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[Leptospirosis and environment. Study of 2 major foci in New Caledonia].

A study of human and animal leptospirosis was carried out in new Caledonia's two most important focuses. This survey showed an annual incidence in the human population of 8.8 p. thousand in the Nera basin and 0.88 p. thousand in the Coulée basin. Male adults with agricultural and livestock occupations are the most exposed, especially from March to May, the end of the hot season. Frequent contacts with fresh water and animals, and the failure to use of gloves and boots, significantly increase the risk of contamination. Two factors of severity are important: serotype and age. Leptospira icterohaemorrhagiae is responsible for serious and fatal clinical forms and patients over 50 years of age have a maximum vital risk. In order to reduce the incidence and the severity of this disease, it appears desirable to vaccinate the farmers and the cattle breeders against L. icterohaemorrhagiae and to institute mass media information campaigns to warn against the risks of contamination.

Adult↗

Leptospirosis: a childhood disease.

A diagnosis of leptospirosis was confirmed in nine children who were admitted to St. Louis Children's Hospital during the past 54 months. Epidemiologic, clinical, cultural, and serologic data which were obtained emphasize (1) the high incidence of urban cases; (2) contact with dogs as the most likely source of infection; and (3) that serotypes other than Leptospira icterohaemorrhagiae may produce severe clinical disease. Unusual or previously unreported manifestations of leptospirosis including acalculous cholecystitis, pancreatitis, abdominal causalgia, desquamating skin rashes, and infarction of the extremities which were noted in these children are discussed.

Adolescent↗

[Less frequent etiology in uveitis].

This material intends to present three clinical observations regarding the uveitis etiology, that is represented by the association of some etiological factors less known: Toxoplasma gondii, Listeria monocytogenes, Leptospira icterohaemorrhagiae. The uveitis described here have been severe in the fast evolution and with trends of reappearence. This work demonstrates that the strict etiological antibacteria and antiparasite therapy is not enough and only corticotherapy is able to fight against the accentuated inflammatory phenomena that go along with type of uveitis.

Adrenal Cortex Hormones↗

The pathogenisis of leptospirosis II. Jaundice in experimental leptospirosis in guinea pigs.

Different mechanisms responsible for the appearance of jaundice in leptospirosis caused by Leptospira icterohaemorrhagiae in guinea pigs were discussed. Hepatocellular damage was demonstrated with the presence to a lesser extent of intrahepatic biliary obstruction. A massive destruction of extravascular red blood cells liberated by the hemorrhagic diathesis, appeared to be the main cause in the genesis of jaundice. The latter was inhibited following the neutralization of the reticuloendothelial system of guinea pigs by an irradiation before the infection.

Animals↗

Comparison of the fatty acid profiles of Borrelia, Serpulina and Leptospira species.

Fatty acid methyl ester (FAME) derivatives were examined as a means of characterizing Borrelia burgdorferi isolates and distinguishing them from other spirochaetes. Analysis was performed using a gas liquid chromatography column in conjunction with Microbial Identification System (MIS) software. Reproducible FAME profiles were produced which distinguished Borrelia species, Serpulina hyodysenteriae and Leptospira icterohaemorrhagiae. Furthermore, the FAME profiles of four recognized Borrelia species (including two American isolates of Borrelia burgdorferi, B31 and JD1) were distinct from one another and from the BSK II medium in which they were grown. The results confirm previous reports that FAME profiles of bacteria represent a diagnostic phenotypic property and suggest that they may have applications in the chemotaxonomic classification of Borrelia species.

Borrelia↗

Effect of cyclophosphamide treatment on clinical and serologic response of rats to infection with Leptospira interrogans serovar icterohaemorrhagiae.

