Dihydrofolate reductase I164L mutations in Plasmodium falciparum isolates: clinical outcome of 14 Kenyan adults infected with parasites harbouring the I164L mutation

Mary J. Hamel, Amanda Poe, Peter Bloland, Andrea McCollum, Zhiyong Zhou, Ya Ping Shi, Peter Ouma, Kephas Otieno, John Vulule, Ananias Escalante, Venkatachalam Udhayakumar, Laurence Slutsker

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Recently, Plasmodium falciparum bearing dihydrofolate reductase (DHFR) I164L was isolated from Africa. Quadruple mutations containing I164L confer high-level resistance to antifolate antimalarials. We prospectively measured the effect of co-trimoxazole (CTX) prophylaxis on P. falciparum antifolate resistance development among HIV-infected persons. HIV-positive patients with CD4 cell count <350 cells/μl (n = 692) received CTX; HIV-positive patients with CD4 cell count ≥350 cells/μl (n = 336) and HIV-negative patients (n = 132) received multivitamins. Malaria microscopy-positive samples (n = 413) and selected microscopy-negative/PCR-positive samples (n = 76) were analysed for DHFR mutations at baseline and during six months follow up. We identified I164L in 14 patients. Seven were malaria microscopy-positive: two failed sulfadoxine-pyrimethamine (SP). Among seven microscopy-negative/PCR-positive patients, none developed patent infections with I164L. I164L was not associated with high-level SP resistance or poor outcome among adults living where malaria is highly endemic. Surveillance to monitor spread of I164L is critical, especially among children and pregnant women, who are potentially a source for I164L amplification.

Original languageEnglish (US)
Pages (from-to)338-345
Number of pages8
JournalTransactions of the Royal Society of Tropical Medicine and Hygiene
Volume102
Issue number4
DOIs
StatePublished - Apr 1 2008

Keywords

  • DHFR
  • Drug resistance
  • Malaria
  • Mutation
  • Plasmodium falciparum
  • Sulfadoxine-pyrimethamine

ASJC Scopus subject areas

  • Parasitology
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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