Screening for mutations related to atovaquone/proguanil resistance in treatment failures and other imported isolates of Plasmodium falciparum in Europe

Ole Wichmann, Nikolai Muehlberger, Tomas Jelinek, Michael Alifrangis, Gabriele Peyerl-Hoffmann, Marion Mühlen, Martin P. Grobusch, Joaquim Gascon, Alberto Matteelli, Hermann Laferl, Zeno Bisoffi, Stephan Ehrhardt, Juan Cuadros, Christoph Hatz, Ida Gjørup, Paul McWhinney, Jiři Beran, Saraiva Da Cunha, Marco Schulze, Herwig KollaritschPeter Kern, Graham Fry, Joachim Richter

Research output: Contribution to journalArticle

Abstract

Background. Two single-point mutations of the Plasmodium falciparum cytochrome b gene (Tyr268Asn and Tyr268Ser) were recently reported in cases of atovaquone/proguanil (Malarone) treatment failure. However, little is known about the prevalence of codon-268 mutations and their quantitative association with treatment failure. Methods. We set out to assess the prevalence of codon-268 mutations in P. falciparum isolates imported into Europe and to quantify their association with atovaquone/proguanil treatment failure. Isolates of P. falciparum collected by the European Network on Imported Infectious Disease Surveillance between April 2000 and August 2003 were analyzed for codon-268 mutations, by use of polymerase chain reaction-restriction fragment-length polymorphism. Results. We successfully screened 504 samples for the presence of either Tyr268Ser or Tyr268Asn. One case of Ser268 and no cases of Asn268 were detected. Therefore, we can be 95% confident that the prevalence of Ser268 in the European patient pool does not exceed 0.96% and that Asn268 is less frequent than 0.77%. In 58 patients treated with atovaquone/proguanil, Tyr268Ser was present in 1 of 5 patients with treatment failure but in 0 of 53 successfully treated patients. Conclusions. Tyr268Ser seems to be a sufficient, but not a necessary, cause for atovaquone/proguanil treatment failure. The prevalence of both codon-268 mutations is currently unlikely to be >1% in the European patient pool.

Original languageEnglish (US)
Pages (from-to)1541-1546
Number of pages6
JournalJournal of Infectious Diseases
Volume190
Issue number9
DOIs
StatePublished - Nov 1 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Wichmann, O., Muehlberger, N., Jelinek, T., Alifrangis, M., Peyerl-Hoffmann, G., Mühlen, M., Grobusch, M. P., Gascon, J., Matteelli, A., Laferl, H., Bisoffi, Z., Ehrhardt, S., Cuadros, J., Hatz, C., Gjørup, I., McWhinney, P., Beran, J., Da Cunha, S., Schulze, M., ... Richter, J. (2004). Screening for mutations related to atovaquone/proguanil resistance in treatment failures and other imported isolates of Plasmodium falciparum in Europe. Journal of Infectious Diseases, 190(9), 1541-1546. https://doi.org/10.1086/424469