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Dr. Robert Gallo co-discovered the HIV virus and subsequently led the development of the first HIV and AIDS blood test. Now, his team at the University of Maryland School of Medicine is initiating human clinical trials of an experimental HIV and AIDS vaccine that aims to prevent the virus from attaching to immune cells. The HIV virus uses a protein on its surface—gp120—to bind onto one part of human immune cells—the CD4 receptor—and then subsequently bind onto a second part of the cell—CCR5. This vaccine candidate interrupts this process by preventing the HIV virus from attaching to CCR5, therefore disrupting the process of infection. While many vaccines target specific viral strains, this candidate is intended to neutralize all strains of the HIV-1 virus. The first phase of the trial will enroll 60 healthy, adult volunteers to determine the vaccine’s safety and to ascertain if it successfully triggers an immune response. A 23-year-old engineer has developed an inflatable incubator that is designed to be easy to transport, use, and maintain, which could dramatically reduce deaths of premature babies in refugee camps. Developer Briton James Roberts has created electronic and functional prototypes which indicate that the incubator, known as MOM, will provide the required warm, stable, and sterile environment. Roberts designed the product with Syrian refugee camps in mind, as an estimated three-fourths of premature infant deaths in camps could be prevented with proper incubation. The incubator can be collapsed (see Figure 1) to fit in care packages commonly distributed in refugee camps and while it does require electricity, it can run off of a car battery or solar power. Roberts recently won two cash prizes to support product development and manufacturing but is continuing to fundraise to support the costly process of regulatory approval for medical devices. Roberts believes the product could be ready for market by 2018. Photo: CDC/ Dr. Scott Smith The US Department of Defense (DoD) and National Institutes of Health (NIH) have both supported the research and development (R&D) of drugs and vaccines for Ebola since the early 2000s. In both agencies, budget constraints halted progress despite promising clinical trials. In 2004, a researcher at army installation Fort Detrick was exposed to Ebola, prompting the DoD to partner with pharmaceutical company Sarepta Therapeutics to rapidly develop an experimental treatment for Ebola. The treatment was given emergency approval by the US Food and Drug Administration (FDA), but the researcher did not become infected and the treatment remained unused. In 2010, the DoD awarded Sarepta a US$291 million contract to continue its work. Sarepta’s drug demonstrated 60 to 80 percent efficacy in clinical trials with primates and proved safe for use in phase 1 human clinical trials. In September 2012, the FDA granted Sarepta’s drug fast-track status—to expedite its regulatory review—but just one month later, the DoD discontinued the project, in light of looming budget cuts that seemed inevitable due to congressional gridlock. In mid-2014, after the onset of the Ebola epidemic in West Africa, Sarepta CEO Chris Garabedian approached the DoD about the possibility of continuing their work, however, the agency chose to fund products that were not as far along as Sarepta’s. While the DoD has since reconsidered—inviting Sarepta to apply for funding for phase II trials—Sarepta declined, and under new leadership, has terminated their Ebola R&D. The US Department of Agriculture (USDA) has contracted two veterinary pharmaceutical companies—Harrisvaccines and Ceva Santé Animale—to manufacture, store, and ship vaccines to prevent the strain of avian influenza which caused an outbreak and consequent shortage of eggs and turkey in the United States earlier this year. The contract requires the companies to store the vaccines for up to five years, regularly testing them for quality assurance, and will ship them within ten days to anywhere in the United States if requested by the USDA National Veterinary Stockpile. To improve clarity and expediency of communication—for which the agency was criticized by veterinary, poultry, and egg groups during this year’s outbreak—the USDA has also worked with Iowa State University to translate avian influenza–related biosecurity materials for Spanish-speaking farm workers.

