Breakthroughs Blog: NTDs

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. During a meeting last week at the United Kingdom’s Royal Society of Medicine, the topic of health research was raised and how it might fit into the post-2015 development agenda. At the meeting, UK Department for International Development Chief Scientific Officer Chris Whitty spoke about the necessity of forward thinking as it relates to global health research. Whitty acknowledged the need to think ahead to what research will be needed from 2020-2040 so that priorities are defined by what the global public health world might look like in the future. Pharmaceutical company GlaxoSmithKline plans to invest up to £130 million in Africa over the next five years to build the continent’s capacity to develop new tools to combat the region’s rising occurrence of noncommunicable diseases (NCDs). New money will go to expanding manufacturing capacity in specific African countries, as well as open the world’s first open-access research and development laboratory for NCDs in Africa. The Bill & Melinda Gates Foundation, the World Bank, and other donors will invest $240 million to fight neglected tropical diseases (NTDs) in low- and middle-income countries. The new funding comes after a pledge by 13 drugmakers two years ago to donate medicines to treat ten NTDs, including river blindness, Guinea worm, and sleeping sickness. Dr. Deborah Birx has been confirmed by the Senate to be the next Global AIDS Coordinator, filling the post to lead the world’s largest health program. Widely praised by global health advocates, Dr. Birx previously led efforts to introduce the President’s Emergency Plan for AIDS Relief-sponsored rollout of life-saving HIV treatments to certain sites in Africa, and launched the first clinical research trials to show proof of concept that an HIV-preventing vaccine was possible.

The US Agency for International Development (USAID) is the nation’s lead foreign assistance agency. Throughout its 50-year history, USAID has worked with other government agencies, the private sector, and nongovernmental organizations to support the development and introduction of affordable health products appropriate for addressing the diseases and health issues in developing countries. The GHTC has launched a new blog series to highlight the impact of USAID’s commitment to global health research and development (R&D). The series will showcase stories from individuals who have benefited from the agency’s support and investment in R&D—as well as people whose lives would vastly improve if USAID were to expand its support for health R&D into new areas. Our third post is by Brian D’Cruz, a volunteer physician who has worked with Médecins Sans Frontières (MSF) in Congo Brazzaville and Central African Republic. Based on his experience with MSF, Brian writes about the urgent need for USAID to support R&D for neglected tropical diseases (NTDs) like sleeping sickness. Q: As an MSF physician working in Congo Brazzaville and Central African Republic, you saw many patients affected by sleeping sickness—an NTD that primarily occurs in the poorest, most rural areas in Africa. Can you tell us about some of your experiences treating this disease during your time with MSF? A: In Central African Republic, I saw firsthand the suffering caused by sleeping sickness. I vividly remember an 11 year old girl named Natacha. She lived in an area where medical care and screening for sleeping sickness had not been available for years due to increasing violence in the area. Our team was the first to treat sleeping sickness there in several years. Several months before we arrived, Natacha started to experience the symptoms of sleeping sickness—including sleep disturbances, memory problems, spasms of her hands, pain all over her body, and seizures. A few weeks before we arrived, she stopped walking. By the time her family was able to get to us, she could no longer speak or feed herself. During this entire time, her family was powerless to help her. By the time they reached our team, we were able to diagnose Natacha and start treatment, but it was too late. She died a few days after reaching us. Brian D’Cruz (second from the left) and other panelists discuss NTDs at a congressional briefing in June 2013. Photo: Research!America Q: What impact does sleeping sickness have on communities and individuals in Congo and Central African Republic? A: Sleeping sickness is fatal if untreated, and what’s more, patients with this disease suffer enormously before their deaths. MSF has been treating patients with sleeping sickness for more than 25 years and we have seen the consequences of this forgotten deadly disease. Natacha’s death is a vivid and terrible example of the suffering that these patients and their families endure. The effort required to find, screen, diagnose, and treat these patients can be enormous, especially as the disease tends to spread in regions with limited access to appropriate care. Sometimes, as in Natacha’s case, the disease spreads because of surrounding violence; other populations are affected because of mass displacement or because they live in very remote locations. Q: As you mentioned, sleeping sickness is fatal if left untreated. As a physician, do you have adequate tools to detect and treat this disease? A: Tools exist to diagnose and treat the disease, but these techniques are cumbersome and require huge resources. To diagnose patients, you need centrifuges, microscopes, and very complex diagnostic tests along with specially trained technicians capable of interpreting the tests. To make a final diagnosis, every patient must have a lumbar puncture, an often very painful procedure which involves collecting spinal fluid from the patient’s back. These tests must often be performed in areas with very little infrastructure (such as lack of electricity) and poor sanitation. Patients in the first stage of the disease may be treated with seven days of daily injections, but treating the advanced stages of the disease is very difficult. Recently, new treatment protocols have been adopted which are safer and easier, but these treatments still have limitations. The current best treatment is a combination therapy, called NECT, developed by the Drugs for Neglected Diseases initiative. This treatment, although a dramatic step forward, still has significant side effects. It also cannot be emphasized enough that active screening and treatment is a constant need; while efforts into research and development for better diagnostic and treatment are essential, we must also ensure that there are people actively finding patients. Q: What kinds of new health tools and products do you think are necessary to help sleeping sickness patients in the Congo and around the world? A: We desperately need a rapid point of care diagnostic test, much like those used for malaria. We need an affordable test which does not require electricity or refrigeration, which could be read by staff with minimal training. This would dramatically increase our ability to screen for this disease. Also, while the disease is curable, current treatment requires intravenous medications administered under close supervision. As the disease tends to spread in areas with very limited medical care, it can be very difficult to give proper care to patients after they’re diagnosed. An oral pill treatment for both stages of the disease would revolutionize our ability to care for patients. New game-changing tools may be available in the near future. Two new oral drugs are now being tested in clinical trials. If they were found to be safe and effective, they could be given to patients who test positive with a rapid test. Just one test and one short-course oral treatment: this simplified protocol would make a huge difference in remote settings. On-going clinical trials with these new tools need to be fully-financed. Q: USAID currently does not invest in research to create new tools for sleeping sickness and other NTDs. How would support from USAID for NTD research help you as a physician? What difference would this support make in the lives of patients? We would save a lot of lives. We would prevent a significant amount of suffering. This disease causes excruciating pain, disability, psychosis, and ultimately death. Increased funding for programs to find patients and treat them, and for better and more patient-adapted diagnostic and treatment tools, would be game-changers. In addition to sleeping sickness, MSF/Doctors Without Borders works on several other of the most neglected of the neglected diseases, including Chagas, Buruli ulcer, and visceral leishmaniasis. These diseases affect very poor, marginalized people, often in some of the remote places. There is no lucrative potential market in developing medicines for people suffering from NTDs. As a result we have limited diagnostics and archaic, sometimes toxic treatments. If we really want to make a difference in the lives of people suffering from NTDs, we will not only need to increase funding for these specific diseases, we’ll have to seriously start looking at ways to create new types of incentives for research and development of new medicines .

