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Leptospirosis is an important zoonotic disease, causing about 60,000 deaths annually. In this review, we have described in detail the immunopathogenesis of leptospirosis, the influence of cytokines, genetic susceptibility on the course of the disease, and the evasion of the immune response. These data are combined with information about immunological and pathomorphological changes in the kidneys, liver, and lungs, which are most affected by Weil’s disease. The review also suggests a possible role of the gut microbiota in the clinical course of leptospirosis, the main mechanisms of the influence of gut dysbiosis on damage in the liver, kidneys, and lungs through several axes, i.e., gut-liver, gut-kidney, and gut-lungs. Modulation of gut microbiota by probiotics and/or fecal microbiota transplantation in leptospirosis may become an important area of scientific research. Keywords: leptospirosis; dysbiosis; Weil’s disease

Resumen La leptospirosis en una enfermedad infecciosa importante en el diagnóstico diferencial de un paciente con síndrome ictérico hemorrágico, especialmente en países de ubicación tropical como Colombia. A continuación, se presenta el caso de un paciente masculino de 21 años, con cuadro clínico agudo caracterizado por presencia de fiebre y elevación de bilirrubinas, asociado a diarrea y trombocitopenia. Inicialmente se hizo diagnóstico presuntivo de dengue, sin embargo, durante su evolución presentó hemorragia y dificultad respiratoria asociada a secreción hemática con necesidad de intubación endotraqueal, por lo que se solicitó serologia IgM seriada de leptospira pensando en esta entidad como diagnóstico diferencial luego de indagar antecedentes epidemiológicos, la cual tuvo reporte positivo. Es importante conocer este tipo de casos debido a la presentación de compromiso pulmonar como una manifestación rara pero altamente asociada a mortalidad. Finalmente, con manejo de soporte y antibiótico adecuado se obtuvo una buena evolución clínica de este paciente. Abstract Leptospirosis is a relevant infectious disease when there is a patient with an ictero-hemorrhagic syndrome, especially in tropical countries such as Colombia. The following is the case of a 21-year-old male patient, with an acute clinical picture given by fever, elevated bilirubin, associated with diarrhea and thrombocytopenia. Initially, a presumptive diagnosis of dengue was made. However, during his evolution, he presented hemorrhage and respiratory distress with a hematic secretion that required endotracheal intubation. After inquiring about the epidemiological data, leptospirosis was considered a differential diagnosis. Serial serology for leptospira IgM was requested and was positive. It is essential to know this type of case due to pulmonary affections as a rare manifestation but highly associated with mortality. Finally, with adequate antibiotic and supportive management, a good clinical evolution of this patient was obtained.

BACKGROUND: Leptospirosis or also commonly called Weil disease is an acute infectious disease that can attack humans and animals and is classified as a zoonotic disease. Leptospirosis is caused by bacteria of the genus Leptospira found in rodents. The difficulty of the diagnosis process causes the case of leptospirosis less reported and is one of the neglected infectious diseases. Patient findings are often not optimal because of underdiagnosis or misdiagnosis. AIM: This study aims to determine the presence of Leptospira serovar bacteria in blood serum of leptospirosis suspect using the microscopic agglutination test (MAT) method. METHODS: This study is a descriptive observational using accidental sampling technique. Sample collection was performed in the Antang Community Health Center, Batua Health Center, and Bangkala Health Center in Manggala District. RESULTS: This study found that there were 31 serum samples. Results of MAT examination on blood serum yielded 11 positive samples of Leptospira (37%) with serovar Hebdomadis, Djasiman, Mini, Icterohaemorrhagiae, Bangkingan, and Bataviae. CONCLUSIONS: The presence of Leptospira bacteria in blood serum of suspected individuals using the MAT method obtained 11 samples of positive blood serum. Special counseling activities are required about leptospirosis and diagnosis enforcement in the community or workers who experience symptoms or leptospirosis suspect.

Leptospirosis or also commonly called Weil disease is an acute infectious disease that can attack humans and animals and is classified as a zoonotic disease. Leptospirosis is caused by bacteria of the genus Leptospira found in rodents. This study aims to determine the presence of Leptospira bacteria serovar in blood serum suspected of leptospirosis using the Microscopic Aglutination Test (MAT) method. This type of research is descriptive observational using accidental sampling technique with a total of 31 samples. Sampling was conducted at the Antang Community Health Center, Batua Health Center and Bangkala Health Center in Manggala District for two weeks. Data analysis in this research is descriptive in which the results are presented through tables and narratives. The results of MAT examination on blood serum yielded eleven positive samples of Leptospira (37%) with serovar Hebdomadis, Djasiman, Mini, Icterohaemorrhagiae, Bangkingan and Bataviae. The presence of Leptospira bacteria in the blood serum of suspected individuals using the MAT Method obtained 11 samples of positive blood serum. Need to conduct and improve special counseling activities about leptospirosis and diagnosis enforcement in the community or workers who experience symptoms or suspected leptospirosis.

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.

