Immunotherapy for Drug‐Refractory Mucosal Leishmaniasis

University of California, San Diego, San Diego, California, United States
The Journal of Infectious Diseases (Impact Factor: 6). 11/2006; 194(8):1151-9. DOI: 10.1086/507708
Source: PubMed


Pentavalent antimony (Sb(v)) is the mainstay therapy for mucosal leishmaniasis (ML), but it is toxic, and relapses are common. Immunotherapy using a mixture of killed parasites, with or without bacille Calmette-Guerin, is an alternative but is used sporadically because of inconsistent results.
We developed a defined immunotherapeutic antigen preparation for use in an observational, open-label trial to treat 6 patients with ML with a history of Sb(v) therapy failure. All patients were treated with the antigens thiol-specific antioxidant, Leishmania major stress inducible protein 1, Leishmania elongation initiation factor, and Leishmania heat shock protein 83, plus granulocyte-macrophage colony-stimulating factor. Patients underwent clinical and pathological evaluations before the initiation of immunotherapy and at 3, 6, 9, 12, 18, 24, and 60 months after.
One month after the third injection, 1 patient showed complete clinical remission (CC) and remained disease free for the duration of the study. At the 9-month follow-up examination, 5 patients showed CC, and all patients were asymptomatic at a subsequent 5-year follow-up examination.
These data support the concept that vaccine therapy with a defined antigen combination, used with standard chemotherapy, is a safe and effective approach to treat drug-refractory ML.

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Available from: Eduardo Martins Netto, Apr 27, 2015
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    • "Moreover the LeIF component was shown to have therapeutic activity in the Balb/c model of cutaneous leishmaniasis 20—24. More importantly, these antigens were recently and successfully used in an immunochemotherapeutic protocol to treat human mucosal leishmaniasis [25]. The three antigens are present in both amastigotes and promastigotes forms of the parasite and are highly conserved among Leishmania sp., a requisite for ensuring cross-species protection [23] [26] [27]. "
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    Vaccine 04/2008; 26(12):1585-94. DOI:10.1016/j.vaccine.2008.01.026 · 3.62 Impact Factor
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    • "Immunotherapy appears to be an unexplored area and has been used recently in refractory cases of mucosal leishmaniasis (Badaro et al. 2006). In the mid-1990s during an ongoing immunotherapeutic trial of leprosy using a heat killed non-pathogenic mycobacterial strain, Mycobacterium w, our team had inadvertently administered it to a patient of nodular PKDL along with antileprosy therapy. "
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    Tropical Medicine & International Health 08/2007; 12(7):848-51. DOI:10.1111/j.1365-3156.2007.01854.x · 2.33 Impact Factor
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    • "Professor R. Badaro presented data on the use of a mixture of four antigens discovered by IDRI together with GM-CSF (as adjuvant) on a compassionate basis for treatment of refractory cases of mucosal leishmaniasis (ML). This work was done at the Federal University of Bahia, Salvador, Brazil, in collaboration with IDRI and Corixa [34,35]. The four antigens were the three antigens later used to construct Leish-111f, plus 6H (LmHSP 83), which was chosen on the basis of its strong human T-cell stimulation. "
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