Workshop Overview

THE CAUSES AND IMPACTS OF NEGLECTED TROPICAL AND ZOONOTIC DISEASES: OPPORTUNITIES FOR INTEGRATED INTERVENTION STRATEGIES

Neglected tropical diseases1 (NTDs) have afflicted humanity since time immemorial and in their long histories have acquired notoriety as chronically disabling and deforming diseases. There is no single consensus definition for this group of diseases. Different organizations such as the World Health Organization, the U.S. Centers for Disease Control and Prevention, the U.S. Agency for International Development, and the Bill & Melinda Gates Foundation to name a few define the suite of these diseases differently. Be that as it may, these diseases, however they are defined, afflict more than 1.4 billion people, many of whom live on less than $1.25 per day. In the past, their serious impact on health and productivity led to considerable knowledge about the diseases, and effective control tools were developed for many. As living conditions improved in many parts of the world, opportunities for transmission were drastically reduced. As a result, these diseases are now rarely seen in populations that enjoy good access to health services and a reasonable standard of living.

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The 13 parasitic and bacterial infections known as the neglected tropical diseases include three soil-transmitted helminth infections (ascariasis, hookworm infection, and trichuriasis), lymphatic filariasis, onchocerciasis, dracunculiasis, schistosomiasis, Chagas disease, human African trypanosomiasis, leishmaniasis, Buruli ulcer, leprosy, and trachoma.These diseases afflict more than 1.4 billion people, most of whom live on less than $1.25 per day (WHO, 2006). On October 14, 2010, the World Health Organization released a major report on this topic with an expanded list of NTDs that includes the following diseases: dengue, rabies, endemic treponematoses, cysticercosis, echinococcosis, and food-borne trematode infections (WHO, 2010b).



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Workshop Overview THE CAUSES AND IMPACTS OF NEGLECTED TROPICAL AND ZOONOTIC DISEASES: OPPORTUNITIES FOR INTEGRATED INTERVENTION STRATEGIES Neglected tropical diseases1 (NTDs) have afflicted humanity since time immemorial and in their long histories have acquired notoriety as chronically disabling and deforming diseases. There is no single consensus definition for this group of diseases. Different organizations such as the World Health Orga- nization, the U.S. Centers for Disease Control and Prevention, the U.S. Agency for International Development, and the Bill & Melinda Gates Foundation to name a few define the suite of these diseases differently. Be that as it may, these diseases, however they are defined, afflict more than 1.4 billion people, many of whom live on less than $1.25 per day. In the past, their serious impact on health and productivity led to considerable knowledge about the diseases, and effective control tools were developed for many. As living conditions improved in many parts of the world, opportunities for transmission were drastically reduced. As a result, these diseases are now rarely seen in populations that enjoy good access to health services and a reasonable standard of living. 1 The 13 parasitic and bacterial infections known as the neglected tropical diseases include three soil-transmitted helminth infections (ascariasis, hookworm infection, and trichuriasis), lymphatic filariasis, onchocerciasis, dracunculiasis, schistosomiasis, Chagas disease, human African trypanoso - miasis, leishmaniasis, Buruli ulcer, leprosy, and trachoma.These diseases afflict more than 1.4 billion people, most of whom live on less than $1.25 per day (WHO, 2006). On October 14, 2010, the World Health Organization released a major report on this topic with an expanded list of NTDs that includes the following diseases: dengue, rabies, endemic treponematoses, cysticercosis, echinococcosis, and food-borne trematode infections (WHO, 2010b). 1