Resumen Introducción. La leptospirosis es una infección bacteriana endémica en Colombia. Su curso clínico puede ser variable y, en ocasiones, fatal. Hay pocos estudios en el país sobre los casos graves de esta enfermedad. Objetivo. Describir las características demográficas y clínicas de los pacientes con diagnóstico de leptospirosis grave hospitalizados en salas generales o atendidos en la unidad de cuidados intensivos de un hospital de cuarto nivel. Materiales y métodos. Se llevó a cabo un estudio observacional descriptivo de los pacientes adultos y niños con diagnóstico serológico de leptospirosis entre el 2010 y el 2016. Resultados. Se analizaron las historias clínicas de 87 pacientes, 74 % de los cuales correspondía a hombres y, el 84 %, a mayores de 18 años. El 35 % tenía alguna comorbilidad y la hipertensión arterial sistémica (16 %) y la diabetes mellitus (9 %) fueron las más comunes. Los síntomas más frecuentes fueron: fiebre, náuseas, astenia, mialgias, artralgias y dolor abdominal. El 34 % requirió atención en la unidad de cuidados intensivos, con una mediana de estancia de 5 días. El 61 % requirió hospitalización en sala general, con una mediana de estancia de 6 días. Todos los casos recibieron tratamiento antibiótico con ceftriaxona o doxiciclina. La tasa de letalidad fue del 1,1 % (n=1). Conclusiones. La infección por Leptospira spp. tiene el riesgo de diagnosticarse de manera tardía por su presentación clínica inespecífica, lo que implica considerar un gran número de diagnósticos diferenciales. La atención temprana de los pacientes con cuadros graves de esta enfermedad en la unidad de cuidados intensivos, puede evitar una mayor incidencia de complicaciones y disminuir la mortalidad. Abstract Introduction: Leptospirosis is an endemic bacterial infection in Colombia. Its clinical course can be variable and occasionally fatal. There are few studies in the country about severe cases of leptospirosis. Objectives: To describe the demographic and clinical characteristics of patients with a diagnosis of leptospirosis, and their management in a high complexity hospital. Materials and methods: This was a descriptive retrospective study of patients with a serologic diagnosis of leptospirosis between 2010 and 2016. Results: We analyzed 87 patients, 74% of them were men, and 84% were older than 18 years; 35% had a comorbidity, the most common being arterial hypertension (16%) and diabetes mellitus (9%). The most frequent symptoms were fever, nausea, fatigue, myalgia, arthralgia, and abdominal pain. The majority of patients required hospitalization in general wards (61%), with a median stay of six days; 34% required management in the intensive care unit, with a median stay of five days. Mortality was 1.1% (n=1). All patients received treatment with either ceftriaxone or doxycycline. Conclusions: There is a risk of leptospira infections having a late diagnosis given their unspecific clinical presentation, which generates a high number of differential diagnoses. The early management in the intensive care unit could decrease the incidence of complications and the mortality of patients with leptospirosis.

A 21-year-old man presented with the chief complaints of fever and sore throat after visiting Cambodia and Thailand. Computed tomography revealed multiple pulmonary nodules. After performing antibiotic therapy, the pulmonary nodules without bacteremia disappeared completely. Paired microscopic agglutination tests revealed seroconversion against Leptospira serogroup Autumnalis. Thus, he was diagnosed with multiple pulmonary nodules caused by leptospirosis. Leptospirosis is a common zoonosis that occurs in tropical and subtropical areas. Its various clinical features include unspecified fever and Weil's disease. Although diffuse alveolar hemorrhaging is known to occur in severe leptospirosis, multiple pulmonary nodules resembling septic emboli or vasculitis are a rare complication.

Leptospirosis is a zoonotic disease of worldwide distribution caused by infection with Leptospira genus bacteria, a pathogenic spirochaete. We present the case of a 29-year-old man admitted to our hospital with fever and multiorgan failure. He provided poor information about his symptoms. No recent travel or occupational history was reported and his clinical presentation did not suggest any infectious foci. His relatives later disclosed that he had been homeless for 3 weeks in the context of behavioural changes, obtaining foodstuff from waste containers and water from rain puddles. In the setting of this epidemiology, his presentation of fever, jaundice, acute renal injury and thrombocytopaenia suggested leptospirosis. Prompt empirical antimicrobial coverage was started, alongside organ support therapy. The diagnosis was later confirmed through microscopical and molecular methods. The patient made a full recovery. Leptospirosis should be considered early in the diagnostic work-up of any patient with acute febrile illness with multiorgan system involvement, with the identification of risk factors being essential to treat early in development of the disease.

Leptospirosis remains the most important zoonosis in the world and is caused by the bacterium of the genus Leptospira. Clinical manifestations vary from oligosymptomatic infections to the severe, ictero-hemorrhagic form, called Weil’s syndrome, which include acute kidney injury (AKI). After reaching the bloodstream, the Leptospira can reach all organs, preferentially affecting the liver, kidneys, heart, and skeletal muscle, causing a vasculitis with endothelial damage and inflammatory infiltrate. The pathogenic mechanisms of leptospirosis can be divided into direct effects caused by Leptospira and the effects of the host immune response. Leptospira isolated from the kidneys of chronically infected animals show an increased amount of lipopolysaccharides (LPS), suggesting that LPS expression facilitates the permanence of the bacteria in the renal tissue. The clinical picture in the early phase is often nonspecific, with fever, headache, anorexia, diarrhea, nausea, vomiting, and malaise, as well as myalgia, more pronounced in the calf region, constituting the most common signs and symptoms. Given this presentation, which comprises approximately 85–90% of cases, the disease is often underdiagnosed and misdiagnosed as viral infections, such as dengue. The two main mechanisms that have been associated with kidney injury by Leptospira are direct nephrotoxic action of the microorganism and toxin effect with immune response induction and indirect effects such as dehydration, rhabdomyolysis, and hypoxia due to hemodynamic changes.

