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Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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A
Contributed Manuscripts

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REGIONAL APPROACHES TO NEGLECTED TROPICAL DISEASES CONTROL IN LATIN AMERICA AND THE CARIBBEAN

Steven Kenyon Ault and Mirta Roses Periago

Pan American Health Organization

Neglected [tropical] diseases impose a huge burden on developing countries, constituting a serious obstacle for socioeconomic development and quality of life … Thus, taking decisive action to eliminate them as a public health problem in the Region, which is an achievable dream—provided the necessary political commitment and resources are in place—for which we are working in PAHO, would also be a clear reassertion of our countries’ deep commitment with human rights as enshrined in international treaties and standards.


—Mirta Roses Periago, Director, Pan American Health Organization (Director’s Blog, April 8, 2008, http://66.101.212.220/mirtaroses/index.php?id=69)

Background

In the Latin America and Caribbean region (LAC) at least 180 million people live below the poverty line. These impoverished and marginalized populations are often heavily burdened with neglected tropical diseases (NTDs) and other infectious diseases of poverty. This group of diseases continues to take a measur-

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

able toll, not only on families and communities but also on the socioeconomic development of nations.

NTDs and Their Impact

The NTDs largely comprise infectious and parasitic tropical diseases. Today, NTDs can be usefully considered as a group because they are concentrated almost exclusively among impoverished populations living in marginalized areas whether rural or peri-urban. These incapacitating diseases, such as lymphatic filariasis, onchocerciasis or river blindness, schistosomiasis (including bilharzia), soil-transmitted helminthiasis (ascariasis, trichuriasis, and hookworm infection), Chagas disease, leishmaniasis, leprosy or Hansen’s disease, and trachoma continue to perpetuate poverty, generate prejudice, or inflict severe incapacity (lymphatic filariasis), disability (e.g., leprosy/Hansen’s, onchocerciasis), and sometimes premature death (e.g., Chagas disease and schistosomiasis) in LAC and other regions of the world. Children with heavy intestinal worm burdens may become stunted or anemic, or they may suffer from maldigestion, malabsorption, and poor physical and cognitive development. These worms can reduce school attendance, attention span in class, and test scores. Infection with NTDs reduces income-earning capacity, and this in turn often creates a loss of the ability to care for a family.

Social Determinants

Although biologically and medically diverse, NTDs share features that allow them to persist in conditions of poverty where they frequently overlap (Brooker et al., 2006). These conditions of poverty include unsafe water, poor sanitation, and refuse disposal, which sustain transmission cycles and favor the proliferation of vectors that transmit disease. Other conditions, such as a lack of access to health services, low levels of literacy, inadequate nutrition and poor personal hygiene all help to increase vulnerability to infection and work against prevention efforts. Addressing these social determinants of poverty complements the use of existing tools to combat and eliminate NTDs. Specific technical opportunities to control and eliminate NTDs in LAC through intersectoral and multidisease approaches while addressing social determinants were recently reviewed (Ault, 2008; Ehrenberg and Ault, 2005; Holveck et al., 2007; Hotez et al., 2008), and provide background for this paper.

Legacy of Slavery

Interestingly, some of the NTDs—for example lymphatic filariasis (LF), onchocerciasis, and schistosomiasis—are parasitic diseases that were imported to the Western Hemisphere through the European slave trade, which targeted

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

Africa. Today, a little more than 200 years after the end of that colonial slave trade, they still cause substantial morbidity and are particularly attractive targets of elimination. As noted by Lammie et al. (2007), “the elimination of diseases that are a consequence of this trade will represent a tangible contribution to the health and well being of people and communities who, arguably, still suffer from the residual affects of slavery.”

Tools and Mandate to Combat

Tools exist today to effectively combat the NTDs, including safe and inexpensive antihelminthics, dose poles, quantitative and rapid mapping methods, and rapid test kits for several parasites, and having these tools in hand makes it an ethical imperative to work toward the control and elimination of NTDs. Since 2007, the Pan-American Health Organization (PAHO) also made headway in the scientific and political debate that guided the development of an elimination agenda and made it possible to subsequently mobilize the necessary will and resources. In 2009, PAHO received a mandate in the form of a resolution (CD49-R19) from its Directing Council (composed of the Ministers of Health of the region) to support the countries in the region in eliminating or significantly reducing the burden of a group of 12 neglected diseases and other poverty-related infections. This chapter discusses this mandate and the region’s plans to tackle and eliminate several NTDs over the next five years.

Elimination Agenda

Working together, the LAC countries and PAHO have had significant success in eliminating several infectious diseases in the region in the recent decades: smallpox (1977), poliomyelitis (1994, wild poliovirus), and measles (2002). As well, at the end of 2010, onchocerciasis transmission has been apparently eliminated in 8 of 13 foci among six endemic countries in the region. The number of human cases of rabies transmitted by dogs in Latin America dropped significantly, by nearly 90 percent, between 1990 and 2007 (PAHO, 2009).

A significant reduction in the transmission of Chagas disease by two important domestic vectors (Rhodnius prolixus and Triatoma infestans) in the 21 endemic countries has been achieved since 1990 principally as a result of systematic indoor spraying with residual pyrethroid insecticides of houses in rural endemic areas, infection and mortality have declined as has the population at risk (Table A1-1). As of 2010, 10 countries have eliminated these vectors and 3 others have eliminated them in parts of their national territories. A reduction in blood transfusion–origin Chagas disease has also been achieved in the region, as endemic countries began universal screening of blood donors at blood banks using a rapid Enzyme-linked immunosorbent assay (ELISA) test.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

TABLE A1-1 Evolution of Change in Epidemiological Parameters of Chagas Disease in LAC

Changas Disease

Epidemiological Parameters

1990

2006

Annual deaths

>45,000

12,500

Human cases of infection

30 million

15 million

New cases per year

700,000

41,200

At-risk population

100 million

28 million

SOURCE: PAHO (2009).

What Is Feasible?

There is broad technical consensus that there are available tools and strategies to combat several neglected tropical diseases that have been included in the World Health Organization’s (WHO’s) 2008–2015 Global Plan to Combat Neglected Tropical Diseases (WHO, 2007). Beginning in 2007, PAHO began to review the data to determine which of these NTDs and other infectious diseases of poverty we can eliminate or significantly reduce transmission of in the entire region by 2015, such as onchocerciasis, LF, and trachoma. PAHO reviewed others that can be eliminated in certain subregions or in a particular country, as in the cases of plague in Peru and Ecuador, schistosomiasis in St. Lucia and Suriname, and malaria in the Caribbean and Central America. The agency focused on identifying successful strategies for control and elimination, collecting epidemiological data on the presence and prevalence of these diseases in the region, and preparing maps down to the first administrative level of where the diseases overlapped geographically. With these data and information in hand, PAHO published its epidemiological profiles of 10 neglected diseases in 14 countries in early 2009 (PAHO, 2009).

Next, a regional elimination strategy was developed during 2009 by the agency’s communicable diseases project for 10 neglected diseases of poverty with input from PAHO technical staff, managers and external experts, and the draft strategy was vetted with the Ministers of Health and approved by the Directing Council in October 2009 as Resolution CD49-R19. In approving the resolution, the Member States of the region have committed to an objective by 2015 to eliminate or reduce neglected diseases and other infections related to poverty for which tools exist, to levels such that these diseases are no longer considered public health problems. This effort requires long-term political and financial commitment and the preparation and implementation of integrated national plans of action (POAs). In 2010, several countries in the region have now established national committees with the objective to develop their POAs for the integrated control and elimination of NTDs.

The PAHO strategy uses two definitions for elimination, depending on the

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

disease. The elimination of a disease is a reduction to zero of the incidence of a given disease in a defined geographic area as a result of deliberate efforts, with continued intervention measures being required (WHO, 1998). Elimination of a disease as a public health problem occurs by drastically reducing the disease’s burden to a level that is acceptable given the current tools available and the region’s health situation. At this level, the prevalence of the disease does not constrain social productivity and community development. Achievable goals have been established for each disease. In this chapter, both definitions are used to select the diseases targeted for elimination, according to previous global and regional mandates for elimination.

PAHO considered the following criteria in selecting the diseases that could feasibly be eliminated or drastically reduced in the region: (a) the “unfinished agenda”—diseases that already had been priority targets for elimination by PAHO or WHO and for which, despite progress made, some areas lagged behind; (b) technical feasibility—including the availability of knowledge and tools for structuring interventions to interrupt or reduce transmission; (c) regional evidence of achievable elimination—existence of successful regional experiences in accomplishing elimination at country or subnational levels; (d) economic criteria—including relatively low unit cost of interventions and demonstrated cost-effectiveness; (e) unequal burden of disease—wherein the more vulnerable populations (such as indigenous and Afro-descendant populations, women, and children who have been historically excluded) suffer from a higher prevalence and social consequences of these diseases, thus perpetuating the cycle of poverty; (f) political relevance—the diseases must be recognized as being of public health importance with a broad international appeal, which could be expressed through existing resolutions approved by the World Health Assembly or PAHO’s Directing Council; and (g) best practices, including those utilized in primary health care, well-accepted interventions such as mass preventive chemotherapy and high-coverage vaccination campaigns, integrated approaches for vector-borne diseases, and local projects with community participation to improve health through intersectoral action. These examples of best practices have already been developed in the region and will provide the basis for the scale-up of local and national proposals for disease elimination.

The selected diseases were classified into two groups, those with greater potential for being eliminated, and those that can be drastically reduced with available tools. Group 1 diseases are those that have a greater potential for being eliminated: Chagas disease (vector-borne and transfusional transmission, both as a public health problem); congenital syphilis (as a public health problem); LF (as a public health problem); onchocerciasis; rabies transmitted by dogs; neonatal tetanus (as a public health problem); trachoma (as a public health problem); leprosy (as a public health problem at the national and first subnational level); malaria (elimination in Haiti and the Dominican Republic and in México and Central America); and plague (as a public health problem). Cost-effective strate-

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

gies and tools exist for elimination, there is evidence of feasibility of elimination in other countries or areas in LAC, or there are global or regional mandates to reach elimination. Next, we highlight two of the Group 1 diseases, onchocerciasis and lymphatic filariasis.

Onchocerciasis is endemic in parts of Africa and in 13 foci in six countries of the Americas where it was introduced through the slave trade. It is estimated that more than half a million people live in areas of México, Guatemala, Colombia, Ecuador, Venezuela, and Brazil where documented transmission of onchocerciasis occurs or has been documented in the recent past. The basic strategy for achieving elimination in this Region is mass drug administration (MDA) using a form of ivermectin (Mectizan®, a donated medicine) given twice a year to at least 85 percent of all eligible population, accompanied by health education and promotion of community participation for at least 10 consecutive years. The minimum required coverage in all the 13 foci in the Region was achieved in 2002 and has been maintained since. New cases of onchocercal blindness were eliminated since 2007. However, some cases of ocular morbidity still occur in a few foci, mainly in the Amazon region of Southern Venezuela and Northern Brazil inhabited by the Yanomami Amerindians. As of January 2011 onchocerciasis transmission has been interrupted in 8 of the 13 foci, with those currently being in the post-treatment surveillance phase. Transmission is suspected to be suppressed in two other foci: South Chiapas in México and the Central focus in Guatemala. Onchocerciasis transmission persists in the three foci (Northeastern focus of Venezuela, and the southern focus of Venezuela and northern focus of Brazil, which share the Yanomami area (epidemiologically, it constitutes one shared focus). The Yanomami area represents the greatest challenge to the regional elimination efforts.

Lymphatic filariasis, another NTD imported to LAC by the trans-Atlantic slave trade, was common in port cities, some Caribbean islands, and coastal areas in the Region until the last century when advances in sanitation began to reduce and then interrupt transmission by its Culex mosquito vector. In the past few decades three countries (Costa Rica, Suriname, and Trinidad and Tobago) have presented evidence of interruption of transmission, together with two cities in Brazil (Belém, Pará state and Maceió, Alagoas state). Today more than 9 million people are considered at risk for lymphatic filariasis in four endemic countries in the Region (one focus in metro Recife, Brazil, and Guyana, Dominican Republic and Haiti), with the highest proportion living in Haiti. People at risk benefit from more than 10 years of effort to eliminate transmission by MDA with the drugs diethlycarbamazine and albendazole. In 2009 about 3.4 million were treated via MDA. The January 2010 earthquake in Haiti and the Dominican Republic complicated the timely delivery of medicines. A meeting convened by PAHO in February 2010 with international partners created solidarity in support of Haiti to continue the work and reach the elimination goal, which helped enable the Haitian Ministry of Health and Population’s MDA program to pick up and con-

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

tinue in 2010. Ministries of Health are intensifying their efforts to eliminate the remaining foci in Brazil, Dominican Republic, and Guyana.

Group 2 diseases are those whose burden can be drastically reduced with available tools: schistosomiasis and soil-transmitted helminthiasis (STH), for which there exist safe and very effective drugs and a record of success in greatly reducing intensity of infection though MDA in a strategy of preventive chemotherapy. In LAC, the parasites targeted are Schistosoma mansoni (the only human schistosome in the region) and the three common types of STHs (Ascaris lumbricoides, Trichuris trichura, and the human hookworms Ancylostoma duodenale and Necator americanus). They persist in some areas (poor rural communities or peri-urban shantytowns), sometimes with a very high prevalence (more than 50 percent) in vulnerable populations like children; however in many countries there is very limited or no recent epidemiological data about their distribution, prevalence, and burden, hampering awareness and adequate interventions.

Soil-transmitted helminthiasis is considered to be present in all the LAC Region’s countries, with prevalence varying. PAHO estimates conservatively that 13 million preschool-age children and 33 million school-age children are at risk of STH infections in the Region, where transmission is closely associated with a lack of access to basic sanitation and safe water. A handful of countries have established national deworming programs, principally for school-age children, while in other countries various international nongovernmental organizations (NGOs) contribute to deworming efforts through their community-targeted interventions. Epidemiological information on STH is sparse, as these infections are not reportable; however, in PAHO’s review of published prevalence rates some surveys have indicted prevalence higher than 50 percent in some groups of school-age children and indigenous populations, and intensity of infection varies but has been seen high enough to be associated with adverse health effects like anemia. The Region’s high-risk countries are being encouraged and supported to scale-up deworming efforts to reach all vulnerable populations.

In LAC, PAHO estimates that approximately 1.8 million persons are infected, and up to 25 million are at risk of schistosomiasis. Schistosomiasis infection occurs in humans in contact with infested freshwater reservoirs when the cercarial stage of the parasitic fluke leaves the intermediate host snail and penetrates the person’s skin and enters the bloodstream. The drug praziquantel is the recommended treatment, which can be provided by MDA or individual treatment. MDA with praziquantel can interrupt transmission. Today the disease is limited to four countries in LAC: parts of Brazil (principally the northeast of the country), St. Lucia, and parts of Suriname and Venezuela. Morbidity appears low, and reported deaths (from Brazil) are few. Brazil’s national schistosomiasis control program has, over the decades, significantly reduced morbidity and mortality, while the other countries treat cases as encountered; Suriname and St. Lucia are taking steps to eliminate the disease while Venezuela is evaluating its epidemiological situation.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

For other infectious diseases, such as leishmaniasis and leptospirosis, the burden of the disease needs to be further assessed, better tools need to be developed for diagnosis (e.g., leishmaniasis), and methods and strategies for achieving cost-effective and sustainable prevention and control need to be established (e.g., leptospirosis, cysticercosis/taeniasis). For these diseases and for others that have epidemiological relevance to some of the region’s countries, more operational research needs to be conducted, new tools need to be assessed, and surveillance systems need to be improved.

Framework for Elimination

The public health strategies and interventions that are used to eliminate or reduce infectious diseases to acceptable levels go beyond routine control measures. In order to strengthen the efforts against diseases related to poverty as a group, endemic countries can develop integrated POAs under the same framework, while considering the following:

  • Available plans at the global, regional, or country level to eliminate or control these diseases.

  • Available guidelines for the selected diseases to support the countries in achieving the goals of elimination or control.

  • Available tools such as drugs and diagnostic techniques to support surveillance systems.

  • Evidence-based decisions for strengthening health surveillance systems, mapping the diseases to identify remaining foci, and identifying overlapping of diseases in geopolitical areas (“hot spots” or areas of co-endemicity) for integrated action.

  • Reducing gaps in tool-ready neglected diseases in deficit areas in the region.

  • Ensuring that the necessary resources are available for the primary care system to integrate NTD control and help reduce inequalities in health.

  • Pursuing inter-programmatic interventions that integrate the various existing plans into a comprehensive vision based on the epidemiology and social determinants of each area identified for intervention (hot spots); interventions should tackle the factors and mechanisms through which social conditions affect the community’s health and, where possible, address them through social and health policies.

  • Pursuing community participation and intersectoral partnerships: the community, stakeholders and all actors and potential partners within and outside the health sector should be enlisted to make actions sustainable.

  • Pursuing horizontal cooperation: identify which countries share problems or borders where the selected diseases occur, to promote joint actions and intercountry plans.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×
  • The increase in donor support from global partners in the fight against neglected tropical diseases and other infections related to poverty.

Progress, Priorities, and Lines of Action for Elimination

PAHO partnered with the Inter American Development Bank (IDB) and the Global Network for Neglected Tropical Diseases (GNNTD, or Global Network [GN]) based in the Sabin Vaccine Institute beginning in 2008. With the IDB and the GN the partners have established a Trust Fund for Neglected Infectious Diseases in the IDB and are working to capitalize the fund in 2011. Additionally the partners have worked together and with Ministries of Health to develop a POA and demonstration project in the State of Chiapas México projects, and another demonstration project in the metropolitan area of Recife, northeast Brazil, which are meant to demonstrate or show proof of principle of integrated approaches to NTD control and elimination in the LAC Region. The Chiapas demonstration project covers trachoma, Chagas disease, leishmaniasis, rabies transmitted by dogs, onchocerciasis, and STHs. The project in metropolitan Recife tackles schistosomiasis, STHs, LF, and leprosy/Hansen’s disease. Each project will become operational in 2011. Meanwhile, several countries, including Guyana, Suriname, Dominican Republic, and Haiti, are developing integrated POAs to combat multiple NTDs, and more countries will begin the process in 2011.

In collaboration with the GNNTD, in 2010 PAHO began a process to map NTDs down to lower administrative levels (municipal levels) in several countries. With the Swiss Tropical Institute and Louisiana State University, PAHO is using environmental and social parameters and Bayesian modeling to map the expected distribution and prevalence of Chagas disease, schistosomiasis and STH in Brazil, Bolivia, and Colombia. This modeling approach is expected to be extended to additional countries in 2011. Additionally, PAHO has worked with the Autonomous University of Yucatán, México, to study the social determinants of STHs, Chagas disease, and dengue in peri-urban and rural communities near the city of Mérida.

To operationalize the strategies and interventions needed to eliminate NTDs in the region, PAHO also prepared a report in 2010 analyzing progress in control and elimination of five NTDs amenable to preventive chemotherapy, prioritizing the associated endemic countries with respect to these five diseases and identifying lines of action to take to achieve elimination by 2015 (PAHO, 2010).

This report, referred to as the Prioritization Report, is a qualitative analysis of gaps and needs in technical cooperation and is presented in order to make progress toward the elimination goals for these five diseases in 33 countries in LAC: onchocerciasis, schistosomiasis, trachoma, LF, and soil-transmitted helminthiasis.

As a result of the analysis, countries were classified and prioritized into four groups.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

Group 1 This group concentrates the majority of population at risk for the main NTDs. These countries have 66.8 and 67.4 percent of preschool-age children (Pre-SAC) and school-age children (SAC) populations, respectively, at risk in LAC for STHs. Four countries have foci of onchocerciasis with 421,000 people at risk. Three countries have foci of schistosomiasis with up to 25 million people at risk. Three countries have foci of trachoma with up to 50 million people living in risk areas, and four countries have foci of LF with more than 9 million people at risk. This group includes countries working to eliminate onchocerciasis, LF, and trachoma, and one country with the possibility to eliminate schistosomiasis; Suriname is expecting external verification of LF elimination. This group needs technical cooperation to develop and implement integrated, interprogrammatic, and intersectoral plans to combat neglected infectious diseases (NIDs) including STHs (Table A1-2).

TABLE A1-2 Diseases, Foci, Population at Risk, and Treatment Coverage in Group 1 Countries

Diseases in Countries of Group 1

Foci

Population at Risk

Treatment Coverage

Onchocerciasis

This group has 9 of 13 onchocerciasis foci in LAC: Brazil (1), Ecuador (1), Guatemala (4), and México (3)

Transmission interrupted in 6 foci: México (2), Guatemala (3), Ecuador (1)

421,000 people

Second Round 2009: Brazil 89%; Guatemala 93%; México 93%; Ecuador 96%

Lymphatic filariasis

This group has all of the lymphatic filariasis foci: Brazil, Dominican Republic, Haiti, and Guyana. Suriname is expecting validation of elimination.

More than 9 million people

MDA in 2009: Haiti 3 million people treated; Brazil 177,000; Guyana: 129,189; Dominican Republic has not carried out MDA for LF since 2007, transmission interruption is being evaluated

Schistosomiasis

Foci in 3 countries: Brazil, Suriname, and Saint Lucia. Transmission to be evaluated in Dominican Republic

Nearly 25 million people at risk

Treatment coverage: Brazil 83% cases treated of cases detected; 21 cases were treated in 2009 in Suriname

Trachoma

Foci in Brazil, Guatemala, and México

50 million people live in risk areas

No data available at national level

SOURCE: Modified from PAHO (2010).

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

Group 2 This group has 26.8 and 26.1 percent of Pre-SAC and SAC populations, respectively, at risk for STHs in LAC. Two countries have foci of onchocerciasis with 115,070 people at risk. One country has foci of schistosomiasis. There is no evidence of LF transmission in this group of countries. However, recently Miller et al. (2010) provided clinical evidence of trachoma in an Amerindian indigenous community in the Department of Vaupés, Colombia documenting the presence of trachoma for the first time in Colombia.

This group includes countries also eliminating onchocerciasis and targeting schistosomiasis. These countries need technical cooperation to improve current interprogrammatic and intersectoral coordination and to include STHs into NID-integrated actions (Table A1-3).

As mentioned above, most of the LAC countries have no updated results of nationwide surveys of prevalence and intensity of infection of STH and schistosomiasis and trachoma. Groups 1 and 2 have the greatest gaps in sanitation coverage and a clear opportunity to integrate intersectoral and interprogrammatic actions for integrated NTD control, in the framework of primary health care systems and addressing the social determinants of health.


Group 3 This group has 5.4 percent of Pre-SAC and SAC population at risk for STHs in LAC. There is no evidence of the presence of onchocerciasis, schistosomiasis, trachoma, or LF. These countries need technical cooperation to focus activities for NIDs at local level and rural areas, with emphasis on STHs.


Group 4 This group has 1.03 and 1.1 percent of Pre-SAC and SAC populations, respectively, at risk for STHs in LAC. There is no evidence of the presence of onchocerciasis, schistosomiasis, trachoma, or LF. Costa Rica and Trinidad and Tobago are expecting external verification of LF elimination.

TABLE A1-3 Diseases, Foci, Population at Risk, and Treatment Coverage in Group 2 Countries

Diseases in Group 2

Foci

Population at Risk

Treatment Coverage

Onchocerciasis

This group has the remaining 4 of the 13 foci of onchocerciasis in LAC: Colombia (1) and Venezuela (3)

115,070 people at risk

Second Round 2009: Venezuela South focus 85%, Northeast focus 95%, North–central focus 99%. The Colombian focus is in posttreatment surveillance

 

Transmission interrupted in Colombia focus

 

Schistosomiasis

Foci in Venezuela

No data available

No data available

SOURCE: PAHO (2010).

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

The classification is used to define the nature of external technical cooperation that each group may require to mobilize resources needed for elimination. It is important to note that if actions were focused on all populations of Groups 1 and 2, the following groups could be reached (see Table A1-4 for details):

  • 84.5 million of people at risk for four diseases (i.e., onchocerciasis, schistosomiasis, LF, and trachoma); and

  • 94 percent (12,088,816) of Pre-SAC and 93.5 percent (29,927,933) of SAC populations at risk for STHs in LAC, who could be reached with deworming activities.

Opportunities for Integration

In the PAHO map below (Figure A1-1), six NTDs are shown in 14 countries for 2008: schistosomiasis, STHs, onchocerciasis, LF, trachoma, and human rabies transmitted by dogs. The diseases are mapped at the first “administrative” level of the country. Among these countries, 275 administrative units (e.g., states, provinces, departments etc.) reflect the co-endemicity of diseases. Three of the units (the states of Maranhão, Pernambuco, and Sergipe in Brazil) have the presence of four of the six NTDs selected for the PAHO study. Twelve other units present with the presence of three of the six diseases, while 41 units had two NTDs present. This 2008 analysis by PAHO revealed that, of the 580 million inhabitants of LAC, some 241 million live in units with the presence of at least one of these diseases.

The mapping efforts of PAHO have shown the potential for integrated control and elimination where two or more NTDs overlap in space and time. Efficiencies and economies of scale can be achieved, and local health workers can be trained to manage multiple diseases in the areas of endemicity.

TABLE A1-4 Pre-SAC and SAC Population at Risk for Soil-Transmitted

Group of Countries

Pre-SAC at Risk of STH

SAC at Risk of STH

Number

Percentage

Number

Percentage

1

8,630,605

66.8

21,569,079

67.4

2

3,458,211

26.8

8,358,854

26.1

3

697,895

5.4

1,727,941

5.4

4

130,844

1.01

349,341

1.09

Total

12,917,455

100

32,005,215

100

SOURCE: PAHO (2010).

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×
FIGURE A1-1 Overlapping of six neglected infectious diseases.

FIGURE A1-1 Overlapping of six neglected infectious diseases.

SOURCE: PAHO (2009).

PAHO has identified several principles for integrating actions for NTD control and elimination. They include the following:

  • Available plans, guidelines, and tools to develop integrated POAs (instead of reinventing the wheels of successful stand-alone programs);

  • Evidence-based decisions (using the data about disease overlap and burden);

  • Reduction of inequalities in health (to justify resources for integrated control);

  • Primary health care systems (as a principal service delivery platform for NTD control);

  • Community participation (in surveillance, control, education, monitoring and evaluation);

  • Gender and ethnicity (as a way to target those most likely deprived);

  • Interprogrammatic and intersectoral interventions to address the social determinants of health (water and sanitation, drainage, housing, and nutrition);

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×
  • Cooperation between countries (where one endemic country is well positioned to help another endemic country); and

  • Global partnerships in the fight against NIDs (allowing significant drug donations and provision of training and other resources).

The agency sees multiple approaches to integrate actions for NTD control and elimination, through inter-programmatic actions within a Ministry of Health. Common interventions may include the following:

  • Screening, drug treatment/MDA

  • Morbidity (case) management (LF, leprosy/Hansen’s disease)

  • Integrated vector management

  • Water Supply, Sanitation, Hygiene, Health Education and Deworming (WASHED) strategy

  • Education and school health for deworming

  • Vitamin A + deworming medicine distribution

  • Other micronutrients (Fe, I, Zn, multi-vitamin) distribution + deworming

  • Food vouchers and complementary nutrition to combat undernutrition, combined with deworming

  • Food security programs to reduce undernutrition and anemia

  • Conditional cash transfers to encourage mothers to bring children to regular medical visits and receive NTD screening and deworming

  • Integrated population, health, and environment programs

    • Agroforesty, home gardens, aquaculture, and beekeeping to reduce undernutrition and anemia

    • Primary environmental care to create protective environments against NTDs

To deliver such interventions, Ministries of health may use other ministry health programs as common delivery platforms for NTD services, for example, for the distribution and delivery of antihelminthics or rapid screening tests, or patient care (case management for leprosy/Hansen’s and LF cases) can be delivered. Some of these platforms include

  • Primary health care

  • Vector control

  • Nutrition/micronutrients

  • Immunizations (children, adolescents, pregnant women)

  • Maternal-child health, family health and wellness

  • Skin disease clinics, diabetes/chronic diseases clinics

  • Food security, food safety

  • Healthy schools, healthy cities

  • Malaria and TB programs

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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Piecing the Puzzle Together

The elimination and control of NTDs can be considered to consist of three categories: information and planning, delivery of services, and the development of integrated POAs. These are depicted in Figure A1-2. The information and mapping category includes an important aspect—stakeholder identification and mapping—allowing ministries to see what NGOs, faith-based groups, academia, and the private sector can bring to the table to support elimination. Additionally, the mapping of disease presence, prevalence, and burden, especially areas of overlap or co-endemicity, allows the visualization of the patches or hot spots where control efforts must be focused. Finally, the mapping of the social determinants of health (water supply and sanitation coverage, housing, agriculture and industry, and zones of malnutrition or unemployment) allows one to find and target populations most likely to be at risk of NTD infection. Delivery of health services for NTD control and elimination in poor communities is often best done through the primary care system, supplemented by other interventions as needed. Sets of minimum packages of treatment or care can be established for each group of co-endemic diseases, and these can be complemented by the necessary (and

FIGURE A1-2 Elimination and control of NIDs in LAC: Putting the pieces together.

FIGURE A1-2 Elimination and control of NIDs in LAC: Putting the pieces together.

SOURCE: PAHO (2010).

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

disease-specific) social and environmental services needed to educate and prevent or mitigate disease transmission and morbidity.

Conclusions

Through the use of existing tools, stepped-up advocacy, political commitment, development of partnerships, resource mobilization, and careful allocation of resources, and reflected in integrated plans of action, a number of NTDs can be eliminated in the LAC region, These include onchocerciasis and LF (and LF and malaria in Hispaniola) in children and adults, trachoma in school-age children, schistosomiasis in the populations of St. Lucia and Suriname, as well as domestic vectoral transmission and transfusional Chagas disease, among other NTDs. This is the most opportune moment in history to eliminate these diseases, and it is an ethical and moral imperative for the region’s citizens and governments.

Acknowledgments

The authors are indebted to many PAHO/WHO technical staff and senior managers that have, over the past decade contributed with intelligence, foresight, advocacy, persistence, and hard labor, especially John Ehrenberg, Ximena Aguilera, Jarbas Barbosa, Marcos Espinal, Rodolfo Rodríguez, Santiago Nicholls, Martha Saboya, Christina Schneider, Roberto Salvatella, Zaida Yadon, Carlos Lara, and interns and medical residents of Spain. Additionally, colleagues from partner institutions have worked closely with PAHO to control and eliminate NTDs in the Region, including the WHO NTD Control Department and WHO/TDR, the U.S. Centers for Disease Control and Prevention, the Carter Center, the Onchocerciasis Elimination Program of the Americas, Sabin Vaccine Institute, Pan American Health and Education Foundation, and indirectly, the Bill & Melinda Gates Foundation.

The efforts of PAHO and the endemic countries to combat NTDs have also been aided by various international cooperation agencies, NGOs, universities, and research institutes. Among the key international cooperation partners are AECID (Spain), JICA (Japan), and CIDA (Canada), and the Inter-American Development Bank. Important collaborating NGOs include the Global Network for Neglected Tropical Diseases, Children Without Worms, Save the Children, and Vitamin Angels. Partners among the universities and research institutes include the University of the West Indies, University of Antioquia (Colombia), St. George’s University (Grenada), Instituto Pedro Kouri (Cuba), FIOCRUZ (Brazil), Liverpool School of Tropical Medicine (UK), and McGill University (Canada), and in the USA: George Washington University, Johns Hopkins University, Emory University, University of Notre Dame, and Case Western Reserve University.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

References

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Brooker, S., N. Alexander, S. Geiger, R. A. Moyeed, J. Stander, F. Fleming, P. J. Hotez, A. Correa-Oliveira, and J. Bethony. 2006. Contrasting patterns in the small-scale heterogeneity of human helminth infections in urban and rural environments in Brazil. International Journal of Parasitology 36(September):1143–1151.

Ehrenberg, J. P., and S. K. Ault. 2005. Debate: Neglected diseases of neglected populations: Thinking to reshape the determinants of health in Latin America and the Caribbean. BMC Public Health 5:119. http://www.biomedcentral.com/content/pdf/1471-2458-5-119.pdf.

Holveck, J. C., J. P. Ehrenberg, S. K. Ault, R. Rojas, J. Vasquez, M. T. Cerqueira, J. Ippolito-Shepherd, M. A. Genovese, and M. Roses Periago. 2007. Prevention, control, and elimination of neglected diseases in the Americas: Pathways to integrated, inter-programmatic, inter-sectoral action for health and development. BMC Public Health 7(January 17):6.

Hotez, P. J., M. E. Bottazzi, C. Franco-Paredes, S. K. Ault, and M. Roses Periago. 2008. The neglected tropical diseases of Latin America and the Caribbean: A review of disease burden and distribution and a roadmap for control and elimination. PLoS Neglected Tropical Diseases 2(9):e300.

Lammie, P. J., J. F. Lindo, W. E. Secor, J. Vasquez, S. K. Ault, and M. L. Eberhard. 2007. Eliminating lymphatic filariasis, onchocerciasis, and schistosomiasis from the Americas: Breaking a historical legacy of slavery. PLoS Neglected Tropical Diseases 1:e71. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2100373/pdf/pntd.0000071.pdf. (accessed February 7, 2011).

Miller, H., G. Gallego, and G. Rodriguez. 2010. Clinical evidence of trachoma in Colombian Amerindians of the Vaupés Province. Biomédica 30(3):432–439.

PAHO (Pan-American Health Organization). 2009. Epidemiological profiles of neglected diseases and other infections related to poverty in Latin America and the Caribbean. Washington, DC: PAHO. http://new.paho.org/hq/dmdocuments/2009/nds-epi-profiles.pdf.

———. 2010 (in press). Control and Elimination of Five Neglected Diseases in Latin America and the Caribbean, 2010–2015. Washington, DC: PAHO.

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———. 2007. Global plan to combat neglected tropical diseases 2008–2015. (WHO/CDS/NTD/2007.3). Geneva: WHO.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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A2
NEGLECTED TROPICAL DISEASES, CONFLICT, AND THE RIGHT TO HEALTH

Chris Beyrer1, Sonal Singh, and Darshan Sudarshi

Center for Public Health and Human Rights, Johns Hopkins Bloomberg School of Public Health

Introduction

The neglected tropical diseases (NTDs) are characterized by their prevalence among the poor of the most impoverished areas of the planet. These are neglected diseases of neglected populations, flourishing in the developing world but long since controlled or eradicated in the developed. NTDs generally affect the poorest people in poor societies—populations with little voice and representation. As a consequence, NTDs have until very recently received little funding and international attention. These diseases typically cause more disability than death. Their clinical features often lead to stigmatization and social isolation, which can further increase their neglect. Combined, as many as 1 billion people worldwide are at risk for NTDs or already suffer from them, and they account for 57 million disability-adjusted life-years lost (Hotez et al., 2007). However, these figures are thought to be an underestimate of the true burden (Hotez et al., 2008), because of a lack of reliable surveillance and of the research necessary to quantify their impacts (J. Jacobson, 2010).

