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1. A Genome-Focused Investigation Reveals the Emergence of a Mycobacterium tuberculosis Strain Related to Multidrug-Resistant Tuberculosis in the Amazon Region of Brazil

Author

Emilyn Costa Conceição, Johannes Loubser, Arthur Emil dos Santos Guimarães, Abhinav Sharma, Liliana Kokusanilwa Rutaihwa, Anzaan Dippenaar, Richard Steiner Salvato, Ricardo José de Paula Souza e Guimarães, Maria Cristina da Silva Lourenço, Wandyra Araújo Barros, Ninarosa Calzavara Cardoso, Robin Mark Warren, Sebastien Gagneux, Beatriz Gilda Jegerhorn Grinsztejn, Philip Noel Suffys, and Karla Valéria Batista Lima

Subjects
tuberculosis, multidrug-resistant, whole-genome sequencing, genotype emergence, MIRU-VNTR, lineage, Biology (General), QH301-705.5
Abstract

A previous study in Pará, Northern Brazil, described a strain of Mycobacterium tuberculosis with a unique genotype (SIT2517/T1) associated with multidrug-resistant tuberculosis (MDR-TB). To improve our understanding of MDR-TB transmission dynamics of these strains within this region, we performed phenotypic and genotypic drug susceptibility testing (pDST/gDST), 24-loci mycobacterial interspersed repetitive units (MIRU-VNTR) genotyping, whole-genome sequencing (WGS) and geo-epidemiology analysis. Of the 28 SIT2517/T1 isolates, 19 (67.9%) could be genotyped by 24-loci MIRU-VNTR and 15 by WGS. All belonged to sublineage 4.1.1.3, distinct from other representative Lineage 4 isolates identified in Brazil. The MDR phenotype determined by pDST was confirmed by gDST, the latter also demonstrating the presence of additional mutations conferring pre-extensively drug-resistance (pre-XDR). Discrepancies between gDST and pDST were observed for pyrazinamide and fluoroquinolones. Thirteen out of 15 isolates analyzed by WGS were clustered when applying a 12 single nucleotide polymorphisms (SNPs) cutoff. The SIT2517/T1 isolates were distributed across the metropolitan regions of Belém and Collares municipalities, showing no geographic clustering. WGS-transmission network analysis revealed a high likelihood of direct transmission and the formation of two closely linked transmission chains. This study highlights the need to implement TB genomic surveillance in the Brazilian Amazon region.

Published
2024
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2. Analysis of potential household transmission events of tuberculosis in the city of Belem, Brazil

Author

Wandyra Araújo Barros, Emilyn Costa Conceição, Cristiane Cunha Frota, Sebastien Gagneux, Harrison Magdinier Gomes, Abhinav Sharma, Luana Nepomuceno Gondim Costa Lima, Yan Corrêa Rodrigues, Maria Luiza Lopes, Arthur Emil dos Santos Guimarães, Ismari Perini Furlaneto, Marília Lima da Conceição, Karla Valéria Batista Lima, Rafael Silva Duarte, Ninarosa Calzavara Cardoso, Liliana K. Rutaihwa, and Philip Noel Suffys

Subjects
0301 basic medicine, Male, Mycobacterium tuberculosis / patogenicidade, T?cnicas de Genotipagem / m?todos, Antitubercular Agents, 0302 clinical medicine, Drug Resistance, Multiple, Bacterial, Genotype, Tuberculosis, Multidrug-Resistant, Tuberculose / transmiss?o, 030212 general & internal medicine, Child, Family Characteristics, Molecular Epidemiology, biology, Sensibilidade e Especificidade, Resist?ncia Microbiana a Medicamentos, Middle Aged, 3. Good health, Infectious Diseases, Phenotype, Tandem Repeat Sequences, Female, Brazil, Microbiology (medical), Adult, DNA, Bacterial, Tuberculosis, Adolescent, 030106 microbiology, Immunology, Microbial Sensitivity Tests, Microbiology, Mycobacterium tuberculosis, 03 medical and health sciences, Minimum inhibitory concentration, Young Adult, Epidemiologia Molecular, Predictive Value of Tests, medicine, Humans, Genotyping, Aged, Bacteriological Techniques, Molecular epidemiology, Whole Genome Sequencing, Reproducibility of Results, Tuberculose / diagn?stico, medicine.disease, biology.organism_classification, Virology, Multiple drug resistance, Interspersed Repetitive Sequences, Infectious disease (medical specialty), Contact Tracing
Abstract

This work was funded by Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES), Institut d'Estudis Catalans (IEC) and the Swiss National Science Foundation (grants 310030_166687 and IZRJZ3_164171). Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Go?s. Rio de Janeiro, RJ, Brazil. Universidade do Estado do Par?. Programa de P?s-gradua??o em Biologia Parasit?ria na Amaz?nia. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Universidade do Estado do Par?. Programa de P?s-gradua??o em Biologia Parasit?ria na Amaz?nia. Bel?m, PA, Brazil. Universidade do Estado do Par?. Programa de P?s-gradua??o em Biologia Parasit?ria na Amaz?nia. Bel?m, PA, Brazil. Universidade do Estado do Par?. Programa de P?s-gradua??o em Biologia Parasit?ria na Amaz?nia. Bel?m, PA, Brazil. Universidade Federal do Par?. Hospital Universit?rio Jo?o de Barros Barreto. Bel?m, PA, Brazil. Universidade Federal do Par?. Hospital Universit?rio Jo?o de Barros Barreto. Bel?m, PA, Brazil. University of Delhi. Delhi College of Engineering. New Delhi, India. Universidade do Estado do Par?. Programa de P?s-gradua??o em Biologia Parasit?ria na Amaz?nia. Bel?m, PA, Brazil / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Funda??o Oswaldo Cruz. Instituto Oswaldo Cruz. Laborat?rio de Biologia Molecular Aplicada as Micobact?rias, Rio de Janeiro, RJ, Brazil. Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Go?s. Rio de Janeiro, RJ, Brazil. Universidade Federal do Cear?. Departamento de Patologia e Medicina Legal. Fortaleza, CE, Brazil. Swiss Tropical & Public Health Institute. Basel, Switzerland / University of Basel. Basel, Switzerland. Swiss Tropical & Public Health Institute. Basel, Switzerland / University of Basel. Basel, Switzerland. Funda??o Oswaldo Cruz. Instituto Oswaldo Cruz. Laborat?rio de Biologia Molecular Aplicada as Micobact?rias, Rio de Janeiro, RJ, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Tuberculosis (TB) is an infectious disease with a higher risk for infection and disease among household contacts (HHC). Here, we report a molecular epidemiology-based approach to study disease transmission and the genetic characteristics of Mycobacterium tuberculosis (Mtb) strains among HHC in the city of Belem, the capital of the state of Para in north Brazil. The study included 63 TB patients belonging to 26 HHC groups (HHC1 to HHC26). Spoligotyping and 24-loci Mycobacterial Interspersed Repetitive Unit - Variable Number of Tandem Repeat (MIRU-VNTR) revealed indistinguishable bacterial genotypes among 26 patients in 14 (53.8%) HHC groups. Drug susceptibility testing (DST) revealed that 45 (71.4%) of the Mtb isolates were multidrug resistant. The major cluster composed of isolates from five HHCs and on three of these, whole genome sequencing (WGS) was performed confirming their high genetic similarity. These results pinpoint the need for improved vigilance for TB control in households in the city of Bel?m. When comparing WGS versus phenotypic resistance detection methods as DST and Minimum Inhibitory Concentration (MIC) our data suggest that depending on the colonies selection, results may present variation.

Published
2018

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