Urine Lipoarabinomannan (LAM) Testing for TB in Children
The urine lipoarabinomannan (LAM) test, particularly the newer Fujifilm SILVAMP TB LAM (FujiLAM) assay, is the recommended urine-based test for tuberculosis diagnosis in children, showing superior sensitivity (64.9%) compared to the older Alere Determine TB LAM test (30.7%) while maintaining high specificity (83.8%). 1
Test Performance and Clinical Utility
The LAM test detects mycobacterial lipoarabinomannan antigen excreted in urine, offering a non-invasive alternative to traditional sputum-based diagnostics that are particularly challenging in children. 2
Diagnostic Accuracy by Test Type
- FujiLAM demonstrates sensitivity of 64.9% and specificity of 83.8% against microbiological reference standards in children with confirmed TB 1
- Alere Determine TB LAM shows lower sensitivity of 30.7% but slightly higher specificity of 87.8% 1
- MTB-LAM-ELISA has pooled sensitivity of 16.0% and specificity of 95.61% across pediatric studies 2
HIV Status Significantly Impacts Performance
LAM testing performs markedly better in HIV-positive children:
- HIV-positive children: FujiLAM sensitivity reaches 70% versus only 13% in HIV-negative children 3
- Alere LAM in HIV-positive: Sensitivity of 50% compared to 0% in HIV-negative children 3
- The pooled sensitivity of Alere LAM is 46.59% in HIV-positive children versus only 32.33% in HIV-negative children 2
Clinical Application Algorithm
When to Use LAM Testing
Primary indications:
- HIV-positive children with suspected TB (highest yield) 3
- Children with severe acute malnutrition (SAM) and TB symptoms 4
- Children unable to produce sputum samples (most young children) 2
- As an adjunct "rule-in" test when clinical suspicion is high but other tests are negative 5
Interpretation Guidelines
Grade-based interpretation for Determine LAM:
- Grades 2-3 positivity: Highly specific (99%) for TB in children with symptoms, warrants immediate treatment initiation 4
- Grade 1 positivity: Less clinically useful, as it occurs with similar frequency (36-37%) in both symptomatic and asymptomatic children 4
Clinical context matters:
- LAM detected TB in 73.2% of confirmed intrathoracic TB cases and 76% of confirmed lymph node TB cases 6
- LAM improved disease detection by 38.5% in intrathoracic TB and 41.6% in lymph node TB beyond reference tests 6
Important Caveats and Limitations
Host Factors Affecting Results
- Proteinuria and low body mass index are independently associated with LAM positivity, potentially causing false positives 3
- LAM excretion typically declines to zero during or at conclusion of anti-TB treatment, allowing for treatment monitoring 3
Diagnostic Limitations
- LAM should never be used alone to exclude TB, as negative results do not rule out disease 2, 6
- The test functions best as a "rule-in" rather than "rule-out" test 5
- Specificity of 92-93% means false positives occur, requiring clinical correlation 6
Integration with Standard Diagnostics
LAM testing should complement, not replace, traditional TB diagnostics in children:
- Sputum/gastric aspirate culture remains the gold standard when obtainable, with three consecutive morning gastric aspirates yielding positive cultures in up to 70% of infants 7
- Tuberculin skin testing (TST) has limited utility, as approximately 10% of children with culture-positive TB have negative TST results initially 7, 8
- GeneXpert MTB/RIF shows 20.6-33% sensitivity in HIV-negative children, lower than FujiLAM 5
Practical Monitoring Approach
For children on TB treatment, LAM can serve as a monitoring tool:
- Baseline LAM testing at diagnosis 3
- Serial testing during treatment to document declining LAM excretion 3
- Most patients show LAM decline to zero by treatment completion 3
The FujiLAM test represents a significant advancement over older LAM assays and should be prioritized when available, particularly for HIV-positive children and those with severe malnutrition where traditional diagnostics are most challenging. 1, 3