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J Infect Dis. 2015 Mar 1;211(5):680-8. doi: 10.1093/infdis/jiu467. Epub 2014 Sep 1.

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

Author information

1
Division of Infectious Diseases, Department of Medicine Duke Global Health Institute, Duke University Medical Center, Durham Department of Epidemiology, Gillings School of Global Public Health.
2
Curriculum in Genetics and Molecular Biology.
3
Graduate School of Biomedical Sciences.
4
Department of Epidemiology of Parasitic Diseases, Malaria Research and Training Center, Faculty of Medicine, Pharmacy, and Odontostomatology, University of Science, Techniques, and Technologies of Bamako, Mali Department of Clinical Sciences, Liverpool School of Tropical Medicine.
5
Faculty of Health Sciences, University of Ouagadougou, Burkina Faso.
6
Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom.
7
Department of Community Health, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi.
8
Navrongo Health Research Centre, Ghana Health Service, Navrongo.
9
Medical Research Council Laboratories, Banjul, Gambia.
10
Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia CDC-Kenya.
11
KEMRI-CDC.
12
Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia.
13
Malaria Alert Center, University of Malawi College of Medicine, Blantyre Department of Community Health, College of Medicine, Lilongwe, Malawi.
14
Malaria Research, Department of Medicine Solna Global Health, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
15
Department of Parasitology, Muhumbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
16
Department of Medicine, University of California, San Francisco.
17
Ecole de Sante Publique, Faculte de Medicine, University of Kinshasa, Democratic Republic of the Congo.
18
Department of Pediatrics.
19
Center for Global Health Research, KEMRI, Kisumu, Kenya.
20
Department of Epidemiology of Parasitic Diseases, Malaria Research and Training Center, Faculty of Medicine, Pharmacy, and Odontostomatology, University of Science, Techniques, and Technologies of Bamako, Mali.
21
Department of Clinical Sciences, Liverpool School of Tropical Medicine Center for Global Health Research, KEMRI, Kisumu, Kenya.
22
Department of Epidemiology, Gillings School of Global Public Health.
23
Division of Transfusion Medicine Program in Bioinformatics and Integrative Biology, University of Massachusetts School of Medicine, Worcester.
24
Curriculum in Genetics and Molecular Biology Divison of Infectious Diseases, School of Medicine, University of North Carolina, Chapel Hill.

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.

KEYWORDS:

artemisinin resistance; drug resistance; falciparum malaria; molecular epidemiology

PMID:
25180240
PMCID:
PMC4402372
DOI:
10.1093/infdis/jiu467
[Indexed for MEDLINE]
Free PMC Article

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