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Institute of Medicine (US) Forum on Microbial Threats. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies. Washington (DC): National Academies Press (US); 2011.

Cover of The Causes and Impacts of Neglected Tropical and Zoonotic Diseases

The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies.

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Policy Cures

New drugs, vaccines, and diagnostics are regularly developed for diseases that affect wealthy countries; however, they are never more needed than for so-called neglected tropical diseases (NTDs). These are infectious diseases such as dengue and helminth infections that collectively afflict hundreds of millions of poor patients in developing countries.

The cost and time to develop new pharmaceutical products is substantial. Taking the cost of failure into account (an important factor in this high-risk area), each new diagnostic is likely to have development costs in the range of US$2 million to US$10 million spread over a development time of 3–5 years (averaging US$0.5 million to US$0.75 million per diagnostic per year). Each new drug is likely to cost in the low hundreds of millions spread over 7–12 years (averaging $15 million to $30 million per drug per year); however, we note that drug reformulations or new fixed-dose combinations of existing drugs can have particularly low risks and costs. And each vaccine can cost up to hundreds of millions invested over 12–15 years of development (averaging US$35 million to US$60 million per vaccine per year).26

However, the level of investment into research and development of new products for NTDs, as reported in the annual Global Funding of Innovation for Neglected Diseases (G-FINDER) surveys, shows that few NTD areas receive anywhere near the level of funding required; and that funding, when it is available, is rarely allocated in a manner likely to move products through the pipeline to patients.

Global Funding of Neglected and Tropical Diseases

The G-FINDER surveys report global funding for neglected disease research and development (R&D) on an annual basis. These show a marked disparity not only between funding for neglected diseases and diseases that affect the developed world, but also among the neglected diseases and, in particular, the NTDs.

The G-FINDER survey defines 31 diseases as neglected, ranging from diseases such as HIV/AIDS, tuberculosis (TB), and malaria through diarrheal diseases and bacterial pneumonia and meningitis, to the NTDs. The 15 NTDs for which G-FINDER reports research and development funding are the following:

  • Kinetoplastids

    Chagas' disease


    Sleeping sickness (human African trypanosomiasis)

  • Dengue
  • Helminth infections

    Roundworm (ascariasis)

    Hookworm (ancylostomiasis and necatoriasis)

    Whipworm (trichuriasis)


    Elephantiasis (lymphatic filariasis)

    River blindness (onchocerciasis)


    Tapeworm (cysticercosis/taeniasis)

  • Leprosy

For each disease, the survey reports global R&D investment into drugs, vaccines, diagnostics, microbicides, or vector-control products, identifying the proportion of funding going to basic research; product discovery and preclinical development; clinical development; and the early product implementation phase (Phase IV trials). The survey collects data from more than 200 funders and recipients, including governments, multinational pharmaceutical firms, biotech companies, product development partnerships (PDPs) and public researchers and developers; and surveys 44 countries including most Organisation for Economic Co-operation and Development (OECD) countries as well as several low- and middle-income countries (India, Brazil, South Africa, Thailand, Ghana, and Colombia).

In 2008, these funders invested just under $3.1 billion ($3 billion in adjusted baseline dollars)27 into R&D for new products for the 31 nominated neglected diseases (see Table A16-1). By comparison, the global spend on all pharmaceutical R&D is around $100 billion (European Commission, 2008).

TABLE A16-1. Neglected Disease R&D Funding 2008.


Neglected Disease R&D Funding 2008.

Nearly three-quarters (72.8 percent) of this funding went to HIV/AIDS, TB, and malaria, diseases that are often prioritized in global health policies and frameworks such as the Millenium Development Goals and the Global Fund to Fight AIDS, Tuberculosis, and Malaria. Collectively, these three diseases received US$2.2 billion of the total global investment, including HIV/AIDS (US$1.2 billion, 39.4 percent), malaria (US$542 million, 18.3 percent), and TB (US$446 million, 15.1 percent).

