Diagnostic Value of a Lateral-flow Urine Lipoarabinomannan Assay in Adults With Active Pulmonary Tuberculosis.

Abstract

Background Tuberculosis, as an infectious illness, remains a leading cause of morbidity and mortality globally. The burden of disease is felt mostly in the middle and low income countries. Among persons living with HIV/AIDS, tuberculosis is the leading cause of morbidity and mortality. Diagnosis of tuberculosis remains a challenge to date despite advances in the diagnostic tests. Currently, there are limited point of care tests in use for diagnosis of tuberculosis. The lateral flow-urine lipoarabinomannan assay is such a point of care test. It detects lipoarabinomannan, a component of the mycobacterial cell wall, using an imunochromatographic assay. The assay is read in about 35 minutes and therefore provides an opportunity to diagnose tuberculosis at first point of contact with the health facility. Objective To determine the diagnostic value of the lateral flow lipoarabinomannan (LF-LAM) assay among adult patients with active pulmonary tuberculosis Methodology This was a cross sectional study conducted at the out-patient TB clinics, chest clinics and the in-patient facilities at Mbagathi County Hospital and Kenyatta National Hospital in Nairobi. The study subjects were adults presenting with features suggestive of pulmonary TB. Urine and sputum samples were obtained from the patients. Tests conducted were urine LAM, sputum ZN microscopy, sputum geneXpert® and sputum TB culture BACTEC MGIT 960. HIV testing was also offered. HIV positive patients had their CD4+ counts determined. The sensitivity, specificity, positive and negative predictive values of the TB diagnostic tests were determined; the liquid culture was used as the gold standard. Results The sensitivity of the urine LAM assay was low when it was applied to a heterogenous population,28.6%(95% CI, 20.6-38.3%). This was lower in the HIV negative population at 12.7% (95%CI 6.4-23.5%). This was in contrast to a sensitivity of 58.8% (95%CI 42.2-73.6%) when it was applied to a HIV positive population. When it was combined with sputum ZN microscopy, the sensitivity of the combined tests increased to 70.6%. The sensitivity increased to 96.2% when the LAM assay was combined with the sputum geneXpert®. The specificity of the urine LAM assay was lower when it was applied to the HIV positive population, than in the HIV negative population, 85.1%(95%CI 74.4-91.8%) versus 93.6% (95% CI, 86.4-97.3%) respectively. Among the HIV positive, it was also noted that the sensitivity of the LAM assay increased as the CD4+ count decreased whereas the specificity decreased as the CD4+ count decreased. Conclusion The lateral flow urine LAM assay was able to diagnose pulmonary TB among HIV positive patients especially those with low CD4+ counts of 200 and below. The sensitivity of the assay was low in an unselected population and among the HIV negative. The LAM assay improved on diagnosis of pulmonary tuberculosis among the HIV positive when used in combination with ZN microscopy or the sputum geneXpert® assay