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2014 年至 2017 年期间从喀麦隆间日疟原虫疟疾患者中分离出的 K-13 螺旋桨基因多态性。

K-13 propeller gene polymorphisms isolated between 2014 and 2017 from Cameroonian Plasmodium falciparum malaria patients.

机构信息

Biological Sciences Department, Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon.

Malaria Research Unit, Centre Pasteur Cameroon, Yaoundé, Cameroon.

出版信息

PLoS One. 2019 Sep 3;14(9):e0221895. doi: 10.1371/journal.pone.0221895. eCollection 2019.

Abstract

The emergence of artemisinin-resistant parasites since the late 2000s at the border of Cambodia and Thailand poses serious threats to malaria control globally, particularly in Africa which bears the highest malaria transmission burden. This study aimed to obtain reliable data on the current state of the kelch13 molecular marker for artemisinin resistance in Plasmodium falciparum in Cameroon. DNA was extracted from the dried blood spots collected from epidemiologically distinct endemic areas in the Center, Littoral and North regions of Cameroon. Nested PCR products from the Kelch13-propeller gene were sequenced and analyzed on an ABI 3730XL automatic sequencer. Of 219 dried blood spots, 175 were sequenced successfully. We identified six K13 mutations in 2.9% (5/175) of samples, including 2 non-synonymous, the V589I allele had been reported in Africa already and one new allele E612K had not been reported yet. These two non-synonymous mutations were uniquely found in parasites from the Littoral region. One sample showed two synonymous mutations within the kelch13 gene. We also observed two infected samples with mixed K13 mutant and K13 wild-type infection. Taken together, our data suggested the circulation of the non-synonymous K13 mutations in Cameroon. Albeit no mutations known to be associated with parasite clearance delays in the study population, there is need for continuous surveillance for earlier detection of resistance as long as ACTs are used and scaled up in the community.

摘要

自 21 世纪末以来,在柬埔寨和泰国边境出现的青蒿素耐药寄生虫对全球疟疾控制构成了严重威胁,尤其是在承担着最高疟疾传播负担的非洲。本研究旨在获得喀麦隆恶性疟原虫kelch13 分子标记物对青蒿素耐药性的最新可靠数据。从喀麦隆中心、滨海和北部地区的不同流行地区采集的干燥血斑中提取 DNA。对kelch13-推进器基因的嵌套 PCR 产物进行测序,并在 ABI 3730XL 自动测序仪上进行分析。在 219 个干燥血斑中,成功测序了 175 个。我们在 2.9%(5/175)的样本中发现了 6 种 K13 突变,包括 2 种非同义突变,V589I 等位基因已经在非洲报道过,一种新的等位基因 E612K 尚未报道。这两种非同义突变仅在滨海地区的寄生虫中发现。一个样本在 kelch13 基因内显示了两种同义突变。我们还观察到两个受感染的样本存在 K13 突变体和 K13 野生型混合感染。总的来说,我们的数据表明喀麦隆存在非 synonymous K13 突变的传播。尽管在研究人群中没有发现与寄生虫清除延迟相关的突变,但只要在社区中继续使用和扩大 ACT,就需要持续监测以尽早发现耐药性。

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