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

Verity, R. J.; Aydemir, O.; Brazeau, N. F.; Watson, O. J.; Hathaway, N. J.; Mwandagalirwa, M. K.; Marsh, P. W.; Thwai, K.; Fulton, T.; Denton, M.; Morgan, A. P.; Parr, J. B.; Tumwebaze, P. K.; Conrad, M.; Rosenthal, P. J.; Ishengoma, D. S.; Ngondi, J.; Gutman, J.; Mulenga, M.; Norris, D. E.; Moss, W. J.; Mensah, B. A.; Myers-Hansen, J. L.; Ghansah, A.; Tshefu, A. K.; Ghani, A. C.; Meshnick, S. R.; Bailey, J. A.; Juliano, J. J.

doi:10.1101/656561

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bioRxiv · 10.1101/656561

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

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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.

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Verity, R. J., Aydemir, O., Brazeau, N. F., Watson, O. J., Hathaway, N. J., Mwandagalirwa, M. K., Marsh, P. W., Thwai, K., Fulton, T., Denton, M., Morgan, A. P., Parr, J. B., Tumwebaze, P. K., Conrad, M., Rosenthal, P. J., Ishengoma, D. S., Ngondi, J., Gutman, J., Mulenga, M., Norris, D. E., Moss, W. J., Mensah, B. A., Myers-Hansen, J. L., Ghansah, A., Tshefu, A. K., Ghani, A. C., Meshnick, S. R., Bailey, J. A., Juliano, J. J.. 2019-05-31. The Impact of Antimalarial Resistance on the Genetic Structure of Plasmodium falciparum in the DRC. https://doi.org/10.1101/656561

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