RESUMO
Canine leishmaniasis (CanL) caused by Leishmania infantum commonly progresses with renal and ophthalmic lesions associated with active systemic disease. As chronic inflammation related to immune complex deposits is a pathophysiological factor in the development of both glomerulonephritis and uveitis, we aimed to evaluate renal and ocular histopathological lesions and analyze whether they were related to each other and the clinical degree of the disease. For that, we evaluated 15 dogs from CanL-endemic areas. L. infantum PCR-positive dogs were studied according to disease severity into two different groups: Group-1 (G1) had data from seven dogs with mild to moderate CanL and no history of treatment, and G2 was formed with eight dogs with severe to terminal disease that had not responded to CanL treatment. Histopathological analysis of kidneys showed higher frequencies and intensities of glomerular basement membrane thickening (p = 0.026), deposits in glomeruli (p = 0.016), epithelial necrosis (p = 0.020), tubular dilatation (p = 0.003) and interstitial fibrosis (p = 0.04) in G2 dogs than in G1 dogs. Surprisingly, the histopathology of eye bulbs showed a higher frequency and intensity of retinitis (p = 0.019) in G1 dogs than in G2 dogs. The comparative analysis showed that there was no correspondence between histopathological findings in kidneys versus eyes in milder or more severe CanL. Our findings suggested that (1) clinically undetectable eye alterations can be more precocious than those in kidneys in the development of CanL, and (2) the lower frequency of eye lesions and higher frequency of renal lesions in dogs with terminal disease even after treatment indicate that therapy may have been effective in reducing CanL-associated ophthalmic disease but not proportionally in reducing kidney disease.
Assuntos
Doenças do Cão , Rim , Leishmania infantum , Leishmaniose Visceral , Animais , Cães , Doenças do Cão/patologia , Doenças do Cão/parasitologia , Masculino , Rim/patologia , Rim/parasitologia , Leishmaniose Visceral/veterinária , Leishmaniose Visceral/patologia , Leishmaniose Visceral/parasitologia , Feminino , Olho/patologia , Olho/parasitologiaRESUMO
As the bone marrow is one of the most organs affected by canine visceral leishmaniasis (CVL), samples from this are frequently taken for parasitological tests, with occurrence of myelodysplastic changes, with consequent anemia, leukopenia, and thrombocytopenia. Thus, this study aimed to investigate the histological and immunohistochemical changes in the bone marrow of the femur and sternal manubrium of dogs reactive for leishmaniasis by DPP® and ELISA tests. For this, thirteen canines from the epidemiological routine for CVL carried out by the Directorate of Zoonosis Surveillance of Goiânia (DVZ), GO, Brazil, were subjected to anatomopathological examination. 46.2% of bone marrow samples from the femur showed a higher proportion of the red series, and 53.9% of bone marrow of the sternal manubrium evidenced a higher proportion of the red series. Also, there were varied macrophage hyperplasia, hemosiderosis, and megakaryocytic emperipolesis. Amastigote forms of Leishmania spp. in the bone marrow of the femur and sternal manubrium to histopathological and immunohistochemical evaluations were observed, with good agreement them, but without difference in the parasite intensity between the bone marrow of these anatomical sites. It was concluded that bone marrow of the femur and sternal manubrium of dogs reactive for leishmaniasis by DPP® and ELISA tests has histological changes resulting from the disease, regardless of the parasite presence or intensity, with macrophage hyperplasia, hemosiderosis, and emperipolesis being the main medullary changes in these animals. Also, the bone marrow of the femur and sternal manubrium are useful anatomical sites for the diagnosis of CVL by direct methods.
Como a medula óssea é um dos órgãos mais acometidos pela leishmaniose visceral canina (LVC), amostras desta são frequentemente colhidas para exames parasitológicos, sendo possível a ocorrência de alterações mielodisplásicas, com consequente anemia, leucopenia e trombocitopenia. Assim, este estudo teve como objetivo investigar alterações histológicas e imunoistoquímicas na medula óssea do fêmur e manúbrio esternal de cães reativos para leishmaniose aos testes DPP® e ELISA. Para isso, 13 caninos da rotina epidemiológica para LVC realizada pela Diretoria de Vigilância de Zoonoses de Goiânia (DVZ), GO, Brasil, foram submetidos ao exame anatomopatológico. 46,2% e 53,9% das amostras de medula óssea do fêmur e do manúbrio esternal apresentaram maior proporção da série vermelha, respectivamente. Além disso, havia variados graus de hiperplasia macrofágica, hemossiderose e emperipolese megacariocítica. Formas amastigotas de Leishmania spp. na medula óssea do fêmur e do manúbrio esternal às avaliações histopatológicas e imunoistoquímicas foram observadas, com boa concordância entre essas, mas sem diferença na intensidade parasitária entre a medula óssea desses sítios anatômicos. Conclui-se que a medula óssea do fêmur e do manúbrio esternal de cães reativos para leishmaniose aos testes DPP® e ELISA apresenta alterações histológicas decorrentes da doença, independente da presença ou intensidade do parasito, sendo hiperplasia de macrófagos, hemossiderose e emperipolese as principais alterações medulares nesses animais. Além disso, a medula óssea do fêmur e do manúbrio esternal compreendem sítios anatômicos úteis ao diagnóstico de LVC por métodos diretos.
