RESUMEN
Toxoplasma gondii is able to manipulate the host immune system to establish a persistent and efficient infection, contributing to the development of brain abnormalities with behavioral repercussions. In this context, this work aimed to evaluate the effects of T. gondii infection on the systemic inflammatory response and structure of the primary somatosensory cortex (PSC). C57BL/6 and BALB/c mice were infected with T. gondii ME49 strain tissue cysts and accompanied for 30 days. After this period, levels of cytokines IFN-γ, IL-12, TNF-α and TGF-ß were measured. After blood collection, mice were perfused and the brains were submitted to immunohistochemistry for perineuronal net (PNN) evaluation and cyst quantification. The results showed that C57BL/6 mice presented higher levels of TNF-α and IL-12, while the levels of TGF-ß were similar between the two mouse lineages, associated with the elevated number of tissue cysts, with a higher occurrence of cysts in the posterior area of the PSC when compared to BALB/c mice, which presented a more homogeneous cyst distribution. Immunohistochemistry analysis revealed a greater loss of PNN labeling in C57BL/6 animals compared to BALB/c. These data raised a discussion about the ability of T. gondii to stimulate a systemic inflammatory response capable of indirectly interfering in the brain structure and function.
Asunto(s)
Corteza Somatosensorial , Síndrome de Respuesta Inflamatoria Sistémica , Toxoplasma , Toxoplasmosis , Animales , Ratones , Interleucina-12/metabolismo , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Corteza Somatosensorial/inmunología , Corteza Somatosensorial/parasitología , Síndrome de Respuesta Inflamatoria Sistémica/inmunología , Síndrome de Respuesta Inflamatoria Sistémica/parasitología , Toxoplasma/patogenicidad , Toxoplasmosis/inmunología , Toxoplasmosis/parasitología , Factor de Crecimiento Transformador beta/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The common signs of canine babesiosis caused by an infection with Babesia canis are fever, anorexia, lethargy, pulse alterations, anemia, and occasionally mild icterus. Dogs with these clinical signs can be divided into two groups: those with acute-phase reaction and those with systemic inflammatory response syndrome (SIRS). Factors associated with the occurrence of SIRS in canine babesiosis have not been thoroughly researched. This article outlines a cross-sectional study of 54 client-owned dogs with an acute B. canis infection, and evaluates the differences in age, gender, laboratory findings, parasite load, and seroreactivity against B. canis between the SIRS and the SIRS-free dogs. We have analyzed a complete blood count, serum biochemistry, serum amyloid A, ceruloplasmin, paraoxonase-1, serology, and PCR testing using standard methodologies. The frequency of SIRS among the investigated dogs reached 0.59. Male dogs and those seronegative against B. canis, were more frequent in the SIRS group, whilst age and parasite load could not be associated with the presence of SIRS. Dogs with SIRS had a lower count of total leukocytes, neutrophils, lymphocytes, and monocytes, and a lower concentration of iron and bilirubin compared with SIRS-free dogs. No significant differences in the concentration of acute-phase proteins have been noticed to exist between the groups of dogs. Further, the seronegative dogs had a lower count of lymphocytes and monocytes and a higher parasite load than the seroreactive dogs. Multivariate logistic regression analysis has identified leukopenia (<6 × 109/L) and monocytopenia (<0.2 × 109/L) as independent associates of SIRS in the investigated dogs, thus implying that these routine tests could be used as reliable markers for SIRS.
