Neglected Tropical Diseases: Background, Responses, and Issues for Congress
Released: 2011-01-21T00:00:00

Summary:
Over the past decade, global health has become a priority in U.S. foreign policy, and U.S. funding for related efforts has more than tripled. Neglected tropical diseases (NTDs), an important focus of U.S. global health assistance, may come under scrutiny as the 112th Congress debates spending levels for ongoing global health programs. NTDs are a group of 17 diseases that are found primarily among the poorest people in 149 countries and territories. Estimates indicate that some 2 billion people are at risk of contracting an NTD, of whom more than 1 billion people are afflicted with one or more. Roughly 534,000 people are believed to be killed by an NTD annually.
Although these diseases are concentrated among the world's poor, population shifts and climate change increase the vulnerability of the United States to some of these diseases, particularly Chagas disease and dengue. While blood centers test for Chagas, some health experts believe that several cases remain undiagnosed in the United States and that Chagas stands as an undetected cause of heart disease and stroke. Some observers are concerned about scientists' expectations that mosquitoes capable of spreading dengue fever are gradually spreading across the United States, particularly because no vaccine or treatment exists for this disease. In addition, travelers from industrialized countries are increasingly contracting NTDs such as schistosomiasis while engaged in tourism. These cases are usually identified once tourists develop severe, acute infection or other unusual problems.
Proponents support funding research on and treatment for NTDs because it is a cost-effective way of making a significant health impact. Roughly 90% of all NTDs are easy to treat with drugs that cost less than $2 per dose and need to be taken only once or twice annually. This means that all people at risk of contracting an NTD worldwide can be treated for less than $2 billion over the next five years. With consistent treatment and control, several NTDs are being eliminated in various parts of the world, especially in Latin America, and guinea worm disease is on the cusp of eradication, meaning there is no risk of contracting the disease.
Some groups argue that the United States should increase funding for NTD programs to improve global health and advance domestic capacity to detect NTD cases that may arise, particularly for diseases like dengue and Chagas. Other groups maintain that countries like Brazil, China, and India that have received support for eliminating NTDs should play a greater role in addressing the health challenge, particularly as their own economies exhibit strong growth. The 112th Congress may debate funding much of the President's FY2011 budget, which includes $155 million for the NTD Program, as well as upcoming FY2012 budget levels. The 112th Congress will likely weigh calls for greater spending on NTDs with other challenges, such as streamlining foreign and global health assistance to make them more effective and efficient, particularly in light of efforts to reduce federal spending. This report will be updated as events warrant.

subsections: section_title: Background
paragraphs: Over the past decade, global health has become a priority in U.S. foreign policy, and U.S. appropriations for health-related efforts have more than tripled. Some observers expect the 112 th Congress to debate the appropriate funding level for ongoing global health programs, to consider ways to make U.S. global health initiatives more effective and efficient, and to encourage other players to become more engaged, particularly countries such as China and India that are receiving assistance from donors to address health challenges while their economies are undergoing considerable growth. 
Neglected tropical diseases (NTDs) have become an important part of U.S. global health assistance, particularly since 2006, when Congress made available $15 million to combat such diseases and President George W. Bush launched the NTD Program. NTDs comprise a group of 17 diseases found mostly among the poorest in 149 countries and territories, primarily in areas with unsafe water, inadequate sanitation, and limited health services. (See Appendix C for a description of NTDs, including their symptoms and prevalence; Appendix D displays their images). The list is not exhaustive of all illnesses found among this population, but it accounts for those being targeted by the World Health Organization (WHO) and its partners. 
Some diseases are transmitted by people; others are spread by vectors like snails, flies, or mosquitoes; and several others are found in contaminated sources (like infested soil or water). At the same time that NTDs afflict primarily the impoverished, some studies indicate that NTDs exacerbate poverty. People crippled by lymphatic filariasis (elephantiasis), for example, often cease to be employable or capable of engaging in income-producing activities. Children afflicted with soil-transmitted helminths (STH) have reduced cognitive functions, poorer health and nutrition, and lower school attendance rates. All of these factors reduce lifetime earning potential. 
In 2003, WHO convened a meeting to discuss challenges in addressing a host of tropical diseases that were widely viewed to be receiving inadequate attention and worsening poverty. Though efforts to address these diseases preceded the meeting, up until that point, national governments and global health groups had focused on each of the diseases separately. Following the meeting, WHO and other health experts dubbed a group of 17 infections "neglected tropical diseases" because data showed that people tended to be infected with more than one of these maladies at once. At least 100 countries face two endemic NTD disease burdens, for example, and 30 countries carry six or more NTD endemic disease burdens ( Figure 1 ). 
Though NTDs are a group of distinct diseases, they share three key characteristics. Specifically, NTDs
are long-standing health problems that have afflicted human beings for centuries, have virtually disappeared in industrialized countries, and have continued to primarily affect the world's poorest populations; cause chronic conditions that have relatively low mortality rates but may bring long-lasting deformities, which are irreversible in some cases, and impair health, quality of life, and earning potential; and could benefit from greater research and development (R&D). Additional research could identify second-line treatments that could be used should the diseases become resistant against drugs. R&D could also identify treatments for incurable ailments like dengue fever and buruli ulcer. For other NTDs like sleeping sickness, innovative research could be used to develop medicines that could supplant commonly used drugs that are toxic, have complex treatment regimens, and carry significant side effects (including death). For all of the NTDs, R&D could be used to identify a vaccine and develop improved diagnostic tools that could be easily used in low-resource settings.
Health experts reconvened in 2005 and developed a framework for implementing an integrative approach to controlling NTDs, which focused on three key strategies:
Preventive Chemotherapy through mass drug administration (MDA)—administering treatments to an affected population irrespective of individual disease status. Vector control —limiting or eradicating disease-carrying insects to reduce transmission of NTDs. Disease surveillance and care —improving the monitoring of NTD cases and the care of those carrying the diseases.
section_title: Prevalence
paragraphs: The best available estimates indicate that some 2 billion people are at risk of contracting an NTD, of whom more than 1 billion people are afflicted with one or more NTD. Roughly 534,000 are killed by an NTD annually ( Table 1 ). 
Despite the common use of the estimates cited above, health experts do not know exactly how many people are infected with NTDs. Uncertainty regarding the number of people suffering from NTDs is rooted in several issues. The majority of people living with NTDs live in marginalized communities that lack sufficient health care, possibly obscuring a diagnosis. The full extent of the global NTD burden may also be hidden behind the symptoms that NTDs cause. Schistosomiasis, for example, can cause anemia and bladder cancer. Additionally, weak health systems may fail to document the true burden of NTDs. One study estimates that one NTD case is reported for every 40 occurrences. 
In addition, health information systems in many developing countries are in poor condition and are not equipped to provide precise data on disease prevalence. As such, disease assessments in developing countries, particularly in sub-Saharan Africa, are often based on projections extrapolated from household surveys rather than medical records establishing a diagnosis. Disease prevalence mapping for NTDs has reportedly been improving, however, as the international community boosts investments in addressing NTDs. According to the U.S. Agency for International Development (USAID), by the end of 2009, the NTD burden of the seven most common NTDs had been identified in most districts throughout the countries supported by the United States ( Figure 2 ).
Of the 14 most common NTDs, roughly 80% are caused by STH—a group of three parasitic worms (roundworms, whipworms, and hookworms) that are contracted through contact with tainted soil or ingestion of eggs found on produce grown in tainted soil ( Figure 3 ). More than 1 billion people are afflicted with STH worldwide, of whom children are the most vulnerable and tend to carry more than one type of worm at a time.
NTDs independently cause high levels of illness and worsen the health of those plagued with other diseases like HIV/AIDS, malaria, and tuberculosis (TB). For example, some research indicates that 
HIV/AIDS and schistosomiasis co-infection is associated with higher HIV viral loads; people infected with schistosomiasis are more susceptible to HIV; and HIV-positive pregnant women who are co-infected with schistosomiasis have higher HIV-transmission rates than their counterparts without schistosomiasis; malaria and STH co-infection lead to higher incidence of anemia (a key cause of maternal and child mortality), and people with STH are more susceptible to malaria; and TB and STH co-infection is linked to higher rates of the conversion of latent TB into active TB, and TB vaccines are less effective in people co-infected with STH. 
