Immunology and Microbiology Laboratory, Department of Human Physiology with Community Health, Vidyasagar University, Midnapore, 721 102, West Bengal, India.
Department of Biotechnology, School of Chemical and Biotechnology, SASTRA University, Thanjavur, 613402, Tamil Nadu, India.
Int J Parasitol Drugs Drug Resist. 2017 Dec;7(3):251-261. doi: 10.1016/j.ijpddr.2017.06.002. Epub 2017 Jun 29.
Chloroquine (CQ) is highly effective against P. vivax, due to the rapid spread of CQ resistance in P. falciparum parasites; it is no longer the drug of choice against P. falciparum. This study elucidates the scenario of chloroquine efficacy at times that coincided with a new drug policy and especially assessed the chloroquine resistant molecular markers after withdrawal of chloroquine in Kolkata and Purulia, two malaria endemic zones of West Bengal, India. In vitro CQ susceptibility was tested in 781 patients with P. falciparum mono infections between 2008 and 2013, of which 338 patients had received CQ in 2008-2009. Genotyping of the pfcrt and the pfmdr1 gene was carried out in all isolates. Early treatment failure was detected in 114 patients {43 (31·39%) from Kolkata and 71 (35·32%) from Purulia} while recrudescence was identified in 13 (9.49%) and 17 (8.46%) patients from Kolkata and Purulia respectively. In vivo chloroquine resistance was strongly associated with CVMNT-YYSNY (p < 0.01) and SVMNT-YYSNY (p < 0.05) allele in Kolkata. In Purulia chloroquine resistance was associated with CVMNK-YYSNY (P < 0.005), SVMNT-YYSNY (P < 0.01) allele. The proportion of in vitro chloroquine resistance increased in subsequent years to 87.23% and 93·10% in 2013, in Kolkata and Purulia, respectively. Isolates with SVMNT-YFSND, SVMNT-YFSNY, CVIET-YFSND and CVIET-YYSNY haplotypes increased gradually (p < 0.05) from 2010 to 2013, leading to a rise in IC (p < 0.05) of chloroquine. An increase in in vitro chloroquine resistance and candidate gene mutations even after five years of chloroquine withdrawal against P. falciparum calls for synchronized research surveillance and proper containment strategies.
氯喹（CQ）对间日疟原虫非常有效，因为恶性疟原虫对 CQ 的耐药性迅速传播；它不再是治疗恶性疟原虫的首选药物。本研究阐明了在新药物政策实施时氯喹疗效的情况，特别是评估了印度西孟加拉邦两个疟疾流行区加尔各答和普鲁利亚在停止使用氯喹后氯喹的耐药分子标志物。2008 年至 2013 年间，对 781 例间日疟原虫单一感染患者进行了体外 CQ 药敏试验，其中 338 例患者在 2008-2009 年接受了 CQ 治疗。对所有分离株进行了 pfcrt 和 pfmdr1 基因的基因分型。114 例患者出现早期治疗失败（43 例来自加尔各答，71 例来自普鲁利亚），13 例（9.49%）和 17 例（8.46%）患者分别来自加尔各答和普鲁利亚复发。在加尔各答，体内 CQ 耐药性与 CVMNT-YYSNY（p<0.01）和 SVMNT-YYSNY（p<0.05）等位基因密切相关。在普鲁利亚，CQ 耐药性与 CVMNK-YYSNY（P<0.005）、SVMNT-YYSNY（P<0.01）等位基因有关。2013 年，体外 CQ 耐药性的比例分别上升到 87.23%和 93.10%，在加尔各答和普鲁利亚。从 2010 年到 2013 年，携带 SVMNT-YFSND、SVMNT-YFSNY、CVIET-YFSND 和 CVIET-YYSNY 单倍型的分离株逐渐增加（p<0.05），导致 CQ 的 IC（p<0.05）上升。在停止使用氯喹五年后，恶性疟原虫的体外 CQ 耐药性和候选基因突变甚至有所增加，这需要同步进行研究监测和适当的遏制策略。
