title: The association between symptoms and microbiologically defined response to tuberculosis treatment.
abstract: BACKGROUND
  The lack of consistent associations between clinical outcomes and microbiological responses to therapy for some infectious diseases has raised questions about the adequacy of microbiological endpoints for tuberculosis treatment trials.
  
  
  OBJECTIVE
  To evaluate the association between symptoms and microbiological response to tuberculosis treatment.
  
  
  METHODS
  We performed a retrospective analysis of four clinical trials in which participants had culture-positive tuberculosis, standardized symptom assessment, and follow-up mycobacterial cultures. Two trials (studies 22 and 23) followed participants to identify recurrent tuberculosis; participants in studies 27 and 28 were only followed to treatment completion.
  
  
  RESULTS
  This analysis included 1,978 participants; 39 (2.0%) had culture-confirmed treatment failure, and 75 (3.9%) had culture-confirmed recurrence. Productive cough was associated with indices of increased mycobacterial burden at diagnosis (acid-fast smear grade, severity of radiographic abnormalities). Fever and sweats improved rapidly with treatment, whereas productive cough decreased more slowly and was present in 20% of visits after treatment completion. During treatment, study participants with productive cough more often had concurrent culture positivity compared with those without productive cough (studies 22 and 23: adjusted odds ratio, 1.80; 95% confidence interval [CI], 1.33-2.44). Finally, symptoms during the latter part of treatment and follow-up were associated with culture-confirmed treatment failure and recurrence in studies 22 and 23 (for cough: adjusted hazard ratio, 2.07; 95% CI, 1.23-3.49; for fever: adjusted hazard ratio, 5.05; 95% CI, 2.76-9.19).
  
  
  CONCLUSIONS
  There are consistent relationships between symptoms and microbiological indices of tuberculosis, including measures of mycobacterial burden at baseline, culture positivity during treatment, and time to culture-confirmed treatment failure and recurrence.
authors.affiliation: Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Craig M
authors.initials: CM
authors.lastname: Hales
authors.forename: Charles M
authors.initials: CM
authors.lastname: Heilig
authors.forename: Richard
authors.initials: R
authors.lastname: Chaisson
authors.forename: Chi Chiu
authors.initials: CC
authors.lastname: Leung
authors.forename: Kwok Chiu
authors.initials: KC
authors.lastname: Chang
authors.forename: Stefan V
authors.initials: SV
authors.lastname: Goldberg
authors.forename: Fred
authors.initials: F
authors.lastname: Gordin
authors.forename: John L
authors.initials: JL
authors.lastname: Johnson
authors.forename: Grace
authors.initials: G
authors.lastname: Muzanyi
authors.forename: Jussi
authors.initials: J
authors.lastname: Saukkonen
authors.forename: Andrew
authors.initials: A
authors.lastname: Vernon
authors.forename: M Elsa
authors.initials: ME
authors.lastname: Villarino
authors.forename: William J
authors.initials: WJ
authors.lastname: Burman
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001682:Biological Availability; D002986:Clinical Trials as Topic / Q000379:methods / Q000706:statistics & numerical data; D060085:Coinfection; D003371:Cough / Q000188:drug therapy / Q000382:microbiology; D005260:Female; D015658:HIV Infections / Q000453:epidemiology*; D006801:Humans; D008297:Male; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000302:isolation & purification; D010043:Outcome and Process Assessment, Health Care / Q000379:methods; D016016:Proportional Hazards Models; D011859:Radiography; D012008:Recurrence; D012189:Retrospective Studies; D012720:Severity of Illness Index; D063189:Symptom Assessment / Q000379:methods / Q000592:standards / Q000706:statistics & numerical data; D017211:Treatment Failure; D014376:Tuberculosis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology / Q000503:physiopathology; D014481:United States / Q000453:epidemiology
chemical_list: D000995:Antitubercular Agents