Endothelial biomarkers as predictors for haemodialysis need in severe leptospirosis patients (Weil's disease).

OBJECTIVE: To investigate the prediction ability of vascular injury biomarkers for haemodialysis requirement in patients with severe leptospirosis. METHODS: Prospective study with severe leptospirosis patients hospitalised in Fortaleza, Brazil. Blood samples were collected hospital admission to quantify vascular injury biomarkers: syndecan-1, ICAM-1, VCAM-1, angiopoietin-2 and FGF-23. Two groups were evaluated according to haemodialysis requirement during hospital stay. RESULTS: Twenty-seven patients were included, with a mean age of 39 ± 18 years. 88.9% were males. 53.8% needed haemodialysis and presented higher levels on hospital admission of syndecan-1 (572 [300-811] vs. 263 [106-421] ng/ml; p = 0.03), angiopoietin-2 (1.52 [0.72-2.72] vs. 0.63 [0.4-1.38] ng/ml; p = 0.01), and FGF-23 (291 [56-2031] vs. 10 [10-806] pg/ml; p = 0.021). Syndecan-1 showed significant correlation with creatinine (r = 0.546; p = 0.05) and total bilirubin levels (r = 0.534; p = 0.013) on hospital admission. Angiopoietin-2 showed significant correlation with creatinine levels (r = 0.513; p = 0.009) on hospital admission and with number of haemodialysis sessions (r = 0.406; p = 0.049). No significant correlation was found with FGF-23. Regarding prognostic performance, combined syndecan-1 and angiopoietin-2 levels had a better ability to predict haemodialysis need in patients with severe leptospirosis (AUC-ROC = 0.744 [95% CI: 0.545-0.943] p = 0.035). CONCLUSION: Syndecan-1 and angiopoietin-2 were associated with haemodialysis need in patients with severe leptospirosis and may be useful to improve therapeutic approach and reduce mortality.

Weil syndrome causing autoimmune haemolytic anaemia.

Weil syndrome is a fulminant form of leptospirosis, usually caused by spirochetal organism Leptospira interrogans. It is characterized by icterus, petechial rashes over the body, signs of renal failure and hepatic failure. Anaemia is a usual manifes- tation of Leptospira infection, but autoimmune haemolytic anaemia is rare. We report a patient with autoimmune haemolytic anaemia following Leptospira infection, which was responsive to high-dose steroid therapy.

[Gastrointestinal bleeding and acute hepatic failure by leptospirosis: an entity that should not be forgotten]. / Hemorragia digestiva e insuficiencia hepática aguda por leptospirosis: una entidad que no debemos olvidar.

Leptospirosis disease is caused by the spirochete Leptospira. It is a worldwide distribution zoonosis, with predominance in the tropics. In Spain, it is not frequent but some cases have been noticed especially in humid areas surrounded by rivers, lakes or ponds, such as Catalonia, Andalucia or the Valencian Community. It is transmitted by a variety of animals such as cows or rats, that are infected either by direct contact with these animals or their urine, or indirectly by consuming or being in contact with water contaminated by their urine. The clinical manifestations are very variable, being asymptomatic or not very symptomatic in most of the patients. Unusually, leptospirosis presents with a first phase with fever, myalgias, liver injury or different organs hemorrhage, followed by a second phase with the presence of jaundice due to hepatic failure. Weil's disease is a kind of severe leptospirosis characterized by hepatic failure with jaundice and acute renal failure, associated with high mortality rates.The diagnosis is based on serological techniques and DNA detection by PCR. The treatment consists of life support measures and antibiotic therapy. A patient with Weil's disease and leptospirosis digestive bleeding is presented, with a fulminant clinical course. In order to achieve an early diagnosis, the need to keep this entity in mind must be emphasized, especially in favorable epidemiological environments as the one of this patient.

Destruction of the hepatocyte junction by intercellular invasion of Leptospira causes jaundice in a hamster model of Weil's disease.

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.

A case of Weil's disease presenting as Stevens-Johnson syndrome.

Leptospirosis presents in a biphasic manner: an early leptospiraemic phase and a late immune phase. In its severe form, it presents with multi-organ failure, also known as Weil's disease. Stevens-Johnson syndrome (SJS) is an autoimmune hypersensitive reaction leading to diffuse fluid filled vesicle formation with detachment of skin and mucous membrane. Though SJS is triggered by different infections and drugs, its association with leptospirosis is not frequently reported. Here we present such a case.

