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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Amodiaquine and artemether-lumefantrine select distinct alleles of the Plasmodium falciparum mdr1 gene in Tanzanian children treated for uncomplicated malaria
Antimicrobial Agents and Chemotherapy, Volume 51, No. 3, Year 2007
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Description
The artemisinin-based combination therapies artemether-lumefantrine (AL) and amodiaquine (AQ) plus artesunate have been adopted for treatment of Plasmodium falciparum malaria in many African countries. Molecular markers of parasite resistance suitable for surveillance have not been established for any of the component drugs in either of these combinations. We assessed P. falciparum mdr1 (Pfmdr1) alleles present in 300 Tanzanian children presenting with uncomplicated falciparum malaria, who were enrolled in a clinical trial of antimalarial therapy. Pfmdr1 genotype analysis was also performed with isolates from 182 children who failed AQ monotherapy and 54 children who failed AL treatment. Pfmdr1 alleles 86Y, 184Y, and 1246Y were more common among treatment failures in the AQ group than among pretreatment infections. The converse was found in the AL-treated group. Children presenting with the 86Y/184Y/1246Y Pfmdr1 haplotype and treated with AQ were significantly more likely to retain this haplotype if they were parasite positive during posttreatment follow-up than were children treated with AL (odds ratio, 33.25; 95% confidence interval, 4.17 to 1441; P, <0.001). We conclude that AL and AQ exert opposite within-host selective effects on the Pfmdr1 gene of P. falciparum. Copyright © 2007, American Society for Microbiology. All Rights Reserved.
Authors & Co-Authors
Humphreys, Georgina S.
Unknown Affiliation
Merinopoulos, I.
Unknown Affiliation
Ahmed, J.
Unknown Affiliation
Whitty, Christopher J.M.
Unknown Affiliation
Mutabingwa, Theonest K.
Unknown Affiliation
Sutherland, Colin J.
Unknown Affiliation
Hallett, Rachel L.
Unknown Affiliation
Statistics
Citations: 244
Authors: 7
Affiliations: 3
Identifiers
Doi:
10.1128/AAC.00875-06
ISSN:
00664804
Research Areas
Genetics And Genomics
Infectious Diseases
Maternal And Child Health
Study Design
Cohort Study
Case-Control Study