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Vaccines for Tropical Diseases and Global Research Priorities Neglected Tropical Diseases and Vaccines in Development Measles, mumps, pertussis, polio, and diphtheria are among the familiar, vaccine-controlled diseases in developed countries. In addition to these infections, populations in low-income countries confront a number of illnesses unfamiliar to most Westerners: human African trypanosomiasis, visceral leishmaniasis, Chagas disease, hookworm, schistosomiasis, lymphatic filariasis, onchocerciasis, dracunculiasis, and others.1,2 These neglected tropical diseases (NTDs), also referred to as "poverty diseases," are responsible for approximately 534,000 deaths annually worldwide and millions more serious but non-fatal illnesses.3 For example, lymphatic filariasis, commonly called elephantiasis, causes massive swelling in the arms, legs, breasts, and genitals. Dracunculiasis, or guinea worm disease, leads to the emergence of 2-3 foot long parasitic worms from painful blisters in the skin. Along with causing emotional distress, they impair children's physical and cognitive growth (primarily through associated anemia).4,5 Human parasitic diseases account for approximately 100 million disability-adjusted life years (DALYs, the number of life years lost to premature death or disability), exceeding the DALYs from diarrheal disease, lower respiratory infections, or HIV/AIDS.6 After HIV/AIDS, malaria, and tuberculosis, neglected tropical diseases as a group represent the fourth largest group of communicable diseases worldwide.7 The inadequacy of currently available treatments adds a sense of urgency to these diseases, as many first-line drugs are toxic, difficult to administer, over 50 years old, or losing effectiveness due to resistance.8 Vaccines offer a promising alternative to standard treatments of NTDs.9 Neglected tropical disease vaccines could potentially prevent 60% of global disability resulting from infectious diseases. Of the 13 poverty diseases, vaccines are in development for hookworm, schistosomiasis, and leishmaniasis. -- Hookworm occurs in approximately 576 million people worldwide, with most of its associated morbidity resulting from anemia and protein malnutrition.10, 11 Children and women of reproductive age are particularly vulnerable. High rates of re-infection and decreasing efficacy of existing drugs have led to increased interest in hookworm vaccine research.12 One hookworm vaccine has undergone Phase 1 clinical trials for safety and immunogenicity, with promising preliminary results.13, 14 Plans are underway to conduct further testing.15 -- Schistosomiasis is a blood fluke (worm) infection affecting approximately 200 million people worldwide.16 High infection rates occur near large bodies of fresh water, especially in Egypt, China, and Africa.17 Chronic consequences result from parasitic egg deposition in the bladder, intestines, and liver.18 Symptoms include anemia, relentless pain, undernutrition, growth failure, and cognitive disabilities, all of which are particularly common in children.19 Multiple vaccine development approaches are being analyzed to determine feasibility, safety, and efficacy, particularly for vaccine use in conjunction with existing treatment.20 In 2009, the Schistosomiasis Vaccine Initiative began manufacturing Sm-TSP-2, an antigen that is hoped to promote immunity when used in conjunction with existing drug therapies. The vaccine will be undergoing pre-clinical studies through 2010 and beyond, if results are positive.21 -- Leishmaniasis is a protozoan parasitic infection that can cause skin sores, fever, damage to the spleen and liver, and anemia. Worldwide prevalence is estimated at 12 million cases, with approximately 350 million individuals at risk for infection.22 Communities have sought protection against leishmaniasis for centuries, actively immunizing themselves in an ancient Middle Eastern and central Asian practice called leishmanization. In the process, an individual is inoculated with live parasites, resulting in a mild illness. The procedure has routinely been sponsored by governments during public health emergencies. Meanwhile, a number of laboratories are investigating vaccine development and several trials are underway, but the translation of animal models to humans has proved a persistent problem, and no vaccine is yet available.23 NTD Vaccine Financing: Problems and Potential Solutions The development of NTD vaccines faces significant economic challenges. With a limited market for such products, pharmaceutical companies lack financial incentives to develop and produce vaccines for low-income countries. Accordingly, only 10% of global health research is devoted to conditions responsible for 90% of the global burden of disease.24 Neglected tropical disease vaccine research and development (R&D) has high risk and a low expected return on investment in large part due to poverty among affected populations.25, 26 Economist Ernst Berndt and attorney John Hurvitz delineate two key vaccine market failures that challenge the development of vaccines against NTDs. First, because knowledge generated by research is a global public good accessed by many countries, no single government has the incentive to meet research costs through higher prices or direct funding.27 The second problem is "time inconsistency." After pharmaceutical companies have invested in vaccine R&D, public sector purchasers (i.e., government health ministries) have incentives to use their power as dominant purchasers to dictate low prices, maximizing access.28 Pharmaceutical companies are less likely to invest in products for these countries, as low prices often do not cover R&D costs, much less lead to profits.29 One solution, advance market commitments (AMCs), have the potential to guarantee commercial markets to manufacturers, advocates of this model argue. Prior to product development, purchasers (governments and international organizations) agree to finance the purchase of vaccines for low-income countries. The market price is fixed and determined in advance.30 These commitments are thought to reduce uncertainty on returns and give investors confidence.31 Difficulties arise, however, in the actual application of these programs. The interests of sponsoring donors, potential vaccine developers, and low-income countries must be balanced.32 Conflicts can occur over pricing, contract design, product diversification, quantity guarantees, and long-term sustainability. In 2007 the Global Alliance for Vaccines and Immunization (GAVI Alliance) piloted an advance market commitment to facilitate the development and availability of a pneumococcal vaccine.33 Manufacturers are permitted to charge no more than $3.50 per dose, the majority of which is funded by GAVI. The governments of the benefiting countries are responsible for a small portion of the price--as little as $0.15 or $0.30.34 GAVI hopes to increase market competition by participating in advance purchase commitments, stimulating R&D, and creating viable markets in developing countries.35 Public-private partnerships (PPPs) like the GAVI Alliance occupy a prominent role in funding vaccine development and distribution in developing countries. GAVI's partners include United Nation agencies and institutions (UNICEF, WHO, World Bank), civil society organizations (e.g., International Pediatric Association), public health institutes (e.g., Johns Hopkins University), governments, the Bill & Melinda Gates Foundation, other private philanthropies, vaccine industry representatives, and members of the financial community.36 PPPs are responsible for major transformations in the way new drugs and vaccines are developed. Their supporters believe these entities bridge commerce and philanthropy, applying a market-driven model to humanitarian initiatives. The international community--both developed and developing countries--must consider ethical questions regarding prevention of neglected tropical diseases. What obligations, if any, does industry have to both local and global communities? In a market economy, it is essential that pharmaceutical companies earn a profit so that they can reinvest in products targeted to underdeveloped countries. Does this justify tiered-pricing models in which developed countries effectively subsidize the use of products globally? What is a 'fair' price and who should make such decisions? As attention to the potential benefit of vaccines against neglected tropical diseases grows, these debates over equity, access, and pricing will continue to demand thoughtful consideration. -- By Katelin Hoskins, University of Pennsylvania (hoskinsk@nursing.upenn.edu); Updated July 2010. Continue to II. Vaccine Research Priorities and Obstacles to Access
1 Yamey G & Hotez P (2007). Neglected tropical diseases. BMJ, 335: 269-70. |
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