Assuntos
Animais , Cães , Medula Óssea , Doenças do Cão/parasitologia , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/patologia , Leishmaniose Visceral/veterinária , Fêmur , ManúbrioRESUMO
Structural changes in the spleen have been reported in several infectious diseases. In visceral leishmaniasis (VL), a severe parasitic disease caused by Leishmania spp., the loss of white pulp accompanies a severe clinical presentation. Hamster model reproduces aspects of human VL progression. In the early stages, a transcriptomic signature of leukocyte recruitment was associated with white pulp hyperplasia. Subsequently, impaired leukocyte chemotaxis with loss of T lymphocytes in the periarteriolar lymphoid sheath occurred. This differential gene expression was subsequently corroborated by transcriptomic profiling of spleens in severe human VL. At the latest stage, spleen disorganization was associated with increasing clinical signs of VL. White pulp disruption was accompanied by decreased DLK1 expression. The expression of CXCL13, CCR5, CCL19, CCR6, CCR7 and LTA decreased, likely regulated by CDKN2A overexpression. Our findings enlighten a pathway implying cell cycle arrest and decreased gene expression involved in spleen organization.
Assuntos
Pontos de Checagem do Ciclo Celular/genética , Quimiotaxia de Leucócito/genética , Leishmaniose Visceral/imunologia , Baço/imunologia , Baço/parasitologia , Animais , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Cricetinae , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Hiperplasia/patologia , Leishmaniose Visceral/patologia , Leucócitos/parasitologia , Leucócitos/patologia , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Baço/patologia , TranscriptomaRESUMO
Dogs are the main reservoir of Leishmania infantum in endemic regions. Canine leishmaniasis, caused by L. infantum, can progress to a chronic disease resulting in death. Vaccines have been developed with a certain degree of success. The pathogenesis of this disease is not completely understood, especially in previously vaccinated dogs. We herein described clinical data, parasite load, serum levels of cytokines, and the reservoir potential in vdogs vaccinated with the fucose-mannose ligand (FML)/QuilA saponin vaccine (Leishmune™) naturally infected (Vi) and compared to vaccinated not infected dogs (Vn). Thirty-four dogs from private owners were divided into two groups: vaccinated/infected and vaccinated/uninfected. Clinical evaluation, hematological and biochemical parameters, and serum levels of cytokines were measured by conventional methods. The parasite burden in the bone marrow was measured by quantitative real-time PCR, and the transmissibility of parasites to sand flies was assessed by xenodiagnosis. Clinical, biochemical, and hematological parameters of vaccinated infected dogs were mostly normal. Vi dogs developed mild disease with low clinical scores. Serum levels of IL-10 were higher in Vi dogs, and a strong correlation was observed in IL-4 levels and the A/G ratio in Vi dogs. These results suggest a role of TH2 response in Vi dogs, although more data is needed to better understand the disease in vaccinated dogs.
Assuntos
Citocinas/sangue , Lectinas/imunologia , Leishmania infantum/imunologia , Vacinas contra Leishmaniose/imunologia , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/veterinária , Vacinação , Animais , Cães , Feminino , Interleucina-4/sangue , Leishmaniose Visceral/sangue , Leishmaniose Visceral/patologia , MasculinoRESUMO
BACKGROUND: Visceral leishmaniasis (VL) is severe and potentially fatal. Brazil is one of the countries with the greatest endemicity for the disease in the world. The reduction of CD4+ T lymphocytes, B cells activation and high levels of inflammatory cytokines (IL-6/IL-8/TNF/IL-1ß), plasma LPS, soluble CD14, anti-Leishmania IgG3 and low leptin levels are involved in the immunopathogenesis of VL, most associated with severe VL. Despite relapses occurring in about 4-5% of patients with VL not associated with HIV infection, the factors underlying relapses are little known. Our aim was to identify clinical, laboratory and immunological parameters that may be associated with recurrences in VL. METHODS: Fifteen VL patients recruited from Hospital Eduardo de Menezes (BH-MG) were grouped into relapsing (R-VL, n = 5) and non-relapsing (NR-VL, n = 10) and evaluated during active disease, immediately after treatment (post-treatment) and 6 months post-treatment (6mpt). Clinical and laboratory data obtained from medical records were correlated with CD4+ and CD8+ T cell counts and anti-Leishmania Igs and IL-6 plasma levels and compared to those parameters of ten healthy controls. RESULTS: During the active phase of VL, despite similarity in the clinical symptoms, the rates of thrombocytopenia, elevated transaminases (AST and ALT) and hyperbilirubinemia were higher in the NR-VL group compared to R-VL (p < 0.05), a profile reversed during the post-treatment phase. All patients had low CD4+ T counts in active phase, however, NR-VL patients had a higher gain of this cell type than R-VL in the post-treatment (p < 0.05). There was a significant reduction in IgG3 levels during the follow-up in the NR-VL group compared to the R-VL, especially at 6mpt (p < 0.05). In addition, IgG3 levels were negatively correlated with CD4+ T counts in the R-VL group (r = - 0.52). Elevated levels of IL-6 were observed in active VL and correlated with clinical markers of severity. CONCLUSIONS: During active phase of VL, the NR-VL patients presented more severe laboratorial abnormalities compared to R-VL, probably because the latter had already received previous treatment. On the other hand, R-VL exhibited greater impairment of immune reconstitution and a high degree of B lymphocyte activation, which must be a factor that favored relapses.