As yet there is no internationally agreed consensus for which diseases come under this classification. In the first launch of a global report on NTDs, the World Health Organization (WHO) has defined 17 key diseases (WHO, 2010c), but several others exist. For the purposes of this review, we have opted to use the most inclusive definition possible, encompassing all NTDs that predominately affect the poor of the global south. In particular, we posit that malaria and poliomyelitis fit these criteria and may also be considered with the NTDs. Though both are less neglected than many other conditions, they affect many of the same populations as the classic NTDs, and they share many social and structural features with them.

Although evidence for the association between poverty and NTDs has been well documented, the impact of conflict on these diseases has been less well studied. With increasing prioritization of NTDs on the international agenda, these links are becoming more apparent. In the past few months, WHO has warned of several impending epidemics of NTDs in conflict settings. Of the four endemic countries for guinea worm, more than 90 percent of cases are currently in

1

Corresponding Author: Chris Beyrer MD, MPH, Dept. of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD 21205, USA.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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conflict-torn Sudan (CDC, 2010a). There has been a recent outbreak of visceral leishmainiasis in Southern Sudan (WHO, 2010b), a disease with high mortality among children. In a similar fashion, the number of cases of the cutaneous form of this disease has been soaring in Afghanistan as a result of the long-standing conflict there (WHO, 2010a).

Understanding the true burden of these diseases in conflict zones is difficult, as there are many political, logistical, and ethical barriers to conducting programs, surveillance, and research. Nonetheless, systematic evaluation of disease burden as well as effectiveness of interventions in the field is crucial to assist decisions with policy, advocacy, and providing care to these communities.

The human rights lens provides a useful ethical and legal framework to examine and address NTDs in conflict settings. Formal human rights conventions are a series of treaties, placing legal obligations on member states to ensure that they are accountable for their conduct. They define the humanitarian imperative for signatory states to respect, protect, and fulfill the basic human rights of their people. Most relevant among these instruments is the right to health, as defined by Article 12 of the 1976 International Covenant on Economic, Social and Cultural Rights. Specifically, Part c is applicable to NTDs, as it is defined by “[t]he prevention, treatment and control of epidemic, endemic, occupational and other diseases.” As of December 2010, 160 of the 192 United Nations member states were party to the Covenant. Like many processes mediated by the United Nations, enforcing these rights has proven to be difficult. Many countries worldwide are arguably in violation of the right to health. Nevertheless, the rights conventions do provide policy frameworks from which to advocate for more research into this area, legal tools for signatory state accountability, and platforms for action on global initiatives, such as the Millenium Development Goals.

We first explored this subject in 2007 (Beyrer et al., 2007). In this review we reassess the current literature and describe ways forward for responding to NTDs in conflict settings. In the first part, we analyze the literature in this field since 2007. In the second part we describe, through four case studies, potential mechanisms through which conflict can affect NTDs, and we review progress in the field.

Literature Review

Methods

We searched PubMed, without restriction on language for studies published between January 1, 2007, and October 15, 2010. Our search had two main components. To assess both the direct and indirect impacts of conflict, we used the following keywords: “conflict,” “war,” “civil unrest,” “political unrest,” “political instability,” “displacement camps,” “refugees,” “refugee camps,” and “internally displaced.” To assess articles that focused on NTDs, we used free text and MESH

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

terms (where available), for all neglected diseases listed at http://www.plosntds.org.static/scope.action. We also included additional search terms on malaria and poliomyelitis.

As a further strategy we looked at recent morbidity and mortality surveys in known areas of conflict to see if NTDs or malaria were mentioned. We also cross-referenced with a recent WHO report (WHO, 2010c) and expert editorials (Hotez, 2009; Hotez and Kamath, 2009) to see if any references were missed.

Exclusion criteria were determined a priori: if the articles described pre-1980 conflicts, or described disease in non-endemic populations (i.e., military, tourists), they were excluded. We also chose not to include editorials, viewpoints, articles focusing on guidelines, isolated case reports, or letters. Also, if primary research was published in multiple journals, only one article was selected. Our full search protocol and results are summarized in Figure A2-1.

FIGURE A2-1 Search protocol and results.

FIGURE A2-1 Search protocol and results.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×
Results

Table A2-1 describes new studies in the area of neglected diseases and conflict since 2007 (n = 67). Research was conducted in sub-Saharan Africa (51%), the Middle East (15%), North America and Australia (13%), Asia (11%), and on a global level (10%). The five most common disease areas investigated were malaria (39%), intestinal parasites (21%), leishmaniasis (12%), trachoma (7%), and trypanosomiasis (6%).

Studies were either classified as primary research (70%), review articles (21%), and/or routine surveillance data (9%). The vast majority of primary research reports (45/47) were based on cross-sectional surveys to investigate the burden of disease in conflict settings.

The majority of papers identified an increased burden of disease in the conflict or postconflict environment. The only exception to this was a study by Mathenge et al. (2007) looking at causes of blindness in Rwanda, in which this association was not seen.

Mechanisms

On examination of the literature it is evident that conflict can impact on neglected diseases through several intermediate factors. These factors appear to act on the two principal points of the neglected disease cycle; either to increase exposure to the infectious agent and/or increase susceptibility to disease (see Box A2-1). As a result there is increased transmission of the neglected disease, and also more severe illness in individual patients.

The precise nature of the mechanisms may depend on the type of neglected disease involved. For example, the burden of vector-borne diseases (malaria, trypanosomiasis, and filariasis) may be increased in conflicts where there is substantial migration, and where there is a breakdown in control programs with limited access to prevention and treatment (Bygberg et al., 2010). Alternatively, the conditions of crowded refugee camps favor the transmission of water-borne diseases such as cholera and intestinal helminthes (Abu Mourad et al., 2008).

Furthermore it is important to note that the effects of conflict should be described in the wider context of other socioeconomic and ecological determinants of health in these settings. Poverty is a key factor along with conflict that impacts on the existing interplay between pathogen, human host, and the environment. In a recent study investigating the impact of the war in Côte d’Ivoire on risk factors for NTDs, Fürst has elegantly provided a conceptual framework to demonstrate these interactions (Figure A2-2).

Case studies can help to explore these mechanisms in further detail. Here we describe the impact conflict has had on the two common protozoan NTDs—trypanosomiasis and leishmaniasis—in diverse conflicts settings in Africa and Asia.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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TABLE A2-1 Studies in Conflict and Neglected Tropical Diseases Since 2007

Region

Disease

Author

Study Type

Outcome(s)

Journal

Year

Northern Uganda

Malaria

Akello-Ayebare et al. (2010)

Questionnaire study

Burden of disease/access to care

Ann Trop Med Parasitol

2010

Afghani refugees in Iran

Malaria

Basseri et al. (2010)

Cross-sectional

Burden of disease

Bull Soc Pathol Exot

2010

Africa

Trypanosomiasis

Berrang-Ford et al. (2010)

Retrospective cohort

Incidence of disease

Soc Sci Med

2010

Global

Arthropod-transmitted diseases

Brouqui (2010)

Review

 

Annu Rev Entomol

2010

Africa

Trypanosomiasis

Brun et al. (2010)

Review

 

Lancet

2010

Global

Vector-borne disease

Bygbjerg (2010)

Review

 

UgeskrLaeger

2010

Côte d’Ivoire

NTDs

Fürst et al. (2010)

Questionnaire study

Risk factors for disease

Emerging Themes Epidemiol

2010

Afghanistan

Malaria

Howard et al. (2010)

Interview-based study

Access to care

Malaria J

2010

Middle East

Leishmaniasis

R. L. Jacobson (2010)

Review

 

Vector Borne Zoonotic Dis

2010

Eritrean refugees in Israel

Malaria

Kopel et al. (2010)

Case series

Burden of disease

European Surveillance

2010

Liberia

Malaria

Kruk et al. (2010)

Population-based survey

Access to care

Bull WHO

2010

Burma

Intestinal parasites and malaria

Mullany et al. (2010)

Cross-sectional

Burden of disease

PLoS Med

2010

Sudan/Mali

Guinea worm

CDC (2010a)

Surveillance data

Burden of disease

MMWR

2010

Global

Polio

CDC (2010b)

Surveillance data

Burden of disease

MMWR

2010

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

Afghanistan

Leishmaniasis

Reithinger et al. (2010)

Cross-sectional

Risk factors for disease

PLoS Neglected Trop Dis

2010

Global

Malaria

Speigel et al. (2010)

Review

Provision of care

Conflict Health

2010

Sudan

NTDs

Sturrock et al. (2009)

Cross-sectional

Burden of disease

PLoS Neglected Trop Dis

2010

DRC

Cholera

Bompangue et al. (2009)

Cross-sectional

Burden of disease

Congo

2009

DRC

Malaria

Coghlan et al. (2009)

Mortality survey

Mortality survey

Disaster Med

2009

Guinea-Bissau

Cholera

Colombatti et al. (2009)

Cross-sectional

Burden of disease

Afr J Med Sci

2009

Côte d’Ivoire

Cholera

Ekra et al. (2009)

Surveillance data

Burden of disease

Bull Soc Pathol Exot

2009

Côte d’Ivoire

NTDs

Fürst et al. (2010)

Questionnaire study

Risk factors for disease

PLoS Neglected Trop Dis

2009

Global

Malaria

Guthmann (2009)

Review

 

Med Sci (Paris)

2009

DRC

Malaria

Hawkes et al. (2009)

Prospective cohort study

Burden of disease/diagnostic test study

Malaria J

2009

Africa

NTDs

Hotez and Kamath (2009)

Review

Burden of disease

PLoS Neglected Trop Dis

2009

Sudan

Trachoma

Kur et al. (2009)

Cross-sectional

Burden of disease

PLoS Neglected Trop Dis

2009

Burma

Malaria

Lee et al. (2009)

Scale-up of program

Disease program scale-up

Global Public health

2009

Afghanistan

Malaria

Leslie et al. (2009)

Cross-sectional

Burden of disease

Emerg Inf Dis

2009

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

Region

Disease

Author

Study Type

Outcome(s)

Journal

Year

East Timor

Malaria

Martins et al. (2009)

Case-based study

Incidence of disease

Conflict Health

2009

Congo (Brazzaville)

Malaria

Mouko et al. (2009)

Cross-sectional

Burden of disease

Sante

2009

Pakistan

Hydatid disease

Mumtaz et al. (2009)

Cross-sectional

Burden of disease

Trop Doctor

2009

Sudan

Cholera

CDC (2009)

Surveillance data

Burden of disease

MMWR

2009

Sudan

Trachoma

Ngondi et al. (2009)

Cross-sectional

Burden of disease

PLoS Neglected Trop Dis

2009

Refugees in Australia

Malaria, schistosomiasis

Raman et al. (2009)

Cross-sectional

Burden of disease

Aust N Z Public Health

2009

Sudan

NTDs

Rumunu et al. (2009)

Review

 

Trends Parasitol

2009

Kenya

Cholera

Shikanga et al. (2009)

Case-control study

Burden of disease

Am J Trop Med Hyg

2009

Kenyan refugee camp

Cholera

Shultz et al. (2009)

Cross-sectional

Burden of disease

Am J Trop Med Hyg

2009

Refugees in U.S.

Intestinal parasites and malaria

Stauffer and Weinberg (2009)

Review

Burden of disease

Curr Opin Infect Dis

2009

DRC

Buruli ulcer

Suykerbuyk et al. (2009)

Cross-sectional

Burden of disease

Am J Trop Med Hyg

2009

Palestine

Leishmaniasis

Abu Mourad et al. (2008)

Descriptive study

Burden of disease

Public Health

2008

Iraq

Leishmaniasis

Al-Hucheimi et al. (2009)

Observational study

Burden of disease/diagnostic test study

Int J Dermatol

2008

West Africa

Trypanosomiasis

Courtin et al. (2008)

Review

Burden of disease

Bull Soc Pathol Exot

2008

Cambodian refugees in U.S.

Intestinal parasites

Goswami et al. (2009)

Cross-sectional

Burden of disease

Am J Trop Med Hyg

2008

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

Afghanisthan

Cholera

Kakar et al. (2008)

Review

 

Trop Doct

2008

Global

NTDs

Gayer et al. (2007)

Review

 

Emerg Inf Dis

2008

West Africa

Lassa fever

Khan et al. (2008)

Cross-sectional

Burden of disease

Antiviral Res

2008

Angola/DRC

Buruli Ulcer

Kibadi et al. (2008)

Case series

Burden of disease

Emerging Inf

2008

Sudan

Trachoma

King et al. (2008)

Cross-sectional

Burden of disease

PLoS Neglected Trop Dis

2008

Uganda/Kenya

Leishmainiasis

Kolaczinski et al. (2008)

Case-control study

Risk factors for disease

Int J Epidemiol

2008

Pakistan

Leishmaniasis

Anwar et al. (2007)

Review

 

East Med H J

2007

Africa-Uganda

Trypanosomiasis

Berrang-Ford (2007)

Review

Burden of disease

Conflict Health

2007

Sri Lanka IDPs

Intestinal parasites

Chandrasena et al. (2007)

Cross-sectional

Burden of disease

Trop Doct

2007

Mozambique

Endemic syphilis (Bejel)

Clyti and dos Santos (2007)

Case series

Burden of disease

Bull Soc Pathol Exot

2007

Karen refugees in Canada

Intestinal parasites

Denburg et al. (2007)

Cross-sectional

Burden of disease

Can Commun Dis Rep

2007

Guinea

Lassa fever

Fair et al. (2007)

Cross-sectional

Burden of disease

Vector Borne Zoonotic Dis

2007

Sudanese refugees in U.S.

Intestinal parasites, schistosomiasis

Franco-Paredes et al. (2007)

Cross-sectional

Burden of disease

Am J Trop Med Hyg

2007

Sierra Leaone IDPs

Intestinal parasites

Gbakima et al. (2007)

Cross-sectional

Burden of disease

Afr J Med Sci

2007

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

Region

Disease

Author

Study Type

Outcome(s)

Journal

Year

Haitian refugees in Jamaica

Malaria

Lindo et al. (2007)

Case study

Burden of disease

Emerging Infect Dis

2007

Sudan

Trachoma

Mathenge et al. (2007)

Cross-sectional

Burden of disease

PLoS Med

2007

Burma

Malaria

Mullany et al. (2007)

Cross-sectional

Burden of disease

J Epidemiol Commun Health

2007

Burundian refugees in U.S.

Malaria

CDC (2008)

Surveillance data

Burden of disease

MMWR

2007

Sudan

Trachoma

Ngondi et al. (2007)

Cross-sectional

Burden of disease

Am J Trop Med Hyg

2007

Somalian and Sudanese

Intestinal parasites

Posey et al. (2007)

Cross-sectional

Burden of disease

Clin Infect Dis

2007

Refugees in Canada

Intestinal parasites

Pottie et al. (2007)

Cross-sectional

Burden of disease

Can Fam Phys

2007

Afghanistan

Leishmainiasis

Reithinger and Coleman (2007)

Cost effectiveness

 

BMC Infect Dis

2007

Burma

Malaria

Richards et al. (2007)

Cross-sectional

Burden of disease

Trop Med Int Health

2007

Refugees in U.S.

Intestinal parasites

Varkey et al. (2007)

Cross-sectional

Burden of disease

Travel Med Infect Dis

2007

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

BOX A2-1

The Impact of Conflict on Neglected Diseases

  1. Factors affecting exposure to infectious agent

    • Increased contact with vector (i.e., mosquito, tsetse fly)

    • Dirty water

    • Poor shelter

    • Crowded conditions

    • Reduced access to preventative therapy

    • Migration

  1. Factors affecting susceptibility to disease

    • Malnourishment and food insecurity

    • Reduced access to treatment

    • Exposure of nonimmune to disease through migration

Case Example: Human African Trypanosomiasis

Human African trypanosomiasis (HAT) is endemic to 36 African countries, putting 60 million people at risk. If not diagnosed early, it causes a severe debilitating disease where mortality approaches 100 percent in untreated cases. It is estimated to cost Africa $1.5 billion in lost productivity. Treatment is available at low cost, and the disease can be successfully controlled with active population screening of cases and prompt administration of care (WHO, 2010).

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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FIGURE A2-2 Conceptual framework for effect of conflict on NTDs.

FIGURE A2-2 Conceptual framework for effect of conflict on NTDs.

SOURCE: Reprinted from PLoS Neglected Tropical Diseases, Fürst et al. (2009).

In the 1960s, the disease was on the verge of eradication following effective disease control programs. However, lack of sustained disease control in the postindependence area, combined with periods of political unrest, led to resurgence of HAT cases in many countries. These cases peaked in 1996. Following several WHO resolutions in 1998 advocating for stronger access to diagnosis and treatment, the number of new cases reported had been reduced by 68 percent in 2005. Nonetheless, the disease continues to pose problems in conflict regions of Africa: In 2010, the three countries with the highest burden of HAT were Congo, Sudan, and Angola, all states with active conflicts or postconflict (WHO, 2010c).

Case Study: Sub-Saharan Africa

A recent study by Berrang-Ford and colleagues (2010) investigated the relationship between HAT incidence and conflict in Africa over a 30-year time period (1976–2004) using quantative epidemiological methods. In this study, the authors were able to obtain population-level data of both HAT incidence and conflicts within the region. In the study period, they demonstrated six significant space-time clusters of disease incidence (Figure A2-3). Four of the six clusters appear to be associated with specific conflicts, and it was postulated that one of the six clusters was indirectly associated (Table A2-2).

The principal mechanism by which HAT incidence increases during and after a conflict appears because of a breakdown in disease control programs, such that transmission will continue because of inadequate diagnosis and treatment.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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FIGURE A2-3 Map of the distribution of sleeping sickness incidence, Africa 1976–2004.

FIGURE A2-3 Map of the distribution of sleeping sickness incidence, Africa 1976–2004.

SOURCE: Reprinted from Social Science & Medicine, Berrang-Ford et al., Conflict and human African trypanosomiasis, Copyright (2010), with permission from Elsevier.

TABLE A2-2 Summary of Six Space-Time Clusters of Sleeping Sickness Incidence, Africa 1976–2004

Country

Years of Incidence

Relative Risk

Association with Conflict

Estimated Lag (years)

DRC

1994–2000

13.3

Political and civil unrest

Unknown

Angola

1996–2002

10.2

Civil war

10

Uganda

1978–1981

10.5

Civil war

5–10

CAR

1995–2001

5.4

Neighbouring conflict

Unknown

Cameroon

1982–1985

3.9

None found

N/A

Sudan

2002–2003

2.1

Civil war

7–12

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

However, as shown in the epidemic of disease in the Central African Republic, major population displacement due to conflicts in neighboring countries may also be an important factor.

The study by Berrang-Ford and colleagues is a major advancement in this field, because it uses quantative methods to assess the impact of conflict on the control of an NTD. Although epidemiological research of this nature cannot prove causality, and there may be several confounding factors to explain the findings (i.e., climatic factors, education, or political systems), it does provide convincing evidence to inform future policy and research.

Case Example: Cutaneous Leishmaniasis

Leishmaniasis is a disease caused by a group of intracellular parasites, which are transmitted from the bites of infected sandflies. Leishmania parasites can cause a spectrum of disease ranging from chronic ulcerating skin lesions (cutaneous leishmaniasis [CL]) or a disease that affects the internal organs of the body (visceral leishmaniasis [VL]), which is fatal if left untreated. There are an estimated 1.6 million cases annually (WHO, 2010c), and it is considered to be second in mortality and fourth in morbidity among all tropical diseases (Mathers et al., 2007).

Treatment of the disease is complex, involving drugs with a myriad of toxic side effects, although promising new regimens have recently been developed (WHO, 2010c). Control of the disease is possible through early access to diagnosis and treatment, as well as measures to reduce exposure to the vector, using periodic indoor spraying, health education, and bednets.

Conflict and civil unrest have been thought to be important factors driving leishmaniasis epidemics throughout the world (Bern et al., 2008). A resurgence in cases of VL has been documented in times of conflict in several sub-Saharan African counties, including northern Uganda, Somalia, and Chad (Hotez and Kamath, 2009). In the Middle East, VL has been documented to increase in wartorn areas in Palestine and Iraq, while CL is a major problem in Afghanistan, Iraq, and Pakistan (R. L. Jacobson, 2010).

Leishmaniasis thrives in conflict conditions, as a result of the breakdown in health infrastructure, forced migrations, destruction of human habitats, and food insecurity. Because of the collapse of health systems, patients are unable to access treatment, and there are few disease control measures available to reduce transmission. Poor housing, combined with a mobile population of refugees and internally displaced people, leads to greater transmission of the disease because of increased exposure to the sand-fly vector. In addition, there is a great deal of stress and malnutrition during war, which impairs the human body’s defense system, increasing susceptibility to the disease.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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Case Study: Afghanistan

Afghanistan has been engaged in conflict for more than 30 years. Health indicators are still among the worst globally, with many preventable diseases such as malaria, measles, and polio rampant throughout the country (Waldmann, 2002).

Kabul, the capital city, is currently the worldwide largest focus of CL with an estimated 67,500 new cases per annum (WHO, 2010a). The majority of CL in Afghanistan is anthroponotic, which means the human population is the main reservoir of infection. Because of the disfiguring nature of the skin disease it causes (i.e., large cutaneous lesions that appear at the biting site of the sand fly), the disease has a significant social impact on the local population. Individuals may become ostracized from society because of stigmatization, and thus the disease may effect their psychological, social, and economic well-being (Kassi et al., 2008). A questionnaire study of individuals in the capital city portrayed the many misconceptions that exist about how the disease is transmitted. Of the 360 respondents, the most common answers were touching (n = 86) and sharing meals (n = 26). As a result of these false beliefs, social exclusion is common. For example, women with lesions may be deemed unsuitable for marriage. They may be separated from their children during the disease, leading to depression and anxiety (Reithinger et al., 2005).

Several epidemics of CL have been described in Afghanistan, corresponding to increases in the intensity of conflict. An important factor in driving the high rates seen in Kabul has been forced migrations of susceptible individuals in the capital (Reyburn et al., 2003). In a similar fashion, outbreaks of disease have been described in neighboring Pakistan and Iran among Afghani refugees (Rowland et al., 1999).

Despite the fact that epidemics of CL have ravaged Afghanistan, there have been few disease control efforts. A few stories of successful public health interventions have been reported among the occupied military forces (Faulde et al., 2008). However, for the vast majority of Afghanis suffering from the disease in neglected areas of conflict, control programs have been non-existent. Because CL does not cause high rates of mortality, control of the disease has not been deemed cost-effective by WHO criteria, further increasing its neglect (Reithinger and Coleman, 2007).

However, control programs for leishmaniasis in conflict settings can be effective. In 2003, a major outbreak of VL was prevented in southern Iraq following the Allied invasion of the country (Jassim et al., 2006). As the burden of CL in Afghanistan expands and affects more vulnerable Afghans, it is imperative that we address the problem.

Ways Forward

In this final section, we highlight some potential interventions to improve the health of those suffering from NTDs in warzones.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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Case Example: Intestinal Parasites

Intestinal parasites comprise both intestinal worms (nematodes) and protozoan infections. More than a quarter of the world’s population is infected with nematodes (WHO, 2010c), and data on the true burden of protozoan infections are not known because many are not diagnosed. The vast majority of these diseases are transmitted via the feco-oral route, through contact with either contaminated water or food. Symptoms are often nonspecific in the early stages and only become evident when the infection is severe. Children and pregnant women are often the most susceptible. Effects include anemia, growth stunting, reduced physical fitness, impaired intellectual development, and poor educational performance (Feasey et al., 2010). Deworming treatment is available at low cost to treat these diseases, but access is very limited to people who need it the most. Preventative strategies focus on the provision of clean water, health education, and improved sanitary measures.

Conflict often results in large numbers of internally displaced individuals and refugees. These populations are ideal targets for intestinal parasites. Overcrowding, dirty water, minimal sanitary measures, and poor sewage systems are rife in displacement camps, creating the perfect environment for transmission. Mobile populations are often malnourished, increasing their susceptibility to more severe disease. Research in these settings has been limited; however, several cross-sectional surveys have shown a high burden of intestinal parasites in displacement camps in Sierra Leone (Gbakima et al., 2007), Sri Lanka (Chandrasena et al., 2007), and Palestine (Abu Mourad et al., 2008). In a similar fashion, high rates of these diseases are seen in refugees and asylum seekers when they reach developed countries including the United States, Canada, and Australia (Franco-Paredes et al., 2007; Posey et al., 2007; Pottie et al., 2007; Raman et al., 2009; Stauffer and Weinberg, 2009).

Case Study: Burma and Helminth Control in Internally Displaced People

The Burmese government has been engaged in civil war with ethnic minority groups for almost 50 years. There has been widespread documentation of human rights violations committed by the ruling government, including murder, torture, rape, forced labor, forced displacement, and destruction of villages (United Nations, 2010). As a result, a complex humanitarian crisis has developed, and there are estimated to be approximately 2 million internally displaced persons (IDPs). There is little sign of the crisis abating, with the recent reinstallment of the military government following what the international communities describe as “sham elections.”

As a result of this long-standing civil war, the health of these IDPs has suffered tremendously. The ruling party is estimated to allocate only 4 percent of the national budget on health care, even though it has been able to spend 40 percent on the military. Furthermore, in 2006 the government imposed new restrictions of international aid, forcing many aid agencies to leave the country (Stover et al.,

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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2007). It is only since 2009 that humanitarian agencies have returned to be able to provide care. As a result, child and infant mortality rates in the ethnic zones are estimated to be some of the highest reported in the world (Lee et al., 2006). Compared to refugees, IDPs are a particularly difficult group for humanitarian agencies to access (Spiegel et al., 2010).

Infectious diseases are abundant, with malaria, HIV, filiariasis, and other neglected diseases being the principal health problems (Beyrer et al., 2006). Owing to the lack of permanent food, shelter, and clean water supply, mobile populations are particularly vulnerable to the effects of many of these diseases. Often it is pregnant women and children who suffer the most.

As a result of the high morbidity and mortality among IDPs living in Burma, local ethnic-based organizations have empowered themselves to provide health care for their respective communities. Through collaboration with international nongovernmental organizations (NGOs) and academic centers, they have set up control programs to tackle various health care problems in the ethnic zones of Burma. One such program is an innovative project to improve coverage of key maternal health services to improve reproductive health known as the the Mobile Obstetric Medics (MOM) project.

The MOM project was set up in 2005 following an initial survey exploring the very high maternal mortality rates seen in the ethnic zones of Burma. Intestinal parasitic infestation is thought to be an important cause of maternal anemia, leading to many pregnancy-related complications. At survey baseline, the presence of maternal anemia was shown to be 7 times more likely in those populations who had experienced food security violations than those who had not (Mullany et al., 2007).

Recently the first evaluation of the MOM project was described (Mullany et al., 2010). The researchers used a two-stage clustering survey to compare the delivery of key maternal interventions, before (2005) and after (2008) the program was implemented in four distinct ethnic areas in eastern Burma. One such intervention was deworming treatment for helminth infection: compared to baseline, pregnant women were 14.2 times (95% CI, 2.69–3.54) more likely to receive antihelminth coverage than before (Mullany et al., 2010). Since albenda-zole is a proven treatment for intestinal worms and there is no drug resistance, this is likely to have resulted in a reduction in helminth disease.

The MOM project provides an example of how community-based organizations have been effective in improving access to key interventions for helminth control for vulnerable populations in unstable conflict settings, which were previously considered inaccessible. This is particularly promising, as the MOM project may be used as a model in other settings to deliver simple interventions for neglected diseases.

Case Example: Malaria

Malaria is a protozoan disease that affects more than a third of the world’s population and is estimated to cause approximately 1 million deaths annually—

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

mainly among young children living in Africa (WHO, 2009). In resource-poor settings, the diagnosis traditionally has been made based on clinical symptoms alone, and confirmed by microscopy where available. In recent years, however, the introduction of rapid diagnostic tests has revolutionized diagnosis, allowing accurate diagnosis of malaria in remote field settings. Control programs are based on vector control measures such as insecticide-treated nets and health education, combined with early identification and treatment of cases. Although drug resistance to malaria has been a major problem, the use of artemisinin combination therapy (ACT) for the most severe form of malaria is still effective in most countries.

Malaria is fueled by conflict through several mechanisms. The breakdown in vector control programs and health infrastructure that occurs in wartime leads to increased transmission. In addition, the environmental destruction that occurs during a war is thought to encourage vector breeding (Rowland and Nosten, 2001). Forced displacement leads to exposure of nonimmune individuals to malaria-prevalent areas, leading to severe disease.

In 2000, WHO announced that approximately 30 percent of malaria deaths in Africa were a result of conflict or natural disasters. Malaria is often considered to be responsible for more deaths than the conflict itself. Outbreaks of malaria have recently been described in many conflict areas. Examples include the Democratic Republic of Congo (Coghlan et al., 2009), Afghanistan (Kolaczinski, 2005), and Burundi (Protopopoff et al., 2007). The increase in malaria incidence in refugees and displaced populations has been well described, for Iran (Basseri et al., 2010), Afghanistan (Basseri et al., 2010), Africa (Mouko et al., 2009), the United States (CDC, 2008), Israel (Kopel et al., 2010), and Jamaica (Lindo et al., 2007). Despite this fact, a recent study shows that almost 50 percent of national malaria strategic plans of African countries have no provision for refugees or internally displaced individuals (Spiegel et al., 2010).

The NGO sector has played a crucial role in delivering malaria care to these conflict areas where possible. There are even a few examples where NGOs have conducted basic clinical research to improve their control programs (Guthmann, 2009). However, it is not the primary agenda of NGOs to conduct such research. Furthermore, it may not be a sustainable solution, because NGOs are often only temporary providers.

The past few years have seen a dramatic increase in international funding for malaria. Despite this, in areas of conflict, malaria control remains underfunded and neglected.

Case Study: Timor Leste

During the civil conflict in Timor Leste in 2006, there was widespread street violence with more than 3,000 homes destroyed and displacement of approximately 15 percent of the country’s population. In the capital city, Dili, more

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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FIGURE A2-4 Malaria in Timor Leste, 2004–2007.

FIGURE A2-4 Malaria in Timor Leste, 2004–2007.

SOURCE: Reprinted from Conflict and Health, Martins et al., Malaria control in Timor-Leste during a period of political instability: what lessons can be learned? 2009,3:11, published by BioMed Central Ltd.

than 60 camps were established to provide temporary shelter for IDPs. These circumstances created the perfect environment for a malaria epidemic; however, through an array of control measures, such an epidemic was avoided (Martins et al., 2009).

Malaria in Timor Leste has always been a major public health problem. The disease incidence often follows a cyclical pattern with incidence increasing in the rainy season. In contrast to other conflict zones, the national malaria trends of 2006 showed no increase in malaria cases reported by the health system through the crisis (Figure A2-4).

The principal reason for this appears to be due to a well-galvanized and effective public health response, to prevent a malaria epidemic. This emergency response was co-coordinated centrally by the Ministry of Health (MOH) and involved all major development parties (MOH staff, WHO, international and national NGOs). Key to the success was the early provision of malaria interventions such as ACT treatment and massive ITN distribution to displacement camps. Although routine diseases surveillance was disrupted at the start of the crisis, the MOH ensured it was resumed as soon as possible, which was vital to ensure that the malaria epidemic could continue to be monitored.

Discussion

In this review, we have summarized interactions between NTDs and conflict. Conflict fuels NTDs for a variety of reasons, leading to increased acquisition of the infectious agent and increased susceptibility to disease.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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Since our original assessment in 2007, there have been promising improvements in the quality of research in this area, enabling better characterization of the problem. Although many of the studies are cross-sectional, there has been an increase in the use of statistical modeling and geographic information systems, allowing diseases and conflicts to be mapped over space and time. New technology has enabled point-of-care testing for several NTDs, including malaria and trypanosomiasis. This has allowed novel methods for diagnosing these diseases in conflict settings but also better characterization of the total disease burden.

Almost all studies conducted in this field show an increase in NTDs in conflict and postconflict environments. Several studies have shown that, as a result of a conflict in one country, the control of the disease is often disrupted in the region as a whole. As such, it has been extremely difficult to enable worldwide eradication of NTDs such as guinea worm and polio, for these reasons.

There have also been some early examples of successful programmatic interventions for controlling NTDs in unstable settings. The MOM project in Burma provides an excellent model in which local communities have empowered themselves, using mobile health care workers, to provide antihelminth treatment to IDPs. With respect to vector-borne epidemics in conflict times, major outbreaks of malaria and leishmaniasis have been prevented by well-organized rapid-response measures. Ultimately, peace is the ideal intervention. However, initial outcomes may be deceptively poor as postconflict often means return of surveillance and a spike in “new” cases, which are really “newly detected cases.”

Despite improvements in research, this field remains underfunded and neglected. The human rights approach places a humanitarian imperative to address these issues. Working under the premise of “shared humanity,” it prioritizes the health and suffering of millions of IDPs, refugees, and victims of war. States can be made accountable to look after the health of all their individuals, regardless of their ethnicity or tribal affiliation.

Tackling NTDs in conflict should be part of a broader approach of improving basic rights to those living in conflict zones, who remain some of the most neglected individuals worldwide.

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Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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A3
PARASITE PREVALENCE AND THE WORLDWIDE DISTRIBUTION OF COGNITIVE ABILITY2

Christopher Eppig3, Corey L. Fincher, and Randy Thornhill

Biology Department MSC03 2020, University of New Mexico, Albuquerque, NM 87131, USA


In this study, we hypothesize that the worldwide distribution of cognitive ability is determined in part by variation in the intensity of infectious diseases. From an energetics standpoint, a developing human will have difficulty building a brain and fighting off infectious diseases at the same time, as both are very metabolically costly tasks. Using three measures of average national intelligence quotient (IQ), we found that the zero-order correlation between average IQ and parasite stress ranges from r = −0.76 to r = −0.82 (p < 0.0001). These correlations are robust worldwide, as well as within five of six world regions. Infectious disease remains the most powerful predictor of average national IQ when temperature, distance from Africa, gross domestic product per capita and several measures of education are controlled for. These findings suggest that the Flynn effect may be caused in part by the decrease in the intensity of infectious diseases as nations develop.