Photo: Heng Chivoan When most people think of hunger, they think of a lack of food—a nation suffering from crop failure and famine, or a family that can’t afford to put enough food on the table. But hunger is a far more complex issue with many dimensions. Tackling hunger is not only about ensuring reliable and affordable access to food, but access to the right types of food that are rich with the nutrients human bodies need to function and thrive. Two billion people—more than a quarter of the world’s population—suffer from micronutrient deficiencies, an affliction GHTC member HarvestPlus calls “hidden hunger.” Micronutrient deficiencies, or insufficient amounts of vitamins and minerals, including vitamin A, zinc, and iron, are a major public health problem, particularly in developing countries where people’s diets rely on inexpensive staple crops that often lack nutrients. While those affected may not show the visible symptoms of hunger and malnutrition, micronutrient deficiencies can still have a devastating impact on health, resulting in stunting, blindness, and lowered IQ in children, as well as increased vulnerability to infectious diseases and complications in pregnancy and childbirth. This World Food Day, we’re joined by Peg Willingham, head of Advocacy and Policy at HarvestPlus, to discuss biofortification—an innovative approach to tackling hunger and malnutrition. What role can biofortification play in eradicating hunger, and in particular, micronutrient deficiency? PW: Ideally, everyone should have access to fruits, vegetables, and protein, or to important interventions like vitamin supplements. Unfortunately, these are often out of reach for smallholder farmers who subsist on the food they grow on an acre or two of land—which constitutes the majority of people living in developing countries. A cost-effective new tool to target these families is biofortification—using conventional breeding techniques to increase the levels of vitamins and minerals in the most widely consumed staple foods in Africa, Asia, and Latin America. Can you talk a bit about the process of biofortification and how these crops are introduced and scaled up in developing countries? PW: Until recently, crop developers have focused on higher yield per acre and resistance to diseases, pests, drought, and heat. With support from HarvestPlus, researchers are now including nutrition as an important trait. They search existing seeds banks—which contain 300,000 plant varieties—to identify ones that are naturally high in these important micronutrients, but which cost the same, produce the same yield, and don’t require any extra inputs like more water or fertilizer. National agricultural research authorities around the world then test these crops locally to make sure they grow properly in different soils and climates. We then work with a broad array of partners to get these healthier crops to farmers. This varies from country to country and from crop to crop. For example, most farmers in Zambia buy their corn seed from local private companies, so we work with those firms to get them to make the switch to seeds that are high in vitamin A. In Uganda, farmers who receive donated vitamin A sweet potato vines share them with other farmers the following season, in a constantly expanding cycle. Ten million people are currently growing and eating these healthier foods in more than 30 countries, and testing is underway in almost 20 more countries. What’s in HarvestPlus’ pipeline of biofortified crops? What crops have already been released or are currently in development? PW: Biofortification is centered on the staple foods that people already eat regularly. More than a dozen crops are currently available to farmers: bananas, beans, black-eyed peas, cassava, corn, lentils, pearl millet, plantains, potatoes, pumpkin, rice, sorghum, sweet potato, and wheat. We are excited by recent data demonstrating the nutritional impact of biofortified crops. A study in Mozambique showed vitamin A sweet potatoes significantly reduced the incidence and duration of diarrhea, one of the leading causes of mortality in African children. Pearl millet extra rich in iron was able to reverse iron deficiency in school-aged Indian children in six months. More studies are underway. What role can policymakers—at the national level, as well at the multilateral and global level—play in advancing biofortification and other innovations to improve nutrition? PW: We have been gratified to see how quickly policymakers have embraced this innovation, paving the way for better health and livelihoods. The World Bank has begun funding countries to scale-up biofortification, and the African Union’s commissioner for Rural Development and agriculture and health ministers around the globe have publicly endorsed it. Several countries have included biofortification in their national health and agriculture strategies and are investing their own money in scaling-up access. Additional resources will accelerate this process.

