Breakthroughs Blog: Zika

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. Earlier this year, the World Health Organization released a list of the eight pathogens most likely to cause the next pandemic. All eight are caused by viruses, and all eight are zoonotic—originating in animals. To experts, this came as no surprise: viruses are able to rapidly evolve to infect different species or become more virulent, and nearly three-fourths of new and emerging diseases are zoonotic. Now, researchers are proposing the Global Virome Project, an initiative to characterize every virus in the world (well, 99 percent of them). Tracking down the estimated 1.3 million viruses in the world would cost nearly US$3.4 billion, however, proponents of the project argue that it would unearth insights into viruses en masse and ensure a basic scientific understanding of potential pandemic threats. New research suggests that nearly half of women infected with Zika during pregnancy will have adverse pregnancy outcomes, including miscarriages and birth defects. The study, which enrolled 125 women in Rio de Janeiro, Brazil, is the first to quantify the frequency of these complications among pregnant women who test positive for the virus. Overall, 46 percent of women experienced significant adverse outcomes, however, the true impact may be even higher. The study only followed infants for the first three months of life, but emerging research indicates that neurological and physical defects may develop throughout the first year of life. Further, the study reveals that risk is greatest for women who are infected during the first trimester (55 percent), though adverse outcomes remain common among women infected during the second (51 percent) and third (29 percent) trimester. Antibiotics and immune cells can only target bacteria when they are growing and dividing. Consequently, bacteria often become inactive to evade detection. Many bacteria rely on a toxin antitoxin system to achieve this. A pernicious environmental factor will prompt the bacteria to produce a toxin that puts themselves to sleep, and the abatement of that factor triggers the release of an antitoxin to wake the bacteria back up. Now, an international team of researchers has discovered that the toxin antitoxin system for E. coli, and potentially other bacteria, relies on oxygen to wake up the bacteria. When E. coli cells are dormant, both the antitoxin and oxygen must be present to destroy the original toxin. These findings suggest that oxygen could be the key to developing antibiotics that can wake up and consequently attack dormant bacteria.

Scientists at University of California, San Francisco have identified several drugs that block the Zika virus from infecting brain cells. After determining the types of brain cells susceptible to Zika, the researchers screened more than 2,000 Food and Drug Administration–approved medicines for their ability to protect these cells from the virus. The project revealed that azithromycin, a commonly used antibiotic, could provide protection against Zika in laboratory-grown brain cells. Not only is azithromycin widely available, it is also safe for use in pregnant women, an important characteristic as Zika infection during pregnancy can impede fetal development and result in devastating birth defects. An existing drug for gastrointestinal disorders has shown promise in treating and potentially even curing HIV in monkeys. Existing treatment—antiretroviral therapy (ART)—suppresses HIV, making the virus nearly undetectable in the blood, however, adherence is critical as just a few weeks off of treatment can result in a resurgence of the virus. Due to the demands of adherence and the expensive and toxic nature of many of these medicines, only one third of patients in the United States manage to keep the virus at these undetectable levels. Now researchers may have found a “functional cure” for HIV. The drug—vedolizumab—is approved to treat ulcerative colitis and Crohn's disease in more than 50 countries. In preclinical trials, vedolizumab kept the virus at bay in monkeys for up to two years after cessation of treatment. The National Institutes of Health recently initiated human clinical trials in which people living with HIV and AIDS will receive infusions of vedolizumab every four weeks. After several months, patients will stop taking ART, and their HIV viral load will be closely monitored to determine if the same curative effect is seen in humans. An experimental vaccine against Middle East Respiratory Syndrome (MERS) has successfully combatted the virus in mouse models and offers new insights into the design of subunit vaccines. Vaccines prompt the immune system to develop antibodies that recognize and attack a specific pathogen. Different proteins on the surface of a virus can elicit the production of distinct antibodies that vary in their ability to mobilize a robust immune response. Rather than using the entire virus, subunit vaccines contain specific proteins found on the surface of the virus. Consequently, scientists are able to include only the proteins that elicit the strongest immune response. However, this approach exposes the immune system to certain parts of the virus (i.e., the underside of these surface proteins) that wouldn’t normally be visible, and this can distract the immune system, prompting it to produce ineffective antibodies. In developing a subunit vaccine against MERS, researchers at New York Blood Center overcame this challenge by masking the spot on the vaccine that was distracting the immune system. The slightly tweaked vaccine has proved to be much more effective in protecting mice from MERS. Not only does this finding offer promise for the MERS vaccine, but this technique could be used to increase the efficacy of other subunit vaccines.

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

Researchers at the US National Institutes of Health (NIH) have developed a test that can rapidly screen chemical compounds for their ability to treat drug-resistant infections. The team at NIH has already put the test to use, evaluating approved medicines, promising compounds, and drug combinations against common drug-resistant bacteria. After screening an estimated 4,000 drugs and compounds, the researchers identified 25 that effectively killed drug-resistant Klebsiella pneumoniae in the lab, including not only antibiotics, but also antifungals, antivirals, antiseptics, and even anticancer medicines. The test has also revealed three drug cocktails—each comprised of three different medicines—that can effectively treat ten common multidrug-resistant bacteria. These findings will enable clinicians to prescribe drug combinations with near certainty that they will treat a drug-resistant infection without waiting on lab results. While the tool is not yet commercialized, it can be mobilized to rapidly respond to emerging drug-resistant infections. A new study has revealed that during the 2014–2015 Ebola outbreak in West Africa, the virus evolved, enhancing its ability to infect humans. Previously, Ebola was thought by many scientists to be relatively static; however, researchers at the University of Massachusetts Medical School and University of Nottingham have independently identified a mutation in the Ebola genome—A82V—that appeared during the outbreak and could have made the virus two to four times more virulent. The mutation affects the cells on the surface of the virus that are responsible for infiltrating a host’s cells. For viral cells, shape matters, as it enables them to latch onto host cells like a key in a lock. The researchers suspect that A82V adjusts the shape of these surface proteins, allowing them to better fit into human cells. The mutation also enhances the virus’ ability to infect the cells of chimps and monkeys, while hampering its ability to infect bats, dogs, cats, rats, and mice. The team also discovered that patients with the new, mutated strain of Ebola were 27 percent more likely to die. Further research is needed to confirm this finding. Last week, the NIH and the Walter Reed Army Institute of Research (WRAIR) initiated clinical trials of an experimental Zika vaccine—the first of five phase 1 trials evaluating the vaccine. The vaccine platform was first used by WRAIR in developing a vaccine against Japanese encephalitis, a fellow flavivirus. The Zika Purified Inactivated Virus (ZPIV) contains complete, inactivated virus particles that will not cause disease but train the immune system to recognize and mount a robust response to the Zika virus. In preclinical trials, the vaccine candidate successfully induced an immune response and protected animals against the virus. The five phase 1 clinical trials will test the vaccine compared to placebos in different doses and schedules, as well as in different populations, including individuals previously exposed to flaviviruses (including Zika, yellow fever, dengue, Japanese encephalitis, and West Nile) and dengue, individuals who have received yellow fever or Japanese encephalitis vaccines, and those who have received the NIH’s experimental DNA-based Zika vaccine.