Nanoparticle boost makes urine test better at finding TB in children

Tuberculosis (TB) in children is hard to diagnose with existing urine tests because they often miss infections. Tania A. Thomas and colleagues set out to see whether a simple laboratory step could make a commonly used urine test more reliable for kids. The team focused on lipoarabinomannan (LAM), a molecule released by TB bacteria that can be detected in urine, and on the Alere lateral flow assay (LF-LAM), a rapid strip test designed to spot LAM. They tested a urine processing step using the Ceres TB-Nanotrap, a nanoparticle product that is intended to capture and concentrate LAM from urine. In a case-control study, researchers recruited children aged 1–18 years from outpatient clinics, including children with TB and non-TB controls. For each participant they ran the LF-LAM test twice: once on the original urine sample and once after concentrating 5 mL of urine with 400 uL of magnetic TB-Nanotrap particles. Band intensity from the LF-LAM strips was read both by visual grading and by digital quantification to compare how much the nanoparticle concentration step changed the test signal.

The core methods and results are straightforward and impressive. The LF-LAM test was performed before and after the TB-Nanotrap concentration step, and band intensity was recorded by visual grading and by a digital measurement system. By visual grading, urine LAM sensitivity was very low before concentration: 4.5% (95% Confidence Interval [CI]: 0.3–18.5). After concentrating samples with the Ceres TB-Nanotrap, visual sensitivity rose to 50.0% (95% CI: 30.0–70.0). When bands were measured digitally, sensitivity was 0.0% (95% CI: 0.0–15.4) before concentration and increased to 63.9% (95% CI: 42.8–81.4) after concentration. Specificity remained high: by visual grading it was 90.0% (62.8–99.4) both before and after concentration; by digital analysis it was 80.0% (44.4–97.5) before and 90.0% (62.8–99.4) after. For TB cases, digital analysis showed median LF-LAM band intensity rising from 0.0 arbitrary units (AU) (IQR 0.00–32.5) in unconcentrated samples to 98.4 AU (IQR 34.9–212.2) after concentration with TB-Nanotrap.

These results indicate that concentrating urine with the Ceres TB-Nanotrap greatly increased the ability of the Alere lateral flow assay (LF-LAM) to detect urinary LAM in children, without reducing the test’s specificity. The jump in sensitivity was especially clear when the team used digital quantitative analysis rather than visual reading, suggesting that combining nanoparticle concentration with objective digital scoring can reveal signals that would otherwise be missed. For clinicians and labs, the method tested here uses a small additional processing step — combining 5 mL of urine with 400 uL of magnetic TB-Nanotrap particles — that could be feasible in many settings, though the study was conducted in a controlled research context with children from outpatient clinics. The authors conclude that use of TB-Nanotrap and digital quantitative analysis improved the diagnostic accuracy of the LF-LAM assay in this pediatric population and recommend validation in larger studies before routine clinical adoption. If confirmed, the approach could make a noninvasive urine test a more useful tool for diagnosing TB in children.