Clinical predictors and accuracy of empiric tuberculosis treatment among sputum smear-negative HIV-infected adult TB suspects in Uganda.

The existing diagnostic algorithms for sputum smear-negative tuberculosis (TB) are complicated, time-consuming, and often difficult to implement. The decision to initiate TB treatment in resource-limited countries is often largely based on clinical predictors. We sought to determine the clinical predictors and accuracy of empiric TB treatment initiation in HIV-infected sputum smear-negative TB suspects using sputum culture as a reference standard.Out-patient HIV-TB integrated urban clinic in Kampala, Uganda.HIV-infected TB suspects were screened using sputum smear microscopy, and mycobacterial sputum liquid and solid cultures were performed. Smear results were made available to the clinician who made a clinical decision on empiric TB treatment initiation for sputum smear-negative patients. Clinic records were reviewed for patients whose sputum smears were negative to collect data on socio-demographics, TB symptomatology, chest X-ray findings, CD4 cell counts and TB treatment initiation.Of 253 smear-negative TB suspects, 56% (142/253) were females, median age 38 IQR (31-44) years, with a median CD4 cell count of 291 IQR (150-482) cells/mm(3). Of the 85 (33.6%) smear-negative patients empirically initiated on TB treatment, 35.3% (n = 30) were sputum culture positive compared to only 18 (10.7%) of the 168 untreated patients (p<0.001). Abnormal chest X-ray [aOR 10.18, 95% CI (3.14-33.00), p<0.001] and advanced HIV clinical stage [aOR 3.92, 95% CI (1.20-12.85), p = 0.024] were significantly associated with empiric TB treatment initiation. The sensitivity and specificity of empiric TB treatment initiation in the diagnosis of TB in HIV-infected patients after negative smear microscopy was 62.5% and 73.7% respectively.In resource-limited settings, clinically advanced HIV and abnormal chest X-ray significantly predict a clinical decision to empirically initiate TB treatment in smear-negative HIV-infected patients. Empiric TB treatment initiation correlates poorly with TB cultures. Affordable, accurate and rapid point-of-care diagnostics are needed in resource-limited settings to more accurately determine which HIV-infected TB suspects have smear-negative TB

Patient enrollment flow diagram showing the number of patients enrolled and analyzed as well as the TB culture results distribution.

<p>Patient enrollment flow diagram showing the number of patients enrolled and analyzed as well as the TB culture results distribution.</p

Comparing characteristics of sputum smear-negative study participants empirically initiated on TB treatment and those who were not treated.

*<p>means the variable number is less than the total N = 253. These were missing data in the clinic patients records most of which were not recorded by the treating clinicians.</p><p><b>Abbreviations</b>: IQR, Interquatile range; CXR, chest X-ray; TB, tuberculosis; WHO, World Health Organization; ART, Antiretroviral therapy.</p

Multivariate analysis for predictors of empiric TB treatment in sputum smear-negative HIV-infected TB suspects^*.

*<p>N = 123 with complete records. The model adjusted for B symptoms, shortness of breath, CXR findings, ART therapy, WHO clinical stage.</p><p><b>Abbreviations</b>: CXR, chest X-ray; TB, tuberculosis; WHO, World Health Organization; ART, Antiretroviral therapy; OR, Odds ratio; aOR, adjusted odds ratio; CI, Confidence intervals.</p

Distribution of sputum TB culture results.

<p>Abbreviations: MTBC, <i>Mycobacterium tuberculosis</i> complex; MOTT, mycobacteria other than tuberculosis; TB, tuberculosis.</p