Breakthroughs Blog: USAID

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. Scientists have identified a gene that stops tuberculosis (TB) from mutating and becoming resistant to antibiotics. Researchers at Centro Nacional de Biotecnología in Madrid and the University of Sussex in Brighton individually deactivated each of the 11,000 genes that make up the TB bacterium, and tested the modified strains against an antibiotic commonly used to treat the disease. The study revealed that the NucS gene, which produces an enzyme that repairs DNA, significantly reduces the frequency of genetic mutations, and consequently, the development of antibiotic resistance. As drug-resistant strains of TB have been reported in more than 100 countries, this discovery could pave the way for improved diagnosis and treatment, making it easier for clinicians and researchers to predict which cases of TB will develop resistance. The US Agency for International Development (USAID) is the largest donor of food aid worldwide, spending US$1.5 billion on wheat, sorghum, rice, and other edible commodities annually. As the food travels around the world, an estimated 1 percent is lost to spoilage, which amounts to 10,000 tons of food worth $15 million. Now, researchers at the Massachusetts Institute of Technology are exploring new ways to package the food to avert spoilage and are testing eight different bags of varying sizes and materials to determine their ability to protect against humidity, water damage, and pests. One model has a completely airtight liner that resists moisture, while another uses a biopesticide that stops insects from reproducing, rather than killing them. The research team is also investigating the use of an airtight liner for the shipping containers, rather than the bags themselves. The final results and recommendations will be available this summer. Gene drives, a promising technique for eliminating mosquitoes and eradicating mosquito-borne diseases, may be stymied by evolution. The novel method involves genetically modifying mosquitoes by introducing an unusually dominant genetic mutation that is passed on to the insects’ offspring, overtaking an entire population of mosquitoes within a few generations. To combat malaria, Zika, and other mosquito-borne diseases, scientists have engineered mosquitoes whose offspring are infertile, and initial trials suggest that gene drives could be a breakthrough in vector control. However, additional research indicates that as these manmade genetic mutations spread through a population, so too do natural mutations that counteract the effect. Furthermore, there is an immense amount of genetic variation among mosquitoes, which limits the potential targets for gene drives. To overcome this, some researchers are introducing multiple genetic mutations at once, however, it remains to be seen whether the manmade or natural mutations will be more powerful.

Secretary of State–designee Rex Tillerson. Photo: Center for Strategic and International StudiesWednesday’s nomination hearing for Secretary of State–designee Rex Tillerson provided an opportunity for the global health community to learn more about his views on the United States’ role in international development and global health.While the majority of the hearing highlighted policy toward Russia, human rights, global terrorism, and how Tillerson’s professional experience in the oil industry will impact his role as chief foreign policy advisor to the President, Tillerson was also questioned on women’s empowerment, family planning, development aid, and the President’s Emergency Plan for AIDS Relief (PEPFAR).Here’s what he said:Gender equity and women’s empowermentIn response to Senator Shaheen’s (D-NH) question on whether he would support programming to increase women’s empowerment, Tillerson described how these types of programs had been a priority for the Exxon Foundation and cited a program Exxon supported in Papua New Guinea. He committed to continuing these programs, noting “I think it’s an important part of our foreign aid assistance efforts, whether it’s through the USAID [US Agency for International Development] or whether it’s through other opportunities we have in more structured ways.”Family planning and reproductive health Senator Shaheen also pushed Tillerson on family planning and reproductive health, asking if he would pledge to “continue to prioritize quality family planning and reproductive health services for women worldwide, and ensure that resources and access to these programs are not conflated with support for abortion.” Tillerson responded that he was aware that the United States spends roughly a half a billion dollars per year on family planning aid, and he thinks this level of funding is “an important level of support.” Asked whether his answer represented a pledge to continue this commitment, Tillerson deferred, and said he would examine these programs further, if confirmed.Development aid and disaster assistanceSenator Flake (R-AZ) discussed the role of soft diplomacy with Africa and USAID programs, questioning what works and what doesn’t. Tillerson replied that it is important that US assistance be used to nudge countries toward diplomacy, punish countries when required, and encourage cooperation. He noted that USAID has two important streams of assistance: disaster relief, to address immediate suffering, and development assistance, which is important for achieving lasting change. He said that recently the proportion of disaster assistance relative to development assistance