By contrast, the 15 NTDs collectively received only 12 percent of global investment, or US$347 million dollars (see Table A16-2). No NTD area (including disease groups such as helminths or kinetoplastids) received more than a 5 percent share of global funding, while three diseases (leprosy, trachoma, and Buruli ulcer) received less than a 0.5 percent share.

TABLE A16-2. NTD R&D Funding 2008.


NTD R&D Funding 2008.

Who Funds NTDs?

Investment into R&D for the NTDs relies on a handful of global funders, with 12 organizations accounting for 86 percent of global NTD funding (see Table A16-3) and two donors (the National Institutes of Health [NIH] and the Bill & Melinda Gates Foundation) accounting for nearly half (49 percent). Contributions by most NTD funders are below US$20 million per year and, in many cases, a few hundred thousand dollars or less (see Figure A16-1).

TABLE A16-3. Top 12 Funders of R&D for NTDs, 2008.


Top 12 Funders of R&D for NTDs, 2008.

A bar graph showing top country funders of NTD R&D


Top country funders of NTD R&D, 2008.

Two points need to be drawn from these global NTD funding patterns. The first is the heavy reliance on U.S. investors, both public and private, who provided one-third (33.5 percent) of all NTD R&D funding. The second is the role of innovative developing country (IDC) governments (Brazil and India) who collectively provided nearly 10 percent of global NTD funding. This differs markedly from diseases such as HIV/AIDS, TB, and malaria, where IDC contributions are generally dwarfed by spending from Western governments and companies, and it appears to reflect both a general Western neglect of NTDs as well as the domestic importance of these diseases to some IDCs.

For all NTDs except dengue, new product development is predominantly or exclusively supported by “charitable” funding from public or philanthropic organizations, with little or no contribution from the pharmaceutical industry. This is the case for leprosy (100 percent, with just over half from IDC governments), kinetoplastid diseases (98 percent), trachoma (95 percent), helminths (92 percent), and Buruli ulcer (85 percent).28 This funding pattern has significant implications for both the type of research being funded and the likelihood of new products being developed, as discussed below.

Funding Patterns Across NTDs

There is a marked discrepancy not only between funding for NTDs and other neglected diseases, but also of funding across NTDs (see Figure A16-2). The kinetoplastid diseases and dengue received more than three-quarters (77 percent) of all NTD funding in 2008, with R&D for leprosy, trachoma, and Buruli ulcer collectively receiving less than 5 percent of the already modest global NTD investment (see Figure A16-2).

A pie chart showing share of NTD funding of disease, 2008


Share of NTD funding by disease, 2008.

There are also marked differences in funding patterns between diseases, including both their funding sources and how funding is allocated within each disease area.


The kinetoplastids are the fourth highest funded neglected disease area globally after HIV/AIDS, TB, and malaria, with kinetoplastid investment in 2008 being around one-third (31 percent) of TB investment. Ninety percent of kinetoplastid R&D funding comes from 12 organizations, virtually all public and philanthropic funders; industry provides only 2 percent of global kinetoplastid investment (see Figure A16-3). As with most other NTDs, NIH and the Gates Foundation are the mainstays of funding, providing more than half (56 percent) the 2008 global investment into kinetoplastid R&D (see Figure A16-3).

A list of the top 12 funders of kinetoplastid R&D, 2008


Top 12 funders of kinetoplastid R&D, 2008.

The high level of kinetoplastid funding relative to other NTDs reflects several factors, the most important being the presence of an active PDP in this area. The Drugs for Neglected Diseases initiative (DNDi) is a PDP developing new kinetoplastid drugs. These include drugs for human African trypanosomiasis (HAT) (fexinidazole in Phase I trials; nitromidazoles and oxaborole in preclinical development); for visceral leishmaniasis (sitamaquine and tafenoquine in clinical trials; new formulations of Amphotericin B in preclinical); and for Chagas disease (azoles and a pediatric formulation of benznidazole in clinical development) (DNDi, 2009). They also have a discovery portfolio across all three diseases. With an active advocacy arm, DNDi generated US$24.4 million for kinetoplastid drug development in 2009, including from many of the top 12 kinetoplastid funders such as NIH, the Gates Foundation, Médecins Sans Frontières, the European Commission, the U.K. Department for International Development (DFID), and Spain.

