title: Pfcrt haplotypes and in-vivo chloroquine response in Sundergarh district, Orissa, India.
abstract: The Plasmodium falciparum chloroquine resistance transporter (Pfcrt) K76T mutation and haplotype (amino acids 72-76) were analyzed as markers of chloroquine (CQ) resistance in the blood samples of patients from two sites of different intensities of malaria transmission (high, n=70; low, n=68) in Sundergarh district of Orissa, India and correlated with the in-vivo response. Early treatment failure (ETF) was significantly more frequent in the high endemic area (32.9 vs. 7.4%, P<0.001), with children below 5 years suffering more. A high frequency of pfcrt K76T mutation was observed in both the areas (87.1 vs. 79.4%, P=0.22). Patients carrying pfcrt 76T were the most likely to develop ETF (odds ratio 36; 95% CI 3.35-1653.3; P<0.001). The ratio of 76T:K76 was 22:9 and 11:14, respectively, in high and low endemic areas (odds ratio 3.1; 95% CI 0.9-11.03; P=0.04), which may be used as a measure of drug pressure. Sequences of pfcrt codons 72-76 showed 16 of the CQ-resistant haplotypes to be SVMNT, 5 CVMNT and 12 CVIET. The CQ-sensitive haplotypes were mostly CVMNK in 10 samples; CVIEK in 2 samples. Both Southeast Asian and South American haplotypes were present, with the latter predominating.
authors.affiliation: Department of Biochemistry and Molecular Biology, Ispat General Hospital, Rourkela-769005, Orissa, India. sspati@rediffmail.com
authors.forename: Sudhanshu S
authors.initials: SS
authors.lastname: Pati
authors.forename: Sarojkanti
authors.initials: S
authors.lastname: Mishra
authors.forename: Sanjib
authors.initials: S
authors.lastname: Mohanty
authors.forename: Debendra N
authors.initials: DN
authors.lastname: Mohapatra
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Sahu
authors.forename: Neelam
authors.initials: N
authors.lastname: Priyadarshi
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.forename: Surya K
authors.initials: SK
authors.lastname: Sharma
authors.forename: Prajesh K
authors.initials: PK
authors.lastname: Tyagi
authors.forename: Chetan E
authors.initials: CE
authors.lastname: Chitnis
authors.forename: Bhabani S
authors.initials: BS
authors.lastname: Das
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D002675:Child, Preschool; D002738:Chloroquine / Q000627:therapeutic use*; D004351:Drug Resistance / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007194:India / Q000453:epidemiology; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology; D026901:Membrane Transport Proteins / Q000235:genetics*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D016133:Polymerase Chain Reaction; D015995:Prevalence; D015800:Protozoan Proteins / Q000235:genetics*; D017211:Treatment Failure
chemical_list: D000962:Antimalarials; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine