ABSTRACT
Weil's disease, the most severe form of leptospirosis, is characterized by jaundice, haemorrhage and renal failure. The mechanisms of jaundice caused by pathogenic Leptospira remain unclear. We therefore aimed to elucidate the mechanisms by integrating histopathological changes with serum biochemical abnormalities during the development of jaundice in a hamster model of Weil's disease. In this work, we obtained three-dimensional images of infected hamster livers using scanning electron microscope together with freeze-cracking and cross-cutting methods for sample preparation. The images displayed the corkscrew-shaped bacteria, which infiltrated the Disse's space, migrated between hepatocytes, detached the intercellular junctions and disrupted the bile canaliculi. Destruction of bile canaliculi coincided with the elevation of conjugated bilirubin, aspartate transaminase and alkaline phosphatase levels in serum, whereas serum alanine transaminase and γ-glutamyl transpeptidase levels increased slightly, but not significantly. We also found in ex vivo experiments that pathogenic, but not non-pathogenic leptospires, tend to adhere to the perijunctional region of hepatocyte couplets isolated from hamsters and initiate invasion of the intercellular junction within 1 h after co-incubation. Our results suggest that pathogenic leptospires invade the intercellular junctions of host hepatocytes, and this invasion contributes in the disruption of the junction. Subsequently, bile leaks from bile canaliculi and jaundice occurs immediately. Our findings revealed not only a novel pathogenicity of leptospires, but also a novel mechanism of jaundice induced by bacterial infection.
Subject(s)
Hepatocytes/microbiology , Intercellular Junctions/microbiology , Jaundice/etiology , Leptospira interrogans/physiology , Leptospirosis/complications , Weil Disease/complications , Alanine Transaminase/metabolism , Alkaline Phosphatase/metabolism , Animals , Aspartate Aminotransferases/metabolism , Bacterial Translocation/physiology , Bilirubin/metabolism , Cricetinae , Disease Models, Animal , Hepatocytes/pathology , Hepatocytes/ultrastructure , Intercellular Junctions/pathology , Intercellular Junctions/ultrastructure , Jaundice/metabolism , Leptospirosis/metabolism , Male , Mesocricetus , Weil Disease/metabolismSubject(s)
Pancreatitis/parasitology , Weil Disease/complications , Academic Medical Centers , Amylases/blood , Creatine Kinase/blood , Creatinine/metabolism , Enzyme-Linked Immunosorbent Assay , Hospital Mortality , Humans , Incidence , India/epidemiology , Metabolic Clearance Rate , Pancreatitis/diagnosis , Pancreatitis/epidemiology , Pancreatitis/metabolism , Pancreatitis/therapy , Prognosis , Prospective Studies , Renal Insufficiency/diagnosis , Renal Insufficiency/metabolism , Renal Insufficiency/parasitology , Sensitivity and Specificity , Treatment Outcome , Weil Disease/diagnosis , Weil Disease/epidemiology , Weil Disease/metabolism , Weil Disease/therapyABSTRACT
Measurements were made of serum and urine myoglobin in 48 patients with leptospiral jaundice (LJ) and 56 patients with various acute infections. At the height of LJ blood myoglobin level reached 28.96 +/- 4.3 micrograms/l (normal concentration 0.315 +/- 0.002 microgram/l). Compared to acute pneumonia, acute viral hepatitis, tonsillitis, erysipelas, diphtheria, health values, the ratio of serum myoglobin to urine myoglobin in leptospirosis made up 45.25 against 5.4, 4.8, 6.8, 3.7, 1.8 and 1.3, respectively. A relationship was found between concentrations of myoglobin, bilirubin, creatinine in the blood and leptospirosis severity. Elevation of serum myoglobin as a manifestation of specific myositis is pathognomic for leptospirosis and contributes to the onset of acute renal failure and disturbance of bilirubin metabolism. Quantitation of blood myoglobin may be helpful as an additional test for leptospirosis severity.
Subject(s)
Myoglobin/analysis , Weil Disease/etiology , Adolescent , Adult , Aged , Antibodies, Bacterial/blood , Blood Donors , Female , Humans , Jaundice/diagnosis , Jaundice/etiology , Jaundice/metabolism , Leptospira interrogans/immunology , Male , Middle Aged , Severity of Illness Index , Weil Disease/diagnosis , Weil Disease/metabolismABSTRACT
The content of autorosettes in the peripheral blood forming from red cells round neutrophils and monocytes was found increased during the acute period of icterohemorrhagic leptospirosis. Autorosette-forming cells are characterized by a high activity of alkaline and acid phosphatases and low NBT-test values. The content of autorosettes directly correlates with the disease severity, bilirubin level, and presence of anemia. Assessment of autorosette-forming cells in patients with leptospirosis may be used as an additional test for evaluating the severity of intoxication, disease course, and for predicting the complications and disease outcome.
Subject(s)
Leukocytes/immunology , Rosette Formation , Weil Disease/immunology , Acid Phosphatase/blood , Adolescent , Adult , Aged , Alkaline Phosphatase/blood , Female , Histocytochemistry , Humans , Leukocytes/metabolism , Male , Middle Aged , Weil Disease/diagnosis , Weil Disease/metabolismABSTRACT
The role of macrophages in host defense was studied in vivo and in vitro. The intravenous administration of silica, an agent reported to selectively inactivate macrophages, increased the sensitivity to leptospiral infection and inhibited bacterial clearance. Active immunization with killed organisms or with leptospiral lipopolysaccharide (L-LPS), and passive immunization with a monoclonal antibody showed powerful protective effects against infection in mice. The effect of immunization decreased in silica-treated mice. These findings were supported by electron microscopic examination and observation of killing by macrophages in vitro.