Assuntos
Anticorpos Antiprotozoários/sangue , Linfócitos T CD4-Positivos/citologia , Imunoglobulina G/sangue , Leishmania/imunologia , Leishmaniose Visceral/patologia , Adulto , Anfotericina B/uso terapêutico , Brasil , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Ácido Desoxicólico/uso terapêutico , Combinação de Medicamentos , Feminino , Infecções por HIV/complicações , Humanos , Interleucina-6/sangue , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/imunologia , Masculino , Pessoa de Meia-Idade , RecidivaRESUMO
In canine leishmaniosis caused by the protozoan Leishmania infantum, little is known about how co-infections with or co-seropositivities for other pathogens can influence aggravation of this disease. Therefore, the objectives of this study were to evaluate the frequency of co-infections with or co-seropositivities for certain pathogens in dogs seropositive for L. infantum and their relationship with clinical signs, histological changes and L. infantum load. Sixty-six L. infantum-seropositive dogs were submitted to clinical examination, collection of blood and bone marrow, culling, and necropsy. Antibodies against Anaplasma spp., Borrelia burgdorferi sensu lato, Ehrlichia spp. and Toxoplasma gondii and Dirofilaria immitis antigens were investigated in serum. Samples from different tissues were submitted to histopathology and immunohistochemistry for the detection of Leishmania spp. and T. gondii. Quantitative real-time PCR was used to assess the L. infantum load in spleen samples. For detection of Coxiella burnetii, conventional PCR and nested PCR were performed using bone marrow samples. All 66 dogs tested positive for L. infantum by qPCR and/or culture. Fifty dogs (76%) were co-seropositive for at least one pathogen: T. gondii (59%), Ehrlichia spp., (41%), and Anaplasma spp. (18%). Clinical signs were observed in 15 (94%) dogs monoinfected with L. infantum and in 45 (90%) dogs co-seropositive for certain pathogens. The L. infantum load in spleen and skin did not differ significantly between monoinfected and co-seropositive dogs. The number of inflammatory cells was higher in the spleen, lung and mammary gland of co-seropositive dogs and in the mitral valve of monoinfected dogs. These results suggest that dogs infected with L. infantum and co-seropositive for certain pathogens are common in the region studied. However, co-seropositivities for certain pathogens did not aggravate clinical signs or L. infantum load, although they were associated with a more intense inflammatory reaction in some organs.
Assuntos
Coinfecção/sangue , Coinfecção/veterinária , Doenças do Cão/sangue , Ehrlichia canis/imunologia , Ehrlichiose/sangue , Ehrlichiose/veterinária , Leishmania infantum/imunologia , Leishmaniose Visceral/sangue , Leishmaniose Visceral/veterinária , Carga Parasitária , Toxoplasma/imunologia , Toxoplasmose Animal/sangue , Animais , Anticorpos Antiprotozoários/sangue , Coinfecção/parasitologia , Coinfecção/patologia , Doenças do Cão/parasitologia , Doenças do Cão/patologia , Cães , Ehrlichiose/parasitologia , Ehrlichiose/patologia , Feminino , Imuno-Histoquímica/métodos , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/patologia , Leucócitos/imunologia , Masculino , Células Mieloides/imunologia , Toxoplasmose Animal/parasitologia , Toxoplasmose Animal/patologiaRESUMO
Visceral leishmaniasis (VL) is an important zoonotic vector-borne disease and domestic dogs are considered the main domiciliary and peri-domiciliary reservoir of Leishmania (Leishmania) infantum in South America. Distinct eco-epidemiological scenarios associated to the prevalence of the disease, clusters of parasite genotypes and chemotypes of vectors population are described in Brazil, especially in the state of São Paulo (SP). In this context, the purpose of the present study is to evaluate the clinical signs, histopathological lesions, parasite load and cytokine profile by immunohistochemistry (IHC) in popliteal lymph nodes of canines naturally infected with L. infantum, from different municipalities of the state of SP. Eighty-three dogs with VL, 61 from northwest SP (NWSP) and 22 from southeast SP (SESP), were clinically classified in stage II, with no babesiosis and ehrlichiosis. Subcapsular inflammatory infiltration and histiocytosis were significantly higher in the SESP group (pâ¯=â¯0.0128; 0.0077, respectively). On the other hand, dogs from NWSP revealed 4.6-fold significantly higher parasite burden (pâ¯=â¯0.0004) and higher IHC scores of IL-1ß (pâ¯=â¯0.0275) and IL-4 (pâ¯=â¯0.0327) in the popliteal lymph node tissues, which may be associated with the susceptibility and progression of the disease in these dogs. Differences in immune response profile associated with higher parasite load in dogs can also contribute to explain the distinct eco-epidemiological patterns of VL in specific geographic regions.
Assuntos
Citocinas/imunologia , Doenças do Cão/imunologia , Leishmania infantum , Leishmaniose Visceral/veterinária , Linfonodos/parasitologia , Animais , Brasil/epidemiologia , Doenças do Cão/epidemiologia , Doenças do Cão/parasitologia , Doenças do Cão/patologia , Cães , Feminino , Leishmania infantum/imunologia , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/patologia , Linfonodos/patologia , Masculino , Carga ParasitáriaRESUMO
Tellurium compounds have been described as potential leishmanicides, bearing promising leishmanicidal and antimalarial effects. Therefore, the present study investigated the pharmacological potential of the organotellurane compound RF07 through preADMET parameters, such as absorption, distribution, metabolism and excretion. After studying the pharmacokinetic properties of RF07, studies were carried out on dogs naturally infected with visceral leishmaniasis after the administration of RF07, in order to assess pathophysiological parameters. Thus, dogs were divided into 4 groups with administration of daily intraperitoneal injections for 3 weeks (containing RF07 or placebo). During the trial, hematological parameters, renal and hepatic toxicity were evaluated. Serum urea, creatinine, alkaline phosphatase, transaminases (GOT and GPT), as well as hemogram results, were evaluated before the first administration and during the second and third weeks after the start of the treatment. In dogs with VL, RF07 improved liver damage, regulated GPT levels and significantly decreased leukocyte count, promoting its regularization. These phenomena occurred at the end of the third week of treatment. The administration of RF07 promoted a significant decrease in the average levels of GOT and GPT after the third week of treatment and did not significantly alter the hematological parameters. The application of RF07 in the treatment of visceral leishmaniasis suggests that it is an alternative to the disease, since the reversal of clinical signs in dogs with VL requires the use of 0.6â¯mg/kg.
Assuntos
Antiprotozoários , Leishmaniose Visceral , Compostos Organometálicos , Compostos de Espiro , Telúrio , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Antiprotozoários/farmacocinética , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Aspartato Aminotransferases/sangue , Contagem de Células Sanguíneas , Peso Corporal/efeitos dos fármacos , Creatinina/sangue , Cães , Absorção Intestinal , Rim/efeitos dos fármacos , Rim/patologia , Leishmaniose Visceral/sangue , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/patologia , Leishmaniose Visceral/veterinária , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Modelos Biológicos , Compostos Organometálicos/farmacocinética , Compostos Organometálicos/farmacologia , Compostos Organometálicos/uso terapêutico , Compostos de Espiro/farmacocinética , Compostos de Espiro/farmacologia , Compostos de Espiro/uso terapêutico , Telúrio/farmacocinética , Telúrio/farmacologia , Telúrio/uso terapêutico , Ureia/sangueRESUMO
BACKGROUND: Visceral leishmaniasis is an important but neglected disease that is spreading and is highly lethal when left untreated. This study sought to measure the Leishmania infantum seroprevalence in dogs, the coverage of its control activities (identification of the canine reservoir by serological survey, dog culling and insecticide spraying) and to evaluate its relationship with the occurrence of the disease in humans in the municipalities of Araçatuba and Birigui, state of São Paulo, Brazil. METHODS: Information from 2006 to 2015 was georeferenced for each municipality and modeling was performed for the two municipalities together. To do this, latent Gaussian Bayesian models with the incorporation of a spatio-temporal structure and Poisson distribution were used. The Besag-York-Mollie models were applied for random spatial effects, as also were autoregressive models of order 1 for random temporal effects. The modeling was performed using the INLA (Integrated Nested Laplace Approximations) deterministic approach, considering both the numbers of cases as well as the coverage paired year by year and lagged at one and two years. RESULTS: Control activity coverage was observed to be generally low. The behavior of the temporal tendency in the human disease presented distinct patterns in the two municipalities, however, in both the tendency was to decline. The canine serological survey presented as a protective factor only in the two-year lag model. CONCLUSIONS: The canine serological coverage, even at low intensity, carried out jointly with the culling of the positive dogs, suggested a decreasing effect on the occurrence of the disease in humans, whose effects would be seen two years after it was carried out.
