Molecular epidemiology of malaria in Cameroon. X. Evaluation of PFMDR1 mutations as genetic markers for resistance to amino alcohols and artemisinin derivatives.
Mutations at five positions in the Plasmodium falciparum multidrug-resistance gene 1 (pfmdr1), initially thought to confer resistance to chloroquine, have been associated with in vitro resistance to amino alcohols and artemisinin derivatives in more recent studies. To assess the possible association between drug resistance phenotype and pfmdrl polymorphisms and establish the baseline pfmdr1 sequence data in Yaoundé, Cameroon, the in vitro drug sensitivity pattern was determined for 64 clinical isolates by isotopic microtest. The pfmdr1 alleles were determined by a polymerase chain reaction and automatic sequencing. A large majority of isolates carried Tyr-86 (88%) and Phe-184 (91%) alleles. With the exception of one isolate with mixed codon 1246, all isolates had wild-type alleles Ser-1034, Asn-1042, and Asp-1246. There was no statistical association between codons 86 and 184 and in vitro response to chloroquine, amino alcohols, and artemisinin derivatives (P > 0.05). Our data do not seem to support the hypothesis that mutations in codons 86 and 184 influence the in vitro response to these drugs. Further monitoring of both in vitro response and pfmdrl polymorphisms is required to evaluate the potential role played by other pfmdr1 alleles in the determination of drug resistance in Africa.
Basco
Leonardo K
LK
Institut de Recherche pour le Développement and Laboratoire de Recherche sur le Paludisme, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale, Yaoundé, Cameroon.
Ringwald
Pascal
P
D000293:Adolescent; D000328:Adult; D000655:Amodiaquine / Q000627:therapeutic use; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use* / Q000633:toxicity; D001483:Base Sequence; D002163:Cameroon / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000627:therapeutic use; D017931:DNA Primers; D004338:Drug Combinations; D018432:Drug Resistance, Multiple / Q000235:genetics; D005819:Genetic Markers; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology*; D017720:Molecular Epidemiology; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011739:Pyrimethamine / Q000627:therapeutic use; D013413:Sulfadoxine / Q000627:therapeutic use
D000962:Antimalarials; D017931:DNA Primers; D004338:Drug Combinations; D005819:Genetic Markers; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D011739:Pyrimethamine