BACKGROUND Mizoram, a northeastern state in India, shares international borders with Myanmar and Bangladesh and is considered to be one of the key routes through which drug-resistant parasites of Southeast Asia enter mainland India. Despite its strategic location and importance, malaria epidemiology and molecular status of chloroquine resistance had not been well documented, and since chloroquine (CQ), as the first-line treatment in Plasmodium falciparum infection was discontinued since 2008, it was expected that CQ-sensitive haplotype would be more abundant. METHODS Malaria epidemiology data for the period 2010 to 2018 was collected from the office of State Vector Disease Control Programme. Plasmodium falciparum-positive blood samples were collected from government district hospitals, community health centres, primary health centres, sub-centres, and diagnostic centres from six malaria-prone districts. The samples were processed and analysed using genes-P. falciparum chloroquine-resistant transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) via sequencing of PCR amplicon from 2015 to 2017. RESULTS Malaria occurred throughout the year and P. falciparum accounted for > 89% of total malaria cases. During 2010-2018, the highest number of malaria incidence was recorded in Lawngtlai (36% of total malaria cases; average API2010-2018 of 34.8) while Champhai remained consistently low (0.4%; average API2010-2018 of 0.04). Males of ≥ 15 years old contributed maximum (35.7%) among gender and age malarial distribution recorded during 2014-2018. Death due to malaria gradually decreased over the years. A higher abundance of mutated pfcrt (58.5% of the total sample analysed) and a lower prevalence of mutated pfmdr1 (48.7%) were observed. All mutations identified for pfcrt belong to the Southeast Asian CVIET haplotype. Only a single point mutation was observed at 86 (N → Y) position in pfmdr1 (48.7%). The key N86Y mutation in pfmdr1 that had been shown to modulate CQR was found in 67.1% of the samples positive for the CVIET haplotype. CONCLUSIONS This is the first report that details malaria epidemiology and also the molecular status of CQ-resistance in P. falciparum population of the region. The efforts of the State Vector Borne Disease Control Programme have proved to be quite effective in controlling the malaria burden in the state. Despite the discontinuation of CQ for a decade, local P. falciparum is observed with decreased CQ-sensitive haplotype. It is believed that the present findings will form a basis for further studies on genetic diversity in P. falciparum, which could confer better understanding of the complexity of the disease in Southeast Asia.

中文翻译：

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印度东北部米佐拉姆邦（与缅甸接壤的疟疾流行地区）的疟疾和氯喹耐药性流行病学。

背景技术印度东北部的米佐拉姆邦与缅甸和孟加拉国具有国际边界，被认为是东南亚耐药性寄生虫进入印度大陆的主要途径之一。尽管其战略位置和重要性，但疟疾流行病学和对氯喹耐药的分子状态尚未得到充分记录，并且自从2008年以来，作为对恶性疟原虫感染的一线治疗停止使用氯喹（CQ）以来，预计对CQ敏感单倍型会更丰富。方法从国家病媒疾病控制计划办公室收集2010年至2018年的疟疾流行病学数据。恶性疟原虫阳性血液样本是从政府区医院，社区卫生中心，初级卫生中心，分中心，和六个疟疾高发区的诊断中心。使用基因-P对样品进行处理和分析。通过PCR扩增子测序，从2015年到2017年，恶性疟原虫抗氯喹转运蛋白（pfcrt）和恶性疟原虫多药耐药性1（pfmdr1）。结果全年发生疟疾，恶性疟原虫占总疟疾病例的89％以上。在2010-2018年期间，劳恩特莱（Langtlai）的疟疾发病率最高（占总疟疾病例的36％; API2010-2018平均为34.8），而占卜一直保持较低水平（0.4％; API2010-2018平均为0.04）。在2014-2018年间，按性别和年龄分布的疟疾分布中，≥15岁的男性贡献最大（35.7％）。这些年来，由于疟疾造成的死亡人数逐渐减少。突变pfcrt的丰度更高（58。观察到分析的总样本量的5％）和较低的pfmdr1突变发生率（48.7％）。鉴定为pfcrt的所有突变均属于东南亚CVIET单倍型。在pfmdr1（48.7％）的86（N→Y）位仅观察到单点突变。在67.1％的CVIET单倍型阳性样本中发现了pfmdr1中的关键N86Y突变可调节CQR。结论这是第一份详细报道疟疾流行病学以及该地区恶性疟原虫种群CQ耐药分子状态的报告。国家媒介传染病控制计划的努力已被证明在控制该州的疟疾负担方面非常有效。尽管CQ中断了十年，但仍观察到局部恶性疟原虫的CQ敏感单倍型减少。