Algorithm for the diagnosis of smear-negative pulmonary tuberculosis in high-incidence resource-constrained settings.

OBJECTIVES: 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.

Incremental yield of bronchial washing for diagnosing smear-negative pulmonary tuberculosis.

OBJECTIVE: To assess the increased diagnostic yield for pulmonary tuberculosis using bronchial washing cultures compared with sputum cultures. METHODS: Study conducted with 61 adults in Lima, Peru, from January 2006 to December 2007. The yield of sputum cultures was compared with the yield of acid-fast bacilli smears and cultures of bronchial washing for diagnosing pulmonary tuberculosis in suspected cases of clinical tuberculosis with negative acid fast bacilli sputum smears. RESULTS: Twenty seven (95%CI 32;58) of the cases were eventually diagnosed with smear-negative pulmonary tuberculosis. Bronchial washing samples detected 23 (95%CI 72;99) of the smear-negative pulmonary tuberculosis cases compared with 15 (95%CI 37;74) for sputum cultures (p = 0.02). The incremental diagnostic yield of acid fast bacilli smear and culture of bronchial washing specimens over sputum culture was 44% (95%CI 25;65). CONCLUSIONS: In function of the epidemiological context and the resources available, bronchoscopy should be deployed as part of a comprehensive work up that optimizes smear-negative pulmonary tuberculosis diagnosis and minimizes risk and costs.

The validity of cerebrospinal fluid parameters for the diagnosis of tuberculous meningitis.

OBJECTIVES: To assess the diagnostic validity of laboratory cerebrospinal fluid (CSF) parameters for discriminating between tuberculous meningitis (TBM) and other causes of meningeal syndrome in high tuberculosis incidence settings. METHODS: From November 2009 to November 2011, we included patients with a clinical suspicion of meningitis attending two hospitals in Lima, Peru. Using a composite reference standard, we classified them as definite TBM, probable TBM, and non-TBM cases. We assessed the validity of four CSF parameters, in isolation and in different combinations, for diagnosing TBM: adenosine deaminase activity (ADA), protein level, glucose level, and lymphocytic pleocytosis. RESULTS: One hundred and fifty-seven patients were included; 59 had a final diagnosis of TBM (18 confirmed and 41 probable). ADA was the best performing parameter. It attained a specificity of 95%, a positive likelihood ratio of 10.7, and an area under the receiver operating characteristics curve of 82.1%, but had a low sensitivity (55%). None of the combinations of CSF parameters achieved a fair performance for 'ruling out' TBM. CONCLUSIONS: Finding CSF ADA greater than 6 U/l in patients with a meningeal syndrome strongly supports a diagnosis of TBM and permits the commencement of anti-tuberculous treatment.

Evaluation of the diagnostic utility of fiberoptic bronchoscopy for smear-negative pulmonary tuberculosis in routine clinical practice.

We evaluated the diagnostic yield of fiberoptic bronchoscopy for the diagnosis of smear-negative pulmonary tuberculosis in patients treated at a referral hospital in Lima, Peru. Of the 611 patients who underwent the procedure, 140 (23%) were diagnosed with tuberculosis based on the analysis of BAL samples. Being young and being male were significantly associated with positive cultures. In addition, 287 patients underwent post-bronchoscopic sputum smear testing for AFB, the results of which increased the diagnostic yield by 22% over that obtained through the analysis of BAL samples alone. We conclude that the analysis of BAL samples and post-bronchoscopic sputum samples provides a high diagnostic yield in smear-negative patients suspected of having pulmonary tuberculosis.