Research Roundup: Identifying people at-risk for TB, a device to aid IUD insertion, and vaccines against cancer

Amid the Zika outbreak and with new vector control approaches in the pipeline, there has been much talk about the feasibility and potential risks and benefits of eradicating mosquitos. National Institute of Allergy and Infectious Diseases (NIAID) Director Dr. Anthony Fauci advocated for mosquito elimination in a recent STAT News article, joking that their only known role in the natural ecosystem is feeding birds. However, Dr. Andrew Dobson, a professor of ecology and evolutionary biology at Princeton University, argues that such an approach would be “naïve and foolish,” noting that there are more than 3,000 mosquito species, hundreds that bite humans, but just three that are responsible for the vast majority of human disease transmission. Further, Dobson suggests that we can’t predict the consequences of mosquito eradication on the natural ecosystem, and that it could lead to the development of insecticide-resistant mosquitos. Meanwhile, NPR asked experts about the feasibility of eradicating even just one mosquito species and the resources required for it to be successful. First, global coordination mechanisms and high-level political will would be required, i.e., through the appointment of a United Nations mosquito czar. Next, financial resources are a must, with Pennsylvania State University Biologist and Entomologist Dr. Andrew Read estimating that US$250-500 million would be required to eliminate the Aedes aegypti mosquito—responsible for transmitting Zika, yellow fever, dengue, and chikungunya—a high pricetag but one that pales in comparison to the $1.5 billion pharmaceutical company Sanofi spent on developing a vaccine against just one of those diseases, dengue fever. With all the resources in place, the czar would then have to determine which vector control approach to take. As pathogens grow resistant to existing insecticides, both new insecticides and mutant mosquito interventions are under development. British biotech company Oxitec is currently testing its sterile-male mosquitos in Brazil. Oxitec’s mosquitos are released into the wild where they mate with female A. aegypti mosquitos, producing offspring that don’t live to adulthood and consequently can’t infect humans. The approach has resulted in an 82 percent decrease in the presence of A. aegypti larvae in the region in just nine months. Another intervention involves releasing mosquitos infected with Wolbachia bacteria, which then spreads among the mosquito population and can reduce the mosquitos’ ability to produce healthy offspring and to transmit viruses to humans. Finally, scientists are developing mosquitos using “gene-drive” technology, which involves releasing mosquitos genetically modified to be unable to lay eggs or transmit diseases. A team of scientists at the University of Texas Medical Branch (UTMB) have created a genetically modified mouse that is susceptible to Zika virus, making it the first animal model that can be used to test drugs and vaccines against the virus. The study, published in The American Journal of Tropical Medicine and Hygiene, provides further evidence that Zika is sexually transmitted and that it impacts the nervous system, as the viral load in mice was highest in the spleen, brain, and testes. The team, led by UTMB Virologist Dr. Shannan Rossi, developed the model in just three weeks, an impressive feat for a process that normally takes several months. UTMB scientists are also using the model to test an antiviral drug, developed for dengue fever, against Zika. The mouse model will be invaluable to scientists, particularly in light of the dearth of research on Zika. However, the mouse amnion—in which fetal development takes place—varies significantly from the human amnion, and thus, scientists are continuing to look for animal models that can shed light on the impact of Zika during pregnancy.

US Senator Bernie Sanders (I-VT) released a plan last week as part of his Democratic presidential bid to incentivize research and development (R&D) for new HIV and AIDS medicines while ensuring they remain affordable. Under his proposal, drug companies would receive a cash prize for market introduction of a novel HIV and AIDS therapy, but would not receive exclusive marketing rights, an idea he first proposed in 2012. The prize would reflect the “therapeutic value” of the treatment as well as the number of people expected to benefit from the product. To finance these cash prizes, the Senator is proposing a Prize Fund for HIV and AIDS of US$3 billion per year. Eliminating exclusive market rights for these new drugs would ensure that generic products could immediately enter the market, spurring competition and lowering prices. However, critics argue that the proposal could take limited research funding away from other diseases and note that the plan does not detail how the size of the cash award would be determined for a given drug or to whom it would be distributed (i.e., the patent holder, the regulatory sponsor, public-sector agencies involved in the basic research, etc.). Photo: CDC The US Food and Drug Administration (FDA) announced last week its tentative approval of a trial of genetically engineered mosquitos to combat mosquito-borne diseases, pending 30 days of public comment. The mosquitos, developed by British company Oxitec, are intended to reduce the population of Aedes aegypti mosquitos, which transmit the Zika, dengue, chikungunya, and yellow fever viruses. The mosquitos are all male and when they reproduce with native mosquitos, their offspring are not viable, dying before reaching adulthood. The trial, if approved, will take place in the Florida Keys; Oxitec’s mosquitos would be released up to three times per week for up to 22 months. After a careful review, the FDA has determined, in collaboration with the US Centers for Disease Control and Prevention and the Environmental Protection Agency, that the trial is safe for humans, animals, and the environment. The agency noted that the trial will be short and that the Aedes aegypti “occupy a fairly uncontested ecological niche,” making it unlikely that another mosquito population would expand to fill the vacuum. The United Nations Children’s Fund (UNICEF) and the government of Malawi are conducting a pilot program to determine the cost, feasibility, and impact of using drones—unmanned aerial vehicles—to expedite HIV and AIDS testing for infants. In Malawi, 10 percent of adults are HIV-positive, and there are 130,000 children living with HIV and AIDS. However, it can take up to ten weeks to get HIV test results for infants born to mothers with HIV and AIDS, who require specialized testing. The blood samples are transported by ambulance or bike to one of only eight labs in the country capable of conducting these tests. It then takes at least two weeks for the tests to be completed, and often the results wait in the lab until there is a large batch. UNICEF and the Malawi government are testing the feasibility of drone delivery at different times and in different weather conditions and will be comparing the costs, which include electricity for charging the device and the hardware itself, to current delivery methods, which include fuel and driver salaries. The goal is to reduce testing time from more than two months to just a few days, ensuring that children with HIV and AIDS can start treatment much sooner.