Lipoarabinomannan (LAM)—a potential biomarker for the diagnosis of tuberculosis from the urine of infected elephants

Abstract

The spread of tuberculosis (TB) in Asian countries is mainly due to co-existence and close association of humans with elephants and other domestic livestock. Infected animals tend to shed the organism in the preclinical period which risks the transmission of the infection from animals to humans and vice versa. Since tuberculosis infection is chronic and lack specific clinical signs, diagnosis remains challenging. The present study focuses on the utilization of lipoarabinomannan (LAM), a glycolipid for the detection of TB infection in elephants. Usage of urine as the biological sample for the diagnosis makes it more advantageous. Seroprevalence of tuberculosis (TB) in elephants in Kerala were found to be 37.2% (n = 86) using Chembio DPP VetTB assay. Nine (10.46%) out of 86 elephants were positive for AFB and 29 (33.7%) out of 86 elephants were positive for LAM antigen. On comparison of efficiency of LF-LAM assay with that of DPP VetTB assay, LF-LAM assay had a sensitivity of 90.63%, specificity 100%, positive predictive value 100%, negative predictive value 94.7%, accuracy 95.51%, and kappa statistic value 0.924 (p value < 0.001). On comparison of LF-LAM with traditional acid fast staining method, LF-LAM assay had the sensitivity of 100%, specificity 74.03%, positive predictive value 31%, negative predictive value 100%, accuracy 76.74%, and kappa statistic value 0.374 (p value < 0.001). The presence of Mycobacterium tuberculosis was confirmed in trunk wash sample using PCR targeting gene IS6110, at 245 bp amplicon size and 25 seropositive elephants (78.2%) were confirmed positive. Custom sequencing and phylogenetic analysis revealed that the isolate obtained was Mycobacterium tuberculosis. This study in elephants prove that TB LAM Ag (LF-LAM) can be used as potent biomarker for diagnosis of tuberculosis in elephants.