Genomic epidemiology of Mycobacterium tuberculosis in Santa Catarina, Southern Brazil

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.

Genomic-based surveillance reveals high ongoing transmission of multi-drug-resistant Mycobacterium tuberculosis in Southern Brazil

“…As characterized previously by recent studies in the region, the population structure of M. tuberculosis is mainly composed of LAM and Haarlem strains [ 4 , 27 ]. The same predominance of LAM strains occurs in the bordering state of Santa Catarina [35] , despite predominance of the 4.3.3 sublineage in the neighbouring state compared with predominance of the 4.3.4.2 sublineage observed in the present study. As well as being able to determine the sublineage of strains not classified by spoligotyping, SNP typing was also able to reclassify a large set of strains previously defined as T sublineage into more plausible sublineages based on their spoligotype pattern.…”

“…Overall, the estimated recent transmission rate of 55.1% among the 305 studied samples, which is higher than that registered in the bordering state of Santa Catarina [35] (mainly susceptible strains) and other regions with a high burden of TB [37] and MDR-TB [38] , shows that important transmission chains are feeding the ongoing transmission in the region. However, the most worrying fact revealed in this study concerns MDR strains, 73.4% of which were grouped in genomic clusters.…”

Detection of Mutations and Genotyping of Drug-Resistant Mycobacterium Tuberculosis Strains Isolated From Patients in Rural Eastern Cape Province

“…The findings of this study supported this assertion, demonstrating mutations at S315T linked with elevated levels of drug resistance to INH. A similar trend of mutation in codon S315T of katG gene have been reported in other countries including Zambia and Brazil [9,29]. Mutations in katG occurred only in codon agc/acc S315Tb in this study but the study of Jagielski et al [30] found that mutations occurred in eleven other codons.…”

Distribution and Current State of Molecular Genetic Characterization in Pathogenic Free-Living Amoebae

“…On the other hand, genomic epidemiology is also applied to understand other types of diseases, mainly those caused by Escherichia coli [ 153 , 154 ], Shigella spp. [ 155 ], Klebsiella pneumoniae [ 156 ], Corynebacterium diphtheriae [ 157 ], Staphylococcus aureus [ 154 , 158 ], Enterococcus faecalis [ 154 ], and Mycobacterium tuberculosis [ 159 ]. Although this discipline is more developed in bacteria and now in viruses, we can find extensive reports on emerging fungal pathogens [ 160 , 161 , 162 , 163 , 164 ] describing antifungal resistance mechanisms or shared synteny among geographically diverse species.…”