title: Prevalence of the K76T mutation in the pfcrt gene of Plasmodium falciparum among chloroquine responders in India.
abstract: Chloroquine-resistant Plasmodium falciparum needs to be monitored in the field for effective malaria control strategies. A point mutation K76T in the P. falciparum chloroquine resistance transporter (Pfcrt) protein has recently been proposed as a molecular marker for the faster detection of chloroquine-resistant falciparum malaria in field. We describe here the evaluation of this marker in Indian P. falciparum isolates. A total of 274 Indian P. falciparum isolates were analyzed for the K76T mutation. This mutation was detected in all the clinical isolates obtained from the in vivo chloroquine non-responders. But majority of the clinical isolates from chloroquine responders (71 of 74 patients, i.e. 96%) also harbored this mutation. The K76T mutation was indeed highly prevalent (91%) among 213 clinical isolates. There was a significant association between K76T mutation and the in vitro chloroquine response (P<0.05) but six isolates showed discordant results. In conclusion, the K76T mutation fails to differentiate majority of the chloroquine responders from that of the non-responders and thus will be of limited use in the field in India.
authors.affiliation: Department of Biotechnology, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Sumiti
authors.initials: S
authors.lastname: Vinayak
authors.forename: Sukla
authors.initials: S
authors.lastname: Biswas
authors.forename: Vas
authors.initials: V
authors.lastname: Dev
authors.forename: Ashwani
authors.initials: A
authors.lastname: Kumar
authors.forename: M A
authors.initials: MA
authors.lastname: Ansari
authors.forename: Y D
authors.initials: YD
authors.lastname: Sharma
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D002648:Child; D002738:Chloroquine / Q000627:therapeutic use*; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D006801:Humans; D007194:India; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy* / Q000469:parasitology*; D008297:Male; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics; D008875:Middle Aged; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction
chemical_list: D000962:Antimalarials; D004269:DNA, Bacterial; D026901:Membrane Transport Proteins; D002738:Chloroquine