Evangelina Inacio Namburete1, Anzaan Dippenaar2, Emilyn Costa Conceição3, Cinara Feliciano4, Margarida Maria Passeri do Nascimento5, Kamila Chagas Peronni6, Wilson Araújo Silva7, Josefo João Ferro8, Lee H Harrison9, Robin Mark Warren10, Valdes Roberto Bollela11. 1. Mycobacteria Research Lab at Clinics Hospital from Ribeirão Preto Medical School, University of São Paulo (FMRP-USP), Brazil; Faculty of Health Science, Catholic University of Mozambique, Beira, Mozambique. Electronic address: evanamburete@gmail.com. 2. DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa. Electronic address: adippenaar@sun.ac.za. 3. Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373 - bloco i - Cidade Universitária, Rio de Janeiro, RJ, 21941-970, Brazil. Electronic address: emilyncosta@gmail.com. 4. Mycobacteria Research Lab at Clinics Hospital from Ribeirão Preto Medical School, University of São Paulo (FMRP-USP), Brazil. Electronic address: cinara.feliciano@gmail.com. 5. Mycobacteria Research Lab at Clinics Hospital from Ribeirão Preto Medical School, University of São Paulo (FMRP-USP), Brazil. Electronic address: mpasseri@fmrp.usp.br. 6. Center for Medical Genomics, Clinics Hospital at Ribeirão Preto Medical School, University of São Paulo (FMRP-USP), Brazil. Electronic address: kcperoni@gmail.com. 7. Center for Medical Genomics, Clinics Hospital at Ribeirão Preto Medical School, University of São Paulo (FMRP-USP), Brazil; Department of Genetics at Ribeirão Preto Medical School, University of São Paulo (FMRP-USP), Brazil. Electronic address: wilsonjr@usp.br. 8. Faculty of Health Science, Catholic University of Mozambique, Beira, Mozambique. Electronic address: josefojoaoferro@yahoo.com.br. 9. Infectious Diseases Epidemiology Research Unit, University of Pittsburgh, Pittsburgh, USA. Electronic address: lharriso@edc.pitt.edu. 10. DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa. Electronic address: rw1@sun.ac.za. 11. Mycobacteria Research Lab at Clinics Hospital from Ribeirão Preto Medical School, University of São Paulo (FMRP-USP), Brazil. Electronic address: vbollela@gmail.com.
Abstract
BACKGROUND: Mozambique is a high-burden tuberculosis (TB) country where TB/HIV co-infection and drug resistant TB (DR-TB) incidence is increasing. Whole genome sequencing (WGS) comprehensively describes the molecular epidemiology of TB, allows prediction of DR-TB phenotypes, lineages strains identification and better understanding of transmission chains. OBJECTIVE: To describe genetic diversity of DR-TB Mycobacterium tuberculosis isolated in Beira, Mozambique. METHODS: Descriptive cross-sectional study with 35 M. tuberculosis isolates, resistant to at least one first-line drug on molecular drug-susceptibility tests (DST). Variant identification, DR prediction and phylogenetic analysis provided by WGS, drug-susceptibility pattern compared to line-probe assay (LPA): Genotype MTBDRTMplus and MTBDRTMsl. FINDINGS: Lineage 4 (L4) was the most prevalent: 25 (71.4%) isolates; 5 (14.3%) L1 and 5 (14.3%) L2. WGS showed 33/35 (94.3%) isolates resistant to at least one drug, two pan-susceptible isolates that were previously diagnosed as DR-TB with genotype MTBDRplus. Concordance between WGS and LPA: 88.6% for isoniazid (INH), 85.7% to rifampicin (RPM), 91.4% for quinolones and 100% to second line injectable drugs. There were three possible TB transmission chains, 10 strains showing recent transmission. CONCLUSION: WGS provided reliable information about the most frequent lineages related to DR-TB in Beira, Mozambique: L4.3 (LAM), L2 (Beijing) and L1 (EAI) and possible recent transmission chain.
BACKGROUND: Mozambique is a high-burden tuberculosis (TB) country where TB/HIV co-infection and drug resistant TB (DR-TB) incidence is increasing. Whole genome sequencing (WGS) comprehensively describes the molecular epidemiology of TB, allows prediction of DR-TB phenotypes, lineages strains identification and better understanding of transmission chains. OBJECTIVE: To describe genetic diversity of DR-TB Mycobacterium tuberculosis isolated in Beira, Mozambique. METHODS: Descriptive cross-sectional study with 35 M. tuberculosis isolates, resistant to at least one first-line drug on molecular drug-susceptibility tests (DST). Variant identification, DR prediction and phylogenetic analysis provided by WGS, drug-susceptibility pattern compared to line-probe assay (LPA): Genotype MTBDRTMplus and MTBDRTMsl. FINDINGS: Lineage 4 (L4) was the most prevalent: 25 (71.4%) isolates; 5 (14.3%) L1 and 5 (14.3%) L2. WGS showed 33/35 (94.3%) isolates resistant to at least one drug, two pan-susceptible isolates that were previously diagnosed as DR-TB with genotype MTBDRplus. Concordance between WGS and LPA: 88.6% for isoniazid (INH), 85.7% to rifampicin (RPM), 91.4% for quinolones and 100% to second line injectable drugs. There were three possible TB transmission chains, 10 strains showing recent transmission. CONCLUSION: WGS provided reliable information about the most frequent lineages related to DR-TB in Beira, Mozambique: L4.3 (LAM), L2 (Beijing) and L1 (EAI) and possible recent transmission chain.
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