Analysis of sulphadoxine/pyrimethamine resistance-conferring mutations of Plasmodium falciparum from Mozambique reveals the absence of the dihydrofolate reductase 164L mutant

Natércia Fernandes, Paula Figueiredo, Virgilio Estólio do Rosário, Pedro Cravo

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12 Citations (Scopus)

Abstract

BACKGROUND: Plasmodium falciparum is the predominant human malaria species in Mozambique and a lead cause of mortality among children and pregnant women nationwide. Sulphadoxine/pyrimethamine (S/P) is used as first line antimalarial treatment as a partner drug in combination with artesunate.

METHODS: A total of 92 P. falciparum-infected blood samples, from children with uncomplicated malaria attending the Centro de Saude de Bagamoyo in the Province of Maputo-Mozambique, were screened for S/P resistance-conferring mutations in the pfdhfr and pfdhps genes using a nested mutation-specific polymerase chain reaction and restriction digestion (PCR-RFLP). The panel of genetic polymorphisms analysed included the pfdhfr 164L mutation, previously reported to be absent or rare in Africa.

RESULTS: The frequency of the S/P resistance-associated pfdhfr triple mutants (51I/59R/108N) and of pfdhfr/pfdhps quintuple mutants (51I/59R/108N + 437G/540E) was 93% and 47%, respectively. However, no pfdhfr 164L mutants were detected.

CONCLUSION: The observation that a considerably high percentage of P. falciparum parasites contained S/P resistance-associated mutations raises concerns about the validity of this drug as first-choice treatment in Mozambique. On the other hand, no pfdhfr 164L mutant was disclosed, corroborating the view that that this allele is still rare in Africa.

Original languageEnglish
Article number35
Number of pages4
JournalMalaria Journal
Volume6
DOIs
Publication statusPublished - 23 Mar 2007

Keywords

  • Adolescent
  • Animals
  • Antimalarials
  • Artemisinins
  • Child
  • Child, Preschool
  • Codon
  • Dihydropteroate Synthase
  • Drug Combinations
  • Drug Resistance, Multiple
  • Female
  • Humans
  • Infant
  • Malaria, Falciparum
  • Male
  • Mozambique
  • Mutation
  • Plasmodium falciparum
  • Pyrimethamine
  • Sesquiterpenes
  • Sulfadoxine
  • Tetrahydrofolate Dehydrogenase
  • Journal Article
  • Research Support, Non-U.S. Gov't

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