2

Reprinted from Eppig, C., Fincher, C. L., and Thornhill R. (2010). Parasite prevalence and the worldwide distribution of cognitive ability, Proceedings of the Royal Society Biological Sciences, with permission from The Royal Society.

3

Author for correspondence (ceppig@unm.edu).

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

Keywords: brain growth; developmental stability; evolution; Flynn effect; infectious disease; life history

1.
Introduction

Since the first publication of quantitative data on average national intelligence quotient (IQ) scores (Lynn & Vanhanen, 2001, 2002, 2006), five empirical studies have attempted to explain the global distribution of variation in intelligence. Barber (2005) hypothesized that IQ—like many other psychological traits—is a highly plastic trait that may increase onto genetically as the rewards of higher intelligence increase, and with exposure to education and other cognitively demanding environments such as non-agricultural labour. He reported that, across 81 nations, average national IQ correlated with enrolment in secondary school (r = 0.72), illiteracy (r = −0.71), agricultural labour (r = −0.70) and gross national product (r = 0.54). He also proposed that health and nutrition may affect intelligence, and found that average national IQ correlated negatively with rates of low birth weight (r = −0.48) and with infant mortality (r = −0.34). While it is plausible that formal education increases intelligence, Barber (2005) admits that it is not possible to determine from the data he used whether the correlation between education and intelligence is owing to education increasing intelligence or whether more intelligent individuals seek more education. Research has shown this relationship to be intractable (reviewed in Ceci, 1991). The same direction-of-causation ambiguity is true for agricultural labour (Barber, 2005). We agree with Barber’s assertions that health and nutrition may affect intelligence, although the variables he studied—low birth weight and infant mortality—are probably rather incomplete measures of these factors.

Lynn (1991) and Rushton (1995, 2000) proposed that temperature and climate provide important Darwinian selective pressures for intelligence, with cold climates selecting for higher intelligence, because low temperatures provide more fitness-related problems for humans that must be solved through cognitively demanding means, and through more complex social organization. Templer & Arikawa (2006) tested and supported predictions of this proposal in a cross-national study and found that average IQ correlated significantly with winter high temperature (r = −0.76), winter low temperature (r = −0.66), summer high temperature (r = −0.31) and summer low temperature (r = −0.41). Templer & Arikawa (2006) also found that average IQ correlated significantly with average skin darkness (r = −0.92). The authors offered little explanation of why this trend exists, except that they believed skin colour was related to exposure to certain climates over evolutionary time.

Kanazawa (2004) hypothesized that intelligence evolved as a domain-specific psychological adaptation to deal with environments that are evolutionarily novel. This hypothesis was tested and supported at the crossnational level (Kanazawa 2008). Results showed that distance from three points in or near central Africa—

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

the evolutionary origin of humans—correlated positively with average national IQ (0° E, 0° N, r = 0.45; South Africa, r = 0.53; Ethiopia, r = 0.22). Kanazawa (2008) did not offer his findings as an alternative to those of Templer & Arikawa (2006), but, rather, as complementary to them. Wicherts et al. (2010a) and Borsboom & Dolan (2006) heavily criticized Kanazawa’s hypothesis; for reasons they give in detail, we seriously question the ability of linear distance from sub-Saharan Africa to measure evolutionary novelty, undermining the foundation of Kanazawa’s hypothesis.

Saadat (2008) and Woodley (2009) suggested that inbreeding depression and associated reduced phenotypic quality is a cause of the variation in cognitive ability across the world. They found cross-national correlations of r = −0.77 (n = 35, p < 0.0001) and r = −0.62 (n = 71, p < 0.01), respectively, between average IQ and measures of inbreeding. Woodley (2009), however, noted that rates of consanguineous marriage itself may not account for the magnitude of this variation because (i) the statistical significance of the effect disappears when education and gross domestic product (GDP) are controlled for, and (ii) the effect of inbreeding on intelligence had previously been shown to be relatively small.

Here, we offer a new hypothesis—the parasite-stress hypothesis—to explain the worldwide distribution of intelligence. The brain is the most complex and costly organ in the human body. In human newborns, the brain demands 87 per cent of the body’s metabolic budget, 44 per cent at age five, 34 per cent at age ten, and 23 per cent and 27 per cent for adult males and females, respectively (Holliday, 1986). Presumably, if an individual cannot meet these energetic demands while the brain is growing and developing, the brain’s growth and developmental stability will suffer. Lynn (1990, 1993) has argued that nutrition is vital to high degrees of mental development. Lynn (1990) suggested that nutrition may account for the Flynn effect (large increases in IQ over short periods of time as nations develop; Flynn, 1987), and later (Lynn, 1993) reviewed evidence showing that undernourished children have smaller heads, smaller brains and lower psychometric intelligence than sufficiently nourished children.

Parasitic infection affects the body, and hence the brain, energetically in four ways. (i) Some parasitic organisms feed on the host’s tissues: the loss must be replaced at energetic cost to the host. Such organisms notably include flukes and many kinds of bacteria. (ii) Some parasites inhabit the intestinal tract or cause diarrhoea, limiting the host’s intake of otherwise available nutrients. These notably include tapeworms, bacteria, giardia and amoebae. (iii) Viruses use the host’s cellular machinery and macromolecules to reproduce themselves, at the energetic expense of the host. (iv) The host must activate its immune system to fight off the infection, at energetic expense. Of these, diarrhoeal diseases may impose the most serious cost on their hosts’ energy budget. First, diarrhoeal diseases are the most common category of disease on every continent, and are one of the two top killers of children under five, accounting for 16 to 17 per cent of all of these deaths worldwide (WHO, 2004a). Second, diarrhoea can prevent the body from

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

accessing any nutrients at all. If exposed to diarrhoeal diseases during their first five years, individuals may experience lifelong detrimental effects to their brain development, and thus intelligence. Parasites may negatively affect cognitive function in other ways, such as by infecting the brain directly, but we focus only on energetic costs.

The worldwide distribution of parasites is well known. Disease-causing organisms of humans are more prevalent in equatorial regions of the world and become less prevalent as latitude increases. Ecological factors contributing to this distribution include mean annual temperature, monthly temperature range and precipitation (e.g. Guernier et al., 2004). Similar trends of parasite distribution have been shown in other host species (e.g. Møller, 1998).

Many studies have shown a negative relationship between intestinal helminth infection and cognitive ability (reviewed in Watkins & Pollitt, 1997; see also Dickson et al., 2000). Although several hypotheses have been proposed to explain this phenomenon, none have considered intestinal worms in the larger context of all parasitic infection, nor have they considered fully the energetic cost of infection and its consequences on the brain. Other studies have shown relationships between helminth infection and economic and educational factors that are related to intelligence. For example, Bleakley (2007) studied the effects of eradication of hookworm in the southern US during the early twentieth century, and found that areas where hookworm infections had been greatly reduced had higher average incomes after treatment than areas that had not received treatment. Jardin-Botelho et al. (2008) found that Brazilian children infected with hookworm performed more poorly on cognitive tests than uninfected children, and that children infected with more than one type of intestinal helminth performed more poorly than children infected with only one.

Thus, from the parasite-stress hypothesis, we predict that average national intelligence will correlate significantly and negatively with rates of infectious disease, and that infectious disease will remain an important predictor of average national intelligence when other variables are controlled for. It is the purpose of this study to introduce this hypothesis to describe the worldwide variation in intelligence, and to provide some supportive evidence using correlations and linear modeling techniques.

2.
Material and Methods

National average intelligence was taken from Lynn & Vanhanen (2006), who present their methods in detail. IQ was measured directly in 113 nations, and estimated for 79 more nations by averaging the IQs of nearby nations with known IQ. These estimates were validated by Lynn & Vanhanen (2006) by comparing them to actual measurements of IQ in the same nations. At least two studies have presented evidence of validation for these data (Lynn & Mikk, 2007; Rindermann, 2007), by showing strong positive correlations between Lynn &

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

Vanhanen’s (2006) national IQ scores and other measures of cognitive ability. Wicherts et al. (2010b) have criticized Lynn & Vanhanen’s (2006) estimates of IQ in sub-Saharan African nations on the grounds that the selection criteria used to include studies in these estimations did not produce national IQ scores that were representative. Using selection criteria that they argue are more appropriate, Wicherts et al. (2010b) proposed new average IQ values for 17 nations in sub-Saharan Africa (but see also Lynn & Meisenberg, 2010). Analyses will be performed using three datasets: Lynn & Vanhanen’s (2006) original data, including estimates (LVE; mean = 84, median = 84.2, s.d. = 11.8); Lynn & Vanhanen’s (2006) data using collected data only (LVCD; mean = 86.7, median = 87.5, s.d. = 11.9); and Wicherts et al.’s (2010b) revisions of Lynn & Vanhanen’s (2006) data with estimates (WEAM; mean = 85.0, median = 85, s.d. = 11.0).

As a measure of infectious disease levels for each nation, disability-adjusted life years lost (DALY) owing to infectious disease were used (WHO, 2004b). This measure combines years of life lost and years spent disabled owing to 28 representative and important human diseases, including tetanus, malaria, tuberculosis, hepatitis, syphilis and leishmaniasis, such that one DALY equals one healthy year of life lost per 100 000 people. Although other cross-national measures of disease exist, we believe this to be the best for our study because (i) data exist for most countries of the world (n = 192), and (ii) this variable is a reasonable measure of the physiological costs of infectious disease, which concerns the parasite-stress hypothesis applied to cognitive ability. The DALY infectious-disease measure correlates strongly with other measures of human infectious disease (e.g. Thornhill et al., 2009). This variable was log-transformed owing to an extreme skew to the right (mean = 3.36, median = 3.28, s.d. = 0.761).

As an independent measure of nutrient stress, DALY owing to nutritional deficiencies (WHO, 2004b) were used. This calculation includes mortality and healthy years lost owing to protein-energy malnutrition, iodine deficiency, vitamin A deficiency and iron-deficiency anaemia. This variable was log-transformed owing to an extreme skew to the right (mean = 2.59, median = 2.65, s.d. = 0.49).

Average winter high temperatures (mean = 15.6, median = 17, s.d. = 12.5) were taken from Templer & Arikawa (2006). Although they used four intercorrelated temperature variables in their analysis, they reported that average winter high temperature was the best predictor of IQ of the four, so we used it.

Although Templer & Arikawa (2006) found a positive relationship between IQ and skin darkness, we will not use skin darkness in our analyses for three reasons: (i) although evidence suggests that skin darkness is a measure of historical infectious disease intensity over evolutionary time, it is unclear exactly what kind of infectious diseases it is indicative of (see discussion); (ii) Templer & Arikawa (2006) argued that the relationship between skin darkness and IQ is not causal; and (iii) Templer & Arikawa (2006) did not sufficiently explain why the association between intelligence and skin darkness exists. Without a reasonable

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

theoretical framework for this association, we did not feel it was appropriate to compare it with other variables for which there is a better theoretical rationale.

Literacy rates (mean = 87.6, median = 96, s.d. = 15.9) were taken from World Bank (2008). This variable is defined as the percentage of the population aged 15 years and older who have at least a basic proficiency at reading. Data were from the most recent year available for each nation between 1990 and 2007. Barber (2005) used data from 1976 for his analysis of literacy because that was the average year in which IQ data were collected for all countries. We felt that a more recent date was more appropriate, however, because the IQ scores for each country we used had been modified based on recorded trends of the Flynn effect to reflect the expected modern IQ score (Lynn & Vanhanen, 2006).

Enrolment in secondary school (mean = 29.0, median = 28.5, s.d. = 16.8), completion of secondary school (mean = 12.0, median = 10.5, s.d. = 9.25) and average years of education (AVED; mean = 6.17, median = 5.81, s.d. = 2.89) were taken from Barro & Lee (2001). These numbers represent the percentage of the population aged 25 and older who have attended some or all of secondary school, and the average number of years of schooling in the population. Data were used for the most recent years available after 1990. Data that were only available for years prior to 1990 were omitted.

Data of GDP per capita in US dollars was taken from the World factbook (CIA, 2007), and were log-transformed for normality (mean = 3.81, median = 3.85, s.d. = 0.53).

Distance from central Africa, or the human environment of evolutionary adaptedness (EEA), was calculated using the Pythagorean Theorem, as done by Kanazawa (2008). Kanazawa used three points at the corners of sub-Saharan Africa, so theoretically any point within this triangle should be a valid centre point from which to calculate distance. We selected 258 latitude, 2258 longitude, which is in the approximate centre of this area, and calculated distance from this point using the same methods as Kanazawa. Despite our own criticism of this variable and that of others (Wicherts et al., 2010a), we included this variable in the interest of thoroughness. This variable was log-transformed for normality (mean = 4.0, median = 3.97, s.d. = 0.710).

Percentage consanguineous marriages was not used in this study because it was the conclusion of Woodley (2009) that this variable is unlikely to account for the worldwide variation in intelligence. Additionally, consanguineous marriage and associated inbreeding may be a strategy for maintaining coadapted gene complexes that defend against local infectious diseases (Denic & Nicholls, 2007; Fincher & Thornhill, 2008).

All analyses were performed using JMP 8.0.2 statistical software.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

3.
Results

Log DALY owing to infectious disease and average national IQ correlated at r = −0.82 (n = 107, p < 0.0001) using LVCD, r = −0.82 (n = 184, p < 0.0001; figure A3-1) using LVE and r = −0.76 (n = 184, p < 0.0001; figure A3-1) using WEAM. Zero-order correlations were also performed for each of Murdock’s (1949) six world regions (see table A3-2). A hierarchical linear model (HLM) was also performed to determine whether this relationship is consistent across the six regions, finding that it is (LVE: R2 = 0.78, p < 0.0001, n = 184; LVCD: R2 = 0.77, p < 0.0001, n = 107; WEAM: R2 = 0.68, p < 0.0001, n = 184).

Log DALY owing to nutritional deficiencies and IQ correlated at r = -0.72 (n = 184, p < 0.0001). Log DALY owing to infectious disease and log DALY owing to nutritional deficiencies correlated at r = 0.89 (n = 192, p < 0.0001). The partial correlation between IQ and DALY owing to nutritional deficiencies with the effects of DALY owing to infectious disease removed was near zero (r = 0.028; n = 184, p = 0.71), while the partial correlation between IQ and DALY owing to infectious disease with the effects of DALY owing to nutritional deficiencies removed remained strong (r = −0.56; n = 184, p < 0.0001). See table A3-1 for other zero-order correlations. The correlations between these variables and IQ are very similar across the three measures of IQ (see the electronic supplementary material, tables A3-S1 and A3-S2).

To select which, if any, education and wealth variables to include in a multiple regression analysis, partial correlations were performed independently between literacy, enrolment in secondary school, completion of secondary school and AVED, and average national IQ, with the effects of infectious disease removed. If a variable was no longer significant when the effects of infectious disease were removed, it was not included in the multiple regression. Only WEAM

FIGURE A3-1 Log DALY owing to infectious disease and average national IQ correlate (a) at r = −0.82 (LVE) and (b) at r = −0.76 (WEAM; n = 184, p < 0.0001). The line is the least-squares line through the points.

FIGURE A3-1 Log DALY owing to infectious disease and average national IQ correlate (a) at r = −0.82 (LVE) and (b) at r = −0.76 (WEAM; n = 184, p < 0.0001). The line is the least-squares line through the points.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

TABLE A3-1 Zero-order correlations among average national IQ (LVE), log DALY owing to infectious disease, average winter high temperature, distance from EEA, literacy, average years of education (AVED), % enrolling in secondary education, % completing all secondary education and GDP. Values below the diagonal are sample sizes (number of countries), values above the diagonal are correlation coefficients. *p < 0.05, **p < 0.01, n.s., indicates p > 0.05. All others p < 0.0001.

 

1

2

3

4

5

6

7

8

9

1. average IQ

 

−0.82

−0.72

0.48

0.61

0.74

0.64

0.36

0.67

2. DALY disease

184

 

0.71

−0.39

−0.66

−0.79

−0.67

−0.32**

−0.79

3. winter high

124

122

 

−0.40

−0.57

−0.76

−0.76

−0.25*

−0.52

4. distance from EEA

190

192

124

 

0.40

0.36

0.25**

0.12 n.s.

0.30

5. literacy

113

113

78

118

 

0.73

0.91

0.17 n.s.

0.65

6. AVED

130

127

86

131

82

 

0.86

0.43

0.81

7. some secondary education

123

120

86

123

78

123

 

0.46

0.67

8. complete secondary education

114

112

73

126

68

95

91

 

0.37

9. GDP

190

192

124

226

117

130

123

120

 

and LVE IQ measures were used for these multivariate analyses in order to have a sample size large enough to make inferences about the individual contributions of each variable. When the effects of log DALY owing to infectious disease were removed, the correlation between IQ and literacy was r = 0.15 (n = 113, p = 0.094) using LVE and r = 0.16 (n = 113, p = 0.1087) using WEAM; IQ and some

TABLE A3-2 Zero-order correlations between average national intelligence and log DALY owing to infectious disease within each of Murdock’s (1949) six world regions. Values not in parentheses used LVE, values in parentheses used LVCD and values in square brackets used WEAM.

world area

correlation (r)

sample size (countries)

p-value

Africa

−0.80 (−0.80) [−0.49]

53 (22) [53]

<0.0001 (<0.0001) [0.0002]

Eastern Eurasia

−0.62 (−0.70)

20 (11)

0.0033 (0.016)

Insular Pacific

−0.85 (−0.83)

17 (12)

<0.0001 (0.0009)

North America

−0.65 (−0.76)

12 (7)

0.022 (0.049)

South America

0.077 (0.043)

23 (16)

0.73 (0.88)

Western Eurasia

−0.65 (−0.73)

59 (39)

<0/0001 (<0.0001)

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

secondary education was r = 0.093 (n = 120, p = 0.32) using LVE, and r = 0.23 (n = 120, p = 0.049) using WEAM; IQ and completion of secondary education was r = 0.17 (n = 110, p = 0.08) using LVE and r = 0.23 (n = 110, p = 0.030) using WEAM; IQ and AVED was r = 0.23 (n = 127, p = 0.0084) using LVE and r = 0.30 (n = 127, p = 0.0005) using WEAM; and IQ and GDP was r = 0.054 (n = 184, p = 0.46) using LVE and r = 0.036 (n = 184, p = 0.61) using WEAM. AVED was the best predictor of IQ when the effects of infectious disease were removed for both measures of IQ, so this education variable was used in regressions. As such, AVED will have the best chance of all the education variables at being significant in the multiple regression. Although GDP was not a statistically significant predictor of IQ when the effects of infectious disease were removed, and the partial correlation coefficients were well below 0.1, we included this variable in some models at the request of a reviewer (table A3-3).

In a multiple linear regression, average national IQ (LVE and WEAM) was predicted using infectious disease, average winter high temperature, distance from sub-Saharan Africa, AVED and GDP (see table A3-3 for model details). Significant predictors in this model were infectious disease, distance from Africa and winter high temperature. AVED was not significant. When GDP was removed from this model, virtually identical patterns emerged (see the electronic supplementary material, table A3-S3 for model details).

4.
Discussion

The negative relationship between infectious disease and IQ was statistically significant at the national level both worldwide and within five of Murdock’s (1949) six world regions. All analyses showed that infectious disease was a significant predictor of average national IQ, whether using either of Lynn & Vanhanen’s (2006) two datasets or Wicherts et al.’s (2010b) data. The zero-order

TABLE A3-3 Multiple regression analyses predicting average national intelligence using LVE and WEAM (in parentheses where different) by log DALY owing to infectious disease, log distance from EEA, average winter high temperature, average years of education (AVED) and log GDP. Whole model: n = 83 countries, p < 0.0001, R2 = 0.889 (0.796).

term

estimate

s.e.

standard beta

VIF

p

intercept

95.7 (95.4)

10.9 (13.6)

<0.0001

DALY disease

−8.30 (−6.50)

1.30 (1.61)

−0.597 (−0.51)

6.03

<0.0001 (0.0001)

Distance from EEA

5.03 (3.91)

0.983 (1.22)

0.231 (0.20)

1.41

<0.0001 (0.0021)

winter high

−0.239 (−0.217)

0.0686 (0.0853)

−0.228 (−0.23)

2.97

0.0008 (0.013)

AVED

−0.0279 (0.394)

0.322 (0.40)

−0.00683 (0.10)

4.30

0.93 (0.33)

GDP

0.265 (–0.262)

0.854 (2.45)

0.0269 (–0.013)

5.22

0.76 (0.92)

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

correlation between DALY owing to infectious disease and average national IQ was higher than that of any other variable for which there is a previously proposed causal explanation. The world regions analysis showed that the international pattern is repeated within five of the six regions despite a region’s generally similar cultural history. The only world region in which this relationship was not significant was South America. This exception may be owing to the presence of several outliers. The group of conspicuous outliers in which IQ was much lower than expected in the worldwide trend (figure A3-1) are all Caribbean countries (St Lucia, Dominica, St Kitts and Nevis, Antigua and Barbuda, Grenada, St Vincent and Grenadines, and Jamaica), which represent 4 of 23 nations in the South America analysis (St Lucia, Dominica, Grenada, and St Vincent and the Grenadines). Because these outliers are in the same geographical location, it is possible that local parasites that are not included in the DALY owing to infectious disease variable are causing these outliers. HLM analysis shows that, despite the nonsignificance of the correlation between IQ and infectious disease within South American nations, this trend is significant overall across Murdock’s (1949) six world areas.

Nutritional stress correlated with average national IQ (r = -0.72), but this relationship was not significant when the effects of infectious disease were removed. This supports the suggested link between intelligence and nutrition. Given the energetic cost of infectious disease, individuals who are burdened with parasites may be more likely to be affected by nutritional deficiencies. Likewise, individuals who are suffering from nutritional deficiencies may be less able to mount an effective immune response.

Multiple regression shows that, of infectious disease, temperature, evolutionary novelty and AVED, infectious disease is the best predictor of intelligence by a large margin. The effects of years of education are not significant, while temperature and evolutionary novelty seem to have distinct predictive power beyond infectious disease. Although this model cannot rule out the independent effect of distance from central Africa, this effect is difficult to interpret because of the doubt cast on the theory underlying this variable (Wicherts et al., 2010a). Although the effects of education and GDP per capita are not statistically significant when other factors are controlled for, this is not to say that these factors are not involved. A nation of more intelligent individuals is likely to produce a higher GDP, but a wealthier nation is also more able to pay for public education, as well as public medical and sanitation services. An indirect link between education and intelligence may also exist, as a better-educated population may be more interested in public health measures—leading to increased IQ by reducing information about germ theory and hygiene. These sources of endogeneity must be considered when interpreting our findings (and see below). It should also be mentioned that we are not arguing that global variation in intelligence is only caused by parasite stress. Rather, variation in intelligence is probably caused by a variety of factors, including those we have mentioned here as well as factors that are yet unknown.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

If the general pathway we propose is correct, there are two plausible mechanisms by which a trade-off in allocation of energy to immune function versus brain development and maintenance may occur. First, parasitic infection may intermittently cause the redirection of energy away from brain development. In this case, during periods of infection, the brain receives fewer energetic resources, but this allocation to brain function will return to pre-infection levels during healthy periods.

During periods of infection, whatever aspects of the brain that are growing and developing will suffer reduced phenotypic quality. Second, exposure to infectious agents may cause a developmental pathway that permanently invests more energy into immune function at the expense of brain growth. In this scenario, large amounts of energy would be allocated into immune function during periods of health, as opposed to only redirecting energy during periods of infection. This could operate through a variety of mechanisms. A plausible mechanism is that higher investment in immune system is triggered by individual exposure to infectious disease at some point during ontogeny. This may include triggering from exposure to maternal antibodies while in utero.

We also propose a complementary hypothesis that may explain some of the effects of infectious disease on intelligence. As we mentioned, it is possible that a conditional developmental pathway exists that invests more energy into the immune system at the expense of brain development. In an environment where there has consistently been a high metabolic cost associated with parasitic infection, selection would not favour the maintenance of a phenotypically plastic trait. That is, the conditional strategy of allocating more energy into brain development during periods of health would be lost, evolutionarily, if periods of health were rare. Peoples living in areas of consistently high prevalence of infectious disease over evolutionary time thus may possess adaptations that favour high obligatory investment in immune function at the expense of other metabolically expensive traits such as intelligence. Data do not currently exist on temporal variation of the severity of infectious disease across the world over human history. For genetically distinct adaptations in intelligence to exist based on this principle, parasite levels must be quite consistent over evolutionary time. If this is not the case, then selection would maintain investment in the immune system and in the brain as a plastic (as opposed to static) trait. The Flynn effect (Flynn, 1987) indicates that conditional developmental causes must be at work at least in part. Large increases in intelligence across a few generations cannot be attributed to genetic differences caused by evolutionary processes. Hence, it does not seem probable that region-specific genetic adaptations are the primary cause of the worldwide variation in intelligence.

Our findings suggest that the heritable variation in intelligence may come from two sources: brain structure and immune system quality. Thus, two individuals may possess identical genes for brain structure, but have different IQ owing

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

to differences in immune system quality reflecting their personal allocation of energy into brain development versus immunity.

Our findings are consistent with a number of other findings in the literature. In particular, the Flynn effect (Flynn 1987) demands that any hypothesis regarding the worldwide variation and distribution of intelligence must be able to account for some factor that allows for large IQ gains over time spans seemingly too short to be attributed to evolution by natural selection. The parasite-stress hypothesis allows for such a factor in the form of reduced parasitic infection. As societies become modernized, decreased parasite stress may occur through multiple pathways. As national wealth increases, medicine, vaccinations and potable water can be purchased by both the government and by individuals. Moreover, there is cross-national evidence that, as democratization increases, there are corresponding increases in public health legislation and infrastructure. Democratization also increases levels of education, better allowing individuals to seek out and understand information that reduces parasitic infection (Thornhill et al., 2009). This source of endogeneity is not a flaw, but a prediction of our hypothesis.

Mackintosh (2001) presented comprehensive evidence that skin darkness and the associated cellular components (e.g. melanocytes) have an important role in defending against infectious disease. Moreover, Manning et al. (2003) found that, in sub-Saharan Africa, rates of HIV infection were negatively associated with skin darkness. Manning et al. (2003) attributed this relationship in part to lower infection rates of other parasites, especially bacteria and fungi, that lead to tissue damage in the genital tract and hence increased opportunity for contracting HIV. Templer & Arikawa (2006) concluded that, despite the strong negative correlation between skin colour and average national IQ, there must be an unknown mediating factor accounting for both because there is no obvious reason for skin darkness to reduce IQ. Given the previous research linking skin colour to infectious disease (Mackintosh, 2001; Manning et al., 2003), the unknown factor linking skin colour and IQ may be infectious disease.

Several studies have shown a positive relationship between IQ and body symmetry (e.g. Furlow et al., 1997; Prokosch et al., 2005; Bates, 2007; Penke et al., 2009; but see also Johnson et al., 2008). There is evidence that body symmetry is a measure of developmental stability, an important component of which is owing to reduced contact with infectious disease (Thornhill & Møller, 1997). Our study suggests that IQ and body symmetry correlate because they are both affected negatively by exposure to high infectious disease. Individuals who are exposed to infectious disease may have many aspects of their body develop imperfectly, including the brain, negatively affecting both their body symmetry and cognitive ability. Indeed, recent research indicates that there is a positive relationship between body asymmetry and atypical brain asymmetries (Yeo et al., 2007).

The hygiene hypothesis proposes that some autoimmune diseases may be caused by low exposure to pathogens during ontogeny (e.g. Strachan, 1989). Previous studies of individual differences have shown that intelligence corre-

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

lated positively with the frequency of asthma and allergies (reviewed in Jensen & Sinha, 1993). According to the parasite-stress hypothesis, high intelligence is allowed in part by low exposure to infectious disease. Thus the relationship between intelligence and autoimmune diseases, such as asthma and allergies (reviewed in Gangal & Chowgule, 2009), is probably mediated through exposure to infectious disease. We predict that this positive relationship between IQ and autoimmune diseases will also be robust across nations, and that it will be mediated by infectious disease.

Although our results support our predictions, further studies must be done to establish causation. Longitudinal methods could be used to test this hypothesis on the individual level. Children’s IQ could be measured at an early age and remeasured later in life, while monitoring for infectious diseases throughout childhood. This would not only provide another test of our hypothesis, but may be able to determine the effects of individual infectious diseases on cognitive development. Additionally, it could be determined which, if either, trade-off mechanism we discussed is responsible for the detrimental effects of infectious disease on intelligence. Both may operate but with geographical differences based on the consistency of infectious disease over time. As nations develop, they could be monitored for declining rates of parasitic infection to determine (i) whether this corresponds with elevated IQ and (ii) whether any IQ gain is sufficient to account for the Flynn effect.

The authors thank Rachael Falcon, Steve Gangestad, Angela Hung, Kenneth Letendre, Paul Watson and Rhiannon West for their comments and suggestions. Three anonymous reviewers provided helpful and polite criticism.

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Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

Data Supplement

TABLE A3-S-1 Zero-order correlations among average National IQ (LVCD), log DALY infectious disease, average winter high temperature, distance from EEA, literacy, average years of education (AVED), % enrolling in secondary education, % completing all secondary education, and GDP. Values below the diagonal are sample sizes (number of countries), values above the diagonal are correlation coefficients. * indicates p < 0.05, ** indicates p < 0.01, ns indicates p > 0.05. All others p < 0.0001.

 

1

2

3

4

5

6

7

8

9

1. average IQ

 

−0.82

−0.72

0.48

0.59

0.75

0.50

0.50

0.73

2. DALY disease

107

 

0.71

−0.39

−0.66

−0.79

−0.67

−0.32**

−0.79

3. winter high

71

122

 

−0.40

−0.57

−0.75

−0.76

−0.25*

−0.52

4. distance from EEA

112

192

124

 

0.40

0.36

0.25**

0.12ns

0.30

5. literacy

66

113

78

118

 

0.73

0.61

0.17ns

0.65

6. AVED

91

127

91

86

82

 

0.86

0.43

0.81

7. some education

89

120

86

123

78

123

 

0.46

0.67

8. complete education

73

112

73

126

68

95

91

 

0.37

9. GDP

 

112

192

124

226

117

130

123

120

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

TABLE A3-S-2 Zero-order correlations among average National (WEAM), log DALY infectious disease, average winter high temperature, distance from EEA, literacy, average years of education (AVED), % enrolling in secondary education, % completing all secondary education, and GDP. Values below the diagonal are sample sizes (number of countries), values above the diagonal are correlation coefficients. * indicates p < 0.05, ** indicates p < 0.01, ns indicates p > 0.05. All others p < 0.0001.

 

1

2

3

4

5

6

7

8

9

1. average IQ

 

−0.76

−0.70

0.40

0.57

0.73

0.65

0.38

0.62

2. DALY disease

184

 

0.71

−0.39

−0.66

−0.79

−0.67

−0.32**

−0.79

3. winter high

124

122

 

−0.40

−0.57

−0.75

−0.76

−0.25*

−0.52

4. distance from EEA

190

192

124

 

0.40

0.36

0.25**

0.12ns

0.30

5. literacy

113

113

78

118

 

0.73

0.61

0.17ns

0.65

6. AVED

130

127

91

86

82

 

0.86

0.43

0.81

7. some education

123

120

86

123

78

123

 

0.46

0.67

8. complete education

114

112

73

126

68

95

91

 

0.37

9. GDP

 

190

192

124

226

117

130

123

120

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

TABLE A3-S-3 Multiple regression analyses predicting average national intelligence using LVE and WEAM (in parentheses when different) by log DALY infectious disease, log distance from EEA, average winter high temperature, and average years of education (AVED).

term

estimate

STD error

STD beta

VIF

p

intercept

98.6

5.98

<0.0001

 

(94.2)

(7.45)

 

 

 

DALY disease

–8.56

0.983

–0.616

3.50

<0.0001

 

(–6.39)

(1.22)

(–0.50)

 

 

distance from EEA

5.05

1.00

0.232

1.41

<0.0001

 

(3.90)

(1.22)

(0.195)

 

(0.0019)

winter high

–0.235

0.0666

–0.224

2.83

0.0007

 

(–0.219)

(0.0828)

(–0.228)

 

(0.0099)

AVED

0.0116

0.294

0.00285

3.62

0.97

 

(0.377)

(0.365)

(0.10)

 

(0.31)

whole model: n = 83 countries, p < 0.0001, r2 = 0.889 (0.796)

A4
THE NEGLECTED TROPICAL DISEASES: CURRENT STATUS OF CONTROL AND THE U.K. CONTRIBUTION

Alan Fenwick

Imperial College, London

Introduction

The neglected tropical diseases (NTDs) are an ever-growing list of infections that predominate in the tropics and are neglected in comparison with the “big three”: malaria, tuberculosis (TB), and HIV/AIDS (Hotez et al., 2008). The current list includes parasitic helminths, bacteria, protozoa, fungi, ectoparasites, and viruses. One subgroup of the NTDs is the group of seven, which are deemed “tool ready” insofar as they can be treated with safe and effective drugs that must be taken usually just once a year, although frequency may be determined by prevalence and intensity or whether the target of the treatment strategy is control or elimination (Hotez et al., 2006b). Because of drug donations by the pharmaceutical industry, these seven are usually targeted using mass drug admin-

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

istration (MDA). The target group may be the whole population of a given area or it may be confined to school-age children, again depending on the prevalence and intensity and the aim of the intervention. One or two of the NTDs may soon be eradicated if final efforts are successful. Some of the NTDs are extremely pathogenic, and so new drugs against them are being sought, usually with donor funding. These diseases do not lend themselves to MDA; rather diagnosis and treatment is the strategy. The rest of the NTDs are probably best described as the “even more neglected tropical diseases” because they are either less pathogenic or less frequently encountered. The exception is dengue fever, which is neglected despite an apparent increase in distribution and prevalence. Many of the NTDs will eventually disappear as they have in the developed world when socioeconomic status improves and clean and safe water and sanitation is available to all. Currently, with 1 billion individuals—one-sixth of the human population—living in poverty and often in extremely unhygienic conditions, such development is some way off.

The Seven Tool-Ready NTDs

The seven include six helminths, lymphatic filariasis (LF; elephantiasis), onchocerciasis (river blindness), schistosomiasis (bilharzia), and soil-transmitted helminths (STHs), of which there are three (ascariasis, trichuriasis, and hookworm), and trachoma, which is caused by the bacteria Chlamydia.

