Genomic epidemiology of Mycobacterium tuberculosis in Santa Catarina, Southern Brazil

Mirela Verza,Marcos André Schorner,Afrânio Kritski,Richard Steiner Salvato,Darcita Buerger Rovaris,Taiane Freitas Medeiros,Isabel Portugal,Maria Luiza Bazzo,Hanalydia De Melo Machado,João Perdigão,Miguel Viveiros,Fernando Hartmann Barazzetti,Mara Cristina Scheffer

doi:10.1038/s41598-020-69755-9

Abstract

Mycobacterium tuberculosis (M.tb), the pathogen responsible for tuberculosis (TB) poses as the major cause of death among infectious diseases. The knowledge about the molecular diversity of M.tb enables the implementation of more effective surveillance and control measures and, nowadays, Whole Genome Sequencing (WGS) holds the potential to produce high-resolution epidemiological data in a high-throughput manner. Florianópolis, the state capital of Santa Catarina (SC) in south Brazil, shows a high TB incidence (46.0/100,000). Here we carried out a WGS-based evaluation of the M.tb strain diversity, drug-resistance and ongoing transmission in the capital metropolitan region. Resistance to isoniazid, rifampicin, streptomycin was identified respectively in 4.0% (n = 6), 2.0% (n = 3) and 1.3% (n = 2) of the 151 studied strains by WGS. Besides, resistance to pyrazinamide and ethambutol was detected in 0.7% (n = 1) and reistance to ethionamide and fluoroquinolone (FQ) in 1.3% (n = 2), while a single (0.7%) multidrug-resistant (MDR) strain was identified. SNP-based typing classified all isolates into M.tb Lineage 4, with high proportion of sublineages LAM (60.3%), T (16.4%) and Haarlem (7.9%). The average core-genome distance between isolates was 420.3 SNPs, with 43.7% of all isolates grouped across 22 genomic clusters thereby showing the presence of important ongoing TB transmission events. Most clusters were geographically distributed across the study setting which highlights the need for an urgent interruption of these large transmission chains. The data conveyed by this study shows the presence of important and uncontrolled TB transmission in the metropolitan area and provides precise data to support TB control measures in this region.

Highlights

Mycobacterium tuberculosis (M.tb), the pathogen responsible for tuberculosis (TB) poses as the major cause of death among infectious diseases
Two classical examples of such studies are those conducted in San Francisco and New York in the late 1980s and early 1990s that enabled the correlation of specific ethnicities, drug resistance and/or residence in specific areas with recent TB transmission as assessed by genetic clustering based on profiles obtained with Restriction Fragment Length Polymorphisms with IS61106,7
The study encompasses 151 patients diagnosed with TB that started on anti-TB treatment between May 2014 and May 2016 in the metropolitan area

Summary

Introduction

Mycobacterium tuberculosis (M.tb), the pathogen responsible for tuberculosis (TB) poses as the major cause of death among infectious diseases. Whole Genome Sequencing (WGS) has emerged as the leading typing strategy to study the dissemination and transmission dynamics at a genome-wide SNP-based resolution that clearly outperforms classical typing methods and, coupled with molecular evolutionary approaches, holds the potential to retrace the evolutionary history of locally circulating s trains[12,13] This level of resolution has enabled the reconstruction of the microevolutionary trajectory of circulating extensively drug resistant strains in Portugal and South Africa along with the breakdown into genomic clusters that are proposed to reflect epidemiological links between p atients[14,15,16].

Methods

Results

Discussion

Conclusion