Breakthroughs Blog: NTDs

The National Institute of Allergy and Infectious Diseases (NIAID) announced last week that two experimental Ebola vaccines appear to be safe for widespread use, based on early results of clinical trials in Liberia. NIAID will now expand its trials to include as many as 1,500 volunteers, testing the vaccine candidates for efficacy. Volunteers will receive either the vaccine candidate developed by GlaxoSmithKline, another developed by NewLink Genetics Corp, or a placebo. Researchers will examine the immune response to the vaccines to see if participants develop antibodies against Ebola. None of the participants will be intentionally exposed to the Ebola virus. Scientists at NIAID have identified several genetic conditions that affect one’s risk for malaria, and which primarily manifest as red blood cell abnormalities. The researchers followed 1,543 children in Mali for three years, during which time they recorded 4,091 cases of malaria. Genetic disorders that either decreased the production of hemoglobin—the protein that transports oxygen in the blood—or led to the creation of hemoglobin C, an abnormal form of the protein, were associated with increased risk for malaria. Two genetic traits—HbAS and homozygous X-linked G6PD deficiency—appear to protect against malaria. The HbAS gene was not only associated with lower risk for malaria, but with less severe cases of malaria in children who contracted it. Researchers at Cornell University have mapped the genome of Ancylostoma ceylanicum, one of two species of hookworm that infect humans. The study identified 31,000 different genes, including those that are active in hookworms during infection. Scientists believe that as many as 70 of those genes could be promising targets for new drugs or vaccines, and plan to start testing experimental vaccines in hamsters this year.

The TB Alliance, a member of the Global Health Technologies Coalition, announced last week that it will be starting Phase 1 clinical trials for a new tuberculosis (TB) drug candidate. The drug, known as TBA-354, is the first new TB drug to advance to clinical trials in six years, despite the paucity of highly effective and easily administered TB treatments. TBA-354 was developed by the TB Alliance, in partnership with the University of Auckland and the University of Illinois-Chicago, using compounds from the nitroimidazole class of chemicals, which are known to be effective against drug-resistant strands of TB. The World Health Organization (WHO) estimates that US$2 billion per year is needed for TB research and development (R&D), yet in 2013, only $676.7 million was invested. The Atlantic took an in-depth look at gaps in reproductive health R&D, highlighting common side effects of leading contraceptives and reviewing the results of clinical trials conducted between 2008 and 2011 for a contraceptive injection for men. The article also identifies contraceptive technologies currently in the pipeline, including a reversible version of a vasectomy, an improved diaphragm, a remote-controlled implant, and more. A drug-resistant form of malaria endemic to Cambodia and found in Southeastern Myanmar has spread north to the border Myanmar shares with India. While the strain is resistant to artemisinin, the most effective agent against malaria, it can still be combatted with other drugs. Dr. Charles Woodrow, the lead author on the study, explained that in Cambodia, treatment for the resistant strain involves "combining three drugs, extending courses from three days up to five days." Scientists fear that if this new strand were to establish a foothold in India, it could rapidly spread across the globe. WHO estimates that US$750 million annually is needed to prevent and treat neglected tropical diseases (NTDs), yet current foreign aid amounts to only $300 million per year. Due to the financial climate in donor countries, WHO is calling for increased domestic funding in countries where NTDs are endemic. Dirk Engels, Director of the Department of Control of NTDs at WHO, has stressed the importance of interventions that combat multiple NTDs, such as large-scale, affordable vector control programs and diagnostic interventions.