Leptospirosisis a zoonosis caused by spirochaetes from the species Leptospira. The more severe form of leptospirosis, known as Weil’s disease, is characterised by the triad of jaundice, renal impairment and haemorrhages. Pulmonary involvement occurs in 20%–70% of the patients, with severity ranging from non-productive cough to respiratory failure mainly due to pulmonary haemorrhage. Recognition of Weil’s disease in patients presenting with pulmonary symptoms can be difficult. This case illustrates a classic case of pulmonary haemorrhagic involvement in Weil’s disease.

Leptospirosis is a potentially fatal disease which can cause multi-organ dysfunction. It can have different rare presentations. Acute pancreatitis is one such rare gastrointestinal manifestation which present as an acute abdomen. Simultaneous presence of features of both acute pancreatitis and acute hyponatremia in a case of Weil's disease characterised by combination of jaundice, acute kidney injury, hypotension and hemorrhagic manifestation is very rare.

We report the clinical history of a paperless migrant living in Belgium who contracted Weil's disease. This historical term refers to the severe form of leptospirosis, an ever more frequent tropical disease in Europe due to the growing globalization background. However, leptospirosis remains underdiagnosed. Actually, common clinical forms are neglected in outpatient medicine and the performance of available diagnostic tests is limited, especially when they are performed in severe, potentially life-threatening forms. In these cases of sepsis or even septic shock, the antibiotic treatment is most often empirical although fortunately adapted thanks to the large sensitivity of the spirochete.Nous rapportons l’histoire clinique d’un sans-papier séjournant en Belgique atteint de maladie de Weil. Ce terme historique désigne la forme sévère de la leptospirose, une maladie tropicale dont l’incidence augmente en Europe, sur fond de mondialisation en essor. La leptospirose reste toutefois sous-diagnostiquée. En effet, les formes cliniques courantes sont négligées en médecine ambulatoire et la performance des tests diagnostiques disponibles est limitée, lorsqu’ils sont demandés face aux formes sévères, potentiellement mortelles. Dans ces cas de sepsis, voire de choc septique, le traitement antibiotique est donc le plus souvent empirique, tout en demeurant, heureusement, adapté de par la multisensibilité du spirochète.

CME: Zoonosis in Switzerland: Leptospirosis

Introduction Leptospirosis is an infection caused by spiral bacteria from the family Leptospiraceae, and is considered to be the most widespread zoonosis in the world. Aim To analyze the clinical and laboratory characteristics of patients with Leptospirosis over five years. Methods The study included 160 patients aged 17-79 years, who in the period 01.01.2014. to 21.12.2018. were hospitalized at the Clinic for Infectious Diseases of the University Clinical Center Tuzla. They were diagnosed based on medical history, clinical examination, laboratory and microbiological results. The definitive diagnosis was confirmed by serological testing from the patients' blood. Results In the observed period, the highest number of patients were in 2014 80/160, and the lowest in 2015 15/160. Male patients were more likely to suffer from 118 (73.8%) than female 42 (26,3%). The mean age was ±56.5 years. The most common symptoms in patients were: fever (95,6%), headache (93,8%), malaise (87,5%) and myalgia (85,6%). In all patients, 160/160 (100%) accelerated erythrocyte sedimentation and elevated C-reactive protein was observed. The following findings were reported from white blood cell findings: leukocytosis in 81/160 (50,6%), neutrophilia in 103/160 (64,4%) and lymphopenia in 128/160 (80%) patients. Liver findings had the following values: elevated AST in 142/160 (88%) and ALT in 130/160 (81,3%) patients. Total bilirubin was elevated in 105/160 (65,6%) and direct in 107/160 (66,9%). Thrombocytopenia was in 142/160 (88%) patients. Urea was elevated in 103/160 (64,4%) and creatinine in 101/160 (61,3%) patients. Conclusion it is very important that physicians in their day to day practice, especially in ambiguous febrile conditions, differentially diagnose leptospirosis and establish a timely diagnosis, this is ley to adequate and timely therapy, and therefore to reducing to development of complications and mortality.

International audience; Early names for leptospirosis often indicate occupational or environmental exposure. Leptospirosis is hard to identify in the tropical setting because of co-circulating diseases. This is not the case in the temperate setting, such as Europe, where the few differential diagnoses at the time are malaria, typhoid, and viral hepatitis. Leptospirosis presumably caused community epidemics in Europe before 1900 and military epidemiologists carefully documented outbreaks in "constrained settings." Achille Kelsch (1841-1911) synthesized available military data and epidemiological perspectives to define "epidemic jaundice" as a nosological continuum, caused by an infectious agent found in muds and water. He viewed Weil's disease as being only one form of that now well-identified disease continuum. The causative pathogen and epidemiological determinants were identified years later. The role of soils and muds as intermediate reservoirs, as suggested by Kelsch, deserves further investigation.

Leptospirosis is a zoonosis caused by a gram negative aerobic spirochete of the genus Leptospira. It is acquired by contact with urine or reproductive fluids from infected animals, or by inoculation from contaminated water or soil. The disease has a global distribution, mainly in tropical and subtropical regions that have a humid, rainy climate and is also common in travelers returning from these regions. Clinical suspicion is critical for the diagnosis and it should be included in the differential diagnosis of any patient with a febrile hepatorenal syndrome in, or returning from endemic regions. The leptospiremic phase occurs early and thereafter there is an immunologic phase in which the most severe form, Weil's disease, occurs. In the latter, multiple organ dysfunction predominates. The appropriate diagnostic test depends on the stage of the disease and consists of direct and indirect detection methods and cultures. Severely ill patients need to be monitored in an ICU with appropriate anti-bacterial agents and early, aggressive and effective organ support. Antibiotic therapy consists of penicillins, macrolides or third generation cephalosporins.

