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. Researchers in Brazil have discovered the structure of the protein responsible for replicating the Zika virus thousands of times in cells, causing the virus to break through the cell wall and infect the body. Through many months of collecting data and studying the origins of the virus, the researchers put together a three-dimensional model of the protein and published their findings in Nature Communications. Zika is a flavivirus and in the same genus as diseases like yellow fever, dengue, and hepatitis C. Because of the genetic similarity, researchers and scientists have found that sofosbovir, a commonly used drug to treat hepatitis C, is a good therapeutic option for those suffering from Zika. The unlocking of Zika’s genetic code will lead to the development of new solutions to the virus. It recently became global news that RTS,S (trade name Mosquirix™), the candidate malaria vaccine furthest along in development, is beginning vaccine pilot programs in three chosen countries: Ghana, Kenya, and Malawi. The vaccine, created through a partnership with PATH’s Malaria Vaccine Initiative and GlaxoSmithKline, is given in four doses over a specific period of time. It is not yet known if tracking of these vaccine doses will be 100 percent. Any vaccine administered in multiple doses, whether for malaria or HPV, requires a lot more work in educating individuals about the need to return for all treatments necessary to ensure the vaccine’s success. UNICEF and members of the vaccine community will work with government authorities to ensure the supply chain delivers vaccines to children in need. If successful, the burden of malaria could decrease drastically. While this vaccine is promising to many individuals in these three countries, the search for a more perfect vaccine is high on the priority list for health researchers around the globe. In order to increase global access to immunization, successful and smooth-moving supply chains are necessary. The problem? Immunization supply chains are complex and every part of the chain needs to be working perfectly to ensure access to the vaccines. Many members of the immunization community have neglected the supply chain facet of vaccine delivery, and as a result, these supply chains have suffered and grown obsolete. With these chains being out-of-date, many children remain unvaccinated from even the most common diseases. A special issue published in Vaccine highlights these issues and brings the need for supply chain renewal to the forefront of the conversation. But even after this publication, more has to be done to ensure all members of the vaccine community work together to guarantee access to vaccines is in reach for all. Despite vaccine initiatives being stronger than ever, there is still a glaring gap in the number of children receiving basic vaccines. Currently, there are over 19 million children who are unvaccinated, leaving them susceptible to diseases that can be protected against. The American Academy of Pediatrics and the Centers for Disease Control worked together to establish the Global Vaccine Action Plan (GVAP) aimed at closing the gap of vaccine inequality around the globe. GVAP has already seen many successes, including fostering a working relationship with government institutions to implement surveillance techniques to figure out what vaccines children need most in each country. Kenya and Nepal, for example, have initiatives through pediatricians to educate families about the importance of vaccines for children’s development and longevity of life. GVAP is in the forefront of bridging the gap of health inequity and bringing immunization to all.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. Nearly three-fourths of new and emerging human diseases are zoonoses, animal diseases that spillover into humans. Now, scientists are reporting “spillback” of human diseases into monkey populations in South America, as Zika virus becomes endemic and as Brazil faces its worst yellow fever outbreak in years. Human strains of Zika have been found in black-striped capuchin monkeys and marmosets, a concerning trend as these species could become a reservoir for the virus. Capuchins are often kept as pets, employed as street entertainers, or hunted as meat, and these routine interactions could lead to future human outbreaks. Meanwhile, Brazil’s yellow fever outbreak has killed nearly 70 people and more than 600 monkeys, threatening rare and endangered species in the Atlantic rainforest. Researchers at the University of Southampton have designed miniscule 3D spheres that can simulate conditions inside the human body, an exciting development that could help scientists better understand how pathogens interact with human cells. The researchers created one such sphere with a collagen matrix, similar to the makeup of human lungs, to study antibiotics that target and kill the tuberculosis bacterium. The 3D spheres can be used four times longer than existing 2D systems, enabling researchers to monitor the progression of infections over time. Colistin is often the last line of treatment for multidrug-resistant infections, however, its use as a growth promoter for livestock in China has led to the development of colistin-resistant bacteria on chicken farms. While colistin resistance was first reported in China in 2015, it has now spread to 25 countries across four continents. Scientists have discovered a specific gene (mrc-1) that confers resistance to colistin and that can be easily spread between bacteria. Now, a new study has revealed that mrc-1 is much more prevalent than previously believed. The gene was found in nearly all bacteria collected from chicken farms in China, even though only half of the samples proved resistance to colistin. The findings also suggest that flies may be accelerating the spread of colistin resistance by transporting resistant bacteria from farms to surrounding communities. A cocktail of three bacteria-killing viruses could provide rapid protection against cholera, filling a critical need during outbreaks, as vaccines do not provide protection until approximately two weeks after administration. The technique is known as phage therapy as it utilizes bacteriophages—viruses that target and kill specific bacteria. While phage therapy has been around for nearly a century, it was largely eclipsed by the advent of antibiotics, but has gained increasing attention in recent years in response to the growing threat of antimicrobial resistance. To develop the regimen, researchers at Tufts University School of Medicine first identified phages that target the cholera bacterium, and then narrowed their focus to those that can survive and function in the human small intestine, where cholera infection takes place. Animal studies suggest that the cocktail could prevent infection when taken just three hours prior to exposure. The research team has established an independent company, PhagePro, and plans to further test and develop the therapy.

