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LMVR Studies Malaria Drug Resistance and Disease Severity

The NIAID Laboratory of Malaria and Vector Research (LMVR) supports a spectrum of clinical and laboratory research projects on malaria and the mosquitoes responsible for its transmission. Among these projects are investigations that focus on two major obstacles to treating and preventing malaria: how malaria parasites become resistant to major antimalarial drugs and why strains of the most deadly malaria parasite, Plasmodium falciparum, infect cells of humans and some non-human primates differently than other hosts.

Microscopic image of Plasmodium falciparum
Plasmodium falciparum, shown here in a magnified blood smear, is the deadliest malaria parasite, responsible for an estimated 90 percent of all deaths from the disease. Credit: CDC

Investigating the Evolution of Resistance

Parasitic resistance to drugs has impeded what had been great progress in the treatment of malaria. For much of the 20th century, chloroquine was the first-line drug for the treatment of malaria—it was effective, easy to use, stable, safe, and, most importantly, affordable to the world’s poorest populations. Starting in the late 1950s, P. falciparum parasites evolved resistance to chloroquine, and when the resistant parasites spread across Africa in the 1980s, hospitalizations and deaths attributable to malaria returned to pre-chloroquine levels.

To determine how malaria parasites evolved resistance to chloroquine and other major antimalarial drugs, LMVR researchers expose clinical samples of parasites to a drug and then watch to see which parasites resist the drugs and survive and which parasites are sensitive to the drug and are eliminated. Data from these studies help scientists to identify which parasites carry drug-resistance genes that allow survival and how new and more effective malaria drug treatments might be designed against them.

Studying Genes to Better Understand Parasitic Infection

The second obstacle in malaria research is that P. falciparum strains infect the cells of humans and certain non-human primates differently than other hosts. This is a major detriment to research as it restricts the study of P. falciparum in other animals. Recent research successes in this area include mapping the genome sequences of P. falciparum and other Plasmodium species, humans, and mosquitoes, so that scientists have new resources to study the life cycle of the malaria parasite and transmission of the disease.

Genetic mapping has allowed scientists to determine which parasite genes are vital to infection in humans and certain other primates and why these genes are so important. Scientists have known that malaria parasites evolved strict mechanisms that regulate which genes express themselves and when. From one large family of genes, the parasites have learned to express or “switch on” only one gene at a time to cause severe disease. LMVR researchers have made new discoveries about how parasites control which genes are expressed and which are silent.

All of these breakthroughs improve knowledge of malaria and support searches for new methods of treatment and prevention like chemotherapies, diagnostic tools, and vaccines. LMVR research on the NIH campus is integrated with field studies in Africa and in Southeast Asia.

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Last Updated February 25, 2009