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A man in his 50s presents with a short history of rigors, back pain and dark urine. This was associated with scleral icterus. He was initially treated as urosepsis due to perinephric fat stranding on his first CT but continued to deteriorate with worsening sepsis requiring intensive care admission. He had a conjugated hyperbilirubinaemia (peak 708 µmol/L) with normal liver enzymes, anaemia, thrombocytopaenia, acute kidney injury requiring filtration and respiratory failure requiring ventilatory support. A subsequent CT revealed mediastinal lymphadenopathy and extensive ground-glass changes with patchy consolidation. When his history was revisited, exposure to rodents was identified, and serological testing for leptospirosis subsequently came back positive. This case explores the causes of hyperbilirubinaemia in leptospirosis, the dangers of tunnel vision in diagnostic medicine and the importance of prompt antibiotic therapy in Weil's disease., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Leptospirosis, a zoonotic disease characterized by a spectrum of influenza-like symptoms, can manifest as severe cases so called Weil's disease. Early diagnosis and treatment are crucial to avoid the potentially fatal course of the disease. Within 24 hours of the initial administration of antibiotics, patients may experience the Jarisch-Herxheimer reaction (JHR), characterized by chills, fever, hypotension, and impaired consciousness. The Okinawa Prefecture, where our hospital is situated, boasts the highest incidence rate of leptospirosis among all regions in Japan. This reports our encounter with the initial leptospirosis case after a period of 16 years within the Okinawa Prefecture. This case exhibited JHR and required the utilization of noradrenaline (NA). Despite evidence indicating that JHR does not correlate with mortality, we contend that diagnosis of Weil's disease necessitates admission to an intensive care unit (ICU) and vigilant monitoring for JHR, as it may result in impairment of general condition and fatal outcome, as observed in our case., Competing Interests: Declaration of competing interest The authors state that they have no Conflict of Interest., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

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., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

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 IgM Leptospira antibodies. 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., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: None

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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.

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., (© Georg Thieme Verlag KG Stuttgart · New York.)

Leptospirosis is an anthropozoonose, an animal disease transmissible to humans, caused by a spirochete of the genus Leptospira that lives mainly among rodents but also in wetlands. It occurs worldwide, particularly in Asia, Latin America and Africa. In Europe, the incidence is small (except in France and Great Britain, where its frequency has increased in recent years) but the frequency may be underestimated. Some areas overseas are particularly affected. In France, the potential epidemic of leptospirosis is subject to climatic variations, justifying a constant monitoring of the disease provided by the National Reference Centre (CNR) of leptospires. Transmission to humans primarily occurs through contact with environments contaminated by the urine of infected animals. The disease can affect the liver and kidneys (hepatonephritis) as cytolysis, cholestasis and renal failure associated with fever. A coagulopathy usually accompanies the clinical table. Its diagnosis is difficult because of the clinical polymorphism. Early diagnosis of leptospirosis allows effective medical care, improving patient outcomes. This is currently based on gene amplification (PCR) or serology positive by the microscopic agglutination test (MAT), which is the reference method. Its evolution is usually favorable with appropriate antibiotic treatment (aminopenicillin). However 5-10% of symptomatic patients have a severe multisystem defaillance. Nearly a century after the discovery of the causative agent, this zoonosis remains a public health problem, zoonosis priority in terms of virulence, its reporting is mandatory in our country. We report the case of a severe form of hepatonephritis due to water contaminated with Leptospira observed in Northern France., (Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.)

In this report, we describe a case of Weil disease. Chest x-ray and computed tomography (CT) findings showed temporary deterioration 1 day after the initiation of antibiotic treatment, and high-resolution CT findings with the patient's physical findings made us suspect pulmonary alveolar hemorrhage (PAH). We believed that the PAH had been induced by Weil disease and subsequently caused Jarisch-Herxheimer reaction. We confirmed the patient's contact history with mice, and symptoms improved immediately after starting appropriate treatments. Leptospirosis is a relatively rare cause of PAH. Therefore, the possibility of this disease should be included in the differential diagnosis, especially when high-resolution CT findings indicate PAH, and the imaging findings deteriorate rapidly after antibiotic therapy.

Leptospirosis in humans is a common zoonotic disease. It is often under-diagnosed, especially when associated with neurological features, resulting in significant morbidity and mortality. This subgroup of patients with neurological manifestations is often empirically treated for cerebral malaria, dengue fever, tuberculous meningitis, hepatic encephalopathy, viral encephalitis, etc. Hence it is important to be aware of uncommon manifestations of this disease. We report one such patient, which highlights the importance of considering leptospirosis as the diagnostic possibility with hepato-renal, pulmonary and nervous system involvement, particularly where diagnostic supports and resources are limited.

Clinical and laboratory diagnosis of severe leptospirosis (Weil's disease) may be difficult when other pathological processes that may cause similar clinical syndromes or affect immune response to infections coexist. In addition, the optimal management of the disease remains to be defined. We report on a case of Weil's disease, in which concurrent chronic hepatitis B virus infection and alcohol abuse caused diagnostic and therapeutic difficulties.

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.

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.

