Getting a Handle on Malaria

MICHELLE GUO

As we began to follow the parasites in Senegal, using the technologies that had been developed in the last 5-10 years, we noticed something very interesting. It appeared that many of the patients had exactly the same parasite. This caused us to rethink what was going on.Dr. Dyann Wirth

Feeding mosquito with human blood Dr. Dyann Wirth, the Richard Pearson Strong Professor of Infectious Diseases
 and Immunology Department Chair at the Harvard School of Public Health, studies how P. falciparum, the parasite that causes malaria, develops drug resistance. Her research focuses on the tendency of the parasite to change its genetic code with unusual speed.

Wirth’s lab has been one of the international leaders in genotyping—studying specific differences in an in individual’s genetic make-up—using single nucleotide polymorphisms. Along with Dr. Pardis Sabeti, of the Broad Institute and professor in the Harvard Department of Organismic and Evolutionary Biology department and scientists from Cheikh Anta Diop University in Senegal, Wirth has been conducting real-time studies of the correlation between the usage of drugs for treating malaria and the parasite’s resistance. Wirth says, “In 2005, I began to realize that the advances in the Human Genome Project meant that we could begin to address malaria with a whole-genome approach.”

According to Sabeti, their collaboration was based on their shared needs. Sabeti tells Brevia that their two fields, molecular biology and computational biology, are closely intertwined. “Even when you’re doing molecular [studies], a lot of statistics and computational tools are very helpful. When you have a computational discovery, it has to be verified experimentally.” On collaborating with Wirth, she says, “I don’t think either of us could have done it without each other.”

Malaria causes about 660,000 deaths annually, with 91% of those deaths occurring in Africa. Malaria is caused by the P. falciparum parasite, which is transmitted by Anopheles mosquitos carrying the parasite in their salivary glands. What makes this disease so deadly in certain regions, but not others? In addition to the problem of inadequate health-care infrastructure, strains found in Africa are among the most virulent and drug-resistant in the world, making them important specimens for Sabeti and Wirth.

Michelle Guo, Article ImageWirth noticed a surprising trend when she focused on the genetic diversity of the parasite in areas of Africa that are significantly affected by malaria. “As we began to follow the parasites in Senegal, using the technologies that had been developed in the last 5-10 years, we noticed something very interesting. It appeared that many of the patients had exactly the same parasite. This caused us to rethink what was going on,” she says. Wirth and her collaborators noticed that as new disease control strategies were implemented – such as greater disease control strategies, including the use of insecticide treated nets (ITNs), rapid diagnostic tests (RDTs) and artemisinin combination therapy (ACT)— the population of the parasite was decreasing and so was its genetic diversity. What Wirth learned from the attempted eradication campaign with chloroquine, however, was that placing pressure on the parasite drives natural selection; strains of chloroquine-resistant P. falciparum plague regions today. Moreover, scientists are hesitant to suggest another eradication campaign because they believe that using artemisinin or any drug on the P. falciparum parasite may promote the survival of resistant species.

While Wirth identifies the specific genetic loci that confer resistance to drugs, Sabeti innovates the techniques for investigating natural selection in the genome of P. falciparum. She rapidly assays the genetic information of the parasite and uses computational biology to study its evolution. Sabeti explains, “the way the genetics falls into it is essentially around surveillance tracking information.” Their methods of genetic tracking create “better diagnostics to give the right regimens to people when they come in, and monitor the efficacy of the intervention program…allowing clinicians as well as public health officials to make more informed decisions by understanding better what’s going on.” These new tools allow scientists to follow natural selection in real time.

Is Sabeti optimistic about eradicating malaria? “I think we’re going to make great strides…this is an extraordinary parasite. It’s been around for many millennia.” Wirth agrees, saying that the road to eradication is one that joins several distinct pathways. One is scientific, and involves developing the correct tools to fight the parasite. Another is political, a difficult undertaking that will require countries to work together to allocate more resources to fight the disease. Logistical complications of getting treatments and vaccines to patients further complicate the eradication effort. Both researchers believe it is important to prepare future generations to study malaria. They actively involve graduate and undergraduate students in their labs. Diana Miao, a senior at Harvard College, has studied new ways of verifying signals of selection in parasite populations. Her research has strong implications for the future of the malaria surveillance Wirth and Sabeti have developed.

Carmen Mejia, the executive director of the Harvard Malaria Initiative (HMI), says there are ways undergraduates can get involved in this field. Last year, HMI held an Undergraduate Colloquium for Malaria, in which students spoke with faculty members about their work on malaria and brainstormed steps toward global eradication. This year, HMI is gearing up for an exciting challenge: the Harvard Malaria Competition, in which $10,000 will go to the student or group of students with the most innovative idea to increase awareness of malaria world-wide using Harvard’s creative and intellectual resources. The best malaria intervention strategies in the world are useless without worldwide understanding of the importance of this health issue. At Harvard, the fight against malaria is a robust ongoing effort, with strong foundations in a range of disciplines with the goal of preventing millions of deaths.

Michelle Guo is a Brevia staff-writer. She can be reached at michelleguo@college.harvard.edu