title: Effect of antiretroviral therapy on the diagnostic accuracy of symptom screening for intensified tuberculosis case finding in a South African HIV clinic.
abstract: BACKGROUND
  Current symptom screening algorithms for intensified tuberculosis case finding or prior to isoniazid preventive therapy (IPT) in patients infected with human immunodeficiency virus (HIV) were derived from antiretroviral-naive cohorts. There is a need to validate screening algorithms in patients on antiretroviral therapy (ART).
  
  
  METHODS
  We performed cross-sectional evaluation of the diagnostic accuracy of symptom screening, including the World Health Organization (WHO) algorithm, to rule out tuberculosis in HIV-infected individuals pre-ART and on ART undergoing screening prior to IPT.
  
  
  RESULTS
  A total of 1429 participants, 54% on ART, had symptom screening and a sputum culture result available. Culture-positive tuberculosis was diagnosed in 126 patients (8.8%, 95% confidence interval [CI], 7.4%-10.4%). The WHO symptom screen in the on-ART compared with the pre-ART group had a lower sensitivity (23.8% vs 47.6%), but higher specificity (94.4% vs 79.8%). The effect of ART was independent of CD4(+) count in multivariable analyses. The posttest probability of tuberculosis following a negative WHO screen was 8.9% (95% CI, 7.4%-10.8%) and 4.4% (95% CI, 3.7%-5.2%) for the pre-ART and on-ART groups, respectively. Addition of body mass index to the WHO screen significantly improved discriminatory ability in both ART groups, which was further improved by adding CD4 count and ART duration.
  
  
  CONCLUSIONS
  The WHO symptom screen has poor sensitivity, especially among patients on ART, in a clinic where regular tuberculosis screening is practiced. Consequently, a significant proportion of individuals with tuberculosis would inadvertently be placed on isoniazid monotherapy despite high negative predictive values. Until more sensitive methods of ruling out tuberculosis are established, it would be prudent to do a sputum culture prior to IPT where this is feasible.
authors.affiliation: Centre for Infectious Disease Research and Epidemiology, School of Public Health and Family Medicine, University of Cape Town, South Africa. mxrangaka@yahoo.co.uk
authors.forename: Molebogeng X
authors.initials: MX
authors.lastname: Rangaka
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
authors.forename: Judith R
authors.initials: JR
authors.lastname: Glynn
authors.forename: Andrew
authors.initials: A
authors.lastname: Boulle
authors.forename: Gilles
authors.initials: G
authors.lastname: van Cutsem
authors.forename: Rene
authors.initials: R
authors.lastname: Goliath
authors.forename: Shaheed
authors.initials: S
authors.lastname: Mathee
authors.forename: Gary
authors.initials: G
authors.lastname: Maartens
mesh_terms: D000328:Adult; D000554:Ambulatory Care Facilities; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D015992:Body Mass Index; D018791:CD4 Lymphocyte Count; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013019:South Africa / Q000453:epidemiology; D014376:Tuberculosis / Q000175:diagnosis* / Q000453:epidemiology / Q000821:virology*
chemical_list: D044966:Anti-Retroviral Agents