Research Roundup: Promising Zika drugs, micro-QR codes to fight counterfeit drugs, and a new antibiotic R&D accelerator

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.

A typical pitch for venture capital investment highlights three topics: the problem a technology solves, the size of the market, and the profit potential of the product. But at the pitches I witnessed from innovators last Thursday at the Saving Lives at Birth DevelopmentXChange, this formula was turned on its head. While the discussion focused on problem solving, the questions being asked were not how large the market, but how great the need, and not how much money can be made, but how many lives could be saved.The DevelopmentXChange marked the final stage of competition in the 6th annual Saving Lives at Birth Grand Challenge, a prize program sponsored by the US Agency of International Development, the government of Norway, the Bill & Melinda Gates Foundation, Grand Challenges Canada, the UK Department of International Development, and the Korea International Cooperation Agency to identify and advance transformative, cost-effective solutions to improve maternal and newborn health. The program operates much like a venture capital firm. Innovators apply and pitch their ideas, and the program determines whether to issue them grants to develop, test, and bring their ideas to scale.This year the program received more than 650 applications from 78 countries, with 49 teams chosen as finalists to compete at this year’s DevelopmentXChange and showcase their innovations. At the conclusion of the event, Saving Lives at Birth announced the selection of 12 winning teams in the validation and seed grant categories, who will receive more than $3.4 million in funding to move their projects forward. Award winners in the transition-to-scale category will be announced later this year.  GHTC members featured among finalistsAmong the 48 finalists were five promising innovations from GHTC member organizations, profiled below: Finalization and validation of a postpartum screening tool focused on identifying risk factors for maternal infection as part of routine, predischarge service delivery Jhpiego Despite widespread availability of treatment, postpartum infections account for 11 percent of maternal deaths worldwide. A number of risk factors are strongly associated with postpartum infection, and symptoms usually manifest within 48 hours after birth. In Uganda, women are increasingly giving birth in hospitals; however, they are often discharged early due to overcrowding.To address this challenge, Jhpiego has developed a simple screening tool to assess a woman’s risk of postpartum infection. The tool is a checklist of the key risk factors, composed of eight yes or no questions. The assessment is easy to use, and the results are even easier to interpret. If the tool proves to be predictive of postpartum infection, it could be used by health workers, including nurses and midwives, to make evidence-based decisions on whether a new mother can be safely discharged or whether she should remain in the hospital for an additional 48 hours. At Saving Lives at Birth, Jhpiego was seeking funding to finalize and validate the tool—to determine its predictive value—by rolling it out in two regional referral hospitals in Uganda. If successful, Jhpiego plans to partner with the ministry of health to expand its use across public- and private-sector hospitals.Field validation of a new protein-to-creatinine (PrCr) strip test: An impactful new tool to improve diagnosis of preeclampsia at the front lines of antenatal care in low-resource settingsPATH At least 16 percent of maternal mortality worldwide is attributable to preeclampsia, a dangerous condition that can cause organ failure, seizures, and maternal and newborn death. Screening for preeclampsia—which is characterized by high blood pressure and protein in urine (proteinuria)—ideally occurs as part of the care a woman receives during pregnancy. Throughout the day, the concentration of urine often fluctuates, and so, too, does the concentration of protein in the urine. Consequently, the gold standard for diagnosing proteinuria involves collecting and analyzing urine samples over 24 hours. However, this approach is unrealistic in many low-resource settings, and current diagnosis involves a protein-only dipstick test that catches just 51 to 68 percent of cases.PATH has developed a simple, low-cost protein-to-creatinine strip test to improve the accuracy of preeclampsia screening in low-resource settings and was seeking funding through the Saving Lives at Birth program to evaluate the feasibility and efficacy of the diagnostic test in Ghana. The test is nearly identical to the commonly used protein-only test. However, where the existing tool only tests for protein concentration, the new device also tests for creatinine concentration. By comparing the concentration of both protein and creatinine, a health worker can control for how diluted or concentrated the urine is at the time. PATH has confirmed that the diagnostic strip remains effective when stored for at least four months at 37 to 45°C, and the tool costs just pennies on the dollar. Due to its similarity to the existing protein-only test, rollout of the test should be straightforward, requiring very little additional training.Developing a Rapid Integrated Sepsis Risk Calculator (RISC) to detect and manage severe sepsis in newbornsPATH PATH's Rapid Integrated Sepsis Risk Calculator. Photo: Matthew Robinson/GHTCSepsis kills an estimated 421,000 infants in the first 28 days of life in low- and middle-income countries every year. To address this glaring need, the World Health Organization (WHO) recently published guidelines for diagnosis and treatment of possible serious bacterial infection (PSBI), which will require primary-level health care providers to be versed in sepsis detection and management. Many providers do not currently have the necessary training or tools.The RISC is a smartphone or tablet-based app and off-the-shelf device measuring oxygen saturation levels in the blood that enables even primary-level providers to identify sick infants and either provide the correct treatment or refer them to higher-level care. The app incorporates algorithms that walk the provider step by step through the diagnostic process, increasing provider confidence and greatly improving the accuracy of diagnoses. Because the app will be built using Open Data Kit (ODK) free open-source software and off-the-shelf hardware, it will be highly cost-effective and adaptable. The app also works offline, which is critical in remote primary care facilities. The team was seeking a Saving Lives at Birth seed award to complete the development of the ODK app and conduct a pilot evaluation of RISC’s usability, feasibility, and acceptability in Ghana.Development and evaluation of the RELI Delivery System—an innovative, simplified, low-cost infusion pump for obstetric and newborn emergenciesPATH With a few pumps of a handle, a health worker can power an intravenous fluid infusion pump for an entire work shift, all without the use of electricity or batteries. That’s the idea behind PATH’s RELI Delivery System—an innovative, low-cost infusion pump for obstetric and newborn care. Controlled intravenous delivery of medicines like antibiotics or anesthesia is the gold standard of care for many diseases and conditions, but it’s often not feasible in low-resource settings. Existing infusion pumps cost thousands of dollars to purchase and maintain, require substantial training to operate, and require electricity or batteries. PATH designed the RELI System to overcome many of these barriers to access in low-resource settings. The device, which requires no electricity or batteries, is powered pneumatically, through air pressure. It requires about two minutes of pumping to generate the power needed to operate the device for an entire 12-hour shift. The system also has a simple-to-use interface and can be manufactured inexpensively, with an expected retail price at less than $100 a machine. With the seed grant it won through the program, PATH plans to take the device to the field to solicit user feedback and then refine the design for further field testing.  Outpatient treatment of neonatal sepsis by rectal administration of gentamicinPATH Neonatal sepsis is a leading cause of infant death worldwide. WHO recommends treatment of the condition with intramuscular injection of the commonly used antibiotic gentamicin. But in many low-resource settings, this is easier said than done. Neonatal dosing is extremely sensitive—just a fraction of a difference in dose size can affect effectiveness and safety—so administration requires a highly trained health worker. Additionally, many health providers may not have access to safe injection devices or may be inclined to reuse needles, promoting the spread of the disease.Unfortunately, gentamicin is not effective when delivered orally, so PATH is exploring the feasibility of an alternative method of gentamicin delivery—rectal delivery. As a needle-free method of administration, rectal delivery could improve access to gentamicin by making it safer for the product to be administered by lower-level health workers, increasing dose accuracy, and removing the risks associated with injections. Existing scientific literature suggests rectal delivery could be a biologically viable option for gentamicin. PATH was seeking a grant to conduct further lab studies to assess how different additives or formulations can improve uptake of gentamicin in colon cells and conduct stakeholder interviews to assess feasibility of the concept.The innovation effectGHTC congratulates both our members and the other teams who were selected as finalists and award winners.This year’s prize winners will join the growing community of over 93 innovators supported by the Saving Lives at Birth program. Many of these innovations are beginning to have an impact as they are brought to scale. To date, the program has supported 1.5 million women and newborns and saved nearly 10,000 lives.The Saving Lives at Birth program has made it clear that by putting innovation at the center of global health, we can accelerate the pace of change and transform lives, faster.Kat Kelley, senior program assistant, and Matthew Robinson, MA, policy officer, contributed to this article.