DEFAR - Artigos publicados em periódicos
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Item Immunotherapy and immunochemotherapy in visceral leishmaniasis : promising treatments for this neglected disease.(2014) Roatt, Bruno Mendes; Soares, Rodrigo Dian de Oliveira Aguiar; Vital, Wendel Coura; Ker, Henrique Gama; Moreira, Nádia das Dores; Souza, Juliana Vitoriano de; Giunchetti, Rodolfo Cordeiro; Carneiro, Cláudia Martins; Reis, Alexandre BarbosaLeishmaniasis has several clinical forms: self-healing or chronic cutaneous leishmaniasis or post-kala-azar dermal leishmaniasis; mucosal leishmaniasis; visceral leishmaniasis (VL), which is fatal if left untreated.The epidemiology and clinical features of VL vary greatly due to the interaction of multiple factors including parasite strains, vectors, host genetics, and the environment. Human immunodeficiency virus infection augments the severity of VL increasing the risk of developing active disease by 100–2320 times. An effective vaccine for humans is not yet available. Resistance to chemotherapy is a growing problem in many regions, and the costs associated with drug identification and development, make commercial production for leishmaniasis, unattractive.The toxicity of currently drugs, their long treatment course, and limited efficacy are significant concerns. For cutaneous disease, many studies have shown promising results with immunotherapy/immunochemotherapy, aimed to modulate and activate the immune response to obtain a therapeutic cure. Nowadays, the focus of many groups centers on treating canine VL by using vaccines and immunomodulators with or without chemotherapy. In human disease, the use of cytokines like interferon-g associated with pentavalent antimonials demonstrated promising results in patients that did not respond to conventional treatment. In mice, immunomodulation based on monoclonal antibodies to remove endogenous immunosuppressive cytokines (interleukin-10) or block their receptors, antigen-pulsed syngeneic dendritic cells, or biological products like Pam3Cys (TLR ligand) has already been shown as a prospective treatment of the disease. This review addresses VL treatment, particularly immunotherapy and/or immunochemotherapy as an alternative to conventional drug treatment in experimental models, canine VL, and human disease.Item Evaluation of a prototype flow cytometry test for serodiagnosis of canine visceral leishmaniasis.(2013) Ker, Henrique Gama; Vital, Wendel Coura; Soares, Rodrigo Dian de Oliveira Aguiar; Roatt, Bruno Mendes; Moreira, Nádia das Dores; Carneiro, Cláudia Martins; Machado, Evandro Marques de Menezes; Carvalho, Andréa Teixeira de; Martins Filho, Olindo Assis; Giunchetti, Rodolfo Cordeiro; Araújo, Márcio Sobreira Silva; Coelho, Eduardo Antônio Ferraz; Lemos, Denise da Silveira; Reis, Alexandre BarbosaCanine visceral leishmaniasis (CVL) is considered one of the most important canine protozoan diseases of zoonotic concern (1). Various species of Phlebotomus and Lutzomyia sandflies are the potential vectors for the pathogenic agent Leishmania infantum (2). In some European, Asian, and African countries and in America, infection in dogs is associated with a risk of human disease (3–5). In Brazil, the Ministry of Health, through the Visceral Leishmaniasis Control and Surveillance Program (VLCSP), has instituted specific measures to reduce morbidity and case fatality rates, including treating human cases, instituting vector control, and, an action that is unique in the world, sacrificing all seropositive/infected dogs and prohibiting the treatment of CVL (6). During the last decade, the criteria for eliminating infected animals were based on enzyme-linked immunosorbent assays (ELISAs) for screening and indirect immunofluorescence antibody tests (IFATs) for the confirmatory diagnosis of CVL (6, 7). That these tests may lead to false-positive results due to crossreactivity with other parasitic diseases is well known (8, 9). Recently, this approach was modified, and testing is now based on a dual-path platform (DPP) for screening and an ELISA for confirmation (10). However, Grimaldi et al. (11) evaluated the DPP test for the serodiagnosis of CVL and showed that it does not perform well in detecting asymptomatic dogs from areas where canine disease is endemic. It has been shown that vaccination with Leishmune may lead to seroconversion in healthy dogs (10). The vaccination of dogs has increasingly become a common practice in areas in Brazil where CVL is endemic; recently, in addition to the Leishmune vaccine, the Leish-Tec vaccine has become available commercially, and new candidates, such as the LBSap vaccine, are being studied (12– 15). In this sense, seroconversion has become an important problem for surveillance/control programs that employ conventional methodologies in their seroepidemiological surveys, because it can lead to the unnecessary euthanasia of healthy dogs. Nevertheless, the role of vaccination in the diagnosis of CVL still has not been studied sufficiently.Item LBSapSal-vaccinated dogs exhibit increased circulating T-lymphocyte subsets (CD4+ and CD8+) as well as a reduction of parasitism after challenge with Leishmania infantum plus salivary gland of Lutzomyia longipalpis.(2014) Soares, Rodrigo Dian de Oliveira Aguiar; Roatt, Bruno Mendes; Ker, Henrique Gama; Moreira, Nádia das Dores; Mathias, Fernando Augusto Siqueira; Cardoso, Jamille Mirelle de Oliveira; Gontijo, Nelder de Figueiredo; Romero, Oscar Bruna; Carvalho, Andréa Teixeira de; Martins Filho, Olindo Assis; Oliveira, Rodrigo Corrêa de; Giunchetti, Rodolfo Cordeiro; Reis, Alexandre BarbosaBackground: The development of a protective vaccine against canine visceral leishmaniasis (CVL) is an alternative approach for interrupting the domestic cycle of Leishmania infantum. Given the importance of sand fly salivary proteins as potent immunogens obligatorily co-deposited during transmission of Leishmania parasites, their inclusion in an anti-Leishmania vaccine has been investigated in the last few decades. In this context, we previously immunized dogs with a vaccine composed of L. braziliensis antigens plus saponin as the adjuvant and sand fly salivary gland extract (LBSapSal vaccine). This vaccine elicited an increase in both anti-saliva and anti-Leishmania IgG isotypes, higher counts of specific circulating CD8+ T cells, and high NO production. Methods: We investigated the immunogenicity and protective effect of LBSapSal vaccination after intradermal challenge with 1 × 107 late-log-phase L. infantum promastigotes in the presence of sand fly saliva of Lutzomyia longipalpis. The dogs were followed for up to 885 days after challenge. Results: The LBSapSal vaccine presents extensive antigenic diversity with persistent humoral and cellular immune responses, indicating resistance against CVL is triggered by high levels of total IgG and its subtypes (IgG1 and IgG2); expansion of circulating CD5+, CD4+, and CD8+ T lymphocytes and is Leishmania-specific; and reduction of splenic parasite load. Conclusions: These results encourage further study of vaccine strategies addressing Leishmania antigens in combination with proteins present in the saliva of the vector.