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.
BACKGROUND: Two single-point mutations of the Plasmodium falciparumcytochrome 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: Luicer A Ingasia; Hoseah M Akala; Mabel O Imbuga; Benjamin H Opot; Fredrick L Eyase; Jacob D Johnson; Wallace D Bulimo; Edwin Kamau Journal: Antimicrob Agents Chemother Date: 2015-01-12 Impact factor: 5.191
Authors: E Bottieau; J Clerinx; R Colebunders; E Van den Enden; R Wouters; H Demey; M Van Esbroeck; T Vervoort; A Van Gompel; J Van den Ende Journal: Eur J Clin Microbiol Infect Dis Date: 2007-03 Impact factor: 3.267
Authors: Ana Afonso; Zoraima Neto; Helena Castro; Dinora Lopes; Ana C Alves; Ana M Tomás; Virgílio D Rosário Journal: Malar J Date: 2010-05-21 Impact factor: 2.979
Authors: Colin J Sutherland; Matt Laundy; Nicholas Price; Martina Burke; Quinton L Fivelman; Geoffrey Pasvol; John L Klein; Peter L Chiodini Journal: Malar J Date: 2008-11-20 Impact factor: 2.979