Screening for mutations related to atovaquone/proguanil resistance in treatment failures and other imported isolates of Plasmodium falciparum in Europe
Research output: Contribution to journal › Journal article › Research › peer-review
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 language | English |
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Journal | Journal of Infectious Diseases |
Volume | 190 |
Issue number | 9 |
Pages (from-to) | 1541-6 |
Number of pages | 5 |
ISSN | 0022-1899 |
DOIs | |
Publication status | Published - 2004 |
Bibliographical note
Keywords: Adolescent; Adult; Aged; Amino Acid Substitution; Animals; Antimalarials; Atovaquone; Chloroguanide; Codon; Cytochromes b; DNA, Protozoan; Drug Combinations; Drug Resistance; Epidemiology, Molecular; Europe; Female; Genes, Protozoan; Humans; Malaria, Falciparum; Male; Middle Aged; Mutation, Missense; Naphthoquinones; Plasmodium falciparum; Point Mutation; Polymorphism, Restriction Fragment Length; Protozoan Proteins; Treatment Failure
ID: 8377825