Weil's Disease-Immunopathogenesis, Multiple Organ Failure, and Potential Role of Gut Microbiota.

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.

Weil's disease (leptospirosis) manifesting as fulminant hepatic failure: report of an autopsy case.

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 after refurbishment of old buildings]. / Leptospirose nach Altbausanierung.

UNLABELLED: HISTORY AND DIAGNOSIS: A 30-year-old patient was hospitalised with fever and jaundice. No long-term medication was taken. The patient worked as a plumber in refurbishment projects. He presented with headaches, myalgia and arthralgia of varying location and a fever of 38.9 °C. Skin and sclerae were visibly jaundiced. His cardiovascular system was normal. Further routine examination did not reveal any additional signs. INVESTIGATIONS: Having ruled out an acute gallbladder infection or mechanical obstruction of the bile ducts by abdominal ultrasound, an infectious etiology appeared likely, alongside possible toxicological and immunological reasons. Clinical history and diagnosis led to an urgent suspicion of leptospirosis which was confirmed by IgM titer rise within five days in ELISA. TREATMENT AND COURSE: The patient was treated immediately with ceftriaxone. During his stay in the hospital, his fever, jaundice and subjective symptoms subsided. Initial pathological markers also showed a significant trend towards reversion to normal levels. The patient was discharged from the hospital without any symptoms after 16 days. CONCLUSION: Leptospirosis is a significant differential diagnosis in patients with fever, jaundice, headaches and myalgia. Clinical history can provide vital clues for diagnosing this illness. Individuals that are prone to be exposed to water contaminated with rodent urine are at heightened risk of developing the disease. Climatic conditions such as heavy rainfalls or flooding also appear to increase the risk of infection.

Human hemorrhagic pulmonary leptospirosis: pathological findings and pathophysiological correlations.

BACKGROUND: Leptospirosis is a re-emerging zoonosis with protean clinical manifestations. Recently, the importance of pulmonary hemorrhage as a lethal complication of this disease has been recognized. In the present study, five human necropsies of leptospirosis (Weil's syndrome) with extensive pulmonary manifestations were analysed, and the antibodies expressed in blood vessels and cells involved in ion and water transport were used, seeking to better understand the pathophysiology of the lung injury associated with this disease. PRINCIPAL FINDINGS: Prominent vascular damage was present in the lung microcirculation, with decreased CD34 and preserved aquaporin 1 expression. At the periphery and even inside the extensive areas of edema and intraalveolar hemorrhage, enlarged, apparently hypertrophic type I pneumocytes (PI) were detected and interpreted as a non-specific attempt of clearence of the intraalveolar fluid, in which ionic transport, particularly of sodium, plays a predominant role, as suggested by the apparently increased ENaC and aquaporin 5 expression. Connexin 43 was present in most pneumocytes, and in the cytoplasm of the more preserved endothelial cells. The number of type II pneumocytes (PII) was slightly decreased when compared to normal lungs and those of patients with septicemia from other causes, a fact that may contribute to the progressively low PI count, resulting in deficient restoration after damage to the alveolar epithelial integrity and, consequently, a poor outcome of the pulmonary edema and hemorrhage. CONCLUSIONS: Pathogenesis of lung injury in human leptospirosis was discussed, and the possibility of primary non-inflammatory vascular damage was considered, so far of undefinite etiopathogenesis, as the initial pathological manifestation of the disease.

Acalculous cholecystitis: a rare presentation of leptospirosis progressing to Weil's disease.

Leptospirosis is a zoonotic infection with higher incidence in tropics. Leptospirosis, is known for its variable manifestations, and is a clinical challenge for physicians in the tropics. Experienced clinicians, at times can mistake leptospirosis for non-medical conditions. A few reports of leptospirosis presenting as acalculous cholecystitis was found in review of literature. We intent to highlight acalculous cholecystitis as a rare but clinically significant presentation of leptospirosis.

