Utility of urine LAM Biomarker for treatment response monitoring during 8 weeks of MDR-TB treatment at Mulago National Referral Hospital

Abstract

Background: The current methods used in monitoring treatment response among MDR - TB patients have low sensitivity, take long to give results, are expensive and require BSL3 facilities. It is known that MTB LAM as a biomarker can be detected in urine. Whether there is a positive correlation between reductions in levels of LAM excreted in urine of MDR-TB patient samples against sputum culture time to positivity remains less answered, and was the main focus of this study. Therefore, this study evaluated the Utility of Urine Lateral flow LAM RDT as alternative method for monitoring treatment response of MDR-TB patients during the initial eight weeks of treatment. Methods: 165 stored urine samples collected by mother study from 33 MDR - TB patients at weeks 0, 2, 4, 6, and 8 were used to run LF-LAM. Urine samples retrieved from biorepository at storage temperature of -800C, were cropped to room temperature at 20-250C. A lateral flow LAM Alere Determine assay (LF-LAM) was run on the samples and reading grades recorded after 25 min in the Mycobacteriology Laboratory. Sputum culture results from records of the mother study that were based on to select for representative samples for this prospective nested study were used. LF-LAM results were correlated against time to conversion of sputum MGIT culture using Spearman’s Rank Correlation test and the means between the different groups were compared using the Wilcoxon –Mann Whitney test. Only values with a P value < 0.05 were taken as statistically significant. Results: There was a positive weak correlation between reducing urine LAM Alere Determine grades and increasing sputum MGIT-culture time to positivity at a coefficient of 0.163 (p=0.365>0.05 and CI;95%). Also a positive weak correlation for age factor of 0.454 (p=0.008<0.5), but weak non-significant correlation for body-mass index at -0.050 (p=0.782>0.05) was observed ANOVA on clinical and demographic factors of samples analysed found a non-significant relationship between urine LAM lateral flow grades with MGIT-culture time to conversion. A good inverse relationship between urine Lam lateral flow grades and MGIT time to positivity obtained was a reliable indication that LAM grades decreased as bacterial load decreased during 8 weeks of treatment. Also linear regression of urine LAM grades with associated factors of sex, family member diagnosed with TB in last 12 months, history of smoking, knowledge of HIV status, ever been diagnosed with TB before, at least two common TB symptoms, showed a positive significant relationship of age but not for other factors. Conclusion: The rapid diagnostic test (LF-LAM) can be relied upon to monitor treatment response among patients of MDR-TB.. However, there is need to evaluate this biomarker in MDR TB studies with large sample size to come up with more reliable findings for a more reliable statistically sound scientific conclusion. Recommendation. LF-LAM may be used as a POC treatment response monitoring tool in MDR TB patients. This may guide timely change of MDR TB regimen for non-responding patients thus reducing wastage of drugs as well as minimizing the risk of death and progress to XDR TB.