NIH funds development of resistance-breaking insecticides to reduce malaria transmission

Blacksburg, Va. – Researchers from Virginia Tech and Molsoft LLC have received a five-year, $3.557 million grant from the National Institute of Allergy and Infectious Diseases (NIAID) to continue their promising work on a new class of resistance-breaking insecticides to reduce malaria transmission.

At present, the first line of defense against the malaria mosquito in sub-Saharan African is insecticide treated nets (ITNs). However, growing resistance to the pyrethroid insecticides used on the nets threatens to render this protection ineffective. The research team led by Paul Carlier (www.files.chem.vt.edu/chem-dept/carlier/), professor of chemistry in the College of Science at Virginia Tech, is striving to develop a new class of insecticides that will be safe for use on nets and effective against pyrethroid-resistant mosquitoes.

The NIAID award builds on results from three years (2005-2008) of research funded by the Foundation for the National Institutes of Health (FNIH) through the Grand Challenges in Global Health initiative of the Bill and Melinda Gates Foundation. This earlier project was led by Jeffrey R. Bloomquist, professor of toxicology and pharmacology in the entomology department of Virginia Tech's College of Agriculture and Life Sciences.

"In 2005, we had a great multidisciplinary team and a promising new idea," said Carlier.

The team combined chemists, entomologists, and biologists in the United States with malaria mosquito control experts in Kenya. The focus was to develop insecticides that strongly interfere with acetylcholinesterase (AChE), a key enzyme in the mosquito brain, while leaving the related human enzyme untouched. The promising new idea was that the malaria mosquito, Anopheles gambiae, would pick up two inactive molecules from a bed net that would then bind to AChE within the mosquito and thus disable it. "That initial concept has not yet been realized," said Carlier.

However, the team made two important advances which form the basis for the NIAID grant for "Development of vector-specific, resistance breaking insecticides to reduce malaria transmission."