Of all global regions, sub-Saharan Africa is most affected by NTDs and by co-infection with HIV/AIDS, TB, and malaria co-infection ( Appendix E ). 
section_title: Control and Treatment Strategies
paragraphs: The international community has long sought to raise awareness about and support for tackling NTDs. In 1949, for example, world health leaders met to discuss schistosomiasis and noted the disease's harmful effects, especially its degenerative effect on economic development and food production. Through ratification of several World Health Assembly resolutions through WHO and implementation of numerous public-private partnerships, the international community has agreed to prioritize combating, eliminating, and eradicating NTDs. Well over 100 groups are engaged in fighting NTDs, including academia, the private sector, global development and health organizations, non-governmental organizations (NGOs), foundations, and national governments ( Table 2 ). Some initiatives focus on one NTD, while others tackle a group of NTDs ( Appendix F ). 
Among the 17 NTDs, 7 account for roughly 90% of the global NTD burden. These are the three soil-transmitted helminthes, schistosomiasis, lymphatic filiariasis, trachoma, and onchocerciasis. Drugs used to treat these seven diseases are donated by pharmaceutical companies or sold at subsidized prices ranging between $0.02 and $1.02, and are taken once or twice annually (depending on the concentration of the disease). At such prices, some 500 million people can be treated for these seven afflictions at roughly $400 million annually. When correctly used, these drugs can be used to control and, in some cases, eliminate some of the NTDs. 
Historically, countries attempted to address each of these diseases in distinct programs. Within the past decade, WHO and other health experts found that national responses to these seven diseases could be integrated to improve the efficacy and reduce costs. Specifically, health experts found that
medicines used to treat each of the seven NTDs could be safely administered to people co-infected with other NTDs (in most cases); one drug could treat more than one disease; individual diagnosis would not be necessary and entire communities could be safely treated, usually once per year, irrespective of each person's disease status; non-health workers, including teachers and community volunteers, could dispense the treatments in non-clinical settings (like schools) rather than in health facilities (which are often poorly resourced and in limited supply in remote areas); and the integration of drug delivery enabled resources to be pooled.
By integrating drug delivery for these seven diseases, countries and their partners have reduced some of the costs related to treating the diseases separately. After integrating mass drug administration (MDA) campaigns, USAID documented cost-efficiencies up to 41% and a 30% reduction in training costs. USAID attributed these savings to streamlining program management, social mobilization, drug supply chains, and trainings. 
The remaining 10 NTDs must be treated individually and can be more difficult and costly to manage. No cures exist for some of the NTDs in this group and for others available treatments can carry significant side effects. Additionally, access to diagnostic tools for some of these diseases may be limited, and treatment tends to be more costly because the medicines often need to be administered by trained health practitioners in health settings for prolonged periods. For some of these diseases, namely Chagas disease, dengue, human African trypanosomiasis, and leishmaniasis, early detection and treatment are vital to avoid irreversible disability or death.
subsections: section_title: Global NTD Plan
paragraphs: The global response to NTDs comprises complex mechanisms. Countries develop national NTD plans, primarily through the ministries of health and education, and receive financial support from donors to help carry out the national MDA plans. WHO and donors such as USAID review drug donation applications and support country-level planning, training, and monitoring, and evaluation. Pharmaceutical companies provide treatments used for national NTD plans, either for free or at highly discounted rates. NGOs and faith-based organizations partner with national ministries to implement the NTD plans. Academic groups, public-private partnerships, and pharmaceutical companies research and develop innovative treatments and control mechanisms. 
In combating NTDs, countries and their supporters adhere to WHO protocols that outline best practices for addressing NTDs. In 2007, WHO released the Global Plan to Combat Neglected Tropical Diseases , which outlined several goals and targets for global control, elimination, and eradication of NTDs by 2015; strategic areas for action; and the policy framework for NTD implementation, monitoring, and evaluation. Three key goals included in the plan were to 
eliminate or eradicate NTDs targeted in resolutions of the World Health Assembly and regional committees; reduce the burden of NTDs that can be treated with MDA; and ensure that interventions using novel approaches are available, promoted, and accessible for NTDs that are costly and difficult to treat.
As of October 2010, the WHO estimates that it would cost $1.7 billion to purchase enough drugs to treat all those at risk of contracting the seven most common NTDs. As of January 2010, donors had committed to provide all but one-third of the funds ($552 million) needed to fund the Global NTD Plan ( Table 3 ). WHO estimates that it would cost an additional $1.2 billion to distribute the drugs.
section_title: Advances in Tackling NTDs
paragraphs: In November 2010, WHO released its first report on NTDs. The report highlighted positive outcomes of long-standing efforts to tackle NTDs. The near eradication of dracunculiasis (guinea worm disease) is one of the most profound cases. Global incidence of guinea worm disease has declined 99% since 1986, when some 3.5 million people in Africa and Asia were infected. By 2009, only 3,190 cases were reported, and as of September 2010, WHO counted 1,613 cases ( Figure 4 ). Today, guinea worm disease is endemic in only four countries: Ethiopia, Ghana, Mali, and Sudan (accounting for about 90% of all cases). Prolonged conflict in Sudan has slowed efforts to eradicate guinea worm disease, though health experts remain optimistic about prospects that the illness could be the first infectious diseases to be eradicated since smallpox in 1979. 
Epidemiologists also celebrate advances in eliminating other NTDs. The Pan American Health Organization (PAHO), for example, reports that lymphatic filiariasis is no longer transmitted in three of seven Latin American countries where the disease was endemic. Likewise, aggressive MDA campaigns have interrupted the transmission of onchocerciasis (river blindness) in one-third of areas where the disease was endemic and eliminated the disease from Colombia. As such, people in 6 of the 13 previously endemic countries are no longer treated for the disease, and no new cases of onchocerciasis-related blindness have been reported in the region since 2007. 
section_title: U.S. Government Responses to NTDs
paragraphs: The United States has long supported efforts to control NTDs, and U.S.-based institutions, including the federal government, pharmaceutical companies, and philanthropic organizations, continue to lead global investments for and participation in fighting NTDs. Key U.S. government (USG) players include USAID, U.S. Centers for Disease Control and Prevention (CDC), National Institutes of Health (NIH), and Department of Defense (DOD). Non-profit and private sector participants include the Carter Center, the Bill & Melinda Gates Foundation, and several private companies, including Merck, Johnson & Johnson, and Pfizer. While each of these play a key role in combating NTDs, this report focuses on efforts conducted and supported by the U.S. government.
In 2006, the U.S. government launched the Neglected Tropical Disease Control Program, its first effort to address a group of NTDs. The program was created in response to language in the FY2006 Foreign Operations Appropriations Act, which made available up to $15 million "to support an integrated response to the control of neglected diseases including intestinal parasites, schistosomiasis, lymphatic filariasis, onchocerciasis, trachoma and leprosy." The language signaled congressional support for calls to integrate and expand access to treatments against the seven most common NTDs. Until that time, most countries and their implementing partners focused on a single disease rather than targeting NTD co-infection. The NTD Program sought to document the feasibility of integrated NTD control and facilitate the advancement of this approach.
At the outset, the NTD program aimed to support the provision of 160 million NTD treatments to 40 million people through integrated programs in 15 countries. President George W. Bush reaffirmed his commitment to the program in 2008 and proposed spending $350 million from FY2008 through FY2013 on expanding the fighting against the seven NTDs to 30 countries. 
