02201nas a2200253   4500000000100000008004100001260001200042653001400054653003400068653001500102653001200117653001400129100001300143700001200156700001600168700001300184700001600197700001400213700001300227700001100240245011100251520157100362022001401933       2020                            d  c03/202010aArmadillo10aDelayed-type hypersensitivity10aGuinea pig10aleprosy10aSkin test1 aDuthie M1 aPena MT1 aKhandhar AP1 aPicone A1 aMacMIllen Z1 aTruman RW1 aAdams LW1 aReed S00aDevelopment of LepReact, a defined skin test for paucibacillary leprosy and low-level M. leprae infection.3 a<p>The persistence of new leprosy cases in endemic areas such as India, Brazil, Bangladesh, and the Philippines has encouraged studies of chemoprophylaxis among contacts of patients. Epidemiological screening tools to enable early detection of infected individuals in endemic populations would be critical to target individuals most in need of intervention. Despite decades of attempts, however, there still are no tests available for the early detection of low-level infection with Mycobacterium leprae. In this report, we describe the development of a leprosy skin test using M. leprae-specific antigens. We selected the chimeric LID-1 fusion protein, formulated to achieve maximum performance at a minimal dose, as a skin test candidate based on its ability to elicit delayed-type hypersensitivity (DTH) reactions in M. leprae immune guinea pigs in a sensitive and specific manner, i.e., with no cross-reactivity observed with other mycobacterial species. Importantly, evaluations in armadillos indicated that intradermal inoculation of formulated LID-1 could distinguish uninfected from M. leprae-infected animals manifesting with symptoms distinctly similar to the PB presentation of patients. Together, our data provide strong proof-of-concept for developing an antigen-specific skin test to detect low-level M. leprae infection. Such a test could, when applied with appropriate use of chemo- and/or immunoprophylaxis, be instrumental in altering the evolution of clinical disease and M. leprae transmission, thus furthering the objective of zero leprosy.</p>  a1432-0614