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Screening for mutations related to atovaquone/proguanil resistance in treatment failures and other imported isolates of Plasmodium falciparum in Europe.
J Infect Dis. 2004 Nov 01; 190(9):1541-6.JI

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.

Authors+Show Affiliations

Institute of Tropical Medicine, Charité, Humboldt University, Berlin, Germany. ole.wichmann@charite.de.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15478057

Citation

Wichmann, Ole, et al. "Screening for Mutations Related to Atovaquone/proguanil Resistance in Treatment Failures and Other Imported Isolates of Plasmodium Falciparum in Europe." The Journal of Infectious Diseases, vol. 190, no. 9, 2004, pp. 1541-6.
Wichmann O, Muehlberger N, Jelinek T, et al. Screening for mutations related to atovaquone/proguanil resistance in treatment failures and other imported isolates of Plasmodium falciparum in Europe. J Infect Dis. 2004;190(9):1541-6.
Wichmann, O., Muehlberger, N., Jelinek, T., Alifrangis, M., Peyerl-Hoffmann, G., Muhlen, M., Grobusch, M. P., Gascon, J., Matteelli, A., Laferl, H., Bisoffi, Z., Ehrhardt, S., Cuadros, J., Hatz, C., Gjorup, 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. The Journal of Infectious Diseases, 190(9), 1541-6.
Wichmann O, et al. Screening for Mutations Related to Atovaquone/proguanil Resistance in Treatment Failures and Other Imported Isolates of Plasmodium Falciparum in Europe. J Infect Dis. 2004 Nov 1;190(9):1541-6. PubMed PMID: 15478057.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Screening for mutations related to atovaquone/proguanil resistance in treatment failures and other imported isolates of Plasmodium falciparum in Europe. AU - Wichmann,Ole, AU - Muehlberger,Nikolai, AU - Jelinek,Tomas, AU - Alifrangis,Michael, AU - Peyerl-Hoffmann,Gabriele, AU - Muhlen,Marion, AU - Grobusch,Martin P, AU - Gascon,Joaquim, AU - Matteelli,Alberto, AU - Laferl,Hermann, AU - Bisoffi,Zeno, AU - Ehrhardt,Stephan, AU - Cuadros,Juan, AU - Hatz,Christoph, AU - Gjorup,Ida, AU - McWhinney,Paul, AU - Beran,Jiri, AU - da Cunha,Saraiva, AU - Schulze,Marco, AU - Kollaritsch,Herwig, AU - Kern,Peter, AU - Fry,Graham, AU - Richter,Joachim, AU - ,, Y1 - 2004/09/28/ PY - 2004/03/04/received PY - 2004/04/19/accepted PY - 2004/10/13/pubmed PY - 2004/12/16/medline PY - 2004/10/13/entrez SP - 1541 EP - 6 JF - The Journal of infectious diseases JO - J Infect Dis VL - 190 IS - 9 N2 - 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. SN - 0022-1899 UR - https://www.unboundmedicine.com/medline/citation/15478057/Screening_for_mutations_related_to_atovaquone/proguanil_resistance_in_treatment_failures_and_other_imported_isolates_of_Plasmodium_falciparum_in_Europe_ L2 - https://academic.oup.com/jid/article-lookup/doi/10.1086/424469 DB - PRIME DP - Unbound Medicine ER -