Clinical and imaging manifestations of hemorrhagic pulmonary leptospirosis: a state-of-the-art review.

Leptospirosis, a spirochetal zoonosis, is frequently unrecognized due to its manifestation as an undifferentiated fever. It is an emerging infectious disease that has changed from an occupational disease of veterinarians, farmers, butchers, and other animal handlers to a cause of epidemics in poor and decayed urban communities in developing countries. Humans are infected when mucous membranes or abraded skin come into direct contact with the urine of infected animals, especially rats and dogs. Mortality from severe leptospirosis is high, even when optimal treatment is provided. The diagnosis of leptospirosis is based on clinical findings, history of direct or indirect exposure to infected animals in endemic areas, and positive serological tests. It should be considered in the differential diagnosis of patients with febrile illnesses associated with pneumonitis and respiratory failure, especially when hemoptysis is present. Severe pulmonary involvement in leptospirosis consists primarily of hemorrhagic pneumonitis. In advanced cases, adult respiratory distress syndrome and massive pulmonary hemorrhage may occur. Chest radiographs show bilateral alveolar infiltrates and/or resemble viral pneumonia, bronchopneumonia, tuberculosis, adult respiratory distress syndrome, and other causes of pulmonary hemorrhage such as Goodpasture syndrome. High-resolution computed tomography scans may show nodular infiltrates, areas of consolidation, ground-glass attenuation, and crazy-paving patterns. Bronchoalveolar lavage and autopsy studies have suggested that ground-glass opacities and air-space consolidations are secondary to pulmonary hemorrhage. Although not specific, the presence of these computed tomography findings in a febrile patient with an appropriate history should suggest a diagnosis of leptospirosis.

Two cases of Weil's disease with acute renal failure in the central Tokyo metropolitan area.

The incidence of leptospirosis, or Weil's disease, in developed countries, particularly in temperate regions, has been dramatically decreasing due to recent improvements in the hygienic environment. In these areas, physicians rarely face this disease and inclusion as a differential diagnosis of acute renal failure seems increasingly uncommon. However, we encountered two cases of severe leptospirosis requiring hemodialysis in central Tokyo. Both cases showed hyperbilirubinemia, thrombocytopenia and mental disturbance in addition to acute renal failure. Severe leptospirosis remains associated with high mortality rates, and early clinical suspicion and laboratory confirmation of the disease are crucial. Detailed history-taking suggested that leptospirosis was caused by transmission from rats in both cases. Rodents inhabit most land areas, implying that the disease can occur all over the world, even in huge metropoles such as Tokyo. These two cases indicate the need for awareness of leptospirosis among physicians working even in urban areas of developed countries.

Profile of patients of leptospirosis in sub-Himalayan region of North India.

CONTEXT: Leptospirosis is an emerging zoonosis world wide; it is being reported in many areas of south-east Asia now. A recent surge in the number of patients with leptospirosis has been noted in the Sub-Himalayan region of North India which was uncommon. We present here a case series of 13 patients who were positive for leptospirosis either by IgM Elisa or PCR method. AIMS: To study the profile of leptospirosis in a sub-Himalayan state of North India i.e. Himachal Pradesh. SETTINGS AND DESIGN: This was a retrospective study of leptospira positive patients who were admitted in IGMC, Shimla. The study was conducted in Indira Gandhi Medical College, Shimla situated at a moderate altitude in North India. METHODS AND MATERIAL: All patients presenting in Medical College Hospital during three months from 1st August to 31st October who tested IgM positive or borderline or PCR positive for leptospirosis were taken into the study. Their presenting complaints, examination findings and lab findings were recorded and analyzed based on the Faine's criteria and modified Faine's criteria. Patients with clinical features of Leptospirosis and who tested positive for IgM Leptospirosis were taken as IgM lepto can be falsely positive. RESULTS: Out of total 13 patients there were 3 males and 10 females, age range was from 24 to 78 yrs and mean was 44 yrs. Predominant complaints were fever, jaundice, myalgia, and headache. All had contact with animals or contaminated environment. LFT's were deranged in 12 and renal functions were deranged in all. Ten had positive results for IgM against leptospira while 2 had borderline positive result. One patient was positive by PCR method using G1, G2 primers. Ten patients had Weil's syndrome and this was the main presentation of leptospirosis in our group, one had acute respiratory distress syndrome (ARDS) and needed ventilator. There were no deaths. All responded to injectable ceftriaxone and oral doxycycline. Applying Faine's criteria only 7 were positive, but using modified Faine's criteria all 13 were positive for leptospirosis. CONCLUSIONS: Leptospirosis was unexpectedly found to be positive in many of our patients who were having pyrexia during the monsoons. A recent surge has been noted in the number of cases with leptospirosis in this state. The possibility of co-infection especially with scrub typhus must be considered in cases with atypical presentation and severe illness. Most of the patients were from rural background with poor hygienic conditions. There was no mortality and main complication was Weil's syndrome in 77 percent.

