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印度东北部米佐拉姆邦的疟疾和氯喹耐药性的流行病学研究,该邦是一个疟疾流行地区,与缅甸接壤。

Epidemiology of malaria and chloroquine resistance in Mizoram, northeastern India, a malaria-endemic region bordering Myanmar.

机构信息

Department of Biotechnology, Mizoram University, Aizawl, Mizoram, India.

Department of Orthopaedics, District Hospital, Government of Mizoram, Serchhip, Aizawl, Mizoram, India.

出版信息

Malar J. 2020 Feb 27;19(1):95. doi: 10.1186/s12936-020-03170-3.

Abstract

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 API of 34.8) while Champhai remained consistently low (0.4%; average API 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.

摘要

背景

印度东北部的米佐拉姆邦与缅甸和孟加拉国接壤,被认为是东南亚耐药寄生虫进入印度大陆的主要途径之一。尽管其地理位置具有战略意义,但疟疾流行病学和氯喹耐药的分子状况并未得到充分记录。自 2008 年以来,作为治疗恶性疟原虫感染的一线药物的氯喹已不再使用,预计氯喹敏感单倍型将更加丰富。

方法

从国家病媒控制计划办公室收集了 2010 年至 2018 年的疟疾流行病学数据。从六个疟疾流行地区的政府区医院、社区卫生中心、初级保健中心、分中心和诊断中心收集了疟原虫阳性的血液样本。从 2015 年至 2017 年,使用基因-恶性疟原虫氯喹耐药转运蛋白(pfcrt)和恶性疟原虫多药耐药 1(pfmdr1)对来自 PCR 扩增子的序列进行分析,对疟原虫阳性血液样本进行处理和分析。

结果

疟疾全年发生,恶性疟原虫占总疟疾病例的 89%以上。在 2010-2018 年期间,劳特兰(Lawngtlai)的疟疾病例发生率最高(占总疟疾病例的 36%;平均 API 为 34.8),而昌迈(Champhai)则一直保持较低水平(0.4%;平均 API 为 0.04)。在 2014-2018 年记录的性别和年龄疟疾分布中,年龄在 15 岁及以上的男性占最大比例(35.7%)。疟疾死亡人数逐年减少。观察到突变 pfcrt 的丰度更高(分析的总样本中为 58.5%)和突变 pfmdr1 的流行率更低(48.7%)。pfcrt 中鉴定的所有突变都属于东南亚 CVIET 单倍型。pfmdr1 中仅观察到 86 位(N→Y)位置的单个点突变(48.7%)。在 CVIET 单倍型阳性的样本中,发现了导致 CQR 调节的关键 N86Y 突变,占 67.1%。

结论

这是首次详细报告该地区恶性疟原虫种群中疟疾流行病学和氯喹耐药的分子状况。州病媒传播疾病控制计划的努力已被证明对控制该州的疟疾负担非常有效。尽管停止使用氯喹已有十年,但当地的恶性疟原虫观察到氯喹敏感单倍型减少。据信,目前的研究结果将为进一步研究恶性疟原虫的遗传多样性奠定基础,这将有助于更好地了解东南亚疾病的复杂性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fc7/7045395/8dbab7f796d7/12936_2020_3170_Fig1_HTML.jpg

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