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2018 年在莫桑比克采集的恶性疟原虫分离株中与青蒿素为基础的联合疗法耐药性相关的多态性的分子监测。

Molecular surveillance for polymorphisms associated with artemisinin-based combination therapy resistance in Plasmodium falciparum isolates collected in Mozambique, 2018.

机构信息

Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique.

Malaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, GA, USA.

出版信息

Malar J. 2021 Oct 12;20(1):398. doi: 10.1186/s12936-021-03930-9.

DOI:10.1186/s12936-021-03930-9
PMID:34641867
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8507114/
Abstract

BACKGROUND

Due to the threat of emerging anti-malarial resistance, the World Health Organization recommends incorporating surveillance for molecular markers of anti-malarial resistance into routine therapeutic efficacy studies (TESs). In 2018, a TES of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) was conducted in Mozambique, and the prevalence of polymorphisms in the pfk13, pfcrt, and pfmdr1 genes associated with drug resistance was investigated.

METHODS

Children aged 6-59 months were enrolled in four study sites. Blood was collected and dried on filter paper from participants who developed fever within 28 days of initial malaria treatment. All samples were first screened for Plasmodium falciparum using a multiplex real-time PCR assay, and polymorphisms in the pfk13, pfcrt, and pfmdr1 genes were investigated by Sanger sequencing.

RESULTS

No pfk13 mutations, associated with artemisinin partial resistance, were observed. The only pfcrt haplotype observed was the wild type CVMNK (codons 72-76), associated with chloroquine sensitivity. Polymorphisms in pfmdr1 were only observed at codon 184, with the mutant 184F in 43/109 (39.4%) of the samples, wild type Y184 in 42/109 (38.5%), and mixed 184F/Y in 24/109 (22.0%). All samples possessed N86 and D1246 at these two codons.

CONCLUSION

In 2018, no markers of artemisinin resistance were documented. Molecular surveillance should continue to monitor the prevalence of these markers to inform decisions on malaria treatment in Mozambique.

摘要

背景

由于抗疟药耐药性的出现威胁,世界卫生组织建议将抗疟药耐药性的分子标志物监测纳入常规疗效研究(TES)。2018 年,在莫桑比克开展了青蒿素-咯萘啶(AL)和青蒿琥酯-阿莫地喹(ASAQ)的 TES,并调查了与耐药性相关的 pfk13、pfcrt 和 pfmdr1 基因的多态性。

方法

6-59 个月的儿童在四个研究点入组。在初始疟疾治疗后 28 天内出现发热的参与者采集血液并在滤纸上干燥。所有样本均首先使用多重实时 PCR 检测法筛查恶性疟原虫,并用 Sanger 测序法调查 pfk13、pfcrt 和 pfmdr1 基因的多态性。

结果

未观察到与青蒿素部分耐药相关的 pfk13 突变。观察到的唯一 pfcrt 单倍型是野生型 CVMNK(72-76 位密码子),与氯喹敏感性相关。pfmdr1 中的多态性仅在 184 位密码子观察到,184F 突变在 109 个样本中的 43 个(39.4%),野生型 Y184 在 109 个样本中的 42 个(38.5%),184F/Y 混合突变在 109 个样本中的 24 个(22.0%)。所有样本在这两个密码子都具有 N86 和 D1246。

结论

2018 年,未发现青蒿素耐药性的标志物。分子监测应继续监测这些标志物的流行率,以告知莫桑比克疟疾治疗决策。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09e5/8507114/9553a503a2c7/12936_2021_3930_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09e5/8507114/205a49b540f5/12936_2021_3930_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09e5/8507114/9553a503a2c7/12936_2021_3930_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09e5/8507114/205a49b540f5/12936_2021_3930_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09e5/8507114/9553a503a2c7/12936_2021_3930_Fig2_HTML.jpg

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