The Pathology and Need for an MDA Control Strategy (Ottesen, 2006)

Lymphatic filariasis (LF) is caused by two similar species of filariasis worms, Brugia malayi and Wuchereria bancrofti. They are each transmitted by mosquitoes, and the adult worms inhabit the lymph glands, which they block and therefore restrict lymph drainage. The gross consequence of LF is first a swelling of limbs, and the grosser deformities that occur are usually the result of secondary infections. In females, the breasts and legs are where the swellings typically appear and the extent can be grotesque. In men, legs and the scrotum can be affected, in which case the resulting hydrocele in males may also result in massive scrotal swellings. The definitive numbers of people suffering from these deformities is not known, but an estimate of 40 million is often quoted. The adult worms live for up to 6 years, and the female worms give birth to larvae (microfilariae), which travel around the skin of the human host waiting to be taken up during a mosquito blood meal. Transmission takes place when another human is bitten by an infected and infective mosquito. It has been discovered that an annual dose of either albendazole with Mectizan (ivermectin) or albendazole with diethylcarbamazine (DEC) will not kill the adult worms but will prevent any larvae from circulating in the skin. The theory, therefore, is that if sufficient people in an endemic area can be treated with these combinations of drugs, no larvae will be

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

available for the biting mosquitoes, and so transmission could be interrupted. If this could be achieved for seven consecutive years—longer than any adult worms will survive in their human host—then elimination of LF might be possible. The distribution of LF globally is widespread, and the Indian subcontinent, the Far East, Africa, and South America are all endemic for LF. The control using MDA is under the umbrella of the Global Alliance for the Elimination of LF (GAELF); however, full control will need significant case management for sufferers with symptoms. Currently, after an exponential increase in coverage from 1998, more than 550 million doses of albendazole are distributed annually—some 80 million with Mectizan and the rest with DEC. The albendazole has all been donated by GlaxoSmithKline (GSK), and more than 2 billion tablets have already been distributed since the start of the programme. Some of the earlier programs have already completed their planned intervention, and transmission has halted in Egypt and Zanzibar. As for case management, washing of swollen limbs regularly with soap has been shown to be very beneficial, and surgery for enlarged scrotal sacs is becoming more available to men with hydroceles.

Funding for GAELF comes from various sources, including the Bill & Melinda Gates Foundation and the British Government Department for International Development (DFID). Other funding for delivery of the donated drugs comes from the U.S. Agency for International Development (USAID), via a contractor and grantees, and a network of nongovernmental organisations (NGOs) also contribute funding and assist with organization of albendazole and Mectizan delivery. The Liverpool School of Tropical Medicine housed the Global Alliance secretariat and now the Centre for Neglected Tropical Diseases, which now works closely with the Schistosomiasis Control Initiative (SCI; see below).


Onchocerciasis (river blindness) is caused by the filarial worm Onchocerca volvulus. Onchocerca volvulus is transmitted by black fly (Simulium species), and the adult worms inhabit nodules in various parts of the body. The adult worms are long lived and, like LF, the female worms give birth to larvae (microfilariae) that travel around the skin of the human host, waiting to be taken up during a Simulium blood meal. Transmission takes place when another human is subsequently bitten by an infective fly. Unfortunately, the many microfilariae cause intense itching in their human host and also cause blindness as the traveling microfilariae damage the retina. The very high infection and blindness rates in villages in close proximity to African rivers in which the Simulium breed led to an intensive vector control campaign in the middle of the 20th century, when many rivers in 11 countries were sprayed with DDT to control the black fly populations. (The Onchocerciasis Control Project [OCP] was launched in 1974.) In the 1980s it was discovered that an annual dose of Mectizan (ivermectin), although it does not kill the adult worms, prevents any larvae from circulating in the skin. Because the larvae do the damage, an annual dose of Mectizan in an endemic area targeting the whole population should prevent blindness. Indeed since 1985

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

many millions of people have been treated annually in a campaign of preventive chemotherapy, and, although this campaign is still needed, the prevalence rates and blindness rates have been very significantly reduced. The distribution of onchocerciasis is mainly in Africa, although there are foci in South America. The OCP was closed in 2002, by which time an estimated 600,000 had been saved from blindness. The OCP was replaced by the African Programme for Onchocerciasis Control (APOC), which now targets 19 different countries, concentrating on getting annual Mectizan treatment out to those who live in hypoendemic areas. The Mectizan is provided to the countries who qualify by the Mectizan Donation Programme, which is housed within the Task Force for Global Health in Atlanta. The key to APOC is community-directed treatment with ivermectin (Boatin, 2008; Boatin and Richards, 2006). The donated ivermectin is distributed by trained community volunteers who deliver the ivermectin annually to the community using a dose pole to get the correct dose.

In some areas a new strategy of delivering two treatments of Mectizan per year has been instigated with a view to trying to kill the adult worms rather than merely reducing the microfilaria levels.

Funding for APOC comes from a number of traditional bilateral donors, including DFID, and in fact DFID recently (2009) donated an additional £5 million to APOC. Other funding for delivery of the donated drugs goes to the countries from USAID, via RTI,4 and a network of NGOs also contributes funding and assists with organization of Mectizan delivery.

Loa loa is another filarial worm with a limited geographical distribution and relative harmless symptoms, whose major significance is the complication it brings to the MDA against onchocerciasis and LF in Africa. Individuals with a heavy Loa loa infection may suffer serious side effects when treated with Mectizan and albendazole because of death of Loa loa microfilariae.


Schistosomiasis (bilharzia) is caused by species of the genus Schistosoma. S. mansoni causes intestinal schistosomiasis and is found in Africa and the Middle East and has been exported to South America and the Caribbean; S. haematobium causes urinary schistosomiasis—recently renamed urogenital schistosomiasis—and is limited to Africa and the Middle East; S. japonicum and S. mekongi cause intestinal schistosomiasis in the Far East, and S. intercalatum causes schistosomiasis in small foci in central Africa. In all it has been estimated that more than 200 million people may have been infected with schistosomiasis both in 1970 and in 2002 although, because of treatment, other control efforts, population increases, and water resource developments, the distribution of the various species may have changed (Steinmann et al., 2006). The adult schistosome worms are each about one centimetre in length and live in pairs in the blood vessels of the human host; each female worm will lay an estimated 300 eggs per day over a life

4

Research Triangle Institute (RTI) is better known by its trade name, RTI International.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

span of 5–6 years for S. haematobium to up to a reported 20 years for S. mansoni. The eggs break through the blood vessels into either the bladder or the intestine, causing detectable blood in the urine and less so in the stool. The eggs that do not leave the body via the excreta cause significant damage; S. mansoni eggs collect in the liver, where they are trapped, and when they die they cause fibrosis over a period of time, which is shorter in heavier infections. S. haematobium eggs cause lesions in the genital areas and also cause fibrosis of the bladder wall. In Egypt, where S. haematobium used to be particularly prevalent, bladder cancer was the most prevalent cancer in the country until the year 2000. A concentrated treatment programme throughout the 1990s and a change in water usage after the construction of the Aswan High Dam led to S. haematobium being all but eliminated from Egypt, and the associated bladder cancer rates have declined dramatically (Fenwick, 2000, 2006). Five large-scale control programmes were carried out during the period 1970–2000. The first was the Blue Nile Health Project in Sudan, which combined malaria control using indoor residual spraying with praziquantel treatment and mollusiciding. Meanwhile, Brazil embarked on a control programme using treatment of identified cases with first oxamniquin and then praziquantel to reduce the cases of massive liver damage. The others, slightly later, were World Bank–funded programmes in China, the Philippines, and Egypt. The current preferred drug against schistosomiasis is praziquantel, which is available as 600 mg tablets, and a dose of 40 mg/kg is considered curative. Merck donates 20 million tablets a year to the World Health Organization (WHO), and it distributes these to countries looking to initiate programmes. Control of schistosomiasis was initially focused on snail control from 1910 to 1950 because the various treatments for schistosomiasis were unpleasant and relatively ineffective. A few promising agents were tried from 1950 through 1980, but each of them proved to have significant side effects. In 1980, the drug praziquantel was marketed by Bayer after multicentre drug trials were successful, but the price of $1 per tablet was prohibitive. By 1990 a competitive process for manufacture by Shin Poong, a company in South Korea, led to a precipitous reduction in price, and by 2002 the tablets were available at 7 cents per tablet—a 93 percent reduction from the original price (Fenwick, 2008). Despite this reduction, African governments did not rush to buy because the demand for treatment was not high, and yet the numbers requiring treatment represented a very high percentage of the rural population. The leadership for control since 2000 has come from SCI, based at Imperial College London, and was established with a grant awarded by the Bill & Melinda Gates Foundation. Control programmes were established in six countries (Burkina Faso, Mali, Niger, Tanzania, Uganda, and Zambia), and the intention was to lead to national coverage. Programmes focused on MDA to school-age children and in areas of prevalence more than 50 percent of children and then whole populations were targeted. Fishermen and farmers using irrigation were especially targeted. SCI combined the treatment for schistosomiasis with a single pill of albendazole because the prevalence of STHs among people infected

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

with schistosomiasis was invariably high. By 2008, SCI had delivered more than 40 million treatments to about 20 million people, but this still represented only about 10 percent of the infected population in Africa, so expansion of this programme was essential (Fenwick et al., 2009). Additional support came from three sources. The first was a private equity company (Legatum) that funded SCI to organize implementation in Burundi and Rwanda, and this programme has completed three years of treatment of schistosomiasis and STH. The second was USAID, which through RTI has purchased praziquantel for donation to a number of endemic countries as part of its support for NTD control. The third is DFID, which has allocated £25 million for schistosomiasis and STH, £9.5 million for implementation and management, and £15 million to purchase the drugs. SCI and Liverpool Centre for Neglected Tropical Diseases work together on this award.

The current status of schistosomiasis control is that programmes are going ahead in a number of African countries funded by bilateral donations from USAID and DFID. However, WHO believes that less than 10 percent of the people in need of treatment in Africa were treated in 2009, which means that many areas are in need of treatment (Hotez and Fenwick, 2009).

A constraint is the funding to purchase praziquantel, but even if the funding was available there is a doubt whether production capacity is available beyond 150 million tablets a year. However, another constraint is the lack of capacity of many countries to deliver praziquantel widely, and so scaling up might well be slower than ideal even if funding was made available. Nevertheless, in many countries now the most serious cases of hepatosplenomegaly seem to be on the decrease. One aspect of schistosomiasis that was recently brought to the attention of the medical community is the association between S. haematobium and HIV/AIDS, which is why the term urogenital schistosomiasis was recently adopted (Kjetland et al., 2010a, 2010b).

We firmly believe that a stronger case needs to be made for the treatment of young children ages 6–14 with an extra focus on ensuring that young girls, whether in or out of school, are reached with schistosomiasis treatment before genital lesions are developed and therefore the chances of HIV/AIDS are significantly reduced (Hotez et al., 2009).


Soil-transmitted helminths (Ascaris lumbricoides, Trichuris trichuris, Necator americanus, and the less common Ancylostoma duodenale) The four species of STH, which actually are three diseases—roundworm, whipworm, and hookworm—infect different parts of the digestive tract and have different modes of infection, although none of them use an intermediate host.


Roundworms It is estimated that more than 800 million individuals are infected with roundworm and that most of these are children. It is also likely that most people are not heavily infected and that 10 percent of those infected harbor 90 percent of the worms. However, 10 percent of 800 million means that 80 mil-

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

lion people have dangerously heavy worm loads. Roundworms live in the small intestine, and their eggs are passed out in the feces. The eggs need to spend time developing in the soil in not-too-hot and not-too-dry conditions, and then they are ready to be ingested. If ingested, the eggs hatch and then migrate through the body until they are coughed up and swallowed. They then pass through to the small intestine where they remain, laying eggs and feeding. In heavy infections, the worms, which are thick and up to 14 inches (35 cm) in length, can cause a serious intestinal blockage.


Whipworms An estimated 600 million people are infected with Trichuris worms, which are generally thought to be the least pathogenic of the STHs. They are relatively small (less than 5 cm or 2 inches) and live in the colon. Heavy infections can cause colitis.


Hookworm The two species of hookworm infect almost 600 million people, and their effect on the human host is much greater than the other two types of STH, despite them being the smallest of the STHs at just 1 cm in length. This is because the hookworms attach to the wall of the small intestine and in fact take blood, causing anaemia, which can be severe in heavy infections. Anaemia is the main cause of poor birth outcomes and so hookworms are responsible for a significant number of underweight babies and for anaemia in children and women of childbearing age (Christian et al., 2004). The eggs of the hookworm are passed out in the faeces and then develop in the egg before hatching, releasing a free-living larva. This larva attaches to bare feet or legs and burrows through the skin to reach the bloodstream. Via the heart, they reach the lungs, migrate up the trachea, and are then swallowed.

All three worms are global in distribution, although, thanks to improved sanitation, areas that 100 years ago were heavily infected with hookworm (the classic example being the southern United States) no longer have any hookworm at all.

The worms can be swept from the human digestive system by treatment with a benzimidazole, either albendazole or mebendazole. Neither drug is 100 percent effective, but even if an individual is not completely cleared of worms a high percentage will be swept through the system (Albonico et al., 2004).

Until very recently, the deworming drugs had to be purchased, and, although they were inexpensive (less than 10 cents per dose), few countries organize deworming programmes. From 2008, Johnson and Johnson began a donation program and up to 50 million mebendazole tablets were donated annually to selected countries. From 2010, Johnson and Johnson has reported that it will increase its donation to 200 million tablets a year. Meanwhile, the 2 billion tablets of albendazole that have been donated by GSK for treatment of LF have dewormed millions of individuals annually. In October 2010, GSK announced an increase in its albendazole tablets by 400 million every year to ensure that all school-age children in Africa will be dewormed (Lorenzo Savioli, WHO, personal

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

communication). Another donor has been “Feed the Children,” a programme that has donated many millions of mebendazole tablets for schoolchildren. It can surely be expected that within 5 years children in Africa and the developing world will show improvements in appetite, physical fitness, growth, hemoglobin, school attendance, and cognitive ability (Jukes et al., 2002; Miguel and Kremer, 2004; Nokes et al., 1992). It may be difficult to demonstrate these improvements because of confounding factors, but most parasitologists are convinced of the accuracy of this hypothesis.

Since the millennium, several organizations have increased their deworming activities. SCI has combined deworming with treatment of schistosomiasis. “Children without worms” has handled the Johnson and Johnson donation of mebendazole, “Deworm the World” has accepted Feed the Children mebendazole, and now GSK will donate 400 million tablets per year for Africa, probably through a WHO mechanism. Many NGOs have deworming programs, USAID has included deworming in the integrated NTD treatment programmes, and the United Nations Children’s Fund has funded many countries to deworm preschool-age children. In several progressive Asian countries, deworming has been adopted and funded by the state. However, despite all this recent activity, WHO still believes that only 10 percent of people are being dewormed annually.


Trachoma caused by the bacterium Chlamydia trachomitis Known as the leading cause of preventable blindess, Chlamydia is reported to infect some 80 million people worldwide, and up to 8 million may be visually impaired as a result of their infection. As with all the above, this is an infection in the poorest of the poor, and could be easily prevented by improved water and sanitation. Without better hygiene, the infection is carried from person to person both by physical contact and by flies. As with the other diseases, there has been an initiative to control trachoma. The International Trachoma Initiative (ITI) was started by Dr. J. Cook when he left the Edna McConnell Clark Foundation (EMCF), which for many years funded Dr. Cook’s tropical disease research. The EMCF provided startup funding, Pfizer joined in with Zithromax donations, and the Bill & Melinda Gates Foundation also supported the programme. In a slightly different approach, ITI insisted on more than just a treatment program and developed a “SAFE” strategy: S, for incorporating simple surgery to correct eyelid deformities and prevent cornea scarring; A, for antibiotics—three annual doses to control active Chlamidia; F, for facial cleanliness to prevent the infection, which leads to conjunctivitis, which will reduce transmission; and finally E, for environmental improvement, including improved water supplies and better sanitation. The first country to eliminate trachoma was Morocco. In 2011 it is estimated that some 70 million doses of Zithromax will be delivered by ITI, which was once independent but is now housed within the Task Force for Global Health.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×
Integration of Activities Against the Seven Tool-Ready NTDs

WHO, in conjunction with the Global Network for Neglected Tropical Diseases, the Bill & Melinda Gates Foundation, and others, led the drive to bring all the vertical single disease programmes together with a view to integration of the annual MDA programmes. The concept was “sold” to USAID, which resulted in a competitive bid in 2006 for $100 million more than 5 years for integrated MDA, awarded to RTI. This has resulted in 10 countries receiving support for integrated NTD treatments and more than 250 million treatments with the four drugs being delivered.

In 2010, further funding for integrated NTD treatment is on the table again from USAID—and this time up to $450 million may be awarded to several contractors. By November 2010 Family Health International had been awarded $100 million for each of Africa and Asia to take established programmes forward.

Other Neglected Tropical Diseases

Guinea Worm: Dracuncula medinensis

Guinea worm is a nasty worm infection that affects man and water fleas. From more than 3 million infected some 20 years ago, it is estimated that in 2010 only 25,000 cases remain in the world; most of those cases are in South Sudan because of hostilities that have prevented clearance. The latest country to be declared free of Guinea worm was Burkina Faso. The larval worm lives in a water flea and is ingested by anyone drinking unclean, unfiltered water from a pond or lake. The larvae are released in the stomach and over several months make their way to the connective tissue in the leg, where the female becomes gravid with eggs. The female worm produces a blister that burns; when the blister bursts, eggs are released into the water to reinfect the water fleas. The effect on the human host is painful, and secondary infection can be very dangerous. Before control efforts were in place, which depend mostly on health education and providing filters for water, whole villages were likely to be infected. There is no drug to treat this worm, but because there is no animal reservoir the chances are great that it will soon be eradicated. The Carter Center and WHO, with support from the Bill & Melinda Gates Foundation and DFID, have worked tirelessly to reduce the number of infections; with the exceptions of Ghana and Sudan, the target of eradication is getting very close (Hopkins et al., 2005; Ruiz-Tiben and Hopkins, 2006).

The Protozoa: Trypanosomiasis and Leishmaniasis (Croft et al., 2005, 2006)

Sleeping sickness and Chagas disease caused by trypanosomes and visceral leishmaniasis are important diseases that have a high mortality rate, killing over 150,000 per year; they have a poor cure rate even when treated. Cutaneous leishmaniasis does not kill but is disfiguring and also difficult to treat.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

Sleeping sickness is transmitted by the bite of the tsetse fly, and once infection has developed to disease, mortality is high. At any one time an estimated 500,000 people may be infected. The drugs available even if cases are diagnosed are old, and there is an urgent need to find new treatments, even though they will never be commercial products. The not-for-profit Drugs for Neglected Diseases initiative (DNDi) based in Geneva is following some promising drug development lines with funding from DFID, the Gates Foundation, and the European Union. Screening for human African trypanosomiasis (HAT) used to be more widespread than it is today because the areas worst affected include current conflict areas in East and Central Africa.

Chagas disease is limited to South America because it is transmitted by a triatoma bug, but still an estimated 9 million are infected and therefore suffer from either an acute stage, which can cause heart failure, or a chronic condition that disturbs the heart, causing palpitations, chest pain, and fainting. Although it is caused by a trypanosome, it is thus very different from HAT. However, this disease should be easily preventable by improving housing conditions or indoor insecticide spraying, which will prevent bedbugs. As with other parasitic infections, it is the poorest people who are infected.

Leishmaniasis affects some 12 million people globally and is transmitted by sandflies. The cutaneous form causes ulcers and can be disfiguring, but the visceral form affects internal organs and is fatal if untreated. However, the treatment often causes side effects and is prohibitively expensive to the poor people who tend to be infected.

The Even More Neglected Tropical Diseases (Hotez et al., 2006a)

Many more diseases occur in the tropics and are even more neglected than those mentioned above. There are helminth infections such as strongy-loidiasis, Toxocariasis and larva migrans, and loiasis. There are food-borne trematodes,which are very common in the Far East because of the eating of poorly cooked fish. These include opisthorchis, paragonimus, and chlonorchis. The additional Cestodes that affect humans are taeniasis, cysticercosis, and echinococcosis, which include the zoonotic parasitic worms.

Other protozoa include giardiasis and amoebiasis, while bacterial infections include Bartonellosis, bovine tuberculosis, Buruli ulcer, leptospirosis, relapsing fever, rheumatic fever, treponematoses, and syphilis. Two important fungal infections include mycetoma and paracoccidiomycosis; then there are ectoparasitic infections such as scabies, myiasis, and tungiasis. The viral infections include dengue fever, yellow fever, Japanese encephalitis, rabies, and the hemorrhagic fevers.

Thus, although the tool-ready infections can be controlled or eliminated using preventive chemotherapy, there are many more infections that mostly affect the poorest of the poor that are still very neglected. To achieve the Millenium Development Goals, it will be necessary to tackle not only the tool-ready diseases

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

but also the others mentioned in this paper, because poverty and these diseases are inextricably linked (Gil Gonzalez et al., 2006).

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Hotez, P. J., D. H. Molyneux, A. Fenwick, E. Ottesen, S. Ehrlich Sachs, and J. D. Sachs. 2006b. Incorporating a rapid-impact package for neglected tropical diseases with programs for HIV/AIDS, tuberculosis, and malaria. PLoS Medicine 3:e102.

Hotez, P. J., D. H. Molyneux, A. Fenwick, L. Savioli, and T. Takeuchi. 2008. A global fund to fight neglected tropical diseases: Is the G8 Hokkaido Toyako 2008 summit ready? PLoS Neglected Tropical Diseases 2:e220.

Hotez, P. J., A. Fenwick, and E. F. Kjetland. 2009. Africa’s 32 cents solution for HIV/AIDS. PLoS Neglected Tropical Diseases 3:e430.

Jukes, M. C., C. A. Nokes, K. J. Alcock, J. K. Lambo, C. Kihamia, N. Ngorosho, A. Mbise, W. Lorri, E. Yona, L. Mwanri, A. D. Baddeley, A. Hall, and D. A. Bundy. 2002. Heavy schistosomiasis associated with poor short-term memory and slower reaction times in Tanzanian schoolchildren. Tropical Medicine and International Health 7:104–117.

Kjetland, E. F., E. N. Kurewa, T. Mduluza, N. Midzi, E. Gomo, H. Friis, S. G. Gundersen, and P. D. Ndhlovu. 2010a. The first community-based report on the effect of genital Schistosoma haematobium infection on female fertility. Fertility and Sterility 94:1551–1553.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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Kjetland, E. F., P. D. Ndhlovu, T. Mduluza, V. Deschoolmeester, N. Midzi, E. Gomo, L. Gwanzura, P. R. Mason, J. B. Vermorken, H. Friis, S. G. Gundersen, and M. F. Baay. 2010b. The effects of genital Schistosoma haematobium on human papillomavirus and the development of cervical neoplasia after five years in a Zimbabwean population. European Journal of Gynaecology and Oncology 31:169–173.

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Ottesen, E. A. 2006. Lymphatic filariasis: Treatment, control and elimination. Advances in Parasitology 61:395–441.

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A5
INTEGRATED IMPLEMENTATION OF PROGRAMS TARGETING NEGLECTED TROPICAL DISEASES THROUGH PREVENTIVE CHEMOTHERAPY: PROVING THE FEASIBILITY AT NATIONAL-SCALE5

Mary Linehan, Christy Hanson, Angela Weaver, Margaret Baker, Achille Kabore, Kathryn L. Zoerhoff,* Dieudonne Sankara, Scott Torres, and Eric A. Ottesen

RTI International, Washington, District of Columbia; United States Agency for International Development, Washington, District of Columbia; Department of International Health, School of Nursing and Health Sciences, Georgetown University, Washington, District of Columbia; Liverpool Associates in Tropical Health, Washington, District of Columbia; World Health Organization, Geneva, Switzerland

Abstract

In 2006, the United States Agency for International Development established the Neglected Tropical Disease (NTD) Control Program to facilitate integration of national programs targeting elimination or control of lymphatic filariasis,

5

Republished with permission of American Society of Tropical Medicine and Hygiene, from Integrated Implementation of Programs Targeting Neglected Tropical Diseases through Preventive Chemotherapy: Proving the Feasibility at National Scale, Linehan M, Hanson C, Weaver A, Baker M, Kabore A, Zoerhoff KL, Sankara D, Torres S, and Ottesen EA, 84(1), 2011; permission conveyed through Copyright Clearance Center, Inc.

*

Address correspondence to Kathryn L. Zoerhoff, Monitoring and Evaluation Associate, Neglected Tropical Disease Control Program, RTI International, 805 15th Street NW, Suite 601, Washington, DC 20005-2207. E-mail: kzoerhoff@rti.org.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

onchocerciasis, schistosomiasis, soil transmitted helminthiasis and blinding trachoma. By the end of year 3, 12 countries were supported by this program that focused first on disease mapping where needed and then on initiating or expanding disease-specific programs in a coordinated/integrated fashion. The number of persons reached each year increased progressively, with a cumulative total during the first three years of 98 million persons receiving 222 million treatments with donated drugs valued at more than $1.4 billion. Geographic coverage increased substantially for all these infections, and the program has supported training of over 220,000 persons to implement the programs. This current experience of the NTD Control Program demonstrates clearly that an integrated approach to control or eliminate these five neglected diseases can be effective at full national scale.

Introduction

The neglected tropical diseases (NTDs) are a group of conditions causing significant morbidity and mortality worldwide but which until recently received only minimal attention from most of the world, largely because they affect the poorest, most vulnerable and most disenfranchised members of society (Hotez et al., 2009). Afflicting more than one billion persons, one-sixth of the world’s population, these diseases cause severe disfigurement, disability, and blindness. The NTDs are among the leading perpetuators of poverty because they significantly diminish economic productivity in affected adults and because they impair the intellectual and physical development of the next generation in disease-endemic areas, setting already vulnerable children on a path to lifelong disability that reinforces a cycle of poverty (Hotez et al., 2009).

Among the 15 most prominent NTDs (Hotez et al., 2006), seven have similar strategies to address their control; namely, single doses of effective treatment , termed preventive chemotherapy (PCT), given once or twice a year to broad segments of the population in disease-endemic areas through mass drug administration (MDA). These seven diseases are lymphatic filariasis (LF), onchocerciasis, schistosomisis, trachoma and three soil-transmitted helminth (STH) infections (ascariasis, hookworm, and trichuriasis) (WHO, 2006). The treatment and diagnostic tools currently available for this group of diseases are sufficiently effective for these NTDs to be targeted either for elimination or for reduction to such low levels that they no longer constitute a significant public health problem.

Most of the drugs used in these single-dose, once- or twice-yearly treatment regimens are donated through large public-private partnerships that bring together public health implementers, public-sector and private-sector donors, and the major pharmaceutical firms producing these drugs (GlaxoSmithKline, Johnson & Johnson, Merck and Co., Inc., Merck-Serono, Pfizer) (Liese et al., 2010).

Historically, many Ministries of Health in disease-endemic countries have supported the control of NTDs through independent, often parallel, programs,

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

with each maintaining its own planning, funding, drug supply chain, MDA campaign, monitoring, and evaluation. If funding were available for one program, that program might have been able to implement preventive chemotherapy while a sister program could not. However, because there is considerable overlap of these diseases in persons and communities, controlling one of the NTDs and not others that could be managed through a similar strategy is inefficient at best. Furthermore, research has provided sufficient evidence to suggest that co-implementation of the integrated PCT programs is safe for persons and communities in all but a few specific settings (e.g., Loa loa co-endemicity with onchocerciasis or LF) (WHO, 2006).

Because of the similarity of their strategic approaches, the epidemiologic overlap among affected populations and the availability of donated drugs, these NTD control programs seemed ideally suited for implementation that could be carried out not in parallel, independent fashion, but, rather, integrated in a way where coordinated treatment interventions for multiple diseases could reduce the duplication of effort expended in treating the diseases separately. Such integration, here considered in the broadest sense as coordination of program activities among different disease-specific programs and as linkages of these activities with other elements of the health care system, should lead to efficiencies of delivery, enhanced effectiveness, increased health benefits, and better use of limited resources that could permit more at-risk people to be reached (Brady et al., 2006). The World Health Organization (WHO) has endorsed such co-implementation of programs as the integrated approach to preventive chemotherapy.

Early pilot studies of NTD program integration generally showed that, despite many practical challenges, such integration was likely to be feasible and to result in at least some of the anticipated efficiencies and cost savings (Garba et al., 2009; Lammie et al., 2006; Richards et al., 2006). While it was clear from these pilot studies that certain elements of program implementation were more amenable to successful integration than others, it was not clear either how successful the scaling up of these integration efforts from pilot studies to national-scale programs could be or just which combinations of activities were most effectively linked.

The opportunity to document the feasibility of integrated approaches to NTD control at full national-scale presented itself when the U.S. Congress in 2006 authorized funds for “the integrated control of neglected tropical diseases” (U.S. Congress, 2006). This authorization led to the establishment of the United States Agency for International Development (USAID) NTD Control Program that envisioned, over a five-year period, facilitating integrated NTD programs in 15 countries. The present report documents the considerable achievements of the first three years of this NTD Control Program towards the development and growth of national integrated NTD programs and in their expansion to full national scale.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

Methods

The NTD Control Program

Goals and approach USAID NTD Control Program initiated activities in September 2006. Its defined target was to enable the provision of 160 million preventive chemotherapy treatments to 40 million people in 15 countries through integrated NTD programs over five years. The stated aims of the Program have been 1) to support and empower national governments to develop integrated NTD control programs embedded, where possible, within existing service delivery platforms and to lead these programs in scaling-up activities to full national levels; 2) to provide technical assistance for planning, budgeting, reporting and complying with international standards and guidelines (Table A5-1) to improve program integration; 3) to promote cost-efficiency, improved integration strategies, and effective advocacy; and 4) to assure national ownership, continued commitment, and resource mobilization for sustained support for NTD control.

The prime contractor, RTI International, has provided grants and coordination for a team of non-governmental organizations (NGOs) and implementing partners to support integrated NTD control programs organized and led by the governments of selected countries. The support from the U.S. Government was intended to build on existing commitments by governments and other donors and fill financial and technical gaps that were preventing national programs from reaching full national scale. The Program was mandated to track and report on the additional numbers of persons reached and treatments provided through support of the NTD Control Program (recognizing that in some countries other support also exists for NTD control).

Participating countries and NGOs

The countries currently involved in the USAID-supported, RTI-coordinated NTD Control Program are identified in Table A5-2, along with the lead NGO responsible in each country for interfacing between the national Ministry of Health and RTI. Those five countries which had earlier pilot programs, initiated with support from the Bill and Melinda Gates Foundation (Leading global health organizations, 2006) and aimed at integrating disease-specific NTD control activities, are referred to as the fast-track countries, because they could begin scaling up activities immediately; additional countries have been brought into the program progressively. By the end of year-3, 12 countries were included in the program, of which seven were actively engaged in yearly MDAs. It is from these first 7 implementing countries that the quantitative measures of the NTD Control Program’s programmatic achievement during its first 3 years (reported below) are derived.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

TABLE A5-1 Disease-Specific Guidelines*

Disease

Diagnostic approach for mapping

Threshold for implementation of pct interventions

Unit of implementation

At-risk population targeted

Drugs

Frequency of intervention

Lymphatic filariasis (in countries where onchocerciasis is co-endemic)

Antigen detection (ICT) or microfilia detection (microscopy) in whole blood

Prevalence ≥1% in adults in some part of an implementation unit

District or other as defined for ease of operation

≥ 5 years old

IVM and ALB

Once per year (anticipated 4-6 years)

Lymphatic filariasis (in countries where onchocerciasis is not co-endemic)

 

 

 

≥ 2 years old

DEC andALB

 

Onchocerciasis APOC

Nodule detection using rapid techniques

Presence of palpable nodules ≥20% in adult men

Meso- or hyperendemic focus (reflecting river basins)

≥ 5 years old

IVM

Once per year, except in special circumstances

Onchocerciasis OEPA

Skin snip

Prevalence of infection ≥1% in an implementation unit

Endemic focus

≥ 5 years old

IVM

Twice per year (anticipated 10-14 years)

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

Disease

Diagnostic approach for mapping

Threshold for implementation of pct interventions

Unit of implementation

At-risk population targeted

Drugs

Frequency of intervention

Schistosomiasis

Parasitological methods

High risk: Prevalence of infection ≥50% in SAC

District, Sub-district or Community

SAC and adults

PZQ

Once per year

 

1) detecting eggs in urine or stool (microscopy)

 

 

 

 

 

2) detecting blood in urine (hemastix or questionnaires)

Moderate-risk: Prevalence of infection ≥10% but <50% in SAC

 

SAC and at-risk adults

 

Once every two years

 

 

Low-risk: Prevalence of infection <10% in SAC

 

SAC presenting at health center

 

Twice during primary schooling

Soil-transmitted helminthiasis (ascariasis, trichuriasis, hookworm)

Detecting eggs in stool (microscopy)

High-risk: Prevalence of any STH ≥50% in SAC

District, Sub-district or Community

SAC, preschool children, women of childbearing age, pregnant women in second and third trimesters, special adult populations

ALB or MEB

Twice per year

 

Low-risk: Prevalence of any STH ≥20% and <50% in SAC

 

 

Once per year

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

Trachoma (blinding)

Eyelid examination for follicular inflammation (TF)

TF prevalence ≥10% in 1-9 year olds

District

Everyone ≥ 6 months old with azithromycin; Children <6 months with tetracycline

AZT and TET

Once per year (AZT); Twice per day for 6 weeks (TET)

* Consistent with established and currently followed WHO recommendations (WHO, 2006), http://whqlibdoc.who.int/publications/2006/9241546. Abbreviations: IVM=Ivermectin; ALB=Albendazole; DEC=Diethylcarbamazine; PZQ=Praziquantel; MBD=Mebendazole; AZITH=Azithromycin; TETRA=tetracycline; SAC=School-aged children; TF=Trachomatous Inflammation.

† Duration of intervention varies for each disease.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

TABLE A5-2 Principal Drug Distribution Strategy in Endemic Districts*

NTD control program

Country

Principal drug distribution strategy in endemic districts

LF

Onchocerciasis

Schistosomiasis

STH

Trachoma

Lead ngo

“Fast-Track” Countries

Burkina Faso

Community

Household

Health center

Mobile

Community

Household

Health center

Mobile

Community

School-based

Household

Health center

Mobile

Community

Household

Health center

Mobile

Community

Household

Health center

Mobile

Schistosomiasis Control Initiative

 

Ghana

Community

Community

School-based

Community

Transmission of blinding trachoma interrupted

World Vision

 

Mali

Community

School-based

Household

Mobile

School-based

Household

School-based

Household

Mobile

Community

School-based

Household

Mobile

School-based

Household

Mobile

Helen Keller International

 

Niger

School-based

Household

N.A.

