Plasmodium falciparum: pfcrtandDHFRMutations Are Associated with Failure of Chloroquine plus Proguanil Prophylaxis in Travelers

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Abstract
To the Editor—French clinicians still support the combination of chloroquine and proguanil for antimalarial chemoprophylaxis in most of West Africa, where falciparum chloroquine resistance (FCR) remains moderate. Recently, a polymorphism in the pfcrt gene was reported as strongly associated with in vitro FCR in parasite lines and in natural isolates [1–3]. In vivo studies demonstrated absolute selection of the pfcrt K76T mutant allele in therapeutic failure [4]. However, in areas where FCR rates are high, the pfcrt mutant allele was ubiquitous and thus was not predictive of clinical outcomes in immune patients [5, 6]. As has been shown previously in many studies, point mutations in Plasmodium falciparum DHFR are linked to antifolate resistance. The aim of the present work was to determine the DHFR and pfcrt genotypes of isolates obtained from travelers who had used combination chloroquine-proguanil prophylaxis

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