The NTD Program continues to be an important part of U.S. global health assistance under the Obama Administration. In May 2009, President Barack Obama announced the Global Health Initiative (GHI), which aims to streamline U.S. global health efforts. The President indicated that a key part of the initiative is to bolster support for U.S. efforts to combat NTDs and to integrate such efforts into other U.S. global health programs. The 2009-2014 Lantos-Hyde United States Government Malaria Strategy, for example, identifies plans to integrate malaria and NTD activities with other U.S. global health programs. The Administration also intends to expand the provision of drugs that expel intestinal worms from children through USAID-supported education programs. 
According to the Obama Administration, the NTD Program is part of a complete package of services the United States provides to improve the health of women, newborns, and children worldwide. Through GHI, the Obama Administration set ambitious NTD targets in which the U.S. government would contribute to 
the administration of 1 billion NTD treatments; a 50% decrease in the prevalence of seven NTDs in 30 countries by 2013 that account for 70% of the global disease burden of the targeted diseases; the elimination of onchocerciasis in Latin America by 2016; the elimination of leprosy in all endemic countries by 2016; and the elimination of lymphatic filariasis globally by 2017.
As of September 30, 2010, the NTD Program had supported the provision of over 385 million treatments ( Figure 5 ). As of October 2010, USAID had identified 21 focus countries: Bangladesh, Burkina Faso, Cameroon, the Democratic Republic of Congo (DRC), Ethiopia, Ghana, Guinea, Haiti, Indonesia, Mali, Mozambique, Nepal, Niger, the Philippines, Uganda, Senegal, Sierra Leone, Sudan (southern region), Tanzania, Togo, and Vietnam.
subsections: section_title: U.S. Agency for International Development
paragraphs: USAID leads the NTD Program. In carrying out the program, USAID partners with foreign governments and other groups to bolster health systems, improve the capacity of the recipient countries to carry out NTD programs, coordinate donors' NTD efforts, and build political commitment to expand and sustain NTD programs. Key functions of the NTD Program include the following:
Supporting national strategic planning— USAID works with governments to develop and/or strengthen their national five-year NTD strategic plans. These efforts involve facilitating the coordination of ongoing donor efforts and bolstering country commitment to and ownership of programs. Supporting implementation of NTD programs— USAID provides technical and financial support to help countries achieve national coverage of integrated NTD programs. Related activities include disease mapping, securing drug donations, procuring non-donated NTD drugs (about 20% of NTD Program budget), training health workers and community volunteers, strengthening supply chains and logistics management, and social marketing. Monitoring and evaluation —USAID supports efforts to measure the impact of NTD programs and develops models for integrating NTD projects into other global health efforts. The models focus on mapping disease prevalence, monitoring mass drug administration (MDA) campaigns to measure effectiveness and detect adverse effects, forecasting drug supplies, and tracking progress in meeting U.S. and global goals for disease elimination. To facilitate sharing of best practices, USAID publishes these findings and serves on several working groups with WHO and other partners. Contributing to global guidelines and policies for NTD control— USAID partners with WHO to share and refine tools, best practices, and lessons learned that have contributed to the refinement of global and regional standards for treating the seven most common NTDs. Some of the tools developed by USAID are now endorsed by WHO and are packaged as a standard "NTD Rollout Package" that countries use to establish or expand integrated NTD control. Leveraging related USG programs —where applicable, USAID leverages resources for programs related to malaria, education, water and sanitation, maternal and child health, and agriculture to NTD programs (e.g., offering deworming tablets in USAID-supported education programs).
section_title: U.S. Centers for Disease Control and Prevention
paragraphs: CDC focuses on the control and elimination of lymphatic filariais, onchocerciasis (river blindness), trachoma, schistosomiasis, and STH. Through technical assistance to global partners and countries, CDC
trains health workers, including ministry officials; conducts research for the development of tools to diagnose and combat NTDs, and to improve the integration of national NTD plans with other health interventions; supports mass drug administration for NTDs; supports monitoring and evaluation of MDA campaigns; develops global policy and guidelines for NTD programs; and studies NTDs not covered under the NTD Program to identify and develop tools and approaches to control and eliminate them. 
section_title: National Institutes of Health
paragraphs: Several institutes within NIH research tools to treat and eradicate NTDs. In FY2009, Congress provided $24 million to establish the Therapeutics for Rare and Neglected Diseases (TRND) program. The program applies expertise found across several institutes to develop new candidate drugs for neglected diseases. Additionally, the National Institute of Allergy and Infectious Diseases (NIAID) incorporates basic research on NTDs into several of its ongoing research efforts, including studies underway in the NIAID Laboratory on Parasitic Diseases and the Vector Biology Research Program, the Filariasis Research Reagent Repository Center, and the Schistosomiasis Resource Center. NIAID also participates in several public-private partnerships to develop new prevention and treatment options for NTDs. 
section_title: Department of Defense
paragraphs: The Department of Defense (DOD) has long recognized the detrimental effects of tropical diseases, especially in relationship to force protection. Through collaborative agreements with the private sector and academia, for example, U.S. military infectious diseases programs played a significant role in the development of widely used vaccines, including those for yellow fever, mumps, measles, and polio. DOD also contributed to identifying the current dosing regimen for cutaneous leishmaniasisis and the vaccine for Japanese encephalitis.
Ongoing efforts related to NTDs, such as research for the development of a vaccine against dengue fever, are carried out in several DOD facilities, including eight infectious disease laboratories located around the world, animal laboratories, biosafety containment laboratories, a pilot vaccine facility, and clinical trials units. Related DOD activities center on 
developing vaccines to prevent and drugs to treat infectious diseases; creating techniques to identify and diagnose infections rapidly; collecting and analyzing data to optimize infectious disease control strategies; and evaluating vector control methods.
section_title: Congressional Actions to Address NTDs
paragraphs: Since the November 2010 congressional elections, observers have speculated whether a change in House leadership and greater minority influence in the Senate might lead to reduced spending on foreign aid in general and global health in particular. However, bipartisan support for global health programs has remained strong in recent years, and interest in addressing NTDs has grown under both Republican and Democratic leadership. In 2008, Representative Donald Payne (D-NJ) and former U.S. Representative John Boozman (R-AR) launched the Congressional Malaria Caucus to raise congressional awareness about U.S. efforts to address malaria worldwide. In 2009, the caucus added NTD control and prevention to its mission and became the Malaria and Neglected Tropical Diseases Caucus. U.S. Representatives Payne and Jeff Fortenberry (R-NE) will co-chair the caucus in the 112 th Congress. 
Congress has also demonstrated its support of controlling NTDs through steady increases in appropriations for addressing the diseases. From FY2006 through FY2010, Congress made available $135 million for NTD programs ( Table 4 ). In each fiscal year between FY2006 and FY2008, Congress provided about $15 million to USAID for NTD programs. In FY2009, Congress made available $25 million for NTDs, some 67% higher than FY2008-enacted levels. Congress more than doubled appropriations for NTDs in FY2010, making available $65 million. The President requested $155 million for the NTD Program in FY2011. Congress has not yet enacted the FY2011 foreign operations appropriations, though the Senate Appropriations Committee reported out $100 million for NTD efforts ( S. 3676 ). Congress did enact the Continuing Appropriations and Surface Transportation Extensions Act, FY2011 ( P.L. 111-322 ), which maintained funding for NTD programs at FY2010 levels through March 4, 2011. 
section_title: Key Issues Related to NTD Control
paragraphs: The term "neglected tropical diseases" describes a group of diseases with distinct characteristics. Some are easily treatable; others are not. Drugs can interrupt the transmission cycle of some NTDs, but treatments cannot eliminate others. The use of this term has helped to raise awareness about these long-standing health challenges, but it risks simplifying a complicated health challenge. Since all of these diseases are mostly rooted in poverty and the poor infrastructure that is usually found in destitute areas, the enduring solution to these illnesses is economic development. Industrialized countries, including the United States, have eliminated these diseases in their territories by combining drug treatment with the construction and use of latrines, modernization of agricultural practices, and utilization of improved water systems. Certainly, increased investments in NTD treatments have ameliorated the suffering of millions. More than 80% of NTDs, however, cannot be eliminated by drug delivery alone. As such, countries and their partners will need to indefinitely support the treatment of schistosomiasis and soil-transmitted helminths if complementary disease control methods are not applied. 
