The stable incidence of new leprosy cases suggests that transmission of infection continues despite worldwide implementation of MDT. Thus, specific tools are needed to diagnose early stage Mycobacterium leprae infection, the likely sources of transmission. M. leprae antigens that induce T-cell responses in M. leprae exposed and/or infected individuals thus are major targets for new diagnostic tools. Previously, we showed that ML1601c was immunogenic in patients and healthy household contacts (HHC). However, some endemic controls (EC) also recognized this protein. To improve the diagnostic potential, IFN-γ responses to ML1601c peptides were assessed using PBMC from Brazilian leprosy patients and EC. Five ML1601c peptides only induced IFN-γ in patients and HHC. Moreover, 24-hour whole-blood assay (WBA), two ML1601c peptides could assess the level of M. leprae exposure in Ethiopian EC. Beside IFN-γ, also IP-10, IL-6, IL-1β, TNF-α, and MCP-1 were increased in EC from areas with high leprosy prevalence in response to these ML1601c peptides. Thus, ML1601c peptides may be useful for differentiating M. leprae exposed or infected individuals and can also be used to indicate the magnitude of M. leprae transmission even in the context of various HLA alleles as present in these different genetic backgrounds. 1. Introduction Leprosy is a treatable infection caused by Mycobacterium leprae (M. leprae) involving skin and peripheral nerves and is influenced by genetic and environmental factors [1–3]. The infection can result in skin lesions, nerve degeneration, and deformities. Despite a spectacular decrease in global prevalence since 1982, transmission of leprosy is sustained as evidenced by the hundreds of thousand new cases of leprosy that keep being detected globally every year: 244,796 new cases of leprosy were detected during 2009 amongst whom 22,485 were children and the registered prevalence at the beginning of 2010 was 211,903 cases [4]. In Brazil, for example, the number of new cases detected during 2009 was 37,610 resulting in a registered prevalence of 38,179 at the end of first quarter of 2010 [4]. These figures demonstrate that M. leprae-infected contacts and persons with subclinical, undiagnosed leprosy, likely the major sources of unidentified transmission, are an incessant source of active transmission. Despite many efforts, prediction of disease development in affected individuals is still not possible nor can we detect asymptomatic M. leprae infection. Diagnosis of leprosy is usually based on clinical features and skin smear results including the
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