Repository of Research and Investigative Information

Repository of Research and Investigative Information

Zahedan University of Medical Sciences

High prevalence of the 437G mutation associated with sulfadoxine resistance among Plasmodium falciparum clinical isolates from Iran, three years after the introduction of sulfadoxine-pyrimethamine

(2010) High prevalence of the 437G mutation associated with sulfadoxine resistance among Plasmodium falciparum clinical isolates from Iran, three years after the introduction of sulfadoxine-pyrimethamine. International Journal of Infectious Diseases. E123-E128. ISSN 1201-9712

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Official URL: <Go to ISI>://WOS:000282643000026

Abstract

Objective: The objective of this study was to determine the frequency of dhfr and dhps resistance-associated haplotypes in Plasmodium falciparum isolates, three years after the introduction of sulfadoxine-pyrimethamine (SP) as the first-line antimalarial treatment in Iran. Methods: Blood samples (N = 182) were collected from patients presenting with falciparum malaria from southeastern Iran, and analyzed by nested-PCR/restriction fragment length polymorphism, followed by sequencing analysis. Results: In pfdhfr, double mutation at positions 59R and 108N was a predominant allele with a prevalence of 95.7. The pure double mutations of pfdhfr (I(51)N(108)) were detected, and showed an increase from 0.7 to 4.3 after the introduction of SP as first-line drug. Furthermore, a significant decrease in double mutations/wild-type of pfdhfr/pfdhps (R(59)N(108)/A(437)) was observed from 2004 (83.5) to 2008 (44) after changes in treatment policy. With regards to pfdhps, the results showed a rapid increase in frequency of the single pure form of pfdhps at position 437G (54.4) and that of triple pfdhfr/pfdhps (R(59)N(108)/G(437)) mutant haplotype (51.7) after three years. Conclusions: The absence of quintuple mutations in the examined isolates supports the continued use of SP as the treatment of choice for uncomplicated malaria as a partner drug to artemisinin combination therapy in Iran. However, the increase in the triple pfdhfr/pfdhps (R(59)N(108)/G(437)) mutant haplotypes indicates that the P. falciparum parasite populations have the potential to evolve into dhfr/dhps quintuple mutants in the near future. Therefore, monitoring the status of dhps alleles as a predictor of the development of clinical resistance to sulfadoxine should be a high priority in this region. (C) 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Item Type: Article
Keywords: Plasmodium falciparum dhfr dhps Drug resistance Sulfadoxine-pyrimethamine dihydropteroate-synthetase genes chlorproguanil-dapsone treatment human malaria parasites dihydrofolate-reductase point mutations in-vivo rapid selection synthase chloroquine india Infectious Diseases
Page Range: E123-E128
Journal or Publication Title: International Journal of Infectious Diseases
Journal Index: ISI
Volume: 14
Identification Number: https://doi.org/10.1016/j.ijid.2009.11.035
ISSN: 1201-9712
Depositing User: خانم مهدیه رضائی پور
URI: http://eprints.zaums.ac.ir/id/eprint/2745

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