Young albino rats were immunosuppressed with cyclophosphamide and exposed to virulent and low-virulence Leptospira interrogans serovar icterohaemorrhagiae 820K. In rats exposed to virulent and low virulence leptospires, microscopic agglutinating antibody responses occurred later, and longer leptospiremic phase and more massive tissue invasion by the organisms were observed in immunosuppressed rats than in immunocompetent controls. Clinical and pathologic signs of illness were more severe in the immunosuppressed animals than in immunocompetent controls. When exposed to low-virulence leptospires, immunosuppressed rats became infected and developed signs of illness and 2 of 16 died. Immunocompetent rats rapidly developed a humoral response and did not develop any signs of illness, and with 1 exception, organisms were not recovered from any tissues.

Animals↗

The pathogenesis of leptospirosis I. Hemorrhages in experimental leptospirosis in guinea pigs.

In experimental infections of guinea pigs with a virulent strain of Leptospira icterohaemorrhagiae widespread hemorrhages were observed. Thrombocytopenia, prolongation of prothrombin, thrombin, partial thromboplastin and coagulation times, decrease of plasma fibrinogen, factor V, factor VIII and the presence of fibrinogen degradation products were demonstrated. Treatment of infected guinea pigs with heparin prolonged life for two to three days. The histological observations revealed that the main lesion is a severe injury of the vasculature, mainly arteries, arterioles and capillaries. Most of the endothelial cells are affected or destroyed and the muscular fibers of arteries and arterioles are injured. With Martius-Scarlet-Blue, Weigert or Picro-Mallory stains it was demonstrated that the organization seen in the vessels is not all made of fibrin. The conclusion reached was that the hemorrhages observed in experimental leptospirosis in guines pigs are due to disseminated intravascular coagulation.

Animals↗

Infections in an Alpine environment: antibodies to hantaviruses, leptospira, rickettsiae, and Borrelia burgdorferi in defined Italian populations.

From 1987 to 1991, a seroepidemiologic survey for antibodies to hantaviruses, leptospira, rickettsiae, and Borrelia was conducted in selected Italian population groups. In the mountainous areas of northeastern Italy, the prevalence of antibody to hantaviruses, as detected by indirect immunofluorescent antibody (IFA) assay, was 7.1%, 4.8%, 4.3%, and 4% in 265 forestry workers, 82 rangers, 395 farmers, and 75 hunters, respectively. Among 299 Alpine soldiers, the prevalence was lower (0.7%). Of those with Hantaan antibody, the reactivity pattern using Hantaan, Puumala, and Fojnica viruses suggested a prevalence of antibody to Hantaan virus, with titers reaching levels of 128. The presence of leptospiral antibodies (by microagglutination test), which included the prevalence of antibodies to Leptospira icterohaemorrhagiae, L. bratislava, and L. saxkoening serotypes, was observed in 10-12% of the farmers and forestry workers in these Alpine mountain regions. Only a few sporadic clinical cases of leptospirosis have been reported from these regions. Antibodies to Borrelia burgdorferi (by IFA) were observed in 19% of the rangers and forestry workers, with lower values in farmers (10%) and hunters (8%). These data suggest the presence of a large number of asymptomatic infections with B. burgdorferi and the leptospires in the densely wooded areas of the Alpine Italian regions. Furthermore, the recent identification of a case of Hantaan acute nephropathy in a man living in the mountainous northeastern area of Italy confirms the presence of hantavirus in the Italian Alpine zones, especially those near the Slovenian border.

Adult↗

Diseases and parasites of cattle in Vanuatu.

A study of cattle diseases was carried out in Vanuatu from 1971 to 1981. Tuberculosis was discovered in 4 herds and eradication was completed by 1981. The number of farms with brucellosis reactors increased from 2 in 1976 to 7 in 1978 despite eradication measures. Antibodies to serovars Leptospira icterohaemorrhagiae, australis, sejroe and canicola were demonstrated by the microscopic agglutination test. Antibodies were demonstrated against infectious bovine rhinotracheitis/infectious pustular vulvovaginitis and bovine virus diarrhoea/mucosal disease complexes. Of the 18 parasites identified, Haemaphysalis longicornis, Haemonchus, sp, Oesophagostomum phlebotomum and Neoascaris vitulorum were the most prevalent. As brucelossis is the only serious disease present, Vanuatu is in a favourable situation with regard to cattle diseases.

