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      Evaluation of an immunochemotherapeutic protocol constituted of N-methyl meglumine antimoniate (Glucantime ®) and the recombinant Leish-110f ® + MPL-SE ® vaccine to treat canine visceral leishmaniasis

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          Summary

          The evaluation of the efficacy of an immunochemotherapy protocol to treat symptomatic dogs naturally infected with Leishmania chagasi was studied. This clinical trial had the purpose to test the combination of N-methyl meglumine antimoniate (Glucantime ®) and the second generation recombinant vaccine Leish-110f ® plus the adjuvant MPL-SE ® to treat the canine leishmaniasis (CanL). Thirty symptomatic naturally infected mongrel dogs were divided into five groups. Animals received standard treatment with Glucantime ® or treatment with Glucantime ®/Leish-110f ® + MPL-SE ® as immunochemotherapy protocol. Additional groups received Leish-110f ® + MPL-SE ® only, MPL-SE ® only, or placebo. Evaluation of haematological, biochemical (renal and hepatic function) and plasmatic proteins, immunological (humoral and cellular immune response) and the parasitological test revealed improvement of the clinical parameters and parasitological cure in dogs in both chemotherapy alone and immunochemotherapy cohorts. However, the immunotherapy and immunochemotherapy cohorts had reduced number of deaths, higher survival probability, and specific cellular reactivity to leishmanial antigens, in comparison with chemotherapy cohort only and control groups (adjuvant alone and placebo).

          These results support the notion of using well-characterized recombinant vaccine as an adjunct to improve the current chemotherapy of CanL.

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          Leishmaniasis--current chemotherapy and recent advances in the search for novel drugs.

          Graham Coombs, S Croft (2003)
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            A retrospective clinical study of canine leishmaniasis in 150 dogs naturally infected by Leishmania infantum.

            P Ciaramella, G Oliva, R D Luna … (1997)
            The clinical and laboratory findings observed in 150 dogs naturally infected by Leishmania infantum, from a large endemic area of southern Italy, are described. There was a gradual onset of clinical signs and the course of the disease was progressive in almost all the cases. The majority of the dogs were mongrels (43.3 per cent), male (64.7 per cent), of medium size (50.6 per cent), three to seven years old (64.7 per cent), and living outdoors (60 per cent). They showed generalised (56.7 per cent) or symmetrical (32 per cent) lymphadenomegaly; the mucous membranes of 87 of the dogs (58 per cent) were pale and moderate or severe splenomegaly was diagnosed in 80 dogs (53.3 per cent); weight loss was observed in 32 per cent of the animals. Skin abnormalities were very common, and included dry exfoliative dermatitis (56 per cent), ulcers (40 per cent) periorbital alopecia ('lunettes') (18 per cent), diffuse alopecia (14 per cent) and onychogryphosis (24 per cent). Ocular signs were observed in 24 dogs (16 per cent) including 16 cases of keratoconjunctivitis (three with keratoconjunctivitis sicca), six cases of moderate uveitis and two cases of panophthalmitis. The acute form of the disease was diagnosed in only six dogs and was characterised by fever and generalised lymphadenomegaly, and by the absence of skin lesions. Another six dogs had severe renal failure without systemic clinical signs of leishmaniasis. The most important laboratory findings were a severe or moderate increase in gammaglobulins, hypoalbuminaemia, hyperproteinemia and anaemia. Cultures or cytology tests for L infantum parasites were positive in 134 of the dogs. Following the standard procedures developed for human lymph node and bone marrow cytology tests, the leishmania density in the dogs varied from 1+ to 2+. Leishmania antibody titres were high (> 1:160) in almost all the dogs. Immunological tests for autoantibodies were positive in 25 of 53 dogs tested in the antinuclear antibody (ANA) test, in 15 of 43 dogs tested in the latex test and in five of 24 dogs tested in the Coombs test.
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              Cellular and humoral immune responses in dogs experimentally and naturally infected with Leishmania infantum.

