Background
Diagnosing tuberculosis (TB) in children is challenging due to its paucibacillary nature and the requirement of invasive respiratory samples. Non-invasive urine-based assays could be a good alternative, though disappointing so far. The PathFast™ TB lipoarabinomannan (LAM) Ag assay has been recently developed for the monitoring of TB treatment on sputum samples, but it has never been evaluated for TB diagnosis in urine. This study evaluated the diagnostic performance of three urine-based assays: LAM Determine™, quantitative LAM PathFast™, and IS6110-targeted urine PCR in a pediatric population hospitalized in Zambia for TB suspicion, and in controls without any TB signs from the orthopedic department.
Methods
The study is a retrospective study on stored samples from the PROMISE-TB trial (#NCT02573623) conducted in 2014. Children aged 0 to 15 years, living (CLHIV,50%) or not (CNLHIV, 50%) with HIV, were classified as microbiologically confirmed TB (MRS) if Xpert MTB/RIF or culture was positive on respiratory samples. Sensitivity was calculated among MRS TB cases, and specificity on controls given that children with probable TB but unconfirmed could still have TB. The Receiver operating characteristic (ROC) curve was calculated for the LAM PathFast assay to determine its optimal diagnostic threshold. For each test, sensitivity and specificity were calculated with their 95% confidence intervals per HIV status.
Results
A total of 378 children with TB suspicion, including 63 MRS TB, and 113 controls underwent at least one urinary test. Regarding the PathFast test, the area under the ROC curve was 0.87, and its optimal threshold had a value of 0.0115 pg/mL. Among CLHIV, the sensitivity of the TB PCR, Determine LAM and PathFast LAM was 0.35 (0.19-0.55), 0.59 (0.39-0.76) and 0.83 (0.65-0.94), respectively. The sensitivity of the 3 tests increased with age, with PathFast LAM increasing to 88% (95%CI: 0.69-0.97) among CLHIV aged 5 years or more. Among CNLHIV, the sensitivity of PCR TB was similar but much reduced for the 2 other tests (cf. Table). Among CLHIV, the specificity was 0.98 (0.87-1.0), 0.93 (0.82-0.99) and 0.95 (0.83-0.99), respectively, with similar values among CNLHIV for each test.
Conclusions
The PathFast™ TB LAM Ag assay in urine stands is very promising for TB diagnosis in children, particularly among CLHIV, reaching performances well above the WHO minimal targets. These findings should be confirmed on other studies.
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