Animals↗

Impact of clinical and laboratory findings on prognosis in leptospirosis.

OBJECTIVE: The aim of this study was to evaluate epidemiological, clinical and laboratory features, and risk factors for mortality in leptospirosis. METHODS: Seventy-two adult leptospirosis cases were reviewed. Categorical clinical and laboratory findings of survivors and non-survivors were assessed by Chi square analysis. Non-categorical findings were assessed by the student t test. Clinical findings and laboratory data with p <0.05 were assessed by stepwise logistic regression analysis for mortality. RESULTS: Of all patients, mean age was 47.3 +/- 15.7 years, 82% were men and, 51% were farmers. Icterus occurred in 75%, and high fever was seen in 61 of the patients. The most frequently detected serotype was Leptospira icterohaemorrhagiae (30%). Overall mortality rate was 17%. In those non-survivors, altered mental status (p = 0.002), hepatomegaly (p = 0.037), haemorrhage (p = 0.019), ALT level (p = 0.008), AST level (p = 0.02), prolonged prothrombin time (p = 0.02) and increased serum potassium levels (p = 0.004) were seen more frequently than in survivors. Altered mental status (p = 0.01, OR: 8.9, CI 95%: 1.6-50.7) and serum potassium levels at hospital admission (p = 0.01, OR: 4.2, CI 95%: 1.4-13.1) were detected as independent risk factors for mortality. CONCLUSIONS: Leptospirosis patients with altered mental status and hyperpotassaemia at hospital admission are at high risk for mortality and should be followed up more closely at the intensive care unit.

Adolescent↗

A study of sutopsy findings in 62 cases of leptospirosis in a metropolitan city in India.

BACKGROUND: Leptospirosis is an important sporadic zoonotic disease caused by the spirochete Leptospira icterohaemorrhagiae . The disease becomes a major public health problem, particularly during the monsoon months. MATERIALS AND METHODS: Analysis of autopsy findings of 62 cases of clinically suspected leptospirosis was carried out to identify the pathology and determine the cause of death. RESULTS: Most patients were young males who presented with fever, breathlessness, haemoptysis, bleeding, oliguria and icterus. They died after a brief stay in hospital. A post-mortem diagnosis of leptospirosis was made on the basis of characteristic organ findings, aided by results of serology, Levaditi's staining and / or immunohistochemistry (IHC) on kidney sections. Massive intra-alveolar haemorrhage (48 cases), acute interstitial nephritis and / or acute tubular necrosis (45 cases) and myocarditis (24 cases) were the main autopsy findings. Haemorrhage in various organs like the heart, gastrointestinal tract, brain, pancreas and adrenals were also seen. Thirty of 54 kidney sections were positive for leptospiral antigens by IHC. There was extensive haemorrhages in the lungs in 48 (77%) cases and that was the cause of death in most of these cases. CONCLUSION: Bleeding into various tissues and organs is the main finding noted in this study. The post-mortem examination of patients dying of leptospirosis revealed that pulmonary haemorrhage was the cause of death in most individuals.

Adolescent↗

[Icterohemorrhagic leptospirosis with acute renal failure (author's transl)].

