Using genomics to shed light on malaria transmission

To fight malaria, it’s crucial to assess the effectiveness of interventions against the mosquito-borne disease. But when malaria transmission declines, traditional methods for estimating transmission—based on mosquito sampling—become difficult. Now, a new study from Harvard T.H. Chan School of Public Health researchers and colleagues in Boston, Seattle, and Senegal suggests that modeling genomic information from a small number of samples of the malaria parasite can shed light on the success of interventions and assist with future malaria eradication efforts.

The study, “Modeling malaria genomics reveals transmission decline and rebound in Senegal,” was published May 4, 2015 in PNAS (Proceedings of the National Academy of Sciences).

“This work demonstrates how genotyping parasites can help determine the efficacy of a malaria control program,” said senior author Dyann Wirth, Richard Pearson Strong Professor of Infectious Diseases, chair of theDepartment of Immunology and Infectious Diseases at Harvard Chan School and faculty director of Harvard’s Defeating Malaria: From the Genes to the Globe initiative. “The collaborative nature of this project and the potential impact of its findings exemplify our ability to meaningfully contribute to complex problems like malaria using a multidisciplinary ‘genes to the globe’ approach.”

Researchers looked at 1,007 samples of the malaria parasite Plasmodium falciparum collected from 2006-13 in Thiès, Senegal, where the national malaria control program had stepped up efforts against the disease in 2006 with the use of rapid diagnostic tests, new antimalarial medications, improved insecticide-treated bed nets, and indoor insecticide spraying. The researchers genotyped these samples using a molecular “barcode” of 24 single nucleotide polymorphisms, or SNPs—parts of DNA with genetic variations that provide clues about organisms’ adaptations to environmental changes. Evidence from the barcodes, paired with epidemiological modeling, revealed genetic adaptations suggesting that malaria transmission fell from 2006-10, then rebounded in 2012-13—which matched actual malaria incidence data from Senegal. While reasons for the parasite’s rebound aren’t clear, researchers offered possible explanations, such as the parasite developing resistance to insecticide-treated nets.

The findings imply that intensive intervention to control malaria, such as the effort in Senegal, can result in rapid and dramatic changes in malaria parasite genomics. Using evidence from these changes—which sheds light on the parasite’s reproductive capability—can help researchers track progress toward malaria elimination.

“It was a great surprise to me, and a highly gratifying one, to see how population studies of the malaria parasite can reveal the effectiveness of intervention to control disease and also show when the effects of intervention begin to wear off,” said co-author Dan Hartl, professor in the Department of Immunology and Infectious Diseases at Harvard Chan School and Higgins Professor of Biology in Harvard University’sDepartment of Organismic and Evolutionary Biology.

Lead author of the study was Rachel Daniels, research scientist in the Department of Immunology and Infectious Diseases. Other authors from Wirth’s lab included Sarah Volkman, principal research scientist; graduate student Wesley Wong; and Nicholas Baro, postdoctoral fellow. Other Harvard Chan School authors included Hsiao-Han Chang, postdoctoral research fellow in the Department of Epidemiology; andDanny Milner, associate professor in the Department of Immunology and Infectious Diseases.

The study was a collaborative effort of researchers at Harvard Chan, Harvard University, Broad Institute, University of Cheikh Anta Diop University in Senegal, and the Institute for Disease Modeling in Seattle.

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