Breakthroughs Blog: Child health

Scientists at the University of Oklahoma are looking for the next breakthrough drug in an unusual place: roadkill. Every animal hosts a unique microbiome—a community of microorganisms, including bacteria, fungi, and molecules with antibacterial and antifungal properties. The research team is collecting swabs from dead animals found along a state highway and has already discovered two compounds (taken from an opossum’s ear) that could prevent the spread of yeast infections. Hypothermia is a significant driver of morbidity and mortality among babies born prematurely, even though the condition is easy to detect and treat. Detection relies on temperature monitoring, and current standard of treatment is Kangaroo Mother Care (skin-to-skin contact). Now, an electronic alert bracelet is being used to prevent hypothermia among preemies in India. If the infant is healthy, the bracelet flashes a blue light every ten seconds; if the infant’s temperature drops, the light turns to red and an alarm goes off. The single-use device is safe and can be used for a month straight—even at home. Though a daily dose of pre-exposure prophylaxis (PrEP) can prevent HIV infection, stigma, cost, and frequent stockouts can impede adherence to the regimen. While only four doses per week is sufficient to protect men from infection, if women miss a single daily dose, they risk infection. To mitigate these barriers, researchers at Intarcia Therapeutics Inc. are developing an implant that would release PrEP over time, meaning just one visit to the doctor’s office would protect patients for an entire year. The device has already undergone advanced testing and is currently under review by the US Food and Drug Administration for the delivery of diabetes drugs. Researchers at the Center for Infectious Disease Research (CIDR) in Seattle are using mosquitoes, rather than syringes, to deliver an experimental malaria vaccine. The vaccine uses live, but weakened malaria parasites, which can only grow inside living mosquitoes. In an initial trial, ten volunteers were vaccinated, none of whom developed malaria and all of whom produced antibodies that could confer immunity against malaria. The antibodies were extracted from volunteers and successfully used to protect mice against malaria, however, additional trials are needed to determine their efficacy in humans. CIDR is partnering with the Maryland-based biotech company Sanaria to develop a more standard and sustainable vaccine delivery system, producing the weakened parasites and extracting them from the mosquitoes, and attempting to grow the parasites outside of the mosquitoes.

It’s that time of year when Americans join together with family and friends and give thanks for the many things in life for which they are most grateful. In the spirit of the Thanksgiving holiday, GHTC asked our members and staff to share what they are most thankful for in global health. Here’s what they had to say: “I am thankful for all patients who take part in clinical trials so that the world will have more effective regimens to end TB, in all its forms.” Willo Brock, Senior Vice President of External Affairs, TB Alliance “I’m thankful there is increasing global interest in the development and production of vaccines for diseases of poverty, like hookworm, schistosomiasis, and Chagas.” Tara Bracken, Communications Associate, Sabin Vaccine Institute “I am thankful that 2016 was a turning point for women’s HIV prevention research—one that brought us hope for one day soon expanding women’s options with a long-acting vaginal ring. I am also grateful for the amazing partners who believe women’s health and empowerment matter!” Zeda Rosenberg, Founder and CEO, International Partnership for Microbicides “I’m thankful for the new generation of emerging R&D leaders who are both generating new knowledge and achieving global health impact.” Dr. Timothy Mastro, Chief Science Officer, FHI 360 “I’m thankful for sustained US government funding to fight emerging epidemics, like Ebola and Zika, through R&D and scientific advancement.” Lindsay Litwin, Jhpiego Innovations “I’m thankful that elimination of sleeping sickness is now a real possibility thanks to new tests being strategically implemented alongside new vector control technologies and improved treatment regimens.” Dr. Joseph Ndung’u, Head of Neglected Tropical Diseases Programme, FIND “I’m thankful that the six antimalarials MMV and partners have brought forward are saving young lives today!” Andrea Lucard, Executive Vice President of External Relations, Medicines for Malaria Venture “I’m thankful for research that has shown promise for an effective six-month regimen to cure XDR-TB [extensively drug-resistant TB].” Rabita Aziz, Policy Research Coordinator, ISDA Global Health “I’m thankful for the inspirational dedication and continued participation of all HIV vaccine clinical