Regional Medical Research Centre for Tribals, Jabalpur, India.
Trop Med Int Health. 2010 Jan;15(1):33-40. doi: 10.1111/j.1365-3156.2009.02425.x. Epub 2009 Nov 11.
To assess the therapeutic efficacy of chloroquine (CQ) treatment against uncomplicated Plasmodium falciparum infections in a tribal population of central India (Madhya Pradesh) and to investigate the prevalence of mutant P. falciparum chloroquine-resistant transporter (pfcrt) gene in the parasite population.
Clinical and parasitological response was determined by in-vivo testing. For molecular testing, the parasite DNA was extracted from blood samples and used to amplify and sequence parts of the pfcrt (44-177 codons), MSP1 (block 2) and MSP2 (central repeat region) genes.
Of 463 patients presenting fever, 137 tested positive for P. falciparum. They were treated with CQ. Of these, 58% participated in the study. Overall, treatment failure occurred in 53% of participants. Children under 5 years of age showed significantly more CQ resistance than adults. Mutant genotype S(72)V(73)M(74)N(75)T(76) was prevalent among both CQ responders (61.29%) and non-responders (66.7%). Interestingly, several patients from the CQ non-responder group (33.3%, n = 39) were harbouring parasite with wild type C(72)V(73)M(74)N(75)K(76) genotype of the pfcrt gene. Microsatellite sequences downstream of exon 2 varied widely among both wild type and mutant pfcrt haplotypes.
The high rate of treatment failure in the present study clearly indicates the need to reassess the use of CQ as first-line antimalarial therapy in central India. This is supported by the presence of mutant pfcrt genotype among majority of the parasite population of the CQ non-responder group of patients. However, the presence of wild type amino acid at codon 76 of the pfcrt gene among several patients with CQ non-responders requires further investigations.
评估氯喹（CQ）治疗印度中部部落人群（中央邦）无并发症恶性疟原虫感染的疗效，并研究寄生虫种群中恶性疟原虫氯喹耐药转运蛋白（pfcrt）基因突变的流行情况。
通过体内试验确定临床和寄生虫学反应。为了进行分子检测，从血液样本中提取寄生虫 DNA，用于扩增和测序 pfcrt（44-177 密码子）、MSP1（块 2）和 MSP2（中央重复区）基因的部分序列。
在 463 名发热患者中，137 名疟原虫检测呈阳性。他们接受了 CQ 治疗。其中，58%的人参加了这项研究。总的来说，53%的参与者治疗失败。5 岁以下儿童的 CQ 耐药性明显高于成年人。CQ 反应者（61.29%）和非反应者（66.7%）中均普遍存在突变基因型 S(72)V(73)M(74)N(75)T(76)。有趣的是，CQ 非反应者组的一些患者（33.3%，n=39）携带野生型 C(72)V(73)M(74)N(75)K(76) pfcrt 基因的寄生虫。外显子 2 下游的微卫星序列在野生型和突变型 pfcrt 单倍型中差异很大。
本研究中高比例的治疗失败率清楚地表明，需要重新评估 CQ 在印度中部作为一线抗疟治疗药物的使用。这一结论得到了大多数 CQ 非反应者寄生虫种群中存在突变型 pfcrt 基因型的支持。然而，CQ 非反应者中一些患者存在 pfcrt 基因 76 密码子的野生型氨基酸，需要进一步研究。
