Allocating just 1%–2% of Global Health Initiative funds to conduct research and development
for neglected tropical diseases drugs, vaccines, and diagnostics would create a new
generation of tools to eliminate our planet's greatest scourges and help shape United
States foreign policy.
On May 5, 2009, the Obama Administration announced its intention to launch an ambitious
United States governmental strategy for global health [1]–[3]. The US Global Health
Initiative (GHI) proposes US$63 billion over 6 years (FY 2009–FY 2014), US$10.5 billion
annually on average, approximately 70% of which would be spent on the US President's
Emergency Plan for AIDS Relief (PEPFAR) [1]. If appropriated each year by Congress,
the GHI would represent a significant response to calls by the Institute of Medicine
of the National Academies for the US government (USG) to invest US$15 billion annually
on development assistance for global health by 2012 [3].
In its current form, most of GHI is devoted to direct implementation of existing treatments
and preventive interventions for the “big three diseases,” i.e., HIV/AIDS, malaria,
and tuberculosis, especially the delivery of antiretroviral drugs and other prevention
measures, antimalarial drugs and bednets, and direct observed therapy, respectively,
as well as other critical interventions to improve maternal and child health and strengthen
health systems [1], [3]. There is also an unprecedented commitment to provide treatments
for the neglected tropical diseases (NTDs), with US$65 million committed in FY2010
for rapid impact packages and related measures targeting the seven most common NTDs,
which comprise the most prevalent infections affecting the world's poor [4]–[8].
The US Commitment to Neglected Diseases R&D
GHI is already making a huge difference in the lives of the world's 1.4 billion poorest
people in developing countries who live below the World Bank poverty figure of US$1.25
per day—a group sometimes referred to as the “bottom billion” [4]. However, currently
GHI largely fails to address research and development (R&D) needs for the manufacture
and testing of a new generation of global health products, i.e., new drugs, vaccines,
diagnostics, and other tools, for neglected diseases, defined broadly here to include
both the big three diseases and the NTDs [9]. To be sure, outside of GHI, the USG's
overall investment in neglected diseases runs deep [9]. According to the 2009 G-FINDER
(Global Funding of Innovation for Neglected Diseases) report in 2008, the USG provided
almost three-quarters of all global public spending on neglected diseases, with an
estimated approximate investment of US$1.25 billion [3], [9]. Approximately 86% (US$1.08
billion) of those funds came from the National Institutes of Health (NIH) and most
of that from the National Institute of Allergy and Infectious Diseases (NIAID), with
80% of the NIAID funds committed for the big three diseases [9]. NIH-NIAID currently
provides intramural support for the Dale and Betty Bumpers Vaccine Research Center
(VRC), whose primary mission is to develop global HIV/AIDS vaccines [10], and the
Laboratory of Malaria Immunology and Vaccinology [11], as well as substantial extramural
support to universities and private research institutes to support basic research,
the development of new drugs to overcome resistance [12]–[15], and some vaccine research.
In addition, the United States Agency for International Development (USAID) provides
substantial resources to support vaccine development for HIV/AIDS through the International
AIDS Vaccine Initiative, a non-profit product development partnership (PDP) [16],
and for malaria vaccine development in collaboration with the Walter Reed Army Institute
for Research [17].
In 2008, over 60 ministers of health, science, technology, and education met in Bamako,
Mali, for a Global Ministerial Forum on Research for Health [18]. The resulting call
to action asked countries to commit themselves to allocate at least 2% of national
health budgets to research, while funders such as the USG were asked to invest at
least 5% of health sector aid for research [18]. The research funds provided by NIH
alone (and indeed just NIAID commitment) are sufficient to meet the challenge laid
out in Mali, and altogether the USG has spent US$1.25 billion annually on neglected
disease research, the equivalent of approximately 12% of funds spent annually on GHI.
R&D Targeted Specifically for the NTDs
A closer analysis of the USG's commitment to global health research reveals that only
a very small percentage of funds for R&D were spent on the NTDs, with minimal support
for the PDPs that produce new products for these conditions. Thus, while the USG invests
heavily for neglected diseases R&D, there is a specific gap for NTD product support.
Why is this significant?
The NTDs are primarily parasitic and bacterial infections, which together with dengue
fever represent the most common conditions of the bottom billion [4]–[6]. The seven
most common NTDs include the three major soil-transmitted helminthiases—ascariasis,
hookworm infection, and trichuriasis (600–800 million cases for each helminth infection
worldwide)—followed by schistosomiasis (200–600 million infections), lymphatic filariasis
(120 million), trachoma (40 million), and onchocerciasis (20–40 million), followed
by liver fluke infection (20 million), leishmaniasis (12 million), and Chagas disease
(8–9 million) [19]–[22]. However, an unknown number of people, possibly as many as
50 million, may also be infected with amebiasis and dengue fever [23], [24]. Practically
speaking, these huge numbers mean that virtually all of the bottom billion, i.e.,
all of the world's poor, suffers from at least one NTD. Moreover, the disabling effects
of NTDs in children, pregnant women, and agricultural workers have been shown to produce
a profound economic impact that actually traps the bottom billion in poverty [7],
[19].
