Stopping Malaria at Its Source - Without Drugs

TROY, New York, August 29, 2007 (ENS) - Malaria kills over one million people around the world, mostly young children. And the problem is growing as the Earth heats up due to global warming. Outbreaks of the deadly parasitic disease are spreading into temperate latitudes a little more each year, health officials report.

Now an international team led by researchers from Rensselaer Polytechnic Institute has found a key link that causes malarial infection in both humans and the mosquitoes that carry the disease.

If this link in the chain of infection can be broken at its source, the mosquito, then the spread of malaria could be stopped without anyone needing to a take a drug.

Malaria is carried by a mosquito (Photo credit unknown)
The researchers’ discovery will be published in the August 31 edition of the "Journal of Biological Chemistry."

The team found that humans and the mosquitoes that carry the malaria parasite share the same complex carbohydrate, heparan sulfate.

In both humans and mosquitoes, heparan sulfate is a receptor for the malaria parasite, binding to the parasite and giving it quick and easy transport through the body.

The team was led by Robert Linhardt, a professor of biocatalysis and metabolic engineering at Rensselaer, who said, "The discovery allows us to think differently about preventing the disease. If we can stop heparan sulfate from binding to the parasite in mosquitoes, we will not just be treating the disease, we will be stopping its spread completely."

Robert Linhardt is internationally known for his work with heparan sulfate. (Photo courtesy RPI)
Malaria parasites are finicky about their hosts, Linhardt explained. Birds, rodents, humans, and primates all can be infected with malaria, but each species is infected by a different species of mosquito and each of those mosquitoes is infected by a different malaria parasite.

There needs to be a perfect match at the molecular basis for malaria to spread from one species to another, Linhardt said. Researchers have long understood this deadly partnership, but the molecular basis for the match had never before been determined.

"The discovery marks a paradigm shift in stopping malaria," Linhardt said "Now, we can work to develop an environmentally safe, inexpensive way to block infection in mosquitoes and not have to worry about drug side effects in humans."

"Unfortunately, there is little direct funding on malaria in this country outside of the Bill and Melinda Gates Foundation, because it is not considered a major threat in this country," Linhardt said. "We do our research on a shoestring. Malaria research funding needs to move higher up on the scientific priority list."

Linhardt and his collaborators were the first to discover the link between the spread of malaria in humans and heparan sulfate in 2003.

Heparan is a major clinical anticoagulant with more than 500 million doses used worldwide each year. heparan and related molecules exhibit a large number of newly discovered biological activities and have great therapeutic potential, he says.

The next step for Linhardt, outlined in the current study, was to determine if heparan sulfate also was present in the species of mosquito known to spread malaria to humans, Anopheles stephensi.

To make this key link, Linhardt and his team enlisted the help of New York University physician and entomologist Photini Sinnis.

Malaria patients and their relatives at Kilifi District hospital in Kenya. (Photo by  Andy Crump courtesy WHO)
After finding heparan sulfate in mashed mosquitoes, Sinnis needed to determine if heparan sulfate was in the mosquito organs known to host the malaria parasite. If so, it was likely that heparan sulfate is the reason malaria spreads from mosquito to human and human to mosquito.

In mosquitoes, the malaria parasite infects the digestive tract. A mosquito bites a human who carries the malaria parasite in his or her bloodstream. The parasites move into the bug’s gut and then to their salivary glands, allowing the mosquito to infect another human during its next blood meal.

To isolate a two-microgram salivary gland and the four-microgram digestive tract from each mosquito required the precise skill of Sinnis and her team.

Once isolated, the guts and glands were analyzed by scientists at Chiba University in Japan. heparan sulfate was found in both mosquito organs.

As a final step, the Rensselaer team had to prove that the heparan sulfate in the mosquito bound to the same malaria parasite as the heparan sulfate found in the human liver. It proved to be a perfect match.

Copyright Environment News Service (ENS) 2007. All rights reserved.