In times of fiscal austerity, countries are re-evaluating their foreign assistance programs and seeking the most cost-efficient and effective approach to supporting international development. On January 19, 2011, USAID Administrator Rajiv Shah discussed the future of USAID and indicated that USAID would will increasingly consider the unit cost of impact when deciding which programs to fund or continue funding. NTD control, through treatment alone, is one of the least expensive health interventions that the United States supports. It costs less than $2 annually to treat each person who needs to be treated for the seven most common NTDs that account for roughly 90% of all illnesses in this group. In contrast, the annual cost of first-line antiretroviral therapy for HIV/AIDS in sub-Saharan Africa averages about $95 per capita. When antiretroviral treatments become less effective, the second-line treatments are considerably more expensive. These are not equally comparable, however, because HIV is always fatal if not treated, and only some NTDs are lethal when untreated. Also, HIV treatments must be taken daily, while treatments for the seven most common NTDs are usually taken once or twice annually. Nonetheless, both illnesses affect affected populations' capacity to live a productive life. 
In FY2010, global HIV/AIDS programs and U.S. contributions to the Global Fund accounted for roughly 70% of all U.S. global health spending. In that fiscal year, U.S. support for NTDs amounted to less than 1% of the total global health budget. The section below explores key debates related to NTD control and includes a discussion on how Congress might address each of these arguments, which include the following: 
Defining NTDs. There is not yet a consensus on which diseases should be considered NTDs. WHO classifies 17 diseases, excluding HIV/AIDS, TB, and malaria, as NTDs. Yet some groups consider these three diseases to be neglected as well. With no agreement on which diseases constitute NTDs, investments in and analysis on this topic can be skewed and disjointed. Evaluating reliance on MDA. Although MDA campaigns have reduced disease prevalence and interrupted transmission, several limitations to MDA remain. For example, countries must have plans for continuing treatment after foreign aid ends, mismanagement and wider use of NTD treatments can result in disease resistance, and MDA does not interrupt transmission cycles of all NTDs. Integrating development and health efforts and strengthening health information systems. Depending on how development projects are implemented, they can exacerbate or decrease NTD infection rates. For instance, irrigation schemes could provide breeding grounds for vectors that spread NTDs, new transport infrastructure could facilitate the spread of parasites and vectors, and population resettlement may introduce parasite carriers to new areas. Funding research and development (R&D). Observers debate whether ongoing R&D efforts meet demands for NTD-related vaccines, treatments, and diagnostic tools. Specific concerns revolve around the toxicity and complicated regimens of some treatments, the absence of field-ready diagnostic tools for some NTDs, a lack of vaccines to prevent disease transmission, and vulnerability to drug resistance.
subsections: section_title: Defining "NTDs"
paragraphs: While experts agree that NTDs are long-standing health problems, cause chronic conditions, and have a high disease burden with low mortality, they do not agree on which diseases should be included in this list. Some health experts advocate an expansive list of diseases, while others promote concentrating resources on the seven most common and easily treated NTDs. In the 111 th Congress, members of the Malaria and NTD Caucus urged USAID Administrator Rajiv Shah to develop a funding strategy for research and development of tools to treat, control, and eliminate leishmaniasis, Human African trypanosomiasis, and Chagas disease, which can be fatal if left untreated. Supporters of expanding the definition also point to the threat some of these diseases could pose to the United States, particularly Chagas disease and dengue.
Arguments against expanding the U.S. approach vary. Some fear that an overly expansive definition might diminish the gains made in raising support for countering these afflictions. Advocates of a concentrated approach, particularly on the seven most common NTDs, argue that these diseases should be eliminated or eradicated first to build momentum in sustained global health efforts. Additionally, when considering the full spectrum of NTDs, the seven most common NTDs are the least expensive to treat, increasing the likelihood that countries might sustain treatment campaigns, where necessary. 
subsections: section_title: Defining NTDs: Issues for Congress
paragraphs: USAID leads U.S. efforts to combat NTDs, though other agencies and departments play a role in addressing the diseases (see " U.S. Government Responses to NTDs "). With the exception of language included in the FY2006 State, Foreign Operations appropriations, Congress has not specified which neglected diseases the United States ought to address. Should Congress decide to do so, it could provide language defining NTDs through legislation similar to the Lantos-Hyde Act ( P.L. 110-293 ), which outlines and authorizes the U.S. strategy to combating HIV/AIDS, TB, and malaria internationally. Alternatively, it could include such language in annual appropriations legislation.
section_title: Evaluating Reliance on Mass Drug Administration
paragraphs: Mass drug administration is at the heart of many NTD programs, including the U.S. NTD Program. In some cases, treating an entire population in an endemic area, irrespective of their disease status, has broken the transmission cycle of infection. In Latin America, for example, aggressive MDA campaigns have significantly reduced the disease burden of lymphatic filariasis. The Pan American Health Organization (PAHO) believes that transmission of the disease has been interrupted in three of seven endemic countries in the region. Likewise, Merck, Inc., reports that onchocerciasis (river blindness) has been interrupted in one-third of areas formerly afflicted by the disease and that the disease has been eliminated from Colombia. 
There is debate, however, on the extent to which the United States should rely on this approach. A number of health analysts assert greater reliance on MDA might divert investments from strategies that could eliminate the diseases through more lasting measures, such as water and sanitation projects. Observers are also concerned that prolonged use of MDA campaigns for diseases that cannot be eliminated with available medicines (such as soil-transmitted helminths and schistosomiasis that account for more than 80% of all NTDs) could hasten drug resistance. Scientists have already detected evidence of some disease resistance against treatments for hookworm, a soil-transmitted helminth. Other health experts counter that these issues should not inhibit application of life-saving and health-enhancing measures that have led to the elimination of some NTDs. Additional issues at the heart of this debate include
the capacity of countries to sustain MDA; the inability of MDA to break the transmission cycle of diseases such as STH; and application of preventive measures and disease surveillance. 
subsections: section_title: Capacity to Sustain MDA
paragraphs: MDA has been used to advance efforts to eliminate some NTDs. Such progress, however, can be compromised if there is no effective long-term plan in place, particularly for NTDs like schistosomiasis and STH, which dwell in water and soil and have complicated life cycles that cannot be interrupted with MDA alone. In such cases, MDA campaigns must be sustained until the parasites are eliminated from the water or soil. At present, the U.S. NTD Program does not support vector management or other strategies that would interrupt the transmission of these diseases (such as latrine construction and improved water supply).
In Mali, for example, WHO and its partners launched a 10-year MDA campaign, which significantly reduced the prevalence of schistosomiasis. In 1992, the Malian government assumed full financial control of the program. The government was not able, however, to consistently procure drugs, maintain drug delivery, or reduce exposure of people to contaminated water. Evaluators felt the treatment campaign that focused exclusively on schistosomiasis burdened the health system and diverted resources from routine health care. After a decade of inconsistent MDA, prevalence rates had rebounded and reflected those seen before the campaign was initiated. In 2004, donors returned and supported the launch of another MDA campaign. This time, however, Mali and its partners launched an integrated treatment campaign that focused on more than one NTD and consolidated health management resources (see " Control and Treatment Strategies ").
In addition to raising questions about the sustainability of some MDA programs, the Mali case also raises a long-standing debate about the extent to which donors should invest directly in health systems. Some development organizations encourage the United States and other donors to reduce their reliance on contractors and channel more health assistance through local governments and organizations. One official from the Ugandan Ministry of Health urges USAID to fully fund its NTD Program through the national health ministry rather than RTI International (an organization contracted to administer the U.S. NTD Program). He is concerned that the ministry will not have the capacity to sustain the program once the financial support ceases since Ugandan stakeholders are not included in all aspects of project management and coordination. 
