Short communication: Prevalence of mutations associated with resistance to atovaquone and to the antifolate effect of proguanil in Plasmodium falciparum isolates from northern Ghana

Marion Muehlen, Jonas Schreiber, Stephan Ehrhardt, Rowland Otchwemah, Tomas Jelinek, Ulrich Bienzle, Frank P. Mockenhaupt

Research output: Contribution to journalArticlepeer-review

Abstract

Atovaquone-proguanil has recently been introduced for the treatment and prophylaxis of malaria. However, resistance of Plasmodium falciparum is increasingly reported. We assessed P. falciparum polymorphisms associated with resistance to atovaquone (cytochrome b, cytb) and to cycloguanil, the active compound of proguanil (dihydrofolate reductase, dhfr) in 100 isolates from northern Ghana. None of these exhibited cytb codon 268 mutations. Moreover, no dhfr V16A, S108T or I164L mutations linked with cycloguanil resistance were detected. However, dhfr triple mutants (S108N-I51L-C59R) conferring resistance to proguanil and sulphadoxine-pyrimethamine were seen in 51% of the isolates. In northern Ghana, P. falciparum cytb codon 268 mutations associated with atovaquone resistance are absent. Although proguanil appears to act synergistically with atovaquone in a way different from its antifolate property, the abundance of dhfr polymorphisms will likely compromise the prevention of dissemination of atovaquone-resistant parasites once emerged.

Original languageEnglish (US)
Pages (from-to)361-363
Number of pages3
JournalTropical Medicine and International Health
Volume9
Issue number3
DOIs
StatePublished - Mar 2004
Externally publishedYes

Keywords

  • Atovaquone
  • Cytochrome
  • Malaria
  • Plasmodium falciparum
  • Proguanil
  • dhfr

ASJC Scopus subject areas

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

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