title: Clinical evaluation of tuberculosis viability microscopy for assessing treatment response.
abstract: BACKGROUND
  It is difficult to determine whether early tuberculosis treatment is effective in reducing the infectiousness of patients' sputum, because culture takes weeks and conventional acid-fast sputum microscopy and molecular tests cannot differentiate live from dead tuberculosis.
  
  
  METHODS
  To assess treatment response, sputum samples (n=124) from unselected patients (n=35) with sputum microscopy-positive tuberculosis were tested pretreatment and after 3, 6, and 9 days of empiric first-line therapy. Tuberculosis quantitative viability microscopy with fluorescein diacetate, quantitative culture, and acid-fast auramine microscopy were all performed in triplicate.
  
  
  RESULTS
  Tuberculosis quantitative viability microscopy predicted quantitative culture results such that 76% of results agreed within ±1 logarithm (rS=0.85; P<.0001). In 31 patients with non-multidrug-resistant (MDR) tuberculosis, viability and quantitative culture results approximately halved (both 0.27 log reduction, P<.001) daily. For patients with non-MDR tuberculosis and available data, by treatment day 9 there was a >10-fold reduction in viability in 100% (24/24) of cases and quantitative culture in 95% (19/20) of cases. Four other patients subsequently found to have MDR tuberculosis had no significant changes in viability (P=.4) or quantitative culture (P=.6) results during early treatment. The change in viability and quantitative culture results during early treatment differed significantly between patients with non-MDR tuberculosis and those with MDR tuberculosis (both P<.001). Acid-fast microscopy results changed little during early treatment, and this change was similar for non-MDR tuberculosis vs MDR tuberculosis (P=.6).
  
  
  CONCLUSIONS
  Tuberculosis quantitative viability microscopy is a simple test that within 1 hour predicted quantitative culture results that became available weeks later, rapidly indicating whether patients were responding to tuberculosis therapy.
authors.affiliation: Innovation for Health and Development (IFHAD), Laboratory for Research and Development, Universidad Peruana Cayetano Heredia, Lima, Peru Infectious Diseases and Immunity and Wellcome Trust Centre for global Health Research, Imperial College London, United Kingdom.
authors.forename: Sumona
authors.initials: S
authors.lastname: Datta
authors.affiliation: Innovation for Health and Development (IFHAD), Laboratory for Research and Development, Universidad Peruana Cayetano Heredia, Lima, Peru Innovacion por la Salud y el Desarollo (IPSYD), Asociación Benéfica Prisma, Lima, Peru.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Sherman
authors.affiliation: Innovation for Health and Development (IFHAD), Laboratory for Research and Development, Universidad Peruana Cayetano Heredia, Lima, Peru Innovacion por la Salud y el Desarollo (IPSYD), Asociación Benéfica Prisma, Lima, Peru.
authors.forename: Marjory A
authors.initials: MA
authors.lastname: Bravard
authors.affiliation: Infectious Diseases and Immunity and Wellcome Trust Centre for global Health Research, Imperial College London, United Kingdom.
authors.forename: Teresa
authors.initials: T
authors.lastname: Valencia
authors.affiliation: Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Gilman
authors.affiliation: Innovation for Health and Development (IFHAD), Laboratory for Research and Development, Universidad Peruana Cayetano Heredia, Lima, Peru Infectious Diseases and Immunity and Wellcome Trust Centre for global Health Research, Imperial College London, United Kingdom.
authors.forename: Carlton A
authors.initials: CA
authors.lastname: Evans
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D001431:Bacteriological Techniques / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D050296:Microbial Viability / Q000187:drug effects*; D008853:Microscopy / Q000379:methods*; D013183:Sputum / Q000382:microbiology; D013997:Time Factors; D014376:Tuberculosis / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents
keywords: early bactericidal activity; fluorescein diacetate; multidrug-resistant tuberculosis; viability stain; vital stain tuberculosis