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.

We present a case of Weil's disease complicated by a Jarisch-Herxheimer reaction (JHR) after initiation of antibiotics while in the emergency department requiring invasive monitoring and vasopressor support. The case is followed by a brief review of the JHR which is rarely observed with treatment of leptospirosis. A healthy 28-year-old female who recently returned from the Caribbean presented to the emergency department with flu-like symptoms. The patient appeared jaundiced with conjunctival suffusion and was ultimately treated with the appropriate antibiotics for leptospirosis in the ED. She decompensated subsequently, requiring supplemental oxygen, central and arterial line placement, and vasopressor support with norepinephrine. Although rarely encountered and not well reported throughout the literature, initiation of antibiotics can cause a JHR reaction given that Leptospira interrogans is a spirochete. This JHR may be self-limited and of short duration, or it can be prolonged and severe, requiring invasive therapies such as central line placement for vasopressor support and intubation. It is suggested that patients started on antibiotics for leptospirosis/Weil's disease should be monitored in the emergency department for a short duration prior to discharge or transfer to a regular medical floor for observation given the possibility for decompensation.

La leptospirosis es una enfermedad causada por la espiroqueta Leptospira. Se trata de una zoonosis de distribución mundial, con predominio en los trópicos. En España no es frecuente pero sí se observan casos en zonas más húmedas o con presencia de ríos, lagos o estanques, como son Cataluña, Andalucía o la Comunidad Valenciana, donde se relaciona con los arrozales. Los transmisores son múltiples animales como vacas o ratas, contagiándose el ser humano mediante contacto directo con estos animales o su orina, o bien de forma indirecta al consumir o estar en contacto con agua contaminada por la orina de éstos. Las manifestaciones clínicas son muy variables, siendo asintomática o poco sintomática en la mayoría de los pacientes. Aunque no ocurre siempre, la leptospirosis cursa con una primera fase con fiebre, mialgias, afectación renal o hemorragia de distintos órganos, seguida de una segunda fase con presencia de ictericia por afectación hepática. La enfermedad de Weil es una forma de leptospirosis grave caracterizada por afectación hepática con ictericia e insuficiencia renal aguda, asociada a una considerable mortalidad. El diagnóstico se basa en técnicas serológicas y detección de DNA mediante PCR. El tratamiento consta de medidas de soporte y antibioticoterapia. Presentamos un paciente con enfermedad de Weil y hemorragia digestiva por leptospirosis, con una evolución clínica fulminante, y hacemos hincapié en la necesidad de tener presente esta entidad, especialmente en ambientes epidemiológicos favorables como el de este paciente, con el fin de lograr un diagnóstico precoz. 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.

We report an autopsy case of a 60-year-old man with Weil's disease who died of fulminant hepatic failure. Ante-mortem blood culture yielded the growth of Leptospira interrogans (serovar icterohaemorrhagiae). At autopsy, the liver weighed 1210 g and showed a typical appearance of "acute yellow liver atrophy". Zone 3 (centrilobular region) showed submassive necrosis of hepatocytes accompanied by marked hemorrhage. Hepatocytes in zones 1 and 2 were well preserved, and the leptospira antigen was immunohistochemically demonstrated in several hepatocytes. Dissociation of liver cell plates was not observed. An immunohistochemical study demonstrated that CD31-positive, sinusoidal endothelial cells had almost completely disappeared in zone 3. This finding suggested that severe and selective damage to endothelial cells in zone 3 was the main cause of the submassive hepatocellular necrosis, which led to fulminant hepatic failure in the present case.

Leptospirosis is a zoonotic disease of global importance caused by pathogenic Leptospira. Weil's disease is the most severe form of human leptospirosis, which is characterized by jaundice, haemorrhage and renal failure (Levett 2001; Bharti et al. 2003). More than 50,000 cases of severe leptospirosis are reported each year with a case fatality rate higher than 10% (WHO 1999). Although jaundice has been one of the well-known symptoms of leptospirosis since its discovery, its mechanism still remains unknown. Jaundice refers to the yellow discoloration of the sclerae, mucous membranes and skin and results from either enhanced bilirubin production or impaired bilirubin handling (uptake, conjugation or biliary excretion) by the liver (Roche & Kobos 2004). As jaundice is caused by dysfunctions at any steps of bilirubin metabolism, in some cases, it is difficult to elucidate its main mechanism. Several kinds of bacterial infection are known to cause jaundice through a variety of mechanisms (Trauner et al. 1998; Chand & Sanyal 2007). Leptospira are spiral-shaped, extremely thin bacteria. They can bore through a gel-like medium in a cork-screw-like manner (Goldstein & Charon 1988). They are able to penetrate abraded skin and mucous membrane and migrate in host tissue (Bharti et al. 2003). Several functional and histopathological studies on leptospirosis-related jaundice have been made on human patients (Ramos-Morales et al. 1959; Arean 1962a; Kobayashi 2001; De Brito et al. 2006) and experimental animals (Arean 1962b; Miller & Wilson 1966; Higgin & Cousineau 1977; Van den Ingh & Hartman 1986; Nally et al. 2004). In human autopsies and animal models of acute Leptospira infection, hepatic cord disarray and dilation of intercellular space are commonly reported (Arean 1962a; Miller & Wilson 1966; De Brito et al. 2006). Degenerative lesions, inflammation and necrosis are minimal (Nally et al. 2004; De Brito et al. 2006). Serum biochemical studies on human patients have demonstrated that concentrations of aspartate transaminase (AST) and alanine transaminase (ALT) are moderately increased, accompanied by minor increase in alkaline phosphatase (ALP) concentration (Ramos-Morales et al. 1959; Kobayashi 2001). From these findings, most researchers have reported that impairment of bile excretion, intrahepatic cholestasis, is related to jaundice (Ramos-Morales et al. 1959; Higgin & Cousineau 1977; Kobayashi 2001; Bharti et al. 2003), but the mechanism is still unclear. Moreover, there are few reports that correlated histopathological findings of liver with serum biochemical studies and localization of the organisms in leptospirosis or that examine the time course of histopathological changes and its association with leptospiral localization. In this study, we examined the association between serum biochemical, histopathological changes and leptospiral localization during the development of jaundice in a hamster model of Weil's disease. Hamsters inoculated with virulent Leptospira strains are used as animal models because their clinical manifestations and histopathological changes are similar to those of human leptospirosis (Haake 2006; Silva et al. 2008). For scanning electron microscope (SEM) observation, freeze-cracking and cross-cutting methods were used to obtain three-dimensional images of the liver. To investigate direct interactions between hepatocytes and the organism, hepatocyte couplets isolated from hamsters were co-cultured with either pathogenic or non-pathogenic leptospires.

