Pati Sudhanshu S, Mishra Sarojkanti, Mohanty Sanjib, Mohapatra Debendra N, Sahu Praveen K, Priyadarshi Neelam, Kumar S, Sharma Surya K, Tyagi Prajesh K, Chitnis Chetan E, Das Bhabani S
Department of Biochemistry and Molecular Biology, Ispat General Hospital, Rourkela-769005, Orissa, India.
Trans R Soc Trop Med Hyg. 2007 Jul;101(7):650-4. doi: 10.1016/j.trstmh.2007.01.008. Epub 2007 Apr 10.
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.
对印度奥里萨邦孙德尔加尔地区两个疟疾传播强度不同地点（高传播强度地区，n = 70；低传播强度地区，n = 68）患者血样中的恶性疟原虫氯喹抗性转运蛋白（Pfcrt）K76T突变及单倍型（氨基酸72 - 76）进行分析，作为氯喹（CQ）抗性标志物，并与体内反应相关联。高流行地区早期治疗失败（ETF）的发生率显著更高（32.9%对7.4%，P < 0.001），5岁以下儿童受影响更大。在两个地区均观察到较高频率的pfcrt K76T突变（87.1%对79.4%，P = 0.22）。携带pfcrt 76T的患者最有可能发生ETF（优势比36；95%置信区间3.35 - 1653.3；P < 0.001）。高流行地区和低流行地区76T:K76的比例分别为22:9和11:14（优势比3.1；95%置信区间0.9 - 11.03；P = 0.04），这可作为药物压力的一种衡量指标。pfcrt密码子72 - 76的序列显示，16种耐CQ单倍型为SVMNT，5种为CVMNT，12种为CVIET。CQ敏感单倍型在10个样本中大多为CVMNK；在2个样本中为CVIEK。东南亚和南美单倍型均有存在，以后者为主。
