莫桑比克贝拉地区耐多药结核分枝杆菌菌株的系统基因组学评估。

Phylogenomic assessment of drug-resistant Mycobacterium tuberculosis strains from Beira, Mozambique.

机构信息

Mycobacteria Research Lab at Clinics Hospital from Ribeirão Preto Medical School, University of São Paulo (FMRP-USP), Brazil; Faculty of Health Science, Catholic University of Mozambique, Beira, Mozambique.

DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa.

出版信息

Tuberculosis (Edinb). 2020 Mar;121:101905. doi: 10.1016/j.tube.2020.101905. Epub 2020 Jan 29.

DOI:10.1016/j.tube.2020.101905

PMID:32063558

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9300053/

Abstract

BACKGROUND

Mozambique is a high-burden tuberculosis (TB) country where TB/HIV co-infection and drug resistant TB (DR-TB) incidence is increasing. Whole genome sequencing (WGS) comprehensively describes the molecular epidemiology of TB, allows prediction of DR-TB phenotypes, lineages strains identification and better understanding of transmission chains.

OBJECTIVE

To describe genetic diversity of DR-TB Mycobacterium tuberculosis isolated in Beira, Mozambique.

METHODS

Descriptive cross-sectional study with 35 M. tuberculosis isolates, resistant to at least one first-line drug on molecular drug-susceptibility tests (DST). Variant identification, DR prediction and phylogenetic analysis provided by WGS, drug-susceptibility pattern compared to line-probe assay (LPA): Genotype MTBDRplus and MTBDRsl.

FINDINGS

Lineage 4 (L4) was the most prevalent: 25 (71.4%) isolates; 5 (14.3%) L1 and 5 (14.3%) L2. WGS showed 33/35 (94.3%) isolates resistant to at least one drug, two pan-susceptible isolates that were previously diagnosed as DR-TB with genotype MTBDRplus. Concordance between WGS and LPA: 88.6% for isoniazid (INH), 85.7% to rifampicin (RPM), 91.4% for quinolones and 100% to second line injectable drugs. There were three possible TB transmission chains, 10 strains showing recent transmission.

CONCLUSION

WGS provided reliable information about the most frequent lineages related to DR-TB in Beira, Mozambique: L4.3 (LAM), L2 (Beijing) and L1 (EAI) and possible recent transmission chain.

摘要

背景

莫桑比克是一个结核病（TB）负担沉重的国家，TB/HIV 合并感染和耐多药结核病（DR-TB）的发病率正在上升。全基因组测序（WGS）全面描述了 TB 的分子流行病学，可预测 DR-TB 表型、谱系菌株鉴定，并更好地了解传播链。

目的

描述莫桑比克贝拉分离的耐多药结核分枝杆菌（Mtb）的遗传多样性。

方法

对 35 株耐至少一种一线药物的分子药敏试验（DST）药物的 Mtb 分离株进行描述性横断面研究。WGS 提供的变异鉴定、DR 预测和系统发育分析、与线探针分析（LPA）的药敏模式比较：基因型 MTBDRplus 和 MTBDRsl。

结果

谱系 4（L4）最为常见：25 株（71.4%）；5 株（14.3%）L1 和 5 株（14.3%）L2。WGS 显示 33/35 株（94.3%）对至少一种药物耐药，两种全敏感株先前用基因型 MTBDRplus 诊断为 DR-TB。WGS 与 LPA 的一致性：异烟肼（INH）88.6%，利福平（RPM）85.7%，喹诺酮类 91.4%，二线注射用药物 100%。有三个可能的结核病传播链，10 株显示近期传播。