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2 NEGLECTED TROPICAL AND ZOONOTIC DISEASES NTDs today are a symptom of poverty and disadvantage. Those most af- fected are the poorest populations often living in remote, rural areas, in urban slums, or in conflict zones. With little political voice, NTDs have a low profile and status in public health priorities. Lack of reliable statistics coupled with the often unpronounceable names of these diseases have all held back efforts to bring them out of the shadows. Although medically diverse, NTDs share features that allow them to persist in conditions of poverty, where they cluster and frequently overlap. Approximately 1.4 billion people—one-sixth of the world’s popula- tion2—suffer from one or more NTDs. Conflict situations or natural disasters aggravate conditions that are conducive to the spread of these diseases. Around half of the world’s population is at risk of contracting these infections. The human NTDs are diseases of poverty, trapping the world’s poorest in a cycle of poverty. The global burden of the NTDs is equivalent to at least half of the combined global burden of HIV/AIDS, tuberculosis (TB), and malaria. Several NTDs are zoonoses—infections that can be transmitted between animal and human hosts. Such infections can be transmitted directly; others are transmitted indirectly either through food and water or by means of a vector. One of the parasites that causes African trypanosomiasis, or sleeping sickness, can infect livestock and wild animals as well as humans and is transmitted by the bite of a tsetse fly. Additional neglected zoonotic diseases (NZDs) such as brucellosis, bovine tuberculosis, and rabies, which are not typically included among the NTDs, profoundly affect impoverished people not only through their direct effects on human health but also by sickening and killing the livestock upon which their livelihoods depend (WHO, 2006). NTDs and NZDs not only share features that allow them to persist in condi - tions of poverty, where they cluster and frequently overlap, but they also present common opportunities for effective, integrated, intervention and control strat - egies. Significant (though imperfect) control measures—including drugs and vaccines, improvements in water and sanitation, and vector control measures, employed singly or in combination—have been developed for most NTDs and NZDs (Hotez and Pecoul, 2010; Spiegel et al., 2010). Policy makers and funding agencies have begun to acknowledge the public health and economic importance of the NTDs and NZDs, leading to increased support for the use of existing tools (such as the mass administration of drugs to combat several NTDs simultane - ously) and the development of more effective integrated programs to control, and in some cases eradicate, these neglected diseases of poverty. The Institute of Medicine’s (IOM’s) Forum on Microbial Threats hosted a two-day public workshop on September 21 and 22, 2010, in Washington, DC, to explore the scientific and policy dimensions of NTDs and NZDs. Through presentations and discussions, workshop participants discussed the origins and impacts of these diseases, both individually and as a collective phenomenon. 2A group sometimes referred to as the “bottom billion.”

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3 WORKSHOP OVERVIEW They reviewed the influence of NTDs and NZDs on human and animal health and on economic productivity, discussed prospects for disease control and mitigation, and considered opportunities for medical diplomacy and global engagement to reduce the profound, yet long-hidden, consequences of neglected diseases. Organization of the Workshop Summary This workshop summary was prepared for the Forum membership by the rapporteurs and includes a collection of individually authored papers and com - mentary. Sections of the workshop summary not specifically attributed to an individual reflect the views of the rapporteurs and not those of the Forum on Microbial Threats, its sponsors, or the IOM. The contents of the unattributed sections are based on the presentations and discussions at the workshop. The workshop summary is organized into sections as a topic-by-topic syn- thesis of the presentations and discussions that took place at the workshop. Its purpose is to present lessons from relevant experience, to delineate a range of pivotal issues and their respective problems, and to offer potential responses as discussed and described by the workshop participants. Manuscripts and reprinted articles, submitted by some but not all of the workshop’s participants, may be found in alphabetical order in Appendix A. Although this workshop summary provides an account of the individual presentations, it also reflects an important facet of the Forum’s philosophy. The workshop functions as a dialogue among representatives from different sectors and allows them to present their beliefs and viewpoints about which areas may merit further attention. This report only summarizes the statements of participants at the workshop. It is not intended to be an exhaustive exploration of the subject matter nor does it represent the findings, conclusions, or recommendations of a consensus committee process. Defining the NTDs Workshop presentations and discussions reflected the dual nature of NTDs 3 as both a public health phenomenon and a medically diverse group of diseases. This section examines common attributes of NTDs and, in particular, their inex - tricable association with poverty and conflict. The next section profiles individual diseases, their origins and effects on individuals and populations, and prospects for prevention and treatment. Brief descriptions of NTDs and NZDs described in this overview are presented in Box WO-6 (which appears on pages 86–107). 3 General statements regarding NTDs in this overview frequently apply to NZDs as well.

