Abstract Background The World Health Organization (WHO) has endorsed the next-generation Xpert MTB/RIF Ultra (Ultra) cartridge, and Uganda is currently transitioning from the older generation Xpert MTB/RIF (Xpert) cartridge to Ultra as the initial diagnostic test for pulmonary tuberculosis (TB). We assessed the diagnostic accuracy of Ultra for pulmonary TB among adults in Kampala, Uganda. Methods We sampled adults referred for Xpert testing at two hospitals and a health center over a 12-month period. We enrolled adults with positive Xpert and a random 1:1 sample with negative Xpert results. Expectorated sputum was collected for Ultra, and for solid and liquid culture testing for Xpert-negative patients. We measured sensitivity and specificity of Ultra overall and by HIV status, prior history of TB, and hospitalization, in reference to Xpert and culture results. We also assessed how classification of results in the new “trace” category affects Ultra accuracy. Results Among 698 participants included, 211 (30%) were HIV-positive and 336 (48%) had TB. The sensitivity of Ultra was 90.5% (95% CI 86.8–93.4) and specificity was 98.1% (95% CI 96.1–99.2). There were no significant differences in sensitivity and specificity by HIV status, prior history of TB or hospitalization. Xpert and Ultra results were concordant in 670 (96%) participants, with Ultra having a small reduction in specificity (difference 1.9, 95% CI 0.2 to 3.6, p=0.01). When “trace” results were considered positive for all patients, sensitivity increased by 2.1% (95% CI 0.3 to 3.9, p=0.01) without a significant reduction in specificity (− 0.8, 95% CI − 0.3 to 2.0, p=0.08). Conclusions After 1 year of implementation, Ultra had similar performance to Xpert. Considering “trace” results to be positive in all patients increased case detection without significant loss of specificity. Longitudinal studies are needed to compare the benefit of greater diagnoses to the cost of overtreatment.

The performance of urine Xpert MTB/RIF Ultra (Xpert Ultra) for pulmonary TB diagnosis is unknown. HIV-positive and HIV-negative adults were enrolled at two health facilities in Kampala, Uganda. We compared the accuracy of urine Xpert Ultra and Determine TB-LAM in reference to sputum-based testing (positive Xpert MTB/RIF or culture), and assessed incremental yield. Urine Xpert Ultra had low sensitivity (17.2%, 95% CI 12.3-23.2) but high specificity (98.1%, 95% CI 94.4-99.6). Sensitivity reached 50.0% (95% CI 28.2-71.8) among HIV-positive patients with CD4 <100 cells/μL. Compared to Determine TB-LAM, urine Xpert Ultra was 9.4% (95% CI 3.8-14.9, P = 0.01) more sensitive, and 17.2% (95% CI 4.5-29.8, P = 0.01) more sensitive among HIV-positive patients. However, the incremental sensitivity of urine Xpert Ultra relative to sputum Xpert MTB/RIF was only 1% (95% CI -0.9 to 2.8). Urine Xpert Ultra could be an alternative for patients with advanced HIV infection unable to produce sputum.

Background HIV is transmitted primarily through sexual intercourse, and the objective of this study was therefore to assess whether there is occult viral replication and resistance in genital secretions in patients on protease inhibitor (PI)-based second-line therapy. Methods HIV-infected adults taking ritonavir-boosted lopinavir with either two nucleoside reverse transcriptase inhibitors (NRTIs), raltegravir or as monotherapy for 96 weeks, were enrolled at seven clinical sites in Uganda. Viral load (VL) was measured in cervico-vaginal secretions or semen and in a corresponding plasma sample. Genotypic resistance was assessed in genital secretion samples and plasma samples. Results were compared between compartments and with the plasma resistance profile at first-line failure. Results Of the 111 participants enrolled (91 female, 20 male), 16 (14%) and 30 (27%) had VL >1,000 and >40 copies/ml, respectively, in plasma; 3 (3%) and 23 (21%) had VL >1,000 copies/ml and >40 copies/ml, respectively, in genital secretions. There was 74% agreement between plasma and genital secretion VL classification above/below 40 copies/ml threshold (kappa-statistic =0.29; P=0.001). RT mutations (both NRTI and non-nucleoside reverse transcriptase inhibitor) were detected in genital secretions in four patients (similar profile to corresponding plasma sample at first-line failure) and PI mutations were detected in two (one polymorphism with no impact on resistance; one with high-level PI resistance). Conclusions High level (>1,000 copies/ml) viral replication and development of new RT or PI resistance in the genital compartment were rare. The risks of transmission arising from resistance evolution in the genital compartment are likely to be low on PI-based second-line therapy.