Fighting malaria by manipulating mosquitoes' sense of smell

Combating the spread of malaria by manipulating the mosquitoes' sense of smell is the object of an ambitious research project, led by Vanderbilt University, that has been selected to receive $8.5 million as part of the Grand Challenges to Global Health.

The initiative, which was launched by the Bill and Melinda Gates Foundation, has just announced the selection of 43 "groundbreaking" research projects to improve health in developing countries that will receive a total of $436 million in support. As part of this effort, mosquito researchers from Vanderbilt University, Yale University, the Wageningen University in the Netherlands, the Ifakara Health Research and Development Centre in Tanzania and the Medical Research Council Laboratories in the Gambia will be developing a fundamentally new approach to malaria control that relies on powerful chemical repellents and attractants deployed in ways that can both interfere with malaria mosquitoes' ability to find human targets and lure the insects to their death.

Malaria is considered to be the most prevalent life-threatening disease in the world, with estimates of the number of new cases that range from 300 million to 660 millions cases per year. Current efforts to control this disease, which combine the use of insecticides with improved access to effective diagnosis and treatment, have great potential to save lives but face enormous challenges and cannot eradicate malaria without the development of complementary control technologies.

Recent advances in the genetics, biology, immunology and behavior of mosquitoes open up new and unexplored avenues for controlling malaria and other mosquito-borne diseases. The goal of the Vanderbilt-led research team is to pursue one of the most promising of these new avenues: developing chemical compounds that interfere with the malaria mosquitoes' exquisite sense of smell. The effectiveness of such an olfactory strategy has been demonstrated by a program with the African tsetse fly that has replaced the practice of treating large tracts of land with persistent insecticides with the use of scented baits. It is widely considered to be an environmental and technological success. Unlike insecticides, the chemicals involved in insect olfaction tend to be relatively non-toxic. They also tend to be specific to closely related species, so widespread application is not likely to impact other beneficial insect populations.

The researchers intend to set up a pipeline for identifying and testing non-toxic chemical odorants that attract, repel or simply confuse the mosquito's olfactory system.

The pipeline begins with the high-tech genetic engineering and molecular biology laboratories at Vanderbilt and Yale, which will identify chemical compounds that interact strongly with receptors in the female mosquito's antennae and appear to be related to host selection. The most promising of these mixtures will be shipped to Wageningen University where their effects on the behavior of live mosquitoes will be determined. Compounds that pass the behavioral tests will be forwarded to Tanzania, where they will be evaluated with laboratory-reared mosquitoes in a large biosphere that simulates the natural environment. Finally, odorants that have passed all these tests will be field tested in cooperating villages near Ifakara and in The Gambia under the supervision of IHDRC and MRC Laboratories' researchers.

"By combining laboratory-based and field-based studies, we expect to establish an effective strategy for developing extremely powerful attractants and repellents for malaria mosquitoes and identifying effective methods for using them to reduce the spread of malaria," says Laurence J. Zwiebel, associate professor of biological sciences at Vanderbilt, who is the lead investigator on the project.

The mixtures developed in the project could be useful against other disease-carrying mosquitoes, such as those that spread dengue fever and those that carry the West Nile virus. In addition the project will test a basic approach that could be directed against a number of other insect species, including agricultural pests and those that carry other human and animal diseases.

The Grand Challenges initiative was launched by the Bill & Melinda Gates Foundation in 2003, in partnership with the National Institutes of Health, with a $200 million grant to the FNIH and is a major international effort to achieve scientific breakthroughs against diseases that kill millions of people each year in the world's poorest countries. It is funded with a $450 million commitment from Gates Foundation, $27.1 from the Wellcome Trust, and $4.5 million from the Canadian Institutes of Health Research (CIHR). The initiative is managed by global health experts at the Foundation for NIH, the Gates Foundation, the Wellcome Trust, and CIHR.

Source : Vanderbilt University