School-based

Household

School-based

Household

School-based

Household

Schistosomiasis Control Initiative

 

Uganda

Community

School-based

Household

Community

Household

Community

School-based

Household

Community

School-based

Household

Health center

Community

School-based

Household

Health center

RTI International

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

Additional Countries

Haiti

School-based

Distribution posts

N.A.

N.A.

School-based

Distribution posts

N.A.

IMA-World Health

 

Sierra

Leone

Community

Household

Community

Household

School-based

Community

School-based

Household

N.A.

Helen Keller International

 

Bangladesh

 

 

 

 

 

RTI International

 

Cameroon

 

 

 

 

 

Helen Keller International

 

Nepal

 

 

 

 

 

RTI International

 

Southern

Sudan

 

 

 

 

 

Malaria Consortium

 

Togo

 

 

 

 

 

Health and Development International

* NTD = neglected tropical disease; LF = lymphatic filariasis; STH = soil-transmitted helminths; NGO = nongovernment organizations; NA = not applicable.

† General features of different distribution strategies described by national programs. Community distribution = in the market, mosque, or other busy places, common in urban settings; Schoolbased distribution = in schools, targeting only children in schools; Household distribution = house-to-house, where the drug distributor brings the drugs to persons in their homes; Health center distribution = at a health center, where persons come to the health center to receive the drugs; Mobile distribution = through distributors traveling by vehicle to find households in remote areas.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×
Drug distribution

All drugs were distributed by the national Ministries of Health whose national NTD control programs determined how best to implement their MDAs (Table A5-2). The drugs were used according to WHO recommendations (Table A5-1). When disease co-endemicity required the use of multiple drugs (including combinations of albendazole, diethylcarbamazine [DEC], ivermectin, mebendazole or praziquantel), these were generally given at the same time, although sometimes the praziquantel treatment was delayed for at least a week after the other drugs were administered. When azithromycin was required, its administration was always at least a week separated from those of the other drugs, as currently recommended.

Albendazole for treatment of LF was donated by GlaxoSmithKline (Gustavsen et al., 2009); when used to treat STH in areas where LF is not endemic, albendazole was obtained from pre-qualified generic manufacturers. Azithromycin (Zithromax) was donated by Pfizer (Knirsch, 2007). Diethylcarbamazine was obtained through WHO from pre-qualified generic manufacturers. Ivermectin (Mectizan) was donated by Merck & Co., Inc. (Thylefors, 2008). Mebendazole was donated by Johnson & Johnson (Liese et al., 2010) to treat persons with STH in countries where its Children Without Worms program operates. Tetracycline eye ointment was obtained from pre-qualified generic manufacturers.

Technical assessments

Mapping. Because knowledge of the distribution of each NTD in a country is absolutely essential for developing any implementation (or integrated-implementation) plan, disease-specific mapping was carried out according to guidelines recommended by WHO and its partners (Table A5-3). Although some of these guidelines are still evolving, for all program assessments, the most up-to-date recommendations were followed.


Program metrics. To document progress toward achieving the program’s targets of 40 million additional people treated with 160 million treatments over 5 years, the following indicators were used to track country-specific program progress: 1) number of countries supported by the NTD Control Program; 2) number of additional districts (implementation units) mapped for each endemic disease; 3) number of people treated (i.e., receiving at least one drug or drug package) and recorded in MDA registers for each round of PCT; 4) number of additional treatments (i.e., made possible through support from the NTD Control Program) provided (i.e., number of times a single drug dose is administered) and recorded in MDA registers for each round of PCT; 5) number of additional implementation units reached and reported by national programs for each round of PCT; 6) programmatic coverage: % targeted population reached with appropriate PCT treatment each round of PCT and calculated from register reports as the number

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

TABLE A5-3 WHO Guidelines for Disease-Specific Mapping

Lymphatic filariasis

Indicator

Prevalence of Wucheria bancrofti antigenemia or Brugia microfilaremia

Persons tested

> 15 years old

Living > 10 years in the community/village

Diagnostic tool

Immunochromatograpy (ICT) antigen test of finger stick blood or parasitologic examination of night blood films

Sample size

Up to 300 to identify at least 1 antigen- or microfilaremia-positive person (i.e., exceeding threshold of 1%)

Sampling frame

At least 1 village/site in an imlementation unit

Convenience sample or otherwise

Onchocerciasis

Indicator

Prevalence of subcutaneous nodules or Onchocerca volvulus microfilariae in the skin

Persons tested

50 adults ≥ 20 years of age and living in the village for > 10 years

Diagnostic tool

Palpation of subcutaneous nodules (also possible: parasitologic examination of skin snip)

Sample size

50 per village; 2-4% of villages in focus

Sampling frame

Convenience or otherwise

Schistosomiasis

Indicator

Questionnaire; prevalence of microhaematuria or parasite eggs in urine for Schistosoma haematobium

Prevalence of parasite eggs in stool for S. mansoni

Persons tested

School age children (7-14 years of age)

Diagnostic tool

Dipsticks for microhaematuria/urine filtration for S. haematobium Kato-Katz or sedimentation test for S. mansoni

Sample size

50 school age children per school or site

Sampling frame

At least 5 villages with expected high prevalence in each ecologic zone In the village: convenience sample

Soil Transmitted Helminths

Indicator

Prevalence of eggs in stool

Persons tested

School age children (7-14 years of age)

Diagnostic tool

Kato-Katz

Sample size

50 SAC per school or site

Sampling frame

5 villages with expected high prevalence in each ecologic zone In the village: convenience sample

Trachoma

Indicator

Prevalence of trachomatous inflammation (TF) and trichiasis (TT)

Persons tested

1-9 year-olds for trachomatous inflammation (TF) > 15 year-olds for TT

Diagnostic tool

Clinical examination of eyes

Sample size

50-100 children per cluster

Sampling frame

20 clusters per implementation unit (district or other) Probability Proportional to Estimated Size

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

treated divided by treatment-eligible populations in the implementation unit (as defined by census reports); 7) geographic coverage: % of endemic districts covered by PCT programs; 8) number of persons trained for integrated NTD control through support from the NTD Control Program.

Program expenditures

Funding levels for each of the program’s first three years approximated $13.5 million per year, with the mandate that at least 80% of total annual resources be allocated to country program implementation and that overall management costs by RTI (whose role was to ensure financial accountability of all funds expended and to provide requested technical assistance to national programs) be no more than 20%. Of the 80% allocated for country implementation activities approximately 20% was earmarked for procurement of essential drugs not available through donation programs (i.e., PZQ for schistosomiasis, DEC for LF, and albendazole for childhood de-worming in areas where LF is not co-endemic).

Results

Mapping the geographic distribution of the targeted NTDs

Because knowing the distribution of the targeted NTDs is essential for developing an implementation strategy, the first efforts of the NTD Control Program in the participating countries focused on cataloging the disease-distribution information available and then supporting on-the-ground efforts to map the distribution of infection where sufficient information was not available.

Table A5-4 aggregates the data from all of the districts in the first seven implementing countries (identified in Table A5-2) and indicates the total number of districts that had been mapped for each of the NTDs prior to the initiation of

TABLE A5-4 Mapping of Districts in NTD Control Program Countries*

Disease

Baseline before NTD Control Program Start

Districts Mapped with USAID Support

Districts Mapped with Other Support

No. remaining districts that need mapping end of year 3

No. districts already mapped

No. districts needing NTD mapping

LF

493

33

8

12

13

Onchocerciasis

379

147

0

143

4

Schistosomiasis

346

180

170

0

10

STH

356

170

170

0

0

Trachoma

423

103

68

24

11

* Aggregated total number of districts in the first 7 implementing countries (identified in Table 2). NTD = neglected tropical disease; USAID = United States Agency for International Development; LF = lymphatic filariasis; STH = soil-transmitted helminths.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

the NTD Control Program. It is clear that mapping was already well advanced for LF. For the other diseases, there was still a great need for additional information on the distribution of these infections.

Table A5-4 also shows the progress made by the end of the first three years of support to the participating countries through the NTD Control Program. For each of the targeted diseases, mapping activities progressively defined the extent of the targeted diseases, and as a result of these efforts and those of other partners, only a small number of districts in these countries remained to be mapped for these NTDs at the end of year 3 (now targeted for subsequent years’ activities).

Persons treated and number of treatments delivered in Years 1-3

Although programs targeting the individual NTDs were active in many countries prior to the inception of the NTD Control Program, few countries approached these diseases with an integrated control strategy. As seen in Figure A5-1A, after the fast track countries, with earlier support for pilot-scale integration studies by the Bill and Melinda Gates Foundation (Leading global health organizations, 2006), began to receive support for integrated programs from the NTD Control Program, there was a progressive increase in numbers of persons reached each year beginning with 16 million additional individuals in the first year and reaching 27 and 55 million additional persons in each of the second and third years. (These numbers identify only those persons whose treatment was made possible by support to national programs from the NTD Control Program, cumulatively, more than 98 million people over three years.)

Because a treated person in these integrated programs often receives a drug package comprising more than one medication, the metric treatments provided was developed to record the number of individual drug treatments received by the target population. As indicated in Figure A5-1B, 222 million drug treatments were provided during the first three years of support to the 7 implementing countries by the NTD Control Program. The details of these treatments provided (drugs treatments distributed by the seven participating national programs) are found in Table A5-5.

Quantity/value of drugs delivered

As the national programs supported by NTD Control Program funds increased in number and expanded in scope, the number of donated tablets of drug delivered to the national NTD programs has also increased. Table A5-6 shows that in year 3 alone more than 300 million drug tablets were donated and delivered to the countries receiving NTD Control Program support. The value of these drugs (as defined by each specific donation program) exceeded $575 million dollars in year 3 and has totaled more than $1.4 billion dollars in the program’s first three years.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×
FIGURE A5-1 A. Persons reached (dark blue bars) and treatments provided (light blue bars) during each of the first three years of the Neglected Tropical Disease (NTD) Control Program. B. Cumulative totals of persons reached (red line) and treatments provided (green line) over the first three years of the NTD Control Program.

FIGURE A5-1 A. Persons reached (dark blue bars) and treatments provided (light blue bars) during each of the first three years of the Neglected Tropical Disease (NTD) Control Program. B. Cumulative totals of persons reached (red line) and treatments provided (green line) over the first three years of the NTD Control Program.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

TABLE A5-5 NTD Control Program-Supported Treatments*

Drug

Year 1

Year 2

Year 3

IVM

12,049,342

15,551,089

43,945,901

DEC

0

0

2,111,826

ALB/MBD

13,263,152

20,221,501

51,906,980

PZQ

2,621,978

8,839,281

10,783,581

AZT/TET

8,881,685

13,417,513

19,106,346

Total

36,816,157

58,029,384

127,854,635

* IVM = ivermectin; DEC = diethylcarbamazine; ALB/MBD = albendazole/mebendazole; PZQ = praziquantel; AZT/TET = azithromycin/tetracycline.

Coverage

The sine qua non for success of preventive chemotherapy programs is high rates of drug coverage in the disease-endemic populations. Although varying among countries and for specific programs within each country, programmatic coverage (the percentage of targeted persons who actually received the drug) was generally very good (Table A5-7). These values were based on numbers reported by the drug distributors and their supervisors; and when these reported values were subjected to validation studies in coverage surveys, there was generally good agreement between the reported and surveyed coverage values (data not shown).

For successful elimination and large-scale control programs using the preventive chemotherapy strategy it is also necessary to have broad geographic coverage (the percentage of disease-endemic districts covered by PCT programs). Figure A5-2 records the numbers of districts under treatment of each disease during the first 3 years. It shows that for each of the NTDs, the geographic coverage increased progressively during the three years of NTD Control Program activity. Because the program can only expand (i.e., increase geographic coverage) in areas where mapping is complete, those NTDs where mapping is more advanced (e.g., onchocerciasis where the African Programme for Onchocerciasis Control has been a strong and consistent source of funding for mapping and implementation) have the greatest geographic coverage. By the end of year 3, geographic coverage in the 7 implementing countries had increased for each of the NTDs, ranging from a high of 95% for onchocerciasis to a low of 50% for schistosomiasis. The treatment gap remaining for each disease in the first seven countries and targeted in the upcoming years can be appreciated in Figure A5-2.

Training/national capacity building

At the heart of all PCT programs is the community that is affected by NTDs. Training is designed to empower these communities to treat NTDs within their

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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TABLE A5-6 Number of Tablets of Donated Drugs Provided* to National NTD Programs in Year 3 of the NTD Control Program

Country

ALB

IVM

PZQ

DEC

Zithromax

MBD

Tetracycline (tubes)

Total Tablets§

Burkina Faso

11,862,300

33,913,000

 

 

8,553,600

 

158,642

54,487,542

Ghana

8,753,500

28,633,500

9,724,000

 

53,280

3,615,000

 

50,779,280

Haiti

6,933,600

 

 

22,300,000

 

 

 

29,233,600

Mali

4,976,900

14,494,500

3,000,000

 

8,972,640

 

198,904

31,642,944

Niger

8,465,000

22,128,500

5,498,500

 

11,509,920

 

200,000

47,801,920

Sierra Leone

4,500,000

16,716,850

3,000,000

 

 

3,797,498

 

28,014,348

South Sudan

324,500

9,215,000

3,000,000

 

505,440

 

2,400

13,047,340

Uganda

13,947,700

30,286,000

 

 

5,598,720

7,000,000

 

56,832,420

TOTAL

59,763,500

155,387,350

24,222,500

22,300,000

35,193,600

14,412,498

559,946

311,839,3944s

* Becase donated drugs are provided to the countries in the year prior to their distribution, the number of drugs delivered (e.g., here in year 3) will not equal the number of treatments provided in the same year. Of the provided drugs, essentially all are utilized for treating the NTDs according to the national strategies (indicated in Table A5-2) and with coverage effectiveness approximated in Table A5-7. Any drugs unused in one year are applied to the requirements for treatment in the following year. NTD = neglected tropical disease; ALB = albendazole; IVM = ivermectin; PZQ = praziquantel; DEC = diethylcarbamazine; MBD = mebendazole.

† In addition, 629,616 bottles of pediatric oral suspension (~3 pediatric doses per bottle) were provided.

‡ Tetracycline ointment tubes are used at the rate of 2 tubes per child for a 6-week course of treatment.

§ Does not include bottles of Zithromax pediatric oral suspension or tubes of tetracycline ointment.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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TABLE A5-7 Programmatic Coverage in NTD Control Program Countries*

NTD Control Program

Country

Year 1

Year 2

Year 3

Fast-track countries

Burkina Faso

82-86

79-97

89-100

 

Ghana

78-88

 

71-92

 

Mali

69-100†

58-88

85-89

 

Niger

91-99

73-88

78-93

 

Uganda

 

57-97

62-97

Additional countries

Haiti

 

 

100**

 

Sierra Leone

 

 

82-93

* Presented as a range across the different drug packages used in each country.

† 100% values likely reflect incomplete census counts of the targeted population.

own populations. The NTD Control Program has supported the training of over 220,000 persons during its first three years, with the most being community-based health workers/drug distributors (Figure A5-3). Working at levels from the central ministries to the communities, a cascade of training has been facilitated to support social mobilization, community outreach, supply chain organization and management, and technical implementation of PCT. The fundamental content of training courses and refresher training is similar for most programs, but local needs dictate local training and organizational strategies.

NTD control program expenditures

Analysis of expenditures during the first three years shows that the program fulfilled its mandate that at least 80% of program funds be spent on country program implementation. During the first three years, the program received $40,728,320 in funding. Program expenditures by the end of year 3 were $37.9 ($2.8 million remaining to be spent), with 81.3% expended for country program activities and purchase of essential drugs and with 18.7% used for overall management of the program (its grants, monitoring and evaluation, reporting, documentation of best practices, technical and representational meetings, and advocacy activities).

The breakdown of program expenditures reflects the diverse set of activities that must be supported to enable treatment of persons at the community level. Of the 81.3% of funds going directly for country program activities and supplies (Figure A5-4), the largest portion (28%) was spent on the MDAs themselves, including for social mobilization, drug distribution and personnel supervision.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×
FIGURE A5-2 Number of districts covered by mass drug administration (MDA) treatment during the first three years of the Neglected Tropical Disease (NTD) Control Program in the seven implementing countries (an aggregated total of 526 districts in these countries). For each of the diseases targeted, the bottom bar depicts the number of districts known to be at risk (dark blue bar), the number known not to be at risk (white bar), and those where uncertainty remains because of incomplete mapping (light blue bar). For each of the diseases, the top bar represents the number of districts implementing MDA with the United States Agency for International Development NTD Control Program support (the red bars indicate the number supported in the first year, the orange bar indicates the additional numbers supported in the second year, and the yellow bar indicates the additional supported in the third year). For each disease, the middle bar (green) indicates the total number of districts receiving MDA treatment supported by any funding source. LF = lymphatic filariasis; Oncho = onchocerciasis; STH = soil-transmitted helminths; Schisto = schistosomiasis. *Ghana interrupted transmission of trachoma during year 2 and therefore did not require treatment in year 3.

FIGURE A5-2 Number of districts covered by mass drug administration (MDA) treatment during the first three years of the Neglected Tropical Disease (NTD) Control Program in the seven implementing countries (an aggregated total of 526 districts in these countries). For each of the diseases targeted, the bottom bar depicts the number of districts known to be at risk (dark blue bar), the number known not to be at risk (white bar), and those where uncertainty remains because of incomplete mapping (light blue bar). For each of the diseases, the top bar represents the number of districts implementing MDA with the United States Agency for International Development NTD Control Program support (the red bars indicate the number supported in the first year, the orange bar indicates the additional numbers supported in the second year, and the yellow bar indicates the additional supported in the third year). For each disease, the middle bar (green) indicates the total number of districts receiving MDA treatment supported by any funding source. LF = lymphatic filariasis; Oncho = onchocerciasis; STH = soil-transmitted helminths; Schisto = schistosomiasis. *Ghana interrupted transmission of trachoma during year 2 and therefore did not require treatment in year 3.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×
FIGURE A5-3 Number of workers in training programs supported by the Neglected Tropical Disease Control Program. For each of the first three years of the program, the number of persons receiving different types of training are recorded (black indicates training for central-level Ministry of Health [MOH], orange indicates training for trainers, green indicates training for supervisors, purple indicates training for drug distributers, and blue indicates training for others).

FIGURE A5-3 Number of workers in training programs supported by the Neglected Tropical Disease Control Program. For each of the first three years of the program, the number of persons receiving different types of training are recorded (black indicates training for central-level Ministry of Health [MOH], orange indicates training for trainers, green indicates training for supervisors, purple indicates training for drug distributers, and blue indicates training for others).

Almost equal portions (19-22%) went to drug procurement, capacity building, and country-led management and program monitoring. The remaining 11% was required for the initial mapping to define disease distribution.

Although not yet specifically documented for this program, it should be noted that previous costing studies of programs to control one or more NTDs have shown that in addition to the external support received by disease-endemic countries, the national ministries contribute approximately an equal level of resources in staff salaries and in-kind resources to achieve success (Goldman et al., 2007).

Discussion

The whole concept of program integration is, undeniably, complex and involves, as described by some (Grépin and Reich, 2008), not only the multiple domains of policy, activity and organizational structure, but also multiple levels of integration intensity: coordination, collaboration, and consolidation. To others,

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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FIGURE A5-4 Distribution of expenditures by the Neglected Tropical Disease Control Program during its first three years. Of the $30.82 million expended on country program implementation during the first 3 years, 22% (dark blue) was spent on capacity building, 28% (red) on mass drug administrations (MDAs) (mobilization, distribution, and supervision), 19% (green) on procurement of non-donated drugs, 20% (purple) on country-level management and monitoring, and 11% (light blue) on disease mapping.

FIGURE A5-4 Distribution of expenditures by the Neglected Tropical Disease Control Program during its first three years. Of the $30.82 million expended on country program implementation during the first 3 years, 22% (dark blue) was spent on capacity building, 28% (red) on mass drug administrations (MDAs) (mobilization, distribution, and supervision), 19% (green) on procurement of non-donated drugs, 20% (purple) on country-level management and monitoring, and 11% (light blue) on disease mapping.

however, integration is more an attitude than a formula – a focus on trying always to find ways to carry out multiple activities with the most efficient and cost-effective use of available resources. From either perspective, the arguments for integrating control programs that target the NTDs remain strong: the populations affected are much the same, the strategic approach (preventive chemotherapy) is essentially identical and the drugs for implementing programs are largely donated, readily available, highly safe and effective. Furthermore, opportunities to embed, or integrate NTD control activities within school-health programs and through other platforms of health service delivery offer the promise of greater efficiency, long-term sustainability and national capacity strengthening.

Early pilot studies confirmed the general feasibility of successful integration of NTD control efforts (Garba et al., 2009; Lammie et al., 2006; Richards et al., 2006), but two major questions have remained. 1) Can the integrated NTD control activities effective in pilot studies be successfully expanded to programs at full national scale? 2) Which elements of individual NTD programs are most successfully integrated and how are they best implemented? The findings in this

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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present report address the first question, showing clearly that integration of multiple disease-specific NTD control programs can be successfully implemented at full national scale. Assessment and analyses addressing the second question to define the most effective and cost efficient ways of integrating specific program activities are still underway.

From the data in Figure A5-1, it is clear that funds from the USAID support of the NTD Control Program have been effective in facilitating national programs to support, organize, implement, and monitor integrated, formerly disease-specific programs targeting WHO’s five ‘tool-ready’ NTDs (WHO, 2006). In the 7 study countries receiving support during the program’s first three years, progressive scaling up resulted in an additional 16 million persons receiving appropriate PCT in the first year, 27 million in the second year, and 55 million in the third year, for a cumulative total of more than 98 million persons reached in three years and quite clearly proving the feasibility for integrated NTD programs to be carried out at full national scale.

Introduction of this funding also effected a major qualitative change in national programs targeting the NTDs. Even though in the year prior to the NTD Control Program, up to 33 million people had received treatment of NTDs in disease-specific programs in the target countries, these national programs were constantly challenged to identify funds, most often on a yearly basis, to support their program activities. With the NTD Control Program, a secure funding source was established, so that these national programs not only could achieve broader disease control in their populations but also could undertake proper planning to address their NTD problems more effectively and cost efficiently.

Different from single-disease programs where each person reached equals one treatment given, in the integrated programs each person reached receives a drug ‘package’ usually containing more than one drug. Therefore, the metric ‘treatments delivered’, the number of times a single drug dose is administered, had to be developed to record this programmatic achievement. More than 222 million treatments were provided by national programs during the first three years of the NTD Control Program. It can be predicted with certainty, based on recent studies assessing the impact of disease-specific NTD programs (Chu et al., 2010; Ottesen et al., 2008), that when the program assesses the health benefits from these treatments after 3-5 years of treatment, its impact on personal, societal, and economic well-being will be seen to be enormous.

What even these numbers by themselves fail to impart, however, is an understanding of the magnitude and importance of the public-private partnership between specific pharmaceutical companies and the public sector. It has been the donation of extraordinary amounts of drugs (by GlaxoSmithKline, Johnson & Johnson, Merck & Co., Inc., and Pfizer) that has made possible the successes of these global efforts to control or eliminate the NTDs. In addition, although the drug manufacturers have without question provided most of drugs used in this program, the generic drugs needed for schistosomiasis and STH control and

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

for LF elimination in countries outside of Africa have also been obtained and provided to national programs in the NTD Control Program by a number of governmental and nongovernmental partner organizations, including the Department for International Development (United Kingdon), the United Nations Children’s Fund, University of Notre Dame, WHO, the World Food Program, and World Vision.

In addition to its role in facilitating integrated national MDA programs to provide treatments for their at-risk populations, the NTD Control Program has, of necessity, supported countries in mapping the distribution of infection and developing, in collaboration with WHO, action plans that will enable them to begin or expand implementation of drug delivery in the coming years. Already the empirical experience gained from three years of program activities in the first seven implementing countries has contributed appreciably to the development of new guidelines, norms and regionalized strategies that will facilitate and accelerate program activities in the many countries still needing to begin their integrated NTD control programs.

Major challenges still lie ahead for creating integrated programs targeting NTD control or elimination, not the least of which is the large number of countries requiring these programs. Such a need provides political challenges not just for the national governments which must commit their limited resources and energy to the programs, but also for the bilateral donors to support these national commitments, the drug manufacturers to sustain their long-term pledges, and the various implementing partners necessary to support national programs to carry out their integrated NTD implementation strategies.

In addition to these political challenges, technical challenges also remain, the very first being definition of the geographic scope of each of the NTDs. Mapping the infections must be completed, not just to identify prevalence, but, even more importantly, to define exactly what action must be taken at which level of prevalence and in which geographic area for each of the NTDs. Then, once it is determined what action is required for each of the NTDs, the treatment gaps for specific diseases (e.g., schistosomiasis [Figure A5-2]) must be addressed and the efficiencies of integration (in terms of both cost and impact) identified and quantified so that cost-efficient integrated programs can be established. It does, of course, remain absolutely essential that the specific goals of each individual program being integrated be met, including those program targets that are not MDA-dependent, such as morbidity control (surgical and otherwise) for LF and trachoma, and the water and sanitation goals of the schistosomiasis, STH, and trachoma programs. Sacrificing a program’s goals simply for the sake of integration is totally inappropriate. Thus, the elimination targets for LF and blinding trachoma by 2020 (Gustavsen et al., 2009; Knirsch, 2007) must be kept, and for onchocerciasis in the Americas and selected foci in Africa, the elimination targets must also be respected (Diawara et al., 2009; Sauerbrey, 2008).

In just three years, the NTD Control Program has exceeded program expecta-

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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tions that had been based on previous pilot program activities. This achievement demonstrates not only the feasibility of going to national scale with an integrated approach but also that efficiencies can be achieved through integration. These efficiencies come, in large part, from removing duplication in the operations of specialized disease programs as co-implementation is introduced. They also stem from the ability of the NTD programs to implement PCT through community networks, schools and existing health service delivery platforms, such as child health days. Going forward, even greater gains may accrue as opportunities are pursued strategically to leverage or complement other development-sector efforts, such as water and sanitation improvements, or other health-sector inputs, such as malaria control activities. This type of integration of NTD control within development efforts and on existing health-service delivery platforms holds promise for even greater program efficiency and its positive impact on strengthening national health systems. Although it is clear that not all integrated NTD program activities will have such health system strengthening effects (Utzinger et al., 2009), it is also clear that many of these integrated program activities can very definitely build stronger systems for delivering healthcare and disease prevention to these most underserved populations in NTD-endemic countries (Gyapong et al., 2010).

Although the creation of integrated NTD control programs has brought with it a wide range of political and technical challenges whose importance should not be underestimated (Utzinger et al., 2009), there can be little question but that today’s increased attentiveness and support for NTD control provide important opportunities to advance the health of the world’s neediest populations towards global health equity in ways never before possible. This current experience of the USAID NTD Control Program has proven already that an integrated approach to these diseases is feasible at full national scale. What still remains now is to draw further on the experiences of this young program to define those elements of disease-specific program integration that can yield the greatest benefits, cost-effectively and cost-efficiently. There appears to be no reason why such integrated NTD programs, following general WHO guidelines and the accumulating experience of a growing number of countries, cannot be replicated in all places where they are needed, so long as necessary political commitment and support can be maintained.

Acknowledgements

We thank the Ministries of Health of the participating countries for their absolutely essential programmatic contributions to the success of the first three years of the NTD Control Program; Abdel Direny, Amadou Garba, John Marfoh, Ambrose Onapa, Mustapha Sonnie, Soumana Thienta, Seydou Toure, Fiona Fleming, Emily Heck, Jan Kolaczinski, Happy Kumah, Chad MacArthur, Anna Phillips, and Ann Varghese for their collaborations with these Ministries; and Barbara Kennedy, Allison Campbell, Amy Doherty, Caius Kim, Jennifer Leopold,

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

Alan Fenwick, David Molyneux, Irene Koek, and Richard Green for their roles in developing the program. Disclaimer: This study is made possible by the generous support of the American people through the United States Agency for International Development (USAID). The contents are the responsibility of the authors and do not necessarily reflect the views of USAID or the United States Government.

Financial support

This study and the NTD Control Program were supported by the United States Agency for International Development.

Authors’ addresses

Mary Linehan, Kathryn L. Zoerhoff, and Eric A. Ottesen, Neglected Tropical Disease Control Program, RTI International, 805 15th Street NW, Suite 601, Washington, DC 20005-2207, E-mails: melinehan@rti.org, kzoerhoff@rti.org, eottesen@taskforce.org, and eottesen@rti.org. Christy Hanson, Infectious Disease Division, U.S. Agency for International Development, 1300 Pennsylvania Avenue NW, 3.7.16, Third Floor, Ronald Reagan Building, Washington, DC 20523, E-mail: chanson@usaid.gov. Angela Weaver, U.S. Agency for International Development, 1300 Pennsylvania Avenue NW, 3.07-27, Third Floor, Ronald Reagan Building, Washington, DC 20523, E-mail: aweaver@usaid.gov. Margaret Baker, Department of International Health, School of Nursing and Health Sciences, Georgetown University, 3700 Reservoir Road NW, Washington, DC 20057-1107, E-mail: mcb93@georgetown.edu. Achille Kabore, Neglected Tropical Disease Control Program, Liverpool Associates in Tropical Health, 805 15th Street, NW Suite 601, Washington, DC 20005-2207, E-mail: akabore@pti.org. Dieudonne Sankara, HTM/NTD/PCT/WHO-HQ, World Health Organization, 20 Avenue Appia, CH-1211 Geneva 27, Switzerland, E-mail: sankarad@who.int. Scott Torres, Indoor Residual Spraying for Malaria Program, RTI International, Mayfair Suites, Second Floor, Parklands Road, PO Box 1181-00621, Nairobi, Kenya, E-mail: storres@rti.org.

Reprint requests

Neglected Tropical Disease Control Program, RTI International, 805 15th Street NW, Suite 601, Washington, DC 20005-2207.

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Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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Utzinger J, Raso G, Brooker S, De Savigny D, Tanner M, Ornbjerg N, Singer B, N’goran E, 2009. Schistosomiasis and neglected tropical diseases: towards integrated and sustainable control and a word of caution. Parasitology;136(13):1859-1874.

WHO, 2006. Preventive chemotherapy in human helminthiasis. Coordinated use of antihelminthic drugs in control interventions: a manual for health professionals and programme managers. Available at http://www.who.int/neglected_diseases/preventive_chemotherapy/pct_manual/en/index.html. Accessed October 29, 2009.

A6
NEGLECTED TROPICAL DISEASES (NTDs) SLATED FOR ELIMINATION AND ERADICATION

Donald R. Hopkins

The Carter Center


More than any of our forebears, our current generation has seen an unprecedented confluence of increased awareness about the needs of neglected populations, thanks to modern communications, modern science’s discovery of powerful new tools to help address the terror of neglected diseases, and awesome generosity in cash and in kind to bring those new tools and some old ones to bear on a grand scale, thanks to recent philanthropy and engagement of related industries.

First, some essential definitions: Eradication means reducing the incidence of a disease to zero worldwide, such that further control measures are unnecessary. It means total interruption of transmission. Certification of eradication comes later, after a specified period with no cases and adequate surveillance. Eradication will always be a rare phenomenon. Elimination should mean stopping transmission of a disease in a limited geographic area, although control measures may still be necessary to combat or prevent reintroduction of the disease from somewhere else. It can also mean reducing manifestations of a disease, such as blinding due to trachoma, to zero. Control means reducing incidence or prevalence of a disease, but control measures are still necessary because transmission continues (CDC, 1993).

The World Health Organization (WHO) has established a list of 17 “official” neglected tropical diseases (NTDs): Buruli ulcer, Chagas disease, cysticercosis, dengue, dracunculiasis, echinococcosis, endemic treponematoses, foodborne trematode infections, human African trypanosomiasis, leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, rabies, schistosomiasis, soil-transmitted helminthiases, and trachoma (WHO, 2010a). Grouping these diseases in one package has been a very effective way to bring attention to these often overlooked causes of much misery. The 17 diseases were chosen because of their adverse impact, relative obscurity, and the availability of tools to combat them.

WHO is the only international body that can legally declare a disease eradi-

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

cated or eliminated, and WHO’s governing body, the World Health Assembly (WHA), or one of the Regional Committees of WHO can officially sanction targeting of a disease for eradication or elimination. Of the 17 NTDs, 1 has been targeted for eradication and 8 have been targeted for elimination by WHO or by a WHO Regional Committee (WHO, 2010a):

  • Dracunculiasis (Guinea worm disease) is targeted for eradication.

  • Onchocerciasis (river blindness) is targeted for elimination (interrupting transmission) of the parasite in the Americas.

  • Lymphatic filariasis is targeted for elimination as a public health problem.

  • Trachoma is targeted for elimination of blinding trachoma.

  • Leprosy is targeted for elimination as a public health problem.

  • Chagas disease is targeted for control and elimination in the Americas.

  • Visceral leishmaniasis (kala-azar) is targeted for elimination in Southeast Asia.

  • Yaws (an endemic treponematosis) is targeted for elimination in Southeast Asia.

  • Human African trypanosomiasis is targeted for elimination as a public health problem.

My more complete thoughts on this aspect of today’s topic are spelled out in an article published in Global Health magazine in 2009, urging quantitative targets and more precise use of the term “elimination” (Hopkins, 2009). A Senegalese proverb comes to mind when I think of how “elimination” is often invoked so loosely. According to the proverb, “You can hold a log under water as long as you like; it will not turn into a crocodile.”

I focus here on four of the NTDs that are targeted for eradication or regional elimination: dracunculiasis, onchocerciasis, lymphatic filariasis, and trachoma, in that order. To varying degrees, progress is being made against each disease.

