Devan Jaganath1,2,3, Peter Wambi4, Tania F Reza2,3, Jascent Nakafeero4, Ernest O Aben4, Emma Kiconco4, Gertrude Nannyonga4, Moses Nsereko4, Moorine P Sekadde5, Mary Mudiope6, Midori Kato-Maeda2,3, Jeffrey Starke7, Alfred Andama8, Swomitra Mohanty9, Eric Wobudeya4, Adithya Cattamanchi2,3,10. 1. Division of Pediatric Infectious Diseases, University of California-San Francisco, San Francisco, California, USA. 2. Division of Pulmonary and Critical Care Medicine, University of California-San Francisco, San Francisco, California, USA. 3. Center for Tuberculosis, University of California-San Francisco, San Francisco, California, USA. 4. Mulago National Referral Hospital, Kampala, Uganda. 5. National TB and Leprosy Program, Ministry of Health, Kampala, Uganda. 6. Infectious Diseases Institute, Kampala, Uganda. 7. Division of Pediatric Infectious Diseases, Baylor College of Medicine, Houston, Texas, USA. 8. Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda. 9. Departments of Chemical Engineering and Materials Science Engineering, University of Utah, Salt Lake City, Utah, USA. 10. Department of Medicine, Center for Vulnerable Populations, University of California-San Francisco, San Francisco, California, USA.
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.
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.
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