The Utility of the Urinary Lipoarabinomannan (U-LAM) Antigen in HIV-Infected Patients with Suspected Tuberculosis

PATHCHAT Edition No. 40
Please contact your local Ampath pathologist for more information.

Authors: Dr. Pieter Ekermans and Dr. Xoliswa Poswa

Introduction

🔹 What is Urinary Lipoarabinomannan (U-LAM)?

• U-LAM is a Mycobacterium tuberculosis (MTB) cell wall component excreted in urine.
• The Determine™ TB-LAM Ag test (Alere) is a lateral flow assay used for rapid detection of TB-LAM in urine.
• It has been marketed as an adjunct diagnostic tool in HIV-infected patients with severe immunosuppression.

✅ Advantages of the U-LAM Test:

• Non-invasive and inexpensive.
• Rapid bedside test (no laboratory infrastructure required).
• Alternative diagnostic tool for sputum-scarce HIV-infected patients.
• Higher sensitivity in HIV-positive patients with CD4 counts <100 cells/mm³.

📌 WHO recommends using U-LAM in hospitalised HIV-infected adults with CD4 ≤100 cells/mm³ or who are seriously ill.

Diagnostic Performance of U-LAM

🔹 Pooled Sensitivity & Specificity (Meta-Analysis Data):

✅ Smear-Positive Cases:

• Sensitivity: 54% (95% CI: 18–86%)
• Specificity: 90% (95% CI: 83–95%)

✅ Smear-Negative Cases:

• Sensitivity: 51% (95% CI: 18–83%)
• Specificity: 90% (95% CI: 79–96%)

✅ HIV-Positive Cases:

• Sensitivity: 47% (95% CI: 26–68%)
• Specificity: 96% (95% CI: 81–100%)

✅ HIV-Negative Cases:

• Sensitivity: 14% (95% CI: 4–38%)
• Specificity: 97% (95% CI: 86–100%)

📌 The test performs better in HIV-positive patients than in HIV-negative patients.

Clinical Study in Cape Town & Uganda

✅ Multi-Centre Study Results (Determine™ TB-LAM Ag Test):

• Study involved 1,013 HIV-infected patients with suspected pulmonary TB (PTB).
• Sensitivity was higher in Uganda (45.6%) than in Cape Town (28.7%) (p=0.0008).
• Overall specificity: 97.6% (95% CI: 95.9–98.7%).

🔹 Subgroup Analysis (CD4 ≤ 100 cells/mm³):

• U-LAM Sensitivity: 37.1% (95% CI: 21.1–42.2%)
• Smear Microscopy Sensitivity: 59.2% (95% CI: 52.0–66.1%)
• Combined U-LAM + Smear Microscopy Sensitivity: 53.7% (95% CI: 48.4–58.9%)

📌 Over half of culture-confirmed TB cases in HIV-infected patients with CD4 ≤ 100 cells/mm³ were detected by U-LAM.

WHO Recommendations (2015)

✅ WHO Policy on U-LAM Use:

1. U-LAM should NOT be used for routine TB diagnosis except in specific cases.
2. U-LAM may be used as an adjunctive test in:
   • HIV-positive adult inpatients with CD4 ≤ 100 cells/mm³ and TB symptoms.
   • HIV-positive patients who are seriously ill, regardless of CD4 count.
3. U-LAM should NOT be used as a TB screening test.

📌 "Seriously ill" is defined as respiratory rate >30/min, temperature >39°C, heart rate >120/min, and inability to walk unaided.

Pros & Cons of U-LAM Testing

✅ Pros:

• Rapid, inexpensive, and non-invasive.
• Useful for sputum-scarce HIV-infected patients.
• Higher sensitivity in severely immunosuppressed patients.
• Associated with improved survival when used to guide TB treatment initiation in hospitalised HIV patients.

🚨 Cons:

• Limited to urine specimens only.
• Negative test does NOT rule out TB (requires culture & molecular TB testing).
• Does not provide TB drug resistance information.
• Risk of false positives from bacterial contamination (e.g., Actinobacteria, Candida spp.).

📌 U-LAM should be interpreted in conjunction with other TB diagnostic tests, including microscopy, culture, and Xpert® MTB/RIF.

Specimen Collection for U-LAM Testing

✅ How to Collect a Urine Sample for U-LAM:

1. Collect a midstream urine sample using a sterile technique.
2. Wipe the perineum with sterile saline or sterile water before collection.
3. If the patient is catheterised, insert a clean catheter before collecting urine.
4. Fresh urine specimens should be tested within 8 hours at room temperature.
5. Urine stored at 2°C to 8°C should be processed within 3 days.

📌 Proper sample collection minimises bacterial contamination and false-positive results.

Conclusion

✅ U-LAM testing should be restricted to:

• Hospitalised HIV-infected adults with severe immunosuppression (CD4 ≤ 100 cells/mm³).
• HIV-positive patients who are seriously ill.

✅ A negative U-LAM result does NOT rule out TB.

• TB culture and molecular testing (PCR) are still required for definitive diagnosis.

✅ U-LAM testing improves early TB detection and reduces mortality in HIV-infected inpatients.

📌 All U-LAM results must be interpreted alongside clinical and radiological findings.