Asunto(s)
Babesiosis/complicaciones , Enfermedades de los Perros/inmunología , Interacciones Huésped-Parásitos/inmunología , Carga de Parásitos/veterinaria , Síndrome de Respuesta Inflamatoria Sistémica/veterinaria , Animales , Babesia , Babesiosis/inmunología , Babesiosis/parasitología , Biomarcadores/sangre , Enfermedades de los Perros/parasitología , Perros , Femenino , Masculino , Síndrome de Respuesta Inflamatoria Sistémica/parasitologíaRESUMEN
The records of all canine patients (86) that had been diagnosed with babesiosis and that were admitted to the Clinic for Internal Diseases, Faculty of Veterinary Medicine, Zagreb from January 2007 to December 2007 were reviewed retrospectively. All dogs that had been diagnosed with canine babesiosis and that had systemic inflammatory response syndrome (SIRS) followed by multiple organ dysfunction syndrome (MODS), and refractory hypotension, were included in this study. Of 86 patients diagnosed with canine babesiosis that were admitted during the study period, 10 had evidence of septic shock and were included in this study. Seven of the 10 dogs had a level of parasitaemia above 1%, with the highest level being 20.2%, seven of the 10 dogs were anaemic and three of the 10 dogs were leucopoenic. Thrombocytopenia was present in nine dogs. Hypoglycaemia was noted in two dogs, and bilirubinaemia in nine dogs. Four patients had involvement of two organs, five had involvement of three organs, and one had involvement of four organs. The organ that was most frequently involved was the kidney (nine cases). Central nervous system dysfunction was the rarest complication noted (one case). The mortality rate in non-septic shock canine babesiosis was 2.6%. All dogs that developed septic shock died between the first and the fourth day after admission. The 100% mortality rate that is reported here reflects the fact that in cases in which progression of the inflammatory response leads to the development of septic shock, an unfavourable outcome should be expected.
Asunto(s)
Babesiosis/veterinaria , Enfermedades de los Perros/patología , Síndrome de Respuesta Inflamatoria Sistémica/veterinaria , Animales , Babesiosis/complicaciones , Babesiosis/mortalidad , Enfermedades de los Perros/mortalidad , Perros , Femenino , Masculino , Insuficiencia Multiorgánica/complicaciones , Insuficiencia Multiorgánica/mortalidad , Insuficiencia Multiorgánica/parasitología , Insuficiencia Multiorgánica/veterinaria , Estudios Retrospectivos , Síndrome de Respuesta Inflamatoria Sistémica/complicaciones , Síndrome de Respuesta Inflamatoria Sistémica/mortalidad , Síndrome de Respuesta Inflamatoria Sistémica/parasitologíaRESUMEN
Canine babesiosis is a tick-borne disease caused by the haemoprotozoan parasites of the genus Babesia. Early detection of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) is of major importance in clinical practice for providing information about severity and outcomes of the disease and therapy. Plasma samples were taken at admission from five dogs with uncomplicated babesiosis caused by B. canis canis, five dogs with babesiosis and SIRS, five dogs with babesiosis and MODS, and five healthy dogs. After two-dimensional electrophoresis and capillary reversed - phase liquid chromatography coupled online with tandem mass spectrometry, 68 differentially expressed spots with level of significance P<0.05 were detected between groups. SIRS in babesiosis was characterised by increases in paraoxonase 1 and apoA-I, whereas MODS with decrease of complement inhibitors leading to prolonged complement activation and decrease of vitamin D binding protein due to haemolysis and activation of the coagulation cascade.
Asunto(s)
Babesia/fisiología , Babesiosis/diagnóstico , Enfermedades de los Perros/diagnóstico , Insuficiencia Multiorgánica/veterinaria , Síndrome de Respuesta Inflamatoria Sistémica/veterinaria , Animales , Babesiosis/parasitología , Biomarcadores/sangre , Cromatografía Liquida/veterinaria , Enfermedades de los Perros/parasitología , Perros , Electroforesis en Gel Bidimensional/veterinaria , Insuficiencia Multiorgánica/diagnóstico , Insuficiencia Multiorgánica/parasitología , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/parasitología , Espectrometría de Masas en Tándem/veterinariaRESUMEN
Babesia rossi is the cause of a highly virulent multisystemic disease with a variable outcome, which is a reliable model of systemic inflammatory response syndrome (SIRS). The objective of this study was to determine the concentration of canine pancreatic-specific lipase (cPL) in a population of dogs with naturally acquired B. rossi infection. In addition, the associations between serum cPL and death and SIRS status were examined. An observational study recruited 87 dogs diagnosed with B. rossi infection and serum cPL concentrations were measured daily until discharge or death. The median concentration of serum cPL was 124.0 µg/L (interquartile range: 51.0 µg/L - 475.5 µg/L) on admission (n = 87) and 145.5 µg/L (62.3 µg/L - 434.0 µg/L) on day two of hospitalisation (n = 40). Twenty-four dogs (28%) had a serum cPL concentration within the diagnostic range for pancreatitis (> 400 µg/L) at admission with 13 dogs (32.5%) presenting as such on the second day of hospitalisation. The median concentration of serum cPL in dogs with SIRS was 158 µg/L (interquartile range: 52.5 µg/L - 571.5 µg/L; n = 53), which was significantly higher than in those without SIRS (75 µg/L; 50.3 µg/L - 131.8 µg/L; n = 32) (P = 0.018). This study demonstrated that an unexpectedly high number of dogs diagnosed with naturally acquired canine babesiosis had a serum cPL concentration within the diagnostic range for acute pancreatitis and a significantly higher serum cPL concentration was found in dogs that were classified as having SIRS.
