Reducing geographic barriers to tuberculosis (TB) care is a priority in high-burden countries where patients frequently initiate, but do not complete, the multi-day TB evaluation process. Using routine cross-sectional study from six primary-health clinics in rural Uganda from 2009 to 2012, we explored whether geographic barriers affect completion of TB evaluation among adults with unexplained chronic cough. We measured distance from home parish to health center and calculated individual travel time using a geographic information systems technique incorporating roads, land cover, and slope, and measured its association with completion of TB evaluation. In 264,511 patient encounters, 4,640 adults (1.8%) had sputum smear microscopy ordered; 2,783 (60%) completed TB evaluation. Median travel time was 68 minutes for patients with TB examination ordered compared with 60 minutes without (P < 0.010). Travel time differed between those who did and did not complete TB evaluation at only one of six clinics, whereas distance to care did not differ at any of them. Neither distance nor travel time predicted completion of TB evaluation in rural Uganda, although limited detail in road and village maps restricted full implementation of these mapping techniques. Better data are needed on geographic barriers to access clinics offering TB services to improve TB diagnosis.

Background

Peripheral blood interferon-gamma release assays (IGRAs) have sub-optimal sensitivity and specificity for diagnosis of active pulmonary tuberculosis (TB). However, assessment of local immune responses has been reported to improve the accuracy of TB diagnosis.

Methods

We enrolled HIV-infected adults with cough ≥2 weeks' duration admitted to Mulago Hospital in Kampala, Uganda and referred for bronchoscopy following two negative sputum acid-fast bacillus smears. We performed an ELISPOT-based IGRA (T-SPOT.TB®, Oxford Immunotec, Oxford, UK) using peripheral blood and bronchoalveolar lavage (BAL) fluid mononuclear cells, and determined the accuracy of IGRAs using mycobacterial culture results as a reference standard.

Results

94 HIV-infected patients with paired peripheral blood and BAL IGRA results were included. The study population was young (median age 34 years [IQR 28-40 years]) and had advanced HIV/AIDS (median CD4+ T-lymphocyte count 60 cells/µl [IQR 22-200 cells/µl]). The proportion of indeterminate IGRA results was higher in BAL fluid than in peripheral blood specimens (34% vs. 14%, difference 20%, 95% CI 7-33%, p = 0.002). BAL IGRA had moderate sensitivity (73%, 95% CI 50-89%) but poor specificity (48%, 95% CI 32-64%) for TB diagnosis. Sensitivity was similar (75%, 95% CI 57-89%) and specificity was higher (78%, 95% CI 63-88%) when IGRA was performed on peripheral blood.

Conclusions

BAL IGRA performed poorly for the diagnosis of smear-negative TB in a high HIV/TB burden setting. Further studies are needed to examine reasons for the large proportion of indeterminate results and low specificity of BAL IGRA for active TB in high HIV/TB burden settings.