The Impact of Antimalarial Resistance on the Genetic Structure of Plasmodium falciparum in the DRC

Robert Verity; Özkan Aydemir; Nicholas F. Brazeau; Oliver John Watson; Nicholas J. Hathaway; Melchior Kashamuka Mwandagalirwa; Patrick W. Marsh; Kyaw L. Thwai; Travis M. Fulton; Madeline Denton; Andrew Parker Morgan; Jonathan B. Parr; Patrick K. Tumwebaze; Melissa D. Conrad; Philip Jon Rosenthal; Deus S. Ishengoma; Jeremiah Ngondi; Julie Gutman; Modest Mulenga; Douglas Eric Norris; William John Moss; Benedicta Ayiedu Mensah; James Leslie Myers-Hansen; Anita Ghansah; Antoinette Kitoto Tshefu; Azra C. Ghani; Steven R. Meshnick; Jeffrey A. Bailey; Jonathan J. Juliano

doi:10.1038/s41467-020-15779-8

GenomicsNature CommunicationsApr 30, 2020

Peer-reviewed journal article

The Impact of Antimalarial Resistance on the Genetic Structure of Plasmodium falciparum in the DRC

Robert Verity iD, Özkan Aydemir iD, Nicholas F. Brazeau iD, Oliver John Watson iD, Nicholas J. Hathaway iD, Melchior Kashamuka Mwandagalirwa, Patrick W. Marsh, Kyaw L. Thwai, Travis M. Fulton iD, Madeline Denton iD, Andrew Parker Morgan iD, Jonathan B. Parr iD, Patrick K. Tumwebaze iD, Melissa D. Conrad iD, Philip Jon Rosenthal iD, Deus S. Ishengoma iD, Jeremiah Ngondi iD, Julie Gutman iD, Modest Mulenga iD, Douglas Eric Norris iD, William John Moss iD, Benedicta Ayiedu Mensah, James Leslie Myers-Hansen iD, Anita Ghansah iD, Antoinette Kitoto Tshefu iD, , Jonathan J. Juliano iD

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Abstract

The Democratic Republic of the Congo (DRC) harbors 11% of global malaria cases, yet little is known about the spatial and genetic structure of the parasite population in that country. We sequenced 2537 Plasmodium falciparum infections, including a nationally representative population sample from DRC and samples from surrounding countries, using molecular inversion probes - a novel high-throughput genotyping tool. We identified an east-west divide in haplotypes known to confer resistance to chloroquine and sulfadoxine-pyrimethamine. Furthermore, we identified highly related parasites over large geographic distances, indicative of gene flow and migration. Our results were consistent with a background of isolation by distance combined with the effects of selection for antimalarial drug resistance. This study provides a high-resolution view of parasite genetic structure across a large country in Africa and provides a baseline to study how implementation programs may impact parasite populations.