Dracunculiasis

Dracunculiasis is a painful parasitic infection that people get by drinking contaminated water. The 2- to 3-feet-long (1-meter-long) worms emerge directly through the skin a year later, when they are seeking to deposit hundreds of thousands of larvae back into the water to continue the cycle. People are crippled temporarily for weeks, with severe impact on agricultural productivity and school attendance. There is no cure or vaccine, there is no animal reservoir of the human infection, and recovered patients are not immune to future infection. It can be prevented by teaching people to always filter their drinking water, by not allowing people with emerging worms to enter a water source, by applying ABATE® Larvicide, or by providing safe water from borehole wells, for example (Ruiz-Tiben and Hopkins, 2008). In addition to the severe constraint of a one-year-long

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

incubation period, Dracunculus medinensis has a serious reproductive potential that can magnify the penalty for a missed case: documented surprise explosions of 58, 85, and 91 cases occurred in three separate incidents one year after a single undetected imported case contaminated a village water supply.

The Carter Center has led this eradication campaign since 1986, in close coordination with the endemic countries, the Centers for Disease Control and Prevention (CDC), the United Nations Children’s Fund, and WHO. This program has benefited from many very generous donors, including Dupont Coporation, which donated nylon filter material; American Cyanamid (now BASF), which donates ABATE; the Bill & Melinda Gates Foundation and the Conrad N. Hilton Foundation, the U.S. Agency for International Development, and many other bilateral donors, including the federal government of Nigeria; the U.S. Peace Corps volunteers, and other foreign volunteers from Japan, Canada, and a few other nations; and national service volunteers in Ghana and Nigeria.

Tens of thousands of grassroots village volunteers are the bedrock of the Guinea Worm Eradication Program. They were the first to show the utility of village volunteers in Africa as the basis for a surveillance network that provides reliable monthly village-based reports of a disease. They also help educate their neighbors about how to prevent Guinea worm disease, and they distribute cloth filters. In addition to benefiting from the work of former U.S. President Jimmy Carter, the Guinea Worm Eradication Program has benefited from exceptionally strong participation by a former head of state of Ghana, Flt. Lt. Jerry Rawlings, President Amadou Toumani Toure of Mali, and Nigerian former head of state General (Dr.) Yakubu Gowon.

What are the results? As shown in Figure A6-1, as of 2009 we were down to less than 3,200 cases, from an estimated 3.5 million cases in 1986, with 645 endemic villages compared to more than 23,000 villages, and down to 4 countries, all in Africa, instead of 20 countries on two continents. The program will probably report less than 2,000 cases worldwide in 2010, and 1, 2, or 3 of the 4 remaining endemic countries may interrupt or have already interrupted Guinea worm transmission in 2010 (Hopkins et al., 2010; WHO, 2010b).

The final battleground is Southern Sudan, which reported 86 percent of all cases in 2009 and 97 percent so far this year, and which is also approaching a crucial referendum in January 2011 to determine whether it will remain a part of Sudan or separate to form a new nation. Since the Comprehensive Peace Agreement was signed in January 2005 to end the 22-year-long civil war, the Southern Sudan Guinea Worm Eradication Program has made good progress despite the many challenges of large area, little infrastructure, low literacy, and sporadic insecurity that disrupted program operations 32 times in different places in 2009, for example. It has an excellent national program coordinator. We are now aiming to stop transmission in Southern Sudan by the end of 2012, political and security conditions permitting. WHO has certified 187 countries as free of dracunculiasis (Hopkins et al., 2010; WHO, 2010b).

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×
FIGURE A6-1 Number of reported cases of dracunculiasis by year: 1989–2009.

FIGURE A6-1 Number of reported cases of dracunculiasis by year: 1989–2009.

SOURCE: The Carter Center.

The global Guinea Worm Eradication Program (GWEP) has progressed over the past 30 years thanks to five key benchmarks: (1) from the outset it had a clear goal; (2) it identified all of the endemic countries; (3) it established effective village-based, active surveillance; (4) it extended interventions throughout the endemic areas; and (5) it monitors and responds to reports of cases and the status of interventions on a monthly basis. When the GWEP succeeds, it will set a precedent as the first parasitic disease of humans to be eradicated, and as the first disease to be eradicated without a vaccine or curative treatment. The GWEP is important evidence of the potential power of health education and community mobilization. Its legacy in endemic areas will include improved health, more productive agriculture, and better school attendance, as well as experienced health workers and village volunteers and changed attitudes.

Onchocerciasis

Onchocerciasis is a potentially blinding parasitic infection spread by repeated bites of black flies, which breed in fast-flowing rivers, rapids, or dams. Increased construction of dams may be increasing suitable habitat for some vector black flies in Africa. Of an estimated 123 million persons at risk in 37 countries, mostly

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

in Africa, some 37 million persons are actually infected. About a half million people are at risk in six countries in the Americas, and a few thousand in Yemen. The infection may also cause severe itching, but it can be treated or prevented by annual doses of Mectizan® (ivermectin). Because treatment with Mectizan only kills the immature microfilariae and not the adult worms, annual treatments must continue for at least a decade until the adult worms die out. Merck & Company, Inc. set an incredible precedent in 1987, when it announced that it would make its newly discovered Mectizan available to treat populations in poor countries affected by onchocerciasis free of charge, in whatever amounts were needed, for as long as necessary. Three regional programs have waged war on this disease—two in Africa and one in the Americas (Cupp et al., 2010).

In the Americas, the River Blindness Foundation (RBF) launched the Onchocerciasis Elimination Program for the Americas (OEPA) in 1993 in association with CDC, the Pan American Health Organization, and the ministries of health of the six affected countries: Brazil, Colombia, Ecuador, Guatemala, Mexico, and Venezuela. When RBF founder John Moores became a member of the Carter Center’s board of trustees, the RBF was absorbed into the Carter Center in 1996 and the Carter Center became OEPA’s sponsoring body, providing funding and technical support to assist the national programs. The OEPA strategy is for the national programs to provide mass treatment with Mectizan at least twice per year with a minimum coverage of 85 percent of the eligible population. (Since 2003, some highly endemic communities in Mexico have been treated four times per year.) With one exception, the species of black fly vectors in the Americas are not as efficient transmitters of onchocerciasis as the vectors in Africa, which is part of what makes elimination more feasible in the Americas. The current goal is to stop transmission of onchocerciasis in the Americas by 2012 (WHO, 2010c).

The impact achieved so far in the Americas is summarized in Table A6-1. Two of the six countries (Colombia and Ecuador) and 8 of the 13 endemic foci have interrupted transmission, and two other countries (Guatemala and Mexico) are on the verge of stopping transmission. The main remaining challenge is the small binational focus in the Amazon among the Yanomami population that straddles the border between Brazil and Venezuela. In 2009, the Brazilian side of this focus surpassed the 85 percent coverage goal for the eighth consecutive year, while the Venezuela side achieved the coverage goal for the third consecutive year. So far, Merck’s donation accounts for 44 percent of the cumulative expense of this initiative, while the six countries themselves have provided 37 percent, which is a big contrast to the endemic countries in Africa.

The Onchocerciasis Control Program (OCP), which was sponsored by WHO, the World Bank, and others, covered 11 West African countries from 1974 to 2002 and was the first regional African program against onchocerciasis. Using a strategy of vector control that involved aerial spraying of rivers with insecticides to prevent breeding of black flies, to which annual mass drug administration (MDA) of Mectizan was added when that became available in 1987, this program

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

TABLE A6-1 Current Situation of Ocular Morbidity and Transmission of Onchocerciasis Within the Americas Region, 2010

Focus

Has Blindness Been Eliminated?

Has Ocular Morbidity Disappeared?

Transmission Status

Santa Rosa, GU

Yes

Yes

Eliminated in 2010

Lopez de Micay, CO

Yes

Yes

Interrupted in 2007

Escuintla, GU

Yes

Yes

Eliminated in 2010

North Chiapas, MX

Yes

Yes

Eliminated in 2010

Huehuetenango, GU

Yes

Yes

Interrupted in 2008

Oaxaca, MX

Yes

Yes

Interrupted in 2008

Esmeraldas, EC

Yes

Yes

Interrupted in 2010

Northcentral, VZ

Yes

Yes

Interrupted in 2010

South Chiapas, MX

Yes

Yes

Suspected suppressed

Central, GU

Yes

Yes

Suspected suppressed

Northeast, VZ

Yes

No (1.0%)

Ongoing

Amazonas, BR

Yes

No (6.5%)

Ongoing

South, VZ

Yes

No (16.3%)

Ongoing

SOURCE: The Carter Center.

completely eliminated transmission of onchocerciasis in most of the vast area, except for a few areas of Ghana, Côte d’Ivoire, and Sierra Leone. The OCP proved that vector control could eliminate onchocerciasis in much of West Africa, but this approach was expensive, and vector control was not as feasible in forested endemic areas. Fortunately, MDA with Mectizan is feasible in forested endemic areas, and that is what began to happen after Merck’s discovery became available (Cupp et al., 2010).

The African Program for Onchocerciasis Control (APOC), sponsored by WHO and the World Bank with intimate involvement of several international nongovernmental organizations, embraces 19 endemic countries in Africa. It was officially launched in December 1995 and is scheduled to end in 2015. It aims to help constituent countries develop sustainable systems to administer Mectizan annually to at least 65 percent of the eligible population in areas where onchocerciasis was found to be hyperendemic or mesoendemic. This program pioneered the development of “community-directed treatment with ivermectin” (CDTI) using village volunteers selected by the community to distribute Mectizan at locations and times determined by the community. APOC has an ultimate treatment goal (UTG) of about 90 million persons. In 2008, it treated 57 million people, or 63 percent of the total UTG, in 15 of the 19 countries. The prevalence of onchocerciasis was reduced from 46.5 percent in 1995 to 28.5 percent in 2008 (WHO, 2010d). However, studies conducted by the Carter Center in Cameroon and Nigeria have shown that transmission of the parasite persists after 11 years of annual MDA with Mectizan (Katabarwa et al., 2008), that transmission continues in some untreated hypoendemic areas (Katabarwa et al., 2010), and that the

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

annual MDA with Mectizan is not yet sustainable by several endemic countries without continued external support (Rakers et al., 2009).

In 2002, WHO and the Carter Center co-hosted a Conference on the Eradicability of Onchocerciasis, which concluded that onchocerciasis could not be eliminated in Africa with current tools, but could be eliminated in the Americas. The conference recommended continued research and elimination where possible in certain vulnerable foci in Africa and Yemen, and it underscored the potentially game-changing value of a macrofilaricide to kill the adult worms (Carter Center and WHO, 2002). However, APOC has recently shown that annual or twice per year MDA with Mectizan alone for 15–17 years eliminated onchocerciasis transmission in some hyperendemic foci in Mali and Senegal (Diawara et al., 2009). In 2006, Sudan launched an effort to eliminate onchocerciasis in an isolated focus at Abu Hamad north of Khartoum, and in the next year Uganda launched a nationwide onchocerciasis elimination program, both using twice per year MDA with Mectizan at a desired minimal coverage level of 90 percent, and with technical assistance provided by the Carter Center (Ndyomugyenyi et al., 2007). Uganda’s bold decision followed on the heels of its successful elimination of Guinea worm disease, and it had already eliminated onchocerciasis in two foci using focal larviciding and annual MDA with Mectizan. The new offensive by the Government of Uganda takes aim first at 6 more of the 18 endemic foci in the country. Yemen is also conducting MDA twice per year, with the aim of stopping transmission in that relatively minor focus. Unfortunately, Mectizan cannot be used safely in all areas in 10 of the 30 onchocerciasis-endemic African countries where Loa loa infections also occur, because of potentially fatal neurological complications.

So onchocerciasis has been eliminated by using vector control and later MDA with Mectizan in most of the OCP area of West Africa. MDA with Mectizan twice or once per year is eliminating transmission in the Americas, and probably in Yemen and perhaps in some parts of the APOC project area. But some endemic areas of countries included in APOC remain inaccessible because of conflict or co-endemic Loa loa, or because onchocerciasis is only hypo-endemic and thus not eligible for MDA under APOC. So far, annual MDA with Mectizan alone has not yet been shown to stop transmission in many APOC areas that have had MDA with Mectizan for more than a decade (Katabarwa et al., 2008). Sustaining annual MDA with Mectizan in Africa indefinitely is a daunting prospect (Hopkins et al., 2005). We really need a macrofilaricide to speed interruption of onchocerciasis transmission, and we need a strategy for stopping transmission of onchocerciasis in areas where there is Loa loa. Meanwhile, the effort to eliminate lymphatic filariasis is providing some additional help against onchocerciasis.

Lymphatic Filariasis (LF)

Lymphatic filariasis (LF) is a parasitic infection, spread by repeated bites of mosquitoes, that causes extreme swelling of the limbs and genitalia. Of the 1.3

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

billion people at risk in about 81 countries in Africa, Asia, and the Americas, an estimated 120 million are infected. This disfiguring chronic disease can be prevented by annual MDA with diethylcarbamazine (DEC) and albendazole, or in Africa (where DEC causes unacceptable side effects) with Mectizan and albendazole combined. MDA must continue for at least five to six years until the adult worms that cause LF die. Surgery can reduce disabling hydroceles in men, and palliative care can mitigate secondary infections and swelling of some limbs, thereby also improving people’s emotional and social health (Bockarie and Molyneux, 2009).

In a landmark partnership, Merck, which produces Mectizan, and GlaxoSmithKline, which produces albendazole, have both agreed to donate their respective drugs for MDA to help eliminate LF in Africa (Gustavsen et al., 2009). As wonderfully positive secondary effects, both drugs also have deworming qualities against certain intestinal helminths such as Ascaris and Trichuris, with consequent positive tertiary effects on children’s growth, development, nutrition, and cognition. To date, Merck estimates that it has donated 2.5 billion Mectizan tablets for onchocerciasis and LF treatments, with a value of US$3.75 billion (Merck & Company, 2009). GlaxoSmithKline has donated approximately 1.5 billion albendazole treatments to 50 countries, at a value of about $67.5 million. In China, addition of DEC to table salt has been the main tool used to stop LF transmission nationwide.

The International Task Force for Disease Eradication (ITFDE) was the first international body to suggest that LF was potentially eradicable, in a report published in 1993 (CDC, 1993). Soon after WHA adopted the resolution in 1997 calling for LF elimination “as a public health problem,” the Global Alliance to Eliminate Lymphatic Filariasis was established in 2000 to help endemic countries achieve annual MDA with the appropriate drugs, aiming for a minimum coverage of 80 percent. Annual treatments to prevent LF have risen from 10 million in 2000 to 385 million, or 29 percent of the population at risk in 53 of the 71 MDA-eligible countries. Thirteen countries have not yet completed mapping for LF as of 2009 (WHO, 2010e). Elimination of LF is progressing, but it needs to be accelerated in order to reach its goal by 2020.

With Carter Center assistance, two Nigerian states have pioneered integrated health education and MDA for onchcocerciasis, LF, and schistosomiasis since 2000 (Njepuome et al., 2009). I believe APOC and the new war on LF should have joined forces immediately to take advantage of synergies. LF is more widespread than onchocerciasis in Africa and so MDA with Mectizan and albendazole for LF not only covers additional villages where onchocerciasis is hypo-endemic and was not being treated, it also adds a second antihelminthic, albendazole, in all onchocerciasis-endemic areas. It is hoped that combined MDA with Mectizan and albendazole for LF will have an enhanced impact on adult onchocercal parasites. Both drugs are contraindicated for mass drug administration in Loa loa areas, but bednets can be used there instead to block transmission of LF and malaria. Other

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

studies in Nigeria by Blackburn et al. (2006) and other colleagues at CDC and the Carter Center have demonstrated the efficacy of using community-based distributors of Mectizan to also distribute bednets. Thus, scaling up integrated MDA and mass distribution of long-lasting insecticidal nets in Africa by mobilizing CDTI-type volunteers could help control or eliminate malaria, LF, onchocerciasis, and schistosomiasis, with significant collateral impact on soil-transmitted helminths. We have the tools and knowledge to do this now; two states in Nigeria are doing it already.

Before turning to trachoma, I want to highlight another initiative proposed by the ITFDE, which is the elimination of LF and malaria from the island of Hispaniola. This island, comprising the Dominican Republic and Haiti, is the main remaining focus of lymphatic filariasis in the Western Hemisphere and the only Caribbean island that is still endemic for malaria (Figure A6-2). It is a source of exported malaria to neighboring countries, including Jamaica, the Bahamas, and the United States. After a 1.5 year-long collaborative project to combat malaria in two adjacent communities on their shared border, in October 2009 the two countries announced a jointly prepared plan to eliminate malaria from the island by 2020 at an estimated cost of $194 million, while Haiti announced a plan to escalate its existing efforts and also eliminate LF by 2020 at a cost of about $49 million. The Dominican Republic expects to stop transmission of LF in 2010. These are expensive plans, but they are put in perspective by knowledge that a single

FIGURE A6-2 Geographic distribution of malaria and lymphatic filariasis on the island of Hispaniola in 2006.

FIGURE A6-2 Geographic distribution of malaria and lymphatic filariasis on the island of Hispaniola in 2006.

SOURCE: The Carter Center.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

outbreak of malaria in 2004 cost the Dominican Republic an estimated $200 million in lost tourism revenues alone, apart from loss of life and productivity.

Trachoma

Trachoma is a blinding bacterial infection that is spread by contaminated hands, cloths, and flies. An estimated 540 million persons were at risk and 84 million infected in about 57 countries in 1998, when WHA established a target to eliminate blinding trachoma (not all infections, and not the bacterium) by 2020 (WHO, 2010a). The “SAFE Strategy” for combatting trachoma consists of (S) surgery to prevent progression to blindness, (A) antibiotic administration to treat active infections and prevent spread, (F) facial cleanliness, and (E) environmental improvement, including access to clean water and building household latrines to suppress breeding of vector flies in human feces deposited on the ground. The minimal coverage target for antibiotic administration is 80 percent. The quantified goals are to reduce scarring trachoma, or trichiasis, to less than 1 case per 1,000 population and reduce active trachoma below 5 percent in 1–9-year-old children. Further recommendations for assessing these targets were considered recently at the third Global Scientific Meeting on Trachoma that was convened by WHO in July 2010. Like the three other elimination and eradication efforts considered here, the trachoma program also has significant ancillary benefits, due to improved personal hygiene, expanded use of household latrines, and advocacy for clean water. An explosion of latrine building is under way in the Amhara Region of Ethiopia (Ngondi et al., 2010) as a result of the trachoma program, totaling almost 1.8 million latrines since 2002. Wider use of latrines also prevents other diseases besides trachoma.

Pfizer has donated Zithromax® for use in this mass campaign with a cumulative total of 160 million treatments between 1999 and 2009. As of 2009, this program was reaching about 40 million (33 percent) of the 120 million people thought to be at risk, but the full extent of the problem is not clear. At least eight countries, including Morocco and Ghana, have reduced key indices below prevalence thresholds established by WHO. Overall, the number of countries where trachoma is endemic has been reduced from 57 to somewhere between 38 and 49, the estimated population at risk from 540 million to 120 million, and the number of persons with active disease from 84 million to about 41 million between 1998 and 2009 (Mariotti et al., 2009; WHO, 2010a). It is believed that probably only 10 countries contain 75 percent of the problem. Ethiopia, perhaps the most severely affected country, has begun an aggressive campaign in its worst affected region, Amhara, but needs to extend those efforts nationwide.

But much more remains to be done. Figure A6-3 illustrates the principle that it is best to start intervening in the most highly endemic countries first, because they will take longer to be brought under control. The ITFDE, which I chair, reviewed the status of the global effort to eliminate blinding trachoma by 2020

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×
FIGURE A6-3 Prevalence of Trachomatus inflammation-follicular (TF) in children 1–9 years of age in Ghana and Ethiopia, 2007–2008.

FIGURE A6-3 Prevalence of Trachomatus inflammation-follicular (TF) in children 1–9 years of age in Ghana and Ethiopia, 2007–2008.

SOURCE: The Carter Center.

at its meeting in October 2010. It concluded that it is still possible to reach the thresholds defined by WHO by 2020, but doing so will require significant acceleration of interventions, ascertaining the status of the disease in remaining endemic countries quickly, and implementing the full SAFE strategy in all affected areas of the highest endemic countries within the next two or three years.

Table A6-2 summarizes the current status of elimination efforts against these four NTDs. Dracunculiasis is approaching eradication, onchocerciasis will soon be eliminated in the Americas, and LF is scaling up to possibly become the second parasitic disease to be eradicated. We eagerly await results from the current initiatives against onchocerciasis in Africa, and from scaling up the campaign to eliminate blinding trachoma.

These times of exceptional opportunities and inspiring progress are as exciting for us professionals as they are important to improving the human condition. Most NTDs cannot be eradicated or eliminated, but all can and should be much better controlled. The few NTDs that may be vulnerable to elimination or eradication should be pursued ruthlessly.

More than 2,000 years ago, St. Paul reminded his contemporaries that they were surrounded by a cloud of witnesses as they ran the races (of life) before

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

TABLE A6-2 Four NTDs Slated for Eradication or “Elimination”

Disease Program

Dracunculiasis

Onchocerciasis

Lymphatic Filariasis

Trachoma

OEPA

APOC

Goal

Eradication 2009

Elimination (interrupt transmission) 2012

Control (public health problem) 2015

Elimination (public health problem) 2020

Elimination (blinding trachoma) 2020 (TF <5% in 1–9 y/o)

Endemic Countries Known?

Yes

Yes

Yes

Mostly

Uncertain

Status of Surveillance

Very good

Excellent

Good

Incomplete

Incomplete

Coverage Target for Intervention

100%

>85% × 2

65%

80%

80%

Extent of Intervention

98% filters (2009)

93% (2009) (0.626 m/0.672 m)

63% (2008) (57 m/90 m)

29% (2009) (385 m/1.333 b)

33% (2009) (40 m/120 m)

Monitor Disease/Intervention

Monthly

Monthly

Annually

Annually

No

SOURCE: The Carter Center.

them. And so are we. We should be mindful of what our own witnesses are seeing, and perhaps, of what they will say when we meet them.

Acknowledgments

The author wishes to thank Ms. Shandal Sullivan for assistance in preparing this manuscript. He also acknowledges the work of Drs. Ernesto Ruiz-Tiben, Frank Richards, and Paul Emerson, all from the Carter Center, which contributed to some of the content of this paper.

References

Blackburn, B. G., A. Eigege, H. Gotau, et al. 2006. Successful integration of insecticide-treated bed net distribution with mass drug administration in Central Nigeria. American Journal of Tropical Medicine and Hygiene 75(4):650–655.

Bockarie, M. J., and D. H. Molyneux. 2009. The end of lymphatic filariasis? British Medical Journal 338:b1686.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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Carter Center and the World Health Organization. 2002. The final report of the Conference on the Eradicability of Onchocerciasis. Atlanta, GA: The Carter Center.

CDC (Centers for Disease Control and Prevention). 1993. Recommendations and reports: Recommendations of the International Task Force for Disease Eradication. Morbidity and Mortality Weekly Report 42:RR–16.

Cupp, E. W., M. Sauerbrey, and F. Richards. 2010. Elimination of human onchocerciasis: History of progress and current feasibility using ivermectin (Mectizan®) monotherapy. Acta Tropica.

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Hopkins, D. R. 2009. The allure of eradication. Global Health Magazine Summer (3):14–17.

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Hopkins, D. R., E. Ruiz-Tiben, M. L. Eberhard, and S. L. Roy. 2010. Progress toward global eradication of dracunculiasis, January 2009–June 2010. Morbidity and Mortality Weekly Report 59(38):1239–1242.

Katabarwa, M. N., A. Eyamba, P. Habomugisha, et al. 2008. After a decade of annual dose mass ivermectin treatment in Cameroon and Uganda, onchocerciasis transmission continues. Tropical Medicine and International Health 13(9):1196–1203.

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Mariotti, S., D. Pascolini, and J. Rose-Nussbaumer. 2009. Trachoma: Global magnitude of a preventable cause of blindness. British Journal of Ophthalmology 93:563–568.

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Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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WHO. 2010c. Report from the 2009 InterAmerican Conference on Onchocerciasis: Progress towards eliminating river blindness in the region of the Americas. Weekly Epidemiological Record 85(33):321–328.

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A7
THE NEGLECTED TROPICAL DISEASES AND THE NEGLECTED INFECTIONS OF POVERTY: OVERVIEW OF THEIR COMMON FEATURES, GLOBAL DISEASE BURDEN AND DISTRIBUTION, NEW CONTROL TOOLS, AND PROSPECTS FOR DISEASE ELIMINATION

Peter J. Hotez6

George Washington University and Sabin Vaccine Institute

Introducing the NTDs and NIoPs

The neglected tropical diseases (NTDs) represent a group of more than a dozen major chronic infectious diseases, most of them parasitic infections, with high endemicity in the developing countries of Africa, Asia, and the Americas. The conceptual framework of the NTDs was formulated in the years following the 2000 launch of the Millennium Declaration (Hotez, 2006, 2008a, 2011; Hotez et al., 2006a, 2007; Molyneux et al., 2005). Both the Millennium Declaration and its eight Millennium Development Goals (MDGs) for sustainable poverty reduction were instrumental in shaping global health policy over the next decade, and they provided a platform and basis for large-scale donor support from both public and private sources. Indeed, MDG 6, “to combat AIDS, malaria, and other diseases,” helped to galvanize a new awareness for the impact of HIV/AIDS, malaria, and to some extent tuberculosis and stimulated the establishment of the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM), the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR), and the U.S. President’s Malaria Initiative (Hotez, 2011), in addition to increased research and development support from the National Institutes of Health and the Bill & Melinda Gates Foundation, among others. A new generation of global health celebrities also actively helped to advocate for these important new measures (Hotez, 2008a).

Unfortunately, the excitement generated by the activities outlined above left behind the third and almost forgotten component of MDG 6, namely “the other diseases.” In response, a group of concerned scientists and public health experts

6

Corresponding Email: PHotez@gwu.edu or peter.hotez@sabin.org.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

committed to the study of parasitic helminth and protozoan infections began meeting under the auspices of the World Health Organization (WHO) to discuss how global efforts to control these conditions could be scaled and expanded along the lines of PEPFAR and GFATM (Fenwick et al., 2005; Molyneux et al., 2005). A key basis of these discussions involved several decades of experience with programs of mass drug administration to control or eliminate some of the most widespread parasitic helminth infections, especially lymphatic filariasis (LF), onchocerciasis, and to some extent schistosomiasis, in addition to a global campaign to eradicate dracunculiasis (Molyneux, 2004). Most of these interventions relied on global cooperation between WHO and key public–private partnerships and were backed by World Health Assembly resolutions (Brady et al., 2006; Hotez, 2009a; Hotez et al., 2006a, 2006b, 2007; WHO, 2010). From these discussions an informal consensus was created that there are 13 major conditions, which could be targeted for mass drug administration or other large-scale interventions (Hotez et al., 2006b, 2007) (Table A7-1). Provided annually and over a period of several consecutive years, mass drug administration could ultimately lead to the elimination of LF, onchocerciasis, leprosy, and possibly trachoma as public health problems; whereas for schistosomiasis and the three major soil-transmitted helminth infections—ascariasis, trichuriasis, and hookworm infection—annual mass drug administration would lead to important reductions in childhood morbidity (Fenwick et al., 2005; Molyneux, 2004; Molyneux et al., 2005). Moreover, based on the recognition that there is widespread geographic overlap among seven of the NTDs (ascariasis, trichuriasis, hookworm infection, schistosomiasis, LF, onchocerciasis, and trachoma), especially in sub-Saharan Africa, it was possible to target these conditions simultaneously by combining the drugs in an integrated “rapid-impact package” (Hotez et al., 2006a; Molyneux et al., 2005), so named because the drugs can be easily and quickly deployed by a contingent of community drug distributors and would result in rapid reductions in disabilities, improvement in well-being, and ultimately interruption in disease transmission for LF, onchocerciasis, and trachoma (Hotez et al., 2007).

In 2005 and 2006, the first peer-reviewed papers using the term “neglected tropical diseases” as a medical subject heading appeared in PubMed and other scientific literature databases (Brady et al., 2006; Hotez et al., 2006a, 2006b; Lammie et al., 2006; Molyneux et al., 2005; Utzinger and de Savigny, 2006). These publications also coincided with the establishment of a new Department of Neglected Tropical Diseases at WHO (http://www.who.int/neglected_diseases/en/) and, shortly thereafter, the open-access journal PLoS Neglected Tropical Diseases (http://www.plosntds.org). A key emphasis of the original list of 13 NTDs was that they exhibited a number of common clinical, epidemiological, and historical features suggesting that the NTDs could be treated as a cohesive group of infections. It was determined that according to some estimates the NTDs exhibited a global burden of disease that was roughly equivalent to that of any of the “big three diseases” targeted by the GFATM (Hotez et al., 2006a, 2007), and

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

TABLE A7-1 The Neglected Tropical Diseases

The 13 NTDs from Hotez et al. (2006b, 2007)a

Approximate Global Prevalence (Hotez et al., 2007, 2009b)

The 17 NTDs from WHO (2010a

Helminth Infections

 

Helminth Infections

Soil-transmitted helminth infections:

ascariasis, trichuriasis, hookworm

Schistosomiasis

Lymphatic filariasis

Onchocerciasis

Dracunculiasis

807 million (ascariasis)

604 million (trchuriasis)

576 million (hookworm)

Soil-transmitted helminth infections:

ascariasis, trichuriasis, hookworm

Schistosomiasis

Lymphatic filariasis

Onchocerciasis

Dracunculiasis

Foodborne trematodiases

Cystic echinococcosis

Cysticercosis

207 million

120 million

37 million

<0.01 million

20–40 million

ND

ND

Protozoan Infections

 

Protozoan Infections

Leishmaniasis

Chagas disease

Human African

trypanosomiasis

12 million

8–9 million

<0.01 million

Leishmaniasis

Chagas disease

Human African trypanosomiasis

Bacterial Infections

 

Bacterial Infections

Trachoma

Leprosy

Buruli ulcer

84 million

0.4 million

<0.01 million

ND

Trachoma

Leprosy

Buruli ulcer

Endemic syphilis (treponematoses)

 

 

Viral Infections

 

50 million

Dengue and other arboviral diseases

 

0.05 million

Rabies

NOTE: ND, no data.

aThe list of 13 NTDs from Hotez et al. (2006b, 2007) treats each of the soil-transmitted helminth infections as a separate NTD, whereas the WHO list of 17 combines the three soil-transmitted helminth infections as a single entity.

global efforts could be expanded in order to control or eliminate them through large-scale interventions (Hotez, 2008a, 2011; Hotez et al., 2006a, 2007; Lammie et al., 2006; Molyneux et al., 2005; Utzinger and de Savigny, 2006). Moreover, the concept of the NTDs became critical for purposes of global advocacy and for explaining to health policy makers (and ultimately donors) the opportunity for tackling the NTDs with the same urgency as for HIV/AIDS, tuberculosis, and malaria (Hotez, 2008a).

The major distinguishing features of the 13 NTDs were summarized previ-

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

ously (Hotez, 2008a, 2010a; Hotez et al., 2006a, 2007, 2009b) and include the following elements:

  • The 13 NTDs represent the most common infections of people living in extreme poverty in sub-Saharan Africa, Asia, and Latin America and the Caribbean.

  • They disproportionately affect the “bottom billion,” which refers to the approximately 1.4 billion people who live below the World Bank poverty figure of US$1.25 per day.

  • Among the bottom billion, the NTDs result in chronic infections lasting years or even decades.

  • The NTDs produce chronic disability that results in impaired child growth and intellectual and cognitive development, impaired pregnancy outcomes, and decreased worker productivity.

  • Through these mechanisms, the NTDs adversely affect not only health but also childhood education and ultimately economic productivity; the NTDs represent an underlying reason why the bottom billion cannot escape poverty.

  • Many of the NTDs also cause blindness and disfigurement that are psychologically devastating and result in social stigma.

  • This high level of morbidity, economic impairment, and stigma does not necessarily translate into large numbers of deaths; overall, the NTDs cause high-morbidity but low-mortality conditions.

  • In contrast to emerging infections such as HIV/AIDS, SARS, and avian influenza, there is a “nonemerging” character about the NTDs. Instead, the NTDs have afflicted humankind for centuries and there are accurate descriptions of some of the NTDs in ancient texts.

In its first report on NTDs published in 2010, WHO listed several additional features (WHO, 2010). In this new document, WHO expands its list of NTDs to also include food-borne trematodiases, cystic echinococcosis, cysticercosis, endemic syphilis and other treponematoses, and selected viral infections, including dengue and other arboviral infections and rabies. In all, WHO considers a total of 17 NTDs by treating the three soil-transmitted helminth infections as a single entity (WHO, 2010). Among the common features that WHO lists for these 17 conditions are the observations that (1) the NTDs are a proxy for poverty and disadvantage; (2) they affect populations with low visibility and little political voice; (3) they do not travel widely; (4) they cause stigma and discrimination, especially of girls and women, and have an important impact on morbidity and mortality; (5) they are relatively neglected by research; and (6) they can be controlled, prevented, and possibly eliminated using effective and feasible solutions (WHO, 2010). Listed in Table A7-2 are diseases that also meet the NTD criteria listed above, but either because they are much less common than the ones in Table A7-1

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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TABLE A7-2 On the Outside Looking In: NTDs of Global Importance Not Typically Found on Lists of Diseases

Helminth Infections

Bacterial Infections

Enterobiasis

Loiasis

Strongyloidiasis

Toxocariasis

Trichinellosis

Bartonellosis

Bovine tuberculosis

Brucellosis

Cholera

Enteric pathogens: Shigella, Salmonella, Escherichia

Leptospirosis

Relapsing fever

Protozoan Infections

Amoebiasis

Cryptosporidiosis

Giardiasis

Toxoplasmosis

Trichomoniasis

Vivax malaria

Fungal Infections

Mycetoma

Paracoccidiomycosis

 

Ectoparasitic Infections

Viral Infections

Myiasis

Scabies

Tungiasis

Viral hemorrhagic fevers

NOTE: Information about some of these diseases can be found at http://www.plosntds.org/static/scope.action.

or because there are insufficient data about their prevalence and intensity, these NTDs have not been included on conventional lists of the major NTDs. Most of these conditions, however, are considered for review by PLoS Neglected Tropical Diseases (http://www.plosntds.org/static/scope.action).

Another important feature about the NTDs is their disproportionate impact on selected populations, especially girls and women (including pregnant women) in part because of their effects on female reproductive health and their ability to exacerbate anemia and promote HIV/AIDS susceptibility (see below; Hotez, 2009b, 2011). In addition, the NTDs disproportionately affect African populations and African Americans who are descendents of the Atlantic slave trade (Hotez, 2009c; Hotez and Kamath, 2009; Lammie et al., 2007); indigenous populations (Hotez, 2010f; WHO, 2010); and populations living under conditions of conflict and postconflict (Beyrer et al., 2007; Hotez and Thompson, 2009).

