Breakthroughs Blog: Tuberculosis

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. GHTC member the International Vaccine Institute and the Institute for Translational Vaccinology have agree to collaborate on vaccine research and development and to promote capacity building in low- and middle-income countries. The partnership will focus on improving available technologies, as well as regulatory processes. The House and Senate Committees on Appropriations have released a fiscal year (FY) 2014 omnibus appropriations bill . Funding for global health programs at the US Agency for International Development saw some increases, while the National Institutes of Health remains woefully underfunded—even with an increase of $1 billion over last year’s post-sequestration levels. Results of an early-stage clinical trial show that stem cells taken from patients’ own bone marrow could be used to treat multidrug-resistant and extensively drug-resistant tuberculosis (TB). More tests will be required before this treatment option is validated as a possible alternative to current TB drugs. New research from Washington University in St. Louis School of Medicine has found that a form of malaria attacks red blood cells by “clamping down on cells with a pair of proteins.” This finding may aid scientists in the design of better vaccines and drugs against malaria.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. Researchers at Rice University have developed a rapid malaria test that uses laser pulse—eliminating the need to draw blood. The test has been found safe in healthy humans and will soon be tested on humans with malaria symptoms. The White House has nominated Dr. Deborah Birx as the next Global AIDS Coordinator and to lead the President’s Emergency Plan for AIDS Relief (PEPFAR). Dr. Birx is currently the director of the Centers for Disease Control and Prevention’s Global AIDS Program and works on PEPFAR implementation at her agency. The US Agency for International Development and GHTC member Population Council have entered into an agreement to develop a non-antiretroviral-based microbicide to block HIV and other sexually transmitted infections. If successful, the partnership could offer a low-risk, easily accessible product for women in low- and middle-income countries. According to the results of an early-stage clinical trial, patients with multi-drug resistant (MDR) or extensively drug-resistant (XDR) tuberculosis (TB) could be treated by using stem cells taken from their own bone marrow. If successful, the treatment could be an alternative for patients with MDR- or XDR-TB who do not respond to conventional drug treatment options.

In this guest post, Kari Stoever—vice president of External Affairs at Aeras—writes about European support for new vaccines against tuberculosis (TB). TB is a disease most often associated with countries in the developing world, particularly in Asia and Africa. While India and China had the largest number of cases in 2012, Europe is not immune. Europe accounts for almost 18 percent of global cases of multidrug-resistant and extensively drug-resistant TB, with the highest burden in Eastern Europe. TB is estimated to cost the European Union around €6 billion (US$8 billion) each year. New vaccines to prevent TB will be the most cost-effective and long-term approach to saving lives and money, so it makes sense that Europe leads the world in the research and development (R&D) of TB vaccines. Europe is a major contributor to the development of vaccines globally, with as much as 75 percent of the global TB vaccine portfolio either originating in Europe or being developed in partnership with European public or private organizations. Of the five major donors contributing to TB vaccine R&D, three of them are European. Since 2000, the European Commission (EC) has invested more than €34 million (over US$46 million) in research for new TB vaccines. Along with European Union Member States, the EC has also invested more than €42 million towards clinical trial site preparedness, capacity building, and support in Africa through the European and Developing Countries Clinical Trials Partnership (EDCTP). Recently the EC announced a €25 million (approximately US$34 million) call for proposals to accelerate the development of new TB vaccines. Europe is a major contributor to the development of vaccines globally, with as much as 75 percent of the global TB vaccine portfolio either originating in Europe or being developed in partnership with European public or private organizations. Credit: PATH. The announcement comes as an important new collaboration between European funders and a global network of researchers is forming. The new initiative, the Global TB Vaccine Partnership (GTBVP), aims to channel finances to TB vaccine R&D to establish a robust and diversified global portfolio of clinical and preclinical candidates. One of the top priorities for the GTBVP will be to strengthen and diversify the preclinical and clinical portfolio to facilitate a more rational, cost-effective, and accelerated vaccine development process through the sharing of technical, financial, and market risks. The GTBVP’s role will be to foster greater alignment among researchers and funders’ objectives, and implement an effective mechanism for collaboration, information-sharing, and decision-making. Aeras, the Netherlands-based TuBerculosis Vaccine Initiative (TBVI), the EC, the European Investment Bank (EIB), the Bill & Melinda Gates Foundation, and the EDCTP are spearheading the development of the GTBVP. The evolution of the collaboration The push for a new financing mechanism and governance structure began in March 2012 when the EC, with support of the EIB, expanded its engagement with TBVI and Aeras to develop a Business Case for Investment. The document provides evidence of a viable market incentive for new TB vaccines, opening the door for more expensive later stage trials to be financed through cost-sharing arrangements with industry and the use of other risk-sharing financial instruments. Public sector grant funding for early stage research would act as a catalyst for this private sector investment, providing significant leverage to donors. By working with researchers around the world, it is envisioned that the GTBVP will play a crucial role in ensuring that research into life-saving TB vaccines continues to progress in the most efficient way possible. Europe’s leadership has been critical to the formation of the partnership, and the EC is to be commended for its excellent commitment to much-needed health interventions, especially a vaccine that would drastically reduce the number of TB cases. TB is a global threat requiring global action, and through the new partnership there is a historic opportunity for donors, disease-endemic countries, researchers, and other stakeholders to work together and achieve the goal of having new, more effective TB vaccines available globally.