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4 NEGLECTED TROPICAL AND ZOONOTIC DISEASES Burden of the “Bottom Billion” NTDs4 comprise some of the most common infections of poverty and some of the leading causes of chronic disability in low- and middle-income countries (Hotez and Pecoul, 2010). As illustrated in Figure WO-1 and discussed further by Hotez in this volume, NTDs represent a group of more than a dozen major chronic, mostly parasitic, infectious diseases, with high endemicity in the de - veloping countries of Africa, Asia, and the Americas (Hotez, 2010a; Musgrove and Hotez, 2009). It has been estimated that every person among the world’s poorest—the destitute “bottom billion”—suffers from co-infections by one or more NTD (Hotez et al., 2009b). The greatest health and economic burden of NTDs is borne by people whose existence is often overlooked: subsistence farm- ers and their families living in remote rural areas, and the teeming poor of urban slums and shantytowns (WHO, 2010b). NTDs are not exclusively restricted to impoverished tropical regions of the world. Several of these diseases were once endemic in the United States and re - main highly prevalent among the nation’s poorest residents (Hotez, 2008b, 2009a; Hotez and Wilkins, 2009). In the relatively poor south of Europe and in Turkey, ascariasis, trichuriasis, and a host of zoonotic helminth infections are associated with intestinal, neurological, and respiratory problems. Dogs in that region also serve as a reservoir for visceral leishmaniasis (Hotez, 2009a). Even impoverished Arctic natives contract helminth and protozoan infections through the consump - tion of undercooked wild animal meat and from contact with infected livestock such as reindeer and elk (Hotez, 2010b). NTDs have plagued life on Earth for millennia. As noted in Box WO-1, accurate descriptions of these often painful and disfiguring parasitic infections appear in ancient texts including the Bible, Talmud, and Vedas; in the works of Hippocrates; and in Egyptian papyri (Cox, 2002; Hotez, 2010a). In a presentation discussing NTDs in the United States, Peter Hotez, of the George Washington University and the Sabin Vaccine Institute, noted that most NTDs in the Americas—with the possible exceptions of Chagas disease and trachoma—were the living legacies of slavery and the slave trade. (Dr. Hotez’s contribution to the workshop summary report can be found in Appendix A, pages 221–293.) As illustrated in Figure WO-2, these parasites traveled to the Americas in the bodies of West African slaves, who worked in the sugar plantations of Latin America and the Carribbean and, to a lesser extent, in the cotton and sugar plan- tations of the American South (Hotez, 2009a). NTDs introduced into the United States by slavery, such as hookworm, schistosomiasis, and lymphatic filariasis (LF), became endemic in the New World (Hotez, 2009a). The burden of hookworm disease in the American South inspired one of the 4 The concept of the “NTDs” was formulated in response to the Millennium Declaration and its eight Millennium Development Goals (MDGs) for sustainable poverty reduction (Hotez, 2006, 2008a; Hotez et al., 2006, 2007b; Molyneux et al., 2005).

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5 WORKSHOP OVERVIEW FIGURE WO-1 Geographical overlap and distribution of the seven most common ne- glected tropical diseases: ascariasis, hookworm infection, trichuriasis, schistosomiasis, WO-1.eps lymphatic filariasis, onchocerciasis, and trachoma. SOURCE: Hotez et al. (2009b). Reprintedbitmap Lancet, Vol. 373, Hotez PJ, Fenwick from The A, Savioli L, and Molyneux DH, Rescuing the bottom billion through control of neglected tropical diseases, pp. 1570–1575, Copyright (2009), with permission from Elsevier. first large-scale, integrated attempts to combat the diseases now known as NTDs, which was launched by the philanthropist John D. Rockefeller in the first decade of the 20th century (CDC, 1993; Ettling, 2000; Humphreys, 2009). Viewing hookworm as a disease that stunted economic development as well as the lives of individuals and communities in the American South, the Rockefeller Sanitary Commission for the Eradication of Hookworm set out in 1909 to achieve the goal of hookworm eradication through the mass treatment of affected populations with anti-helminthic therapy. Although this effort reduced the severity of disease in infected individuals, it failed to eliminate the source of infection and re-infection occurred following the termination of therapy. Hookworm remained endemic to the American South until profound eco - nomic development and urbanization occurred in the years prior to the beginning of World War II (Humphreys, 2009). The same can be said for three additional diseases of poverty that plagued the American South during the 19th and early 20th centuries: yellow fever, malaria, and pellagra. Humphreys (2009) observed that “the southern liberation from disease paralleled the end of sharecropping and the rise of prosperity in the South. It also occurred in decades that saw a vast migration from the countryside to the city and from the South to the North.” Similar transformations are now taking place in China, Hotez added. Over the