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.

2016 was a year that ushered in significant shifts in the global health landscape. We witnessed the waning of the Ebola epidemic and the waxing of the Zika outbreak; important leadership changes among the biggest institutional players in global health; and the development and introduction of new innovations that could turn the tide against leading infectious disease killers. As the year comes to an end, GHTC is reflecting on the top stories in global health innovation that made news in 2016. Here are seven of those top moments: 1. Scientists mobilize against Zika A vial of the National Institute of Allergy and Infectious Diseases (NIAID) Zika Virus Investigational DNA Vaccine (Photo: NIAID).Once considered an obscure virus responsible for a mild illness, Zika took the world by storm in 2016. As the virus gained a foothold in more than 60 countries, its association with devastating birth defects and neurological conditions was firmly established. Prior to Zika’s emergence in the Americas, only 25 research papers had been published on the virus. As the epidemic grew, scientists around the world joined the fight against Zika, often sharing their data and research in real time to speed progress. Thanks to the efforts of these researchers, over the past year our scientific understanding of Zika has grown exponentially, and we have advanced a robust pipeline of new tools to prevent, detect, and treat Zika. Today, there are more than 35 Zika vaccine candidates under development; 13 Zika diagnostics have been authorized for use by the US Food and Drug Administration; and researchers are screening novel compounds and evaluating existing drugs to advance treatments for the disease. 2. The world commits to the fight against antimicrobial resistance United Nations General Assembly (Photo: GHTC/Matthew Robinson). 2016 marked the year the world finally got serious about tackling antimicrobial resistance. On the heels of several major analyses examining the potentially devastating health and economic impact of antimicrobial resistance, the United Nations (UN) General Assembly convened global leaders for a high-level summit on antimicrobial resistance—the fourth time such a meeting has been held on a health-related topic during the UN’s 71-year history. At the close of the summit, UN member states unanimously endorsed and adopted a political declaration committing to developing action plans and policies; mobilizing resources; and supporting public awareness, surveillance, and R&D efforts to combat antimicrobial resistance. It is our hope that 2017 will mark the year political commitment translates to concrete action to advance the development of new antibiotics. 3. New strategies deployed to stymie mosquito-borne diseases Mosquito-borne diseases remain an age-old scourge, but 2016 saw the advancement of several novel strategies to combat these tiny foes. Efforts to combat mosquito-borne diseases with the transmission blocking–bacteria Wolbachia took an important leap forward this year. Past studies have shown that when the Wolbachia bacteria is introduced to Aedes aegypti mosquitos—which carry viruses like Zika and yellow fever—it prevents the viruses from replicating and blocks further transmission. Because the bacteria can be passed from one generation of mosquitoes to the next, the bacteria offers hope for eliminating a virus’s presence within a local mosquito population. After several years of conducting small-scale tests of this method, the Eliminate Dengue Program announced in 2016 it would begin conducting two large-scale trials in South America to determine whether this approach is effective in halting the spread of mosquito-borne diseases in large urban settings. This year the biotech company Oxitec also advanced efforts to test the use of genetically modified mosquitoes to reduce mosquito populations and disease transmission. The company has engineered mosquitoes that mate with A. aegypti mosquitoes, producing offspring that are unable to mature to adulthood. Early last year, Oxitec introduced the mosquitoes into the Brazilian city of Piracicaba, resulting in an 82 percent decrease in the population of A. aegypti mosquitoes in just nine months. Now, Oxitec has expanded the trial to a larger geographical area and is also initiating trials in the Florida Keys and the Cayman Islands. 