Department of Parasitology, U.S. Naval Medical Research Unit No, 6 (NAMRU-6), Lima, Peru.
Emerge, Emerging Diseases and Climate Change Research Unit, School of Public Health and Administration, Universidad Peruana Cayetano Heredia, Lima, Peru.
Malar J. 2020 Dec 4;19(1):450. doi: 10.1186/s12936-020-03519-8.
The high incidence of Plasmodium vivax infections associated with clinical severity and the emergence of chloroquine (CQ) resistance has posed a challenge to control efforts aimed at eliminating this disease. Despite conflicting evidence regarding the role of mutations of P. vivax multidrug resistance 1 gene (pvmdr1) in drug resistance, this gene can be a tool for molecular surveillance due to its variability and spatial patterns.
Blood samples were collected from studies conducted between 2006 and 2015 in the Northern and Southern Amazon Basin and the North Coast of Peru. Thick and thin blood smears were prepared for malaria diagnosis by microscopy and PCR was performed for detection of P. vivax monoinfections. The pvmdr1 gene was subsequently sequenced and the genetic data was used for haplotype and diversity analysis.
A total of 550 positive P. vivax samples were sequenced; 445 from the Northern Amazon Basin, 48 from the Southern Amazon Basin and 57 from the North Coast. Eight non-synonymous mutations and three synonymous mutations were analysed in 4,395 bp of pvmdr1. Amino acid changes at positions 976F and 1076L were detected in the Northern Amazon Basin (12.8%) and the Southern Amazon Basin (4.2%) with fluctuations in the prevalence of both mutations in the Northern Amazon Basin during the course of the study that seemed to correspond with a malaria control programme implemented in the region. A total of 13 pvmdr1 haplotypes with non-synonymous mutations were estimated in Peru and an overall nucleotide diversity of π = 0.00054. The Northern Amazon Basin was the most diverse region (π = 0.00055) followed by the Southern Amazon and the North Coast (π = 0.00035 and π = 0.00014, respectively).
This study showed a high variability in the frequencies of the 976F and 1076L polymorphisms in the Northern Amazon Basin between 2006 and 2015. The low and heterogeneous diversity of pvmdr1 found in this study underscores the need for additional research that can elucidate the role of this gene on P. vivax drug resistance as well as in vitro and clinical data that can clarify the extend of CQ resistance in Peru.
间日疟原虫感染的高发病率与临床严重程度以及氯喹（CQ）耐药性的出现，给旨在消除这种疾病的控制工作带来了挑战。尽管关于间日疟原虫多药耐药 1 基因（pvmdr1）突变在药物耐药性中的作用存在相互矛盾的证据，但由于其变异性和空间模式，该基因可以作为分子监测的工具。
采集了 2006 年至 2015 年间在秘鲁北部和南部亚马逊流域以及北部海岸进行的研究中的血液样本。通过显微镜检查制备厚和薄血涂片进行疟疾诊断，并通过 PCR 检测间日疟原虫单感染。随后对 pvmdr1 基因进行测序，并利用遗传数据进行单倍型和多样性分析。
共对 550 份阳性间日疟原虫样本进行了测序；445 份来自北部亚马逊流域，48 份来自南部亚马逊流域，57 份来自北部海岸。在 pvmdr1 的 4395bp 中分析了 8 个非同义突变和 3 个同义突变。在北部亚马逊流域（12.8%）和南部亚马逊流域（4.2%）检测到 976F 和 1076L 位置的氨基酸变化，在研究过程中北部亚马逊流域这两种突变的流行率波动似乎与该地区实施的疟疾控制计划相对应。在秘鲁共估计了 13 种带有非同义突变的 pvmdr1 单倍型，总体核苷酸多样性为 π=0.00054。北部亚马逊流域是多样性最高的地区（π=0.00055），其次是南部亚马逊流域和北部海岸（π=0.00035 和 π=0.00014）。
本研究表明，2006 年至 2015 年间，北部亚马逊流域 976F 和 1076L 多态性的频率存在高度变异性。本研究中 pvmdr1 发现的低且异质多样性强调了需要进行更多的研究，以阐明该基因在间日疟原虫药物耐药性中的作用，以及体外和临床数据，以澄清秘鲁 CQ 耐药性的程度。