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6 NEGLECTED TROPICAL AND ZOONOTIC DISEASES BOX WO-1 Ancient Scourges, New Names The illnesses we now call neglected tropical diseases have been plaguing humanity since the beginning of recorded history. Indeed, public health experts sometimes refer to NTDs as the “biblical diseases” because of their long history of causing human suffering (Hotez, 2006). Descriptions of parasitic worm and skin infections can be found in Egyptian papyri and the Vedas dating back to 1500 BC. These conditions are also described numerous times in the Bible, in the Talmud, and in the writings of ancient scholars such as Hippocrates (Cox, 2002; Hotez, 2010a). Early Descriptions of Parasitic Worm Infections Ancient Egyptian papyri represent some of the earliest written descriptions of parasitic worms infecting and causing disease in humans. For instance, the Eb- ers Papyrus, which dates back to 1500 BC, includes instructions for how to use pomegranate root to treat roundworm infections (Grove, 1990). Detailed descriptions of worm infections and ancient treatments for them can also be found in the writings of Hippocrates. In his Treatise on Diseases IV, Hip- pocrates outlines his theories on the origins of both flat and round worms, describ- ing the courses of infection for each. For example, he writes, “When it [the worm] matches the gut in size, it keeps growing; and the parts which exceed the length of the gut separate off at the anus along with the feces, and what is expelled is like a cucumber seed, or often even larger” (Lonie,1981). The Bible also contains passages that scholars believe refer to parasitic worm infections. In Numbers, there is a passage that describes how God sent “fiery ser- pents” to attack the Israelites who had spoken out against him. Once the Israelites repent for their sins, God instructs Moses to “Make a fiery serpent and set it on a pole, and everyone who is bitten, when he sees it, shall live” (Numbers 21:8). Many historians believe that this passage is a reference to Guinea worm (Kristoff, 2010). Indeed, wrapping the worm around a stick and slowly pulling it from the body remains the standard method for removing the worms today. Early Descriptions of Skin Infections The Bible, the Talmud, and the Vedas all contain numerous references to skin diseases, which are often described as punishments for those who do not follow religious laws. For example, the Bible mentions “leprosy” (which religious scholars now believe refers to a number of different skin diseases including what we now consider leprosy) in Leviticus, Numbers, Samuel, Kings, Chronicles, Matthew, Mark, and Luke. Leviticus contains a detailed passage describing what to do when a person has a case of “leprosy.” In the passage, God explains to Moses and Aaron, “When a man is afflicted with a leprous disease, he shall be brought to the priest, and the priest shall look. And if there is a white swelling in the skin that has turned the hair white, and there is raw flesh in the swelling, it is a chronic leprous disease in the skin of his body, and the priest shall pronounce him unclean” (Leviticus 13:9–11). Similarly, Treatise XV of the Talmud discusses the signs and proper ways to handle skin diseases at length and includes detailed instructions on how they should be identified, inspected, and properly treated according to religious law (Barclay, 1878).

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7 WORKSHOP OVERVIEW FIGURE WO-2 Depiction of the classical model of the Triangular trade. The use of Af - rican slaves was fundamental to growing colonial cash crops, which were then exported to Europe. European goods, in turn, were used to purchase African slaves, which were then brought on the sea lane west from Africa to the Americas, the so-called middle passage. SOURCE: Triangular trade. http://en.wikipedia.org/wiki/Triangular_Trade (accessed No - vember 12, 2010). past decade, as the number of its people who live on less than a dollar a day has declined from 60 percent to 16 percent, there have been equally dramatic decreases in the prevalence of neglected infections of poverty, he stated. Nevertheless, NTDs remain endemic to many less fortunate places left be- hind by socioeconomic progress. Collectively, these diseases cause an estimated 530,000 deaths per year and annual disability equivalent to 57 million life-years (Hotez et al., 2006, 2007b; Sachs and Hotez, 2006) (see Table WO-1). The heavy burden of disability associated with NTDs—which exceeds that of malaria and TB (Hotez at al., 2006)—reflects the chronic nature of these infections, coupled with the lack of health care delivery available to the vast majority of people who suffer from them. As several speakers observed throughout the meeting, NTDs frequently present as co-infections with each other, as well as with malaria, TB, or HIV/ AIDS (Brooker et al., 2006, 2007). Hotez noted that the geographic ranges of

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8 NEGLECTED TROPICAL AND ZOONOTIC DISEASES TABLE WO-1 High-Prevalence and Other Vector-Borne Neglected Tropical Diseases Disability- Approximate Adjusted Global Life-Years Deaths Prevalence Approaches to Control High-prevalence 14.9–52.1 24,000–415,000 1.0–1.2 MDA with rapid effect diseases million billion package Hookworm 1.8–22.1 3,000–65,000 600 million MDA with rapid effect Infection million package or albendazole Ascariasis 1.2–10.5 3,000–60,000 800 million MDA with rapid effect million package or albendazole or mebendazole Trichuriasis 1.6–6.4 3,000–10,000 600 million MDA with rapid effect million package or albendazole or mebendazole Lymphatic 5.8 million <500 120 million MDA with rapid filariasis effect package or diethylcarbamazine+ albendazole or ivermectin+albendazole Schistosomiasis 1.7–4.5 15,000–280,000 200 million MDA with rapid effect million package or praziquantiel Trachoma 2.3 million <500 84 million SAFE strategy with azithromycin Onchocerciasis 0.7 million <500 37 million MDA with rapid effect package or ivermectin Vector-borne 5.0 million 132,000 70 million Integrated vector management protozoan and or case detection and viral diseases management or both Dengue fever 0.7 million 19,000 50 million Integrated vector management Leishmaniasis 2.1 million 51,000 12 million Case detection and management and integrated vector management Chagas disease 0.7 million 14,000 8–9 million Integrated vector management Human African 1.5 million 48,000 <0.1 million Case detection and trypanosomiasis management, and tsetse control NOTE: MDA, mass drug administration. SOURCE: Hotez et al. (2009b).

