Evaluation of the Performance of Stool Samples to Diagnose Pediatric Pulmonary Tuberculosis in Routine Care: A Cohort Study From Pakistan

Background: The World Health Organization (WHO) recommends stool as an alternative respiratory sample (RS) for diagnosing pulmonary tuberculosis (PTB) in children <10 years. This study assessed stool-Xpert-Ultra diagnostic performance against microbiologically confirmed (MC-PTB) cases identified based on the composite reference standard (CRS) in children <15 years, stratified by age and nutritional status. Methods: Children <15 years with presumptive PTB were assessed at 2 tertiary-care hospitals in Pakistan. Stools and RS were tested using Xpert MTB/RIF-Ultra (Xpert-Ultra) and culture. Using the CRS, PTB cases were MC-PTB or clinically confirmed. Nutritional status was classified using WHO criteria. Stool-Xpert-Ultra diagnostic performance was assessed against MC-PTB or positive RS-Xpert-Ultra. Logistic regression identified predictors of microbiological yields. Results: Among 650 children, we obtained 587 RS, 258 stool and 195 both stool and RS. Of 650, 264 (41%) had MC and 136 (21%) had clinically confirmed PTB. Stool-Xpert-Ultra had sensitivity, specificity, and accuracy of 47%, 88%, 77%, and 72%, 73%, 72% against MC-PTB in children <10 and ≥10, respectively. Stool-Xpert-Ultra performed similarly against RS-Xpert-Ultra in each age group. Stool-Xpert-Ultra detected 11% additional MC-PTB cases when RS was negative or unavailable. Stool-Xpert-Ultra had high sensitivity (64%) in severely acute malnourished (SAM) children. Age ≥10, female, SAM and TB-consistent chest X-rays were strongly associated with stool and RS microbiological positivity. Conclusions: Stool-Xpert-Ultra demonstrated moderate sensitivity against MC-PTB in <10. It identified additional MC-PTB cases when RS was unavailable or/negative, making it a valuable noninvasive alternative, especially in children ≥10 and with SAM, where it missed fewer cases.