Finally, there exists a group of infections that are closely related to the NTDs but, because they occur among impoverished people living in the midst of great wealth in the United States, Canada, and Europe, they are referred to as the neglected infections of poverty (NIoPs; see Table A7-3) (Hotez, 2008b, 2009c, 2010f). In the United States, the NIoPs tend to cluster in areas of extreme poverty, such as the Mississippi Delta and post-Katrina Louisiana, the border with Mexico, Appalachia, inner cities, and selected tribal lands. In such areas, the NIoPs disproportionately affect under-represented minorities living in poverty, including African Americans, Hispanics, and Native Americans (Hotez, 2008b), with the

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

TABLE A7-3 Neglected Infections Amid Wealth: Major Neglected Infections of Poverty in the United States and Europe

United States of America

Europe

Helminth Infections

Helminth Infections

Soil-transmitted helminth infections: ascariasis, enterobiasis, trichuriasis, strongyloidiasis

Toxocariasis

Cysticercosis

Soil-transmitted helminth infections: ascariasis, enterobiasis, trichuriasis, strongyloidiasis

Toxocariasis

Trichinellosis

Protozoan Infections

Protozoan Infections

Chagas disease

Cutaneous leishmaniasis

Cryptosporidiosis

Giardiasis

Toxoplasmosis

Trichomoniasis

Chagas disease

Visceral leishmaniasis

Cryptosporidiosis

Giardiasis

Toxoplasmosis

Trichomoniasis

Bacterial and Viral Infections

Bacterial and Viral Infections

Congenital CMV

Haemophilus influenzae type A

Dengue fever

Brucellosis

Leptospirosis

Nondengue arboviral infections

major NIoPs sometimes referred to as “the 3Cs and the 3Ts”—Chagas disease, cysticercosis, congenital cytomegalovirus infection, toxocariasis, toxoplasmosis, and trichomoniasis. In addition, dengue fever has emerged as an important NIoP in the United States (Hotez, 2008b). Thus, three of the NIoPs are also NTDs listed in Table A7-1. Recently, Congressman Hank Johnson. Jr., of Georgia introduced legislation known as the Neglected Infections of Impoverished Americans Act of 2010 (H.R. 5986), which calls on the U.S. Department of Health and Human Services to collect additional information about these important yet neglected conditions.

Global Disease Burden

The NTDs are considered high-morbidity but low-mortality infections. Estimates for the number of deaths that result from the 13 NTDs range from 146,000 (Hotez et al., 2006b) to 534,000 (Hotez et al., 2006a) annually. On the basis of deaths alone and in terms of their attention by global health policy makers, the NTDs cannot compete with HIV/AIDS, tuberculosis, or malaria, each of which results in 1 million deaths or more annually. Instead, the adverse health impact of the NTDs is better understood in terms of disability-adjusted life-years (DALYs), that is, the number of healthy life-years lost from premature death or disability. It is the chronic disabling features of the NTDs that provide a more complete

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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picture of their global health impact. Estimates of the DALYs lost that result from the NTDs range from approximately 20 million DALYs (Hotez et al., 2006b), which would place the NTDs among the top 20 global health conditions, all the way to almost 57 million DALYs (Hotez et al., 2006a, 2007), which would place the NTDs on par with any of the big three conditions. The basis for this wide range in DALY estimates reflects a number of factors, but primarily there is an ongoing scientific debate on whether to incorporate the chronic morbidities associated with long-standing anemia, malnutrition, inflammation, and pain that result from the very high prevalence of soil-transmitted helminth infections and schistosomiasis (King and Dangerfield-Cha, 2008; King et al., 2005).

Still another important feature of the NTD global disease burden is the observation, especially in sub-Saharan Africa, that these conditions geographically overlap with HIV/AIDS and malaria and may affect the susceptibility or clinical progression of these two killer diseases (Hotez et al., 2006a). For example, in the case of malaria there is a high degree of geographic overlap with hookworm infection (Brooker et al., 2006), with evidence to show that co-infections of malaria and hookworm result in severe anemia (Brooker et al., 2007; Hotez and Molyneux, 2008). Similarly, urinary tract schistosomiasis, which occurs in more than 100 million people in sub-Saharan Africa (Van der werf et al., 2003), commonly results in female genital schistosomiasis that is associated with a threefold increased susceptibility to HIV/AIDS (Hotez et al., 2009a; Kjetland et al., 2006). Thus, the NTDs have important collateral effects on the AIDS and malaria epidemics in Africa (Hotez and Molyneux, 2008; Hotez et al., 2006a).

The Geography of the NTDs

The NTDs and NIoPs occur in the setting of extreme poverty, especially in sub-Saharan Africa, South Asia, Southeast Asia, and in tropical regions of the Americas (Hotez, 2011; Hotez et al., 2009b). Sub-Saharan Africa is estimated to account for approximately one-third of the world’s soil-transmitted helminth infections, most of the world’s cases of schistosomiasis and onchocerciasis, and all of the world’s cases of dracunculiasis and human African trypanosomiasis (Hotez and Kamath, 2009). In many areas of sub-Saharan Africa it is not unusual to find seven or more NTDs in one area—the three major soil-transmitted helminth infections, schistosomiasis, LF, onchocerciasis, and trachoma (Molyneux et al., 2005). Latin America and the Caribbean region also exhibit high rates of NTDs, especially in Brazil, where these conditions (with the exception of Chagas disease and possibly trachoma) were imported during the 500 years of the Middle Passage of the African slave trade (Hotez, 2011; Hotez et al., 2008; Lammie et al., 2007). Southeast Asia is also responsible for one-third of the cases of soil-transmitted helminth infections and almost all of the food-borne trematodiases, in addition to high rates of dengue and other arbovirus infections (Hotez, 2011; Hotez and Ehrenberg, 2010). There are no published studies about the overall

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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prevalence of NTDs in central Asia, but in India, Bangladesh, and Nepal it is believed the rates of these infections (especially LF and the soil-transmitted helminth infections) are extremely high (Hotez, 2011). There are approximately 10 million cases of NIoPs in the United States and an unknown number in Europe and Australia (Hotez, 2008b, 2009c).

There are also a number of interesting geopolitical features about the NTDs (Hotez, 2010b). Among them is the finding that high rates of infection occur in conflict zones (Hotez and Thompson, 2009) as well as in certain Islamic countries, such as Indonesia, Bangaldesh, Sudan, and the west African countries of Mali, Chad, Niger, and Nigeria (Hotez, 2009d). Overall, up to 40 to 50 percent of the world’s NTDs occur in the nations that comprise the Organisation of the Islamic Conference (Hotez, 2009d). Similarly, another one-third of the world’s NTDs occur in large middle-income countries such as India, China, Pakistan, and Iran, which are also considered nuclear weapons countries (Hotez, 2010c). As shown below, these geopolitical features connect the control of the NTDs with elements of U.S. foreign policy (Hotez, 2010b, 2010c, 2010d, 2010e).

Approaches to Control and Elimination Through Mass Drug Administration

WHO points out that the NTDs can be controlled, prevented, and possibly eliminated using effective and feasible solutions (WHO, 2010). Possibly the most obvious example is the near eradication of dracunculiasis (Guinea worm) through the filtering and treatment of water contaminated with larval-infected copepods, together with case detection and management (Hopkins et al., 2008; Molyneux, 2004; WHO, 2010). Over the next few years it is expected that dracunculiasis would become only the second human infection to ever be eradicated and the first disease eradicated without the requirement of a vaccine. However, in addition to dracunculiasis, there are at least five other NTDs that, through the World Health Assembly or the Pan American Health Organization resolutions, have also been targeted by WHO for elimination as public health problems: LF, onchocerciasis, trachoma, Chagas disease, and leprosy (WHO, 2010). With the exception of Chagas disease (which relies largely on insecticidal spraying and improved housing), these other NTDs would be eliminated primarily through mass drug administration, in which large populations are simultaneously treated with one or two drugs on a once-yearly or twice-yearly basis (LF, onchocerciasis, and blinding trachoma) or through multidrug therapy (leprosy) (Brady et al., 2006; Hotez, 2009a; Lammie et al., 2006; Molyneux, 2004). Over time, this approach would lead to reductions in disease prevalence to the point where transmission of these infections is interrupted (WHO, 2010).

For the most part, mass interventions comprised of population-based drug administration (often together with other allied measures) have been extremely successful in terms of reaching large numbers of affected populations, even in

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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the most remote areas of Africa, Asia, and the Americas, and in achieving control and elimination targets. In part, these successes have occurred because the medicines used in mass drug administration have an excellent safety profile and can be administered to large populations based on community-wide prevalence assessments (Hotez, 2009b; WHO, 2006). Once a threshold prevalence of a particular NTD has been ascertained, WHO has established algorithms for treating large populations regardless of whether it has been determined if any given individual is currently infected (WHO, 2006). This practice obviates the requirement of bringing in trained microscopists or other skilled workers, as well as expensive equipment, into the field. Also of critical importance, the drugs used in mass administration are either being donated by some of the major multinational pharmaceutical companies or they can be purchased as extremely low-cost generics (WHO, 2010). To date, the number of people who have received mass drug administration is one of the more impressive achievements in global public health over the past century (Hotez et al., 2007; Molyneux, 2004). For instance, more than 500 million people, that is, almost one-half of the more than one billion people at risk for LF, have received either diethylcarbamazine citrate or ivermectin (usually coadministered with albendazole; Ottesen et al., 2008), while more than one-half of the world’s people at risk for onchocerciasis have received or are receiving ivermectin (Hotez, 2009a; WHO, 2010). To date, elimination of LF has been achieved in China, Cape Verde, Costa, the Republic of Korea, the Solomon Islands, Suriname, and Trinidad and Tobago (WHO, 2008); onchocerciasis has been eliminated from Mali and Senegal (Diawara et al., 2009); and blinding trachoma has been eliminated from Gambia, Morocco, Iran, Oman, and Mexico (Burton et al., 2010). In addition, leprosy has been eliminated as a public health problem (defined as a prevalence below 1 case per 10,000 populations) in all but 3 of the 122 previously endemic countries (WHO, 2010). The control and elimination programs for these diseases rely on established public–private partnerships that work closely with the disease-endemic countries and WHO (Hotez et al., 2009b).

For other extremely high-prevalence diseases, such as the three major soil-transmitted helminth infections and schistosomiasis, each affecting hundreds of millions of people in low- and middle-income countries, the coverage through mass drug administration has not been nearly as successful (Hotez, 2009a; WHO, 2010). Even though mass drug administration for these conditions has been shown to improve child growth, development, and cognition, currently only about 10 percent of school-aged children in areas affected by soil-transmitted helminth infections receive regular treatments with either albendazole or mebendazole, while fewer than 10 percent of children receive praziquantel for schistosomiasis (Hotez et al., 2010b; WHO, 2010). These helminth infections, but especially hookworm infections, cause important adverse effects in pregnancy and up to one-third of pregnant women in sub-Saharan Africa are affected (Brooker et al., 2008). In order to increase coverage for the seven most common NTDs, includ-

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

ing the three major soil-transmitted helminth infections, schistosomiasis, LF, onchocerciasis, and blinding trachoma (Table A7-4), it was proposed in 2005 to bundle the drugs in mass drug administration for these conditions in a “rapid impact package,” costing as little as US$0.50 per individual (Brady et al., 2006; Hotez, 2009a, 2010a; Hotez et al., 2006a; Lammie et al., 2006; Molyneux et al., 2005; Utzinger and de Savigny, 2006; WHO, 2006). Safety data are now in place to support the coadministration of albendazole, ivermectin, and praziquantel, with studies under way to also examine the addition of azithromycin (Hotez, 2009a).

Today, through support from the U.S. Agency for International Development, national programs of integrated NTD control for the seven most common NTDs in Table A7-4 are under way in the African countries of Burkina Faso, the Democratic Republic of Congo, Ghana, Mali, Niger, Sierra Leone, Southern Sudan, Tanzania, and Uganda, as well as Bangladesh and Nepal in Asia, and Haiti (http://www.neglecteddiseases.gov). In 2010 the U.S. President’s Global Health Initiative established targets to reduce the prevalence of the seven NTDs by 50 percent among 70 percent of affected populations and to contribute to the elimination of onchocerciasis in the Americas by 2016, the elimination of LF globally by 2020, and the elimination of leprosy (http://www.neglecteddiseases.gov). In addition, the British Department for International Development (DFID) is supporting national control programs, as is a Global Network for NTDs, which is currently supporting NTD control in Burundi and Rwanda with additional countries planned through funds raised privately (Hotez, 2010a). In all, there are approximately 56 countries with multiple NTDs that should be targeted for rapid

TABLE A7-4 The Seven Major NTDs Targeted for Integrated Control and Elimination with “Rapid Impact Packages”

Seven Major NTDs Targeted by Rapid Impact

Major Drugs Used

Additional NTDs Targeted by Rapid Impact

Soil-transmitted helminth infections:

ascariasis, trichuriasis, hookworm

Albendazole or mebendazole

Strongyloidiasis

Schistosomiasis

Praziquantel

Taeniasis

Food-borne trematodiases

Lymphatic filariasis

Ivermectin or diethylcarbamazine citrate + albendazole

Strongyloidiasis

Scabies

Onchocerciasis

Ivermectin

Strongyloidiasis

Scabies

Trachoma

Azithromycin

Other bacterial infections

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

impact packages (Hotez et al., 2007, 2008a). However, providing global coverage at this scale will require the participation of wealthy nations beyond the United States and the United Kingdom, including other European nations, countries of the Gulf Cooperation Council, and some of the larger emerging economies such as Brazil, China, and India, which have the capacity to control or eliminate some of their indigenous NTDs (Hotez, 2010e).

There are additional NTDs of great public health importance for which mass drug administration approaches are not immediately relevant but which in some cases could still be controlled or eliminated. The example of dracunculiasis was mentioned earlier; in addition, human African trypanosomiasis rates in West Africa caused by Trypanosoma brucei gambiense have been greatly curtailed by aggressive case identification and treatment and tsetse control, particularly in postconflict countries such as Angola and the Democratic Republic of Congo, and currently Sudan, which suffered some of the worst epidemics in the 1970s, 1980s, and 1990s (Hotez, 2008a; Jannin et al., 2001). Between 1999 and 2008 the number of new reported cases of this infection fell by 62 percent, to approximately 10,000 cases; similarly, the number of new cases of east African trypanosomiasis caused by T. brucei rhodesiense fell by 58 percent to only a few hundred reported reported cases (WHO, 2010). Through insecticide spraying, improved housing, and case detection and treatment, Chagas disease has been eliminated as a public health problem in the Southern Cone countries of Argentina, Brazil, Chile, Paraguay, the Plurinational State of Bolivia, and Uruguay (WHO, 2010), although an estimated 8 to 9 million cases remain in Latin America, with the greatest number of cases in Bolivia. A program to reduce the incidence of visceral leishmaniasis in Bangladesh, India, and Nepal—the three countries with highest disease burden—is under way through a program of early case finding, delivering oral treatment, and vector control (WHO, 2010). Treatments for several of the NIoPs including Chagas disease, cysticercosis, toxocariasis, toxoplasmosis, and trichomoniasis, are available even if the treatments are underused because of their overall neglect by the public health community in the United States (Hotez, 2008b).

Collateral Benefits: Malaria, HIV/AIDS, and Other Co-Infections

Beyond the seven NTDs and leprosy, mass drug administration is expected to have a number of other important collateral effects. For instance, the drugs that comprise the rapid impact package would also target additional high-prevalence NTDs (listed in Tables A7-1 and A7-2) such as strongyloidiasis; taeniasis; the food-borne trematodiases clonorchiasis, opisthorchiasis, and paragonimiasis; and scabies (Hotez et al., 2006a). A recent study conducted in Ethiopia also showed that once-yearly azithromycin used for mass drug administration to combat blinding trachoma resulted in dramatic overall reductions in child mortality (Porco et al., 2009), possibly as a result of reducing bacterial colonization that would otherwise lead to other respiratory or gastrointestinal bacterial infections. It is also

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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possible that by reducing anemia from hookworm and schistosomiasis the rapid impact package could indirectly reduce severe anemia in sub-Saharan Africa that results from malaria co-infections (Brooker et al., 2007).

Two additional studies suggest that NTD control is of potentially great importance on the HIV/AIDS pandemic, but especially in sub-Saharan Africa. To date, three randomized controlled trials evaluating the effects of deworming on HIV/AIDS progression showed a benefit in reducing plasma viral loads and/or increasing CD4 counts (Walson et al., 2009), while female genital schistosomiasis was shown to result in a threefold increase in horizontal transmission of HIV/AIDS (Kjetland et al., 2006). These studies suggest that widespread administration of praziquantel or the rapid impact package could represent an inexpensive and highly cost-effective intervention to complement widespread AIDS control measures currently being implemented by the GFATM or PEPFAR (Hotez et al., 2006a). In the coming years, an extensive program of operational research and implementation science will be required to maximize use of the rapid impact package and how it can interface with global malaria and HIV/AIDS control efforts.

Access to Innovation

For almost all of the NTDs, there is a desperate need for research and development leading new innovations for control, including improved diagnostics, medicines, or vaccines (Hotez and Pecoul, 2010). The older concept of “tool-ready” versus “tool-deficient” NTDs has been discredited as most of the tool-ready diseases currently targeted by the rapid impact package still require a new generation of improved anthelminthic drugs and vaccines, while tool-deficient diseases such as human African trypanosomiasis, Chagas disease, and leishmaniasis can still be controlled or even eliminated in some areas using currently available insecticides and medicines (Hotez and Pecoul, 2010). Among the diseases now targeted by the rapid impact package, high rates of mebendazole drug failure have been reported for hookworm infection, with a recent meta-analysis reporting only a 15 percent cure rate for single-dose mebendazole (Hotez et al., 2010a; Keiser and Utzinger, 2008). Similarly, single-dose albendazole exhibits a low cure rate for trichuriasis (Keiser and Utzinger, 2008), while high rates of post-treatment re-infection have been described for all of the soil-transmitted helminth infections and schistosomiasis (Hotez et al., 2010a; Keiser and Utzinger, 2008). Several potential backup anthelminthic drugs previously developed for veterinary purposes could potentially be transitioned into human medicines, and there is a need to establish a product development public–private partnership (PD-PPP) for this purpose (Hotez and Pecoul, 2010). Alternatively, the Sabin Vaccine Institute is a PD-PPP developing new vaccines to prevent hookworm infection and schistosomiasis (Hotez et al., 2010a). Such vaccines are sometimes referred to as the “antipoverty vaccines” because of their potential economic impact as well as their

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

effects on health (Hotez and Ferris, 2006). There is also a need for a new macro-filaricide for onchocerciasis to reduce the number of years for which ivermectin treatments must be provided annually (Hoerauf, 2008). The drug moxidectin is a potential macrofilaricide under development jointly between WHO-TDR (the Special Programme for Research and Training on Tropical Diseases) and Pfizer, as are antimicrobial drugs that target bacterial endosymbionts and also exhibit a macrofilaricidal effect (Hoerauf, 2008; Hotez and Pecoul, 2010). For all seven NTDs targeted for rapid impact packages, there is a pervasive need for new diagnostics (Hotez and Pecoul, 2010).

For human African trypanosomiasis, Chagas disease, and leishmaniasis, there is an urgent need for new and safer drugs to replace the ones now in use, many of which were developed in the early part of the 20th century (Hotez and Pecoul, 2010; McKerrow et al., 2009; Priotto et al., 2009; Yun et al., 2009). Also needed are improved diagnostics, and there is a need for new vaccines, including possibly new therapeutic vaccines for these kinetoplastid diseases (Hotez and Ferris, 2006). Several PD-PPPs are in place for new drugs for kinetoplastid infections, including the Drugs for Neglected Diseases Initiative (DNDi) and the Institute for One World Health (iOWH), while the Infectious Diseases Research Institute (IDRI) is developing a leishmaniasis vaccine, and the Foundation for Innovative Diagnostics (FIND) is investigating new kinetoplastid diagnostics.

For some of the other diseases not yet mentioned, there are also needs to develop new biomarkers to predict the onset of bile duct cancer from the food-borne trematodiases clonorchiasis and opisthorchiasis, in addition to new anticancer vaccines for these helminthiases (Sripa et al., 2010); veterinary transmission blocking vaccines for cysticercosis and echinococcosis (Lightowlers, 2010); and new Buruli ulcer drugs, vaccines, and diagnostics (Hotez and Pecoul, 2010; Portaels et al., 2009). Currently at least five candidate dengue vaccines are under development both by major multinational pharmaceutical companies as well as the International Vaccine Institute (Durbin and Whitehead, 2010). Of interest, today many of the PD-PPPs are partnering with both private- and public-sector manufacturers located in middle-income countries—sometimes referred to as innovative developing countries—such as Brazil, China, Cuba, India, and Indonesia (Morel et al., 2005). For the NIoPs there is an urgent need to develop improved diagnostics, especially for each of the 3C and 3T diseases, and for efforts to accelerate the development of new vaccines combat congenital CMV infection, Chagas disease, and toxoplasmosis (Hotez, 2008b).

Implications for U.S. Foreign Policy

The observation that most of the world’s NTDs occur in countries of geopolitical interest to the Untied States has potential foreign policy implications for the U.S. government (Hotez, 2009d, 2010b, 2010c, 2010d). The human right to live in a world free of NTDs has been pointed out previously (Beyrer et al., 2007;

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

Hotez, 2008a; Hunt, 2006), thereby providing a framework for NTD control as a low-cost yet high-profile U.S. humanitarian intervention (Hotez, 2006). However, the potential for NTDs to actually cause poverty and promote conflicts in the world’s Islamic nations and nuclear weapons states (Hotez and Thompson, 2009) provides added urgency for the United States to intervene today through wide-scale interventions with rapid impact packages in all these nations and, ultimately, all of the 56 affected developing countries (Hotez, 2008, 2010b). Finally, there are important opportunities to look to joint research and development cooperation between the United States and some of the world’s more advanced Islamic countries and NTD-affected nuclear weapons states in order to develop a new generation of antipoverty vaccines, just as the United States and former Soviet Union cooperated on joint polio and smallpox vaccine development during the middle of the 20th century (Hotez, 2010c, 2010d).

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Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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A8
NEGLECTED INFECTIONS OF POVERTY IN THE UNITED STATES OF AMERICA7

Peter J. Hotez8

Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University and Sabin Vaccine Institute, Washington, DC, United States of America


Abstract: In the United States, there is a largely hidden burden of diseases caused by a group of chronic and debilitating parasitic, bacterial, and congenital infections known as the neglected infections of poverty. Like their neglected tropical disease counterparts in developing countries, the neglected infections of poverty in the US disproportionately affect impoverished and under-represented minority populations. The major neglected infections include the helminth infections, toxocariasis, strongyloidiasis, ascariasis, and cysticercosis; the intestinal protozoan infection trichomoniasis; some zoonotic bacterial infections, including leptospirosis; the vector-borne infections Chagas disease, leishmaniasis, trench fever, and dengue fever; and the congenital infections cytomegalovirus (CMV), toxoplasmosis, and syphilis.

7

Reprinted with permission from Hotez, P. J. 2008. Neglected infections of poverty in the United States of America. PLoS Negl Trop Dis 2(6):e256.

8

E-mail: PHotez@gwu.edu or mtmpjh@gwumc.edu.

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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These diseases occur predominantly in people of color living in the Mississippi Delta and elsewhere in the American South, in disadvantaged urban areas, and in the US–Mexico borderlands, as well as in certain immigrant populations and disadvantaged white populations living in Appalachia. Preliminary disease burden estimates of the neglected infections of poverty indicate that tens of thousands, or in some cases, hundreds of thousands of poor Americans harbor these chronic infections, which represent some of the greatest health disparities in the United States. Specific policy recommendations include active surveillance (including newborn screening) to ascertain accurate population-based estimates of disease burden; epidemiological studies to determine the extent of autochthonous transmission of Chagas disease and other infections; mass or targeted treatments; vector control; and research and development for new control tools including improved diagnostics and accelerated development of a vaccine to prevent congenital CMV infection and congenital toxoplasmosis.

Introduction

In the United States of America, the mortality rate resulting from infectious diseases has declined precipitously over the course of the twentieth century (Armstrong et al., 1999), and major scourges such as typhoid fever and malaria are no longer serious public health threats (Humphreys, 2001). However, among the poorest populations living in the US there remains highly prevalent a group of serious parasitic and bacterial diseases such as Chagas disease, cysticercosis, and toxocariasis (Hotez, 2007), which, like the neglected tropical diseases (NTDs), are characterized by their high prevalence, chronic and disabling features, and disproportionate effect on the poor (Hotez, 2007; Hotez et al., 2007). These infections occur outside of tropical regions of Africa, Asia, and Latin America, and I refer to them as neglected infections of poverty, because they not well known to the US public-health community, and they promote poverty because of their impact on child development, pregnancy outcomes, and worker productivity (Hotez and Ferris, 2006). In this review I highlight the largely underappreciated burden of the neglected infections of poverty in the US and make policy recommendations for addressing such health disparities.

The Distressed Regions of Poverty in the United States

Demographers and other social scientists measure poverty in a number of ways (Iceland, 2006; Rector and Johnson, 2004), but since the 1960s, the US Census Bureau has used a set of income thresholds that vary by family size and composition (U.S. Census Bureau, 2007a, 2007b). In 2006, there were 36.5 million Americans living in poverty, and the official US poverty rate was 12.3% (Historical poverty tables, 2007; U.S. Census Bureau, 2007b). However, among

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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under-represented minorities and children, the poverty rate is much higher, particularly in single parent households headed by women (Table A8-1). Poverty in the US is not evenly distributed, but instead it is focally concentrated into several defined geographic regions, each with unique socioeconomic characteristics. Glasmeier has identified six major distressed regions of poverty: Appalachia, the Mississippi Delta, other areas of rural poverty especially in the American South, Native American tribal lands, the borderlands between the United States and Mexico, and highly racially segregated urban areas including mostly black metro areas adjacent to the Great Lakes and in the Northeast (Glasmeier, 2006). Holt has conducted a spatial analysis of the poverty in the United States at the county level and independently identified similar areas of poverty (Figure A8-1) (Holt, 2007).

A robust dataset links poverty to both lower life expectancies from chronic diseases (especially cancer and heart disease) and increased infant and child mortality (Braveman, 2007; Bloche, 2007; Kaplan, 2007; Murray et al., 2005). Partly on this basis, and building on an analysis of mortality by race and ethnicity in 2,077 counties or county clusters, Murray et al. divided the US population into eight groups with different epidemiologic patterns and mortality rates (Murray et al., 2005). Among these eight “Americas” were four socioeconomically disadvantaged groups with substantially higher mortality from chronic diseases: America 4 is defined as poor whites living in Appalachia and the Mississippi Valley; America 5, Native Americans living on reservations in the West; America 7, poor blacks living in the rural South; and America 8, blacks living in high-risk urban environments (Murray et al., 2005).

Using a hybrid of these classifications it is possible to identify groups of individuals based on race, ethnicity, and socioeconomic status that are at particular risk for specific neglected infections of poverty. In this paper I review the prevalence of the major neglected diseases of poverty in the US This analy-

TABLE A8-1 Selected US Census Bureau 2006 Poverty Data

Category

Poverty Rate

Reference

Official poverty rate

12.3%

U.S. Census Bureau (2007b)

Non-Hispanic white

8.2%

U.S. Census Bureau (2007b)

Non-Hispanic black

24.3%

U.S. Census Bureau (2007b)

Hispanic

20.6%

U.S. Census Bureau (2007b)

Children under age 18 y

17.4%

U.S. Census Bureau (2007b)

Black female householder, no husband present, with children under age 18 y

43.6%

Historical poverty tables (2007)

Hispanic female householder, no husband present, with children under age 18 y

42.5%

Historical poverty tables (2007)

doi:10.1371/journal.pntd.0000256.t001

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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FIGURE A8-1 Location of counties that represent spatial clusters in which poverty rates are at least two standard deviations higher than the national mean. Top: Counties south of the Continental Divide. Bottom: Counties north of the Continental Divide.

FIGURE A8-1 Location of counties that represent spatial clusters in which poverty rates are at least two standard deviations higher than the national mean. Top: Counties south of the Continental Divide. Bottom: Counties north of the Continental Divide.

SOURCE: Holt (2007).

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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sis was conducted in January 2008 using the online database PubMed (U.S. National Library of Medicine, 2008) for 1972–2007 with the Medical Subject Headings (MSHs) “neglected diseases”, “poverty”, the specific geographic regions and racial, ethnic, and socioeconomic groups listed above (Glasmeier, 2006; Holt, 2007; Murray et al., 2005), and the specific diseases listed as NTDs on the PLoS Neglected Tropical Diseases journal scope page (PLoS Neglected Tropical Diseases, 2008), as well as major congenital infections associated with impaired child development including cytomegalovirus (CMV) infection, toxoplasmosis, and syphilis. I also reviewed reference lists of identified articles and hand-searched reviews. I report here either previously published estimates of the number of cases of each neglected infection, or I provide a range of estimates based on reported prevalence rates among selected communities multiplied by published estimates of the population at risk having similar socioeconomic, racial, and ethnic demographics (Table A8-2). For some neglected infections, particularly the soil-transmitted helminth infections, no new surveys have been reported since the 1980s. Some of the regional and national prevalence estimates were modified from a chapter in my recently published book on neglected tropical diseases (Hotez, 2008).

Appalachia

The hilly and mountainous region known as Appalachia comprises parts of 13 states (Figure A8-1) (Glasmeier, 2006). Poverty and isolation is particularly severe in Central Appalachia, which includes parts of West Virginia, Eastern Kentucky and Tennessee, and the southwestern tip of Virginia (Glasmeier, 2006). The plight of the poorest people in this region, typically those working in the coal mining industry, was brought to national attention both during the early 1960s when John F. Kennedy made a presidential campaign swing through the region (Mangum et al., 2003) and with the 1962 publication of Michael Harrington’s book, The Other America: Poverty in the United States (Harrington, 1962). In 2000, it was estimated that 169,000 housing units in Appalachia, particularly Central Appalachia, had no indoor plumbing (Glasmeier, 2006). Almost 3% of the region overall lacks complete plumbing, although in some counties plumbing is incomplete in upwards of 25% of the housing units (Glasmeier, 2006).

Ascariasis.

The parasitic worm infection ascariasis is one of the world’s most common neglected tropical diseases (Hotez et al., 2007), and a leading global cause of impaired child development (Bethony et al., 2006). In very young children, high-intensity Ascaris lumbricoides infections also cause intestinal obstruction (Bethony et al., 2006; Blumenthal and Schultz, 1975). During the 1930s, the profound poverty and inadequate sanitation in Appalachia was linked to high rates of

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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TABLE A8-2 Estimated Prevalence of Neglected Infections of Poverty in the US

Neglected Disease Category

Disease

Estimated Number of Cases

Major Regions or Populations at Risk

References

Soil-transmitted helminth infections

Ascariasis

<4 million

Appalachia, American South

Warren (1974)

 

Toxocariasis

1.3-2.8 million

Inner cities, American South, Appalachia

Murray et al. (2005); Sharghi et al. (2000); Wohn et al. 2007)

 

Strongyloidiasis

68,000-100,000

Appalachia, African refugees

Murray et al. (2005); Hotez 2008); Walzer et al. (1982) Centers for Disease Control and Prevention (2002)

 

Trichenollosis

16 (insufficient data)

Arctic Alaska

Centers for Disease Control and Prevention (2007)

Platyhelminth Infections

Cysticercosis

41,400-169,000

US-Mexico borderlands

Hotez (2008); Pew Hispanic Center (2008); DeGiorgio et al. (2005)

 

Schistosomiasis

8,000

African refugees

Franco-Paredes et al. (2007); Posey et al. (2007

 

Echonococcis

Insufficient data

Tribal Lands and Arctic Alaska

__

Protozoan Infections

Giardiasis

2.0-2.5 million

All regions

Mead et al. (1999); Yoder et al. (2007)

 

Trichomoniasis

880,000 (black women)

American South, Inner cities

Murray et al. (2005); Sutton et al. (2007)

 

Cryptosporidiosis

300,000

All regions

Mead et al. (1999)

 

Chagas disease

3,000 to >1 million

US-Mexico borderlands, American South

Glasmeier (2006); Hanford et al. (2007); Leiby et al. (2002); Milei et al. (1992); Tobler et al. (2007)

 

Cyclosporiasis

16,624

All regions

Mead et al. (1999)

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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Neglected Disease Category

Disease

Estimated Number of Cases

Major Regions or Populations at Risk

References

 

Congenital toxoplasmosis

≤4,000 annually

American South, inner cities, US-Mexico borderlands, Arctic Alaska

Jones et al. (2007)

 

Leishmaniasis

Insufficient data

US-Mexico borderlands

__

 

Amebiasis

Insufficient data

US-Mexico borderlands

__

Bacterial Infections

Congenital syphilis

1,528 between 2000 and 2002

American South, Inner cities

Centers for Disease Control and Prevention (2002)

 

Brucellosis

1,554

US-Mexico borderlands

Troy et al. (2005); Mead et al. (1999)

 

Bovine tuberculosis

129 cases between 1994 and 2000

US-Mexico borderlands

LoBue et al. (2003)

 

Leprosy

166

US-Mexico borderlands

Truman et al. (2005)

 

Trench fever

Insufficient data

Inner cities

__

 

Leptospirosis

Insufficient data

Inner cities

__

Viral Infections

Dengue fever

110,000-200,000 new infections annually

US-Mexico borderlands, American South

Glasmeier (2006); Brunkard et al. (2007); Pew Hispanic Center (2008)

 

Congenital CMV

27,002 annually; 6,652 in blacks; 4,196 in Hispanics

American south, Inner cities

Colugnati et al. (2007)

 

Human rabies

2

All regions

Centers for Disease Control and Prevention (2007)

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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ascariasis (Otto and Cort, 1934). For instance, it was noted that among children aged 5–14 y, the prevalence in Breathitt County in Eastern Kentucky was 75%, higher than in many developing countries (Otto and Cort, 1934). During the late 1970s Walzer et al. reported that approximately 14% of schoolchildren in Clay County (Eastern Kentucky) were infected with A. lumbricoides and almost 13% were also infected with the whipworm Trichuris trichiura (Walzer et al., 1982), while other investigators also reported that ascariasis was still highly endemic in the region (Blumenthal, 1977; Dauer et al., 1968; Jones, 1983). Warren previously estimated that four million people are infected with A. lumbricoides in the US (Table A8-2) (Warren, 1974): however, no surveys for ascariasis have since been conducted.