Assuntos
Formigas/parasitologia , Doenças do Cão/diagnóstico , Doenças do Cão/patologia , Leishmaniose Visceral/patologia , Animais , Teorema de Bayes , Brasil/epidemiologia , Doenças do Cão/epidemiologia , Cães , Humanos , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/epidemiologia , Distribuição de Poisson , Fatores de Risco , Estudos SoroepidemiológicosRESUMO
INTRODUCTION: Visceral leishmaniasis (VL) represents a public health concern in several areas of the world. In the American continent, VL transmission is typically zoonotic, but humans with active VL caused by Leishmania infantum are able to infect sandflies. Thus, individuals with cutaneous parasitic infections may act as reservoirs and allow interhuman transmission. Additionally, the skin may be responsible for reactivation of the disease after therapy. This study's objective was to evaluate cutaneous parasitism in humans with VL in an American endemic area. METHODS: A cross-sectional hospital-based study was conducted in northeast Brazil from October 2016 to April 2017. Biopsies of healthy skin for histopathology and immunohistochemistry were performed prior to treatment in all study patients. RESULTS: Twenty-two patients between the ages of five months to 78 years were included in the study. Seven patients (31.8%) tested positive for HIV. Only one patient had cutaneous parasitism, as confirmed by immunohistochemistry prior to treatment. Parasitism was not detected after treatment. CONCLUSIONS: Cutaneous parasitism in the healthy skin of humans with visceral leishmaniasis, although unusual, may be a source of infection for phlebotomine sandflies.
Assuntos
Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/parasitologia , Pele/parasitologia , Adolescente , Adulto , Idoso , Biópsia , Criança , Pré-Escolar , Estudos Transversais , Escolaridade , Doenças Endêmicas , Feminino , Humanos , Imuno-Histoquímica , Lactente , Leishmaniose Visceral/patologia , Masculino , Pessoa de Meia-Idade , Pele/patologia , Adulto JovemRESUMO
INTRODUCTION: In canine visceral leishmaniasis (CVL), lymphopenia, and the disorganization of lymphoid organs such as spleen and lymph nodes have been demonstrated. However, the involvement of thymus in CVL has not been evaluated so far. Herein, we investigated whether the thymus can be colonized by Leishmania infantum in naturally infected dogs. METHODS: Thymus were obtained from 16 of 58 dogs and samples of this organ were submitted to immunohistochemistry for laminin and fibronectin detection, histopathology, in situ hybridization and polymerase chain reaction (PCR) targeting the gene ITS-1 for Leishmania and sequenced. Samples of spleen, skin and popliteal lymph nodes were collected and submitted to immunohistochemistry and parasitological culture followed by multilocus enzyme electrophoresis. RESULTS: L. infantum was identified in all dogs. DNA and amastigote forms of Leishmania were detected in the thymus from 16 dogs by PCR and in eight by immunohistochemistry. Besides thymus, parasites were detected in spleen, lymph nodes, and skin. A granulomatous or pyogranulomatous thymitis was observed in eight dogs associated to intact amastigotes forms of this parasite. Fibronectin deposition in thymus was higher in dogs with more clinical signs. CONCLUSIONS: These results demonstrate that the thymus of dogs can be parasitized by L. infantum, which may generate inflammatory reactions leading to alterations in thymic microarchitecture.
Assuntos
DNA de Protozoário/isolamento & purificação , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/veterinária , Timo/parasitologia , Animais , DNA de Protozoário/genética , Doenças do Cão/parasitologia , Cães , Feminino , Leishmania infantum/genética , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/patologia , Linfonodos/parasitologia , Masculino , Carga Parasitária , Pele/parasitologia , Baço/parasitologiaRESUMO
Leishmania infantum is a trypanosomatid that causes parasitic dermatopathy in dogs. Trypanosoma caninum is another trypanosomatid, which infects the skin of dogs, although cutaneous abnormalities are absent. This study aimed to investigate the occurrence of T. caninum infection and its associated cutaneous and histological changes and compare it with the occurrence of L. infantum infection in dogs. The study included 150 dogs, of which T. caninum infection was identified in 3 (2%) and L. infantum infection in 15 (10%) of them, with no association (p>0.05) of these infections with the breed, gender, age, or cutaneous abnormalities. The cutaneous abnormalities were based on 1 (4.8%) and 12 (57.1%) dogs infected by T. caninum and L. infantum, respectively. The dermatohistopathological abnormalities in the dogs infected with T. caninum included mild perivascular lymphohistioplasmacytic infiltrates in the clinically asymptomatic ones, while in those with dermatological abnormalities, acanthosis, epidermal orthokeratotic hyperkeratosis, melanomacrophages, and co-infection with Microsporum sp. and Trichophyton sp. were observed. InL. infantum infected, the histopathological findings included chronic granulomatous inflammatory infiltrates and structures compatible with amastigotes. Despite the low frequency of T. caninum infection, our findings suggest that this trypanosomatid, unlike L. infantum, does not cause any macroscopic skin abnormalities.
