Pfcrt haplotypes and in-vivo chloroquine response in Sundergarh district, Orissa, India.
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.
Pati
Sudhanshu S
SS
Department of Biochemistry and Molecular Biology, Ispat General Hospital, Rourkela-769005, Orissa, India. sspati@rediffmail.com
Mishra
Sarojkanti
S
Mohanty
Sanjib
S
Mohapatra
Debendra N
DN
Sahu
Praveen K
PK
Priyadarshi
Neelam
N
Kumar
S
S
Sharma
Surya K
SK
Tyagi
Prajesh K
PK
Chitnis
Chetan E
CE
Das
Bhabani S
BS
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
D000962:Antimalarials; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine