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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.

The delegation checks out the mosquitoes that CDC is studying at its lab in Atlanta. Photo: Courtney Carson/GHTCLast month, Global Health Council (GHC) and PATH led a delegation of global health advocates to the US Centers for Disease Control and Prevention (CDC) headquarters in Atlanta.Since the founding of CDC more than 70 years ago, this US federal agency has played a vital role in global health. Its laboratories routinely work with some of the most deadly germs in the world.While many Americans tend to only hear about CDC during the flu season or epidemics like Ebola and Zika, the agency leads an impressive array of efforts that are vital to protecting the lives of US citizens and promoting the health and security of communities around the world.The delegation of advocates met with leaders across the agency’s divisions, including Dr. Tom Frieden, Director of CDC, and Dr. Rebecca Martin, Director of the Center for Global Health, to learn more about CDC’s work and to share their perspectives from Capitol Hill. They gained new insight into the agency’s science, policy, partnerships, and evidence-based public health programs, and learned more about the agency’s work in immunization, health research and development (R&D), global health security, HIV and AIDS, tuberculosis, and malaria. The delegation also had the opportunity to tour the CDC’s Emergency Operations Center and the Insectary and Parasitic Diseases Laboratory. They ended their trip with a presentation to CDC staff on how their global health advocacy efforts in Washington, DC support the CDC.We asked the delegation of global health advocates to share what they learned from the trip. Here’s what they had to say:“CDC’s Global Disease Detection program detects 30–40 outbreaks a day. The reason we don’t hear about those outbreaks—and why they don’t transform into epidemics and pandemics—is due to CDC’s swift response and ongoing capacity building programs that train local epidemiologist to detect, prevent, and respond to new and emerging disease threats.” — Bob Noziglia, Lutheran World Relief “Every CDC center is involved with Zika. It’s the most complicated response they’ve ever mounted, particularly because this is the first mosquito-borne disease with fetal birth defects since Rubella. But CDC is coordinating its response with other agencies, including a CDC-designed diagnostic that has been distributed to more than 100 countries around the world alongside lab training to use it.” — Lissy Moskowitz, Gavi, the Vaccine Alliance “The world is on the verge of one of the greatest public health achievements in human history: the eradication of polio. CDC has played a key role in these efforts, helping to develop a global network of polio surveillance, health workers, and laboratories that have become the backbone of many developing countries’ health system. This infrastructure goes beyond polio to support a wide range of essential health services, including providing vitamin A supplements, measles vaccinations, and surveillance of other diseases, like neonatal tetanus, and CDC continues to play a key role in ensuring health services continue.” — Brian Massa, United Nations Foundation/Shot@Life “CDC’s greatest resource is their people. Staff have an incredible career longevity—spending decades with the agency—which results in a depth of expertise across global health issues, tight coordination across teams, and development of unique skill sets. For instance, CDC has two staff that can identify unknown pathogens within an hour—morning, noon, and night—while others help countries with surveillance, lab capacity, and training, or serve as key health advisors across multilaterals. This is one reason CDC is internationally recognized as “the world’s 9-1-1,” serving as the first line of defense for health departments and ministries globally.” — Brandon Ball, PATH “Unless Congress acts, funding for global health security at CDC will reach a fiscal cliff in FY19. To truly build and sustain the global networks to prevent, detect, and respond to disease threats, predictable long-term funding is needed; while emergency supplemental funds are valuable, they often come too late. Targeted, but flexible funding is needed so that local experts are resourced to act quickly to stop threats in their tracks.” — Erin Fry Sosne, PATH The delegation checks out the mosquitoes that CDC is studying at its lab in Atlanta. Photo: Courtney Carson/GHTC“CDC's malaria and parasitic disease program not only conducts research to advance new diagnostics, vaccines, and countermeasures for malaria, but also works to make sure we are using existing malaria interventions effectively. In their insectary, CDC tests bednets to determine how many, and where tears and holes can exist before the nets are rendered ineffective. This work is vital to leveraging US investments in the Presidents Malaria Program and ensuring we are using US global health funds responsibly and productively.” — Erin Will Morton, Global Health Technologies Coalition “CDC’s Center for Malaria and Parasitic Diseases works every day to improve treatment and develop new tools to address diseases that kill an estimated 534,000 people worldwide, but many Americans never see up close—neglected tropical diseases (NTDs). Not only does CDC leverage donations from pharmaceutical companies to administer drugs for treatable NTDs at less than fifty