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东非疟原虫中氯喹耐药分子标志物的流行情况:一项系统评价与荟萃分析

Prevalence of molecular markers of chloroquine resistance in malaria parasites in East Africa: A systematic review and meta-analysis.

作者信息

Abebe Wagaw, Mekuanint Amare, Asmare Zelalem, Woldesenbet Dagmawi, Mihret Yenesew, Setegn Abebaw, Emagneneh Tadele

机构信息

Department of Medical Laboratory Sciences, College of Health Sciences, Woldia University, Woldia, Ethiopia.

Department of Clinical Chemistry, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia.

出版信息

J Glob Antimicrob Resist. 2025 Mar;41:117-137. doi: 10.1016/j.jgar.2024.12.019. Epub 2024 Dec 25.

Abstract

BACKGROUND

Malaria is a serious global public health problem, which is caused by genus Plasmodium. Resistance of the human malaria parasite to antimalarial drugs is a public health concern in malaria endemic countries. Chloroquine is resistant for both P. vivax and P. falciparum. Chloroquine resistance is understood throughout all of Africa's P. falciparum endemic regions. Molecular markers play a crucial role in tracking and understanding the prevalence of antimalarial drug resistance. Currently, there is inadequate information on the prevalence of molecular markers of chloroquine resistance in malaria parasites.

OBJECTIVE

This systematic review and meta-analysis aimed to determine the pooled prevalence of molecular markers of chloroquine resistance in malaria parasites in East Africa.

METHODS

Systematic search was performed to retrieve articles from PubMed, Scopus, Science Direct, and the Google Scholar search engine. Twenty potential studies that provided important data on markers of chloroquine resistance in malaria parasites were systematically reviewed and analyzed. Five antimalarial drug resistance markers of chloroquine resistance were extracted separately into Microsoft Excel and analyzed using STATA 17.0. The Inverse of variance (I) was done to evaluate heterogeneity across studies. The funnel plot and the Egger's test were used to determine the existence or absence of publication bias. A trim-and-fill meta-analysis was carried out to generate a bias-adjusted effect estimate. A random effect model was used to determine the pooled prevalence of molecular markers associated with chloroquine resistance in malaria parasites. Subgroup analysis was performed based on country and year of publication.

RESULTS

A total of 20 studies were included for this systematic review and meta-analysis. The molecular markers like K76T, 76T, N86Y, Y184F, and 86Y were selected for meta-analysis. From this meta-analysis, the pooled prevalence of K76T, 76T, N86Y, Y184F, and 86Y was 34.5%, 47.3%, 43.8%, 58.3%, and 29.2%, respectively. After adjusting for publication bias, the estimated pooled prevalence of K76T, 76T, N86Y, Y184F, and 86Y were 34.5%, 47.3%, 43.8%, 58.3%, and 29.2%, respectively. Meta-analysis showed a significant difference in all molecular marker prevalence like K76T and 86Y among studies on year of publication except 76T, N86Y, and Y184F. In addition, the meta-analysis showed a significant difference in all molecular marker prevalence like K76T, 76T, N86Y, Y184F, and 86Y among studies at the country level.

CONCLUSIONS

The findings of this systematic review and meta-analysis concerning the molecular markers of chloroquine resistance of malaria parasites in East Africa revealed a significant prevalence of antimalarial drug resistance markers of chloroquine. As a result, continued surveillance and monitoring of the prevalence of molecular markers of chloroquine resistance, identification and limitation of drug-resistant malaria parasite strains, and development of new antimalarial treatments are required to guide malaria treatment policies, interventions, control, and elimination of malaria worldwide.

摘要

背景

疟疾是一个严重的全球公共卫生问题,由疟原虫属引起。人类疟原虫对抗疟药物的耐药性是疟疾流行国家的一个公共卫生问题。氯喹对间日疟原虫和恶性疟原虫均有耐药性。在非洲所有恶性疟原虫流行地区,氯喹耐药情况均已为人所知。分子标记在追踪和了解抗疟药物耐药性的流行情况方面起着至关重要的作用。目前,关于疟原虫中氯喹耐药分子标记的流行情况信息不足。

目的

本系统评价和荟萃分析旨在确定东非疟原虫中氯喹耐药分子标记的合并流行率。

方法

进行系统检索以从PubMed、Scopus、Science Direct和谷歌学术搜索引擎中检索文章。对20项提供疟原虫氯喹耐药标记重要数据的潜在研究进行系统评价和分析。将氯喹耐药的5种抗疟药物耐药标记分别提取到Microsoft Excel中,并使用STATA 17.0进行分析。采用方差倒数法评估各研究间的异质性。采用漏斗图和Egger检验确定是否存在发表偏倚。进行了修剪填充荟萃分析以生成偏差调整后的效应估计值。采用随机效应模型确定疟原虫中与氯喹耐药相关的分子标记的合并流行率。根据国家和发表年份进行亚组分析。

结果

本系统评价和荟萃分析共纳入20项研究。选择K76T、76T、N86Y、Y184F和86Y等分子标记进行荟萃分析。通过该荟萃分析,K76T、76T、N86Y、Y184F和86Y的合并流行率分别为34.5%、47.3%、43.8%、58.3%和29.2%。在调整发表偏倚后,K76T、76T、N86Y、Y184F和86Y的估计合并流行率分别为34.5%、47.3%、43.8%、58.3%和29.2%。荟萃分析显示,除76T、N86Y和Y184F外,在发表年份的研究中,K76T和86Y等所有分子标记的流行率存在显著差异。此外,荟萃分析显示,在国家层面的研究中,K76T、76T、N86Y、Y184F和86Y等所有分子标记的流行率存在显著差异。

结论

本系统评价和荟萃分析关于东非疟原虫氯喹耐药分子标记的结果显示,氯喹抗疟药物耐药标记的流行率显著。因此,需要持续监测氯喹耐药分子标记的流行情况,识别和限制耐药疟原虫菌株,以及开发新的抗疟治疗方法,以指导全球疟疾治疗政策、干预措施、控制和消除疟疾。

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