While the USG (through the NIH) and the major pharmaceutical companies are engaged
in a global enterprise for developing new drugs and vaccines for HIV/AIDS, malaria,
and tuberculosis, by comparison NTD product development is being neglected [6]. A
list of the most urgently needed new control tools for the NTDs was highlighted previously
[6]. The priority list includes safer and more effective drugs for kinetoplastid infections,
such as Chagas disease, leishmaniasis, and human African trypanosomiasis; a macrofilaricide
drug; and new vaccines to combat leishmaniasis, Chagas disease, hookworm infection,
schistosomiasis, dengue, and enteric bacterial pathogens [6]. Such biotechnologies
have been referred to as “antipoverty vaccines,” a term that reflects the reality
that most of the NTDs actually cause poverty because of their adverse impact on child
development and cognition and worker productivity. Thus, NTD vaccines (and presumably
drugs and diagnostics as well) represent critical interventions for promoting economic
development as well as health in low-income countries [4], [7], [8]. A more complete
list of needed antipoverty technologies is provided in Table 1 [6], [9].
10.1371/journal.pntd.0001133.t001
Table 1
New products required or under development for the major NTDs.a
Disease
New Drugs
New Vaccines
New Diagnostics
New Vector Control Products or Zoonotic Animal Reservoir Products to Block Transmission
to Humans
Protozoan NTDs
Amebiasis
−
+
+
−
Balantidiasis
−
−
−
−
Chagas disease
+
+
+
+
Giardiasis
−
−
+
−
Hum. African trypanosomiasis
+
+
+
+
Leishmaniasis
+
+
+
+
Heliminth NTDs
Taeniasis-cysticercosis
+
−
+
+
Dracunculiasis
−
−
−
−
Echinococcosis
+
−
+
+
Food-borne trematodiases
+
+
+
+
Loiasis
+
−
+
−
Lymphatic filariasis
+
−
+
+
Onchocerciasis
+
+
+
+
Schistosomiasis
+
+
+
+
Ascariasis
−
−
+
+
Hookworm
+
+
+
−
Trichuriasis
+
−
+
−
Strongyloidiasis
+
+
+
−
Toxocariasis
+
−
+
+
Viral NTDs
Dengue and other flaviviruses
+
+
+
+
Rabies
+
+
+
+
Rift Valley fever
+
+
+
+
Bacterial NTDs
Baronellosis
+
−
+
−
Bovine tuberculosis
+
+
+
+
Buruli ulcer
+
+
+
−
Cholera
+
+
+
−
Enteric pathogens (Gram neg)
+
+
+
−
Leprosy
+
+
+
−
Leptospirosis
+
+
+
−
Rheumatic fever
−
+
−
−
Trachoma
−
+
+
−
Treponematoses
+
+
+
−
Fungal NTDs
Mycetoma
+
−
+
−
Paracoccidiomycosis
+
+
−
−
Ectoparasitic infections
+
−
+
−
a
List of NTDs modified from http://www.plosntds.org/static/scope.action.
+, New product needed or under development; −, new product not required or need not
yet determined, based on information compiled from [6], [9], and the additional opinions
of the author.
Because the NTDs occur almost exclusively among the bottom billion, most of the antipoverty
technologies have no commercial value even though they offer the promise of tremendous
public health benefit [6]–[9]. It follows that in the absence of substantial financial
returns, with a few exceptions (such as the development of a vaccine for dengue, which
also has a potential market for Singapore, the Gulf Coast of the United States, and
the wealthier Brazilian coastal cities, for example), most of the major pharmaceutical
companies have not embarked on substantial R&D programs for NTD products. Instead,
today many of the antipoverty technologies are being developed by PDPs, i.e., non-profit
organizations that employ industrial business practices in order to develop new technologies
for neglected diseases [25], together with scientific R&D institutes and organizations
in disease-endemic countries. Today, the PDPs depend on support from European governments
in addition to substantial funds from the Bill & Melinda Gates Foundation [25], with
comparatively modest support from the USG.
Thus, while the NIH is a significant contributor to global health research, the agency
spends a high percentage of its funds on the big three diseases, with less than 10%
of its overall neglected disease research budget to fund the most common NTDs, including
the kinetoplastid infections ($49 million), dengue ($27 million), and all of the helminth
infections ($23 million). Moreover, most of these NIH funds are allocated to basic
research and not product development. In addition, USAID provides no funds for PDPs
committed to the NTDs. This situation has started to turn around with a new effort
by NIAID to fund PDPs [26], together with two decades of support for overseas Tropical
Medicine Research Centers [27], but overall the USG, and USAID in particular, has
not made major commitments to PDPs for NTD product development and clinical trials.
