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恶性疟原虫 Kelch13 突变与在亚马逊流域国家传播的风险

Kelch13 mutations in Plasmodium falciparum and risk of spreading in Amazon basin countries.

机构信息

Laboratoire de parasitologie, Centre Nationale de Référence du Paludisme, World Health Organization Collaborating Center for surveillance of antimalarial drug resistance, Institut Pasteur de la Guyane, 97306 Cayenne, French Guiana.

Ecole Doctorale n°587 « Diversités, Santé, et Développement en Amazonie », Université de Guyane, 97300 Cayenne, French Guiana.

出版信息

J Antimicrob Chemother. 2021 Oct 11;76(11):2854-2862. doi: 10.1093/jac/dkab264.

Abstract

BACKGROUND

The first potential focus for artemisinin resistance in South America was recently confirmed with the presence of the C580Y mutation in the Plasmodium falciparum kelch 13 gene (pfk13) in Guyana.

OBJECTIVES

This study aimed to strengthen pfk13 monitoring in the Amazon basin countries, to compile the available data and to evaluate the risk of spreading of mutations.

METHODS

Sanger sequencing was done on 862 samples collected between 1998 and 2019, and a global map of pfk13 genotypes available for this region was constructed. Then, the risk of spreading of mutations based on P. falciparum case importation between 2015 and 2018 within countries of the Amazon basin was evaluated.

RESULTS

No additional pfk13 C580Y foci were identified. Few mutations (0.5%, 95% CI = 0.3%-0.8%) in the propeller domain were observed in the general parasite population of this region despite a high proportion of K189T mutations (49.1%, 95% CI = 46.2%-52.0%) in the non-propeller domain. Case information revealed two patterns of intense human migration: Venezuela, Guyana and the Roraima State in Brazil; and French Guiana, Suriname and the Amapá State in Brazil.

CONCLUSIONS

There are few pfk13 mutant foci, but a high risk of dispersion in the Amazon basin, mainly from the Guiana Shield, proportionate to mining activities. Therefore, access to prompt diagnosis and treatment, and continuous molecular monitoring is essential in these geographical areas.

摘要

背景

最近在圭亚那发现了疟原虫 falciparum kelch 13 基因(pfk13)中的 C580Y 突变,这是南美洲青蒿素耐药的第一个潜在焦点。

目的

本研究旨在加强亚马逊流域国家 pfk13 的监测,编译现有数据并评估突变传播的风险。

方法

对 1998 年至 2019 年间采集的 862 个样本进行 Sanger 测序,并构建了该地区 pfk13 基因型的全球图谱。然后,评估了 2015 年至 2018 年期间,亚马逊流域国家内疟疾病例输入引起的突变传播风险。

结果

未发现其他 pfk13 C580Y 焦点。尽管非螺旋桨结构域中 K189T 突变(49.1%,95%置信区间 46.2%-52.0%)比例很高,但在该地区寄生虫种群中仅观察到少数(0.5%,95%置信区间 0.3%-0.8%)在螺旋桨结构域中的突变。病例信息揭示了两种密集的人类迁移模式:委内瑞拉、圭亚那和巴西的罗赖马州;以及法属圭亚那、苏里南和巴西的阿马帕州。

结论

pfk13 突变焦点较少,但亚马逊流域的传播风险很高,主要来自圭亚那地盾,与采矿活动有关。因此,在这些地理区域,及时诊断和治疗以及持续的分子监测至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3a7/8521405/4a006d4f7d49/dkab264f1.jpg

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