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9 WORKSHOP OVERVIEW hookworm and schistosomiasis frequently overlap, as do schistosomiasis and HIV/AIDS, especially in rural areas. The additive effects of such multiple infec - tions include profound anemia, complications of pregnancy, and physical and mental stunting in children, he said. Subsequent descriptions of the disability and disfigurement caused by individual diseases (collected in Box WO-6 and discussed in the next section of this overview), and of their magnified effects on women, children, and people living in conflict (below), further illustrate the broad and insidious public health impact of NTDs. NTDs and Poverty Poverty is by far the greatest risk factor for NTD infections, Hotez observed; and, he asserted, it is equally true that NTDs promote poverty and interfere with economic development. He and several other speakers featured poverty among their lists of common attributes of countries or regions afflicted with NTDs; workshop participants frequently connected the control of NTDs with the Mil - lennium Development Goals (MDGs) (UNDP, 2010), a set of important bench - marks for poverty reduction, global health, and political equity.5 A major report on NTDs from WHO, released in the weeks following the workshop (WHO, 2010b), stated that “working to overcome the impact of NTDs represents a largely untapped development opportunity to alleviate the poverty of many populations and thereby make a direct impact on the achievement of the Millennium Develop- ment Goals (MDGs).” NTDs and poverty are linked in numerous ways. Lack of access to clean water, sanitation, hygiene, housing, and health care leaves the poor vulnerable to a host of infections, including NTDs (Spiegel et al., 2010). Previous Forum work- shops have examined how water, sanitation, and hygiene coupled with additional environmental factors—including climate change, extreme weather events, land use patterns, and ecosystem disruption—contribute to the persistence and geo - graphic expansion of the NTDs, within the broader context of infectious disease emergence (IOM, 2008a,b, 2009). Water is an important common denominator in many of the NTDs. Water may serve as a medium through which parasites such as helminths are transmitted; as a breeding ground for vector species such as mosquitoes and tsetse flies; or as the habitat for intermediate hosts, such as snails that transmit schistosomiasis (see Table WO-2) and, therefore, represents an important route to NTD control. Each of the three workshop presentations summarized below discussed addi- tional important links between NTDs and poverty: the disproportionate burden of NTDs borne by women and children, the persistent effects of NTDs on cognitive 5 Among the eight MDGs, the sixth goal—“to combat HIV/AIDS, malaria and other diseases”—is now widely interpreted to include NTDs (Hotez and Pecoul, 2010; WHO, 2010b).

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10 NEGLECTED TROPICAL AND ZOONOTIC DISEASES TABLE WO-2 Environmental Classification of Water- and Excreta-Related Infections Category Examples Control Strategies A. Fecal-oral Viral Improve water quality (Potentially Hepatitis A, E, and F (to prevent water-borne water-borne or Poliomyelitis transmission), improve water-washed) Viral diarrhoeas water availability, hygiene Bacterial promotion (to prevent water- Campylobacteriosis washed transmission) Cholera Pathogenic E. coli Salmonellosis Typhoid, paratyphoid Protozoal Amoebiasis Cryptosporidiosis Giardiasis B. Purely Skin and eye infections Improve water availability, water-washed Scabies hygiene promotion Conjunctivitis Trachoma Louse-borne infections Relapsing fever C. Soil- Ascariasis Sanitation, hygiene transmitted Trichuriasis promotion, treatment of helminths Hookworm infection excreta before re-use Strongyloidiasis D. Food-borne Bacterial As C above, plus meat diseases Cholera inspection and cooking Campylobacter Salmonellosis and Shigellosis Viral infections Hepatitis A and E Norovirus Helminth infections Trichinellosis Food-borne trematode infections Clonorchiasis Opisthorchiasis Paragonimiasisis Tapeworms Diphyllobothrium infection Taenia solium infection Taenia saginata infection

