title: Challenges presented by nerve damage in leprosy.
abstract: The basis of nerve damage in leprosy is the unique tendency of Mycobacterium leprae to invade Schwann cells. alphaBeta-Dystroglycan on the basement membrane of Schwann cells binds to laminin alpha2, in turn binding to receptors on the M. leprae surface, comprising a histone-like protein and phenoglycolipid-1. When nerve damage during reversal reactions was found to be associated with an abrupt increase in delayed type hypersensitivity against M. leprae antigenic determinants released from Schwann cells, it suggested that the nerve is damaged as an innocent bystander during the immune response. This strongly influenced the introduction of therapy based on immunosuppression combined with continued anti-mycobacterial medication. Lysis of Schwann cells presenting M. leprae antigenic determinants by activated CD4+ T cells and interaction of M. leprae with Toll-like receptors on Schwann cells are additional mechanisms implicated in nerve damage. Persistence of M. leprae antigen in local lesions after regular multiple drug therapy (MDT) is an important risk factor for late reactions. In spite of significant advances in the provision of MDT globally, early diagnosis, together with effective treatment of the disease and associated nerve damage at initial presentation remains a major challenge for the health services. Reduced prevalence as a result of MDT should not be taken to indicate that the challenges of leprosy control are diminished as long as nerve damage is not controlled and new case detection rates are not declining.
authors.affiliation: Institute of Immunology, University of Oslo, Rikshospitalet, Norway. morten.harboe@labmed.uio.no
authors.forename: Morten
authors.initials: M
authors.lastname: Harboe
authors.forename: Abraham
authors.initials: A
authors.lastname: Aseffa
authors.forename: Ruth
authors.initials: R
authors.lastname: Leekassa
mesh_terms: D004359:Drug Therapy, Combination; D006801:Humans; D007918:Leprosy / Q000150:complications*; D009166:Mycobacterium leprae / Q000276:immunology; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D012583:Schwann Cells / Q000276:immunology