A new briefing paper from the Infectious Diseases Society of America Center for Global Health Policy explores the state of tuberculosis (TB) research and development (R&D) including challenges for products currently in the pipeline and gaps in TB research. The paper notes that existing TB diagnostic tools are not practical for low-resource settings, as the leading device is expensive and requires electricity and skilled health workers. Alternative diagnostic approaches are unreliable, missing nearly half of cases, and there’s a paucity of tools to detect drug-resistant strains. In terms of treatment, there is very limited access to novel drugs, due in part to delayed regulatory review and delivery. While the report notes that the “world still waits for a significant tuberculosis vaccine breakthrough,” more than a dozen experimental vaccines are currently being tested in clinical trials. New research suggests that malaria in pregnancy could impact fetal brain development, which is particularly concerning as pregnant women are at increased risk for malaria. The study, which was conducted in mice, suggests that a mother’s immune response to malaria disrupts the production of certain proteins involved in brain development, resulting in depression or cognitive disorders. Upon further investigation, the team was able to prevent the immune system disruption and successfully prevent any brain damage. While this approach would be impractical and too expensive for scale-up in humans in low-resource settings, the team plans to confirm the phenomenon in humans and search for a safe, affordable alternative. A patient with lymphatic filariasis (Photo: CDC) Last week, three researchers were awarded the Nobel Prize for Physiology and Medicine for discovery of artemisinin and avermectin, the leading treatments for malaria and two filarial diseases caused by roundworm parasites: lymphatic filariasis and onchocerciasis. Both treatments were identified in the 1970s and are currently facing challenges: resistance to artemisinin has been growing and avermectin treats the symptoms of these filarial diseases by killing the larvae, but is unable to kill the adult worms, ultimately requiring years of treatment. A team led by Professor Mark Taylor of the Liverpool School of Tropical Medicine is searching for new ways to treat filarial diseases by targeting Wolbachia, a bacterium that is critical to roundworms’ ability to both mature and elicit the symptoms associated with lymphatic filariasis and onchocerciasis. In the 1990s, Taylor’s team determined that the antibiotic doxycycline could combat Wolbachia, killing the adult worms in three-fourths of patients within 18 months. However, as ensuring access to doxycycline and retaining patients over 18 months can be challenging, Taylor’s team has been searching for alternatives through the Anti-Wolbachia Consortium (A-WOL), established in 2007 and funded by the Bill & Melinda Gates Foundation. A-WOL has facilitated the screening of nearly sixty thousand chemical compounds and is currently testing the antibiotic minocycline for treatment of lymphatic filariasis and onchocerciasis in Ghana and Cameroon. Early results suggest that minocycline, a more expensive drug, is 50 percent more effective than doxycycline. Neither are safe for use in children or pregnant women, however, Professor Taylor believes the team has enough drug candidates to overcome this challenge, as they’ve developed dozens of promising compounds to test further.

In this guest post, Dr. Monica Parise—deputy director for program and science—and Dr. Larry Slutsker—director of the Division of Parasitic Disease and Malaria—at the US Centers for Disease Control and Prevention (CDC) Center for Global Health—discuss the role of research in advancing efforts to detect, prevent, and eliminate parasitic diseases. Research is critical to preventing, detecting, and eliminating parasitic diseases. Photo: PATH/Gabe Bienczycki It’s an inspiring time for those of us working on parasitic diseases. Combined, the two of us have spent several decades working to address these infectious diseases that are major causes of death, disability, and suffering for millions of people. Since 2000, we’ve witnessed tremendous successes in reducing the devastating toll from malaria and several of the neglected tropical diseases (NTDs). None of this happened by accident. Sustained commitment from global partners, combined with unrelenting work and attention, has produced results. Massive scale-up of malaria interventions has saved more than 4.2 million lives since 2000, and globally, child deaths have fallen by 47 percent and in sub-Saharan Africa, by 54 percent. There has been similarly impressive progress in eliminating lymphatic filariasis, also known as elephantiasis, with an estimated 97 million cases prevented. We have also seen massive reductions in cases of Guinea worm disease, with only 126 cases from the four remaining endemic countries reported globally in 2014 compared to 3.5 million in 1986. Based on these gains, several NTDs, including lymphatic filariasis, onchocerciasis, and trachoma, have been slated