Funding is spread unevenly across the kinetoplastid diseases, even though all three need investment into basic research, drugs, vaccines, and diagnostics, while Chagas disease and sleeping sickness also require funding of new vector-control products. Leishmaniasis receives 41 percent of global funding, sleeping sickness receives 25 percent, while Chagas' disease is particularly poorly served, receiving only 11 percent of overall kinetoplastid investment. (The remaining 23 percent is cross-disease research.)

A closer examination of how the US$139 million of kinetoplastid funding is invested shows it is unlikely to result in generation of several badly needed new products (see Figure A16-4). Around 45 percent (US$62.9 million) of total funding was directed to basic research, a further 38 percent (US$53.5 million) to drug development (of which nearly half went to DNDi), and 8 percent (US$11.5 million) to diagnostics. Ongoing investments into these product areas at these levels, if allocated to high-capacity groups, are sufficient to move product development forward even if not as quickly as desirable. However, vaccine development received only US$7.8 million (6 percent of annual kinetoplastid funding), and there was no reported funding of vector-control R&D in 2008. At the disease level, the picture was even grimmer, with Chagas disease having no realistic investment for drugs, vaccines, or diagnostics despite the wide therapeutic gaps it currently suffers from, and HAT vaccine research was almost nonexistent (only US$131,000 was invested in 2008).

Pie charts showing kinetoplastid investment by research area for each disease, 2008


Kinetoplastid investment by research area for each disease, 2008.

It is important to note that these funding patterns do not reflect an evidence-based assessment of need; rather they are the cumulative effect of who provides the funding and who is available for product development. In the kinetoplastid field, nearly two-thirds of global funding comes from governments, who generally show a preference for basic research over high-cost and high-risk product development; there is only one vaccine in development29; and there are no companies or product development groups working to develop new control products. Only in the drug field are there both funders willing to invest and product development groups available to create new kinetoplastid products—explaining the predominance of drug R&D funding over that for other kinetoplastid products.


Currently, dengue management relies on the control of transmission and on supportive therapy to minimize patient dehydration and shock from hemorrhagic fever. Investment is needed in a vaccine that covers all four dengue serotypes; diagnostics able to detect early stage disease, to differentiate between serotypes, and to distinguish dengue from other fevers (WHO, 2007)30; and antiviral drugs that are effective once infection has occurred.

In 2008, dengue was the second-best funded of the NTDs, receiving a little less than the kinetoplastids (US$126.8 million in 2008) and just over one-quarter of the funding invested in TB research each year. It has the distinction of being the only “commercial” NTD, with the pharmaceutical industry providing just over one-third (35 percent, US$43.8 million) of R&D funding. Dengue is more attractive to companies than other NTDs because its disease burden is concentrated in higher-income developing countries in Asia and Latin America, where governments can afford to purchase new tools and may wish to defray the high costs of treating dengue, particularly hemorrhagic dengue fever, which requires hospitalization and intensive care support.

If industry figures are excluded, it is apparent that dengue funding is otherwise highly concentrated, with NIH and the Gates Foundation providing well over half (57 percent) the remaining global funding (see Figure A16-5). The role of IDC funders seeking to address their local dengue burden is also notable—Brazil in particular, but also India, collectively providing 12 percent (US$15 million) of global dengue R&D funding. This means that, unlike all other NTDs, dengue product development does not rely chiefly on “charitable” funding but is rather driven by commercial industry interests and the needs of emerging IDC governments: together, these two sectors provided nearly half (46 percent) of the 2008 global investment into new dengue products.

A list of top 12 funders of dengue R&D, 2008


Top 12 funders of dengue R&D, 2008.