Introduction Leptospirosis is a zoonosis of worldwide distribution and tropical predominance. Its incidence could be underestimated in template regions. We describe the manifestations of leptospirosis in an area of Southwestern Spain. Patients and methods Eighty-six cases of leptospirosis (April 1997–April 2013) were retrospectively analyzed. The diagnosis was based in clinical and serological (Leptospira IgM ELISA) judgment. Epidemiological, clinical, laboratory, and prognostic dates were recorded. Results The mean age was 43.1 ± 13.8 years (84.9% males). The mean annual incidence was 1.99/100,000. There were activities of risk in 94%:82.5% contact with animals (57.4% pigs, 38.1% dogs, 31.7% cows, 22.2% sheeps), and 31.7% contact with pooled water. The most frequent symptoms were fever (94.1%), arthromyalgias (60.7%), and cephalalgia (53.3%). The main laboratory alterations were hypertransaminemia (48%), renal insufficiency (26.3%), and thrombocytopenia (16.9%). A lymphocytic meningitis was associated in 11 cases (12.5%) and a picture of Weil's disease was observed in 13 patients (15.1%). The patients with meningitis were younger (31.2 ± 9.2 versus 44.8 ± 15.2, p = 0.004). The patients with Weil's disease were older (53.5 ± 15.8 versus 41.2 ± 14.5, p = 0.007). Fifty seven patients were hospitalized (66.3%) and 6 patients died (7.0%). Factors independently associated with mortality were age > 60 years (odds ratio [OR] 45.0, confidence interval 95% [CI 95%] 4.7–434.6) and diagnosis of Weil's disease (OR 15.8, CI 95% 2.5–98.7). Conclusions In our experience, leptospirosis have a not despicable incidence and tends to show fever and arthromyalgias in men with risk activities. Leptospirosis should be included in the differential diagnosis of lymphocytic meningitis. Mortality is associated with older age.

This year, 2014, marks the centennial of the discovery of Leptospira as the Weil's disease pathogen by Ryokichi Inada, Yutaka Ido and their colleagues. Leptospirosis is a worldwide zoonosis especially in countries with tropical and subtropical climates. Recently, the number of patients with leptospirosis dramatically decreased in Japan because public hygiene has greatly improved, the mechanization of agriculture was introduced, and farmers started using rubber boots and gloves while working in the field. The opportunities for percutaneous infection with Leptospira was reduced, but have not been totally eliminated in Japan.We previously reported a novel combination of five antimicrobial agents for selective isolation of Leptospira from contaminated samples. This cocktail, after being incorporated into Leptospira growth medium, inhibited the growth of contaminants and allowed successful detection of leptospires in environmental samples. We collected soil and environmental water and cultured them using this selective medium. It was revealed that not only saprophytic Leptospira but also pathogenic Leptospira are widely living in the environment. We hypothesized that soil serves as reservoir for Leptospira and infectious source for leptospirosis. In this review, we also discuss the Leptospira-rat-human relationship in the Philippines, natural defense of host against oral and percutaneous infection by Leptospira, the mechanism of jaundice in leptospirosis, and the development of immunochromatography-based methods for detection of leptospiral antigen in urine.

A 35-year-old male patient reached the emergency department after an episode of massive haemoptysis a few hours ago. Fever and dyspnea were mentioned to be present the last 5 days. His medical history included only malaria, successfully treated 2 years ago. Clinical examination revealed high fever, jaundice, cyanosis, tachypnea and bilateral rales on pulmonary auscultation. Laboratory investigation showed high erythrocyte sedimentation rate and C reactive protein, leucocytosis, anaemia, mild thrombocytopaenia, renal impairment, hyperbilirubinaemia and abnormal liver function tests; arterial blood gas analysis showed respiratory alkalosis with severe hypoxia. Thoracic X-ray revealed bilateral pulmonary infiltrates, whereas abdominal and heart ultrasound detected hepatomegaly and small pericardial infusion, respectively. The diagnosis of leptospirosis along with acute respiratory distress syndrome was confirmed by positive IgMLeptospiraantibodies. Empirical treatment with triple antibiotic therapy and corticosteroids was applied. The patient was discharged after 1 week, without any symptoms and with almost normal laboratory tests.