Leptospiral nephropathy.

Leptospirosis is recognized as a globally re-emerging zoonosis. Interstitial nephritis is the principal feature of the disease. Leptospirosis-induced acute kidney injury typically is nonoliguric and includes hypokalemia. Tubular function alterations precede a decrease in the glomerular filtration rate, which could explain the high frequency of hypokalemia. Studies in human beings and animals have shown increased urinary fractional excretion of potassium and sodium, as well as an increased potassium/sodium ratio, suggesting increased distal potassium secretion caused by increased distal sodium delivery consequent to functional impairment of proximal sodium reabsorption. Confirming these findings, Western blot studies have shown lower renal expression of the sodium/hydrogen exchanger isoform 3 and of aquaporin 2, together with higher renal expression of the Na-K-2Cl cotransporter NKCC2, in infected animals. The severe form (Weil's disease) manifests as diffuse alveolar hemorrhage, pulmonary edema, acute respiratory distress syndrome, or a combination of these features, accompanied by acute kidney injury and can be highly lethal. Antibiotic treatment is efficient in the early and late/severe phases. For critically ill leptospirosis patients, the following are recommended: daily hemodialysis, low daily net fluid intake (because of the risk for pulmonary hemorrhage), and lung-protective strategies (low tidal volumes and high positive end-expiratory pressures after recruitment maneuvers).

[Ophthalmic manifestation in icterus--hemorrhagic leptospirosis]. / Leptospiroza ictero-hemoragicâ--manifestari oculare.

We present the case of a 19-year-old male, admitted in the Ophthalmology Clinic for Macular Chorioretinitis, hemorrhagic form. Laboratory findings shown high titres of icterus-hemorrhages leptospirosis.

Leptospirosis-induced meningitis and acute renal failure in a 19-month-old male child.

An unusual case of leptospirosis is described in a 19-month-old male child presenting with meningitis and acute renal failure without jaundice. Some aspects concerning the pathogenesis and treatment of this potentially life-threatening disease are also discussed. Leptospirosis was diagnosed on the basis of history and serological tests.

Influence of leptospirosis on reproductive performance of sows in Brazil.

The purpose of this study was to investigate the association between seropositivity for the most frequent Leptospira serovars and reproductive losses in sows in Brazil. Serum samples from 351 sows from 18 herds (in the state of Rio de Janeiro, Brazil) with low reproductive efficiency were tested (microscopic agglutination) for antibodies against serovars of Leptospira. Antibodies were detected in serum samples of 66.1% of all sows, most frequently serovar icterohaemorrhagiae (43.1%), followed by pomona (18.1%) and tarassovi (9.9%). Seroreactivity to icterohaemorrhagiae and pomona were associated (P<0.05) with impaired reproductive performance (and substantial economic loss). Seroreactivity for pomona was associated (P<0.05) with stillborn piglets and mummified fetuses, whereas seroreactivity to icterohaemorrhagiae was associated (P<0.05) with the number of piglets born dead.

Leptospirosis Presenting with Rapidly Progressing Acute Renal Failure and Conjugated Hyperbilirubinemia: A Case Report.