Dengue funding patterns correlate moderately well with product needs, with nearly two-thirds (63 percent, US$80.9 million) of funding channeled into vaccine development, which is the most commercially viable area and also supported by a strong public health case (because supportive treatment for dengue is effective but only if instituted very early, which can be difficult in some developing world settings) (see Figure A16-6) There are currently at least two dengue vaccine candidates that have advanced to Phase II clinical trials, one that is in Phase I and four in preclinical stages. However, investment into dengue diagnostics (US$5.4 million) was modest, even taking into account their low development costs, while funding for development of drugs (US$7.6 million) and vector control products (US$2.0 million) was well below the level needed to create either of these.

A pie chart showing dengue funding by product area, 2008


Dengue funding by product area, 2008.


The large family of helminth infections was significantly underfunded, with 2008 funding for all helminth R&D being US$66.8 million, around half the annual dengue investment and only 6 percent of the annual R&D investment for HIV/AIDS.

As with other NTDs, helminth R&D was heavily reliant on a small handful of donors (when industry investment is excluded, 11 donors provided 86 percent of helminth R&D funding), in particular NIH and the Gates Foundation, who between them funded two-thirds (67 percent) of helminth research and product development (see Figure A16-7).

A list of the top 12 funders of helminth R&D, 2008


Top 12 funders of helminth R&D, 2008.

This R&D funding was distributed very unevenly across the helminth infections, even though all need basic research and new drugs; three diseases (schistosomiasis, onchocerciasis, and strongyloides) need new diagnostics; and four diseases (schistosomiasis, onchocerciasis, lymphatic filariasis [LF], and tapeworm) need new vector-control products. Vaccine development—by the far the most expensive R&D area with costs in the hundreds of millions—is also needed for schistosomiasis, onchocerciasis, strongyloides, and hookworm (see Figure A16-8).

A pie chart showing helminth funding by product area, 2008


Helminth funding by product area, 2008.

Several points can be drawn from helminth funding patterns. The first is that funding is simply too low across the board to create new helminth products in a timeframe that could be considered reasonable. The maximum 2008 funding for drug development for any helminth disease was US$4.7 million (for LF) while maximum vaccine funding was US$7.2 million (for hookworm). For most other helminth products, funding was well below these levels; for example, hookworm drug development received only US$721,000 and onchocerciasis vaccine development just under US$11,000.

The second is that helminth funding has little or no correlation with product need for each disease: for instance, both schistosomiasis and onchocerciasis need new products in all areas as well as basic research, yet schistosomiasis received 29 percent (US$19.7 million) of global helminth R&D funding while onchocerciasis received only 9 percent (US$5.9 million).

However, the most striking conclusion is that the vast majority of helminth funding is invested not in new product development but in basic research, ranging from 40 percent for elephantiasis to 60 percent for tapeworm, 71 percent for schistosomiasis, 97 percent for strongyloides, and 100 percent of investment into roundworm and whipworm.

The exceptions to this pattern (hookworm and onchocerciasis) are worth exploring. The high relative spend (70 percent, US$7.2 million) on vaccines for hookworm is directly linked to the presence of the Human Hookworm Vaccine Initiative, a PDP based at the Sabin Institute that is focused on new vaccine development. Likewise, 70 percent (US$4.1 million) of onchocerciasis funding is directed to drug development by two product development groups (a major drug company, and a small investment by the African Programme for Onchocerciasis Control). In other words, as with kinetoplastids, the presence of a dedicated product developer tends to encourage investment in applied research but, in their absence, funders lean strongly toward investing in basic research. The more promising investment pattern for hookworm and onchocerciasis should also not distract readers from the fact that in both cases funding is still far too small to generate the desired products in any reasonable timeframe.


Leprosy R&D was grossly underfunded in 2008, receiving only 0.3 percent of total global funding for neglected diseases and less than 3 percent of global funding for NTDs. All funding came from public and philanthropic organizations, with 12 organizations providing 99 percent of funds (see Figure A16-9). As with most other NTDs, NIH was the lead funder (32 percent of all investment); however, India and Brazil contributed 51 percent of global funding (just under US$5 million), reflecting the local leprosy burden in each of these countries.

A list of the top 12 funders of leprosy R&D, 2008


Top 12 funders of leprosy R&D, 2008.

