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Attacking malaria on several fronts

by Apr. 27, 2011, 4:48 PM

Illustration shows the life cycle of the malaria parasite (red arrows), and what happens when it is transmitted by mosquito bite into the human (blue arrows). (Illustration courtesy of the U.S. Centers for Disease Control and Prevention)
Illustration shows the life cycle of the malaria parasite (red arrows), and what happens when it is transmitted by mosquito bite into the human (blue arrows). (Illustration courtesy of the U.S. Centers for Disease Control and Prevention)

Malaria kills more young children than any other disease.

Monday, April 25 was World Malaria Day, a date chosen by the World Health Organization to draw annual attention to the terrible toll of this disease – more than 780,000 deaths a year, most of them in Africa.

Several scientists at Vanderbilt are working on ways to improve malaria diagnosis and treatment and prevent the mosquito-transmitted disease.

Coffee ring diagnostics

David Wright, associate professor of chemistry, and Rick Haselton, professor of biomedical engineering, are developing a low-cost, low-tech diagnostic test for malaria. In 2009, they received a Grand Challenges Explorations grant from the Bill & Melinda Gates Foundation to develop a simple at-home test with easy-to-interpret results that can be used in resource-limited settings.

“The ideal malaria diagnostic test would be comparable to the ease of a pregnancy test,” Haselton said. Early diagnosis is important because timely treatment reduces illness and prevents death.

The result of their research, a “Coffee Ring Stain Diagnostics for Malaria,” is based on the phenomenon that causes coffee-ring stains on the kitchen counter: When a liquid like coffee that contains fine particles evaporates from a flat surface, the particles tend to gather along the outer edge of the stain. This diagnostic technology would use colorimetric results, for example, a green result would signify no sign of malaria, while a red result would indicate an infection.

Wright and Haselton are now studying whether their test can diagnose malaria infection from a sample of saliva. They hope to use saliva because people in Sub-Saharan Africa have a cultural aversion to having their blood tested. Wright is also using drug discovery methods to find potential new medications for malaria, which has become resistant to many current therapies.

Clues in saliva..

Julián Hillyer, assistant professor of biological sciences and mosquito biologist, dedicates most of his research to studying mosquito physiology including immunology and blood flow. In addition, he is trying to understand better how the malaria parasite travels through the insect.

Hillyer’s lab is looking for receptors in the mosquito salivary gland to which the malaria parasite must bind in order to complete its life cycle and enter a new host. Although this research project is still in the preliminary stages, finding such receptors and blocking them could lead to ways to prevent the bite of the mosquito from transmitting the parasite.

…and in sweat

Mosquitoes use chemical signals in the environment to guide them to different behaviors – to feed, to mate or to deposit their fertilized eggs. (Illustration courtesy of Laurence Zwiebel)
Mosquitoes use chemical signals in the environment to guide them to different behaviors – to feed, to mate or to deposit their fertilized eggs. (Illustration courtesy of Laurence Zwiebel)

Laurence Zwiebel, professor of biological sciences and pharmacology, and his colleagues are targeting the mosquito’s odorant receptors, proteins found primarily in sensory hairs on its antennae that enable it to find its host. Supported by a Grand Challenge in Global Health grant from the Gates Foundation, the researchers have found that some of these receptors bind specifically to chemicals found in human sweat.

The Zwiebel lab is now identifying chemical compounds that, by binding to the receptors, will either attract mosquitoes into a trap, where they are killed, or will repel them away from nearby humans. With additional funding from the Gates Foundation and with help from the Vanderbilt University Office of Technology Transfer and Enterprise Development, Zwiebel’s team is on the path toward developing an anti-malarial product that would go to market with the help of private sector partnerships and non-governmental organizations.

“Our project has transitioned from discovery to development in our quest for chemical agents to reduce the close encounters between malaria vector mosquitoes and potential human hosts,” Zwiebel said. “This is extraordinarily challenging work involving medicinal chemistry (in collaboration with the Vanderbilt Institute of Chemical Biology), behavioral validation in the lab and field, as well as the uncharted territory of regulatory approval within the context of developing robust private sector partnerships.

“While our project may have come to the end of its beginning,” Zwiebel said, “it has by no means reached the beginning of its end.”

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