Fundação Oswaldo Cruz-Fiocruz, Instituto Gonçalo Moniz, Salvador, BA, Brasil.
Universidade Federal da Bahia, Faculdade de Medicina, Programa de Pós-Graduação em Ciências da Saúde, Salvador, BA, Brasil.
Mem Inst Oswaldo Cruz. 2024 Sep 2;119:e230240. doi: 10.1590/0074-02760230240. eCollection 2024.
Leishmaniasis is a neglected zoonosis caused by parasites of Leishmania spp. The main drug used to treat cutaneous leishmaniasis (CL) is the antimoniate of meglumine. This drug, which has strong adverse and toxic effects, is usually administered intravenously, further complicating the difficult treatment. Factors such as Leishmania gene expression and genomic mutations appear to play a role in the development of drug resistance.
This systematic review summarises the results of the literature evaluating parasite genetic markers possibly associated with resistance to pentavalent antimony in CL.
This study followed PRISMA guidelines and included articles from PubMed, SciELO, and LILACS databases. Inclusion criteria were studies that (i) investigated mutations in the genome and/or changes in gene expression of Leishmania associated with treatment resistance; (ii) used antimony drugs in the therapy of CL; (iii) used naturally resistant strains isolated from patients. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess article quality and risk of bias.
A total of 23 articles were selected, of which 18 investigated gene expression and nine genomic mutations. Of these 23 articles, four examined gene expression and genomic mutations in the same samples. Regarding gene expression, genes from the ABC transporter protein family, AQP1, MRPA, TDR1 and TRYR were most frequently associated with drug resistance. In one of the articles in which mutations were investigated, a mutation was found in HSP70 (T579A) and in three articles mutations were found in AQP1 (A516C, G562A and G700A). A limitation of this review is that in most of the included studies, parasites were isolated from cultured lesion samples and drug resistance was assessed using in vitro drug susceptibility testing. These approaches may not be ideal for accurate genetic evaluation and detection of treatment failure.
The development of further studies to evaluate the genetic resistance factors of Leishmania spp. is necessary to elucidate the mechanisms of the parasite and improve patient treatment and infection control.
利什曼病是一种由利什曼原虫属寄生虫引起的被忽视的动物源性传染病。用于治疗皮肤利什曼病（CL）的主要药物是葡甲胺锑。这种药物具有强烈的不良反应和毒性，通常通过静脉注射给药，这进一步增加了治疗的难度。利什曼原虫基因表达和基因组突变等因素似乎在耐药性的发展中起作用。
本系统综述总结了评估寄生虫遗传标记物与 CL 中五价锑耐药性可能相关的文献结果。
本研究遵循 PRISMA 指南，纳入了来自 PubMed、SciELO 和 LILACS 数据库的文章。纳入标准为：（i）研究与治疗耐药性相关的利什曼原虫基因组突变和/或基因表达变化的文章；（ii）使用抗锑药物治疗 CL 的文章；（iii）使用从患者中分离的天然耐药株的文章。使用 Joanna Briggs 研究所批判性评价清单评估文章质量和偏倚风险。
共选择了 23 篇文章，其中 18 篇研究了基因表达，9 篇研究了基因组突变。在这 23 篇文章中，有 4 篇同时研究了基因表达和基因组突变。在涉及基因表达的研究中，ABC 转运蛋白家族、AQP1、MRPA、TDR1 和 TRYR 基因最常与耐药性相关。在一项研究中发现 HSP70（T579A）突变，在另外三项研究中发现 AQP1 突变（A516C、G562A 和 G700A）。本综述的一个局限性是，在大多数纳入的研究中，寄生虫是从培养的病变样本中分离出来的，并且使用体外药物敏感性试验评估了药物耐药性。这些方法可能不适用于准确的遗传评估和治疗失败的检测。
有必要开展进一步的研究来评估利什曼原虫属的遗传耐药因素，以阐明寄生虫的机制，并改善患者的治疗和感染控制。
