A prospective multicountry diagnostic accuracy study evaluated and compared three stool processing methods for Xpert MTB/RIF Ultra (Xpert Ultra) testing in children with presumed pulmonary tuberculosis (TB): the Simple Processing Kit (SPK), the Stool Optimization and Standardization (SOS) method, and the Optimized Sucrose Flotation (OSF) method. Children younger than 15 years were consecutively enrolled between June 2019 and March 2021 from tertiary hospitals and referral networks in India, South Africa, and Uganda. The study also assessed laboratory staff perceptions of the acceptability and usability of these stool processing approaches.
A total of 607 children were included. Eligible participants had microbiologically confirmed TB or at least one symptom suggestive of pulmonary TB, including prolonged cough, fever, failure to thrive, weight loss, or a chest radiograph consistent with TB. Children who had received anti-TB treatment for more than 72 hours were excluded. All participants underwent standardized TB evaluation including clinical assessment, chest radiography, and respiratory specimen collection. Respiratory samples were tested with Xpert Ultra and mycobacterial culture. Stool specimens were collected, processed within 72 hours, and tested using one or more of the three stool processing methods. Confirmed TB was defined by positive sputum Xpert Ultra or culture. Stool Xpert Ultra results were excluded from case classification. Laboratory personnel processing stool samples completed anonymous surveys evaluating usability and acceptability.
Among the 607 children, 61.1% were enrolled in Uganda, 60.5% were younger than 5 years, 50.7% were underweight, and 15.5% were living with HIV. Confirmed TB was diagnosed in 147 children (24.2%), and 92.5% of these cases were sputum Xpert Ultra positive. The proportion of valid stool test results was similar across methods, ranging from 87.4% for OSF to 90.3% for SPK. Positive stool Xpert Ultra results ranged from 9.3% (OSF) to 11.2% (SOS). Against the microbiological reference standard (MRS), all methods showed high specificity (97.1% to 98.2%) but modest sensitivity: 36.9% for SPK, 38.6% for SOS, and 31.3% for OSF. Sensitivities were substantially higher among children with higher sputum bacillary burden, reaching 95.8% to 100% when sputum Xpert Ultra semiquantitative results were low or higher, compared with only 16.7% to 22.6% among children with trace or very low sputum results (P < .001).
Among the 179 children tested with all three methods, diagnostic performance was similar, with overlapping 95% confidence intervals. Compared with sputum culture, sputum Xpert Ultra sensitivity was 82.4% (95% CI, 56.6% to 96.2%), higher than stool Xpert Ultra, although the difference was not statistically significant. Combining stool and sputum testing increased sensitivity by 17.6% to 23.5% compared with stool testing alone, while adding stool testing to sputum Xpert Ultra increased sensitivity by up to 11.8% at the expense of a small reduction in specificity (2.1% to 2.9%). Survey responses from 17 laboratory staff indicated that all methods were acceptable and perceived as beneficial. SOS was viewed as the least time-consuming method, and 75% of respondents believed it could be performed by nonlaboratory staff in peripheral facilities.
The three stool processing methods demonstrated similar diagnostic accuracy, characterized by high specificity but limited sensitivity for childhood pulmonary TB. The SOS method appeared most favorable operationally because of its ease of use and lower time requirements. Key limitations include incomplete testing of all children with all three methods, variation in method implementation over time, and reliance on a microbiological reference standard that may miss pediatric TB cases. As a prospective multicountry diagnostic accuracy study, the evidence supports stool Xpert Ultra as a useful noninvasive adjunct to respiratory testing, particularly in settings where sputum collection is challenging.
Source: Jaganath D, Nabeta P, Nicol MP, Castro R, Wambi P, Zar HJ, Workman L, Lodha R, Singh UB, Bavdekar A, Sanghavi S. Stool processing methods for Xpert ultra testing in childhood tuberculosis: a prospective, multicountry accuracy study. Clinical Infectious Diseases. 2026 Mar 15;82(3):526-34.
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