In the past, the United States has contributed to important breakthroughs in global health—from the eradication of smallpox to a 74 percent drop in measles deaths worldwide. Because of longstanding US leadership and support for global health research and development (R&D), Americans and millions around the world no longer live in fear of diseases like polio and measles, and many more are on treatment for diseases like HIV and AIDS and malaria. In fact, the US government is the largest supporter of global health R&D in the world, supporting the development and delivery of vaccines, drugs, diagnostics, microbicides, and devices. However, as we sit at a very important moment in global health product development, the political and economic environment in the United States is causing some to worry. Budget constraints have put funding at risk at many of the federal agencies involvement in global health R&D. Because of longstanding US leadership and support for global health research and development (R&D), Americans and millions around the world no longer live in fear of diseases like polio and measles, and many more are on treatment for diseases like HIV and AIDS and malaria. Photo: PATH/Evelyn Hockstein Today, the GHTC launches a new fact sheet outlining the important contributions the US government has made to global health R&D and why it’s critical the United States continues to robustly support the global health research pipeline. There are currently more global health products in the pipeline than ever before—with more than 365 new tools under development as of April 2012. Contributing to the success of many of these products is the US government’s partnerships with nonprofit product developers. These organizations partner with the public and private sectors to maximize resources and create tools for patients in low- and middle-income countries. Increased investments in global health research by the United States have the potential to increase the amount of tools combating global diseases. Just some of the products currently in the research pipeline include: The RTS,S malaria vaccine candidate, which is currently being tested and a policy recommendation for its use could be issued as early as 2015. Such a vaccine could reduce the burden of sickness and death from malaria. A new oral drug for sleeping sickness, fexinidazole, which recently entered late-stage clinical trials in patients in the Democratic Republic of the Congo. As a simple, short-course oral pill, fexinidazole could transform care for African sleeping sickness, which is fatal without treatment, and could potentially reduce its incidence among the most afflicted populations and accelerate elimination of the disease. Cost-effective diagnostics that are under development for malaria, tuberculosis, and neglected tropical diseases. These diagnostics could be administered in a variety of health care settings and could rapidly and accurately identify sick patients. An antiretroviral‐based microbicide which offers hope for women’s HIV prevention. Though more testing is needed following promising results from a 2010 advanced clinical trial, a microbicide could give women the power to protect themselves with or without their partners’ cooperation. In sub-Saharan Africa, where the epidemic has hit hardest, women 15 to 24 years old are at least twice as likely to be infected with HIV as young men.   In the research pipeline for global health products, 200 of the 365 products under development have some sort of US government support. With so much investment from the United States, there is even more at risk if funding is cut. Over the past several years, the US Congress has not been able to agree on a long-term budget for the federal government. Policymakers have allowed sequestration, or widespread automatic budget cuts, to affect all federal programs. These constraints have the potential to push back or halt promising research supported by several federal agencies involved in global health R&D—including the Centers for Disease Control and Prevention, the Department of Defense (DoD), the US Food and Drug Administration, the National Institutes of Health (NIH), and the US Agency for International Development (USAID). Due to sequestration: DoD is expected to receive budget cuts between 8 and 10 percent in fiscal year (FY) 2013. The DoD has been instrumental in the development of several global health technologies, many of which are used to protect Americans soldiers serving abroad. These cuts could affect the Walter Reed Army Institute of Research, the Naval Medical Research Center, and the Military HIV Research Program. NIH, the largest funder of global health R&D in the world, was forced to cut $1.7 billion from its budget by the end of FY 2013. NIH conducts nearly half the early-stage global health research, and supports thousands of domestic jobs all around the United States. USAID—with a presence in more than 100 countries—is best suited to support the clinical trials in low- and middle-income countries that ensure basic research is translated into appropriate health products. USAID is the largest supporter of HIV vaccine and microbicide development—both of which will be essential to achieve an AIDS-free generation. For many of the products currently in the global health research pipeline, continuous US support is essential. Without it, much of the breakthrough research that pushed these products to later-stage development will be lost—sometimes forever. US leaders should seize upon the recent successes in global health R&D and pass a long-term budget that ensures America’s legacy as a leader in innovation and science is not forgotten.