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大湄公河次区域葡萄糖-6-磷酸脱氢酶(G6PD)突变的分子特征和定位。

Molecular characterization and mapping of glucose-6-phosphate dehydrogenase (G6PD) mutations in the Greater Mekong Subregion.

机构信息

Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.

Centre for Tropical Medicine & Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

出版信息

Malar J. 2019 Jan 23;18(1):20. doi: 10.1186/s12936-019-2652-y.

DOI:10.1186/s12936-019-2652-y
PMID:30674319
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6343352/
Abstract

BACKGROUND

Plasmodium vivax malaria elimination can only be achieved by the deployment of 8-aminoquinolines (primaquine and tafenoquine) in combination with ACT to kill both blood and liver-stage parasites. However, primaquine and the other 8-aminoquinolines cause dose-dependent haemolysis in subjects with G6PD deficiency, an X-linked disorder of red blood cells that is very common in populations living in tropical and subtropical areas. In order to inform safer use of 8-aminoquinolines in the Greater Mekong Subregion, a multi-centre study was carried out to assess the prevalence of G6PD deficiency and to identify the main G6PD variants in samples collected in Cambodia, Lao PDR, Myanmar, Thailand and Vietnam.

METHODS

Blood samples were collected in the five countries during National Malaria Surveys or during Population Surveys. During Population Surveys samples were characterized for G6PD phenotype using the Fluorescent Spot Test. Samples were then genotyped for a panel of G6PD mutations.

RESULTS

G6PD deficiency was found to be common in the region with an overall mean prevalence of deficient or mutated hemizygous males of 14.0%, ranging from a mean 7.3% in Thailand, 8.1% in Lao PDR, 8.9% in Vietnam, 15.8% in Myanmar and 18.8% in Cambodia. Mahidol and Viangchan mutations were the most common and widespread variants found among the nine investigated.

CONCLUSIONS

Owing to the high prevalence of G6PD deficiency in the Greater Mekong Subregion, strategies for vivax malaria elimination should include point-of-care G6PD testing (both qualitative and quantitative) to allow safe and wide treatment with 8-aminoquinolines.

摘要

背景

只有部署 8-氨基喹啉(伯氨喹和他非诺喹)与 ACT 联合使用才能消灭间日疟原虫疟疾,以杀死血液和肝期寄生虫。然而,伯氨喹和其他 8-氨基喹啉在葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症患者中引起剂量依赖性溶血,这是一种非常常见的 X 连锁红细胞疾病,存在于生活在热带和亚热带地区的人群中。为了在大湄公河次区域更安全地使用 8-氨基喹啉,进行了一项多中心研究,以评估 G6PD 缺乏症的流行率,并确定在柬埔寨、老挝人民民主共和国、缅甸、泰国和越南采集的样本中的主要 G6PD 变异体。

方法

在五个国家的国家疟疾调查或人口调查期间采集血液样本。在人口调查期间,使用荧光斑点试验对 G6PD 表型进行特征分析。然后对一组 G6PD 突变进行基因分型。

结果

该地区普遍存在 G6PD 缺乏症,缺乏或突变的杂合男性总体平均患病率为 14.0%,范围从泰国的平均 7.3%、老挝人民民主共和国的 8.1%、越南的 8.9%、缅甸的 15.8%和柬埔寨的 18.8%。Mahidol 和 Viangchan 突变是在调查的九个变异体中最常见和分布最广的变异体。

结论

由于大湄公河次区域 G6PD 缺乏症的高流行率,间日疟原虫消除策略应包括即时检测(定性和定量)G6PD,以安全和广泛地使用 8-氨基喹啉治疗。

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