Researchers are targeting a possible new weapon in the fight against malaria, science that could also be applied in the fight against other devastating mosquito-borne illnesses, according to a Vanderbilt study published in PLOS ONE.
The scientists, including Vanderbilt University School of Medicine investigators, have isolated a chemical that causes kidney failure in mosquitoes, leaving some of the mosquitos too bloated to survive after feeding.
The research, a collaboration that also includes Ohio State and Cornell Universities, was conducted on species that are known to carry malaria, West Nile virus, dengue and yellow fever.
“The principle behind the research is simple,” said Jerod Denton, Ph.D., assistant professor of Anesthesiology and Pharmacology. “By introducing a specific chemical, we cause kidney failure in mosquitoes, and they can’t eliminate fluids after a blood meal. They become bloated and unable to fly, which makes them highly susceptible to predators. Most importantly, they meet an untimely death. In layman’s terms, the mosquito’s kidneys shut down, it can’t pee, and it nearly explodes.”
According to the Tennessee Department of Health, in 2012, 33 human cases of West Nile virus were reported in the state, with one recorded death. Since the first recorded human case in 2002, there have been 230 human cases of West Nile virus confirmed statewide. Thus far this year, there have been four active cases of malaria and two cases of dengue fever in Tennessee; in 2012 there were 11 cases of malaria and six cases of dengue fever. All involved travel outside of the United States.
Current insecticides work primarily by targeting the mosquito nervous system, but these chemicals are becoming less effective as insects evolve to develop resistance. There are also increasing concerns about the long-term impact of these chemicals on other life forms, Denton said.
Rene Raphemot, a 29-year-old doctoral student working in Denton’s laboratory, is the lead author of the study detailing their research. As a native of Gabon, Africa, he knows firsthand how a single mosquito bite can lead to extreme suffering and even death; as a child he twice became severely ill from malaria.
“I’m excited to be doing research to fight a disease that has such devastating impact on my home country,” Raphemot said. “I’ve witnessed the suffering these mosquitos cause my entire life, and to now be a lead investigator on something that could one day eliminate that suffering is unbelievable.”
Although the laboratory research is very promising, that doesn’t mean it’s ready for store shelves. Denton said the chemical could also have toxic effects in humans with direct exposure. Work is underway at Vanderbilt to develop mosquito-specific compounds to address this issue. Regardless, mosquitoes could not transfer large enough quantities of the chemicals to affect humans, he added.
Denton is collaborating with Peter Piermarini, Ph.D., assistant professor of Entomology at the Ohio State University (OSU) and Klaus Beyenbach, Ph.D., professor of Physiology at Cornell University. Corey Hopkins, Ph.D., research assistant professor of Pharmacology and Chemistry and associate director of Medicinal Chemistry for the Vanderbilt Center for Neuroscience Drug Discovery, also collaborated on the project.
The study is funded by a $1.4 million grant from the Foundation for the National Institutes of Health’s “New Insecticides for Malaria Control” program, which is supported by the Bill & Melinda Gates Foundation, grants 1R01DK082884 and PIER11VCTR.
