

Pneumococcal conjugate vaccine for childhood immunization -WHO position paper

World Health Organization

Variant Creutzfeldt-Jakob disease. Fact sheet no. 180; revised February

Water sanitation health: facts and figures on water quality and health

West Nile Virus. Fact sheet no

Neglected tropical diseases

WHO guidelines on hand hygiene in health care, first global patient safety challenge

Geneva: WHO

Working to overcome the global impact of neglected tropical disease

Executive summary. Geneva: WHO

World Health Organization European Region

This research has similarities with the infamous Tuskegee trial, which was primarily unethical for allowing syphilisinfected study subjects to remain untreated. This is partially because the director of the research conducted in Guatemala, John Cutler, a US Public Health Service medical officer, also served as an investigator in the Tuskegee experiments. Moreover, further evidence indicates that the Surgeon General at that time, General Thomas Parran Jr, knew of the nature of the experiments Cutler and his colleagues were conducting.An official apology was subsequently rendered to the government of Guatemala. The US Presidential Commission on Bioethics has highlighted this case as an awakener to ensure that something of this magnitude, grossly violating the rights of study participants, is never repeated. Current regulations dictate rules for medical research on human participants. These regulations are indispensable requirements for researchers and funding agencies, and limitations for publication. Implementation of and appropriate compliance with the regulations are equally important. Ignoring this protection for study participants in research in another country does not absolve anyone from responsibility and compliance towards ethical standards.Deception was a major factor in this study of participants recruited from vulnerable populations. This notorious experiment undermined human rights, medicine, ethics, and the principle of protecting patients. Effort to determine new treatments and advances in medicine with the intention of helping patients must be conducted according to internationally accepted rules of procedure, such as those of the Helsinki Declaration of 1964 and its subsequent formulations (see Chapter 15). 1946 -1948 : another tragic history lesson. JAMA 2010304:2063-4. http:// dx.doi.org/10.1001/jama.2010.1554. Available at: ama.jamanetwork.com/ article.aspx?articleid=186859 [Accessed 10 January 2013