In vivo and in vitro analysis of chloroquine resistance in Plasmodium falciparum isolates from Senegal.
To determine the predictive value of chloroquine (CQ) resistance markers in Senegal, Plasmodium falciparum DNA polymorphisms in pfmdr1and pfcrt were examined in relation to clinical outcome. Despite CQ treatment, 17% of patients had parasitemia after 28 days. Examination of molecular markers of CQ resistance revealed that 64% of all isolates had the T76 resistant allele at the pfcrt locus, while 30% carried the Y86 resistant allele at the pfmdr1 locus. The pfcrt T76 allele was present not only in all in vivo resistant isolates, 89% of in vitro resistant isolates, but also in 35% of in vitro sensitive isolates. The pfmdr1 N86Y polymorphism did not correlate with in vitro or in vivo CQ resistance. Our data suggest that the pfcrt T76 allele alone is required but not a sufficient predictor for in vivo CQ resistance.
Sarr
Ousmane
O
Laboratory of Bacteriology and Virology, Hopital Aristide Le Dantec, Dakar, Senegal.
Myrick
Alissa
A
Daily
Johanna
J
Diop
Bernard M
BM
Dieng
Therese
T
Ndir
Omar
O
Sow
Pape Salif
PS
Mboup
Souleymane
S
Wirth
Dyann F
DF
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000818:Animals; D000977:Antiparasitic Agents / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology*; D016054:DNA, Protozoan / Q000032:analysis; D004352:Drug Resistance, Microbial / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D015800:Protozoan Proteins / Q000235:genetics*; D012675:Senegal; D017422:Sequence Analysis, DNA
D018528:ATP-Binding Cassette Transporters; D000977:Antiparasitic Agents; D016054:DNA, Protozoan; D005819:Genetic Markers; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; C059987:mdr gene protein, Plasmodium; D002738:Chloroquine