Investment into new leprosy products was very modest, with well over half (58 percent, US$5.7 million) of all funding going to basic research. Development of new drugs to replace current 6–12-month multidrug treatment regimens received only US$0.7 million (8 percent of total leprosy funding) and investment into improved diagnostics was only US$0.5 million (5 percent) (see Figure A16-10).

A pie chart showing leprosy funding by product area, 2008


Leprosy funding by product area, 2008.

These very modest investments partly reflect the fact that leprosy is targeted for eradication, with numbers of new leprosy patients declining from 763,000 in 2001 to 296,000 in 2005. Although a very positive outcome from the public health perspective, this disease trajectory means that investment into leprosy products for new and existing patients can be a far less compelling story for funders (and developers) than investment into NTDs with large and/or increasing burdens of mortality and morbidity.


Trachoma is among the most neglected of the NTDs, receiving just over US$2 million in 2008 and having only five identified R&D funders, all public organizations (see Figure A16-11). The very modest industry contribution (US$96,000, 5 percent of total trachoma funding) reflects work on existing trachoma treatments rather than development of novel products.

A list of the top 12 funders of trachoma R&D, 2008


Top 12 funders of trachoma R&D, 2008.

As with leprosy, trachoma R&D suffers from a perception that a good treatment already exists, since face-washing and a one-off oral dose of azithromycin are highly effective. Yet the public health community has identified a need for new point-of-care trachoma diagnostics to replace current complex and expensive tests, or sometimes unreliable clinical diagnosis, as well as a trachoma vaccine. Neither of these products are likely to eventuate in the next 50 to 100 years if current investment patterns continue, with trachoma vaccines receiving only $99,000 in 2008 (typical vaccines cost several hundred million dollars to develop) and diagnostics only US$68,000 (diagnostics can typically be developed for $2 million to US$10 million) (see Figure A16-12).

A pie chart showing trachoma funding by product area, 2008


Trachoma funding by product area, 2008.

Buruli Ulcer

The most neglected of the 15 NTDs covered by G-FINDER was Buruli ulcer, with 2008 R&D funding under US$2 million. Of this, only a tiny sum was devoted to product development (US$310,000 in total for Buruli drugs, vaccines, and diagnostics), the majority of which came from industry (US$286,000, 91 percent of product development funding) (see Figure A16-13). Beyond this, only eight public and philanthropic organizations funded Buruli ulcer R&D, investing most of their funds into basic research (see Figure A16-14).

A pie chart showing Buruli ulcer funding by product area, 2008


Buruli ulcer funding by product area, 2008.

A list of the top 12 funders of Buruli ulcer R&D, 2008


Top 12 funders of Buruli ulcer R&D, 2008.

We note that a focus on basic research is necessary since one of the obstacles to developing new products is lack of knowledge of the cause, vectors, and epidemiology of Buruli ulcer. Nevertheless, even a modest investment in diagnostics would allow Buruli ulcer to be diagnosed sufficiently early to begin antibiotics, thus preventing development of the disfiguring ulcers that require surgical excision. Given the localized nature of Buruli ulcer, which occurs predominantly in Western Africa, and its predilection for children under 15 (WHO, 2007), development of a new vaccine could be an effective option, particularly because TB vaccines are already known to give short-term protection against the infection.

However, the chief obstacle to greater investment is that Buruli ulcer affects relatively few people compared to other NTDs, with WHO estimating around 7,000 (WHO, 2008) new cases of Buruli ulcer per year. These patients are also chiefly in sub-Saharan Africa rather than in middle-income countries, who could afford a greater R&D investment and can represent a more substantial market.


The funding patterns above highlight several key points. Research and development of new products for NTDs is severely underfunded, the only exceptions being dengue vaccines and drug development for some of the kinetoplastid diseases. Funding is not only insufficient but is generally poorly targeted, with investment patterns often bearing little relationship to identified product needs. Diseases for which expensive vaccine R&D is considered necessary, such as onchocerciasis, can receive less funding than diseases such as LF, which do not; funding in general is neither commensurate with nor matched to the product needs identified by the public health community.

