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Background: Leprosy is a neglected tropical disease caused by <i>Mycobacterium leprae</i>, leading to disabilities if untreated. The ELISA based on phenolic glycolipid I (PGL-I), or its synthetic version ND-O-BSA, is almost universally positive in multibacillary leprosy and thus extensively used in endemic countries. Household contacts with a positive antibody titer have ~6-fold higher probability to develop the disease than those with a negative titer. Thus, the aim of the study was to evaluate the performance of this ELISA in the setting of a non-endemic country. Methods: We calculate the cut-off using optimized O.D. thresholds, generated by receiver operating characteristics (ROC) curve analysis, testing 39 well-characterized sera obtained from lepromatous leprosy patients with strongly positive ND-O-BSAELISA titer and 39 sera from healthy non-endemic patients never exposed to <i>M. leprae</i> or <i>M. tuberculosis</i>. Indeed, we tested a second set of sera from suspected or confirmed leprosy or household contacts (SLALT group, n=50), and patients with tuberculosis (control group, n=40). Results: We detected 56.4% of SLALT and 22.5% of tuberculosis as positive, consistent with the literature. Conclusion: The ELISA based on ND-O-BSA may thus be considered a good option to be used in a non-endemic area as a screening tool in at risk population usually coming to our center.