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莫桑比克抗疟药物耐药性图谱:ACT实施后遗传标记的系统评价

Mapping Antimalarial Drug Resistance in Mozambique: A Systematic Review of Genetic Markers Post-ACT Implementation.

作者信息

Chaves Celso Raul Silambo, da Silva Clemente, Salamandane Acácio, Nogueira Fatima

机构信息

Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation Towards Global Health (LA-REAL), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), Rua da Junqueira 100, 1349-008 Lisboa, Portugal.

Faculdade de Ciências de Saúde, Universidade Lúrio, Campus Universitário de Marrere, Nampula 4250, Mozambique.

出版信息

Int J Mol Sci. 2024 Dec 20;25(24):13645. doi: 10.3390/ijms252413645.

Abstract

Malaria continues to be a significant public health burden in many tropical and subtropical regions. Mozambique ranks among the top countries affected by malaria, where it is a leading cause of morbidity and mortality, accounting for 29% of all hospital deaths in the general population and 42% of deaths amongst children under five. This review presents a comparative analysis of data on five critical genes associated with antimalarial drug resistance: , , , , and , along with the copy number variation (CNV) in genes and . These are genes associated with parasite response to antimalarials currently used to treat uncomplicated malaria in Mozambique. The review synthesizes data collected from published studies conducted in Mozambique after the introduction of artemisinin-based combination therapies (ACTs) (2006) up to June 2024, highlighting the presence or absence of mutations in these genes across Mozambique. We aimed at mapping the prevalence and distribution of these molecular markers across the country in order to contribute to the development of targeted interventions to sustain the efficacy of malaria treatments in Mozambique. Four databases were used to access the articles: PubMed, Science Direct, Scopus, and Google scholar. The search strategy identified 132 studies addressing malaria and antimalarial resistance. Of these, 112 were excluded for various reasons, leaving 20 studies to be included in this review. Children and pregnant women represent the majority of target groups in studies on all types of antimalarials. Most studies (87.5%) were conducted in the provinces of Maputo and Gaza. The primary alleles reported were CVMNK, and in the most recent data, its wild-type form was found in the majority of patients. A low prevalence of mutations in the gene was identified reflecting the effectiveness of ACTs. In , only mutation A578S was reported in Niassa and Tete. CNVs were observed in studies carried out in the south of Mozambique, with a frequency of 1.1-5.1% for and a frequency of 1.1-3.4% for . This review indicates that molecular markers linked to malaria resistance show considerable variation across provinces in Mozambique, with most up-to-date data accessible for Maputo and Gaza. In contrast, provinces such as Zambezia and Inhambane have limited data on several genes, while Nampula lacks data on all drug resistance markers.

摘要

疟疾在许多热带和亚热带地区仍然是一项重大的公共卫生负担。莫桑比克是受疟疾影响最严重的国家之一,疟疾是发病和死亡的主要原因,占普通人群所有医院死亡人数的29%,五岁以下儿童死亡人数的42%。本综述对与抗疟药物耐药性相关的五个关键基因(,,,,和)的数据以及基因和中的拷贝数变异(CNV)进行了比较分析。这些基因与寄生虫对目前用于治疗莫桑比克非复杂性疟疾的抗疟药物的反应有关。本综述综合了自基于青蒿素的联合疗法(ACTs)引入后(2006年)至2024年6月在莫桑比克开展的已发表研究中收集的数据,突出了莫桑比克各地这些基因中突变的有无情况。我们旨在绘制这些分子标记在全国的流行情况和分布,以助力制定有针对性的干预措施,维持莫桑比克疟疾治疗的疗效。使用了四个数据库来检索文章:PubMed、Science Direct、Scopus和谷歌学术。检索策略共识别出132项涉及疟疾和抗疟药物耐药性的研究。其中,112项因各种原因被排除,最终有20项研究纳入本综述。儿童和孕妇是各类抗疟药物研究中的主要目标群体。大多数研究(87.5%)在马普托省和加扎省进行。报告的主要等位基因是CVMNK,在最新数据中,大多数患者中发现的是其野生型形式。基因中突变的低流行率表明ACTs的有效性。在中,尼亚萨省和太特省仅报告了A578S突变。在莫桑比克南部开展的研究中观察到了CNV,基因的频率为1.1 - 5.1%,基因的频率为1.1 - 3.4%。本综述表明,与疟疾耐药性相关的分子标记在莫桑比克各省之间存在相当大的差异,马普托省和加扎省可获取的最新数据最多。相比之下,赞比西亚省和伊尼扬巴内省等省份关于几个基因的数据有限,而楠普拉省则缺乏所有耐药性标记的数据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8314/11728251/ce7dd953ce02/ijms-25-13645-g001.jpg

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