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11 WORKSHOP OVERVIEW TABLE WO-2 Continued E. Water-based Bacterial Reduce contact with/ diseases Cholera consumption of infected Legionellosis water, sanitation, treatment Leptospirosis of excreta before re-use Helminthic Schistosomiasis Clonorchiasis, and, Dracunculiasis F. Insect vector Water-related Reduce number of potential diseases Dengue breeding sites and need to Yellow fever pass near them, improve Malaria surface water drainage, use West African trypanosomiasis repellent/insecticide where Excreta-related appropriate Bancroftian filariasis Trachoma Fly- and cockroach-borne excreted infectionsa G. Rodent-borne Rodent-borne excreted infections Rodent control, hygiene diseases Leptospirosis promotion, reduce contact Tularaemia with infected water aExcreted infections comprise all those in categories A, C, and D plus helminthic diseases in cat - egory E. SOURCE: Adapted from Bartram and Cairncross (2010). development, and the role of conflict in making people more vulnerable to NTD infection and its consequences. Impact on women’s and children’s health Speaker Marian McDonald, of the Centers for Disease Control and Prevention (CDC), examined the NTDs in terms of the MDGs and also of the “convergence model,” a framework for examining risk factors for disease emergence proposed in a seminal IOM report (IOM, 2003) that has informed much of the Forum’s work. (Dr. McDonald’s contribution to the workshop summary report can be found in Appendix A, pages 357–388.) As seen in Figure WO-3, the model consists of four sets of intersecting factors. In the case of NTDs, these factors influence the burden of disease for women and children, as follows: • Genetic and biological factors. Women are biologically “at risk” for acquiring NTDs during pregnancy and birth, McDonald said. These vulnerabilities in turn affect children’s development. For example, she noted, soil-transmitted helminths (STHs) contribute to anemia in pregnant women, jeopardizing the health of both mother and fetus. Hotez noted

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104 NEGLECTED TROPICAL AND ZOONOTIC DISEASES BOX WO-6 Continued TRACHOMA FIGURE WO-6-19 Trachoma. Chlamydia trachomatis infection can lead to con- junctivitis (as seen here) and to blindness. SOURCE: CDC, Public Health Image Library (PHIL 4076). Infectious agent: Chlamydia trachomatis, a bacterium Routes of transmission to humans: Human-to-human contact; eye-seeking flies Health effects: Scarring of cornea leads to blindness (leading infectious cause of blindness) Incidence, prevalence, and mortality (estimated): 84 million people infected, of whom 2.9 million become blind and 3.5 million have impaired vision Prevention: Access to clean water; improved sanitation and hygiene (face washing); reduction in fly breeding sites Treatment: Surgery to correct scarring and reverse inturned eyelashes

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105 WORKSHOP OVERVIEW TRICHURIASIS (WHIPWORM) A B FIGURE WO-6-20 Trichuriasis (Whipworm). (A) Close-up of the prolapsed rectum of a child with numerous Trichuris trichiura clinging to the rectal mucosa. (B) Nematode (Trichuris spp.) helminth (whipworm), intestinal parasite. SOURCES: Palmer and Reeder/USUHS, courtesy of Dr. Herman Zaiman; http://www.denniskunkel. com/product_info.php?products_id=668 (accessed January 19, 2011). Copyright Dennis Kunkel Microscopy, Inc. Infectious agent: Trichuris trichiura, a parasitic roundworm Routes of transmission to humans: Ingestion of eggs from contaminated soil; worm embeds in wall of large intestine Health effects: Cognitive impairment, colitis and inflammatory bowel disease, delayed physical and mental development Incidence, prevalence, and mortality (estimated): 604 million people infected of whom 27 million are “highly infected” Prevention: Improved hygiene and sanitation; periodic drug treatment of at-risk populations Treatment: Antihelminthic therapy continued

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106 NEGLECTED TROPICAL AND ZOONOTIC DISEASES BOX WO-6 Continued HUMAN AFRICAN TRYPANOSOMIASIS (ZOONOTIC SLEEPING SICKNESS) A B C FIGURE WO-6-21 Human African Trypanosomiasis (Trypanosoma brucei). (A) A young woman watches over her husband who is comatose, suffering from sleeping sickness. (B) Child suffering from convulsion due to treatment toxicity, Democratic Republic of Congo. (C) Trypanosoma parasite in peripheral blood. SOURCES: WHO/TDR/Wellcome; WHO; CDC Public Health Image Library (PHIL 613). Infectious agent: Protozoan parasites Trypanosoma brucei gambiense (West and Central Africa), T. brucei rhodesiense (eastern and southern Africa) Routes of transmission to humans: Insect bites, especially from tsetse flies Health effects: Central nervous system damage; fatal if untreated Incidence, prevalence, and mortality (estimated): Limited to Africa; 50,000–70,000 infections and up to 24,000 deaths per year Prevention: Vector control Treatment: First- and second-stage drug treatments; second-stage drugs, which cross the blood–brain barrier, are highly toxic and difficult to administer

