title: Detection of multidrug-resistant Mycobacterium tuberculosis strains isolated in Brazil using a multimarker genetic assay for katG and rpoB genes.
abstract: Multidrug-resistant tuberculosis (MDRTB) is a serious world health problem that limits public actions to control tuberculosis, because the most used anti-tuberculosis first-line drugs fail to stop mycobacterium spread. Consequently, a quick detection through molecular diagnosis is essential to reduce morbidity and medical costs. Despite the availability of several molecular-based commercial-kits to diagnose multidrug-resistant tuberculosis, their diagnostic value might diverge worldwide since Mycobacterium tuberculosis genetic variability differs according to geographic location. Here, we studied the predictive value of four common mycobacterial mutations in strains isolated from endemic areas of Brazil. Mutations were found at the frequency of 41.9% for katG, 25.6% for inhA, and 69.8% for rpoB genes in multidrug-resistant strains. Multimarker analysis revealed that combination of only two mutations ("katG/S315T+rpoB/S531L") was a better surrogate of multidrug-resistant tuberculosis than single-marker analysis (86% sensitivity vs. 62.8%). Prediction of multidrug-resistant tuberculosis was not improved by adding a third or fourth mutation in the model. Therefore, rather than using diagnostic kits detecting several mutations, we propose a simple dual-marker panel to detect multidrug-resistant tuberculosis, with 86% sensitivity and 100% specificity. In conclusion, this approach (previous genetic study+analysis of only prevalent markers) would considerably decrease the processing costs while retaining diagnostic accuracy.
authors.affiliation: Laboratório de Farmacogenômica e Epidemiologia Molecular (LAFEM), Universidade Estadual de Santa Cruz (UESC), Ilhéus, BA, Brazil.
authors.forename: Luita Nice
authors.initials: LN
authors.lastname: Café Oliveira
authors.affiliation: Laboratório de Farmacogenômica e Epidemiologia Molecular (LAFEM), Universidade Estadual de Santa Cruz (UESC), Ilhéus, BA, Brazil.
authors.forename: Jairo da Silva
authors.initials: Jda S
authors.lastname: Muniz-Sobrinho
authors.affiliation: Instituto Nacional de Ciência e Tecnologia em Medicina Molecular (INCT-MM), Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil; Faculdade Infórium de Tecnologia, Mestrado em Tecnologia da Informação Aplicada a Biologia Computacional, Belo Horizonte, MG, Brazil.
authors.forename: Luiz Alexandre
authors.initials: LA
authors.lastname: Viana-Magno
authors.affiliation: Departamento de Ciências Biológicas, Universidade Estadual de Santa Cruz (UESC), Ilhéus, BA, Brazil.
authors.forename: Sônia Cristina
authors.initials: SC
authors.lastname: Oliveira Melo
authors.affiliation: Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso (UFMT), Cuiabá, MT, Brazil.
authors.forename: Antonio
authors.initials: A
authors.lastname: Macho
authors.affiliation: Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso (UFMT), Cuiabá, MT, Brazil. Electronic address: fabriciorios@yahoo.com.
authors.forename: Fabrício
authors.initials: F
authors.lastname: Rios-Santos
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D002374:Catalase / Q000235:genetics*; D004269:DNA, Bacterial; D012321:DNA-Directed RNA Polymerases / Q000235:genetics*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012293:Rifampin / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D018088:Tuberculosis, Multidrug-Resistant / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D005819:Genetic Markers; C505805:rpoB protein, Mycobacterium tuberculosis; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis; D012321:DNA-Directed RNA Polymerases; D007538:Isoniazid; D012293:Rifampin
keywords: Biomarkers; Diagnosis; Multidrug-resistance; Mycobacterium tuberculosis