has been growing, which constrains the government’s ability to use aid as a tool for change. He suggested when possible, the United States should tie assistance to behavior change and then follow up. He also said that assistance should be targeted, designed to support American values, and help countries continue their own development. He noted that tying aid to governments meeting obligations is hard to do with disaster relief, and that he understands and appreciates this difference.PEPFARWhen questioned about PEPFAR by Senator Flake, Tillerson called it “one of the most extraordinarily successful programs in Africa.” He described how he saw the success of global health programs up close through Exxon’s work to eradicate malaria in central Africa. He noted that PEPFAR broadly has generated much goodwill from Africa and “recognition of the goodwill and compassionate nature of American people,” calling PEPFAR one of the best projections of America to the African people.Questioned by Senator Markey (D-MA) on his views of PEPFAR and the Global Fund to Fight AIDS, Tuberculosis and Malaria, and his commitment to strengthening these programs in the years ahead, Tillerson replied: “PEPFAR is one of the remarkable successes of the past decade or more…I think what’s notable about PEPFAR is that there are measurable results…I think it serves as a model for us to look to as we’re thinking about other ways in which to project America’s values, project our compassion to want to solve these threats that are in other parts of the world that by and large we’re not threatened by a lot of this here in this country. Malaria was eradicated decades ago, TB well under control, AIDS—great treatment programs are available to people. Projecting that into other parts of the world is a marvelous way to send a message of the compassion of the American people that we care about people’s lives all over the world. So PEPFAR is a terrific model to look at in the future as we look at other areas that may be useful for us to put additional programs in place.”At GHTC, we will continue to monitor Tillerson’s views on US support for global health and development aid and urge strong support for programs that further the development and rollout of urgently needed global health technologies.

Reducing unnecessary antibiotic use is widely considered a priority action in combating the spread of antimicrobial resistance. In the United States, one-third of antibiotic prescriptions are unnecessary and each year, there are 27 million gratuitous prescriptions for respiratory infections alone. Rapid, point-of-care diagnostics that can discern if an infection is bacterial could significantly reduce this practice, preventing antibiotic prescriptions for viral, parasitic, or fungal infections. There are now several tests in the pipeline which evaluate the level of C-reactive protein (CRP) in the bloodstream, a molecule associated with inflammation. CRP levels increase significantly in response to bacterial infections, but only slightly in response to viral infections. Not only have several of these tests proven reliable, but new research conducted by the Oxford University Clinical Research Unit in Vietnam indicates that such a test can successfully decrease antibiotic prescriptions for respiratory infections in low-resource settings. The study monitored antibiotic use for 2,000 patients at ten primary health centers, and use of the test reduced prescriptions from 78 to 64 percent, without impacting clinical recovery or patient satisfaction rates. Scientists have identified a compound that shows promise in treating three different parasitic diseases—Chagas disease, sleeping sickness, and leishmaniasis—that effect 20 million people and result in 50,000 deaths each year. The three diseases are caused by distinct parasites and transmitted by different vectors. Chagas disease results in cardiac complications, sleeping sickness causes neurological symptoms, and leishmaniasis manifests as skin sores and liver and/or spleen damage. Existing treatments are toxic, expensive, and difficult to administer in low-resource settings. The compound—GNF6702—was developed by pharmaceutical company Novartis and discovered after screening 3 million molecules in the company’s compound library. The molecule was then modified, resulting in a drug with 20 times the original potency. The compound targets proteasome—which breaks down waste—in all three parasites, but does not have the same effect in mammal cells. The drug has proven effective in mice, and will undergo additional safety tests before the initiation of human clinical trials.  The US Agency for International Development (USAID) announced last week the initial winners of its Combating Zika and Future Threats Grand Challenge, through which the agency will be providing more than US$15 million for the development and introduction of 21 innovative tools and interventions. In just two months, USAID received and reviewed nearly 900 applications, addressing various parts of outbreak prevention, detection, and control, including vector control, personal and household protection, vector and disease surveillance, community engagement, and diagnostic innovations. The winners include an electric force field to repel mosquitoes; a flip phone–based app that can distinguish between mosquito species, enabling crowdsourced vector surveillance; insecticide-treated sandals; and a human-scented mosquito trap. The agency will announce additional winners in the next month and will invest up to $30 million total.

