This study seeks to determine which rifampin-containing treatment modality is the most effective leprosy PEP regimen regardless of a) the immune status of the host and b) whether the leprosy infection is caused by M. leprae or M. lepromatosis.
The Use of Molecular Methods in Subclinical Murine Models of Leprosy to Examine the Efficacy of Proposed Post-Exposure Prophylaxis (PEP) Regimens
While multidrug therapy has considerably reduced the global impact of leprosy by lowering the overall prevalence of disease, it has not eliminated the incidence of new cases, particularly in areas of high endemicity. This indicates that transmission of leprosy is ongoing despite effective treatment. Persons with subclinical leprosy infections, possibly acquired from contact with confirmed leprosy cases, are believed to be one of the leading causes of this continuing transmission in areas with a high number of cases. Treatment of those known to have been exposed to leprosy, also known as post-exposure prophylaxis (PEP), could decrease the level of subclinical infections and, subsequently, transmission of the disease from person to person. This study will evaluate various PEP regimens and provide experimental evidence on their level of effectiveness. In order to achieve this, subclinical infections with leprosy bacteria will be established in three different mouse strains (Balb/c, Interferon-γ knockout (GKO), and athymic nude), which have distinct levels of immune competence. Upon infection, each of these strains exhibits features consistent with specific areas across the leprosy spectrum. Therefore, the team will model the interplay of the host immune status with the different PEP drug treatments. Drug efficacy will be evaluated using state-of the-art genetic tests with high specificity and sensitivity. The goal is to determine the most effective PEP regimen, regardless of the level of immune functionality in the host. Furthermore, the study will compare the efficacy of the different regimens against subclinical infections of both Mycobacterium leprae and Mycobacterium lepromatosis to ascertain if there is any difference in the treatment required between these two leprosy-causing bacterial species. In summary, this study is aimed at determining PEP regimens that are effective against both M. leprae and M. lepromatosis, regardless of the functioning of the host immune system or the lack there of. The study will provide useful experimental information to assist in the design of future PEP clinical trials.
Co-financer: Turing Foundation