Abstract
SummaryBackgroundUrine tests for mycobacterial lipoarabinomannan might be useful for point-of-care diagnosis of tuberculosis in adults with advanced HIV infection, but have not been assessed in children. We assessed the accuracy of urine lipoarabinomannan testing for the diagnosis of pulmonary tuberculosis in HIV-positive and HIV-negative children.MethodsWe prospectively recruited children (aged ≤15 years) who presented with suspected tuberculosis at a primary health-care clinic and paediatric referral hospital in South Africa, between March 1, 2009, and April 30, 2012. We assessed the diagnostic accuracy of urine lipoarabinomannan testing with lateral flow assay and ELISA, with mycobacterial culture of two induced sputum samples as the reference standard. Positive cultures were identified by acid-fast staining and tested to confirm Mycobacterium tuberculosis and establish susceptibility to rifampicin and isoniazid.Findings535 children (median age 42·5 months, IQR 19·1–66·3) had urine and two induced specimens available for testing. 89 (17%) had culture-confirmed tuberculosis and 106 (20%) had HIV. The lateral flow lipoarabinomannan test showed poor accuracy against the reference standard, with sensitivity of 48·3% (95% CI 37·6–59·2), specificity of 60·8% (56·1–65·3), and an area under the receiver operating characteristic curve of 0·53 (0·46–0·60) for children without HIV and 0·64 (0·51–0·76) for children with HIV. ELISA had poor sensitivity in children without HIV (sensitivity 3·0%, 95% CI 0·4–10·5) and children with HIV (0%, 0·0–14·3); overall specificity was 95·7% (93·4–97·4).InterpretationUrine lipoarabinomannan tests have insufficient sensitivity and specificity to diagnose HIV-positive and HIV-negative children with tuberculosis and should not be used in this patient population.FundingUS National Institutes of Health, the National Health Laboratory Services Research Trust, the Medical Research Council of South Africa, and the Wellcome Trust.
Highlights
Microbiological confirmation of pulmonary tuberculosis in children is difficult
The lateral flow lipoarabinomannan test showed poor accuracy against the reference standard, with sensitivity of 48·3%, specificity of 60·8% (56·1–65·3), and an area under the receiver operating characteristic curve of 0·53 (0·46–0·60) for children without HIV and 0·64 (0·51–0·76) for children with HIV
Suspected pulmonary tuberculosis was defined on the basis of cough of any duration and one of the following: household contact with an infectious tuberculosis source case within the preceding 3 months, loss of weight or failure to gain weight in the preceding 3 months, a positive tuberculin skin test to purified protein derivative (2TU, PPD RT23, Staten Serum Institute, Denmark, Copenhagen), or a chest radiograph suggesting pulmonary tuberculosis
Summary
Microbiological confirmation of pulmonary tuberculosis in children is difficult. Collection of a sample from the lower respiratory tract is challenging because young children rarely spontaneously produce sputum. Sputum induction or gastric lavage are useful methods for obtaining respiratory samples,[1] but require trained staff and basic equipment. Even when appropriate samples can be obtained, smear microscopy is rarely positive in children and mycobacterial culture is often required.[2] The main drawback of culture is that treatment decisions often need to be made before results are available because the clinical course of tuberculosis can be rapid in children younger than 5 years. Culture requires advanced infrastructure and trained staff and is seldom available in countries with the greatest burden of disease. We recently reported on the accuracy of Xpert MTB/RIF testing of induced sputum[3] and nasopharyngeal aspirate[4] specimens, which holds promise as a rapid and feasible alternative to culture in low-resource settings
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