Assuntos
Doenças do Cão/patologia , Leishmania infantum/genética , Leishmaniose Visceral/veterinária , Trypanosoma/genética , Tripanossomíase/veterinária , Animais , Brasil/epidemiologia , Coinfecção , DNA de Protozoário/genética , Doenças do Cão/epidemiologia , Cães , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/patologia , Reação em Cadeia da Polimerase , Prevalência , Tripanossomíase/epidemiologia , Tripanossomíase/patologiaRESUMO
Although the domestic dog is the most important reservoir of visceral leishmaniasis in urban areas, there have been an increasing number of reports of naturally occurring leishmaniasis in non-human primates. Reported cases affecting neotropical and Old World non-human primates as well as their potential role as reservoirs were reviewed.
Assuntos
Reservatórios de Doenças/veterinária , Leishmaniose Visceral/veterinária , Doenças dos Macacos/patologia , Animais , Reservatórios de Doenças/parasitologia , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/patologia , Doenças dos Macacos/parasitologia , PrimatasRESUMO
BACKGROUND: The timely identification of visceral leishmaniasis (VL) patients with a higher risk of death is essential for meeting the target of reducing case-fatality rates in the Americas. This study aimed to identify factors associated with death from VL in the State of Piaui, Brazil. METHODS: Case-control study evaluating the following putative risk factors for death from VL: gender and age of the patient, local of residence, signs, and symptoms, laboratory data, comorbidities and days of evolution of the disease. The associations between risk factors and death were expressed as odds ratios and their respective 95% confidence intervals. RESULTS: In the period analyzed a total of 2525 VL patients were admitted to the hospital, corresponding to 9,3% of all VL admissions in Brazil. Among them, 177 patients died (case-fatality rate of 7.0%). In the multivariate analysis the following variables showed a statistically significant association with death: ≥60 years, vomiting, edema, diarrhea, platelets<50.000/mm³, jaundice, splenomegaly, and pneumonia. CONCLUSIONS: The identified factors associated to death from VL can be easily assessed at the time of or up to 48h after admission and may be used to inform clinical decisions, improving the clinical and laboratory monitoring of patients.
Assuntos
Mortalidade Hospitalar , Leishmaniose Visceral/mortalidade , Adolescente , Adulto , Brasil/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Leishmaniose Visceral/complicações , Leishmaniose Visceral/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Adulto JovemRESUMO
Abstract INTRODUCTION: Visceral leishmaniasis (VL) represents a public health concern in several areas of the world. In the American continent, VL transmission is typically zoonotic, but humans with active VL caused by Leishmania infantum are able to infect sandflies. Thus, individuals with cutaneous parasitic infections may act as reservoirs and allow interhuman transmission. Additionally, the skin may be responsible for reactivation of the disease after therapy. This study's objective was to evaluate cutaneous parasitism in humans with VL in an American endemic area. METHODS: A cross-sectional hospital-based study was conducted in northeast Brazil from October 2016 to April 2017. Biopsies of healthy skin for histopathology and immunohistochemistry were performed prior to treatment in all study patients. RESULTS: Twenty-two patients between the ages of five months to 78 years were included in the study. Seven patients (31.8%) tested positive for HIV. Only one patient had cutaneous parasitism, as confirmed by immunohistochemistry prior to treatment. Parasitism was not detected after treatment. CONCLUSIONS: Cutaneous parasitism in the healthy skin of humans with visceral leishmaniasis, although unusual, may be a source of infection for phlebotomine sandflies.
