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Berlin Institute of Tropical Medicine, Berlin, Germany
We thank Meshnick and Trumpower [1] for their comments regarding the usefulness of cytochrome b mutations as molecular markers for the resistance of Plasmodium falciparum to atovaquone. We support their point that further testing and sequencing of the cytochrome b gene can provide results with high sensitivity. This is exactly what was done in our study [2], as is shown in the Results section and later in the article. Isolates from patients who had therapeutic failure with atovaquone/proguanil treatment were sequenced at the cytochrome b gene, to detect mutations other than the one used for screening purposes. A 716-bp fragment of the cytochrome b gene that contains the encoding region of the putative atovaquone-binding domain was amplified [3]. Sequencing revealed the absence of all mutations previously described as being involved in atovaquone resistance in vivo and in vitro [4], except the mutation at codon 268 in 1 of the samples [2].
Still, only mutations at codon 268 have been associated with drug resistance in P. falciparum field samples [2]. This is why we chose the detection of this mutation as a screening method for all samples. However, as was indicated by our results, the usefulness of codon 268 as the only target for the surveillance of plasmodial atovaquone/proguanil resistance has to be questioned.
References
1. Meshnick SR, Trumpower B. Multiple cytochrome b mutations may cause atovaquone resistance . J Infect Dis 2005; 191:822 (in this issue). First citation in article
2. Wichmann O, Muhlberger 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; 190:15416. First citation in article
3. Gil JP, Nogueira F, Stromberg-Norklit J, et al. Detection of atovaquone and malarone resistance conferring mutations in Plasmodium falciparum cytochrome b gene (cytb). Mol Cell Probes 2003; 17:859. First citation in article
4. Korsinczky M, Chen N, Kotecka B, Saul A, Rieckmann K, Cheng Q. Mutations in Plasmodium falciparum cytochrome b that are associated with atovaquone resistance are located at a putative drug-binding site. Antimicrob Agents Chemother 2000; 44:21008. First citation in article