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107 WORKSHOP OVERVIEW YAWS A B FIGURE WO-6-22 Yaws infection (Treponema pertenue). (A) Tibial ‘‘saber” deformity as a result of yaws. (B) Child presenting lesions caused by yaws, Côte d’Ivoire, 2009. SOURCES: Rinaldi (2008), previously published in PLoS Neglected Tropical Diseases; WHO. Infectious agent: Treponema pertenue, a bacterium Routes of transmission to humans: Person-to-person via skin contact (infects only humans) Health effects: Chronic disfigurement due to skin and cartilage lesions; painful bone lesions; rarely fatal Incidence, prevalence, and mortality (estimated): No recent estimates; in the 1990s, WHO determined that 2.5 million people were infected, of which 460,000 represented new cases Prevention: A candidate for eradication via antibiotic treatment to interrupt transmission Treatment: Antibiotic therapy SOURCE: Adapted from Health Affairs (2009) with additional information from Ayele et al. (2004), CDC (2009, 2010a), Cosivi et al. (1998), Hotez (2010a), Hotez and Wilkins (2009), Pappas et al. (2006), and WHO (2008a–g, 2010c–g); The Merck Manual (http://www.merckmanuals.com/ professional/sec14/ch183/ch183h.html (accessed on January 21, 2011).

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110 NEGLECTED TROPICAL AND ZOONOTIC DISEASES Fenwick, A., Y. Zhang, and K. Stoever. 2009. Control of the neglected tropical diseases in sub-Saharan Africa: The unmet needs. International Health 1:61–70. Genser, B., A. Strina, L. A. dos Santos, C. A. Teles, M. S. Prado, S. Cairncross, and M. L. Barreto. 2008. Impact of a city-wide sanitation intervention in a large urban centre on social, environ - mental and behavioural determinants of childhood diarrhoea: Analysis of two cohort studies. International Journal of Epidemiology 37(4):831–840. Global Network (Global Network for Neglected Tropical Diseases). 2010. “About NTDs.” Sabin Vaccine Institute. Washington, DC. http://globalnetwork.org/about-ntds (accessed November 16, 2010). Goodman, P. 2009. Emphasis on growth is called misguided. New York Times, September 23. Grove, D. I. 1990. A history of human helminthology. Wallingford, UK: CAB International. Gryseels, B. 1989. The relevance of schistosomiasis for public health. Tropical Medicine and Para- sitology 40(2):134–142. Hamburg, M. A. 2010. Margaret A. Hamburg, M.D., Commissioner of Food and Drugs—remarks at the medical countermeasures review roll out. http://www.fda.gov/NewsEvents/Speeches/ ucm226351.htm (accessed November 3, 2010). Hanson, 2010. Keynote Remarks. Presentation given at the September 21–22, 2010, public workshop, “The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Implications for Global Health and Opportunities for Novel Intervention Strategies,” Forum on Microbial Threats, In - stitute of Medicine, Washington, DC. Health Affairs. 2009. Tropical diseases: The price of neglect (editorial). Health Affairs (Millwood) 28(6):1688–1690. Hopkins, D. 2009. The allure of eradication. Global Health Magazine Summer 2009(03):14–17. ———. 2010. NTDs slated for elimination and eradication. Paper read at “The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Implications for Global Health and Opportunities for Novel Intervention Strategies,” September 21, 2010, Washington, DC. Hotez, P. J. 2006. The “biblical diseases” and U.S. vaccine diplomacy. Brown Journal of World Af- fairs 12:247–258. ———. 2008a. The giant anteater in the room: Brazil’s neglected tropical diseases problem. PLoS Neglected Tropical Diseases 2(1):e177. ———. 2008b. Neglected infections of poverty in the United States of America. PLoS Neglected Tropical Diseases 2(6):e256. ———. 2009a. Neglected diseases amid wealth in the United States and Europe. Health Affairs (Millwood) 28(6):1720–1725. ———. 2009b. Mass drug administration and integrated control for the world’s high-prevalence neglected tropical diseases. Clinical Pharmacology and Therapeutics 85(6):659–664. ———. 2009c. The neglected tropical diseases and their devastating health and economic impact on the member nations of the Organisation of the Islamic Conference. PLoS Neglected Tropical Diseases 3(10):e539. ———. 2010a. A plan to defeat neglected tropical diseases. Scientific American 302(1):90–94, 96. ———. 2010b. Neglected infections of poverty among the indigenous peoples of the Arctic. PLoS Neglected Tropical Diseases 4(1):e606. ———. 2010c. Peace through vaccine diplomacy. Science 327(5971):1301. ———. 2010d. Nuclear weapons and neglected diseases: The “ten-thousand-to-one gap.” PLoS Neglected Tropical Diseases 4(4):e680. Hotez, P. J., and B. Pecoul. 2010. “Manifesto” for advancing the control and elimination of neglected tropical diseases. PLoS Neglected Tropical Diseases 4(5):e718. Hotez, P. J., and P. P. Wilkins. 2009. Toxocariasis: America’s most common neglected infection of poverty and a helminthiasis of global importance? PLoS Neglected Tropical Diseases 3(3):e400. Hotez, P. J., D. H. Molyneux, A. Fenwick, E. Ottesen, S. Ehrlich Sachs, and J. D. Sachs. 2006. Incor- porating a rapid-impact package for neglected tropical diseases with programs for HIV/AIDS, tuberculosis, and malaria. PLoS Medicine 3(5):e102.

