Oral Swab Testing With Xpert MTB/RIF Ultra for the Diagnosis of Tuberculosis in Children Aged <5 Years in Uganda: An Exploratory Interim Analysis of Diagnostic Accuracy in the NOD-pedFEND Cohort

Background. Obtaining respiratory samples to diagnose tuberculosis in young children is challenging. Oral swabs are alternative noninvasive specimens for microbiology. Methods. We conducted an interim prospective diagnostic accuracy evaluation of Xpert MTB/RIF Ultra (Ultra) on oral swabs for pulmonary tuberculosis in children aged <5 years in Uganda. Most children had 2 consecutive swabs collected in a single cryovial (double swabs). Reference tests consisted of Ultra and culture on 2 nasopharyngeal aspirates and 1 gastric aspirate and Ultra on 1 stool. Children were classified as having confirmed tuberculosis, unconfirmed tuberculosis, or unlikely tuberculosis per the National Institutes of Health. Diagnostic accuracy was determined against a microbiological reference standard and a composite reference standard. Results. From August 2021 to February 2024, 444 children were enrolled, of whom 399 had complete classifications: 33 had confirmed tuberculosis, 269 had unconfirmed tuberculosis, 70 had unlikely tuberculosis, and 27 were unclassifiable. The median age was 16 months and 17% had HIV. Most children (398/399) had oral swabs collected, all with conclusive Ultra results. The sensitivity of double swabs was 6.9% with a microbiological reference standard (95% CI, 1.9%–22.0%) and 1.8% with a composite reference standard (95% CI, .8%–4.1%). Specificity was at least 99%. Swabs detected tuberculosis in 4 children with negative reference test results, of whom 3 had unconfirmed tuberculosis. Conclusions. The low sensitivity of Ultra on double swabs precludes its role as a principal diagnostic approach in young children. However, detection of tuberculosis in children who were not otherwise microbiologically diagnosed suggests the utility of oral swabs as add-on samples to increase yield.