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Infect Genet Evol. 2015 Mar;30:318-322. doi: 10.1016/j.meegid.2014.12.010. Epub 2014 Dec 13.

Plasmodium falciparum field isolates from areas of repeated emergence of drug resistant malaria show no evidence of hypermutator phenotype.

Author information

1
Johns Hopkins University School of Medicine, Baltimore, MD, USA; Howard Hughes Medical Institute/Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, USA.
2
Howard Hughes Medical Institute/Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, USA.
3
Institute for Genome Sciences and Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
4
Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Pharmacy, University of Science, Techniques and Technology of Bamako, Bamako, Mali.
5
Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Center for Tropical Medicine, Nuffield Department of Medicine, Churchill Hospital, University of Oxford, Oxford, United Kingdom.
6
Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
7
Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Austria and Malaria Research Initiative Bandarban, Bandarban, Bangladesh.
8
Department of Medical Research (Lower Myanmar), Yangon, Myanmar.
9
Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao Democratic People's Republic; Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Lao Democratic People's Republic.
10
Centre for Tropical Medicine Oxford University Clinical Research Unit Vietnam (OUCRU), Ho Chi Minh City, Viet Nam.
11
Laboratory of Molecular Evolution, Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD, USA. Electronic address: mike@umiacs.umd.edu.

Abstract

Multiple transcontinental waves of drug resistance in Plasmodium falciparum have originated in Southeast Asia before spreading westward, first into the rest of Asia and then to sub-Saharan Africa. In vitro studies have suggested that hypermutator P. falciparum parasites may exist in Southeast Asia and that an increased rate of acquisition of new mutations in these parasites may explain the repeated emergence of drug resistance in Southeast Asia. This study is the first to test the hypermutator hypothesis using field isolates. Using genome-wide SNP data from human P. falciparum infections in Southeast Asia and West Africa and a test for relative rate differences we found no evidence of increased relative substitution rates in P. falciparum isolates from Southeast Asia. Instead, we found significantly increased substitution rates in Mali and Bangladesh populations relative to those in populations from Southeast Asia. Additionally we found no association between increased relative substitution rates and parasite clearance following treatment with artemisinin derivatives.

KEYWORDS:

Artemisinin; Drug resistance; Molecular evolution; Mutation rate; Plasmodium falciparum

PMID:
25514047
PMCID:
PMC4316729
DOI:
10.1016/j.meegid.2014.12.010
[Indexed for MEDLINE]
Free PMC Article

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