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Idoso , Adulto Jovem , Pele/parasitologia , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/parasitologia , Pele/patologia , Biópsia , Imuno-Histoquímica , Estudos Transversais , Doenças Endêmicas , Escolaridade , Leishmaniose Visceral/patologia , Pessoa de Meia-IdadeRESUMO
Abstract Leishmania infantum is a trypanosomatid that causes parasitic dermatopathy in dogs. Trypanosoma caninum is another trypanosomatid, which infects the skin of dogs, although cutaneous abnormalities are absent. This study aimed to investigate the occurrence of T. caninum infection and its associated cutaneous and histological changes and compare it with the occurrence of L. infantum infection in dogs. The study included 150 dogs, of which T. caninum infection was identified in 3 (2%) and L. infantum infection in 15 (10%) of them, with no association (p>0.05) of these infections with the breed, gender, age, or cutaneous abnormalities. The cutaneous abnormalities were based on 1 (4.8%) and 12 (57.1%) dogs infected by T. caninum and L. infantum, respectively. The dermatohistopathological abnormalities in the dogs infected with T. caninum included mild perivascular lymphohistioplasmacytic infiltrates in the clinically asymptomatic ones, while in those with dermatological abnormalities, acanthosis, epidermal orthokeratotic hyperkeratosis, melanomacrophages, and co-infection with Microsporum sp. and Trichophyton sp. were observed. InL. infantum infected, the histopathological findings included chronic granulomatous inflammatory infiltrates and structures compatible with amastigotes. Despite the low frequency of T. caninum infection, our findings suggest that this trypanosomatid, unlike L. infantum, does not cause any macroscopic skin abnormalities.
Resumo Leishmania infantum é um tripanosomatídeo que causa dermatopatia parasitária em cães. Trypanosoma caninum é outro tripanosomatídeo, que infecta a pele de cães, embora anormalidades cutâneas sejam ausentes. Este estudo teve como objetivo investigar a ocorrência da infecção por T. caninum e suas alterações cutâneas e histológicas associadas e compará-las com a ocorrência da infecção por L. infantum em cães. O estudo incluiu 150 cães, dos quais a infecção por T. caninum foi identificada em 3 (2%) e a infecção por L. infantum em 15 (10%) deles, sem associação (p>0,05) dessas infecções com a raça, sexo, idade ou anormalidades cutâneas. As alterações cutâneas foram observadas em 1 (4,8%) e 12 (57,1%) cães infectados por T. caninum e L. infantum, respectivamente. As anormalidades dermato-histopatológicas nos cães infectados por T. caninum incluíram infiltrados linfo-histioplasmocitários perivasculares leves nos clinicamente assintomáticos, enquanto naqueles com anormalidades dermatológicas, foram observados acantose, hiperqueratose ortoqueratótica epidermal e melanomacrófagos e co-infecção por Microsporum sp. e Trichophyton sp. Nos cães infectados por L. infantum, os achados histopatológicos incluíram infiltrados inflamatórios granulomatosos crônicos e estruturas compatíveis com amastigotas. A despeito da baixa frequência da infecção por T. caninum, nossos achados sugerem que esse tripanosomatídeo, diferentemente de L. infantum, não causa anormalidades macroscópicas na pele.
Assuntos
Animais , Cães , Trypanosoma/genética , Tripanossomíase/veterinária , Leishmania infantum/genética , Doenças do Cão/patologia , Leishmaniose Visceral/veterinária , Tripanossomíase/patologia , Tripanossomíase/epidemiologia , Brasil/epidemiologia , Reação em Cadeia da Polimerase , Prevalência , DNA de Protozoário/genética , Doenças do Cão/epidemiologia , Coinfecção , Leishmaniose Visceral/patologia , Leishmaniose Visceral/epidemiologiaRESUMO
The objectives of this work were to study some pathological aspects of kidneys obtained from dogs naturally infected with Leishmania infantum and from dogs experimentally infected with two different strains of L infantum with special emphasis on fibrotic process. Seventy eight specimens of paraffin-embedded kidney fragments were collected as follows: (a) CNI group composed by 62 kidney samples of adult mongrel dogs, naturally infected with L infantum; (b) BH401 group composed by five kidney samples of adult Beagles experimentally infected with L infantum strain MCAN BR/2002/BH401; (c) BH400 group composed by eleven kidney samples of adult Beagles experimentally infected with L infantum strain MCAN/BR/2000/BH400, at the same dose and same route of the previous group, denominated group BH400; Control group (CC) composed by four kidney samples of adult Beagles. All animals revealed glomerular and interstitial fibropoiesis associated with different types of glomerulonephritis and chronic interstitial nephritis. Fibrosis was markedly more intense in the BH401 group, followed by animals in the CNI group. Markers for myofibroblasts (mesenchymal markers) such as alpha-actin (α-SMA), vimentin and the cytokine transforming growth factor beta (TGF-ß) were done by immunohistochemistry. BH401 group showed higher expression of all these markers than others. Intracellular amastigotes forms of Leishmania was mainly found in BH401. These results could be indicating that the MCAN/BR/2002/BH401 strain is a good choice for the study of renal LVC experimental model.
