Abstract Body

Background:

Rapid urine-based TB diagnostics, including lateral flow urinary lipoarabinomannan (LF-LAM), reduce mortality in HIV-positive in-patients. Xpert MTB/RIF Ultra (Ultra) has improved sensitivity on sputum, and may be a useful urine-based diagnostic test for disseminated TB.

Methods:

We conducted a cross-sectional diagnostic accuracy study at two hospitals in East London, South Africa. From August 2018 – February 2019, consecutive HIV-positive adults admitted with ≥1 WHO TB symptom or clinical concern for TB were enrolled and underwent TB cultures of blood, sputum, and urine. Urine was obtained for bedside urine Alere LF-LAM testing and Ultra was performed on the pellet of 15ml centrifuged urine. Vital status was assessed by phone call at 12 weeks. Diagnostic classifications were: ‘definite TB’ (positive TB culture or molecular test), ‘probable TB’ (clinico-radiological features of TB and response to TB therapy), and ‘not TB’ (remained well without TB therapy). The primary outcome was sensitivity of urine Ultra for definite TB. We also calculated diagnostic yield (proportion positive tests among TB cases) and compared the diagnostic performance of urine-based tests and sputum Ultra.

Results:

238 participants were enrolled. Median age was 39 years (IQR 32- 48), 124 (52%) female, median CD4 count 76 cells/mm3 (IQR 22- 203). Definite TB was diagnosed in 62 (26%) and either definite or probable TB in 92 (39%). Diagnostic yields for definite TB were 34% (n=21) for sputum Ultra, 45% (n=28) for urine LF-LAM, 68% (n=42) for urine Ultra, and 73% (n=45) for urine LF-LAM and urine Ultra combined. Respective yields for definite plus probable TB were 23% (n=21), 39% (n=36), 57% (n=52), and 64% (n=59). The sensitivity and specificity using definite TB as a reference were 55% and 90% for urine LF-LAM, and 70% and 100% for urine Ultra, respectively. Positive urine Ultra results were 68.5% (n=37) rifampicin susceptible, 9.3% (n=5) resistant, and 22.2% (n=12) indeterminant, with no discordancies with culture or sputum Ultra rifampicin susceptibility results.

Conclusions:

Combined urine testing (Ultra + LF-LAM) identified three-quarters of HIV-positive medical in-patients with definite TB. Urine Ultra had improved sensitivity and specificity compared to LF-LAM and has added benefit of providing rapid rifampicin susceptibility results.