              E Pinelli, R. Killick-Kendrick, J. Wagenaar … (1994)
              In this paper we describe a number of immunological parameters for dogs with a chronic Leishmania infantum infection which exhibit patterns of progressive disease or apparent resistance. The outcome of infection was assessed by isolation of parasites, serum antibody titers to Leishmania antigen, and development of clinical signs of leishmaniasis. Our studies show that 3 years after experimental infection, asymptomatic or resistant dogs responded to L. infantum antigen both in lymphocyte proliferation assays in vitro and in delayed-type hypersensitivity reaction, whereas no serum antibodies to parasite antigen were shown. In contrast, symptomatic or susceptible animals failed to respond to parasite antigen in cell-mediated assays both in vitro and in vivo and showed considerably higher serum antibodies to leishmanial antigens. In addition, significantly higher level of interleukin 2 (IL-2) and tumor necrosis factor were found in supernatants from stimulated peripheral mononuclear cells from asymptomatic dogs compared with those from symptomatic and control uninfected dogs. IL-6 production did not vary significantly among the groups studied. Finally, we observed similar results with a group of mixed-breed dogs with natural Leishmania infections also grouped as asymptomatic or symptomatic on the basis of clinical signs of canine visceral leishmaniasis. These results demonstrate that serum antibody titers, antigen-specific proliferative responses, delayed-type hypersensitivity skin reactions, and IL-2 and tumor necrosis factor production by peripheral mononuclear cells can be used as markers of disease progression.
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                Author and article information

                Contributors
                Evaldo Nascimento
                Journal
                Journal ID (nlm-ta): Vaccine
                Journal ID (iso-abbrev): Vaccine
                Title: Vaccine
                Publisher: Elsevier Ltd.
                ISSN (Print): 0264-410X
                ISSN (Electronic): 1873-2518
                Publication date PMC-release: 4 February 2008
                Publication date (Print): 17 March 2008
                Publication date (Electronic): 4 February 2008
                Volume: 26
                Issue: 12
                Pages: 1585-1594
                Affiliations
                [a ]Laboratório de Leishmanioses e Vacinas, Departamento de Parasitologia, Instituto de Ciências Biológicas (ICB), Universidade Federal de Minas Gerais (UFMG), Avenida Antônio Carlos 6627, Pampulha CEP 31270-901, Belo Horizonte, MG, Brazil
                [b ]Centro de Pesquisas René Rachou (CPqRR/FIOCRUZ), Belo Horizonte, MG, Brazil
                [c ]Fundação Nacional da Saúde, Ministério da Saúde (FUNASA), MG, Brazil
                [d ]The Forsyth Institute, Boston, MA, United States
                [e ]The Infectious Disease Research Institute, Seattle, WA, United States
                Author notes
                [* ]Corresponding author at: Laboratório de Leishmanioses e Vacinas, Departamento de Parasitologia, Instituto de Ciências Biológicas (ICB), Universidade Federal de Minas Gerais (UFMG), Avenida Antônio Carlos 6627, Pampulha CEP 31270-901, Belo Horizonte, MG, Brazil. Tel.: +55 3134992859; fax: +55 3134992859. evaldo@ 123456icb.ufmg.br
                Article
                Publisher ID: S0264-410X(08)00034-0
                DOI: 10.1016/j.vaccine.2008.01.026
                PMC ID: 7127155
                PubMed ID: 18328956
                SO-VID: 4f6edc41-ef51-44b9-99f2-4e327a3c1283
                Copyright © Copyright © 2008 Elsevier Ltd. All rights reserved.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 18 September 2007
                Date revision received : 22 December 2007
                Date accepted : 3 January 2008
                Categories
                Subject: Article

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: leishmania chagasi,leishmaniasis,canine visceral leishmaniasis,immunochemotherapy
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: leishmania chagasi, leishmaniasis, canine visceral leishmaniasis, immunochemotherapy

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