University of Maryland, Baltimore
Dr. Plowe is also a professor of medicine, of microbiology and immunology, and of epidemiology and preventive medicine at the University of Maryland, Baltimore, School of Medicine.
Genetic Diversity and Malaria Drug and Vaccine Efficacy
Christopher Plowe, who lives in Fulton, Maryland, is a frequent traveler to Mali and Malawi, two African nations plagued by malaria. While much of today's research on that disease focuses on developing drugs or vaccines that might save lives in the future, Plowe's antimalarial strategy aims to save lives in Africa right now. He is building the molecular tools needed to track the spread—or falloff—of drug-resistant malaria parasites in Africa and using the knowledge to tailor combinations of drug therapies to people in the affected regions.
Plowe has developed and validated molecular markers that can be used to monitor the parasite's resistance to the two most important malaria drugs of the 20th century, chloroquine and sulfadoxine-pyrimethamine. Using that information—and the tools of modern genomics—Plowe and his colleagues have developed strategies to extend the useful life of those drugs. The rapid molecular tests that Plowe has developed to document drug resistance are now being used worldwide. Plowe, Head of the Malaria Section in the University of Maryland School of Medicine's Center for Vaccine Development, is also working toward developing a vaccine that might eventually prevent the disease and eliminate the need to use those therapeutic drugs at all.
Much of his work takes place at the two field research sites he has established in Mali and Malawi. Together with colleagues in Mali and at the University of Maryland, he has developed techniques to test drops of blood from malaria patients for evidence of drug resistance in the parasite. Once Plowe's group developed that technique, they realized they had a tool that would help them determine which of the malaria drugs in use today would be effective in particular populations.
In work done in the southeastern African country of Malawi, Plowe and his collaborators documented a remarkable change in the parasite's resistance to chloroquine.
Long regarded as a cheap and effective drug, chloroquine had been the cornerstone of earlier campaigns against malaria. But spreading resistance to the drug had so reduced its effectiveness that Malawi ceased using it in 1993. The result of that change, however, was an unexpected and startlingly rapid drop in the parasite's resistance to chloroquine. By 2005, Plowe found, chloroquine was as effective in a group of children with acute malaria infections as it had ever been.
Malawi has not returned to the widespread use of chloroquine, because drug-resistant parasites would likely sweep back into the country from surrounding regions. But monitoring drug resistance allows public health officials to mix and match drugs for maximum effect. “I now have the opportunity to use what I've learned over the past 15 years studying these old drugs to extend the useful life of new malaria drugs,” Plowe said.
Plowe also has helped lead vaccine trials in the western African nation of Mali to test new ways to prevent malaria. The malaria parasite is remarkably diverse genetically, and that has made it difficult for scientists to develop an effective vaccine. “If we can understand the impact of diversity on vaccine efficacy here in the field, we can go back to the lab and engineer a more broadly protective vaccine,” Plowe said.
New genomic databases and technologies have greatly expanded Plowe's research horizon. In his University of Maryland laboratory, he and his colleagues have been studying the evolution of the parasite's genome to understand how it has adapted to human immune responses and drug treatments. That knowledge, in turn, could lead to better ways to prevent and treat the disease. The goal, said Plowe, is to hit malaria hard and then keep it from regaining its strength. It's an ambitious quest for someone who said he “took up research as a way to travel to the tropics.”
Plowe said his outlook has changed a lot since he was in his first year of medical school at Cornell University Medical College and he first realized that he wanted to practice medicine in the tropics. Born and raised in South Dakota, he had never been out of the United States—“except for Niagara Falls,” he said. “But I was turned on by tropical medicine, by the romance and adventure of it.”
In his fourth year in medical school, Plowe went to Kenya to study the immune system's reaction to malaria infection. “That lit a fire in me,” he said. “I got hooked on malaria.”
Back in the United States in the early 1990s, he was doing a fellowship at the National Institutes of Health (NIH) when a chance hallway encounter with the head of NIH's malaria genetics program gave him a chance to return to Africa. He had been studying mutations in specific genes of the malaria parasite that make the pathogen resistant to antimalarial drugs. Why not adapt the technique for use in the field, his colleague suggested. He never looked back. “I've been doing work in Mali ever since,” Plowe said.