In this guest post, Jaclyn Schiff—American Society of Tropical Medicine and Hygiene (ASTMH) Director of Communications—highlights news in global health research presented during the recent ASTMH Annual Meeting. Just two week ago, more than 3,700 attendees gathered in Washington, DC, to announce, share, and discuss the latest research findings on a broad range of global health issues, including neglected tropical diseases, surgery in the developing world, and malaria. Just two week ago, more than 3,700 attendees gathered in Washington, DC, to announce, share, and discuss the latest research findings on a broad range of global health issues at the ASTMH Annual Meeting. Credit: ASTMH. Though the meeting attracted one of the largest crowds ever, the absence—due to federal travel budget cuts—of key researchers from the Centers for Disease Control and Prevention, National Institutes of Health, the Army, and Navy was noticeable. This also significantly affected the Annual Meeting last year, and the cuts persist with no sign of letting up. One unfortunate consequence is that scientific collaboration suffers at the Annual Meeting and at countless other research-focused gatherings. When science is stifled, we all lose out. But our colleagues who were able to make it, got on with it, and the media reported extensively on their findings. News coming out of the Annual Meeting covered a lot of ground—from gender bias in global health science to plague surveillance involving traditional healers in Uganda. So just in case you weren’t able to take it all in, here are three critical pieces of research from this year’s meeting: Potential danger from the Plasmodium vivax parasite: The malaria vector may be rapidly evolving to overcome the natural resistance conferred by a blood type found in millions of Africans. Science Now reported on the findings: To enter human blood cells, the parasite usually uses the so-called Duffy blood group protein, a protein on the surface of red blood cells. But because up to 95 percent of the population across sub-Saharan Africa lacks the protein—a genetic trait called “Duffy negative”—they have long been thought to be protected from infection. Yet reports have emerged in recent years of Duffy-negative people who are nevertheless infected with vivax malaria. “If vivax can establish itself in Africa, it can really undo a lot of the malaria progress we’ve made,” study co-author Peter Zimmerman, PhD, of Case Western Reserve University told the New York Times . Moving towards improved hookworm treatments: Researchers presented findings showing that they had completely cured lab animals of parasitic hookworm. To achieve the results, scientists used a modified version of a common human dietary supplement. The findings represent an “important development in our effort to find a safe, affordable and effective way to confront a major global health problem,” the study’s lead researcher said. In its report on the research, Xinhua  notedthat “the only drugs available to treat hookworms in humans were originally developed to combat parasites that infect farm animals.” The study researchers say that current treatments are not effective enough and that drug- resistance is rising. Strange dengue patterns in the United States: As dengue fever continues to spread from Key West north into the Florida mainland, it remains a mystery as to why this dangerous mosquito-borne illness is not yet common around Tucson, Arizona—even though outbreaks routinely occur in nearby Mexico and mosquitoes that can carry dengue are now common in the state. As The Verge reports, researchers think human or biological factors somehow explain why dengue hasn’t spread in Tucson. "It may be that the temperatures in Tucson are so hot," Mary Hayden, a scientist at the National Center for Atmospheric Research, told the BBC . She added “the relative humidity is so low that the mosquitoes may not be able to survive in that climate long enough for the virus to cycle within them.” Additional highlights, original news stories, and interviews are available on the #TropMed2013 Tumblr.

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.