In this guest post, Isabela Ribeiro, MD—head of the Chagas program at the Drugs for Neglected Diseases initiative (DNDi)—discusses the devastating toll of Chagas and ongoing efforts to develop new treatments and drug regimens for the disease. Valentine’s Day seems like a fitting occasion to shine some needed light on a disease that can begin with a late-night “kiss” but ends with a broken heart. I’m talking about Chagas, the leading cause of infectious heart disease in Latin America. The T. cruzi parasite that causes the illness is transmitted by the “kissing bug,” a blood-sucking insect found in the Americas that thrives in houses made from straw, sticks, and adobe brick. Kissing bugs feed at night, biting the face, sometimes around the lips (hence their name), where they can deposit feces infected by the T. cruzi parasite. Chagas disease can also be transmitted from mother to child or even through blood transfusions. The acute stage of Chagas disease happens soon after infection. But the chronic stage lasts a lifetime as the parasites hide in the heart and other organs. More than 30 percent of those infected will develop serious cardiac, digestive, or neurological disorders. Up to eight million people are infected and more than 12,000 deaths occur each year, in most cases from heart failure. What is so remarkable about this silent killer is the deep neglect that surrounds it. Chagas is endemic to all countries in Latin America and increased migration and population movement means there are now cases throughout the world, including approximately 300,000 in the United States. Less than 1 percent of those infected around the globe are estimated to be on treatment. Only two drugs exist to treat Chagas disease—benznidazole and nifurtimox. Both are effective, but have undesirable side effects and require a long treatment course. Nevertheless, governments can and must do much more to scale up access to testing and treatment with these existing tools. In the United States, neither drug has been approved by the US Food and Drug Administration. Treatments are only available through the US Centers for Disease Control and Prevention under investigational protocols and compassionate use. The past decade has seen new actors enter into Chagas research and development (R&D), including DNDi, the Sabin Vaccine Institute, and other institutions. New technologies are enabling researchers to screen much larger libraries of compounds for potential drug candidates. The first clinical trials for Chagas in more than 40 years are being held, providing both new formulations and new regimens of existing drugs and desperately-needed knowledge and data about this poorly understood disease. Drug discovery is a slow process with many ups and downs. One class of antifungals known as “azoles” generated a good deal of hope, but recent clinical trials have shown that they are not as effective as current drugs. Nevertheless, DNDi is currently looking into combination treatments with these drugs. Increased open collaboration should hopefully lead to new drug candidates. One important development is DNDi’s Lead Optimization Latin America project, which is a rare example of early R&D for neglected diseases taking place in an “endemic” region. There is still a long way to go to break the silence around this disease and ensure the needs of millions of neglected patients are met. As is often the case with neglected diseases, it is the poorest and most vulnerable communities that are the most affected. New technologies to test, treat, and prevent the parasite hold the key to future progress against Chagas disease, but a larger global effort is needed today to scale up access to treatment for those who need it most.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. US Food and Drug Administration (FDA) Commissioner Dr. Margaret Hamburg announced last week that she intends to resign from her position in March. The FDA’s Chief Scientist Dr. Stephen Orstroff will serve as the interim Commissioner. Dr. Robert Califf, founding director of the Clinical Research Institute at Duke University, and recently appointed deputy commissioner for Medical Products and Tobacco at the FDA, is expected to be the principal candidate to fill the role permanently. The Global Health Innovative Technology (GHIT) Fund and the Gates Foundation launched a Grand Challenge last week to combat neglected diseases, including malaria, tuberculosis, Chagas disease, and visceral leishmaniasis. The Fund intends to grant US$2 million per year for the research and development (R&D) of new drugs, vaccines, or diagnostics, and up to $1 million per year for each product. GHIT also announced last week that it will invest $637,000 into the development and testing of chemical compounds in the pursuit of more effective products to prevent and treat malaria. The funding will be directed into a partnership between GHTC member Medicines for Malaria Venture and Japanese pharmaceutical company Daiichi Sankyo. Policy Cures—an independent research group and author of the annual G-FINDER report which analyzes global spending on global health R&D—released its first-ever report on reproductive health R&D for developing countries. The report reveals that just $88 million was spent on developing country-specific reproductive health R&D in 2013, $63 million of which was spent on contraceptive R&D. The report explores the limited funding and major gaps in reproductive health R&D, highlighting the need for affordable products that are easily delivered, administered, or stored; have multiple purposes; and do not have major side-effects. A recent study reveals that the United Kingdom’s top 25 universities—in terms of public funding for medical research—spend just 1.7 percent of their health research budgets on neglected diseases. The London School of Hygiene & Tropical Medicine topped the list, spending 68 percent of their health research on diseases that impact people in developing countries, however, all but 5 of the top 25 allocated less than 10 percent of their medical research budgets to neglected diseases.