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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Independent emergence of artemisinin resistance mutations among Plasmodium falciparum in Southeast Asia
Journal of Infectious Diseases, Volume 211, No. 5, Year 2015
Notification
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Description
Background: The emergence of artemisinin-resistant Plasmodium falciparum in Southeast Asia threatens malaria treatment efficacy. Mutations in a kelch protein encoded on P. falciparum chromosome 13 (K13) have been associated with resistance in vitro and in field samples from Cambodia. Methods: P. falciparum infections from artesunate efficacy trials in Bangladesh, Cambodia, Laos, Myanmar, and Vietnam were genotyped at 33 716 genome-wide single-nucleotide polymorphisms (SNPs). Linear mixed models were used to test associations between parasite genotypes and parasite clearance half-lives following artesunate treatment. K13 mutations were tested for association with artemisinin resistance, and extended haplotypes on chromosome 13 were examined to determine whether mutations arose focally and spread or whether they emerged independently. Results: The presence of nonreference K13 alleles was associated with prolonged parasite clearance half-life (P = 1.97 × 10-12). Parasites with a mutation in any of the K13 kelch domains displayed longer parasite clearance half-lives than parasites with wild-type alleles. Haplotype analysis revealed both population-specific emergence of mutations and independent emergence of the same mutation in different geographic areas. Conclusions: K13 appears to be a major determinant of artemisinin resistance throughout Southeast Asia. While we found some evidence of spreading resistance, there was no evidence of resistance moving westward from Cambodia into Myanmar. © The Author 2014.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC4334802/bin/supp_211_5_670__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC4334802/bin/supp_jiu491_jiu491supp.docx
Authors & Co-Authors
Takala-Harrison, Shannon L.
United States, Baltimore
University of Maryland, Baltimore Umb
Jacob, Christopher G.
United States, Baltimore
University of Maryland, Baltimore Umb
Arze, Cesar A.
United States, Baltimore
University of Maryland, Baltimore Umb
Cummings, Michael P.
United States, College Park
University of Maryland, College Park
Silva, Joana C.
United States, Baltimore
University of Maryland, Baltimore Umb
Dondorp, A. M.
Thailand, Bangkok
Mahidol Oxford Tropical Medicine Research Unit
Fukuda, Mark M.
Thailand, Bangkok
Armed Forces Research Institute of Medical Sciences, Thailand
Hien, Tran Tinh
Viet Nam, Ho Chi Minh City
Oxford University Clinical Research Unit
Mayxay, Mayfong
Laos, Vientiane
University of Health Sciences
United Kingdom, Oxford
University of Oxford
Noedl, Harald
Austria, Vienna
Medizinische Universität Wien
Nosten, François Henry
Thailand, Bangkok
Mahidol Oxford Tropical Medicine Research Unit
United Kingdom, Oxford
University of Oxford
Kyaw, Myat Phone
Unknown Affiliation
Thuy-Nhien, Nguyen Thanh
Viet Nam, Ho Chi Minh City
Oxford University Clinical Research Unit
Imwong, Mallika
Thailand, Nakhon Pathom
Mahidol University
Bethell, Delia B.
Thailand, Bangkok
Armed Forces Research Institute of Medical Sciences, Thailand
Se, Youry
Thailand, Bangkok
Armed Forces Research Institute of Medical Sciences, Thailand
Lon, Chanthap
Thailand, Bangkok
Armed Forces Research Institute of Medical Sciences, Thailand
Tyner, Stuart D.
Thailand, Bangkok
Armed Forces Research Institute of Medical Sciences, Thailand
United States, Fort Sam Houston
U.s. Army Institute of Surgical Research
Saunders, David L.
Thailand, Bangkok
Armed Forces Research Institute of Medical Sciences, Thailand
Ariey, Frédéric
Unknown Affiliation
Mercereau-Puijalon, Odile
France, Paris
Institut Pasteur, Paris
Menard, Didier
Cambodia, Phnom Penh
Institut Pasteur du Cambodge
Newton, Paul N.
United Kingdom, Oxford
University of Oxford
Khanthavong, Maniphone
Unknown Affiliation
Hongvanthong, Bouasy
Unknown Affiliation
Starzengrüber, Peter
Austria, Vienna
Medizinische Universität Wien
Fuehrer, Hans Peter
Austria, Vienna
Medizinische Universität Wien
Austria, Vienna
Veterinarmedizinische Universitat Wien
Swoboda, Paul
Austria, Vienna
Medizinische Universität Wien
Khan, Wasif Ali
Bangladesh, Dhaka
International Centre for Diarrhoeal Disease Research Bangladesh
Pyae Phyo, Aung Pyae P.
Thailand, Bangkok
Mahidol Oxford Tropical Medicine Research Unit
Thailand, Nakhon Pathom
Mahidol University
Nyunt, Myaing Myaing
United States, Baltimore
University of Maryland, Baltimore Umb
Nyunt, Myat Htut
Unknown Affiliation
Brown, Tyler S.
United States, Baltimore
University of Maryland, Baltimore Umb
Adams, Matthew
United States, Baltimore
University of Maryland, Baltimore Umb
Bailey, Jason A.
United States, Baltimore
University of Maryland, Baltimore Umb
Tan, John C.
United States, Madison
Roche Nimblegen, Inc.
Ferdig, Michael T.
United States, Notre Dame
University of Notre Dame
Clark, Taane Gregory
United Kingdom, London
London School of Hygiene & Tropical Medicine
Miotto, Olivo
Thailand, Bangkok
Mahidol Oxford Tropical Medicine Research Unit
United Kingdom, Hinxton
Wellcome Sanger Institute
MacInnis, Bronwyn L.
United Kingdom, Hinxton
Wellcome Sanger Institute
Kwiatkowski, Dominic P.
United Kingdom, Hinxton
Wellcome Sanger Institute
White, Nicholas J.
Thailand, Bangkok
Mahidol Oxford Tropical Medicine Research Unit
Ringwald, Pascal
Switzerland, Geneva
Organisation Mondiale de la Santé
Plowe, Christopher Vv
United States, Baltimore
University of Maryland, Baltimore Umb
Statistics
Citations: 317
Authors: 44
Affiliations: 19
Identifiers
Doi:
10.1093/infdis/jiu491
ISSN:
00221899
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases
Study Design
Cross Sectional Study