4. World’s first kid-friendly TB medicine launches Children who receive tuberculosis (TB) medicines require a different dose than adults, yet until this year, there were no TB medicines designed specifically for children, so parents were forced to split or crush adult pills in an attempt to administer the right dose to their child. This year, that all changed with the launch of the world’s first kid-friendly TB medication. Developed by TB Alliance, the medicine is designed with the unique needs of children in mind: It is fruit-flavored, dissolvable in water, easy to administer, and appropriately-dosed. Already, more than 30 countries have adopted the new medicines, and enough orders have been placed to treat half of childhood TB cases worldwide. 5. Unique HIV prevention option for women reaches important development milestone Image captionMonthly vaginal dapivirine ring helps protect women against HIV (Photo: International Partnership for Microbicides). Women may soon have a powerful new tool at their disposal to prevent HIV infection. Earlier this year, the International Partnership for Microbicides (IPM) announced the results of two large phase 3 clinical trials demonstrating that a monthly vaginal ring containing the antiretroviral drug dapivirine can help protect women from HIV. While initial results indicated that the dapivirine ring reduced HIV risk by approximately 30 percent, further analysis revealed that the ring reduced infection rates by 75 percent in women who used the ring consistently. Now, IPM is seeking regulatory approval for the dapivirine ring and is conducting open-label studies, enabling trial participants to continue using the ring as IPM collects additional data. The dapivirine ring is the only long-acting, female-initiated HIV prevention tool to have proven successful in phase 3 clinical trials. Young women in sub-Saharan Africa are more than twice as likely to be infected with HIV than their male counterparts, and thus female-centered prevention tools are needed stem the epidemic. 6. Roll out begins of world’s first malaria vaccine candidate After decades of development and testing, the world’s first malaria vaccine candidate will soon be introduced in several communities in sub-Saharan Africa. The vaccine—RTS,S—was developed by PATH and GlaxoSmithKline and received a positive opinion from the European Medicines Agency last year following completion of phase 3 clinical trials. In November, the World Health Organization (WHO) announced it would pilot and evaluate the vaccine in real-life settings, thanks to funding from The Global Fund; UNITAID; and Gavi, the Vaccine Alliance. Pending results of these pilot tests, WHO will determine whether to deploy the vaccine on a wider scale. 7. New global health technologies advance through the pipeline PATH launches an easy-to-use, rapid diagnostic for onchocerciasis (Photo: PATH/Dunia Faulx) Over the past year, several other promising new health innovations have moved through the development pipeline and one step closer to reaching the hands of patients: Two important health tools—a novel, affordable oral cholera vaccine developed by the International Vaccine Institute, and the Woman’s Condom developed by PATH and partners—received WHO prequalification this year, paving the way for their procurement by UN agencies and other international procurement organizations. Two new rapid diagnostic tests for the neglected tropical diseases onchocerciasis (river blindness) and lymphatic filariasis were launched this year. Developed by PATH, these tests provide results in just 30 minutes and can be stored at a wide range of temperatures. Development has begun for an affordable therapy for hepatitis C. In 2013, the world’s first cures for hepatitis C hit the US market, however, treatment remains out of reach for many patients due to the high price tag. This year, the Drugs for Neglected Diseases initiative announced it would begin testing an alternative therapy in phase 2 and 3 clinical trials, with a guarantee from the manufacturer that, if successful, the entire regimen will be sold for no more than US$294.  As 2016 draws to a close and 2017 begins, it is time for the global health community to redouble our efforts to make sure this vital progress in global health innovation continues to ensure that people around the world will have access to lifesaving and life-improving health technologies.