Abstract
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.
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Acknowledgments
We thank Richard Cabullos and Raodoh Mohamath for technical assistance producing the antigens used.
Funding
This research was conducted under NIH SBIR contract HHSN272201800019C, along with grants from the American Leprosy Missions, and an interagency agreement AAI15006 between the US Department of Health and Human Services Health Resources and Services Administration (HRSA) and NIAID. The funders had no input to the production of this manuscript, and the opinions provided are the authors’ own.
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Duthie, M.S., Pena, M.T., Khandhar, A.P. et al. Development of LepReact, a defined skin test for paucibacillary leprosy and low-level M. leprae infection. Appl Microbiol Biotechnol 104, 3971–3979 (2020). https://doi.org/10.1007/s00253-020-10505-2
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DOI: https://doi.org/10.1007/s00253-020-10505-2