Prospective evaluation of GeneXpert for the diagnosis of HIV- negative pediatric TB cases

BACKGROUND The GeneXpertMTB/RIF (Xpert) assay is now recommended by WHO for diagnosis of tuberculosis (TB) in children but evaluation data is limited. METHODS One hundred and fifty consecutive HIV negative children (<15 years of age) presenting with suspected TB were enrolled at a TB referral hospital in Ho Chi Minh City, Vietnam. 302 samples including sputum (n = 79), gastric fluid (n = 215), CSF (n = 3), pleural fluid (n = 4) and cervical lymphadenopathic pus (n = 1) were tested by smear, automated liquid culture (Bactec MGIT) and Xpert. Patients were classified retrospectively using the standardised case definition into confirmed, probable, possible, TB unlikely or not TB categories. Test accuracy was evaluated against 2 gold standards: [1] clinical (confirmed, probable and possible TB) and [2] 'confirmed TB' alone. RESULTS The median age of participants was 18 months [IQR 5-170]. When test results were aggregated by patient, the sensitivity of smear, Xpert and MGIT against clinical diagnosis as the gold standard were 9.2% (n = 12/131) [95%CI 4.2; 14.1], 20.6% (n = 27/131) [95%CI 13.7; 27.5] and 29.0% (n = 38/131) [21.2;36.8], respectively. Specificity 100% (n = 19/19), 94.7% (n = 18/19), 94.7% (n = 18/19), respectively. Xpert was more sensitive than smear (P = <0.001) and less sensitive than MGIT (P = 0.002). CONCLUSIONS The systematic use of Xpert will increase early TB case confirmation in children and represents a major advance but sensitivity of all tests remains unacceptably low. Improved rapid diagnostic tests and algorithm approaches for pediatric TB are still an urgent research priority.