One study evaluating the first three years of the U.S. NTD Program, written in part by USAID officials, appears to contradict the assertion of the Ugandan official, indicating health system strengthening is an integral part of U.S. support. Specifically, the article highlights how resources provided through the NTD program were used to train more than 220,000 people, primarily community-based health workers and drug distributors, during the first three years of the program. The authors assert, "[t]raining is designed to empower these communities to treat NTDs within their own populations."
section_title: Capacity to Sustain MDA: Issues for Congress
paragraphs: Several actions by the Obama Administration indicate an effort to enhance country ownership of global health programs. For example, country ownership has been highlighted as a key goal of the Global Health Initiative, USAID Administrator Rajiv Shah has made public statements endorsing country ownership, and the Office of the Global AIDS Coordinator (OGAC) advocates applying a "Partnership Framework" to HIV/AIDS programs funded through the President's Emergency Plan for AIDS Relief (PEPFAR). The Partnership Framework outlines the role of the United States and recipient governments and describes how country ownership will ultimately assume full control of the programs. In Nigeria, for example, the government commits to funding half of the PEPFAR program by 2015. According to one USAID official, key components of the NTD Program are to measure and document recipient country contributions to NTD responses; develop clear funding plans that outline the role of the donors and recipient country; and require commitments from participating countries to sustain and/or expand national financing of NTD control, including ensuring duty-free import of NTD drugs and dedicating at least one staff person to manage the NTD programs. 
Although USAID reportedly requires NTD focus countries to demonstrate political commitment to sustaining NTD plans, Congress might encourage or require the President to apply the Partnership Framework or similar approaches more broadly across all U.S. global health programs, including those aimed at NTDs and implemented in non-GHI or -NTD focus countries. Though it is too early to evaluate the Partnership Framework, the plan appears to include some of the processes that the Mali NTD program lacked: a clear strategy for preparing countries to assume full ownership of health projects, an outline of roles and responsibilities, alignment with national health plans, and investment in the national health system. 
Several health and development experts argue that health systems of recipient countries must be strengthened if NTD programs supported by donors are to be sustained. One consortium of aid organizations recommends that donors allocate 15% of their budgets aimed at specific diseases to health system strengthening. Should the 112 th Congress support this idea, it could encourage or require that a portion of funds for the NTD Program (or other U.S. health programs like PEPFAR) be used on health system strengthening. The 112 th Congress might also consider legislation similar to the Global HEALTH Act ( H.R. 4933 ), which was introduced in the 111 th Congress. The bill called for addressing some of the issues related to broad-based health training, and directed the President to develop a five-year global health strategy that emphasizes country ownership, integrated and coordinated U.S. global health assistance, and funding based on performance. 
Other groups argue that concerns about the capacity of recipient countries to sustain NTD programs are unfounded for several reasons. First, donors are supporting plans developed largely by endemic countries. As such, countries receiving support have already prioritized and allocated some of their own resources to combating the diseases. Second, NTD treatment programs aimed at the seven most common NTDs pose little burden to health systems, as they can be administered by non-health workers (like teachers) outside of clinical settings. This community-based approach, some argue, bolsters weak health systems because it reaches people living in remote areas that usually have little access to health services, and increases demand for health services and awareness of health conditions in marginalized regions. Finally, budgets for treating the seven most common NTDs can be decreased as the diseases are eliminated. MDA cannot be independently applied to eliminate STH, however, which accounts for 80% of the NTD disease burden. Eggs from these parasites persist for years in soil, and the parasites can continue to thrive in other hosts, such as cattle.
section_title: Health Information Systems and Preventive Measures
paragraphs: NTDs are diseases of poverty. Strategies used to alleviate poverty can also help to prevent, eliminate, or eradicate these diseases. For example, development activities related to agricultural irrigation, dam construction, and forest clearance can facilitate the interruption of disease transmission. At the same time, if such projects are implemented without identifying disease prevalence through health impact assessments and integrating certain health measures, they can offer breeding grounds to several disease-carrying vectors, such as mosquitoes, and accelerate disease transmission. Examples abound of development projects facilitating the spread of vector-born diseases. In Tanzania, for example, abandoned and poorly maintained sanitation projects have been identified as breeding grounds for mosquitoes carrying malaria or lymphatic filariasis. Dam projects have led to the increase or introduction of schistosomiasis in Cameroon, Cote d'Ivoire, Ghana, Mali, Namibia, Senegal, and Sudan. 
Development experts need access to reliable data, however, to know where these diseases exist. Available data in most poor countries, however, are often outdated and based on small household surveys (see " Prevalence "). If managers of large-scale development programs worked with health practitioners to ensure that disease prevalence surveys are conducted, then the inadvertent spread of disease during development projects could be avoided. At the same time, health practitioners could gain a better understanding of disease prevalence, which could help in the planning, implementation, and monitoring of health initiatives. 
The process of combating diseases through an approach that combines responses by practitioners across sectors, particularly those related to health, agriculture, water, construction, and waste disposal, is known as integrated vector management (IVM). WHO calls for an intersectoral approach to controlling NTDs that is based on five areas: MDA; intensified case-management; vector control; safe water, sanitation, and hygiene; and veterinary public health (that is, applying veterinary sciences to ensure the health and well-being of humans). Most countries, including the United States, that have successfully eliminated NTDs have utilized an IVM approach, particularly in the areas of water and sanitation. Experts at the CDC assert that water and sanitation improvement should be a central component of any effective and sustainable approach to controlling NTDs. One estimate indicates that improved sanitation and water safety can reduce the prevalence rates of schistosomiasis by 75% and blinding trachoma by 25%. Water and sanitation improvement are particularly important when addressing pathogens that cannot be eliminated by drugs alone, such as STH and schistosomiasis. 
A comprehensive approach to NTD control might look like one that China is reportedly preparing to launch in sub-Saharan Africa. China is reportedly modeling the program after its own schistosomiasis control methods, which have led to interrupted transmission cycles in several regions across the country. The Chinese are reportedly planning to support the construction of latrines, the conversion of human and animal excrement into biofuel, and the procurement of tractors (to minimize contact with snail-infested water while farming). Other examples of successful intersectoral approaches have included
collaboration among the health and agricultural sectors in rice-growing regions of Asia to control malaria and Japanese encephalitis; collaboration among the health and agricultural sectors to reduce the prevalence of soil-transmitted helminths in Korea; and collaboration among the health and housing sectors to eliminate Chagas in Argentina.
subsections: section_title: Health Information Systems and NTD Prevention: Issues for Congress
paragraphs: While arguments for improving health information systems often focus on determining when mass drug administration campaigns can be stopped and detecting disease resurgence, USAID also identified cost-efficiencies in improving these mechanisms. During the first two years of implementing the NTD Program, USAID purchased treatments for schistosomiasis according to country requested levels. USAID found, however, that countries did not always use prevalence data to estimate drug quantities or follow WHO treatment guidelines. This led to inefficiencies, including drug overstocks in some areas and shortages in others. In the third year, USAID developed a new procurement system that improved drug management and forecasting processes. After improving the drug management system, USAID found that fewer drugs needed to be procured. 
Observers maintain cost-efficiencies can also be found by better integrating NTD programs with other health programs. Proponents assert the community networks that provide NTD drugs could also distribute insecticide-treated bednets and treatments against HIV/AIDS, TB, and malaria. Conversely, bednets used in malaria programs could also help to prevent people from contracting lymphatic filariasis. The Lantos-Hyde United States Government Malaria Strategy identifies plans to integrate malaria and NTD activities but does not specify how this will occur.
Improved integration of NTD activities into projects funded through the Senator Paul Simon Water for the Poor Act ( P.L. 109-121 ) may present another opportunity to intensify NTD control. The act authorized the President to develop an integrated strategy for improving water and sanitation worldwide. According to a 2010 report to Congress, the Administration has developed strategies for 34 countries, which include all NTD focus countries. The United States might also consider sharing resources provided through the Millennium Challenge Corporation (MCC) for water and sanitation programs. Although MCC water programs tend to emphasize reducing diarrheal-related deaths, populations suffering from diarrhea are often afflicted with other water-borne diseases like schistosomiasis (though the diseases may not be detected). 
