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. 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.

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.

Researchers at Massachusetts Institute of Technology and Harvard Medical School have designed a star-shaped pill that releases medicines over the course of two weeks. The long-acting pill has six arms that can be folded into a capsule. Once the capsule reaches the stomach, its outer layer is dissolved, causing the six arms to pop out. Due to its size, the expanded pill is able to remain in the stomach until its arms detach and are digested one by one. The research team used the antimalarial ivermectin to test this delivery system in pigs. The medicine was continually released for two weeks—an impressive feat as oral medicines rarely last longer than a day. Long-acting medicines can significantly improve adherence to complicated treatment regimens. The researchers are now using the platform to develop drugs for neuropsychiatric disorders, HIV and AIDS, diabetes, and epilepsy. Someday soon, one drop of blood and a USB stick could be all that’s required to determine a patient’s HIV viral load. The system uses an electronic chip to detect the virus and transform it into an electronic signal, which is then picked up by the USB, enabling users to access their results off by computer. The device was used to evaluate nearly 1,000 blood samples and proved to be accurate 95 percent of the time, providing results in 21 minutes on average. Current techniques to assess viral load take three days. Patients in remote areas often have to wait much longer because their samples must be transported to laboratories. The HIV virus can develop resistance to antiretroviral treatment, resulting in increasing levels of the virus in the blood. Patients could use this tool to regularly monitor their viral load, ensuring early detection of resistance. During infection, bacteria deploy minute molecules—siderophores—to steal iron from human cells. Microbes need iron to reproduce and interfering with this process could debilitate bacteria, preventing infection. Scientists have sought to develop vaccines that train the immune system to respond to the presence of siderophores; however, the molecules are too small to prompt an adequate immune response. Now, two independent groups of researchers have demonstrated that attaching siderophores to large proteins boosts the immune response. One team used siderophores from the strain of E. coli that causes urinary tract infections, while the other used the strain of Salmonella that causes food poisoning. Both teams vaccinated mice and then exposed them to the bacteria several weeks later. While neither vaccine provided complete protection, infections were much less severe in vaccinated mice. Mice that were vaccinated against E. coli had one-tenth the bacterial load in their urine and kidneys and less inflammation in their kidneys and bladders. The Salmonella-based vaccine triggered the production of antibodies against the siderophores, resulting in a bacterial load 20,000-fold fewer in vaccinated mice.