title: Detection of katG and inhA mutations to guide isoniazid and ethionamide use for drug-resistant tuberculosis.
abstract: Depending on the presence of mutations that determine isoniazid (INH) susceptibility (katG and inhA), Mycobacterium tuberculosis may be susceptible to high doses of INH or ethionamide (ETH).
  
  
  
  To describe the INH resistance profile and association of katG mutation with previous INH treatment and level of drug resistance based on rapid molecular drug susceptibility testing (DST) in southern Brazil and central Mozambique.
  
  
  
  Descriptive study of 311 isolates from Ribeirão Preto, São Paulo, Brazil (2011-2014) and 155 isolates from Beira, Mozambique (2014-2015). Drug resistance patterns and specific gene mutations were determined using GenoType(®) MTBDRplus.
  
  
  
  katG gene mutations were detected in 12/22 (54.5%) Brazilian and 32/38 (84.2%) Mozambican isolates. inhA mutations were observed in 9/22 (40.9%) isolates in Brazil and in 4/38 (10.5%) in Mozambique. Both katG and inhA mutations were detected in respectively 1/22 (5%) and 2/38 (5.2%). The difference in the frequency of katG mutations in Brazil and Mozambique was statistically significant (P = 0.04). katG mutations were present in 68.8% (33/48) of patients previously treated with INH and 31.2% (15/48) of patients without previous INH. This difference was not statistically significant (P = 0.223).
  
  
  
  INH mutations varied geographically; molecular DST can be used to guide and accelerate decision making in the use of ETH or high doses of INH.
authors.affiliation: Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: V R
authors.initials: VR
authors.lastname: Bollela
authors.affiliation: Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: E I
authors.initials: EI
authors.lastname: Namburete
authors.affiliation: Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: C S
authors.initials: CS
authors.lastname: Feliciano
authors.affiliation: Laboratório Nacional de Referencia da Tuberculose, Instituto Nacional de Saúde-Moçambique, Maputo, Mozambique.
authors.forename: D
authors.initials: D
authors.lastname: Macheque
authors.affiliation: Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: L H
authors.initials: LH
authors.lastname: Harrison
authors.affiliation: Servicio de Neumología, Hospital General de Gran Canaria Dr Negrin, Las Palmas, Spain; International Union Against Tuberculosis and Lung Disease, Paris, France.
authors.forename: J A
authors.initials: JA
authors.lastname: Caminero
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000235:genetics*; D001938:Brazil / Q000453:epidemiology; D002374:Catalase / Q000235:genetics*; D000066491:Clinical Decision-Making; D004252:DNA Mutational Analysis; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D005000:Ethionamide / Q000627:therapeutic use*; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use*; D008826:Microbial Sensitivity Tests; D009073:Mozambique / Q000453:epidemiology; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D010088:Oxidoreductases / Q000235:genetics*; D018579:Patient Selection; D011237:Predictive Value of Tests; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D010088:Oxidoreductases; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis; C085257:InhA protein, Mycobacterium; D005000:Ethionamide; D007538:Isoniazid