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.

Leptospirosis is an uncommon infectious disease that has protean clinical manifestations ranging from an innocuous ‘flu-like’ illness to potentially life-threatening multi-organ failure. Here we describe a case of Weil's disease that presented on the acute medical take with fever, jaundice and acute renal failure. We highlight the importance of careful history taking at the time of admission and how understanding the epidemiology and pathophysiology of leptospirosis enables a definitive diagnosis to be reached.

Leptospirosis is a zoonosis caused by a pathogenic spirochete “leptospira interrogans.” Severe form of leprospira infection is usually associated with jaundice and renal involvement, leading to major hemorrhagic complications. Lung involvement can vary from subtle clinical features to deadly pulmonary hemorrhage and acute respiratory distress syndrome (ARDS). We recently managed a case of leptospirosis with isolated lung involvement as alveolar hemorrhage and ARDS. Our patient had acute febrile illness with respiratory symptoms associated with radiological picture of pulmonary hemorrhage. Patient was managed with noninvasive ventilation with high flow oxygen, antibiotic and pulse steroids therapy. In conclusion, leptospirosis can present with predominant pulmonary involvement, instead of the classical triad of Weil disease. High index of suspicion should be kept in acute febrile illness patients with respiratory symptoms and alveolar hemorrhage. Early diagnosis and management with oxygenation, antibiotics and immunosuppresents can prevent complications and mortality.

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.

Leptospirosis is one of the most widespread zoonoses in the world, and its most severe form in humans, "Weil's disease," may lead to jaundice, hemorrhage, renal failure, pulmonary hemorrhage syndrome, and sometimes,fatal multiple organ failure. Although the mechanisms underlying jaundice in leptospirosis have been gradually unraveled, the pathophysiology and distribution of leptospires during the early stage of infection are not well understood. Therefore, we investigated the hamster leptospirosis model, which is the accepted animal model of human Weil's disease, by using an in vivo imaging system to observe the whole bodies of animals infected with Leptospira interrogans and to identify the colonization and growth sites of the leptospires during the early phase of infection. Hamsters, infected subcutaneously with 104 bioluminescent leptospires, were analyzed by in vivo imaging, organ culture, and microscopy. The results showed that the luminescence from the leptospires spread through each hamster's body sequentially. The luminescence was first detected at the injection site only, and finally spread to the central abdomen, in the liver area. Additionally, the luminescence observed in the adipose tissue was the earliest detectable compared with the other organs, indicating that the leptospires colonized the adipose tissue at the early stage of leptospirosis. Adipose tissue cultures of the leptospires became positive earlier than the blood cultures. Microscopic analysis revealed that the leptospires colonized the inner walls of the blood vessels in the adipose tissue. In conclusion, this is the first study to report that adipose tissue is an important colonization site for leptospires, as demonstrated by microscopy and culture analyses of adipose tissue in the hamster model of Weil's disease.

Leptospirosis is a common zoonotic infection in human caused by spirochete Leptospira. The disease is often underdiagnosed because of the difficulties in its clinical diagnosis and lack of suitable confirmatory laboratory tests. In this case report, we describe a case which highlights the importance of considering leptospirosis as the diagnostic possibility with hepatic, renal, and hematologic system involvement particularly where diagnostic support and resource are limited.

The recent high-profile death of a British Olympic rower from leptospirosis has raised awareness to this uncommon but potentially fatal disease. The re-emergence of the disease abroad is well documented in the literature, but less is known about cases in the UK. The increase in participation in water sports, foreign travel and often a combination of the two, has increased the exposure of tourists subsequently returning to the UK from areas of high prevalence. Leptospirosis is a zoonotic infection. The bacteria are shed in the urine of animals to the environment from where humans are infected by incidental hosts. There is a wide spectrum of severity of symptoms, from a self-limiting febrile illness to fatal pulmonary haemorrhage, renal or liver failure. It is thought that cases remain unrecognized every year in the UK, largely due to the mild nature of symptoms and the wide differential for febrile illness and partly due to lack of awareness among clinicians. This review examines the epidemiology of leptospirosis in the UK, over the period 2006-10, the clinical features, diagnostic techniques and treatment.

After a typhoon in September 2009, an outbreak of leptospirosis occurred in Metro Manila, the Philippines; 471 patients were hospitalized and 51 (10.8%) died. A hospitalbased investigation found risk factors associated with fatal infection to be older age, hemoptysis, anuria, jaundice, and delayed treatment with antimicrobial drugs., Emerging Infectious Diseases, 18(1), pp.91-94; 2012

The aim of this study is to investigate the changes in clinical pattern and therapeutic measures in leptospirosis-associated acute kidney injury; a retrospective study with 318 patients in Brazil. Patients were divided according to the time of admission: 1985–1996 (group I) and 1997–2010 (group II). Patients were younger in group I (36 ± 13 versus 41 ± 16 years, P = 0.005) and the numbers of oliguria increased (21% versus 41% in group II, P = 0.014). Higher frequency of lung manifestations was observed in group II (P < 0.0001). Although increased severity, there was a significant reduction in mortality (20% in group I versus 12% in group II, P = 0.03). Mortality was associated with advanced age, low diastolic blood pressure, oliguria, arrhythmia, and peritoneal dialysis, besides a trend to better mortality with penicillin administration. Leptospirosis is occurring in an older population, with a higher number of oliguria and lung manifestations. However, mortality is decreasing and can be the result of changes in treatment.