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111 WORKSHOP OVERVIEW Hotez, P., S. Raff, A. Fenwick, F. Richards, Jr., and D. H. Molyneux. 2007a. Recent progress in inte - grated neglected tropical disease control. Trends in Parasitology 23(11):511–514. Hotez, P. J., D. H. Molyneux, A. Fenwick, J. Kumaresan, S. E. Sachs, J. D. Sachs, and L. Savioli. 2007b. Control of neglected tropical diseases. New England Journal of Medicine 357(10):1018–1027. Hotez, P. J., J. M. Bethony, S. C. Oliveira, P. J. Brindley, and A. Loukas. 2008a. Multivalent an - thelminthic vaccine to prevent hookworm and schistosomiasis. Expert Review of Vaccines 7(6):745–752. Hotez, P. J., M. E. Bottazzi, C. Franco-Paredes, S. K. Ault, and M. R. Periago. 2008b. The neglected tropical diseases of Latin America and the Caribbean: A review of disease burden and distribu - tion and a roadmap for control and elimination. PLoS Neglected Tropical Diseases 2(9):e300. Hotez, P. J., A. Fenwick, and E. F. Kjetland. 2009a. Africa’s 32 cents solution for HIV/AIDS. PLoS Neglected Tropical Diseases 3(5):e430. Hotez, P. J., A. Fenwick, L. Savioli, and D. H. Molyneux. 2009b. Rescuing the bottom billion through control of neglected tropical diseases. Lancet 373(9674):1570–1575. Hotez, P. J., J. M. Bethony, D. J. Diemert, M. Pearson, and A. Loukas. 2010. Developing vaccines to combat hookworm infection and intestinal schistosomiasis. Nature Reviews Micriobiology 8(11):814–826. Humphreys, M. 2009. How four once common diseases were eliminated from the American South. Health Affairs (Millwood) 28(6):1734–1744. Iglehart, J. K. 2004. Advocating for medical diplomacy: A conversation with Tommy G. Thompson. http://content.healthaffairs.org/cgi/content/full/hlthaff.w4.262v1/DC1 (accessed August 1, 2010). IOM (Institute of Medicine). 2003. Microbial threats to health: Emergence, detection, and response. Washington, DC: The National Academies Press. ———. 2008a. Global climate change and extreme weather events: Understanding the contributions to infectious disease emergence. Washington, DC: The National Academies Press. ———. 2008b. Vector-borne diseases: Understanding the environment, human health, and ecological connections. Washington, DC: The National Academies Press. ———. 2009. Global issues in water, sanitation, and health. Washington, DC: The National Acad- emies Press. Kanazawa, S. 2008. Temperature and evolutionary novelty as forces behind the evolution of general intelligence. Intelligence 36. Keiser, J., and J. Utzinger. 2008. Efficacy of current drugs against soil-transmitted helminth infec - tions: Systematic review and meta-analysis. Journal of the American Medical Association 299(16):1937–1948. King, C. H. 2007. Lifting the burden of schistosomiasis—defining elements of infection-associated disease and the benefits of antiparasite treatment. Journal of Infectious Diseases 196(5):653–655. ———. 2010. Parasites and poverty: The case of schistosomiasis. Acta Tropica 113(2):95–104. Kissinger, P., W. E. Secor, J. S. Leichliter, R. A. Clark, N. Schmidt, E. Curtin, and D. H. Martin. 2008. Early repeated infections with Trichomonas vaginalis among HIV-positive and HIV-negative women. Clinical Infectious Diseases 46(7):994–999. Kjetland, E. F., P. D. Ndhlovu, E. Gomo, T. Mduluza, N. Midzi, L. Gwanzura, P. R. Mason, L. Sandvik, H. Friis, and S. G. Gundersen. 2006. Association between genital schistosomiasis and HIV in rural Zimbabwean women. AIDS 20(4):593–600. Kristoff, N. 2010. Winning the worm war. New York Times, April 28. http://www.nytimes. com/2010/04/29/opinion/29kristof.html (accessed August 20, 2010). Lebel, J. 2003. In focus: Health—an ecosystem approach. Ottawa: International Development Re- search Centre. Lima, M. D. R. Q., R. M. R. Nogueira, H. G. Schatzmayr, and F. B. D. Santos. 2010. Comparison of three commercially available dengue NS1 antigen capture assays for acute diagnosis of dengue in Brazil. PLoS Neglected Tropical Diseases 4(7):e738.

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