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March 28, 2006

Malaria Conference Highlights Complexity of the Fight against Malaria

Most of us don’t think of the dreaded Anopheles mosquito as an underdog, a hapless creature that is easily infected by the Plasmodium falciparum parasite and needs our help in fighting off this invader. But that’s exactly how many malaria researchers perceive this universally disliked pest: They are trying to help it fight off its Plasmodium infection. At the March 20–21 Third International Malaria Research Conference at the Johns Hopkins Bloomberg School of Public Health, they shared the progress they are making in finding a cure for this disease, which cripples whole nations in the developing world.

In his keynote address, Fotis C. Kafatos, PhD, told of identifying a rich array of killing mechanisms within the mosquito’s immune system, some of which can destroy as many as 99 percent of the invading parasites at various stages of Plasmodium’s lifecycle. Kafatos’s lab is working to boost the killing efficiency of some of these processes to 100 percent. Conversely, Kafatos, director-general of the European Molecular Biology Laboratory (EMBL), and his colleagues have also been locating agonist genes, those that help Plasmodium to survive. By over-expressing the genes antagonistic to the parasite and repressing expression of the agonists, the scientists are trying to find ways Anopheles can rid itself of infection.

Zul Premji, PhD, head of the department of parasitic infections at the Muhimbili University College of Health Sciences, Institute of Public Health, Dar es Salaam, Tanzania, is not a microbiologist; instead, he uses epidemiologic methods to take a macro approach to fighting malaria. He told of some surprising epidemiologic findings his team has made. Not only has Tanzania’s incidence of malaria dropped from 2.1 per 100,000 in 1995 to 0.17 currently (a finding also reported in Zambia), but the disease is also attacking greater numbers of young adults. Premji offered some explanations of these shifts, among them an increased awareness of the disease among the population, a serious drought in East Africa, improved roads, greater use of bed nets (40 percent of the population now use them, up from 2 percent), and the easy availability of new medications.

At the same time that some processes are reducing the incidence of malaria, Premji also noted that malaria is getting a boost from such things as the spread of HIV (which aggravates malaria), the lack of good diagnostic tools and malaria’s continued resistance to drugs. These opposing processes make it difficult to determine the true direction malaria incidence is going to take. Premji stressed that a fast and accurate diagnostic test is particularly crucial because as many as 50 percent of the children currently receiving antimalarials do not have the disease.

Didier Fontenille, PhD, of the Laboratoire de Lutte Contre les Insectes Nuisibles, Institut de Recherche pour le Développement in Montpellier, France, is another investigator looking at the big picture. Dr. Fontenille addressed the complexity of vector species composition in malaria endemic regions of Africa. For instance, malaria in Cameroon is transmitted by a couple of main vector species—along with another nine secondary vectors that also can carry the parasite. “And these species,” he said, “are really very different from one another. The same village can be plagued by several different species.” He has not yet determined whether these different vectors each carry a different variation of Plasmodium. “There are huge differences between mosquitoes within 50 km of each other, and these are not areas with big climate differences either.” He now is looking at whether the numbers of Plasmodium oocysts (cysts located in the outer wall of the mosquito midgut) and infection rates differ among these mosquito subspecies.

Fontenille noted that chromosomal variations in mosquitoes can be linked to climate and environment. By studying hosts and breeding sites—standing pools, and even cattle and camel hoof prints—he has determined that An. gambiae, for instance, has five different chromosomal arrangements, each corresponding to a somewhat different moisture level, ranging from very wet to nearly dry.

If this Third Annual Malaria Conference underscored the seemingly unending and ever-expanding complexities of malaria research, Kafatos was still hopeful: “The next period of time will see a multi-pronged approach to malaria that will usher in one of the great chapters in the history of science.” —Rod Graham