Asunto(s)
Babesiosis/inmunología , Enfermedades de los Perros/inmunología , Lipasa/sangre , Pancreatitis/inmunología , Síndrome de Respuesta Inflamatoria Sistémica/veterinaria , Animales , Babesia/aislamiento & purificación , Babesiosis/parasitología , Enfermedades de los Perros/parasitología , Perros , Femenino , Masculino , Pancreatitis/etiología , Reacción en Cadena de la Polimerasa/veterinaria , Síndrome de Respuesta Inflamatoria Sistémica/inmunología , Síndrome de Respuesta Inflamatoria Sistémica/parasitologíaRESUMEN
OBJECTIVE: Owing to the increasing number of patients with acquired immunodeficiency syndrome and immunosuppressed transplant patients, disseminated Toxoplasma gondii has emerged as a potentially fatal pathogen. Common presentations include encephalitis, pneumonia, and myocarditis. The objective of this report is to describe the clinical course, histologic features, and outcome in two immunocompromised patients with disseminated toxoplasmosis presenting with parasitemia and panniculitis. MATERIALS AND METHODS: Two cases of disseminated toxoplasmosis presenting with parasitemia (patient 1) and panniculitis (patient 2) were retrieved from the clinical, surgical, and autopsy pathology archives of Vanderbilt University Medical Center, Nashville, Tenn. The histology and diagnostic approaches used are reported. Charts were reviewed for primary diagnosis, therapy protocols, clinical presentation of infection, and outcome. RESULTS: Patient 1 developed a clinically unexplained sepsis syndrome shortly after heart transplantation; T gondii parasitemia was diagnosed by examination of peripheral blood smears. The diagnosis was confirmed at autopsy. Patient 2 was a child undergoing induction chemotherapy for lymphoma who developed rapidly progressive neurologic deterioration accompanied by a maculopapular skin rash; T gondii panniculitis was diagnosed retrospectively when histologic examination was combined with immunohistochemistry. Autopsies performed in both cases confirmed widely disseminated infection. CONCLUSIONS: Disseminated toxoplasmosis should be considered in the differential diagnosis of immunocompromised patients with culture-negative sepsis syndrome, particularly if combined with neurologic, respiratory, or unexplained skin lesions. Examination of Wright's-stained peripheral blood smears or antitoxoplasma immunoperoxidase studies of skin biopsies may be diagnostic and allow rapid initiation of antibiotic therapy. Autopsy findings contributed to both of our cases by documenting the wide-spread heavy parasite burden and demonstrating numerous diagnostic T gondii cyst forms.
