Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in HIV-positive adults
Maunank Shah1, Colleen Hanrahan2, Zhuo Yu Wang3, Nandini Dendukuri3, Stephen D Lawn4, Claudia M Denkinger5, Karen R Steingart6
1. Johns Hopkins University School of Medicine, Department of Medicine, Division of Infectous Diseases, Baltimore, Maryland, USA
2. Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, Maryland, USA
3. McGill University, Department of Epidemiology, Biostatistics and Occupational Health, Montreal, Canada
4. London School of Hygiene and Tropical Medicine, Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London, UK
5. FIND, Geneva, Switzerland
6. Liverpool School of Tropical Medicine, Cochrane Infectious Diseases Group, Liverpool, UK
Shah M, Hanrahan C, Wang ZY, Dendukuri N, Lawn SD, Denkinger CM, Steingart KR. Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in HIV-positive adults. Cochrane Database of Systematic Reviews 2016, Issue 5. Art. No.: CD011420. DOI: 10.1002/14651858.CD011420.pub2.
Tuberculosis (TB) is a common cause of death in people with human immunodeficiency virus (HIV) infection, but diagnosis is difficult, and depends on testing for TB in the sputum and other sites, which may take weeks to give results. A rapid and accurate point-of-care test could reduce delays in diagnosis, allow treatment to start promptly, and improve linkage between diagnosis and treatment.
Test evaluated by this review
The lateral flow urine lipoarabinomannan assay (LF-LAM, Alere DetermineTM TB LAM Ag, Alere Inc, Waltham, MA, USA) is a commercially available point-of-care test for active TB (pulmonary and extrapulmonary TB). The test detects lipoarabinomannan (LAM), a component of the bacterial cell walls, which is present in some people with active TB. The test is performed by placing urine on one end of a test strip, with results appearing as a line (that is, a band) on the strip if TB is present. The test is simple, requires no special equipment, and shows results in 25 minutes. During the period we conducted the review, the manufacturer issued new recommendations for defining a positive test. We collected data based on both the original and the new recommendations
We aimed to see how accurately LF-LAM diagnosed TB in people living with HIV with TB symptoms, and how accurately LF-LAM diagnosed TB in people living with HIV being screened for TB whether or not they had TB symptoms.
We examined evidence up to 5 February 2015 and included 12 studies: six studies evaluated LF-LAM for TB diagnosis and six studies evaluated the test for TB screening. All studies were conducted in low- or middle-income countries.
Quality of the evidence
We assessed quality by describing how participants were selected for the studies, details of the test and reference standards (the benchmark test), and study flow and timing, using the standard QUADAS-2 approach. Few studies used multiple types of specimens for the reference standard (higher quality standard) and most relied on sputum culture alone (lower quality standard), which may have affected results.
What do the results mean?
In a population of 1000 HIV-positive individuals with TB symptoms, where 300 actually have TB, the test will correctly identify 135 people as having TB, but miss the remaining 165 people; for the 700 people who do not have TB, the test will correctly identify 644 people as not having TB, but will misclassify 56 as having TB.
The sensitivity of the test is higher in people living with HIV with low CD4 cell counts who are at risk of life-threatening illnesses. In patients with a CD4 ≤ 100 cells per µL, LF-LAM sensitivity was 56% (41% to 70%) versus 26% (16% to 46%) in patients with a CD4 count > 100 cells per µL.
If the test is used in screening HIV-positive people for TB, in a population of 1000 where 10 actually have TB, LF-LAM will correctly identify none of the 10, or up to four of the 10; on the other hand, the test will miss six to 10 people with TB; in the remaining 990 who do not have TB, the test will correctly identify 931 to 941 people as not having TB while misclassifying 49 to 59 as having TB.
The main limitations of the review were the use of a lower quality reference standard in most included studies, and small number of studies and participants included in the analyses. The results should, therefore, be interpreted with caution.
In this Cochrane review, we found that LF-LAM, whether the test is used for diagnosis or screening, has low sensitivity to detect TB. However, in HIV-positive people with low CD4 counts who are seriously ill, LF-LAM may help with the diagnosis of TB.