BACKGROUND Unexplained renal insufficiency combined with hepatic failure is a common problem encountered by clinicians. As with many disease processes involving multi-organ systems, reversible causes are usually not readily identifiable, and for many patients their health deteriorates rapidly. We present a rare cause of acute renal failure and hyperbilirubinemia occurring simultaneously, with leptospirosis presenting as Weil's disease. CASE REPORT A 53-year-old male presented to our clinic with complaints of anuria over the past two days. His symptoms started with dark urine, severe cramps in the thighs, and chills. The patient was a visitor to the United States from Guyana. Positive physical examination findings included mild tachycardia and hypotension, scleral icterus, and tenderness over abdomen, costovertebral angles, and thighs. The patient had a high white blood cell count, thrombocytopenia, renal/hepatic insufficiency, and an urinary tract infection (UTI). The patient was initially treated under the suspicion of acute kidney injury secondary to rhabdomyolysis and pyelonephritis. The patient continued to deteriorate with decreasing platelet counts, worsening renal function, hyperbilirubinemia, and respiratory distress, with no improvement with hemodialysis. Broad-spectrum antibiotics were administered, including doxycycline, due to a high suspicion of leptospirosis. The patient's condition drastically improved after initiation of doxycycline. On subsequent days, the patient's Leptospira antibody results were available, showing titers of more than 1:3200. Hemodialysis was discontinued as the patient started producing urine with improved kidney function. CONCLUSIONS As world travel becomes more economically feasible, we will continue to encounter foreign endemic diseases. Leptospirosis presenting as Weil's disease is a common cause of renal and hyperbilirubinemia in endemic areas. Often, as was the case for our patient where the time from presentation to acute respiratory distress syndrome (ARDS) was 72 hours, the diagnosis evolves over the course of several days. Antibody testing often takes time and delays in treatment can cause rapid clinical deterioration. In such cases, we recommend beginning empiric treatment before confirmation of laboratory tests.

Case report: Weil's disease with multiple organ failure in a child living in dengue endemic area.

BACKGROUND: There were few reports in the literature of Weil's disease with multiple organ failures, especially in children living in dengue endemic areas. CASE PRESENTATION: A 12-year-old child was admitted to Tangerang district hospital with a provisional diagnosis of dengue infection. On the third day of hospitalization, dengue diagnostic tests were negative. As fever still remained and was followed by jaundice, decreasing hemoglobin, increasing bilirubin with abnormal value of liver enzymes; other causes of disease were investigated. Leptospirosis was confirmed by rapid IgM test (SD(®)) for leptospira; and micro-agglutination test which indicated Leptospira serogroup bataviae infection. The patient developed Weil's disease during the course of illness. Renal function was back to normal on the 21st day of hospitalization, while hemoglobin and bilirubin returned to normal three weeks after discharged. CONCLUSIONS: Our report highlights the importance of considering leptospirosis as a differential diagnosis in children with acute febrile illness; even when the signs and symptoms for the more common diagnoses such as dengue or typhoid fever were pathognomonic. A normal leukocyte count with neutrophilia and negative dengue NS1, dengue IgM, and Salmonella typhi IgM on admission should raise suspicion of leptospirosis, and prompt diagnostic assays for leptospirosis should be conducted.

A 23-year-old Man with Leptospirosis and Acute Abdominal Pain.

Leptospirosis is a zoonosis caused by the spirochete Leptospira interrogans. Most cases of leptospirosis are mild to moderate, and self-limited. The course of disease, however, may be complicated by multiorgan dysfunction such as in Weil's disease. We present a case of Weil's disease with pancreatitis in a young Caucasian man residing in Hawai'i. Although leptospirosis is common in Hawai'i, few patients present with pancreatitis. This report of leptospirosis-induced pancreatitis should help raise awareness of clinicians to assess for pancreatitis when evaluating a patient with leptospirosis and acute abdominal pain.

Weil's disease: an unusually fulminant presentation characterized by pulmonary hemorrhage and shock.

A case of fulminant leptospirosis is presented, manifesting as rapid progression from acute undifferentiated febrile illness to refractory shock, jaundice, renal failure and massive pulmonary hemorrhage. The patient received aggressive intensive care unit support including prolonged intubation and ventilation. This case emphasizes that acute leptospirosis may well not be characterized by the classic scenario of a biphasic illness, but rather by a fulminant, monophasic illness.