Absence of Putative Artemisinin Resistance Mutations Among Plasmodium falciparum in Sub-Saharan Africa: A Molecular Epidemiologic Study.

Taylor, Steve M, Parobek, Christian M, DeConti, Derrick K, Kayentao, Kassoum, Coulibaly, Sheick Oumar, Greenwood, Brian M, Tagbor, Harry, Williams, John, Bojang, Kalifa, Njie, Fanta, Desai, Meghna, Kariuki, Simon, Gutman, Julie, Mathanga, Don P, Mårtensson, Andreas, Ngasala, Billy, Conrad, Melissa D, Rosenthal, Philip J, Tshefu, Antoinette K, Moormann, Ann M, Vulule, John M, Doumbo, Ogobara K, terKuile, Feiko ORCID: https://orcid.org/0000-0003-3663-5617, Meshnick, Steven R, Bailey, Jeffrey A and Juliano, Jonathan J (2014) 'Absence of Putative Artemisinin Resistance Mutations Among Plasmodium falciparum in Sub-Saharan Africa: A Molecular Epidemiologic Study.'. Journal of Infectious Disease, Vol 211, Issue 5, pp. 680-688.

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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 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.

Item Type:	Article
Subjects:	QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified. QX Parasitology > Protozoa > QX 135 Plasmodia WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries WB Practice of Medicine > Therapeutics > WB 330 Drug therapy WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria WC Communicable Diseases > Tropical and Parasitic Diseases > WC 770 Therapy
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1093/infdis/jiu467
Depositing User:	Martin Chapman
Date Deposited:	23 Oct 2014 15:59
Last Modified:	07 Dec 2018 10:34
URI:	https://archive.lstmed.ac.uk/id/eprint/4477

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