cents per person per year, but they also conduct research to develop new diagnostics and treatment regimens to more effectively combat hard or expensive-to-treat NTDs. For example, CDC is working to transform a laboratory diagnostic for NTD schistosomiasis to a point-of-care urine test that is both more cost effective and more appropriate for use in low-income, rural settings where the disease is most prevalent.” — Courtney Carson, Global Health Technologies Coalition “Through the CDC Foundation, CDC is able expand the reach of its work through partnerships with corporations and individuals. Established by Congress as an independent nonprofit organization, since 1995 the CDC Foundation has raised over US$680 million, launched 800 programs around the world, and interacted with over 200 private sector entities. Most recently, through its Global Disaster Fund, the foundation raised $56 million from donors to assist with the response to the Ebola outbreak.” — Lanice Williams, Global Health Council “Although CDC had been working on the global response to HIV and AIDS since 1999, PEPFAR changed how CDC worked globally. With the inception of PEPFAR in 2003, CDC expanded its global work by opening more country offices and working closely with ministries of health. Today, through its regional offices, CDC continues to monitor Ebola in West Africa, trains epidemiologists through its Field Epidemiologists Training Program, and work on the Zika response. And its work in PEPFAR continues: providing over 7 million men, women, and children with antiretroviral treatment (ART) and care, as well as support for 5 million orphans and vulnerable children and the training of over 140,000 health care workers.” — Danielle Heiberg, Global Health Council “Through the use of lab technology advancement, CDC has significantly driven down the cost of genome sequencing testing. CDC’s Advancing Molecular Detection (AMD) initiative focuses on using the latest technology advances in pathogen identification to protect Americans from infectious disease outbreaks. This initiative is fundamentally changing how CDC scientists conduct lab work and diagnostics on diseases such as tuberculosis, malaria, Zika, and tropical diseases such as leishmaniasis, and by providing a thousand times more information in a shorter time frame.” — Karen Goraleski, American Society for Tropical Medicine and Hygiene This blog was originally published on The Collective Voice, the blog of the Global Health Council.

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.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. Could a US Food and Drug Administration (FDA) approved drug to fight Zika already exist? A new research paper suggests it could be possible. A group of researchers at the University of Texas Medical Branch at Galveston screened 774 FDA-approved drugs to see if they could protect isolated human cells from the virus and found that 24 of the drugs showed some ability to block Zika from infecting certain cell types. Due to the lag time between when a pregnant woman contracts the virus and when the virus passes from mother to fetus, if scientists could find a drug to halt infection, a woman could take it as soon as infection is discovered and prevent the virus from reaching her fetus. Using an existing drug already shown to be safe could help expedite the research and regulatory process to bring it to market. A chemist at the University of Albany has developed at tiny, edible QR bar code he believes could be a solution to fighting the problem of counterfeit drugs. Made of edible materials, the code is smaller than 200 micrometers, or around the size of a dust particle, and can be printed on the surfaces of capsules or embedded in pills. The code, which is able to be read by a cell phone microscope available for about US$10, could contain manufacturing information such as the product number and production date. In low- and middle-income countries, counterfeit drug sales are a major health challenge. Up to 30 percent of drugs on the market are counterfeit. A new study has found that infection with the worm Wucheria bancrofti—which cause lymphatic filariasis—increases risk of HIV infection by two-to threefold. The study followed 1,055 individuals in southwest Tanzania and found that those with the worm infection had a 3.2-fold increased risk of HIV infection in the age group 14 to 25 and a 2.4-fold increased risk in those between 25 to 45 years. The study adds to a growing collection of scientific literature linking infection with neglected tropical diseases with increased HIV infection risk. A new public-private partnershipwill deploy more than $350 million over the next five years to encourage pharmaceutical companies to develop new antibiotics to combat the growing problem of drug resistance. The partnership—Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X)—is a joint initiative of the Boston University School of Law, the Biomedical Advanced Research Authority, the Wellcome Trust, and the Antimicrobial Resistance Centre. With few large pharmaceutical companies in the antibiotic development market today, the program will focus on researchers and smaller biotech firms who may be interested in developing new antibiotics but have little access to funding. The program will provide grants to these developers as well as business and research support through one of four accelerator sites, which will aid these developers with mentoring, business strategy, and other coaching.