Strongyloidiasis.

Strongyloidiasis, caused by the threadworm Strongyloides stercoralis, is another important soiltransmitted helminth infection, associated with chronic enteritis, impaired child development, eosinophilia, and hyperinfection in immunocompromised hosts (Dada-Adegbola and Bakare, 2004; Milder et al., 1981; Siddiqui and Berk, 2001). The disease is underreported partly because of the difficulty of diagnosing the infection by fecal examination (Kithcne et al., 2000; Siddiqui and Berk, 2001). A review of several studies conducted during the 1960s, 70s, and 80s and determined that the prevalence in Central Appalachia ranged from 0.4% (Charleston, West Virginia) to 4.0% (Harlan County, Kentucky, and Johnson City, Tennessee) (Siddiqui and Berk, 2001). Based on 3,271 fecal examinations in Kentucky, Walzer et al. estimated that the overall prevalence was approximately 1% (Walzer et al., 1982). A high percentage of the patients with strongyloidiasis were found to be older white males, most of whom had underlying chronic illnesses including chronic obstructive pulmonary disease (Berk et al., 1987; Kitchen et al., 2000; Milder et al., 1981; Walzer et al., 1982). These infections may have been acquired in coal mines. Murray et al. determined that 11 million people compose the poor white Appalachians in America 4 (Murray et al., 2005), while the Centers for Disease Control and Prevention (CDC) reported that the population of rural Appalachia is approximately 6.8 million (Centers for Disease Control and Prevention, 2002). Based on Walzer’s prevalence determination of 1%, I estimate there are approximately 68,000 (Hotez, 2008) to 110,000 Appalachians infected with S. stercoralis (Table A8-2).

Mississippi Delta and the American South

Throughout the twentieth century and continuing today, the Mississippi Delta (“the Delta,” composed predominantly of the Delta regions of Mississippi, Louisiana, Arkansas, and Tennessee, but also including the adjacent “boot-heel” of Missouri) and the areas of the former Cotton Belt in the American South, have re-

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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mained among the poorest regions in the nation (Figure A8-1) (Glasmeier, 2006). High rural poverty rates, inadequate housing, and poor health are the hallmarks of poverty in the Delta and adjacent regions (Felix and Stewart, 2005; Glasmeier, 2006). More than one-half of the population is black (McKinnon, 2001), and over one third of the total Delta black population lives in poverty, as does almost one-half of the rural black Delta population (Glasmeier, 2006). Overall, 5.8 million people live in America 7, the poor blacks of the rural American South (Murray et al., 2005).

In the first half of the twentieth century as many as 42% of black schoolchildren in the Delta had splenomegaly indicative of active malaria infection, and almost twice as many blacks died from malaria as whites (Humphreys, 2001). The high rates of malaria among blacks were attributed to exposure to Anopheles mosquitoes as a result of crowding and inadequate housing located next to swampy land, and diminished host resistance because of malnourishment and overwork (Humphreys, 2001). Throughout the American South during the early twentieth century, malaria combined with hookworm infection and pellagra to produce a generation of anemic, weak, and unproductive children and adults (Bleakley, 2007; Hotez, 2008; Humphreys, 2001; Martin and Humphreys, 2006). By the 1960s these infections were no longer endemic in the Delta, but the health status (as measured by cancer and heart disease mortality rates and infant mortality rates) of the eight states that make up the this region still consistently ranks at the bottom among all the United States (Felix and Stewart, 2005). Tuberculosis rates among southern blacks are also considerably higher than whites (Acevedo-Garcia, 2000; Centers for Disease Control and Prevention, 2004; Richardus and Kunst, 2001). Poverty is a major determinant but not the only one (Centers for Disease Control and Prevention, 2004), as incarceration and other involuntary social forces also account for high rates of tuberculosis and some sexually transmitted infections (Centers for Disease Control and Prevention, 2004; Richardus and Kunst, 2001; Thomas, 2006; Thomas and Torrone, 2006). For the blacks living in the Delta and elsewhere in the American South, several parasitic and congenital infections rank among the most important neglected infections of poverty, especially in post-Katrina Louisiana.

Neglected infections in pre- and post-Katrina Louisiana.

Despite the apparent eradication of malaria and hookworm infection from the American South (Hotez, 2008; Humphreys, 2001; Martin, 1972; Martin and Humphreys, 2006), other important parasitic infections remain, particularly in Louisiana. Even before Hurricane Katrina, the Delta region of Louisiana exhibited some of the highest poverty rates in the nation—in 2000, approximately 36% of blacks lived below the poverty level in this area (Glasmeier, 2006). It was previously determined that, outside of Appalachia, Louisiana exhibited some of the highest rates of ascariasis in the US [24], and during the 1970s and

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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1980s considerable numbers of the rural residents of Louisiana and elsewhere in the American South were infected (Adams and Perkin, 1985; Blumenthal and Schultz, 1975, 1976; Miller et al., 1978; Morgan et al., 1972; Schultz, 1982). Some children exhibited parasite intensities high enough to produce acute intestinal obstruction (Blumenthal, 1977; Blumenthal and Schultz, 1975). Although A. lumbricoides infections were highest in rural Louisiana, they were also prevalent among kindergarten children living in New Orleans (Hubbard et al., 1974). In addition, during the 1970s and 1980s Louisiana children were at risk for infection with the dog roundworm, Toxocara canis (Smith et al., 1984), and up to 30% of rural black children, mostly in the South, were seropositive for this infection (toxocariasis will be discussed in the section on inner cities) (Herrmann et al., 1985). Unfortunately, no surveys for either ascariasis or toxocariasis in Louisiana have been published since the 1980s.

Following the devastation of Hurricane Katrina in 2005, prolonged flooding combined with poverty to create conditions that could promote the emergence of additional neglected infections, including vector-borne viral diseases such as dengue fever (Gubler et al., 2001; Moore et al., 1988; Morens and Fauci, 2008) and Chagas disease (Diaz, 2007; Dorn et al., 2007). Chagas disease is of particular concern, because of the noted rise in domestic triatomines, especially Triatoma sanguisuga, which transmits the causative American trypanosome Trypanosoma cruzi (Diaz, 2007; Dorn et al., 2007). In Louisiana, almost 30% of the armadillos and 38% of the opossums are infected with T. cruzi, and a case of Chagas disease was recently reported in post-Katrina New Orleans (Dorn et al., 2007). Therefore, many of the requirements for autochthonous Chagas disease transmission are in place in Louisiana (Diaz, 2007), with an established case already present. In the coming decade, global warming and increased flooding in the region could combine to promote dengue and Chagas disease epidemics among the poor in Louisiana (Gubler et al., 2001).

The feminization of poverty.

The term ‘‘feminization of poverty’’ refers to the observation that in the US and elsewhere women often have fewer economic resources than do men and are more likely to be heads of single-parent families (Starrels et al., 1994). Poverty is particularly feminized among black women (Starrels et al., 1994). As shown in Table A8-1, almost one-half of black female heads of single-parent households live below the poverty level, and black mothers are twice as likely to have premature or low birth weight infants or to have infants that die in infancy than white mothers (Braveman, 2007). Congenital infections, typically the result of primary cytomegalovirus (CMV) infection, toxoplasmosis, or syphilis during pregnancy, are important factors underlying these high rates of poor birth outcome. These congenital infections cause devastating long-term neurological

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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dysfunction including cognitive impairments, intellectual retardation, and hearing and vision loss (Centers for Disease Control and Prevention, 2002; McLeod et al., 2006; Prober and Enright, 2003). In this way, the major congenital infections are also important poverty-promoting factors causing billions of dollars in economic losses (Prober and Enright, 2003). In the US, black children and their mothers bear a disproportionate congenital disease burden (Staras et al., 2006). With respect to congenital CMV, black women exhibit a 4-fold increase in primary infection during pregnancy compared to white women, and when stratified for women between the ages of 12 and 19 there is almost a 50-fold increase (Colugnati et al., 2007). Of the estimated 27,002 primary CMV infections in pregnancy in the US estimated to occur annually, 6,652 of them occur in black women (Table A8-2) (Colugnati et al., 2007). Similarly, almost 55% of the cases of congenital syphilis occur among blacks (Centers for Disease Control and Prevention, 2002), and blacks suffer from higher rates of toxoplasmosis than do whites (Table A8-2) (Jones et al., 2007). In addition to primary infections during pregnancy and congenital infections, black women also exhibit an approximately 10-fold higher prevalence of trichomoniasis (13.3%) than white (1.3%) women (Sutton et al., 2007). Based on Murray’s estimate that 13.3 million blacks live either in America 7 (rural South) and in America 8 (high-risk urban environments; Murray et al., 2005), I estimate that approximately 880,000 black women in the US are infected with the protozoan parasite Trichomonas vaginalis (Table A8-2).

Disadvantaged Urban Enclaves (Inner Cities)

High-poverty areas in American inner cities are sometimes defined as neighborhoods where more than 40% of the population is poor (Jargowsky, 1997). Jargowsky described such neighborhoods as ones that ‘‘tend to have a threatening appearance marked by dilapidated housing, vacant units with broken or boarded up windows, abandoned or burned out cars, and men ‘hanging out’ on street corners’’ (Jargowsky, 1997). One measure of inner city poverty used by sociologists and economists is a dissimilarity index, which measures the degree of segregation by race and income, with blacks living in the poorest neighborhoods (Glasmeier, 2006). The cities with the highest dissimilarity index are the Northeastern cities and the Midwestern cities near the Great Lakes (Figure A8-1) (Glasmeier, 2006). Several neglected infections are present in these and other disadvantaged urban enclaves.

Rat-borne and louse-borne bacterial infections.

Over the last two decades, outbreaks of leptospirosis, a bacterial infection transmitted through rat urine and responsible for a serious hemorrhagic complication known as Weil’s disease, have been reported among the poor living in

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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Baltimore (Vinetz et al., 1996) and Detroit (Demers et al., 1985; Thiermann and Frank, 1980). Similarly, bartonellosis, caused by the gram-negative bacterium Bartonella quintana, has emerged among the homeless (Brouqui and Raoult, 2006; Jackson et al., 1996; Spach et al., 1995). B. quintana is the cause of louse-borne trench fever, so named because it was common among soldiers living under extreme conditions in the trenches during World War I (Jackson et al., 1996; Spach et al., 1995). Beginning in the 1990s, small outbreaks of B. quintana bacteremia and endocarditis was noted among the homeless living in Seattle, Washington, and elsewhere (Brouqui and Raoult, 2006; Jackson et al., 1996; Spach et al., 1995). With global warming and increased flooding such rat- and louse-borne infections may increase among the homeless (Gubler et al., 2001).

Toxocariasis.

Toxocariasis is an important neglected infection of poverty among socioeconomically disadvantaged black children (Despommier, 2003; Herrmann et al., 1985; Sharghi et al., 2000). Playgrounds and sandboxes in poor urban neighborhoods are often contaminated with eggs of the dog roundworm, Toxocara canis (Chorazy and Richardson, 2005; Sharghi et al., 2000). When children accidentally ingest these roundworms eggs the released larvae migrate through tissues to cause visceral larval migrans and eosinophilic granuloma of the liver (Despommier, 2003; Kaplan et al., 2001; Sharghi et al., 2000) or ocular larva migrans (Despommier, 2003; Stewart et al., 2005). Another form of the disease, covert toxocariasis, has been associated with asthma (Buijs et al., 1997; Sharghi et al., 2000, 2001), and may possibly be linked to the rise in asthma observed in inner city children (Busse and Mitchell, 2007), as well as impaired cognitive development and lower intelligence (Marmor et al., 1987; Nelson et al., 1996; Sharghi et al., 2000). Based on serologic studies that measure antibody to T. canis antigens, the prevalence rate of toxocariasis among inner city blacks living in Connecticut cities was found to be 10% and even higher among inner city Hispanics (Sharghi et al., 2001). As noted previously, the prevalence among socioeconomically disadvantaged blacks in the American South was as high as 30% (Herrmann et al., 1985). In an unpublished study from the CDC it was recently estimated that approximately 21% of blacks are seropositive (Won et al., 2007; Peter Schantz, personal communication), indicating exposure to the parasite. I previously estimated that approximately 500,000 blacks are seropositive for T. canis antibody (Hotez, 2008). However, based on the estimate that 13.3 million impoverished blacks live in America 7 and 8 (Murray et al., 2005) and prevalence estimates between 10% and 21%, as many as 1.3 million to 2.8 million individuals may be exposed or infected (Table A8-2).

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
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African Refugees and Other Special Immigrant Groups

Since the 1980s, the US has relocated and successfully treated populations of refugees from Southeast Asia and other developing regions with high prevalence rates of helminth infections—especially hookworm infection, filarial infections, and strongyloidiasis (Garg et al., 2005; Nutman et al., 1987; Seybolt et al., 2006)—tuberculosis, and hepatitis B (Barnett, 2004). Beginning in 2000, the immigration of refugees from sub-Saharan Africa markedly increased (Franco-Paredes et al., 2007), and today the US settles an estimated 70,000 refugees annually, including 25,000 refugees from Africa (Posey et al., 2007). Notable among the refugees are the ‘‘Lost Boys and Girls of Sudan,’’ raised initially in poor Ethiopian refugee camps before relocating to Kenya (Franco-Paredes et al., 2007). Since 2000, almost 4,000 Lost Boys and Girls have been settled in the US. By serologic testing it was determined that almost one-half of these special immigrants are seropositive for both schistosomiasis (mostly Schistosoma mansoni infection) and strongyloidiasis (Posey et al., 2007). In addition, an estimated 8,000 Somali Bantu have been relocated to the US, with up to three-fourths of them seropositive for schistosomiasis (most likely Schistosoma haematobium infection) and one-fourth positive for strongyloidiasis (Posey et al., 2007). It is generally accepted that seropositivity for these two parasitic infections is a result of chronic and persistent untreated infections (Franco-Paredes et al., 2007). Therefore, of the roughly 4,000 Sudanese immigrants and 8,000 Somali immigrants there are approximately 8,000 cases of schistosomiasis and 3,000 cases of strongyloidiasis (Table 8-2). Accordingly, the CDC now recommends presumptive treatment for these special immigrant populations with anthelminthics (Franco-Paredes et al., 2007; Miller et al., 2000; Posey et al., 2007).

The Borderlands of Mexico

An estimated 10 million people live in the border region between the US and Mexico, many of whom are of Hispanic heritage (the majority American citizens) (Figure A8-1) (Glasmeier, 2006). These border communities are among the poorest in the US, and substandard or inadequate housing is common to the region (Glasmeier, 2006). Several important neglected infections of poverty occur in this setting, including vector-borne diseases, helminth infections, and other zoonoses. A related at-risk population is the estimated 750,000 to 12 million migrant farm laborers from Mexico and Central America (Holmes, 2006).

Vector-borne diseases: Dengue, Chagas disease, and leishmaniasis.

Poor housing without plumbing, air conditioning, or window screens is a key factor in promoting vector-borne diseases (Reiter et al., 2003). It has been estimated that this situation describes more than 30,000 border households, in addition to large numbers of mobile homes in the region (Glasmeier, 2006). Over

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

the 20-y period between 1980 and 1999 there were 65,514 cases of dengue fever reported from the Mexico side of the border, compared to only 64 cases in the US (Brunkard et al., 2007; Gubler et al., 2001; Reiter, 2001). An earlier assessment suggested that the higher-quality dwellings on the US side accounted for this disparity (Gubler et al., 2001); however, more recent studies indicate that dengue is under-reported in the US near the Mexican border (Brunkard et al., 2007). A cross-sectional survey in Brownsville, Texas and Matamoros Tamaulipas, Mexico detected 2% and 7.3% recent infections, respectively, with evidence of past infection in 40% of Brownsville residents (Brunkard et al., 2007). Risk factors and predictors of dengue among the Brownsville residents include low weekly family income, absence of air conditioning, and inadequate street drainage (Brunkard et al., 2007). Assuming that 10 million people live in the US–Mexico borderlands, a 2% prevalence of recent infections (Brunkard et al., 2007) translates to approximately 200,000 people with recent dengue fever (Table A8-2). Alternatively, the Pew Hispanic Center estimates that there are 26,784,268 Mexican Americans living in the US (Pew Hispanic Center, 2008). At an overall poverty rate of 20.6% for Hispanics in the US (Table A8-1), there are almost six million impoverished Mexican Americans in the US. If 2% of this population suffers from a recent dengue infection, I estimate there are 110,000 recent dengue infections in the US (Table A8-2).

In addition to evidence for Chagas disease in post-Katrina Louisiana as described above, the US borderlands with Mexico have also emerged as an endemic region (Beard et al., 2003; Bern et al., 2007; Centers for Disease Control and Prevention, 2006, 2007; Dodd and Leiby, 2004; Hanford et al., 2007; Leiby et al., 2000, 2002; Milei et al., 1992; Navin et al., 1985; Rassi et al., 2000; Tarleton et al., 2007; Tobler et al., 2007). Because of concerns about the risk of new contamination of the national blood supply with T. cruzi (Bern et al., 2003; Centers for Disease Control and Prevention, 2007; Dodd and Leiby, 2004; Leiby et al., 2002), with a recent estimate that between 1 in 4,655 and 1 in 25,000 US blood donors are seropositive for T. cruzi antibodies and presumed infected (Centers for Disease Control and Prevention, 2007; Tobler et al., 2007), there is great interest in expanding current blood screening efforts (Bern et al., 2007). In 2006, the US Food and Drug Administration approved a new commercial ELISA test for blood donation screening that utilizes parasite lysate antigens for detection of antibodies (Bern et al., 2007; Centers for Disease Control and Prevention, 2007). Estimates of the prevalence of Chagas disease along the Mexico border and in the US vary widely. Previously, it was estimated that 50,000 to 100,000 Latin American immigrants in the US are infected (Leiby et al., 2002), but more recently it was found that of 10,192 blood specimens from El Paso, Texas, of which 73% were from donors of Hispanic origin, three donors were positive (Tobler et al., 2007). With an overall prevalence of 0.03% (Tobler et al., 2007) and 10 million people living in the US–Mexico borderlands (Glasmeier, 2006), I estimate that approximately 3,000 people have Chagas disease in the region. Other estimates are considerably

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

higher. Milei et al. argued that there are 370,000 T. cruzi–infected individuals in the US during the 1990s (Milei et al., 1992), while Hanford et al. revised these estimates to suggest that over one million Hispanics in the US have Chagas disease (with almost 270,000 in Texas alone) and that at least 150,000 Latin America–born immigrants are expected to develop clinically apparent chronic Chagas disease (Hanford et al., 2007). Congenital Chagas disease may also occur (Bern et al., 2007; Muñoz et al., 2007). Of particular concern is the possibility that T. cruzi transmission to humans today occurs in the US–Mexico borderlands. In South Texas and elsewhere along the US–Mexico borderlands, dogs and coyotes are seropositive and there is a domestic canine transmission cycle (Beard et al., 2003). In addition, wood rats are common hosts, and the infection occurs among domestic cattle, horses, and sheep (Hanford et al., 2007). Infected vectors or hosts are present in 64 of the 254 counties in Texas (Hanford et al., 2007), so people living in the estimated 30,000 poor-quality dwellings in the borderlands region are at high risk for transmission.

Another vector-borne neglected disease, cutaneous leishmaniasis, is transmitted by sandflies and is endemic in Mexico and Central America. Infection with Leishmania mexicana has been reported from South Texas, including among individuals with no travel history (Enserink, 2000; Maloney et al., 2002); wood rats or other rodents may also serve as reservoir hosts.

Cysticercosis and other zoonoses.

Cysticercosis results when humans accidentally ingest eggs of the pork tapeworm, Taenia solium, which are shed or excreted by close household or family contacts. This condition is now a leading cause of epilepsy, seizures, and other neurological sequelae in the US–Mexico borderlands (DeGiorgio et al., 2005a, 2005b; del la Garza et al., 2005; Ong et al., 2002; Shandera et al., 1994; Sorvillo et al., 2007; Wallin and Kurtzke, 2004; White and Atmar, 2002), accounting for approximately 10% of seizures presenting to emergency rooms in Los Angeles and, presumably, other border cities as well (Ong et al., 2002). With an incidence rate of 8 to 10 per 100,000 per year among Hispanic populations (Shandera et al., 1994; Wallin and Kurtzke, 2004), I previously estimated that up to 3,500 new cases of cysticercosis occur annually (Hotez, 2008). In a seroprevalence study of rural Ventura County, California, it was found that 1.8% of that population have cysticercosis (DeGiorgio et al., 2005a, 2005b). I previously reported that there are 41,400 Hispanics in the US with cysticercosis (Hotez, 2008), but based on the observation that 9.4 million Hispanics live in poverty in the US (Pew Hispanic Center, 2008), the number of people with cysticercosis may be substantially higher. If 1.8% of this population is also infected, there may be as many as 169,000 cases of cysticercosis among Hispanics in the US (Table A8-2).

There are two other zoonoses of medical importance in the US–Mexico borderlands. Brucellosis is one of the most common zoonosis worldwide and a

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

leading cause of disability (Pappas et al., 2006). Goat and cow dairy products are an important source of infection from Mexico (Troy et al., 2005), with 1,056 cases of brucellosis reported between 1993 and 2002 (although Mead et al. (1999) estimated that 1,554 cases occur annually, of which almost 80% of the cases occur among individuals of Hispanic origin; Troy et al., 2005). Between 1994 and 2000, 129 cases of bovine tuberculosis (Mycobacterium bovis) were reported, nearly all among patients of Hispanic origin, particularly children (LoBue et al., 2003).

Neglected infections among migrant farm workers.

Approximately 95% of the several million migrant agricultural workers in the US were born in Mexico, and almost all of them live below the poverty line (Holmes, 2006). They have significant health disparities, with case fatality rates more than five times the US average. In addition to very high rates of HIV, tuberculosis, and chronic diseases (Centers for Disease Control and Prevention, 1992; Holmes, 2006; Poss, 1998; Villarejo, 2003), the Mexican-born migrant workers living in the US often suffer from high rates of parasitic infection, including ascariasis and hookworm infection (Bechtel, 1998; Ciesielski et al., 1992; Holmes, 2006; Ortiz, 1980) (for which there is evidence of autochthonous transmission on US farms; Ciesielski et al., 1993), cysticercosis and Chagas disease (Ciesielski et al., 1993; Villarejo, 2003), and other neglected infections (Centers for Disease Control and Prevention, 1992; Holmes, 2006).

Tribal Lands and Arctic Native Americans

Approximately 4 million Native Americans are distributed among 500 tribes in the United States, with approximately one fourth living on tribal lands or lands specifically designated as Native American lands (Figure A8-1) (Glasmeier, 2006). Almost 30% of those living on tribal lands live in poverty, where the child poverty rates are more than 40% (Glasmeier, 2006).

Neglected infections in continental US tribal lands.

Across the US, Native Americans are highly susceptible to diabetes mellitus and obesity, and almost one-third of Native Americans die before the age of 45 (Glasmeier, 2006). Up to 40% of Native Americans also live in overcrowded conditions (Glasmeier, 2006), and because of this and for additional reasons of genetic susceptibility and low vaccine coverage, high rates of invasive bacterial and viral respiratory infections occur among Native Americans, especially the Navajo and Apache (Benin et al., 2005; Bockova et al., 2002; Millar et al., 2005; Watt et al., 2007). On some reservations up to one in five homes lack complete

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

in-house plumbing, a rate that is 20 times the national average (Glasmeier, 2006). In this setting, certain neglected infections of poverty are common. Over the last twenty years in the American Southwest, trachoma has been common among the Navajo (Ludlam, 1978; Rearwin et al., 1997), while cystic echinococcosis has been endemic among the Navajo, Zuni, and Santo Domingo Indians because of an enzootic dog–sheep cycle on tribal lands and elsewhere in the region (Katz et al., 1980; Pappaioanou et al., 1977; Schantz et al., 1977).

Neglected infections among the Inuit.

Because of their dietary reliance on meat from sea mammals and polar bear the Inuit living in Alaska and the Canadian Arctic are at risk of foodborne parasitic diseases, including echinococcosis, toxoplasmosis and congenital toxoplasmosis, and trichinellosis (Hotez, 2008). Cystic echinococcosis in the Arctic is due to an enzootic cycle involving moose, reindeer, and elk (Rausch, 2003), while trichinellosis caused by Trichinella spiralis nativa is prevalent because of high rates of infection among walruses and polar bear (Proulx et al., 2002). Toxoplasmosis and congenital toxoplasmosis are also extremely common among the Inuit, and are due to consumption of infected seal and caribou meat (McDonald et al., 1990).

Other Regions

The most diagnosed parasitic in the infection in the US is giardiasis (Kappus et al., 1994; Yoder et al., 2007), with as many as 2.0–2.5 million cases occurring annually (Furness et al., 2000; Mead et al., 1999). The greatest number of cases occurs between June and October and among children aged 1–4 and 5–9 y and adults aged 35–39 y (Yoder et al., 2007). An estimated 300,000 cases of cryptosporidiosis also occur annually (Mead et al., 1999), and this infection has emerged as a leading cause of recreational water outbreaks of diarrhea in the US and among patients with HIV/AIDS (Yoder et al., 2007). A 10-fold increase in cryptosporidiosis transmission occurs during the summer and early fall (Yoder et al., 2007). Although both giardiasis and cryptosporidiosis are common, there is no evidence to suggest that they disproportionately affect poor and underrepresented minority populations. In contrast, the intestinal protozoan disease amebiasis does disproportionately affect the poor, but no US prevalence data are available for this disease. Among the notifiable neglected infections of poverty there were 166 cases of leprosy (with most of the cases in Texas, California, New York and Louisiana; Truman et al., 2005), 16 cases of trichinellosis, and two cases of human rabies reported in 2005 (Table A8-2) (Centers for Disease Control and Prevention, 2007).

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

Policy Recommendations

Based on my estimates of prevalence (Table A8-2) and other health and socioeconomic impacts, the most important neglected helminth infections of poverty in the US are the helminth diseases toxocariasis (inner cities and the American South), ascariasis (Appalachia and the American South), strongyloidiasis (Appalachia), and cysticercosis (US–Mexico borderlands). Among the important vector-borne neglected infections are dengue and Chagas disease in the US–Mexico borderlands and in post-Katrina Louisiana. Congenital infections such as congenital CMV and congenital syphilis stand out as health disparities in inner cities and the American South. Trench fever and leptospirosis are important among the homeless and other disadvantaged urban populations.

Among the common features of these neglected infections are (1) their highly disproportionate health impact on people of color and people living in poverty; (2) their chronic, largely insidious, and disabling features; and (3) their ability to promote poverty because of their impact on child development, pregnancy outcome, and productive capacity. It is important to note that, while some of these neglected infections occur exclusively among recent immigrant populations, most do not. Instead, poverty is the single most important determinant. Control of these neglected infections needs to be prioritized by policy makers and public health experts because it is both a highly cost-effective mechanism for lifting disadvantaged populations out of poverty and consistent with our shared American values of equity and equality (Putsch and Pololi, 2004). The World Health Organization also recognizes that control of neglected diseases represents a fundamental human right (Hunt, 2006).

An important obstacle to the control or elimination of the neglected infections of poverty in the US is the absence of reliable population-based estimates of prevalence and disease burden data about these conditions (Hotez, 2007, 2008). These neglected infections are underdiagnosed and most are not reportable to the CDC. The estimates I provide here are preliminary and based on very few active surveillance studies, including some obtained by analyses of sera collected from National Health and Examination Surveys. For some of the neglected infections of poverty, seropositivity may be equated with active infection (Brunkard et al., 2007; DeGiorgio et al., 2005a; Franco-Paredes et al., 2007; Posey et al., 2007; Tobler et al., 2007), whereas for others it may reflect both current and past infections (Despommier, 2003; Herrmann et al., 1985). For infections such as Chagas disease estimates reported here vary widely. We also lack a system for the national collection of fecal samples for intestinal parasitic infections. Expanded measures are urgently needed to implement active surveillance and obtain population-based estimates of the neglected infections (Table A8-3). An added measure would be to expand newborn screening for toxoplasmosis (Hotez, 2007; Kim, 2006), and possibly congenital Chagas disease. Screening for congenital toxoplamosis would also likely benefit persons of all socioeconomic circumstances (McLeod et al.,

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

2006). Such efforts would create opportunities to determine the extent and true disease burden of these neglected infections.

There is also an urgent need to better define the transmission dynamics of some of the neglected diseases (Table A8-3). For Chagas disease, and to some extent, dengue and leishmaniasis, the full extent of authochthonous transmission in Louisiana and the US–Mexico borderlands is poorly understood. A full appreciation of Chagas disease transmission mechanisms would include molecular genotyping of the parasite to determine whether different strains or demes are endemic, and a complete characterization of the different vectors and animal reservoir hosts. Similarly, the extent of autochthonous cysticercosis transmission in the US is largely unstudied, as it is for many of the bacterial zoonoses including urban foci of leptospirosis and trench fever. For toxocariasis, the contribution of feral versus domesticated animal reservoirs to transmission is also not well understood.

Following enhanced surveillance and improved understanding of transmission dynamics, there are several opportunities to treat or prevent neglected infections of poverty in the US using existing drugs or other control tools (Table A8-3). Through either populationbased drug administration or case identification and treatment, the soil-transmitted helminths could be controlled by administration of albendazole and ivermectin (Bethony et al., 2006), while expanded use of praziquantel would treat schistosomiasis among selected immigrant populations (Posey et al., 2007) and prevent transmission of T. solium eggs and possibly reduce the incidence of cysticercosis (Garcia et al., 2007). Metronidazole and tinidazole are available for the treatment of trichomoniasis and giardiasis (Nailor and Sobel, 2007; Tinidazole, 2004), and nitazoxanide is available for cryptosporidiosis and giardiasis (Nitazoxanide, 2003; Yoder et al., 2007). Pyrimethamine plus sulfadiazine is used for the treatment of toxoplasmosis, and the optimal length of treatment and its impact on child development and neurological sequelae need to be determined (McLeod et al., 2006). Antibiotics are available for the treatment of leptospirosis and other bacterial zoonoses (Griffith et al., 2006). An important role also exists for veterinary public health interventions to prevent zoonotic transmission to humans, possibly including the mass treatment of Toxocara-infected dogs, Toxoplasma-infected cats, and other measures (Jones et al., 2008). The control of almost all of the neglected infections of poverty would also benefit from improvements in environmental sanitation, piped clean water, and improvements in housing in some of the poorest endemic areas. For Chagas disease, dengue, and leishmaniasis, consideration of expanded vector control approaches is warranted (Gubler et al., 2001; Yamagata and Nakagawa, 2006).

Development of new control and prevention tools is needed (Table A8-3). Currently, the serologic-based diagnostic tests for most of the parasitic infections rely on extracts or crude preparations of parasite antigens and would benefit from the development of improved and widely available diagnostic kits that utilize standardized and purified recombinant antigens. For Chagas disease there is a

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

TABLE A8-3 Priority Needs for Enhanced Surveillance, Treatment, and Prevention Efforts for the High Priority Neglected Infections of Poverty

Disease Category

Disease

Expanded Active Surveillance and Treatment

Newborn Screening and Treatment

Epidemiological Transmission Studies

New Diagnostics

New Drugs

New Vaccines

Helminth Infections

Ascariasis

+

 

+

 

 

 

 

Toxocariasis

+

 

+

+

 

 

 

Strongyloidiasis

+

 

+

+

 

 

 

Cysticercosis

+

 

+

+

+

 

Protozoan Infections

Giardiasis

+

 

 

 

 

 

 

Cryptosporidiosis

+

 

+

 

+

 

 

Trichomoniasis

+

 

 

 

 

 

 

Chagas disease

+

+

+

+

+

+

 

Leishmaniasis

+

 

+

+

+

+

 

Congenital

+

+

+

+

+

+

 

toxoplasmosis

 

 

 

 

 

 

Bacterial Infections

Congenital syphilis

 

+

+

 

 

 

 

Brucellosis

+

 

+

 

 

 

 

Bovine tuberculosis

+

 

+

 

 

 

 

Trench fever

+

 

+

 

 

 

 

Leptospirosis

+

 

+

 

 

 

Viral Infections

Dengue fever

+

 

+

 

+

+

 

Congenital CMV

+

+

+

 

+

+

Suggested Citation:"Appendix A: Contributed Manuscripts." Institute of Medicine. 2011. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington, DC: The National Academies Press. doi: 10.17226/13087.
×

particularly urgent need for rapid diagnostic tests and polymerase chain reaction-based assays for detection of acute and congenital infections. Furthermore, no drugs adequately and reliably treat Chagas disease (Rocha et al., 2007), dengue (Keller et al., 2006), or congenital CMV infection (DeVries, 2007). Although vaccines for dengue (Pediatric Dengue Vaccine Initiative, 2008) and CMV infection (Schleiss and Heineman, 2005) are under development, progress has been slow because of inadequate resources and commercial incentives (Hotez and Ferris, 2006). A pediatric dengue vaccine initiative was recently established through support by the Gates Foundation (Pediatric Dengue Vaccine Initiative, 2008). For CMV infection, both a live attenuated vaccine and a recombinant vaccine have been developed (Schleiss and Heineman, 2005), but clinical testing in pregnant women to determine the impact of these vaccines on vertical transmission has been severely lagging because of inadequate support—a tragedy, given that more than 10,000 congenital CMV infections occur among infants of color annually (Colugnati et al., 2007).

In 2006, the annual budget of the National Institute of Allergy and Infectious Diseases (NIAID) was $4.4 billion, with approximately $1.6 billion of this amount spent on biodefense (U.S. Department of Health and Human Services, 2008). Of the selected disease-specific areas targeted for funding by the NIAID in their published annual report, none specifically mentions a neglected infection of poverty (U.S. Department of Health and Human Services, 2008). A consequence of this lack of targeted funding for neglected diseases is that the development of critically needed new tools for these conditions has lagged behind those for biodefense. The Global Forum on Health Research has coined the term “the 10/90 gap” to describe how only 10% of resources are devoted to 90% of the global burden of disease, i.e., that represented by disease disproportionately occurring in developing countries (Bell, 2005). The absence of development of new tools for neglected infections of poverty, such as those outlined above, highlights a unique American 10/90 gap for poor people and people of color in the US.

Acknowledgements

I wish to thank Drs. Mark Eberhard and Peter Schantz from the US Centers for Disease Control and Prevention for their helpful discussions and insights.

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