Conventional and Molecular Methods for the Diagnosis of Smear Negative Pulmonary TB and Concordance of Empirical TB Diagnosis with Culture Assay.

Background: Ethiopia is among high TB burden countries. The proportion of smear negative patients among pulmonary TB cases was 51%. Nevertheless, microscopy is still a primary tool for TB diagnosis. In the absence of sensitive diagnostic methods, clinicians often make the diagnosis of smear-negative pulmonary TB with information obtained through the clinical history, physical examination and chest X-ray. The treatment of smear negative TB patients with those criteria largely depends on the treating clinician. There is limited data on the utilization of clinical criteria commonly used to initiate TB treatment empirically when culture is used as the reference method. Beside this, there are a number of sensitive diagnostic methods that have a substantial contribution for the diagnosis of smear negative TB patients, but only few studies were conducted in Ethiopia to address this issue.

Objective: To assess the contribution of conventional and molecular methods for smear-negative patients and describe the concordance rate of empiric TB treatment with culture assay.

Methods: A cross-sectional study was designed on smear negative TB presumptive patients referred to St. Peter's TB Specialized Hospital from December 2014 to June 2015. Consecutive smear negative TB presumptive patients, aged greater or equal to 15 and willing to participate were included in the study. Socio-demographic and clinical data were collected using the data collection form designed for the study purpose. The data collection form was designed to capture patient demographic data, signs and symptoms, chest X-ray findings and empirical TB treatment initiations. Spot-Moring-spot sputum was collected using sterile falcon tubes for routine diagnostic purpose. Direct ZN examination was done on Spot-Moring-spot sputum at St. Peter's TB Specialized Hospital. The morning sputum was used for culture (LJ and MGIT), TB-LAMP, Xpert MTB/RIF assay and fluorescent microscopy examination. Data were captured and analyzed using SPSS.

Results: This study enrolled 459 smear negative presumptive TB patients. Most (57%) of the study participants were female; with median age of 40 IQR (28-55) years. HIV test results were available for 41% of the study participants and the prevalence of HIV among the study participants was 30%. Three hundred eighty three cases were having both treatment and lab results. Forty six cases were treated empirically. The sensitivity and specificity of empiric TB treatment when compared to culture were 45.8% and 90% respectively. The overall culture positivity rate was 6.8% (30/439), of which 6.6% (26/391) was by MGIT and 5.3% (23/436) was by LJ method. Direct and concentrated fluorescent microscopy adds 0.9% and 1.3% detection rate compared to the direct ZN. The overall sensitivity and specificity of TB-LAMP was 61.5% (16/26) and 96.6% respectively. The overall sensitivity and specificity of Xpert MTB/RIF was 70.8% (17/24) and 97.2% respectively.

Conclusion: TB-LAMP and Xpert MTB/RIFassaycan provide confirmatory results for at least two third of TB cases.