New insights on tuberculosis transmission dynamics and drug susceptibility profiles among the prison population in Southern Brazil based on whole-genome sequencing

ABSTRACT Background: The rate of tuberculosis (TB) infection among the prison population (PP) in Brazil is 28 times higher than that in the general population, and prison environment favors the spread of TB. Objective: To describe TB transmission dynamics and drug resistance profiles in PP using whole-genome sequencing (WGS). Methods: This was a retrospective study of Mycobacterium tuberculosis cultivated from people incarcerated in 55 prisons between 2016 and 2019; only one isolate per prisoner was included. Information about movement from one prison to another was tracked. Clinical information was collected, and WGS was performed on isolates obtained at the time of TB diagnosis. Results: Among 134 prisoners included in the study, we detected 16 clusters with a total of 58 (43%) cases of M. tuberculosis. Clusters ranged from two to seven isolates with five or fewer single nucleotide polymorphism (SNP) differences, suggesting a recent transmission. Six (4.4%) isolates were resistant to at least one anti-TB drug. Two of these clustered together and showed resistance to rifampicin, isoniazid, and fluoroquinolones, with 100% concordance between WGS and phenotypic drug-susceptibility testing. Prisoners with clustered isolates had a high amount of movement between prisons (two to eight moves) during the study period. Conclusions: WGS demonstrated the recent transmission of TB within prisons in Brazil. The high movement among prisoners seems to be related to the transmission of the same M. tuberculosis strain within the prison system. Screening for TB before and after the movement of prisoners using rapid molecular tests could play a role in reducing transmission.

Molecular epidemiology of Mycobacterium tuberculosis in Brazil before the whole genome sequencing era: a literature review

Molecular-typing can help in unraveling epidemiological scenarios and improvement for disease control strategies. A literature review of Mycobacterium tuberculosis transmission in Brazil through genotyping on 56 studies published from 1996-2019 was performed. The clustering rate for mycobacterial interspersed repetitive units - variable tandem repeats (MIRU-VNTR) of 1,613 isolates were: 73%, 33% and 28% based on 12, 15 and 24-loci, respectively; while for RFLP-IS6110 were: 84% among prison population in Rio de Janeiro, 69% among multidrug-resistant isolates in Rio Grande do Sul, and 56.2% in general population in São Paulo. These findings could improve tuberculosis (TB) surveillance and set up a solid basis to build a database of Mycobacterium genomes.

Mycobacterium tuberculosis spoligotypes and drug-resistant characterization from Beira compared to genotypes circulating in Mozambique

Abstract INTRODUCTION Mozambique is one of three countries with high prevalence of tuberculosis (TB), TB/human immunodeficiency virus coinfection, and multidrug-resistant TB. We aimed to describe Mycobacterium tuberculosis spoligotypes circulating among drug resistant (DR) strains from Beira, Mozambique comparing them with genotypes in the country. METHODS: We performed spoligotyping of 79 M. tuberculosis suspected of DR-TB compared all spoligotype patterns published on the international database and PubMed. RESULTS: Both in Beira and Mozambique (n=578), the main clades were Latin-American-Mediterranean, East-African-Indian, Beijing and T, with no extensively DR TB cases. CONCLUSIONS: Beira and Mozambique share the same population genetic structure of M. tuberculosis.

A predictive score followed by nucleic acid amplification for adult tuberculous meningitis diagnosis in Southern Brazil.

From 2012 to 2013, 300 adults under investigation of tuberculous meningitis (TBM) were tested with polymerase chain reaction (PCR) in central spinal fluid (CSF), followed by TBM score calculation. There were 33(11%) confirmed TBM cases based on clinical findings, CSF-culture; biopsy/necropsy exams and clinical improvement after tuberculosis specific treatment. Other 267 adults were classified as non-TBM. Based on the original score there were 143 possible cases (6≤score≤11) and 20(60.6%) out of 33 TBM; among 27 probable TBM (score≥12) there were 13/33 (39.4%) confirmed cases. The CSF-PCR detected 48% (16/33) of TBM. Based on these findings, a new cut-off point was proposed to differentiate probable (score≥10) from possible (6≤score≤9) TBM. After score adjustment, there were 61 probable TBM with 26/33 (78.8%) TBM, and among the 109 possible TBM there were 7/33(21.2%) confirmed cases. In both systems, there were 130 non-TBM (score≤5) and no confirmed TBM. The association of adjusted score (≥10) and CSF-PCR showed high sensitivity (90.9%) and specificity (86.9%), positive and negative predictive value of 46.2% and 98.9%, respectively. The combination of CSF-PCR and TBM score is a useful tool for the management of adults under investigation of TBM, but the best cut-off point may need local/regional adjustments.