Stool Xpert MTB/RIF and urine lipoarabinomannan for the diagnosis of tuberculosis in hospitalized HIV-infected children

Abstract

Background: Tuberculosis (TB) causes substantial morbidity and mortality in HIV-infected children. Sample collection and the paucibacillary nature of TB in children makes diagnosis challenging. Rapid diagnostic tools using easily obtained specimens are urgently needed.

Methods: Hospitalized, HIV-infected children aged 12 years or less enrolled in a randomized controlled trial (NCT02063880) comparing urgent to post-stabilization antiretroviral therapy initiation in Kenya underwent TB evaluation. At enrollment, sputum or gastric aspirates were collected for TB culture and Xpert, stool for Xpert, and urine for lipoarabinomannan (LAM). When possible, a second sputum/gastric aspirate for culture was obtained. Stool Xpert and urine LAM performance were compared to reference sputum/gastric aspirate culture.

Results: Among 165 HIV-infected children, median age was 24 months [interquartile range (IQR) 13-58], median CD4% was 14.3 (IQR 8.9-22.0%), and 114 (69.5%) had severe immunosuppression. Thirteen (7.9%) children had confirmed TB (positive culture and/or Xpert). Sputum/gastric aspirate Xpert, stool Xpert, and urine LAM sensitivities were 60% [95% confidence interval (CI) 26-88%], 63% (95% CI 25-92%), and 43% (95% CI 10-82%), respectively. Specificity was 98% (95% CI 94-100%) for sputum/gastric aspirate Xpert, 99% (95% CI 95-100%) for stool Xpert, and 91% (95% CI 84-95%) for urine LAM. Stool Xpert and urine LAM sensitivity increased among children with severe immunosuppression [80% (95% CI 28-100) and 60% (95% Cl 15-95%)].

Conclusion: Stool Xpert had similar performance compared with sputum/gastric aspirate Xpert to detect TB. Urine LAM had lower sensitivity and specificity, but increased among children with severe immunosuppression. Stool Xpert and urine LAM can aid rapid detection of TB in HIV-infected children using easily accessible samples.

Figure 1

Participant flow of children in TB diagnostic sub-study evaluating performance of stool Xpert and urine LAM compared to culture and Xpert on induced sputum or gastric aspirate among hospitalized newly diagnosed HIV-infected children. ^aParent trial randomized 183 participants, 2 of which were later excluded (1 due to TB meningitis, 1 due to false positive HIV-test) and therefore not included in the enrolled population of the sub-study. ^bOf 165 children with at least 1 sputum/gastric aspirate culture, 165 had Xpert and 164 had at least one culture (146 of whom had results from two consecutive cultures). Children were intended to have both stool Xpert and urine LAM performed, however 148 had a valid stool Xpert result, 130 had a valid urine LAM result, and 116 had both. ^cIntention-to-diagnose: At least one reference test performed (culture or Xpert) on sputum or gastric aspirate ^dDiagnosed-per-protocol: All three reference tests (2 consecutive cultures and 1 Xpert) performed on sputum or gastric aspirate Confirmed, Unconfirmed, and Unlikely TB per international consensus clinical case definitions for pediatric TB (Graham et al. 2015)

Figure 2

Overlap of urine LAM and stool Xpert with reference sputum/gastric aspirate Xpert and/or culture. ^aIncludes nine children with sputum/gastric aspirate Xpert or culture results negative (2 with Unconfirmed TB and 7 with Unlikely TB) and one child who did not have sputum/gastric aspirate sample collected who was urine LAM positive. ^bIncludes one child who did not have sputum/gastric aspirate sample collected who was stool Xpert positive.