trial volunteers. Without you, the important work of finding a safe and effective HIV vaccine would not be possible.” Dr. Fran Priddy, Chief Medical Officer, International AIDS Vaccine Initiative “I’m thankful for the over 200 members of Congress who have co-sponsored the Reach Act to accelerate efforts to end preventable deaths of mothers and children around the world.” Brandon Ball, Policy and Advocacy Officer, PATH "I'm thankful for low-cost interventions like chlorhexidine gel for umbilical cord care being made more accessible to Sub-Saharan Africa to reduce newborn mortality." Assumpta Nantume, Communications Associate/Global Health Corps Fellow, Global Health Council “I'm thankful a new generation of Middle Eastern scientists are advancing the development, production, and characterization of new vaccines to help endemic countries better respond to the threat of infectious diseases like MERS, schistosomiasis, and leishmaniasis.” Chris Bennett, Senior Program Officer, Sabin Vaccine Institute “I’m thankful for pioneering donors such as UNITAID for funding development of new hepatitis C tests for countries where fewer than 1 percent of people living with hepatitis C have been diagnosed.” Catharina Boehme, Chief Executive Officer, FIND “I’m thankful for scientists and researchers who devote their lives to important global infectious disease work to help people around the world and to protect Americans here at home and the funding the US government provides for such important work.” Karen Goraleski, Executive Director, American Society for Tropical Medicine and Hygiene “I’m thankful for the tremendous progress we’ve made in advancing child and maternal survival and excited for the prospect of saving the lives of more than 6 million mothers and children by 2030 if we work together to advance and scale-up 11 promising innovations.” Heather Ignatius, Multilateral, US, and Europe Policy & Advocacy Team Lead, PATH “I’m thankful for researchers across the globe whose efforts have, with unprecedented speed, deepened our scientific understanding of and advanced new tools to prevent, detect, and treat Zika.” Kat Kelley, Senior Program Assistant, GHTC “I'm thankful so many good dengue vaccine candidates are in development that could help curb the growing global dengue epidemic.” Tara Bracken, Communications Associate, Sabin Vaccine Institute "I'm thankful for increased awareness on global antibiotic resistance and WHO's new evidence-based Infection Prevention and Control Guidelines." Danielle Heiberg, Advocacy Manager, Global Health Council “I'm thankful for the lives of mothers and babies that have been saved, sustained, and supported by midwives across the globe.” Shannon Egan, Jhpiego Innovations “I’m thankful that malaria rapid tests have contributed to better malaria control, which in turn has helped fuel a massive decline in childhood mortality over the past decade—and that partners around the world are working together to find innovative new solutions for identifying non-malarial causes of fever. Diagnosis matters!” Dr. Iveth J. González, Head of Malaria and Acute Febrile Syndrome programme, FIND “I’m thankful for the support of MMV’s committed donors and partners that make our work to develop new antimalarials for vulnerable populations possible.” Andrea Lucard, Executive Vice President of External Relations, Medicines for Malaria Venture “I’m thankful to be a part of the #StartStayAIDSFree initiative which aims to end AIDS in children by 2020.” Catherine Connor, Senior Director of Public Policy and Advocacy, Elizabeth Glaser Pediatric AIDS Foundation “I’m thankful that members of both major US political parties have continued to demonstrate strong, bipartisan support for global health research and development and US efforts to save lives around the world.” Marissa Chmiola, Communications Officer, GHTC

This weekend, Kenya became the first country to roll out the world’s first and only pediatric tuberculosis (TB) medicines. TB infects one million children each year, resulting in 140,000 deaths, and yet, children have historically been treated with crushed up pills in estimated doses. The new formulations, which were developed by TB Alliance, are not only appropriately dosed for kids, but they are fruit-flavored and dissolvable—making them much more kid-friendly than a handful of bitter pills that must be swallowed. Kids must remain on treatment for six months, and the improved dose, flavor, and delivery are expected to have a significant impact on adherence to the regimen, preventing the development of drug-resistant strains. An additional 17 countries have placed orders and plan to introduce the medicines in the coming months. Vaccines and drugs could soon be manufactured on-the-go with the use of a portable, handheld kit developed by researchers at Harvard University. The kit contains all the ingredients needed to produce biologics (medical products derived from biological, rather than chemical sources): both the DNA that triggers the production of proteins to fight disease and the proteins that synthesize the final product. The DNA and proteins are freeze-dried into pellets, making them easy to store and transport, and with just the addition of water, the vaccine or therapy is ready to use. The team put the kit to work, successfully producing four different biologics, however, the vaccine candidate had to be purified before use. More research and testing is needed, and it could be more than a decade before such a system would be safe and appropriate for use in low-resource settings. Diarrheal diseases are a leading cause of death among children under five, and a new study suggests that 89 percent of cases are caused by pathogens. Further, 78 percent of cases are caused by just six pathogens, including rotavirus, Shigella, enterotoxigenic Escherichia coli (ETEC), Cryptosporidium, Campylobacter, and adenovirus. The researchers analyzed stool samples from more than 10,000 children under five, half of whom had diarrhea, to determine the leading causes of childhood diarrhea. Of the six, there is currently only a vaccine against rotavirus, however, GHTC member PATH is currently developing vaccines against Shigella and ETEC. Scientists are exploring whether the powerful antimicrobials created by certain species of ants could be used to fight infection in humans. Over the past 15 million years, more than 200 ant species have evolved to farm fungi—a symbiotic relationship in which the ants collect plants, feed them to fungi, and in turn, the ants feed off of the fungi. However, some ant species are vulnerable to hostile fungi that attack the ants’ nests and farmed fungi and have consequently adapted to fight off pathogens. These species cultivate bacteria—which appear as white patches along the ants’ bodies—that produce antibacterial and antifungal compounds. So far, the results have been encouraging: 1 in every 15 of these antimicrobial agents have proved promising in the lab, compared to just one in a million of those discovered through soil sampling.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. In this edition, we cover new insights into the impact of the Zika virus on the brain. Researchers have released medical images of 46 fetuses and infants born to women who were infected with the Zika virus during pregnancy, revealing serious brain damage beyond microcephaly. The images, which include 23 MRI scans, 41 CT scans, and 93 ultrasounds, were taken at Instituto de Pesquisa in Campina Grande State Paraiba in northeastern Brazil and analyzed by neurologists at the Instituto in partnership with a team at the Beth Israel Deaconess Medical Center in Boston. The brain damage manifests in distinct ways: many of the scans showed skulls filled with cerebrospinal fluid, and in one case there was so little brain tissue that the skull collapsed in on itself, resulting in a flattened skull with extra skin. The images indicated damage to the brain stem, which regulates breathing and heart rate; the cerebellum, which is responsible for motor control; and the cortex, which is involved for learning, memory, emotion, and language. New research suggests that Hofbauer cells, found in the placenta and tasked with protecting the fetus from pathogens, may be the key to the Zika virus' ability to cross the maternal-fetal barrier. Hofbauer cells are macrophages, immune cells that combat pathogens by consuming them. However, dengue virus—a flavivirus related to Zika—is able to hijack macrophages, using them to replicate and disseminate throughout the body. While the researchers have confirmed that the Zika virus is able to survive within Hofbauer cells, they suspect that the immune cells may also be enabling the virus to travel to the fetal brain. The study also confirms that the virus can replicate within fibroblasts, a critical component of the placenta’s structure, a finding described as, “a bit of a surprise,” by one of the study’s authors. Scientists at Rockefeller University have also described their recent findings as "kind of a surprise," in this case, that certain adult brain cells are also susceptible to the virus. Fetal brains are primarily comprised of neural progenitor cells; while these stems cells are not as ubiquitous in adults, they play a critical role in learning and memory. Earlier this year, researchers determined that fetal neural progenitor cells are particularly vulnerable to Zika. Now, the team at Rockefeller has confirmed that adult neural progenitor cells are no exception. The study revealed an increase in cell death but a decrease in the production of new brain cells in infected adult mice. More research is needed to determine how this translates to humans, however, such damage could increase risk for cognitive challenges, depression, and Alzheimer’s disease.