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1/3. Successful use of a defined antigen/GM-CSF adjuvant vaccine to treat mucosal leishmaniasis refractory to antimony: A case report.

    immunotherapy has been proposed as a method to treat mucosal leishmaniasis for many years, but the approach has been hampered by poor definition and variability of antigens used, and results have been inconclusive. We report here a case of antimonial-refractory mucosal leishmaniasis in a 45 year old male who was treated with three single injections (one per month) with a cocktail of four Leishmania recombinant antigens selected after documented hypo-responsiveness of the patient to these antigens, plus 50 microg of GM-CSF as vaccine adjuvant. Three months after treatment, all lesions had resolved completely and the patient remains without relapse after two years. Side effects of the treatment included only moderate erythema and induration at the injection site after the second and third injections. We conclude that carefully selected microbial antigens and cytokine adjuvant can be successful as immunotherapy for patients with antimonial-refractory mucosal leishmaniasis.
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keywords = antigen
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2/3. Differential interferon- gamma production characterizes the cytokine responses to Leishmania and mycobacterium leprae antigens in concomitant mucocutaneous leishmaniasis and lepromatous leprosy.

    BACKGROUND: Tegumentary leishmaniasis and leprosy display similar spectra of disease phenotypes, which are dependent on cell-mediated immunity to specific antigens. Diffuse cutaneous leishmaniasis and lepromatous leprosy represent the anergic end of the spectrum, whereas mucocutaneous leishmaniasis and tuberculoid leprosy are associated with marked antigen-specific cellular immune response. methods: We characterized and compared the cell-mediated response to Leishmania and mycobacterium leprae antigens in a patient with an intriguing association of mucocutaneous leishmaniasis with lepromatous leprosy, which are at opposite ends of the immunopathological spectra of these diseases. This was done by performance of skin tests and by assessment of the cell proliferation and cytokine production of peripheral blood mononuclear cells (PBMCs). RESULTS: Strong skin-test reactions and PBMC proliferation were observed in response to Leishmania antigens but not to M. leprae antigens. The stimulation of PBMCs with Leishmania and M. leprae antigens induced comparable levels of tumor necrosis factor- alpha , interleukin-5, and interleukin-10. However, the interferon- gamma response to Leishmania antigens was remarkably high, and that to M. leprae antigens was almost nil. CONCLUSIONS: We found that concomitant leprosy and tegumentary leishmaniasis can produce opposite polar forms associated, respectively, with absent or exaggerated cell-mediated immune responses to each pathogen. This suggests that independent mechanisms influence the clinical outcome of each infection. Moreover, interferon- gamma appears to play a major role in the clinical expression of these intracellular infections.
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ranking = 1.5
keywords = antigen
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3/3. Impaired production of cytokines in a case of human leishmaniasis.

    A patient presented with the unique clinical picture of diffuse cutaneous and mucosal leishmaniasis caused by leishmania tropica. Elevated serum levels of several cytokines including interleukin (IL) 2, interferon gamma (IFN-gamma), and tumor necrosis factor alpha were found. All cytokine levels returned to normal during therapy. No IL-10 or IL-4 levels were detectable. In whole blood cultures, induction of IFN-gamma by lipopolysaccharide (LPS) was completely negative, even after therapy. concanavalin a (Con A)-induced release of IFN-gamma, like Con A-induced release of the other cytokines, was only initially impaired but returned to normal during therapy. Induction of the other cytokines by LPS was never impaired. The low expression of human leukocyte antigen DR on monocytes increased during IFN-gamma therapy but dropped when IFN-gamma treatment was ceased. We conclude that in this patient one or more of the routes of IFN-gamma production was impaired, thus resulting in insufficient IFN-gamma production in the infected lesions (although IFN-gamma was systemically present).
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ranking = 0.125
keywords = antigen
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