Leptospira interrogans serovar Copenhageni causes pulmonary hemorrhages with respiratory failure, a major cause of death in leptospirosis patients. Protective immunity to Leptospira is known to correlate with the production of leptospiral lipopolysaccharide (L-LPS)-specific agglutinating antibodies. We generated L-LPS-specific mouse monoclonal antibodies (MAbs) and investigated if these MAbs can protect guinea pigs against fatal pulmonary hemorrhages caused by serovar Copenhageni. The MAbs L8H4 and L9B11 against 22 kDa L-LPS agglutinated leptospires and completely protected guinea pigs from the development of fatal pulmonary hemorrhages by serovar Copenhageni, whereas the MAb L4C1 against 8 kDa L-LPS neither agglutinated the bacteria nor protected the animals against the fatal pulmonary hemorrhages.

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.

Background: Leptospirosis, a spirochetal zoonosis, is considered an occupational disease of persons engaged in agriculture, sewage works, forestry, and butchery. Objective: To determine the environmental sources and the knowledge, attitude and practices for leptospirosis among butchers and slaughterhouse workers, as well as the seroprevalence of leptospirosis among cattle and pigs presented for slaughter. Methods: Using an interviewer administered questionnaire, all 110 butchers and other slaughterhouse workers in the parishes of Kingston and St. Andrew, Jamaica were surveyed. In addition, 179 blood samples from animals presented for slaughter were tested for anti-Leptospira antibodies using the microscopic agglutination test (MAT). Results: Analyses indicated that people with the studied occupations are at risk for developing leptospirosis due to several environmental risk factors that exist in slaughterhouses. Among the risk factors, limited knowledge of the disease and its transmission, lower educational level attained, younger age and unhealthy behaviors (e.g., hand washing and improper or lack of use of personal protective gears), presence of stray dogs and rodents, and inadequate maintenance of physical plants, were found to be important. Of the total number of animal samples tested, 20 (11%) were positive. Canicola and Hardjo (among cattle) and Bratislava (among pigs) were the major seroreactors. Conclusion: Butchers and slaughterhouse workers engaged in animal handling and slaughtering could be frequently exposed to leptospirosis, and hence control strategies targeting at these populations should be implemented.

In the years before English settlers established the Plymouth colony (1616–1619), most Native Americans living on the southeastern coast of present-day Massachusetts died from a mysterious disease. Classic explanations have included yellow fever, smallpox, and plague. Chickenpox and trichinosis are among more recent proposals. We suggest an additional candidate: leptospirosis complicated by Weil syndrome. Rodent reservoirs from European ships infected indigenous reservoirs and contaminated land and fresh water. Local ecology and high-risk quotidian practices of the native population favored exposure and were not shared by Europeans. Reduction of the population may have been incremental, episodic, and continuous; local customs continuously exposed this population to hyperendemic leptospiral infection over months or years, and only a fraction survived. Previous proposals do not adequately account for signature signs (epistaxis, jaundice) and do not consider customs that may have been instrumental to the near annihilation of Native Americans, which facilitated successful colonization of the Massachusetts Bay area.

Leptospirosis is a zoonotic disease with global distribution, caused by spirochaetes of the genus Leptospira. Transmission of Leptospira interrogans serovar Icterohaemorrhagiae, the causative agent of Weil's disease, to humans usually results from exposure to the urine of infected, but mostly asymptomatic, rodents, either by direct contact or indirectly through contaminated soil or water. Although regarded as a re-emerging infectious disease, human leptospirosis is probably underdiagnosed due to its often unspecific clinical appearance and difficulties in culturing leptospires. Therefore, more rapid and specific diagnostic procedures are needed. Here we describe a novel real-time quantitative PCR system developed for the accurate and fast diagnosis of pathogenic Leptospira spp. Its usefulness in the management of a patient with rat bite-associated multiorgan failure is demonstrated.

A 77-year-old man developed a fever up to 38.4 degrees C, with diarrhoea, acute renal failure (creatinine up to 8.7 mg/dl; urea up to 308 mg/dl) and marked jaundice (total bilirubin up to 24.3 mg/dl). In addition there was thrombocytopenia, conjunctivitis and epistaxis, as well as cerebral symptoms with somnolence and general slowing up. At first he was thought to have cholangitis resulting from previously diagnosed gall-stones, and he was therefore treated with ampicillin, 2 g two times daily, and metronidazole, 0.5 g two times daily. The fewer regressed, but the renal failure required haemodialysis and haemofiltration under strict fluid control. Endoscopy excluded obstructive jaundice, but a suspicion of inflammatory liver disease or possibly cirrhosis was raised in the differential diagnosis. Serology revealed an increased titre for Leptospira interrogans var. sejroe (1:200, later 1:1600). Liver biopsy finding was compatible with the diagnosis of leptospirosis. Because of the high inflammatory activity in the liver, 2 mega units of penicillin G were administered three times daily for six days. Gradually the renal functions and jaundice improved and, on discharge on the 36th day, the patient was again in generally good health, although creatinine and bilirubin values were still slightly elevated (1.7 mg/dl each).

