Whole genomic sequencing as a tool for diagnosis of drug and multidrug-resistance tuberculosis in an endemic region in Mexico
Por:
Madrazo-Moya CF, Cancino-Muñoz I, Cuevas-Córdoba B, González-Covarrubias V, Barbosa-Amezcua M, Soberón X, Muñiz-Salazar R, Martínez-Guarneros A, Bäcker C, Zarrabal-Meza J, Sampieri-Ramirez C, Enciso-Moreno A, Lauzardo M, Comas I and Zenteno-Cuevas R
Publicada:
5 jun 2019
Ahead of Print:
5 jun 2019
Categoría:
Multidisciplinary
Resumen:
Background
Whole genome sequencing (WGS) has been proposed as a tool for diagnosing drug resistance in tuberculosis. However, reports of its effectiveness in endemic countries with important numbers of drug resistance are scarce. The goal of this study was to evaluate the effectiveness of this procedure in isolates from a tuberculosis endemic region in Mexico.
Methods
WGS analysis was performed in 81 tuberculosis positive clinical isolates with a known phenotypic profile of resistance against first-line drugs (isoniazid, rifampin, ethambutol, pyrazinamide and streptomycin). Mutations related to drug resistance were identified for each isolate; drug resistant genotypes were predicted and compared with the phenotypic profile. Genotypes and transmission clusters based on genetic distances were also characterized.
Findings
Prediction by WGS analysis of resistance against isoniazid, rifampicin, ethambutol, pyrazinamide and streptomycin showed sensitivity values of 84%, 96%, 71%, 75% and 29%, while specificity values were 100%, 94%, 90%, 90% and 98%, respectively. Prediction of multidrug resistance showed a sensitivity of 89% and specificity of 97%. Moreover, WGS analysis revealed polymorphisms related to second-line drug resistance, enabling classification of eight and two clinical isolates as pre- and extreme drug-resistant cases, respectively. Lastly, four lineages were identified in the population (L1, L2, L3 and L4). The most frequent of these was L4, which included 90% (77) of the isolates. Six transmission clusters were identified; the most frequent was TC6, which included 13 isolates with a L4.1.1 and a predominantly multidrug-resistant condition.
Conclusions
The results illustrate the utility of WGS for establishing the potential for prediction of resistance against first and second line drugs in isolates of tuberculosis from the region. They also demonstrate the feasibility of this procedure for use as a tool to support the epidemiological surveillance of drug-and multidrug-resistant tuberculosis.
Filiaciones:
Madrazo-Moya CF:
Instituto de Salud Pública, Universidad Veracruzana, Veracruz, México
Programa de Maestría en Ciencias de la Salud, Instituto de Ciencias de la Salud, Universidad Veracruzana, Veracruz, México
Cancino-Muñoz I:
Biomedicine Institute of Valencia IBV-CSIC, Valencia, Spain
Cuevas-Córdoba B:
Laboratorio de Farmacogenómica, Instituto Nacional de Medicina Genómica, Ciudad de México, México
González-Covarrubias V:
Laboratorio de Farmacogenómica, Instituto Nacional de Medicina Genómica, Ciudad de México, México
Barbosa-Amezcua M:
Laboratorio de Farmacogenómica, Instituto Nacional de Medicina Genómica, Ciudad de México, México
Soberón X:
Laboratorio de Farmacogenómica, Instituto Nacional de Medicina Genómica, Ciudad de México, México
Muñiz-Salazar R:
Laboratorio de Epidemiología y Ecología y Molecular, Escuela de Ciencias de la Salud, Universidad Autónoma de Baja California, Ensenada, Baja California, México
Martínez-Guarneros A:
Laboratorio de Micobacterias, Instituto Nacional de Diagnóstico y Referencia Epidemiológica, Ciudad de México, México
Bäcker C:
Laboratorio de Micobacterias, Instituto Nacional de Diagnóstico y Referencia Epidemiológica, Ciudad de México, México
Zarrabal-Meza J:
Laboratorio Estatal de Salud Pública, Secretaria de Salud, Veracruz, México
Sampieri-Ramirez C:
Instituto de Salud Pública, Universidad Veracruzana, Veracruz, México
Enciso-Moreno A:
Unidad de Investigación Biomédica de Zacatecas, IMSS, Zacatecas, Zacatecas, México
Lauzardo M:
Division of Infectious Diseases and Global Medicine, College of Medicine, University of Florida, Gainesville, Florida, United States of America
:
Biomedicine Institute of Valencia IBV-CSIC, Valencia, Spain
CIBER of Epidemiology and Public Health, Madrid, Spain
Zenteno-Cuevas R:
Instituto de Salud Pública, Universidad Veracruzana, Veracruz, México
Programa de Maestría en Ciencias de la Salud, Instituto de Ciencias de la Salud, Universidad Veracruzana, Veracruz, México
Open Access
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