USAID's 2015 Health-Related Research and Development Progress Report. Photo: USAIDLast month the US Agency for International Development (USAID) released its annual Health-Related Research and Development Progress Report detailing the agency’s research and development (R&D) activities to address global health challenges.Breakthroughs Blog is joined by Neal Brandes—team leader for USAID’s Health Research Program (HaRP) in the Bureau for Global Health—to learn more about the report and USAID’s ongoing support for global health R&D. The HaRP team coordinates the cross-bureau effort to produce this publication and has been advocating collaborative and coordinated research and research utilization efforts to accelerate the research-to-use process.Q: GHTC is always excited to dig into this great report each year. Can you highlight for our readers what is new in this year’s report with regard to new programmatic developments at USAID or major scientific developments in USAID-supported biomedical R&D? NB: There are many new developments that we’re excited about in this year’s report. To highlight just a few: The Ebola epidemic this past year emphasized the need for processes to solicit new ideas and rapid solutions based on sound evidence. This year’s report highlights the exciting products of the Fighting Ebola Grand Challenge, as well as the ongoing good works to produce innovations through the Saving Lives at Birth Grand Challenge. On the newborn front, we report on the progress on care of newborns with possibly severe infection or sepsis—one of the leading preventable causes of death. The World Health Organization (WHO) recommends that sick newborns be referred to hospitals for in-patient care, but also recognizes there are significant barriers to families in low- and middle-income settings accessing that essential care. A multicountry and multidonor initiative supported research establishing that newborns unable to access hospital care can be treated by a trained health worker in lower-level health facilities. This treatment is provided on an outpatient basis with a shorter course of antibiotics. The WHO has recently updated its guidance based upon this new evidence, and we are already in the midst of implementation research to test, adapt, and support its effective and safe application in real-world health systems. Finally, there was encouraging progress on research to combat the HIV and AIDS epidemic. Findings from two dapivirine ring trials are highlighted. These are landmark studies because they are the first to test the efficacy of a woman-controlled method of HIV prevention that uses a nongel microbicide.  Q: This year’s report marks the end of USAID’s 2011–2015 Health Research Strategy. Looking back at the last five years of USAID-supported biomedical R&D, what are some of the most exciting and impactful developments or innovations that have resulted? Are there disappointments or areas in which not as much progress was made as the agency had hoped? NB: Research operates across a continuum. Fortunately, in recent years we’ve had the opportunity to witness some of these efforts come to fruition. For example, take the chlorhexidine story. Chlorhexidine was an early effort to invest in a promising idea through a managed research-to-use process. We began with a careful assessment and then a modest series of concurrent proof-of-principle studies; research utilization efforts; and collaborative efforts with governments, universities, nongovernmental organizations, and pharmaceutical companies that demonstrated the potential and established a foundation to save lives. Nepal was both an early adopter and a global champion for the results of this work. Today these efforts have led to global engagement, rigorous introduction, and scale-up planning in 10 countries. We also understand that the nature of research involves uncertainty and planning for failure. Because of the commitment of our partners and the agency’s culture of learning, we are able to see setbacks as opportunities to improve our processes and extract value from our missteps that will improve the next efforts to address complex challenges.Q: The report illustrates how USAID is working with other US agencies across the continuum of R&D to develop new tools to combat tuberculosis (TB) as part of the US government TB strategy. Could you tell us more about how USAID is coordinating with other US agencies to advance development of critically needed tools in other health areas?A lab technician test tuberculosis samples at a lab in Bandung's Public Health Laboratory. Photo: USAID IndonesiaNB: We work with many stakeholders, foremost of which are the host governments. Because we are stewards of the public’s money, we collaborate with US government agencies as well as other donor development agencies such as the United Kingdom Department for International Development and philanthropies on almost every area of our portfolio—whether it’s to keep each other informed to ensure our efforts are aligned and coordinated or coordinating cofunding to advance the R&D agenda with a goal of advancing research investments to save lives. For example, our malaria portfolio consists of many operational research projects that are done through the President’s Malaria Initiative—a joint effort between USAID and the US Centers for Disease Control and Prevention (CDC). The Ebola Grand Challenge efforts were based on a coordinated partnership with USAID, the White House Office of Science and Technology, CDC, and the US Department of Defense. To introduce new tools and measurements in behavior science (like Big Data), we are working with the White House Social and Behavior Science team.Q: Why is it important for USAID to continue to play a strong role in health research, and what’s next for USAID in this area? Should we expect a 2016–2021 strategy, and how might it look similar to or different from the current strategy? NB: We still have many health challenges ahead of us, and our success is dependent on garnering strong evidence to inform decision-making and action. USAID has the advantage as a development agency to provide technical leadership and an on-the-ground presence working in conjunction with our partner countries and other stakeholders to accelerate the application and development of science and innovation.We are actively discussing our new research strategy. Like our previous strategies, it will address the unique needs of each of our technical areas. However, we are also working together to articulate a number of broad principles that define our work—placing emphasis on how our work includes implementation science, innovation, and partnerships.