Asunto(s)
Huésped Inmunocomprometido , Toxoplasma/aislamiento & purificación , Toxoplasmosis/patología , Animales , Niño , Resultado Fatal , Femenino , Humanos , Inmunohistoquímica , Pulmón/parasitología , Pulmón/patología , Masculino , Persona de Mediana Edad , Neutrófilos/parasitología , Neutrófilos/patología , Piel/inmunología , Piel/parasitología , Piel/patología , Síndrome de Respuesta Inflamatoria Sistémica/parasitología , Síndrome de Respuesta Inflamatoria Sistémica/patología , Toxoplasma/inmunología , Toxoplasma/ultraestructuraRESUMEN
INTRODUCTION: The objective of the study is to identify the main risk factors for death by New World visceral leishmaniasis and establish a coherent pathogenic substrate of severe disease based on clinical findings. METHODS: Seventy-six deceased inpatients and 320 successfully treated inpatients with VL were studied in a case control study. RESULTS: Bacterial infection and bleeding were mutually exclusive events leading to death. Five risk factors were unique for death by bacterial infection (malnutrition, pulmonary rales, severe anemia, severe absolute neutropenia and higher neutrophil count), while another six were unique for death by bleeding (jaundice, severe relative neutropenia, severe thrombocytopenia, liver injury, kidney failure, higher bone marrow parasite load). Bacterial infection, bleeding, severe anemia, diarrhea, dyspnea, edema, jaundice and bone marrow parasite load were the main syndromes of visceral leishmaniasis among successfully treated patients. CONCLUSIONS: The data support the idea that bacterial infections are due to immune paralysis. Broad organ and system involvement is plausibly due to the high production of proinflammatory cytokines, whose actions fit well with visceral leishmaniasis. The syndromes and causative mediators are typical of a slowly developing systemic inflammatory response syndrome.
Asunto(s)
Leishmaniasis Visceral/mortalidad , Síndrome de Respuesta Inflamatoria Sistémica/mortalidad , Adolescente , Adulto , Estudios de Casos y Controles , Causas de Muerte , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Factores de Riesgo , Índice de Severidad de la Enfermedad , Síndrome de Respuesta Inflamatoria Sistémica/parasitología , Adulto JovenRESUMEN
INTRODUCTION: The objective of the study is to identify the main risk factors for death by New World visceral leishmaniasis and establish a coherent pathogenic substrate of severe disease based on clinical findings. METHODS: Seventy-six deceased inpatients and 320 successfully treated inpatients with VL were studied in a case control study. RESULTS: Bacterial infection and bleeding were mutually exclusive events leading to death. Five risk factors were unique for death by bacterial infection (malnutrition, pulmonary rales, severe anemia, severe absolute neutropenia and higher neutrophil count), while another six were unique for death by bleeding (jaundice, severe relative neutropenia, severe thrombocytopenia, liver injury, kidney failure, higher bone marrow parasite load). Bacterial infection, bleeding, severe anemia, diarrhea, dyspnea, edema, jaundice and bone marrow parasite load were the main syndromes of visceral leishmaniasis among successfully treated patients. CONCLUSIONS: The data support the idea that bacterial infections are due to immune paralysis. Broad organ and system involvement is plausibly due to the high production of proinflammatory cytokines, whose actions fit well with visceral leishmaniasis. The syndromes and causative mediators are typical of a slowly developing systemic inflammatory response syndrome.
INTRODUÇÃO: O objetivo do estudo foi i dentificar os principais fatores de risco para morte na leishmaniose visceral do Novo Mundo e estabelecer um substrato patogênico baseado nos achados clínicos coerente para doença grave. MÉTODOS: Em um estudo caso-controle, foram estudados 76 pacientes internados que faleceram e 320 pacientes internados tratados com sucesso. RESULTADOS: Infecção bacteriana e sangramento foram eventos que levaram à morte, mutuamente exclusivos. Cinco fatores de risco foram únicos para morte por infecção bacteriana (desnutrição, estertores pulmonares, anemia grave, neutropenia absoluta grave e número de leucócitos aumentados), enquanto outros seis foram exclusivos para morte por sangramento (icterícia, neutropenia relativa grave, trombocitopenia grave, lesão hepática, insuficiência renal, maior carga de parasitas na medula óssea). Entre os pacientes tratados com sucesso, as principais síndromes de leishmaniose visceral foram infecções bacterianas, sangramento, anemia grave, diarreia, dispneia, edema, icterícia e carga de parasitas na medula óssea. CONCLUSÕES: Os dados apoiam a ideia de que as infecções bacterianas são secundárias a imunoparalisia. O amplo envolvimento de órgãos e sistemas é de forma plausível devido a elevada produção de citocinas pró-inflamatórias, cujas ações se encaixam com a leishmaniose visceral. As síndromes e os mediadores causais são típicos da síndrome de resposta inflamatória sistêmica, desenrolando-se lentamente.