In contrast, several European governments, including the British Department for International
Development [28] and the Dutch Ministry of Foreign Affairs [29], have recently committed
substantial PDP support, as well as the Brazilian Ministry of Health, which now supports
PDPs for NTDs [30].
Overall, it has been estimated that approximately US$1 billion per year over the next
10 years will be required to put experimental treatments and vaccines in the PDP pipeline
through large human trials and file them with regulators [31]. Other unpublished estimates
have quoted considerably higher dollar amounts. Ultimately, a significant portion
of this level of support could be provided by the USG, as well as European governments
and the European Commission, and even some emerging market economies [32]. The Institute
of Medicine of the National Academies 2009 report, The U.S. Commitment to Global Health:
Recommendations for the Public and Private Sectors, specifically recommended support
for PDPs committed to developing novel global health technologies and interventions
[3].
R&D for Vaccine Diplomacy
There are several important reasons why the USG should support NTD product development
and testing by providing funds for both PDPs and for science and technology agencies
of NTD-endemic countries. These activities are consistent with our nation's humanitarian
principles because there is a key human rights dimension to NTD mitigation [33]. It
has been previously argued that just as the world's poorest people have a fundamental
right to have access to essential medicines, they also have rights to biomedical innovation
[6]. But even beyond this humanitarian rationale there is an equally important element
of enlightened self-interest for the USG and other governments to invest in R&D for
antipoverty technologies.
The control and elimination of the NTDs potentially has US foreign policy implications.
Most of the world's NTDs are believed to occur in areas of greatest US geopolitical
interests [5]. The most heavily affected nations include those comprising the Organisation
of the Islamic Conference, as some of the worst affected nations include the poorest
Islamic countries, such as Indonesia, Bangladesh, Sudan, Mali, and Chad [34]; they
also include powerful middle-income nations with nuclear weapons capabilities such
as India, Pakistan, Iran, and North Korea [35]. Additionally, a further relationship
has been noted between nations with NTDs and conflict such that the countries with
the highest prevalence of NTDs are the most likely to have been engaged in war over
the last two decades [36]. Indeed, the links between geopolitical interests, conflict,
and neglected diseases provide a rationale for launching the GHI under the auspices
of USAID and the Department of State, rather than through the NIH, CDC, or other agencies
of the Department of Health and Human Services.
Because the NTDs have such a major geopolitical dimension, R&D for new antipoverty
vaccines and drugs may therefore represent more than simply promoting new technologies
for improving health. Instead, over the next decade the antipoverty technologies could
emerge as powerful new interventions to enhance US foreign policy. I have used the
term “vaccine diplomacy” to describe joint R&D activities between nations, especially
those with major ideological differences [37]–[40]. This concept arises in part from
an interesting Cold War history that led to the joint US–Soviet development of the
oral polio vaccine [37]–[40]. With this paradigm in mind, could GHI funds be spent
in order for American scientists to conduct similar science and technology diplomacy
with selected middle-income countries, including some so-called innovative developing
countries, specifically those with both high rates of NTDs and a sophisticated infrastructure
for conducting scientific R&D [39]–[41]?
Concluding Remarks
Setting aside approximately 1%–2% of the GHI (roughly US $100–200 million annually)
for R&D on new antipoverty vaccines and drugs would dramatically increase the current
support for new NTD antipoverty technologies, and simultaneously provide capacity
building activities for key disease-endemic countries of strategic interest to the
US. It could also provide a new and exciting role for PDPs committed to the NTDs,
many of which are US based, to engage in vaccine diplomacy, and ultimately lead to
the development of a new generation of poverty-reducing biotechnologies. The mechanisms
by which funds are distributed could require the establishment of peer-reviewed study
sections, possibly not too dissimilar to those established by the NIH in order to
ensure that only the best science is funded, and in addition there could be specific
requirements and oversight to place the science in a diplomatic context. There are
also opportunities to bring in key international agencies and organizations, including
WHO-TDR, the Special Programme for Research and Training in Tropical Diseases [42],
and IVI, the International Vaccine Institute based in Korea and supported in part
by the United Nations Development Program [43]. Such science and technology diplomatic
outreach could lead to new peacetime roles for foreign scientists currently engaged
in nuclear weapons development, meet President Obama's 2009 challenge in Cairo when
he called on the US to reach out to the Islamic world [44], and simultaneously create
a new dimension in US foreign policy that also plays to America's great strengths
and intellectual prowess in biomedical R&D.