The heavy reliance on public funding for many NTDs leads to a strong tendency toward investment in basic research rather than product development (which carries risks that many public funders are uncomfortable with); overreliance on a handful of public and philanthropic funders, particularly NIH and the Gates Foundation, for all diseases except dengue makes the situation even more tenuous.

Piecemeal funding, without a coherent and agreed strategy, is the hallmark of R&D funding for NTDs. However, there are noteworthy exceptions. These are diseases such as dengue and kinetoplastids, where active product development groups not only generate substantial funds (these two diseases now represent three-quarters of all NTD funding) but also focus these funds tightly onto R&D of the desired products. For dengue, this is chiefly due to industry groups and a PDP working on dengue vaccines, while kinetoplastids have benefited from the presence of an active drug PDP. A further positive trend is the role of IDC governments, who now represent nearly 10 percent of global investment into R&D for NTDs and an even higher percentage in diseases areas of particular relevance to them, such as dengue or leprosy.

The outcome of these findings is crucial for public and philanthropic funders. A great deal of the nearly US$350 million spent each year on R&D for NTDs is unlikely to generate the products that patients need. Providing small amounts of funding across many diseases and product areas is likely to be wasteful and ineffective; and, even if more funding is provided, it is unlikely to generate new NTD products unless the funding is targeted to the right areas, and those areas have product development groups in place who can successfully translate those funds into new products.

To ensure that current funding, and ideally significantly increased future funding, achieves its goal, we believe it is important that funders rethink the current approach. Funders and the global health community will need to decide what products should be prioritized, to create or identify groups able to develop these, and to provide sufficient funds to achieve their agreed objectives.

As a first step along this path, it will be important to create a methodology for assessing health return on R&D investment, so that funders can prioritize their valuable investments toward those diseases and products where they are likely to generate the greatest health impact. Pharmaceutical companies routinely assess likely market returns on investment to guide their decisions, while many governments also assess the cost-benefit of new health technologies before listing them on national health insurance schemes. However, there is no similar tool to guide investment decisions in the neglected disease R&D field.

Such a tool would need to take many factors into account, including the treatment gap, investment gap, and burden of disease in a given area, as well as the type of product needed, the state of the science (including the existence of relevant researchers and product developers), and the state of the existing product pipeline (see Figure A16-15). This task is complex but necessary because, in its absence, investment will in many cases continue to be ad hoc, inefficient, and targeted to areas where it is unlikely to deliver the desired outcomes.

A diagram showing the process of assessing health return on investment


Assessing health return on investment.

By working together, the public, philanthropic, and private sectors can make a difference in the health outcomes for many millions of patients throughout the developing world.


  1. DNDi (Drugs for Neglected Diseases initiative). Financial & Performance report. 2009.
  2. European Commission. The 2008 EU Industrial R&D Investment Scoreboard. 2008. [December 7, 2010]. http://iri​​.eu/research/scoreboard_2008.htm.
  3. WHO (World Health Organization). Buruli ulcer disease. 2007. [December 7, 2010]. http://www​​/factsheets/fs199/en/
  4. WHO (World Health Organization). Buruli ulcer progress report 2004–2008, Weekly Epidemiological Record. 2008. [December 7, 2010]. pp. 145–154. http://www​ [PubMed: 18437758]



For example, discovery and development costs of a novel tuberculosis (TB) drug have been estimated at US$115 to US$240 million, including cost of failure, while vaccine development from research and discovery through to registration has been estimated at US$200 to US$500 million—also including cost of failure), with other estimates being even higher.


All G-FINDER funding figures are adjusted for inflation and reported in 2007 U.S. dollars, as this is the baseline year against which investment trends are tracked.


We note that the relatively larger percentage industry investment in Buruli ulcer translates into a very modest dollar amount, because global funding for this disease is below US$2 million per year.


The Infectious Disease Research Institute and GlaxoSmithKline Biologics is developing leish-111f + MPL-SE, which is in Phase I.


Currently available diagnostic kits also need to be evaluated.

Copyright © 2011, National Academy of Sciences.
Bookshelf ID: NBK62528


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