Se presenta el caso de un joven de quince años de edad que consulta a un hospital privado por enfermedad febril aguda de origen desconocido, asociada a elevación discreta de transaminasas y otras alteraciones inespecíficas de los exámenes de laboratorio. Fue referido para observación a un hospital de la Caja Costarricense de Seguro Social, donde se le maneja como cuadro de dengue clásico. La atención en la clínica privada se restableció luego de su egreso, se confirmó el diagnóstico de leptospirosis por parte del laboratorio del Centro Nacional de Referencia de Leptospirosis del iNCIENSA y se manejó con antibióticos hasta su resolución. El artículo enfatiza la importancia del diagnóstico de la leptospirosis mediante un alto grado de sospecha, una historia clínica precisa, un buen examen fisico y la confirmación diagnóstica por laboratorio con el fin de tratarla apropiadamente.A case of a 15 year old young man is presented, who consulted at a private hospital for acute fever, initially of unknown origin, associated with mild elevation of transaminases and other unspecific alterations of laboratory tests. He was referred for observation to a Hospital, where he was treated as a case of classic dengue fever. Afier his discharge his case was re-taken by a private practitioner, his diagnosis of leptospirosis was confirmed by the laboratory of the National Leptospirosis Referal Center in the INCIENSA, and he was properly treated with antibiotics until complete resolution of his episode. This article emphasizes the importance of a high level of suspicion, a precise and thorough clinical history, as well as a meticulous physical examination, followed by laboratory evidence, in order to diagnose and treat this illness in a proper way.

Introduction. Leptospirosis is an acute zoonotic infection, caused by spirochetes of the genus Leptospira. It is characterized by extensive vasculitis. It is usually transmitted indirectly, per contaminated water, rarely directly, through contact with infected animals. Leptospira bacteria commonly enter the body through damaged skin or mucous membranes. The clinical syndromes may vary from a subclinical infection and mild febrile condition to severe clinical symptoms with jaundice and renal failure. Case report. This is a case report of a patient with leptospirosis (Weil's disease) whose clinical manifestations included: icterus, renal failure, hemorrhagic syndrome and disturbances of consciousness. After the use of antibiotics, symptomatic and substitution therapy, all symptoms resolved completely. However, in our patient, hemodialysis was necessary due to renal failure, as a palliative measure. Discussion. Weil?s syndrome is a severe form of leptospirosis, which can be fatal. Early clinical diagnosis of the disease, as well as serologic verification of infection, are very important prerequisites, followed by antibiotic and other symptomatic therapy, as soon as possible. Conclusion. This is a case report of a patient with rare clinical manifestations of leptosirosis. Although presenting with severe symptoms, thanks to palliative therapeutic measures, complete and fast recovery was achieved. We especially point out the role of hemodialysis in the treatment of this patient. .

Background Leptospirosis is one of the most important neglected tropical infectious diseases worldwide. Icterohaemorrhagiae has been throughout recent history, and still is, the predominant serogroup of this pathogen in China. However, very little in detail is known about the serovars or genotypes of this serogroup. Methodology/Principal Findings In this study, 120 epidemic strains from five geographically diverse regions in China collected over a 50 year period (1958~2008), and 8 international reference strains characterized by 16S rRNA sequencing and MLST analysis. 115, 11 and 2 strains were identified as L. interrogans, L. borgpetersenii, and L. kirschneri, respectively. 17 different STs were identified including 69 ST1 strains, 18 ST17, 18 ST128, 9 ST143 and 2 ST209. The remaining 12 strains belonged to 12 different STs. eBURST analysis demonstrated that, among the clonal complexes isolated (CCs), CC1 accounted for 73.3% (88/120) strains representing three STs: ST1, ST128 and ST98. ST1 was the most likely ancestral strain of this CC, followed by singleton CC17 (17/120) and CC143 (11/120). Further analysis of adding 116 serogroup Icterohaemorrhagiae strains in the MLST database and studies previously described using global eBURST analysis and MST dendrogram revealed relatively similar ST clustering patterns with five main CCs and 8 singletons among these 244 strains. CC17 was found to be the most prevalent clone of pathogenic Leptospira circulating worldwide. This is the first time, to our knowledge, that ST1 and ST17 strains were distributed among 4 distinct serovars, indicating a highly complicated relationship between serovars and STs. Conclusions/Significance Our studies demonstrated a high level of genetic diversity in the serogroup Icterohaemorrhagiae strains. Distinct from ST17 or ST37 circulating elsewhere, ST1 included in CC1, has over the past 50 years or so, proven to be the most prevalent ST of pathogenic leptospires isolated in China. Moreover, the complicated relationship between STs and serovars indicates an urgent need to develop an improved scheme for Leptospira serotyping., Author Summary Leptospirosis, caused by pathogenic Leptospira spp, is a globally widespread zoonosis. In this study, our focusing on serogroup Icterohaemorrhagiae strains of Leptospira using MLST as a tool for phylogenetic analysis that has led to a better understanding of evolution of Leptospira. This totally consisted of 120 epidemic strains from five geographically diverse regions were isolated over the past 50 years in China and 8 strains from seven different countries. 17 STs were identified in these 128 strains by MLST analysis. Adding 116 serogroup Icterohaemorrhagiae in the Leptospira MLST database and studies previously described, 22 STs were identified in the 244 isolates. The genetic diversity of Leptospira belonging to serogroup Icterohaemorrhagiae from China was generally different from that of isolates elsewhere. Results of the 16S rRNA sequencing typing and MLST genotyping method were nearly consistent. Here, MLST revealed the high diversity of STs among the serogroup Icterohaemorrhagiae strains in China. Our present study provides a blueprint for further phylogenetic research. More convenient molecular techniques have to be developed to identify and characterize Leptospira species and STs.