Assuntos
Doenças do Cão/patologia , Rim/patologia , Leishmania infantum , Leishmaniose Visceral/patologia , Leishmaniose Visceral/veterinária , Actinas , Animais , Cães , Fibrose , Imuno-Histoquímica , Rim/metabolismo , Rim/parasitologia , Leishmania infantum/genética , Fator de Crescimento Transformador beta , VimentinaRESUMO
BACKGROUND: The liver plays a central role in the development of canine visceral leishmaniasis. Studies of natural infection in animals and humans indicate a direct relationship between resolution of infection and the formation and maturation of granulomas in the liver. However, in contrast to other reports in the literature, the present study found no differences in the characteristics of hepatic granulomas that could be related to resistance or susceptibility to Leishmania. Here, we describe the hepatic alterations observed in dogs with differing clinical manifestations of visceral leishmaniasis in an endemic area in the state of Bahia, Brazil. METHODS: We examined 148 animals in an endemic area. The animals were clinically examined, and the infection was determined by ELISA, spleen aspirate culture and quantitative PCR. The animals were grouped into asymptomatic or symptomatic based on the number of signs of LV. The histological liver evaluation was performed in a blinded way. RESULTS: Our results indicated no association between the characteristics of granulomas and clinical presentation. We found an association between the intensity of this inflammatory response and parasite load in the animals' spleens. It is important to note that while hepatic alterations, such as portal and perivascular inflammation and the presence of larger amounts of granulomas, were linked with higher parasite loads, we found the inverse to be true with respect to intrasinusoidal lymphocytosis, the formation of intrasinusoidal inflammatory cell aggregates and Kupffer cell hypertrophy. CONCLUSIONS: Our findings suggest that the presence of mononuclear inflammatory cells inside the sinusoids is more important than that of organized granulomas in terms of the containment of parasitism by the host. We suggest that the presence of granulomas indicates the failure of a first line of defense mechanism in the control of parasite infection, which could be related to the presence of inflammatory cells and Kupffer cell hypertrophy inside the sinusoids. We further demonstrated that dogs with active Leishmania spp. infection present a higher frequency of inflammatory changes in the liver. In addition to being correlated with the severity of clinical manifestation, these hepatic alterations were also associated with changes in hematological and biochemical parameters.
Assuntos
Doenças do Cão/patologia , Leishmania infantum/patogenicidade , Leishmaniose Visceral/veterinária , Fígado/patologia , Animais , Brasil , Doenças do Cão/parasitologia , Cães , Doenças Endêmicas/veterinária , Granuloma/parasitologia , Granuloma/patologia , Granuloma/veterinária , Leishmaniose Visceral/patologia , Fígado/parasitologia , Hepatopatias Parasitárias/parasitologia , Hepatopatias Parasitárias/patologia , Hepatopatias Parasitárias/veterinária , Baço/parasitologiaRESUMO
Canine visceral leishmaniosis (CVL) is an important zoonotic disease, which is endemic in Brazil and several other parts of the world. The disease may affect multiple organs, but lesions in the oral cavity are considered uncommon. Twenty-three cases of oral lesions compatible with CVL were diagnosed from 2015 to 2018 in the Federal District, Brazil. Six cases were confirmed to be CVL based on histopathology, immunohistochemistry and polymerase chain reaction amplification of Leishmania infantum kDNA. Most of the affected dogs were >9 years of age, of mixed breed and were classified as having stage C of the disease. The most important gross findings were ulcerated nodular lesions in the tongue, lip, gingiva and hard palate. Microscopically, there was lymphoplasmacytic to granulomatous inflammation that was diffuse, moderate to severe and associated with ulceration. CVL should be considered in the differential diagnosis of nodular and ulcerative oral lesions in dogs.
Assuntos
Doenças do Cão/patologia , Leishmaniose Visceral/veterinária , Boca/patologia , Animais , Cães , Leishmania infantum , Leishmaniose Visceral/patologia , Estudos RetrospectivosRESUMO
In canine visceral leishmaniasis (CVL), splenic white pulp (SWP) disorganization has been associated with disease progression, reduced cytokine and chemokine expression and failure to control the parasite load. This profile is compatible with the cellular exhaustion previously shown in human visceral leishmaniasis. The present study aimed to evaluate the in situ expression of cellular exhaustion markers and their relation to clinical signs, SWP disorganization and parasite load. Forty dogs naturally infected by Leishmania infantum were grouped according to levels of SWP organization and parasite load. SWP disorganization was associated with reductions in the periarteriolar lymphatic sheath and lymphoid follicles/mm2 and worsening of the disease. Apoptotic cells expressing CTLA-4+ increased in dogs with disorganized SWP and a high parasite load. In the same group, PD-L1 and LAG-3 gene expression were reduced. A higher number of CD21+TIM-3+ B cells was detected in disorganized spleens than in organized spleens. Apoptosis is involved in periarteriolar lymphatic sheath reduction and lymphoid follicle atrophy and is associated with CTLA-4+ cell reductions in the splenic tissue of dogs with visceral leishmaniasis (VL). Failure to control the parasite load was observed, suggesting that cell exhaustion followed by T and B cell apoptosis plays a role in the immunosuppression observed in CVL.