Síndrome de Weil y embarazo / Weil's disease at pregnancy

Se informa el caso de una paciente de 37 años de edad, con 34,4 semana de gestación, ingresada con el diagnóstico de síndrome febril agudo. Dados los antecedentes epidemiológicos, se halló, luego de una pesquisa adecuada, positividad para infección por Leptospira. Evolutivamente presentó íctero intenso y fallo renal agudo que necesitó de diálisis, lo cual mejoró la función renal y finalmente se recuperó la actividad hepática. Se concluyó que el cuadro era una forma de presentación del Síndrome de Weil durante el embarazo. El parto eutócico se presentó a las 34 sem con un recién nacido femenino de 2 200 g con buena evolución(AU)

Case of a patient aged 37 with 34, 4 weeks of gestation, admitted con a diagnosis of acute febrile syndrome. According to epidemiologic backgrounds, after a appropriate investigation, we found a positivity to infection from Leptospira. From the evolutionary point of view, she had intensive icterus and acute renal failure needing dialysis, which improved the renal function with recovery of hepatic activity. We conclude that picture was a presentation way of Weil's syndrome during pregnancy. Spontaneous labor occurred at 34 weeks with a female fetus weighing 2200 gr and a good evolution(AU)

Síndrome de Weil y embarazo / Weil's disease at pregnancy

Se informa el caso de una paciente de 37 años de edad, con 34,4 semana de gestación, ingresada con el diagnóstico de síndrome febril agudo. Dados los antecedentes epidemiológicos, se halló, luego de una pesquisa adecuada, positividad para infección por Leptospira. Evolutivamente presentó íctero intenso y fallo renal agudo que necesitó de diálisis, lo cual mejoró la función renal y finalmente se recuperó la actividad hepática. Se concluyó que el cuadro era una forma de presentación del Síndrome de Weil durante el embarazo. El parto eutócico se presentó a las 34 sem con un recién nacido femenino de 2200 g con buena evolución.

Case of a patient aged 37 with 34, 4 weeks of gestation, admitted con a diagnosis of acute febrile syndrome. According to epidemiologic backgrounds, after a appropriate investigation, we found a positivity to infection from Leptospira. From the evolutionary point of view, she had intensive icterus and acute renal failure needing dialysis, which improved the renal function with recovery of hepatic activity. We conclude that picture was a presentation way of Weil's syndrome during pregnancy. Spontaneous labor occurred at 34 weeks with a female fetus weighing 2200 gr and a good evolution.

Leptospirosis: clinical presentation and correlation with serovars.

A total of 2400 patients with pyrexia of unknown origin and or suspected leptospirosis were included in this study. Dark field microscopy detected Leptospira in 690 cases, Leptospira serological Investigations proved positive in 570 out of these 690 patients. Among them 212 had the classical icteric and the other 358 had anicteric type of presentation. Notably eptospira interrogans serovar ictero haemorrhagiae infection was encountered in 212 patients. In 30 patients, who had multi organ dysfunction which included renal failure, hepatic dysfunction or meningitis was due to Leptospira interrogans Serovar cannicola. Coexsistense of leptospirosis and hepatitis B virus infection were noted in 15 patients. Antibody to Leptospira interrogans was demonstrated by Micro agglutination test (MAT) in addition to dark field microscopy positivity in these cases. Similarly HIV antibody was demonstrated in 30 of the 330 anicteric patients. 554 out of 570 cases responded to intra venous penicillin (216), and oral Doxycycline (182) and Augmentin (156), and the remaining 16 patients succumbed to death.

[Clinicomorphological characteristics of icterohemorrhagic leptospirosis].

Thirty three cases of death from icterohemorrhagic leptospirosis were clinically and morphologically analyzed. The disease is characterized by the affliction of two major target organs: the kidney and liver. Infectious-toxic shock underlies the pathogenesis of specific fetal complications of icterohemorrhagic leptospirosis. In the latter, acute renal-hepatic failure is always followed by the structural damage and dysfunction of other organs, which are less pronounced and, at the same time, presents multiple organ dysfunction.

