Comprehensive genomic surveillance reveals transmission profiles of extensively drug-resistant tuberculosis cases in Par��, Brazil.
Davi Josu�� Marcon, Abhinav Sharma, Alex Brito Souza, Rafaella Bonfim Barros, Valnete das Gra��as Dantas Andrade, Ricardo Jos�� de Paula Souza Guimar��es, Luana Nepomuceno Gondim Lima, L��cia Helena Martins Tavares Monteiro, Ana Judith Pires Garcia Quaresma, Layana Rufino Ribeiro, Philip Noel Suffys, Robin Mark Warren, Carlos Augusto Abreu Alberio, Karla Val��ria Batista Lima, Emilyn Costa Concei����o
Author Information
Davi Josu�� Marcon: Programa de P��s-Gradua����o em Biologia Parasit��ria na Amaz��nia, Bel��m, Brazil.
Abhinav Sharma: South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Alex Brito Souza: Programa de P��s-Gradua����o em Biologia Parasit��ria na Amaz��nia, Bel��m, Brazil.
Rafaella Bonfim Barros: Laborat��rio Central do Estado do Par��, Bel��m, Par��, Brazil.
Valnete das Gra��as Dantas Andrade: Laborat��rio Central do Estado do Par��, Bel��m, Par��, Brazil.
Ricardo Jos�� de Paula Souza Guimar��es: Se����o de Epidemiologia do Instituto Evandro Chagas, Ananindeua, Par��, Brazil.
Luana Nepomuceno Gondim Lima: Programa de P��s-Gradua����o em Biologia Parasit��ria na Amaz��nia, Bel��m, Brazil.
L��cia Helena Martins Tavares Monteiro: Secretaria de Estado da Sa��de do Par��, Bel��m, Par��, Brazil.
Ana Judith Pires Garcia Quaresma: Programa de P��s-Gradua����o em Biologia Parasit��ria na Amaz��nia, Bel��m, Brazil.
Layana Rufino Ribeiro: Se����o de Bacteriologia do Instituto Evandro Chagas, Ananindeua, Par��, Brazil.
Philip Noel Suffys: Laborat��rio de Biologia Molecular Aplicada a Micobact��rias, Instituto Oswaldo Cruz, Funda����o Oswaldo Cruz, Rio de Janeiro, Brazil.
Robin Mark Warren: South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Carlos Augusto Abreu Alberio: Hospital Universit��rio Jo��o de Barros Barreto, Ambulat��rio de Tuberculose Multiressistente, Universidade Federal do Par��, Bel��m, Par��, Brazil.
Karla Val��ria Batista Lima: Programa de P��s-Gradua����o em Biologia Parasit��ria na Amaz��nia, Bel��m, Brazil.
Emilyn Costa Concei����o: South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Bedaquiline, an antimicrobial used to treat drug-resistant tuberculosis (DR-TB), was introduced in Brazil in October 2021. Monitoring the emergence and transmission of DR-TB is crucial for implementing public health to control the spread of DR strains of . To measure its impact on the multi-drug treatment scheme in the state of Par��, we aimed to conduct genomic surveillance of DR-TB after Bedaquiline was introduced in Brazil. Individuals treated for DR-TB between October 2021 and December 2022, in the reference hospital to treat DR-TB cases from the state of Par��, were included in the study. Clinical and bacteriological information was obtained from the National Laboratory Management Environment and the Special TB Treatment Information System. Genomic DNA was extracted from bacterial cultures performed at the Par�� Central Laboratory (LACEN-PA). Whole-genome sequencing (WGS) was obtained using Illumina Nextera-XT and NextSeq 550 and genomes were analyzed using the MAGMA and TB-Profiler pipelines interpreted according to the World Health Organization (WHO) mutations catalog 2nd edition. Geoprocessing was performed based on the patient's residences. Cutoffs of 5-12 single nucleotide polymorphisms (SNPs) were used for transmission analysis. From the 103 patients reported as DR-TB, viable cultures were obtained from 67. Forty isolates were selected randomly for WGS. Among these, a mixed infection of L1 and L4 and a co-infection of and were observed. The genotypic drug susceptibility profile of TB stains (39/40) was as follows: sensitive (1/2, 5%), rifampicin mono-resistant (RR) (4/10%), isoniazid mono-resistant (1/2%), multidrug-resistant (MDR) (21/52%), extensively drug-resistant (XDR) (3/7%), pre-XDR (8/20%), and other (1/2%). Among the 38 isolates of strains without mixed infection, using a cutoff of 12 SNPs and suggestive of recent TB transmission, 14 (37%) were grouped into five clusters (C1-C5) and included RR (C5), MDR (C3, C4, C5), pre-XDR, and XDR (C2) strains. We recommend greater attention from the regional public health authorities to detect and track resistance to new drugs, especially in areas with pre-XDR and XDR cases. This is the first report on the detection and transmission of XDR-TB in Par��, Brazil, after the recent re-definition of XDR-TB by the WHO in 2021.
