Leishmania spp. genetic factors associated with cutaneous leishmaniasis antimony pentavalent drug resistance: a systematic review.

IF 2.5 4区医学 Q2 PARASITOLOGY

Memorias do Instituto Oswaldo Cruz Pub Date : 2024-09-02 eCollection Date: 2024-01-01 DOI:10.1590/0074-02760230240

Raphaela Lisboa Andrade Nery, Thaline Mabel Sousa Santos, Luana Leandro Gois, Aldina Barral, Ricardo Khouri, Caroline Alves Feitosa, Luciane Amorim Santos

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引用次数: 0

Abstract

Background: 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.

Objectives: This systematic review summarises the results of the literature evaluating parasite genetic markers possibly associated with resistance to pentavalent antimony in CL.

Methods: 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.

Findings: 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.

Main conclusions: 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.

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与皮肤利什曼病五价锑抗药性相关的利什曼属遗传因素：系统综述。

背景：利什曼病是由利什曼属寄生虫引起的一种被忽视的人畜共患疾病。治疗皮肤利什曼病（CL）的主要药物是甲氧苄氨嘧啶。这种药物具有强烈的不良反应和毒性，通常采用静脉注射，使治疗更加困难。利什曼病菌基因表达和基因组突变等因素似乎在耐药性的产生中起到了一定的作用：本系统综述总结了对可能与利什曼原虫对五价锑产生耐药性有关的寄生虫遗传标记进行评估的文献结果：本研究遵循 PRISMA 指南，纳入了 PubMed、SciELO 和 LILACS 数据库中的文章。纳入标准为：(i) 调查利什曼病基因组突变和/或基因表达变化与耐药性相关的研究；(ii) 使用锑药物治疗利什曼病的研究；(iii) 使用从患者体内分离的天然耐药菌株的研究。采用乔安娜-布里格斯研究所的批判性评估清单来评估文章质量和偏倚风险：共选取了 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 篇对同一样本的基因表达和基因组突变进行了研究。在基因表达方面，ABC转运蛋白家族的基因、AQP1、MRPA、TDR1和TRYR最常与耐药性相关。在一篇调查基因突变的文章中，HSP70（T579A）发生了突变，在三篇文章中，AQP1（A516C、G562A 和 G700A）发生了突变。本综述的局限性在于，在大多数纳入的研究中，寄生虫都是从培养的病变样本中分离出来的，而耐药性则是通过体外药敏试验来评估的。这些方法对于准确评估基因和检测治疗失败可能并不理想：主要结论：有必要开展进一步研究，评估利什曼原虫的遗传抗药性因素，以阐明寄生虫的作用机制，改善患者治疗和感染控制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Memorias do Instituto Oswaldo Cruz 医学-寄生虫学

CiteScore

5.00

自引率

3.60%

发文量

审稿时长

3-8 weeks

期刊介绍： Memórias do Instituto Oswaldo Cruz is a journal specialized in microbes & their vectors causing human infections. This means that we accept manuscripts covering multidisciplinary approaches and findings in the basic aspects of infectious diseases, e.g. basic in research in prokariotes, eukaryotes, and/or virus. Articles must clearly show what is the main question to be answered, the hypothesis raised, and the contribution given by the study. Priority is given to manuscripts reporting novel mechanisms and general findings concerning the biology of human infectious prokariotes, eukariotes or virus. Papers reporting innovative methods for diagnostics or that advance the basic research with these infectious agents are also welcome. It is important to mention what we do not publish: veterinary infectious agents research, taxonomic analysis and re-description of species, epidemiological studies or surveys or case reports and data re-analysis. Manuscripts that fall in these cases or that are considered of low priority by the journal editorial board, will be returned to the author(s) for submission to another journal.