Observers have cited instances in which U.S. aid agencies operating in the same country have used different implementing partners, consulted with different stakeholders when planning the projects, and partnered with different government officials, even when focusing on the same health challenge. While acknowledging duplication in some areas of U.S. health aid, Secretary of State Hillary Clinton contended GHI aims to address this challenge. Nonetheless, with little available documentation on GHI, not much is known on the extent to which the initiative is curbing such practices. USAID also maintained these criticisms do not apply to U.S.-supported NTD programs because they support national NTD plans. Where possible, ambassadors in recipient countries could ensure that USG agencies implementing health and development projects operate from joint working agreements and align their activities (including training, reporting, funding, and target populations), especially in non-GHI focus countries. The 2010 Quadrennial Diplomacy and Development Review appears to endorse this idea.
section_title: Funding Research and Development of Innovative Tools
paragraphs: Widespread use of the term NTD belies the complexity of the health challenge. The existence, efficacy, and availability of tools to diagnose, cure, and control each disease vary. Progress in controlling, eliminating, and eradicating NTDs also varies among the geographical locations. The seven most common NTDs that account for 90% of all NTD cases can be treated with relatively inexpensive drugs that are effective in low-resource settings. Through massive treatment programs, two of these seven diseases, onchocerciasis and lymphatic filariasis, have been nearly eliminated in some settings. People living in areas endemic with two other NTDs (schistosomiasis and STH) that account for 80% of all NTD cases, however, must be treated indefinitely if other public health measures are not taken (e.g., building and using latrines and ensuring proper use of purified water). Other NTDs, like dengue and buruli ulcer, have no known cure. Another NTD, human African trypanosomiasis (sleeping sickness), is always fatal if not treated; another, leishmaniasis, is treated with drugs that are extremely toxic and difficult to administer. To address these challenges, several health advocates call for greater investments in R&D in four key areas: 
Drug and vaccine development —While donor funding has led to an unprecedented capacity to treat NTDs, some analysts are concerned about drug resistance and urge prudence in drug administration, particularly for diseases that cannot be eliminated through MDA. Others argue that these concerns should not hinder the provision of drugs that alleviate human suffering and save lives. Several experts also call for researchers to develop vaccines that can prevent people from contracting NTDs and to create innovative treatments for diseases with no cure, or for which available drugs are toxic or carry complicated regimens (both in terms of the complexity of administering the medicine and the duration of treatment). Vector Control— For most NTDs, there are no vaccines to prevent infection and MDA programs cannot independently eradicate the pathogen. In such circumstances, vector control often plays a vital role. However, several peer-reviewed articles highlight challenges related to vector control, including growing pesticide resistance caused in part by improper application or overuse. Diagnostic Tools— Disease monitoring and surveillance are critical for detecting drug resistance and treatment-related complications, identifying interruptions in disease transmission, determining when MDA can be ceased, and identifying disease resurgence (especially after a disease has been eliminated). However, available diagnostic tools may not be useful in low-resource settings that lack sufficient quantities of laboratory equipment and trained health practitioners. As such, some epidemiologists are concerned that poorer countries may not be able to assume full control of disease surveillance tasks. Operational Research —Some health experts encourage further consideration of factors that might affect drug efficacy or safety, such as co-application of traditional remedies and treatments for HIV/AIDS, TB, and malaria. Some evidence indicates, for example, that the vaccine against TB is less effective among people infected with schistosomiasis. More research could also be useful to study the impact of NTD treatments on those infected with other NTDs. Researchers found, for example, that people co-infected with onchocerciasis and loaisis should not be treated with a drug (ivermectin) commonly used to cure onchocerciasis, as they could experience serious side effects or death. Observers also call greater attention to factors related to NTDs that are more complicated to treat, such as maintaining drug efficacy without refrigeration. These issues buttress calls for bolstering research and development in developing countries, particularly in sub-Saharan Africa. 
The weak medicine regulatory authorities (MRAs) in several developing countries also warrant consideration. In order to ensure the safety and efficacy of a proposed drug, MRAs need access to fully functioning laboratories and well-trained technicians capable of testing samples and determining whether medicines meet quality criteria. In a 2007 WHO study, almost all high-income countries reported having a quality management system in place to monitor adverse drug reactions (ADRs), while only 50% of low-income countries reportedly evaluated medicines to detect ADRs. Without the resources to evaluate properly the safety, efficacy, and quality of new medicines, one team of experts found that MRAs in most low-income countries, particularly in Africa, rely heavily on MRAs in high-income countries. For NTD treatments, however, regulatory authorities in high-income countries may not have sufficient safety and efficacy data on which to conduct comprehensive risk-benefit assessments when approving drugs intended for poorer countries and may not consider complications that are pervasive in poorer areas.
subsections: section_title: Funding Research and Development: Issues for Congress
paragraphs: According to a study conducted by the George Institute for International Health, the United States is the world's largest funder of research and development for the treatment and control of NTDs ( Table 5 ). In FY2008, the USG accounted for roughly 41% of all funding for NTD-related R&D and about 48% of all spending by the top 12 donors. If contributions by the Bill & Melinda Gates Foundation are added, total U.S. support for R&D for NTDs accounted for 62% of all spending and 71% of outlays by the top 12 donors. Nonetheless, NTD activists call for greater investments in NTD research, particularly since HIV/AIDS, TB, and malaria accounted for 72% of these funds in 2008 ( Table 6 ). Some analysts believe that investments in these diseases outpace spending on other NTDs, because high-income countries are also susceptible to and affected by HIV/AIDS and TB.
The U.S. government has demonstrated support for higher spending on R&D for global health overall and for NTDs in particular. In a March 2010 letter to USAID Administrator Shah, several members of Congress called on USAID to determine an appropriate funding strategy that considers R&D funding for NTDs. The Agriculture, Rural Development, Food and Drug Administration, and Related Agencies Appropriations Act, Fiscal Year 2010 directed the FDA to establish internal review groups to address rare and neglected diseases, to report to Congress one year after establishing the review groups and to issue guidance relating to rare and neglected diseases. In March 2010, the Food and Drug Administration (FDA) established two new expert working groups, the Rare Disease Review Group and the Neglected Disease Review Group. In September 2010, the neglected diseases group hosted a public hearing to share ideas with stakeholders on how FDA should tackle neglected diseases. The Neglected Disease Review Group is expected to submit a report to Congress that includes recommendations on how FDA should address NTDs. Ahead of the findings, the FDA has already indicated that it needs additional resources to provide training and hire additional staff with expertise in NTDs.
Congress has also authorized market incentives to encourage R&D on NTDs. The Orphan Drug Act of 1983 ( P.L. 97-414 ) and the Rare Diseases Orphan Product Development Act (ODA) of 2002 ( P.L. 107-281 ), for example, offer tax credits, market exclusivity, and priority review vouchers. Despite these actions, relatively few innovative NTD products have been developed. One study indicated that between 1983 and 2008, the FDA approved 325 orphan drug products, two of which were for NTDs. One expert at the Center for Global Development contended that all of the NTD products that were developed "had limited or no value because their formulation and pricing were inappropriate for developing country settings." Some health analysts have contended that major pharmaceutical companies have produced a limited number of NTD products because the low profit margins (if any) of NTD products leave little incentive to invest in R&D. 
In response to relatively low spending levels on NTD R&D by larger pharmaceutical companies, some advocates call for enhancing R&D capacity in developing countries and supporting public-private partnerships that include specialists from poorer countries. Innovative partnerships with experts hailing from endemic areas have reportedly developed tools that were cheaper and better adapted for field use. Some proponents call for boosting U.S. funding for consortiums such as the Special Program for Research and Training in Tropical Diseases (TDR) and the Drugs for Neglected Diseases initiative (DND i ), which have played a critical role in identifying innovative NTD tools. The $4.8 million the United States donated to TDR during the 2008-2009 budget period amounted to about 6% of all contributions. The $1.4 million the United States contributed to DND i accounted for 0.9% of all donations. 
