Absence of putative artemisinin resistance mutations among Plasmodium falciparum in Sub-Saharan Africa: a molecular epidemiologic study.

Abstract

Plasmodium falciparum parasites that are resistant to artemisinins have been detected in Southeast Asia. Resistance is associated with several polymorphisms in the parasite's K13-propeller gene. The molecular epidemiology of these artemisinin resistance genotypes in African parasite populations is unknown. We developed an assay to quantify rare polymorphisms in parasite populations that uses a pooled deep-sequencing approach to score allele frequencies, validated it by evaluating mixtures of laboratory parasite strains, and then used it to screen P. falciparum parasites from >1100 African infections collected since 2002 from 14 sites across sub-Saharan Africa. We found no mutations in African parasite populations that are associated with artemisinin resistance in Southeast Asian parasites. However, we observed 15 coding mutations, including 12 novel mutations, and limited allele sharing between parasite populations, consistent with a large reservoir of naturally occurring K13-propeller variation. Although polymorphisms associated with artemisinin resistance in P. falciparum in Southeast Asia are not prevalent in sub-Saharan Africa, numerous K13-propeller coding polymorphisms circulate in Africa. Although their distributions do not support a widespread selective sweep for an artemisinin-resistant phenotype, the impact of these mutations on artemisinin susceptibility is unknown and will require further characterization. Rapid, scalable molecular surveillance offers a useful adjunct in tracking and containing artemisinin resistance.

DOI: 10.1093/infdis/jiu467

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@article{Taylor2015AbsenceOP, title={Absence of putative artemisinin resistance mutations among Plasmodium falciparum in Sub-Saharan Africa: a molecular epidemiologic study.}, author={Steve M. Taylor and Christian M Parobek and Derrick K DeConti and Kassoum Kayentao and Sheick Oumar Coulibaly and Brian Greenwood and Harry K Tagbor and John E. Williams and Kalifa A Bojang and Fanta Njie and Meghna Desai and Simon Kariuki and Julie Gutman and Don P. Mathanga and Andreas M{\aa}rtensson and Billy E. Ngasala and Melissa D. Conrad and Philip J. Rosenthal and Antoinette Kitoto Tshefu and Ann M. Moormann and John Vulule and Ogobara K. Doumbo and Feiko O Ter Kuile and Steven Richard Meshnick and Jeffrey A. Bailey and Jonathan J. Juliano}, journal={The Journal of infectious diseases}, year={2015}, volume={211 5}, pages={680-8} }