Reversal of renal tubule transporter downregulation during severe leptospirosis with antimicrobial therapy.

Tubular dysfunction is a hallmark of severe leptospirosis. Antimicrobial therapy is thought to interfere on renal involvement. We evaluated the expression of a proximal tubule type-3 Na+/H+ exchanger (NHE3) and a thick ascending limb Na+-K+-2Cl(-) cotransporter (NKCC2) in controls and treated hamsters. Animals infected by a serovar Copenhageni isolate, were treated or not with ampicillin (AMP) and/or N-acetylcysteine (NAC). Leptospiral antigen(s) and expression of renal transporters were evaluated by immunohistochemistry, and serum thiobarbituric acid (TBARS) was quantified. Infected hamsters had high amounts of detectable leptospiral antigen(s) in target tissues while renal expression of NHE3 and NKCC2 decreased. Ampicillin treatment was associated with minimal or no detection of leptospiral antigens, normal expression of NHE3 and NKCC2 transporters, and reduced levels of TBARS. NAC effect was restricted to lowering TBARS. Early and late AMP treatment rescued tubular defects in severe leptospirosis disease, and there was no evidence of benefit from antioxidant therapy.

Leptospirosis: presentación de dos casos clínicos y revisión de la literatura / Leptospirosis: presentation of two clinical case and literature reviewed

Se presenta dos casos de leptospirosis, atendidos en hospitales de Viña del Mar, con el objeto de llamar la atención sobre esta patología de cuadro clínico polimórfico, cuya gravedad puede variar desde procesos inaparentes hasta cuadros que pueden ocasionar la muerte del paciente. Se analiza la bacteriología, fisiopatología, el cuadro clínico, su diagnóstico diferencial y tratamiento. Se revisa especialmente la bibliografía chilena, la que orienta a demostrar que la magnitud de esta enfermedad es mayor a lo considerado anteriormente.

[Leptospirosis: report of a fulminant fatal case and review]. / Leptospirosis: presentación de una infección fulminante y revisión de la literatura.

In relation to the explosive increase of new and reemerging infectious diseases that threaten the humanity, and as a result of this clinical case, a literature review is done on Leptospirosis stressing out the necessity of having in mind the leptospirosis in the differential diagnostic for fever and jaundice syndrome.

Leptospirosis: Presentación de una infección fulminante y revisión de la literatura / Leptospirosis: Report of a fulminant fatal case and review

Entre las nuevas y re-emergentes enfermedades infecciosas que amenazan a la humanidad, y como resultado de este caso clínico, se hace una revisión bibliográfica acerca de leptospirosis insistiendo en la necesidad de tenerla in mente en el diagnóstico diferencial de un cuadro febril con ictericia.

[Respiratory distress due to pulmonary hemorrhage in leptospirosis]. / Dístrés respiratorio debido a hemorragia pulmonar por leptospirosis.

Two patients who lived in Buenos Aires suburbs died from leptospirosis in July 2000 and March 2001. They developed a nonspecific febrile illness followed by hemorrhagic pneumonia and respiratory distress in absence of typical manifestations such as jaundice, nephropathy, thrombocitopenia or hemorrhages in other organs. In the house and surroundings of one patient rodents were captured and three strains of leptospira, serogroup Icterohaemorrhagiae were isolated. Laboratory guinea pigs were inoculated and they were sacrificed as soon as respiratory symptoms appeared. Necropsy showed primary lung injury, which was similar to the histopathological lesions found in one of the patients. Neither jaundice, nor renal damage was found. Pericardiac hemorrhages were considered as a possible cause of cardiopulmonary collapse. This clinical form has not been reported previously in this region, where conditions are indeed suitable for the human illness to appear.

