Absence of putative Plasmodium falciparum artemisinin resistance mutations in sub-Saharan Africa: A molecular epidemiologic study.

Taylor SM1, Parobek CM2, DeConti DK3, Kayentao K4, Coulibaly SO5, Greenwood BM6, Tagbor H7, Williams J8, Bojang K9, Njie F9, Desai M10, Kariuki S11,Gutman J12, Mathanga DP13, Mårtensson A14, Ngasala B15, Conrad MD16, Rosenthal PJ16, Tshefu AK17, Moormann AM18, Vulule JM19, Doumbo OK20, Ter Kuile FO21, Meshnick SR22, Bailey JA23, Juliano JJ24.

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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-resistant genotypes in African parasite populations is unknown. We developed an assay to quantify rare polymorphisms in parasite populations using a pooled deep-sequencing approach to score allele frequencies, validated it using mixtures of laboratory parasite strains, and then employed it to screen over 1,100 African P. falciparum 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. Though 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.