In addition to calls for greater U.S. support for NTD-related R&D, supporters urge the 112 th Congress to consider enacting legislation similar to a bill introduced in the 111 th Congress called the 21 st Century Global Health Technology Act (111 th Congress, H.R. 3560 / S. 1591 ), which would have authorized $5 million in each fiscal year from 2010 through 2014 to improve laboratory capabilities in developing countries. Other recommendations for encouraging companies to develop drugs for the poor and strengthening medicine regulatory capacity in low-income countries include
aligning U.S. regulatory guidelines with those of the WHO; encouraging pharmaceutical companies to use and develop patent pools; including regulators from endemic areas when conducting regulatory reviews of novel NTD products; and applying U.S. regulatory expertise to the review of novel NTD products produced outside the United States.
section_title: Final Discussion
paragraphs: As noted, neglected tropical diseases are diseases that primarily plague the poorest people in the poorest parts of the world. Changes in the environment and population flows, however, make industrialized countries, including the United States, vulnerable to some NTDs as well. In May 2009, CDC reported that 28 people who lived in or had visited Key West, FL, had contracted dengue. With the exception of a few dengue cases that occurred along the Texas-Mexico border in the 1990s, the Florida Keys cases were the first dengue cases reported in the continental United States since 1946. Some observers are concerned that mosquitoes capable of spreading dengue fever are gradually spreading across the United States, particularly since there is no vaccine or treatment against this disease. Without the care of trained physicians, about 20% of those infected with dengue haemorrhagic fever (DHF) die. Access to health practitioners who are trained to identify DHF and treat its effects can reduce that rate to about 1%. Mosquitoes capable of spreading dengue are now found across the southeastern United States, along the eastern seaboard up to southern New England, and around areas bordering the Mississippi River and its watershed up to Chicago. Scientists expect the mosquitoes to broaden their range.
In recent years, cases of Chagas have also emerged within the continental United States (thought by some to have been brought by migrants from Latin America). While blood centers are now required to test for Chagas, some health experts surmise that several cases remain undiagnosed in the United States and that Chagas stands as an undetected cause of heart disease and stroke. In addition, travelers from industrialized countries are increasingly contracting NTDs like schistosomiasis while engaged in eco-tourism and other travel "off the beaten track." These cases are usually identified once tourists develop severe, acute infection or other unusual problems.
Concerns about domestic vulnerability to NTDs bolster the view that improving global health and countering NTDs is mutually beneficial for recipient and donor countries. While poor countries could benefit from U.S. research and development of innovative tools to treat and detect NTDs, for example, the United States could be better protected by an improved capacity to detect and respond to emergent cases of tropical diseases within its borders. The 112 th Congress might consider introducing a bill similar to one that the House passed in the 111 th Congress that calls for the Secretary of the Department of Health and Human Services to report to Congress on "the epidemiology of, impact of, and appropriate funding required to address neglected diseases of poverty." Included among the diseases specified in the bill are Chagas and soil-transmitted helminths.
The United States offers more resources to tackle NTDs than any other country. The U.S. approach to addressing this problem, however, faces several complicating factors. These include the following:
Conflict —When conflict erupts, treatment programs are frequently interrupted, which provides the disease an opportunity to resurge. Additionally, NTDs can easily spread in the crowded and sometimes unsanitary conditions of refugee camps.
Global urbanization —Trends indicate that by 2050, 75% of the world's populations will live in urban areas. Much of this growth is expected to occur in poor countries already struggling to meet the basic needs of their populations. Unfettered population shifts from rural to urban areas coupled with poor urban planning could lead to increased NTD outbreaks in urban areas. People carrying soil-transmitted helminths, for example, could move to urban areas and spread the disease, particularly in slums where access to clean water, sanitation, and health services is limited. 
Other donor support —Efforts by philanthropy groups and pharmaceutical companies aside, few donors have pledged to provide sufficient resources to fund NTD-related resolutions (though they may be engaged in bilateral efforts). At the 2008 G8 summit, members committed to support global NTD efforts and to reach at least 75% of people infected with NTDs. Following the summit, Britain pledged to spend £50 million (about $92 million in 2008) over five years to combat NTDs, and the United States announced its plan to spend $350 million on NTDs over five years (see " U.S. Government Responses to NTDs "). Additionally, in May 2010, the Netherlands pledged to provide up to €70 million (about $87 million) over four years for the development of medicines and vaccines against several diseases, including NTDs. 
Some groups call for countries like Brazil, China, and India to contribute more to the global fight against NTDs, especially since they have received financial assistance to address NTDs and their economies have demonstrated strong growth. One study indicates that the global disease burden for soil-transmitted helminths, lymphatic filariaisis, and trachoma could be reduced by 20% if Brazil, China, India, and Russia assumed full control over their own NTD control and elimination efforts. This assertion is particularly provocative, as one report discusses the emergent role of Brazil, China, India, Russia, and South Africa in addressing global health challenges worldwide. Similarly, one expert calls on the Organization of Islamic Conference to contribute to the Global NTD Plan, particularly since member countries including Bangladesh, Chad, Mali, Niger, Nigeria, Indonesia, Somalia, Sudan, and Yemen all have NTDs. 
Veterinary Capacity —WHO and other experts express concern about limited expertise in addressing NTDs in some countries and declining knowledge in others, particularly in the areas of vector control, case-management, pesticide management and veterinary health. Since some NTDs are zoonotic infections—human infections originating in animals—monitoring and controlling the diseases in animals are critical and often overlooked parts of NTD control. WHO recommends a five-pronged approach to tackling NTDs, which includes strengthening veterinary capacity.
At a January 2011 speech, USAID Administrator Shah indicated the agency would increasingly make tough decisions while considering which health and development efforts to fund. Specifically, the unit cost of impact would be the key determinant. Measuring the cost effectiveness of health programs could be a complicated endeavor. For example, what factors should be weighed more heavily: mortality rates, disease prevalence, or contagiousness? How might the United States address diseases that countries might not prioritize, but could be easily spread? Should countries receive assistance based on their ability to fund a national response or based on their portion of the global disease burden? 
For NTDs in particular, several other questions might arise. How might countries graduate from U.S. health assistance if NTDs that cause more than 80% of the NTD disease burden cannot be eliminated by treatment alone and affected countries have several other health challenges to consider? If the United States reduces support for a more expensive health issue, like HIV/AIDS, would countries maintain less expensive programs that carry a lower mortality rate like NTDs? While there appears to be consensus on the need to reevaluate U.S. foreign assistance programs, experts do not yet agree on the best approach to this challenging exercise.
Appendix A. Acronyms
Appendix B. Glossary
Anemia —abnormally low hemoglobin concentration in the blood. Hookworm, for example, can cause iron deficiency anemia or loss of iron in the blood.
Chemotherapy —the use of chemicals or antibiotics to treat an infection, a malignancy, or other condition with the aim of curing it or preventing its further progress.
Coverage —the proportion of people in a target population or group who have taken a drug or drug combination.
Disability-adjusted life years —a measure of overall disease burden, expressed as the number of years lost due to ill-health, disability, or early death.
Disease burden —the amount of ill health from a given cause (disease, injury, cause of disease, or risk factor) in a population of interest.
Disease mapping —a method for displaying spatial distribution of cases of disease.
Elimination —the control of a previously prevalent communicable disease by reducing case transmission to a predetermined low level, although not necessarily to zero. The aim is to achieve a situation where the infecting agent cannot sustain itself in the population until the disease no longer presents a major public health problem.
Endemic —the constant presence in a population of a condition such as a communicable disease.
Eradication —ending all transmission of an infectious disease agent by bringing about the extermination of the disease agent. Diseases such as guinea worm, measles, and polio have been eradicated regionally. Smallpox, however, is the only disease to have been eradicated globally.
Incidence —the occurrence of new disease events or cases. 
Incidence rate —the rate at which new events occur in a population.
