Kat Kelley

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.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. The location of pig farms can influence human flu patterns, as farmworkers may be among the first exposed to new strains of swine flu. Researchers at Duke University compared a map of North Carolina’s concentrated animal feeding operation (CAFOs) to the location and timing of flu outbreaks in the state, concluding that counties with high numbers of CAFOs experience early peaks of flu cases during years in which a strain of swine flu is in circulation. However, the same effect was not seen in years when the most common strains of influenza did not originate in pigs. The trend is likely attributable to transmission of swine flu from pigs to farmworkers, and subsequently to their family and friends. While efforts targeting CAFOs, such as animal surveillance or vaccination, could decrease human risk for swine flu, a more affordable and immediate solution is for farmworkers and their families to get a flu shot as early as possible each year. Extensively drug-resistant tuberculosis (XDR TB) may be more infectious than previously believed, according to new research out of South Africa. Tuberculosis (TB) is difficult to treat as patients must take multiple pills a day over months or even years. When patients are unable to complete the regimen, the bacteria can grow resistant to the medicines, resulting in multidrug-resistant and XDR TB. However, a study of 404 XDR patients in South Africa suggests that only one-third of cases are due to treatment failures, whereas the remaining cases resulted from person-to-person transmission. These findings indicate that combatting XDR TB will require both improved treatment for TB patients and enhanced prevention and detection efforts. A common fungal infection, Candida auris, is growing increasingly drug resistant. Strains that are resistant to all three classes of antifungals have been reported in five continents. As with antibiotic resistance, antifungal resistance has emerged as a result of inappropriate and overuse of antifungals, and while it may not be as widespread, there are fewer classes of antifungals, providing few alternatives if a treatment fails. An investigation of 54 samples of C. auris found that nearly all were resistant to the first-line medicine (fluconazole), 22 were resistant to both the first and second-line treatments, and 2 were resistant to all three classes of antifungals. Further, standard approaches to disinfecting hospital rooms and equipment are insufficient to eliminate C. auris, increasing the risk of hospital-acquired infections. While cases remain limited, the fungus has an extremely high fatality rate, killing 60 to 70 percent of those infected. Nine recently approved and widely used hepatitis C medicines may have serious, unexpected side effects, including liver failure. The new antivirals cure nearly all patients, have fewer side effects than older medicines, and significantly shorten the duration of treatment. However, a new report published by the Institute for Safe Medication Practices details adverse effects, including potentially fatal liver failure and reactivation of the closely related hepatitis B. At this time, cases are rare and the findings are inconclusive, as the Institute did not have access to patients’ medical records that could shed light on whether the side effects preceded treatment. Now, the Food and Drug Administration is calling on physicians to screen and monitor for hepatitis B in patients taking the new medicines, and a similar approach might be needed to rule out the risk of liver failure.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. An English springer spaniel has been trained to sniff out Clostridium difficile, a drug-resistant bacterium that infects nearly half a million Americans and costs the US health system an estimated US$1 billion annually. The two-year-old pup—Angus—was tapped for the job after Teresa Zurberg, who normally trains dogs to sniff out bombs and drugs, almost lost her life to C. difficile. Zurberg’s husband, a nurse, had read about a now-retired beagle in the Netherlands that had been trained to smell the bacteria on patients, and the couple approached the local health authorities, suggesting their new pup would be a prime candidate for such a job. Now, after extensive training, Angus is an official employee of Vancouver General Hospital, where he moves from room to room, searching for traces of the bacteria, which are then destroyed using ultraviolet light. As nearly two-thirds of C. difficile cases are acquired in hospitals, dogs like Angus could have a significant impact in not just detecting, but preventing, new cases of C. difficile. Launched last week at the World Economic Forum in Davos, the Coalition for Epidemic Preparedness Innovations (CEPI) seeks to develop vaccines against the diseases most likely to cause the next major pandemic. The coalition was established by the governments of Norway, Japan, and Germany in partnership with philanthropic organizations the Wellcome Trust and the Bill & Melinda Gates Foundation. Collectively, these partners have pledged US$460 million to the initiative, half of what is needed for CEPI’s first five years of operation. During its initial phase, CEPI will focus on advancing two experimental vaccines for each of the three viruses that have been identified by the World Health Organization as leading contenders for the next major pandemic: Lassa fever, Middle East respiratory syndrome (MERS), and Nipah virus. Carbapenem-resistant Enterobacteriaceae (CREs), a class of deadly, drug-resistant bugs that have been deemed “nightmare bacteria” by the director of the Centers for Disease Control and Prevention may be more prevalent and virulent than previously realized. These bacteria often contain specific genes that enable them to evade different types of antibiotics, including carbapenems, potent drugs that are often reserved as the last line of treatment against drug-resistant infections. To better understand their evolution and spread, researchers at Harvard University and the Massachusetts Institute of Technology sequenced the genomes of 263 CREs, collected from patients at four hospitals. The results revealed that carbapenem resistance is emerging across diverse types of bacteria and that the genes that confer resistance can be transferred between distinct bacterial families. Even more alarming: some CREs don’t have any of the known resistance genes, meaning that there are either more, unidentified resistance genes than we are aware of or that CREs have developed other ways to resist antibiotics. The study also indicates that CREs can be carried and transmitted asymptomatically, making surveillance of these dangerous infections all the more difficult.

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 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.