A Prospective Evaluation of Xpert MTB/RIF Ultra for Childhood Pulmonary Tuberculosis in Uganda

Abstract

Background Xpert MTB/RIF Ultra (Xpert Ultra) has improved the sensitivity to detect pulmonary tuberculosis (TB) in adults. However, there have been limited prospective evaluations of its diagnostic accuracy in children. Methods We enrolled children undergoing assessment for pulmonary TB in Kampala, Uganda, over a 12-month period. Children received a complete TB evaluation and were classified as Confirmed, Unconfirmed, or Unlikely TB. We calculated the sensitivity and specificity of Xpert Ultra among children with Confirmed vs Unlikely TB. We also determined the diagnostic accuracy with clinical, microbiological, and extended microbiological reference standards (MRSs). Results Of the 213 children included, 23 (10.8%) had Confirmed TB, 88 (41.3%) had Unconfirmed TB, and 102 (47.9%) had Unlikely TB. The median age was 3.9 years, 13% were HIV-positive, and 61.5% were underweight. Xpert Ultra sensitivity was 69.6% (95% confidence interval [CI]: 47.1-86.8) among children with Confirmed TB and decreased to 23.4% (95% CI: 15.9-32.4) with the clinical reference standard. Specificity was 100% (95% CI: 96.4-100) among children with Unlikely TB and decreased to 94.7% (95% CI: 90.5-97.4) with a MRS. Sensitivity was 52.9% (95% CI: 35.1-70.2) and specificity 95.5% (95% CI: 91.4-98.1) with the extended MRS. Of the 26 positive Xpert Ultra results, 6 (23.1%) were “Trace-positive,” with most (5/6) occurring in children with Unconfirmed TB. Conclusions Xpert Ultra is a useful tool for diagnosing pulmonary TB in children, but there remains a need for more sensitive tests to detect culture-negative TB.

Detection of pulmonary tuberculosis in children using the Xpert MTB/RIF Ultra assay on sputum: a multicenter study

“…While when all the children with active TB were tested by MTB culture using three consecutive sputa, MTB culture on the second and third sputum detected an additional 24 cases with active TB. When using three MTB culture results as the reference, the sensitivities of Ultra and Xpert in children with culture-negative TB decreased to 28.9% and 13.5%, respectively, which is similar with the recently published data in children [21]. In addition, we observed the diagnostic efficiency using the combination of one single MTB culture and one single Ultra was equivalent to the combination of repeated MTB culture and one single Ultra.…”

Clinical Characteristics of Pulmonary Tuberculosis in Children Tested by Xpert MTB/RIF Ultra

“…26 Consistent with recently published study, considering the patients in our study had signs and symptoms of TB, have no previous TB disease, and all had clinical improvement after anti-TB treatment, the finding in our study supports the clinical diagnosis of active TB in children with trace results and also supports the notion that trace results can be considered to be truepositive results in children with clinical symptoms as previous reported studies. [26][27][28] As Ssengooba et al pointed out that it was challenge to accurately assess a novel diagnostic assay in the absence of gold standard. 27 For the children who were positive only by Xpert Ultra trace results, 1 of the explanations was that the samples may have a bacillary load too low to be detectable by culture.…”

Diagnostic Advances in Childhood Tuberculosis—Improving Specimen Collection and Yield of Microbiological Diagnosis for Intrathoracic Tuberculosis

“…Not infrequently, such trace calls are associated with negative cultures if performed on the same samples, especially among recently treated patients, which is not commonly the case in children, raising the possibility of falsepositive results [33]. However, as paucibacillary TB is most common in high-risk patient groups, including children, HIV-infected individuals, and in extra-thoracic TB (such as TB meningitis), WHO has recommended that trace calls be regarded as microbiological confirmation in these high-risk groups [7,34]. Recently, TB symptoms, extra-pulmonary TB, and no prior TB have been identified as independently associated with culture-positive TB in adults and children with trace calls [35].…”