Infectious disease —an illness due to a specific agent or its toxic products that arises through transmission of that agent or its products from an infected person, animal, or reservoir to a susceptible host, either directly or indirectly through an intermediate plant or animal host, vector, or the inanimate environment. 
Integrated Vector Management —a decision-making process for the management of vector populations, so as to reduce or interrupt transmission of vector-borne diseases. An integrated vector management approach takes into account the available health infrastructure and resources and integrates all available and effective measures across all sectors.
Mass drug administration —delivery of a preventive or therapeutic regimen to the entire population or to selected portions of it.
Morbidity —sickness, the state or condition of being unwell. Morbidity rate measures the proportion of people who have become sickened by a particular disease over a given time period (usually measured annually). Also, incidence rate.
Mortality —death. Mortality rate —measures the proportion of people who have died from a given cause within a certain time (usually measured annually). 
Pathogen —an organism that causes disease.
Prevalence —the total number of designated conditions, such as cases of a disease or patterns of behavior, that are present in a population at a point in time, regardless of the duration of time for which the condition or disease has been experienced by individuals in the population.
Reservoir —a receptacle for storage. Reservoir of infection , for example, refers to human or animal hosts of infectious pathogens.
Second-line treatment —offered to patients when initial therapy (first-line treatment) fails.
Vector —a living creature, usually an insect, that carries an infectious pathogen to a susceptible human host.
Appendix C. NTDs: Prevalence, Characteristics, and Regional Distribution
Appendix D. Images of Neglected Tropical Diseases
Soil-trasmitted helminths
Appendix E. Geographic Representation of NTD Co-Infection with HIV/AIDS, TB, and Malaria
Appendix F. Key Initiatives to Fight NTDs
Appendix G. Other NTD Programs
Over the past two decades, several groups have sought to increase the availability and access to treatment for NTDs in high-burdened countries. These outfits are diverse in their mission; some were established to provide treatment for a specific NTD, such as onchocerciasis, while others are regional elimination efforts. A majority of these partnerships focus on the procurement and supply of drugs, while some incorporate advocacy functions and others focus on R&D for new drugs. Below are prominent examples of groups that offer NTD programs. This list is not exhaustive. 
Bill & Melinda Gates Foundation
The Gates Foundation targets a specific set of NTDs, including cysticercosis, dengue, guinea-worm disease, soil-transmitted helminths, Human African trypanosomiasis, Human papillomavirus, Japanese encephalitis, lymphatic filariasis, onchocerciasis, schistosomiasis, trachoma, and lesishmaniasis. Between 1998 and 2009, the Gates Foundation provided more than $717 million for 163 NTD projects and contributions to international organizations and public-private partnerships, including WHO, the Guinea Worm Eradication Program and the Global Network for Neglected Tropical Diseases.
Carter Center
The Carter Center the Center focuses on six diseases: dracunculiasis (guinea worm), onchocerciasis (river blindness), trachoma, schistosomiasis, lymphatic filariasis, and malaria. The Carter Center is possible best known for its leading role in eliminating guinea worm. Efforts launched in 1986 by the Carter Center have contributed to a 99% reduction in global incidence of guinea worm. In 1997, the Carter Center expanded its focus on diseases to include health system strengthening. 
Children Without Worms
Children Without Worms is a partnership between Johnson & Johnson and The Task Force for Global Health (formerly the Task Force for Child Survival and Development) working to reduce the burden of soil-transmitted helminth infections in children from eight countries in Latin America, Africa, and Asia. Children Without Worms uses annual donations of medendazole from Johnson & Johnson and targets its distribution based on the size and need of local populations. 
Drugs for Neglected Diseases Initiative (DNDi)
In 2003, seven organizations launched DNDi to work in partnership with the pharmaceutical industry, academia and non-governmental organizations to develop new treatments for NTDs and strengthen research capacity in African and Asian countries. DNDi focuses on the development of new drugs for the most neglected diseases, such as Human African trypanosomiasis (sleeping sickness), visceral leishmaniasis, and Chagas disease. The primary objective of DNDi is the delivery of six to eight new treatments for leishmaniasis, Human African trypanosomiasis, Chagas disease, and malaria by 2014. 
Global Network for Neglected Tropical Diseases
The Global Network for Neglected Tropical Disease is a partnership launched in September 2006 to advocate for controlling and reducing the burden of NTDs. This partnership seeks to raise the profile of NTDs as a global health issue through advocacy, resource mobilization and global coordination efforts. Communicating success stories is an important component of the Network's work, through sharing personal stories, highlighting disease-specific achievements, and communicating progress in the field. 
International Vaccine Institute
The International Vaccine Initiative (IVI) is an international center of research, training, and technical assistance that aims to develop vaccines against diseases that plague developing countries. As of October 2010, 33 countries became signatories and an additional 16 countries were party to the initiative. The United States is not a signatory or party to the South Korean-based initiative, though WRAIR and CDC partners with IVI in various capacities (e.g., researching a vaccine against dengue) and the Bill & Melinda Gates Foundation serves as a key donor. IVI scientists have developed a vaccine against cholera and an IVI-developed vaccine against typhoid fever was 80% effective during a phase 4 trial.
Infectious Diseases Research Institute
The Infectious Diseases Research Institute (IDRI) is a Seattle-based non-profit research center aimed at applying innovative science to the research and development of products to prevent, detect and treat infectious diseases of poverty. IDRI is currently researching treatments against leishmaniasis, TB, malaria, leprosy, and Chagas.
Institute for One World Health
The Institute for One World Health is a non-profit organization aimed at developing safe, effective, and affordable new medicines to treat infectious diseases that are commonly found in poorer countries. The institute is currently focusing on developing new treatments against leishmaniasis, diarrheal diseases, malaria, Chagas, and soil-transmitted diseases.
Pharmaceutical Industry
Primarily through large donations of NTD treatments for little or no cost, the pharmaceutical industry plays an important role in global NTD initiatives. Key pharmaceutical companies include Bayer HealthCare, GlaxoSmithKline, Johnson & Johnson, MedPharm, Merck Inc., Merck KGaA, Novartis, Pfizer, and Sanofi-aventis. One example of the pharmaceutical industry's central role to the global response to NTDs is Merck's Mectizan Donation Program. Launched in 1987, the effort stands as the longest-running disease-specific drug donation program. Merck initiated the initiative with large quantities of free Mectizan to treat onchocerciasis and expanded the program in 1998 to target lymphatic filariasis. In a 2008 report, Merck indicated that it had donated more than 2.5 billion tablets of Mectizan that were used to treat 80 million people in Latin America, Africa, and the Middle East. 
Sabin Vaccine Institute
The Sabine Vaccine Institute is a non-profit organization that advocates for and engages in R&D of innovative vaccines to prevent the spread of infectious and neglected tropical diseases. The institute is currently focusing on developing vaccines against hookworm, schistosomiasis, and malaria. The Sabin Institute also supports technology transfer to less developed countries, such as efforts with Brazil.
Special Program for Research and Training in Tropical Diseases
The Special Program for Research and Training in Tropical Diseases (TDR) was established in 1975 to support the development of new tools to fight tropical diseases and strengthen the research capacity of affected developing countries. The program is executed by WHO and co-sponsored by UNDP, the United Nations Children's Fund (UNICEF), and the World Bank. TDR anticipates facilitating the elimination of four NTDS globally: Chagas disease, leprosy, lymphatic filariasis, and onchocerciasis. It also aims to eliminate visceral leishmaniasis in Latin America. According to the TDR Business Plan for 2008-2013, none of the targeted diseases can be eradicated with current tools and investments, though regional elimination can be achieved. Donor contributions to TDR have increased over the past decade from $57 million in the 2000-2001 budget period to $77.5 million between 2008 and 2009. The United States is a key donor to TDR, though U.S. contributions have declined over the past decade. During 2000-2001, the U.S. contributed $9.2 million, or 16% of total contributions. Between 2008 and 2009 U.S. contributions totaled $4.8 million, amounting to roughly 6% of all contributions.