Immunotherapy for drug-refractory mucosal leishmaniasis
ABSTRACT 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.
The Journal of Antibiotics 04/2014; 67(8). DOI:10.1038/ja.2014.47 · 2.04 Impact Factor
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ABSTRACT: Introduction: Numerous therapeutic strategies are used to treat leishmaniasis. The treatment of cutaneous leishmaniasis (CL) is solely depends on antimonate derivatives with safety issues and questionable efficacy and there is no fully effective modality to treat CL caused by Leishmania tropica and Leishmania braziliensis. Areas covered: There is no prophylactic vaccine available against any form of leishmaniasis. Immunotherapy for CL has a long history; immunotherapy trials of first and second generation vaccines showed promising results. The current article briefly covers the prophylactic vaccines and explains different immunotherapy strategies that have been used to treat leishmaniasis. This paper does not include experimental vaccines and only lays emphasis on human trials and those vaccines which reached human trials. Expert opinion: Immunotherapy is currently used to successfully treat several disorders; Low cost, limited side effects and no possibility to develop resistance make immunotherapy a valuable choice especially for infectious disease with chemotherapy problems. Efforts are needed to explore the immunological surrogate marker(s) of cure and protection in leishmaniasis and overcome the difficulties in standardization of crude Leishmania vaccines. One of the reasons for anti-leishmaniasis vaccine failure is lack of an appropriate adjuvant. So far, not enough attention has been paid to develop vaccines for immunotherapy of leishmaniasis.Expert Opinion on Biological Therapy 07/2014; 14(11):1-9. DOI:10.1517/14712598.2014.945415 · 3.65 Impact Factor
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ABSTRACT: Visceral leishmaniasis (VL) is a vector-borne chronic infectious disease caused by the protozoan parasite Leishmania donovani or Leishmania infantum. VL is a serious public health problem, causing high morbidity and mortality in the developing world with an estimated 0.2-0.4 million new cases each year. In the absence of a vaccine, chemotherapy remains the favored option for disease control, but is limited by a narrow therapeutic index, significant toxicities, and frequently acquired resistance. Improved understanding of VL pathogenesis offers the development and deployment of immune based treatment options either alone or in combination with chemotherapy. Modulations of host immune response include the inhibition of molecular pathways that are crucial for parasite growth and maintenance; and stimulation of host effectors immune responses that restore the impaired effector functions. In this review, we highlight the challenges in treatment of VL with a particular emphasis on immunotherapy and targeted therapies to improve clinical outcomes.Frontiers in Immunology 06/2014; 5:296. DOI:10.3389/fimmu.2014.00296