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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Molecular markers of in vivo Plasmodium vivax resistance to amodiaquine plus sulfadoxine-pyrimethamine: Mutations in pvdhfr and pvmdr1
Journal of Infectious Diseases, Volume 198, No. 3, Year 2008
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Description
Background. Molecular markers for sulfadoxine-pyrimethamine (SP) resistance in Plasmodium vivax have been reported. However, data on the molecular correlates involved in the development of resistance to 4-aminoquinolines and their association with the in vivo treatment response are scarce. Methods. We assessed pvdhfr (F57L/I, S58R, T61M, S117T/N, and I173F/L) and pvmdr1 (Y976F and F1076L) mutations in 94 patients who received amodiaquine (AQ) plus SP in Papua New Guinea (PNG). We then investigated the association between parasite genotype and treatment response. Results. The treatment failure (TF) rate reached 13%. Polymorphisms in pvdhfr F57L, S58R, T61M, and S117T/N and in pvmdr1 Y976F were detected in 60%, 67%, 20%, 40%, and 39% of the samples, respectively. The single mutant pvdhfr 57 showed the strongest association with TF (odds ratio [OR], 9.04; P = .01). The combined presence of the quadruple mutant pvdhfr 57L+58R+61M+117T and pvmdr1 mutation 976F was the best predictor of TF (OR, 8.56; P = .01). The difference in TF rates between sites was reflected in the genetic drug-resistance profile of the respective parasites. Conclusions. The present study identified a new molecular marker in pvmdr1 that is associated with the in vivo response to AQ+SP. We suggest suitable marker sets with which to monitor P. vivax resistance against AQ+SP in countries where these drugs are used. © 2008 by the Infectious Diseases Society of America. All rights reserved.
Authors & Co-Authors
Marfurt, Jutta
Switzerland, Allschwil
Swiss Tropical and Public Health Institute Swiss Tph
Australia, Darwin
Menzies School of Health Research
de Monbrison, Frédérique Conquere
France, Villeurbanne
Université Claude Bernard Lyon 1
Brega, Sara
France, Villeurbanne
Université Claude Bernard Lyon 1
Barbollat, Laetitia
France, Villeurbanne
Université Claude Bernard Lyon 1
Müller, Ivo
Papua new Guinea, Goroka
Papua new Guinea Institute of Medical Research
Sie, Albert
Papua new Guinea, Goroka
Papua new Guinea Institute of Medical Research
Goroti, Mary
Papua new Guinea, Goroka
Papua new Guinea Institute of Medical Research
Reeder, John C.
Papua new Guinea, Goroka
Papua new Guinea Institute of Medical Research
Australia, Melbourne
Burnet Institute
Beck, Hans Peter
Switzerland, Allschwil
Swiss Tropical and Public Health Institute Swiss Tph
Picot, Stèphane
France, Villeurbanne
Université Claude Bernard Lyon 1
Genton, Blaise
Switzerland, Allschwil
Swiss Tropical and Public Health Institute Swiss Tph
Tanzania, Ifakara
Ifakara Health Institute
Statistics
Citations: 75
Authors: 11
Affiliations: 6
Identifiers
Doi:
10.1086/589882
ISSN:
00221899
Research Areas
Cancer
Genetics And Genomics
Study Design
Case-Control Study
Study Locations
Guinea