title: Algorithm for the diagnosis of smear-negative pulmonary tuberculosis in high-incidence resource-constrained settings.
abstract: OBJECTIVE
  Diagnosis of smear-negative pulmonary tuberculosis (SNPT) remains a challenge, particularly in resource-constrained settings. We evaluated a diagnostic algorithm that combines affordable laboratory tools and a clinical prediction rule (CPR).
  
  
  METHODS
  We derived, based on published evidence, a diagnostic algorithm for SNPT. Sputum concentration constitutes its first step. In suspects with negative results, SNPT probability is classified with a CPR as low (excluded), high (confirmed) or intermediate. For intermediate patients, sputum Middlebrook 7H9 liquid culture is performed, and they are assessed after 2 weeks. If clinically deteriorated, with still negative liquid culture, bronchoscopy is offered. Otherwise, results of Middlebrook 7H9 culture are awaited. We prospectively evaluated this algorithm against a reference standard of solid and liquid cultures in two reference hospitals in Lima, Peru.
  
  
  RESULTS
  670 SNPT suspects were included from September 2005 to March 2008. The prevalence of SNPT was 27% according to the reference standard. The algorithm's overall accuracy was 0.94 (95% CI 0.91-0.95), its sensitivity was 0.88 (95% CI 0.82-0.92) and its specificity, 0.96 (95% CI 0.94-0.98). Sputum concentration, the CPR, Middlebrook 7H9 sputum culture and bronchoscopic samples defined a diagnosis of SNPT according to the algorithm in 57 (37%), 25 (16%), 63 (41%) and 8(5%) of patients, respectively. 65% of patients were diagnosed within 3 weeks.
  
  
  CONCLUSIONS
  The algorithm was accurate for SNPT diagnosis. Sputum concentration, CPR and selective Middlebrook 7H9 culture are essential components.
authors: General Epidemiology and Disease Control Unit, Institute of Tropical Medicine, Antwerp, Belgium.
authors: Alonso
authors: A
authors: Soto
authors: Lely
authors: L
authors: Solari
authors: Juan
authors: J
authors: Agapito
authors: Eduardo
authors: E
authors: Gotuzzo
authors: Roberto
authors: R
authors: Accinelli
authors: Dante
authors: D
authors: Vargas
authors: Vilma
authors: V
authors: Acurio
authors: Francine
authors: F
authors: Matthys
authors: Patrick
authors: P
authors: Van der Stuyft
mesh_terms: D000328:Adult; D000465:Algorithms; D005260:Female; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification*; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D013183:Sputum / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis*; D055815:Young Adult
keywords: algorithms; decision-making; diagnosis; pulmonary; smear-negative; tuberculosis