Icterohemorrhagic leptospirosis is a zoonosis which is relatively frequent in rural agricultural or cattle areas. In the severe forms of the disease renal affection is frequent, but the incidence of acute renal insufficiency is far lesser. Three cases of acute renal insufficiency in adult male patients secondary to an infection by Leptospira icterohaemorrhagiae are presented. Two of the patients resided in urban areas and only one of which presented professional risk. The clinical polymorphysm of the illness is confirmed, having observed not only the absence of fever but also that of jaundice. The former history of chronic alcoholism, present in two cases, determined diagnostic difficulties with acute alcoholic hepatitis. The serologic diagnosis is often positive only at the end of the second week, and the need to carry out a series of seroaglutinations is to be insisted upon. The types of renal impairment in leptospirosis are reviewed and the presence of acute renal insufficiency is stressed, including those patients with less severe forms of the disease, and especially those without Weil's syndrome. All of the patients had to be treated with dialysis, although two of them had a conserved diuresis after an initial brief period of oliguria.

Acute Kidney Injury↗

[Possibilities and current technics of dialysis in leptospirosis with severe renal damage].

Three patients with severe liver and renal failure admitted to the Infectious Diseases Department of the Alessandria for suspected leptospirosis in the second half of 1979 are presented. In one case, the agent responsible was Leptospira icterohaemorrhagiae AB Wjnberg strain, in another Gram-negative sepsis, and in the third acute pancreatitis associated with serious Escherichia coli infection. An account is given of the peritoneal dialysis technique that led to successful resolution of the serious liver and renal failure.

Acute Kidney Injury↗

Serum biochemical changes in dogs with experimental Leptospira interrogans serovar icterohaemorrhagiae infection.

Inoculation of 2 groups of dogs with 1 X 10(9) and 4 X 10(9) Leptospira interrogans serovar icterohaemorrhagiae produced disease varying from transient fever to uremia and death. Clinical signs of disease in the severely affected dogs were fever, dehydration, depression, and icterus. Laboratory changes in serum of infected dogs included increased urea nitrogen, creatinine, phosphorus, alkaline phosphatase, total bilirubin, aspartate aminotransferase, and alanine aminotransferase. Chloride concentration decreased in the serum of dogs with severe disease. The icterus in the infected dogs did not appear to be related to hemolytic anemia.

Alanine Transaminase↗

Physical and genetic maps of the Leptospira interrogans serovar icterohaemorrhagiae strain Ictero no.1 chromosome and sequencing of a 19-kb region of the genome containing the 5S rRNA gene.

We report the construction of physical and genetic maps of the chromosome of Leptospira interrogans serovar icterohaemorrhagiae strain Ictero No.1 using pulsed-field gel electrophoresis of DNA fragments generated by digestion with enzymes SrfI, AscI, FseI, and NotI and using reciprocal hybridization. We also sequenced the 19-kilobase (kb) DNA segment including the one gene for 5S rRNA (rrf) of pathogenic Leptospira. The size of the chromosome of the strain Ictero No.1 was estimated to be 4673kb and was found to be similar to those of the chromosomes of the leptospira strains Verdun (serovar icterohaemorrhagiae) and RZ11 (serovar pomona). The strains Verdun and RZ11 carry a small 350-kb replicon (minichromosome), and the strain Ictero No.1 also contained the same kind of molecule together with the chromosome. The physical maps of the strains Ictero No.1 and Verdun were almost identical, as were the locations of the selected genes, except for the location of one of the 16S rRNA genes. Overall, the genetic organization appeared to be conserved within the serovar icterohaemorrhagiae strains. In the sequenced region, we identified 10 putative ORFs and one rrf sequence, and the transcription orientations were all the same. A homology search for the products deduced from the sequenced data revealed that the orf H exhibited high similarity to malic acid enzyme of Haemophilus influenzae and fumarate hydratase of Escherichia coli (orf J). The rest of the putative products encoded by ORFs in the sequenced region showed little similarity with the proteins contained in the databases and were considered to be unknown proteins.

Bacterial Proteins↗

In vivo apoptosis of hepatocytes in guinea pigs infected with Leptospira interrogans serovar icterohaemorrhagiae.