Dístrés respiratorio debido a hemorragia pulmonar por leptospirosis / [Respiratory distress due to pulmonary hemorrhage in leptospirosis]

Two patients who lived in Buenos Aires suburbs died from leptospirosis in July 2000 and March 2001. They developed a nonspecific febrile illness followed by hemorrhagic pneumonia and respiratory distress in absence of typical manifestations such as jaundice, nephropathy, thrombocitopenia or hemorrhages in other organs. In the house and surroundings of one patient rodents were captured and three strains of leptospira, serogroup Icterohaemorrhagiae were isolated. Laboratory guinea pigs were inoculated and they were sacrificed as soon as respiratory symptoms appeared. Necropsy showed primary lung injury, which was similar to the histopathological lesions found in one of the patients. Neither jaundice, nor renal damage was found. Pericardiac hemorrhages were considered as a possible cause of cardiopulmonary collapse. This clinical form has not been reported previously in this region, where conditions are indeed suitable for the human illness to appear.

[Aspergillosis of the heart and liver in leptospirosis]. / Aspergillez serdtsa i pecheni pri leptospiroze.

A study made in three autopsies suggested development during the second to third week of leptospirosis icterohaemorrhagica against the background of secondary immunodeficiency (due to severity of the underlying condition or induced by glucocortocoid and antibiotic therapy) Aspergillus affection of the heart that had significantly aggravated the clinical course of leptospirosis and appeared to be the immediate provoking cause of acute cardiovascular insufficiency with a fatal result to follow. Two cases demonstrated an isolated fungal infection of the myocardium. In one of these running a longer (20 days in duration) course there took place a hematogenic dissemination of the aspergilli present in the liver during the development of the metastatic focus in the myocardium. The observations done suggest that each case requires individual consideration as to part the fungus infection plays in the outcome of the pathological process depending upon its type and extension in the organ.

[The pathomorphology and pathogenetic problems of liver involvement in icterohemorrhagic leptospirosis]. / Patomorfologiia i nekotorye voprosy petogeneza porazheniia pecheni pri ikterogemorragicheskom leptospiroze.

Morphologic findings on the liver during different time periods of Leptospira infection suggest the leading role in the pathogenesis of the damaged organ early in the course of the disease of a toxic vascular affection of the microcirculatory bed presenting with hyperpermeability of the vascular wall, interstitial edema, dyscomplexation of the liver crosspieces together with inflow of bile to the sinusoidal capillaries. To a lesser extent jaundice is related to the hepatocyte dystrophic and necrotic changes as evidenced by the absence of marked disturbances in the protein-synthetizing function of the liver and low enzymatic activity. At week 2 to 3 of the illness against the background of diminution of the edema and partial or complete restoration of the liver constitution (especially so in less afflicted peripheral portions of the lobes) jaundice with high bilirubinemia is caused by a toxic affliction of hepatocytes and advancing centrolobular cholestasis. High values for bilirubin might be related not only to grave alternative changes in hepatocytes but to microcirculatory abnormalities as well, which fact accounts for the absence in leptospirosis of a direct relationship of the blood level of bilirubin to the degree of affliction of the hepatic cells.

Incidence of leptospiral abortion in Brazilian dairy cattle.

We examined dams' paired serum samples and foetal kidneys (histopathologically and attempting leptospiral cultures) from 120 Brazilian Holstein abortions from 10 herds near Sao Paulo, Brazil, in 1996. Leptospiras was isolated from 15 foetuses. The Leptospira interrogans serovar hardjo was obtained from four, pomona from three and wolffi from eight foetuses. Ten of these 15 foetuses showed a four-fold rise in titres between the day of abortion and the second samples taken 15 days later. Fifty-seven other foetuses had histologic evidence of leptospires; 27 of their dams (47%) had four-fold rises in titres. In total, 72 of 120 aborted foetuses had evidence of leptospiral infection.