Molecular markers of in vivo Plasmodium vivax resistance to amodiaquine plus sulfadoxine-pyrimethamine: mutations in pvdhfr and pvmdr1.
Details
Serval ID
serval:BIB_6E7BBFBEBF97
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Molecular markers of in vivo Plasmodium vivax resistance to amodiaquine plus sulfadoxine-pyrimethamine: mutations in pvdhfr and pvmdr1.
Journal
Journal of Infectious Diseases
ISSN
0022-1899[print], 0022-1899[linking]
Publication state
Published
Issued date
2008
Volume
198
Number
3
Pages
409-417
Language
english
Abstract
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.
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.
Keywords
Amodiaquine/pharmacology, Animals, Antimalarials/pharmacology, Child, Preschool, Drug Combinations, Drug Resistance, Female, Genetic Markers, Humans, Infant, Malaria, Vivax/drug therapy, Malaria, Vivax/parasitology, Male, Mutation, Missense, P-Glycoprotein/genetics, Papua New Guinea, Plasmodium vivax/drug effects, Plasmodium vivax/genetics, Polymorphism, Genetic, Protozoan Proteins/genetics, Pyrimethamine/pharmacology, Sulfadoxine/pharmacology, Tetrahydrofolate Dehydrogenase/genetics, Treatment Outcome
Pubmed
Open Access
Yes
Create date
03/07/2010 9:18
Last modification date
20/08/2019 15:27