Breakthroughs Blog: Research Roundup

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. For many years, ineffective treatment plans and archaic diagnostic tools have stood as a barrier to tackling tuberculosis (TB). More recently, new drugs and diagnostics have emerged. Yet, availability has not always translated to widespread access. For example, despite the availability of new rapid diagnostic tools like GeneXpert, it is estimated that over 40 percent of new TB cases go undiagnosed or are not reported and use of older, less accurate sputum tests still outpace use of the GeneXpert. Though new drugs like bedaquiline and delamanid are not available, more than 75 of patients who need them do not have adequate access. A number of hurdles to adoption and scale-up exist from lack of funding for TB programs to high costs to implementation failures Action is needed by global leaders and innovators to break down these barriers if the global community wants to achieve its goal of eradicating TB by 2030. Malaria is more complex than scientists previously thought. In a recent study published in the Proceedings of the National Academy of Sciences, scientists used DNA fingerprinting to track malaria on a cellular level. They found that the parasite has a heightened level of genetic recombination developed during meiosis, leading to a wide variety of malaria strains. This suggests that malaria can evade immune system response, acting as a chronic disease—and it means there is no one-cure-fits-all solution. Because of the incredible amount of genetic diversity malaria can have in the body, one vaccine solution may not work for all individuals, casting doubt on the efficay of vaccines now in development. While this discovery makes malaria harder to prevent and eradicate, scientists have also discovered that malaria isn’t as transmissible as it first seemed, with the parasite only causing five or six secondary cases from one original infection, whereas it was previously thought one case could subsequently infect dozens of individuals. The International Partnership for Microbicides (IPM) has announced a clinical trial that is hopeful to significantly reduce cases of HIV in Sub-Saharan Africa and around the world. The clinical trial will use the IPM-developed dapivirine ring, a small silicone ring inserted in the vagina, releasing a contraceptive (levonorgestrel) and an anti-HIV drug (dapivirine). The ring is easy to insert and lasts three months. Building on the previous ring that only released dapivirine, having the ring also act as a contraceptive will not only reduce the likelihood of HIV infecting women, but will also provide women with the choice to protect against unwanted pregnancy. This trial is especially important because women are most at-risk for contracting HIV, especially in countries with low rates of condom use. IPM hopes to have the ring ready for shipment globally by 2020.    

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. Over the last ten years, the WHO has convened global partners to address the incidence and health impact of neglected tropical diseases (NTDs). There has been clear progress, as countries have taken major steps toward combating increasing rates of NTD screening and treatment. Currently, all Latin American countries screen for the Chagas virus in their blood donors. African trypanosomiasis (sleeping sickness) is on track for eradication, with under 3,000 reported cases per year. Nonetheless, the challenges surrounding eradication of all NTDs are apparent, with the majority of vaccinations and medicinal treatments coming in the form of donations to the poorest countries in the world. The WHO highlights these efforts in their 2030 Sustainable Development Goals (SDGs), which includes goals to achieve the eradication of all NTDs, but recognizes the challenges that hinder progress as politics and public health priorities shift. An estimated ten percent of children in Kenya are affected by tuberculosis (TB), with more fatal cases of TB occurring in children than in adults in Kenya who contract TB. However, a recent initiative to deploy child-friendly medicines (water-soluble pills rather than bitter pills) has been associated with an increase in child survival. Issues surrounding TB in Kenyan children include cases that are not diagnosed, leading to severe forms of TB—including tuberculous meningitis, which is incredibly debilitating. The Kenyan Ministry of Health has been open about obstacles and successes regarding TB treatment, and has urged parents to be a part of the process to get their children diagnosed and treated. Polio incidence has been at a historic low, and only Afghanistan, Nigeria, and Pakistan remain on the endemic list for the disease. Despite these levels being lower than they have ever been, new obstacles have slowed progress toward global eradication. These obstacles include a vaccine shortage and instability within the countries. The shortage of the inactivated polio vaccine currently affects 35 countries, and the supply will not be restored until at least 2018. The majority of polio cases in Afghanistan and Pakistan occur along the border, suggesting that there are geographic implications of the endemic. Nigeria, which was previously polio-free, had two cases of polio that set the country back. Pakistan is optimistic about eradicating the virus, and is launching a campaign to vaccinate over 37 million children. The CDC estimates over 300,000 individuals in the United States suffer from Chagas, a parasitic disease that causes irreversible heart damage. Mosquitos carrying Chagas currently live in 27 states and take up much of the southern United States, meaning many Americans living in the south are susceptible to infection. Early detection and treatment are necessary to combat heart failure, and US agencies like the CDC and FDA must work with urgency to treat this as a national public health issue.

Surgical masks are a popular accessory worn in public spaces during outbreaks of airborne diseases, however, in reality, they provide limited protection against pathogens; they may trap viruses, but they can’t kill them. Consequently, even just the act of removing the mask can expose the wearer to a virus. A team of scientists at University of Alberta are hoping to change that. They have adapted the standard surgical mask so that it can both trap and deactivate viruses. The inspiration for the mask came from a challenge faced by lead researcher Dr. Hyo-Jick Choi in his work adapting vaccines for oral administration: when liquids (i.e., vaccines) turn into solids (i.e., pills), they crystallize, damaging the viral components that make the vaccine effective. Dr. Choi realized he could turn this challenge into an advantage to target viruses that come in contact with surgical mask. He and his team developed and applied a safe, salt-based solution to the masks. As predicted, when a virus—in this case, influenza—came in contact with the mask, it was destroyed, as the droplet carrying it crystallized. Dr. Choi has received a provisional patent and plans to further advance the innovation. Advocates are calling for greater inclusion of pregnant women in clinical trials, a necessary step to address critical knowledge gaps and improve health care for pregnant women and their fetuses. In the United States, nearly two-thirds of women receive at least one prescription during pregnancy, yet more than 90 percent of drugs approved by the US Food and Drug Administration over the past three decades have not been proven safe for use in pregnancy. The hesitancy to include pregnant women in clinical trials is well-founded: drugs and vaccines can cross the placental barrier, resulting in complications or birth defects. However, pregnant women need safe, effective medicines, and clinical trials ensure that negative side effects are caught early, limiting the number of patients impacted. Further, pregnant women are more susceptible to certain pathogens, and as illustrated by the ongoing Zika outbreak, pathogens can cross the placental barrier too, making treatment during pregnancy all the more imperative. Additionally, women may process drugs at higher rates during pregnancy, consequently requiring higher doses. Advocates argue that while testing experimental drugs in pregnant women is risky, it is much safer than allowing a medicine to enter the market, leaving the decision to physicians and patients. The Defense Advanced Research Projects Agency (DARPA), an entity within the US Department of Defense, invests in high-risk, high-reward research, developing innovative technologies to advance US national security, with its health portfolio spanning research from neural and psychiatric health to infectious diseases. Through its Biological Technologies Office, DARPA scientists are taking an innovative approach to drug development. Rather than relying on chemicals to generate novel drug compounds, researchers are genetically modifying yeast, bacteria, and other microbes to do the job. Already, BARDA’s work with yeast has resulted in nearly 100 new molecules, and officials hope to reach 1,000 over the next three years. DARPA is also devising new platform technologies to expedite the development and improve the efficacy of vaccines against emerging infections. One method uses nucleic acids (i.e., RNA and DNA) to signal to the immune system how to respond to a pathogen, rather than introducing a pathogen and allowing the immune system to learn how to respond on its own. If successful, this technology could be adapted for different diseases and would provide instantaneous protection—a significant advantage as most vaccines take at least two weeks to provide protection.