title: Do we need to detect isoniazid resistance in addition to rifampicin resistance in diagnostic tests for tuberculosis?
abstract: BACKGROUND
  Multidrug-resistant tuberculosis (MDR-TB) is resistant to both rifampicin (RIF) and isoniazid (INH). Whereas many TB diagnostics detect RIF-resistance, few detect INH-monoresistance, which is common and may increase risk of acquired MDR-TB. Whether inclusion of INH-resistance in a first-line rapid test for TB would have an important impact on MDR-TB rates remains uncertain.
  
  
  METHODS
  WE DEVELOPED A TRANSMISSION MODEL TO EVALUATE THREE TESTS IN A POPULATION SIMILAR TO THAT OF INDIA: a rapid molecular test for TB, the same test plus RIF-resistance detection ("TB+RIF"), and detection of RIF and INH-resistance ("TB+RIF/INH"). Our primary outcome was the prevalence of INH-resistant and MDR-TB at ten years.
  
  
  RESULTS
  Compared to the TB test alone and assuming treatment of all diagnosed MDR cases, the TB+RIF test reduced the prevalence of MDR-TB among all TB cases from 5.5% to 3.8% (30.6% reduction, 95% uncertainty range, UR: 17-54%). Despite using liberal assumptions about the impact of INH-monoresistance on treatment outcomes and MDR-TB acquisition, expansion from TB+RIF to TB+RIF/INH lowered this prevalence only from 3.8% to 3.6% further (4% reduction, 95% UR: 3-7%) and INH-monoresistant TB from 15.8% to 15.1% (4% reduction, 95% UR: (-8)-19%).
  
  
  CONCLUSIONS
  When added to a rapid test for TB plus RIF-resistance, detection of INH-resistance has minimal impact on transmission of TB, MDR-TB, and INH-monoresistant TB.
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America ; McGill International TB Centre & Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada.
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Denkinger
authors.affiliation: McGill International TB Centre & Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada ; Respiratory Epidemiology & Clinical Research Unit, Montreal Chest Institute, Montreal, Montreal, Quebec, Canada.
authors.forename: Madhukar
authors.initials: M
authors.lastname: Pai
authors.affiliation: Department of Epidemiology, Bloomberg School of Public Health, Baltimore, Maryland, United States of America ; Center for Tuberculosis Research, Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: David W
authors.initials: DW
authors.lastname: Dowdy
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use; D003955:Diagnostic Tests, Routine; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D006801:Humans; D015994:Incidence; D007194:India / Q000453:epidemiology; D007538:Isoniazid / Q000494:pharmacology / Q000627:therapeutic use; D008826:Microbial Sensitivity Tests; D015233:Models, Statistical; D009026:Mortality; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D063868:Patient Outcome Assessment; D011159:Population Surveillance; D012293:Rifampin / Q000494:pharmacology / Q000627:therapeutic use; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology* / Q000635:transmission*
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin