Molecular surveillance of chloroquine resistance in Plasmodium vivax isolates from malaria cases in Yunnan Province of China using pvcrt-o gene polymorphisms.
Molecular surveillance of chloroquine resistance in Plasmodium vivax isolates from malaria cases in Yunnan Province of China using pvcrt-o gene polymorphisms.
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DOI：
10.1186/s12936-023-04776-z
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发表时间：
2023-11-08
期刊：
影响因子：
3
通讯作者：
Lin, Yingkun
中科院分区：
文献类型：
--
作者：
Ding, Hongyun;Dong, Ying;Deng, Yan;Xu, Yanchun;Liu, Yan;Wu, Jing;Chen, Mengni;Zhang, Canglin;Liu, Li;Lin, Yingkun
关键词：
由于缺乏适当的检测方法，很少对氯喹治疗间日疟疾的疗效进行评估。本研究的目的是对云南省间日疟患者的间日疟原虫进行氯喹耐药分子监测，重点分析间日疟原虫氯喹耐药转运蛋白同源基因（pvrt -o）的多态性。按照队列研究的原则，收集了2020 - 2022年云南省诊断为单一间日疟原虫感染的疟疾病例的血液样本。采用片段式PCR扩增血液样本中的pvrt -o基因，并对其产物进行测序。对测序数据进行整理，得到该基因的全编码DNA序列（CDS）和启动子区序列。将CDSs与间日疟原虫SalI分离物的参考序列（XM_001613407.1）比对，确定突变位点。从375份间日疟病例血样中，共获得272份pvrt -o基因全基因cdna序列（1272 ~ 1275 bp）和启动子DNA序列（707 bp）。在整个cds中，有7个单核苷酸多态性位点，其中c.7次要等位基因频率（MAF）位点为A>G，检出率为4.4%（12/272）。突变检出率由2020年的9.8%（10/102）下降至2021年的1.1%（1/92）、2022年的1.3%(1/78)，差异有统计学意义（χ2 = 11.256, P < 0.05）。在鉴定的12个单倍型中，以野生型居多（75.7%;206/272）。这4种突变单倍型（Hap_3、Hap_5、Hap_9和Hap_10）被归为“K10插入型”，占12.1%（33/272）。Hap_3检出率从2020年的1.0%（1/102）上升到2021年的13.0%（12/92）和2022年的14.1%(11/78)，差异有统计学意义。共有23.8%（65/272）的样本在启动子区域出现了14 bp （bp）的缺失，其中野生型单倍型（Hap_1）的缺失率最高，为28.6%（59/206）。近年来，云南省间日疟患者感染pvrt -o基因启动子区存在“K10插入”和部分序列缺失的间日疟毒株比例显著，需要引起警惕。在线版本包含补充材料，可在10.1186/s12936-023-04776-z获得。
The efficacy of chloroquine treatment for vivax malaria has been rarely evaluated due to a lack of an appropriate testing method. The objective of this study was to conduct molecular monitoring of chloroquine resistance in Plasmodium vivax strains from vivax malaria patients in Yunnan Province, focusing on the analysis of polymorphism in the P. vivax chloroquine resistance transporter protein orthologous gene (pvcrt-o). In accordance with the principles of a cohort study, blood samples were collected from malaria cases diagnosed with a P. vivax mono-infection in Yunnan Province from 2020 to 2022. Segmental PCR was used to amplify the whole pvcrt-o gene in the blood samples and their products were subsequently sequenced. The sequencing data were arranged to obtain the full coding DNA sequence (CDS) as well as the gene’s promoter region sequences. The CDSs were aligned with the reference sequence (XM_001613407.1) of the P. vivax SalI isolate to identify the mutant loci. From a total of 375 blood samples taken from vivax malaria cases, 272 both whole gene CDSs (1272–1275 bp) and promoter DNA sequences (707 bp) of pvcrt-o gene were obtained. Among the whole CDSs, there were 7 single nucleotide polymorphic sites in which c.7 A>G was the minor allele frequency (MAF) site with 4.4% (12/272) detection rate. The mutation detection rate showed a significant decrease from 9.8% (10/102) in 2020 to 1.1% (1/92) in 2021 and 1.3% (1/78) in 2022, indicating statistical significance (χ2 = 11.256, P < 0.05). Among the identified 12 haplotypes, the majority of which were wild type (75.7%; 206/272). These four mutant haplotypes (Hap_3, Hap_5, Hap_9, and Hap_10) were classified as “K10 insertion type” and accounted for 12.1% (33/272). The detection rate of Hap_3 increased from 1.0% (1/102) in 2020 to 13.0% (12/92) in 2021 and 14.1% (11/78) in 2022, indicating statistical significance. A total of 23.8% (65/272) of the samples exhibited 14 bp (bp) deletions in the promoter region, occurring most frequently in the wild type haplotype (Hap_1) samples at a rate of 28.6% (59/206). In recent years in Yunnan Province, a notable proportion of vivax malaria patients are infected by P. vivax strains with a “K10 insertion” and partial sequence deletions in the promoter region of the pvcrt-o gene, necessitating vigilance. The online version contains supplementary material available at 10.1186/s12936-023-04776-z.
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患有严重间日疟原虫疟疾的患者中 pvcrt-o 和 pvmdr1 基因的表达水平增加。
影响因子：
3
作者：
Fernández-Becerra C;Pinazo MJ;González A;Alonso PL;del Portillo HA;Gascón J
通讯作者：
Gascón J
影响因子：
6.4
作者：
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通讯作者：
Genton, Blaise
影响因子：
1.5
作者：
Carlton, JMR;Muller, R;Dame, JB
通讯作者：
Dame, JB
影响因子：
16
作者：
Fidock, DA;Nomura, T;Wellems, TE
通讯作者：
Wellems, TE
影响因子：
1.8
作者：
Carvalho, T. L.;Ribolla, P. E. M.;Mota, L. S. L. S.
通讯作者：
Mota, L. S. L. S.