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Polymorphisms in the pfcrt and pfmdr1 Genes of Plasmodium falciparum and in Vitro Susceptibility to Amodiaquine and Desethylamodiaquine

Diego F. EcheverryInternational Center for Medical Research and Training (CIDEIM), Cali, Colombia; Malaria Research Unit, Department of Infectious Diseases, Division of Medicine, Karolinska Institute, Stockholm, Sweden

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Gabrielle HolmgrenInternational Center for Medical Research and Training (CIDEIM), Cali, Colombia; Malaria Research Unit, Department of Infectious Diseases, Division of Medicine, Karolinska Institute, Stockholm, Sweden

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Claribel MurilloInternational Center for Medical Research and Training (CIDEIM), Cali, Colombia; Malaria Research Unit, Department of Infectious Diseases, Division of Medicine, Karolinska Institute, Stockholm, Sweden

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Juan C. HiguitaInternational Center for Medical Research and Training (CIDEIM), Cali, Colombia; Malaria Research Unit, Department of Infectious Diseases, Division of Medicine, Karolinska Institute, Stockholm, Sweden

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Anders BjörkmanInternational Center for Medical Research and Training (CIDEIM), Cali, Colombia; Malaria Research Unit, Department of Infectious Diseases, Division of Medicine, Karolinska Institute, Stockholm, Sweden

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Jose P. GilInternational Center for Medical Research and Training (CIDEIM), Cali, Colombia; Malaria Research Unit, Department of Infectious Diseases, Division of Medicine, Karolinska Institute, Stockholm, Sweden

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Lyda OsorioInternational Center for Medical Research and Training (CIDEIM), Cali, Colombia; Malaria Research Unit, Department of Infectious Diseases, Division of Medicine, Karolinska Institute, Stockholm, Sweden

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The potential role of polymorphisms in the pfcrt and pfmdr1 genes and in vitro susceptibility to amodiaquine and desethylamodiaquine were explored in 15 chloroquine-resistant Colombian Plasmodium falciparum isolates. Single nucleotide polymorphisms in the pfcrt gene, including a newly reported mutation (S334N), were seen in isolates with decreased susceptibility to amodiaquine and desethylamodiaquine. The lowest susceptibility found to amodiaquine was observed in an isolate carrying a pfcrt and pfmdr1 Dd2-like haplotype, whereas a pfcrt haplotype related to the 7G8 Brazilian strain was found in a Colombian isolate with the lowest susceptibility to desethylamodiaquine. This exploratory study suggests that polymorphisms in the pfcrt and pfmdr1 genes play a role in amodiaquine and desethylamodiaquine resistance and warrants further study.

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