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PATHOGENESIS OF VISCERAL LEISHMANIASIS: THE DOG MODEL
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Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Abstract
Initially, VL was considered an eminently rural disease, but more recently, it has expanded to medium and large urban areas and has become a growing public health problem in the country and in other areas of the American continent. Due to its proximity to humans, the dog has been pointed as the main reservoir of L. infantum in China, the Mediterranean basin and the Americas. In addition to the importance of the dog as a reservoir, canine disease is also considered as valuable for the understanding of human disease. The clinical picture presented in canine disease is similar to the picture observed in human disease, with except for the cutaneous involvement observed in canine disease, which is more exacerbated than that observed in human disease. In addition, the natural history of canine disease has many similarities with human disease, which makes canine VL be an important model of study for human LV. An important aspect to be observed is the diversity of possible presentations of canine disease. Infected dogs may present from no clinical signs, and these animals are called asymptomatic, until a high number of signs, considered polysymptomatic. Due to this polymorphism, it has been sought to identify possible disease markers for the disease in order to define the profile of resistant animals and animals susceptible to visceral leishmaniasis. To date, some parameters have been used as markers of susceptibility and resistance, such as the presence of parasites in lymph nodes and other organs, such as the spleen, determined through culture. Identification of the parasite in tissue culture of the host indicates an inability of the host to control the proliferation of Leishmania in the organism, and consequently, to control the infection. The presence of clinical signs is an important marker. Animals with resistance to infection tend to remain asymptomatic for long periods, and may never show signs of disease, whereas susceptible animals present a series of clinical signs. However, the great variety and lack of specificity of the clinical signs attributed to VL makes it difficult to evaluate. Another important marker of resistance or susceptibility to visceral leishmaniasis is the result in the leishmanin skin test (LST). The positive LST result indicates that the animal produces a cellular response when in contact with the Leishmania antigen, and since immunity to the parasite is mediated by T cells, a positive cellular response may indicate a resistance profile to infection. An aspect to be evaluated is the production of specific antibodies. Asymptomatic animals have been shown to produce IgG1 in greater amounts, while symptomatic animals produce more IgA, IgE and IgG2. It was also observed that animals with higher levels of IgG1 present lower parasite burden in the bone marrow, whereas animals with higher levels of IgA, IgM and IgG2 present higher parasitic burden in organs such as skin, bone marrow, lymph node and spleen. Our group demonstrated that there is an association between the presence of severity markers and the disruption of the spleen lymphoid tissue observed in VL. Animals with splenic parasitism identified in culture and negative result in LST showed more often the disruption of the splenic lymphoid tissue than those animals that did not present splenic parasitism and had a positive result in LST. These findings, together with the fact that the spleen is a highly parasitic organ in animals with susceptibility profile to VL, show that the spleen is an organ of great importance in the context of LV. Thanks to the large number of naturally infected dogs in regions where LV is endemic, there is the possibility of different analyzes of the markers mentioned above. Such analyzes and their correlations with data from human studies make the dog an excellent study model for VL, and the understanding of the pathogenesis of canine disease becomes of great value for the understanding of the disease in humans, also contributing for advances in the search for better alternatives in the treatment of the disease.
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