Tuberculosis diagnostic accuracy of stool Xpert MTB/RIF and urine AlereLAM in vulnerable children.

Abstract

Non-sputum based diagnostic approaches are crucial in children at high risk of disseminated tuberculosis [TB] who cannot expectorate sputum. We evaluated the diagnostic accuracy of Xpert MTB/RIF from stool and urine AlereLipoarabinomannan [LAM] test in this group of children. Hospitalised children with presumptive TB and either age <2 years, HIV-positive or severe malnutrition were enrolled in a diagnostic cohort. At enrolment, we attempted to collect two urine, two stool and two respiratory samples. Urine and stool were tested with AlereLAM and Xpert MTB/RIF, respectively. Respiratory samples were tested with Xpert MTB/RIF and mycobacterial culture. Both a microbiological and a composite clinical reference standard were used. The study enrolled 219 children; median age 16.4 months, 72 (32.9%) HIV-positive and 184 (84.4%) severely malnourished. Twelve (5.5%) and 58 (28.5%) children had confirmed and unconfirmed TB respectively. Stool and urine were collected in 219 (100%) and 216 (98.6%) children. Against the microbiological reference standard the sensitivity and specificity (n/N, 95% confidence intervals) of stool Xpert MTB/RIF was 50.0% (6/12, 21.1-78.9) and 99.1% (198/200 96.4-99.9), while that of urine AlereLAM was 50.0% (6/12, 21.1-78.9) and 74.6% (147/197, 67.9-80.5) respectively. Against the composite reference standard sensitivity was reduced to 11.4% (8/70) for stool and 26.2% (17/68) for urine, with no major difference by age group (<2 and >2 years) or HIV status. The Xpert MTB/RIF assay has excellent specificity on stool, but sensitivity is suboptimal. Urine AlereLAM is compromised by poor sensitivity and specificity in children.