for elimination within the next five years. Equally significant, the newly released Global Technical Strategy for Malaria calls for eliminating malaria in at least 35 new countries by 2030. But this progress is fragile. This is no time to be complacent. While the documented and real successes should be applauded, they’ve also produced a changing epidemiological landscape that has altered such things as the infection levels, where transmission still occurs, and other factors. Increasing resistance of parasites to drugs and mosquitoes to insecticides threatens to unravel progress in malaria elimination. NTD elimination programs are reaching a point where they now require better and different tools for making decisions about when to stop mass drug administration and how best to monitor for disease reoccurrence. To succeed we must adapt so that we keep pace with rapid changes in our foes—the parasites and their vectors. We must identify new tools and approaches to continue to achieve gains. That requires introspection and the willingness to occasionally stop and ask hard but essential questions. As scientists, as well as public health professionals, we constantly ask ourselves: Do we as a community have what it takes to get to the end? Do we have the information, tools, and interventions needed to successfully support a path to elimination? If not, what do we need to do about it? Over the past several months, the two of us, along with colleagues in CDC’s Division of Parasitic Diseases and Malaria, reflected on these challenges and considered possible solutions. The result is a set of strategic priorities to guide our work over the next five years. An important area of focus is research to develop new tools and approaches—to further drive down transmission, overcome technical challenges, and measure progress. We identified specific gaps that need to be addressed: Strengthening the evidence base to support elimination of malaria and NTDs: Additional guidance is needed to help define when a program should stop mass drug administration and transition from control to elimination strategies. Guidelines are also needed to identify which interventions are most appropriate in low transmission settings. Developing and evaluating tools and interventions targeting both the malaria parasite and its mosquito vector: Drug and insecticide resistance are forcing us to think about novel ways to battle those long-time foes, including evaluation of promising vaccines and novel vector control strategies such as spatial repellents—airborne chemicals that prevent human-vector contact with given space—and insecticide-treated durable wall linings. Malaria screening undertaken by community health workers. Photo: PATH/Lynn Heinisch Developing interventions to improve management of malaria cases: Achieving further reductions in malaria burden will require moving diagnosis, treatment, and risk mapping beyond the health facilities and community health workers providing clinical care, to developing strategies for population-based approaches such as focused screening and treatment, mass screening and treatment, and mass drug administration. Optimizing the effectiveness and mix of interventions: Whether it is a promising vaccine or a new method of vector control, no single intervention is likely to be a “magic bullet” for malaria control and elimination. Adding new tools and interventions into the mix of ones currently in use will require an understanding of which tools—used when and how—are needed. Evaluating the impact of parasitic disease control programs on other endemic diseases: Because individuals are commonly infected with more than one parasite or other disease-causing organism, opportunities and efficiencies exist for integrating interventions. Evaluating how parasitic disease control programs impact other endemic diseases can provide additional information on how to maximize resources and further integrate programs. Improving global research capacity for parasitic disease prevention and control through technical assistance and training: Ultimately, the goal is for governments and their academic partners in endemic countries to develop the capacity to lead research efforts to advance disease control and elimination within their own setting. The advancement of parasitic disease research is dependent upon strong research collaborations both with ministries of health and their partners in endemic countries and here in the United States. While adequate research infrastructure exists in some areas, there is a need to strengthen capacity through technical assistance and training that will facilitate collaborative research. We should celebrate the successes of the work so far that has saved millions of lives and eased suffering worldwide. But there is more—much more—to do. We must continue to scale-up existing technologies to sustain progress while at the same time advancing scientific research that will inform the way forward. With a strong base in science to support effective programs and policies, we are in a far stronger position to meet the challenges we face on the path towards elimination.