To investigate the contribution of the previously demonstrated in vitro apoptosis to the pathogenesis of leptospirosis, guinea pigs were infected with Leptospira interrogans serovar icterohaemorrhagiae strain Verdun and sequentially killed to collect target organs involved in the natural history of the disease (liver, kidneys, lungs, spleen and heart). The combination of histopathological procedures and a specific TUNEL assay showed a significant Leptospira-induced programmed cell death of hepatocytes with a peak at 48 h post inoculation. Hepatocyte nuclei showed morphological changes including fragmented and condensed nuclei. This phenomenon occurred early in the course of the disease at a time where infecting leptospires were present at a low density between the liver parenchyma cells.

Animals↗

Toll-like receptor 4 protects against lethal Leptospira interrogans serovar icterohaemorrhagiae infection and contributes to in vivo control of leptospiral burden.

The roles of innate immune responses in protection from or pathogenesis of severe leptospirosis remain unclear. We examined the role of Toll-like receptors (TLRs) in mouse infection and macrophage responses to Leptospira. C3H/HeJ mice (TLR4 deficient) and C3H/HeJ-SCID mice, but not C3H/OuJ mice (TLR4 intact), died after intraperitoneal infection with Leptospira interrogans serovar Icterohaemorrhagiae. Death in both C3H/HeJ mouse strains was associated with jaundice and pulmonary hemorrhage, similar to the patient from whom the isolate was obtained. In chronic sublethal infection, TLR4-deficient mice harbored more leptospires in liver, lung, and kidney than control mice. Heat-killed Leptospira stimulated macrophages to secrete proinflammatory cytokines, tumor necrosis factor alpha, interleukin-6, and macrophage inflammatory protein 2 not inhibited by polymyxin B, suggesting that leptospiral lipopolysaccharide (LPS) did not drive these responses. Anti-TLR4 and anti-MD-2 but not anti-CD14 monoclonal antibodies inhibited cytokine production. Peritoneal macrophages from CD14-/- and TLR2-/- mice exhibited no defect in cytokine responses to Leptospira compared to controls. Macrophages from C3H/HeJ, TLR4-/-, and MyD88-/- mice secreted far-lower levels of cytokines than wild-type macrophages in response to Leptospira. TLR4 plays a crucial role in protection from acute lethal infection and control of leptospiral burden during sublethal chronic infection. Cytokine responses in macrophages correlated with leptospiral clearance. These TLR4-dependent but CD14/TLR2-independent responses are likely mediated by a leptospiral ligand(s) other than LPS.

Adolescent↗

Morphological characterization of lung and kidney lesions in C3H/HeJ mice infected with Leptospira interrogans serovar icterohaemorrhagiae: defect of CD4+ and CD8+ T-cells are prognosticators of the disease progression.

Neonates and young C3H/HeJ mice were highly susceptible to lethal infection with Leptospira interrogans serovar icterohaemorrhagiae. The main pathological changes were seen by light microscopy in the lung and kidneys of 3-week-old mice at 11 days after inoculation. Lung histological lesions included small and medium-sized vasculitis with fibrinoid changes, hemorrhages, moderate infiltrate of mononuclear inflammatory cells and fibrin thrombi. In the kidney there was mild to severe acute tubular necrosis associated with interstitial nephritis. Repair of damaged tubules in surviving mice was observed within 17 days after inoculation. Pathological findings of CD4+ and CD8+ cell-depleted mice were clearly more severe than that seen in untreated animals by 17 days after inoculation. Comparatively, CD4+/CD8+ cell-depleted mice had more marked lung and kidney lesions than in the CD8+ or CD4+ cell-depleted mice. A very high level of tubular alterations was seen in the kidneys of all treated groups. Increased degrees of interstitial nephritis also reflected the T-cell subsets depletion related events. Leptospires were clearly demonstrated by immunoperoxidase close to the sites of histological damage in all infected mice. C3H/HeJ mice represent a useful model for further studies in pathogenicity of leptospires and natural resistance of the host.

Animals↗