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 which is caused by Leptospira species, may present with clinical features that vary from a mild flu-like illness to an acute life-threatening condition. Weil's disease, the most severe form of leptospirosis is characterized by multiorgan involvement including liver, kidney and lungs. In this report a severe Weil's disease was presented. A 43 years old male patient who had a history of swallowing water while swimming in the creek, was admitted to the hospital with the complaints of weakness, cough, bloody sputum, generalized jaundice and dark urine. Acute renal failure, bilateral lung infiltration, hyperbilirubinemia, leukocytosis and thrombocytopenia were detected, and the patient has undergone to hemodialysis. Ceftriaxone and ciprofloxacin treatment was applied to the patient after collection of blood, urine and sputum cultures and serum samples for serological tests. None of the cultures yielded pathogenic microorganisms. Microscopic agglutination test (MAT) was applied to two serum samples which were collected with 10 days interval. The first serum sample revealed antibody positivity at 1/200 titer against L. semeranga Patoc I, while the second serum revealed antibody positivity at 1/400 titer against both L. semeranga Patoc I and L. icterohaemorrhagiae Wijnberg. By the administration of antibiotic therapy and early supportive care the patient was cured completely. In conclusion Weil's disease should be taken into consideration in the patients with multiple organ involvements.

Leptospirosis is rarely reported in children. It is easily treated with antibiotics but can be fatal if treatment is delayed. A 12-year-old girl was diagnosed with Weil syndrome, a severe form of leptospirosis, 10 days after returning from Mainland China. She presented with fever, hypotension, jaundice, and acute renal failure. She had used well water for bathing and swum in freshwater.

Leptospirosis, the most common vasculitic zoonosis in the world, is characterized with jaundice and acute renal failure. However, pancreatitis is an uncommon complication of leptospirosis. In this report, an acute pancreatitis case due to Weil's disease has been presented. A 31-year-old female patient with high levels of glucose, blood urea nitrogen, creatinine, creatine kinase, bilirubin, amylase and lipase, has been diagnosed to have leptospirosis by the high positive result (1/800) of microscopic agglutination test against Leptospira interrogans serogroup icterohemorrhagiae. The patient has been treated with supportive and symptomatic therapy, and with penicillin G for leptospirosis. Following triple hemodialysis, all the blood biochemistry tests returned to normal on the tenth day of therapy. This case was reported to draw attention to Leptospira infections which should be considered in the differential diagnosis of patients with jaundice and pancreatitis.

Leptospirosis is a rare disease in Switzerland. However its incidence is probably underestimated, due to its broad spectrum of presentations, including subclinical benign forms and the ictero-hemorragic form of the Weil's syndrome, whose mortality is high. We describe here a case of Weil's syndrome acquired in Switzerland with a favourable outcome under antibiotherapy. Even in the absence of any travel, the association of an acute renal insufficiency and jaundice with only moderate hepatic cytolysis should lead to the suspicion of leptospirosis. Clinical and epidemiological aspects of the disease are discussed in the article.

History and Clinical Findings: A 65 year-old man was transferred to our department from a neighbouring hospital with anuria and epistaxis. A few days prior to hospitalization, he had experienced severe muscular and joint pain accompanied by chills. A careful history revealed that, in recent weeks, the patient had frequently collected wild walnuts growing, for the most part, on the banks of a small stream, known to have an infestation of rats. The physical examination revealed pronounced jaundice of the skin and sclerae, and petechia on the lower legs., Investigations: Laboratory results showed marked thrombocytopenia, hyperbilirubinaemia, appreciably elevated urine retention parameters and increased C-reactive protein. During the subsequent course of his illness, serum leptospiral antibody titres were elevated, indicating an acute leptospiral infection manifesting as Weil's syndrome. Silver staining (>>Warthin-Starry<<) revealed rod-shaped bacteria, presumably representing leptospires, in some bone marrow macrophages., Treatment and Course: Treatment with i. v. penicillin was immediately initiated, and urine output established by intravenous fluid resuscitation in the intensive care unit, so that haemodialysis was not necessary. The platelet count returned to normal and bilirubin began to decrease again. The patient was discharged home after 2 weeks in the hospital., Conclusion: When a patient presents with the triad of renal failure, jaundice and thrombocytpenia in the setting of a possible infection, then the severe form of leptospirosis known as Weil inverted question marks syndrome must be considered, and antibiotic treatment initiated without delay. Of importance for the definitive diagnosis is the repeated determination of the titres of antibodies to leptospires in the serum and urine, which usually become positive only in the second week of the illness. In our case, we detected bacteria directly in some bone marrow macrophages as well.

The epidemiological and clinical observations of 240 patients with Weil's disease and 10 patients with canicola fever, and these observations in two epidemics of canicola fever, are presented. Early diagnosis is most important for the prognosis of patients with the severe form of leptospirosis. It depends on the clinical features, clinical laboratory findings, and the epidemiological situation. The most characteristic clinical signs for early diagnosis were febrile illness of sudden onset, severe general malaise, muscular pain, and conjunctival congestion. Proteinuria, leukocytosis with neutrophilia, and raised erythrocyte sedimentation rate were the most indicative clinical laboratory findings for early diagnosis. Although jaundice and hemorrhage are the most important signs of the severe form of leptospirosis, Weil's disease, these are rarely useful in early diagnosis. Of a variety of antibiotics used, penicillins and cephems had the lowest minimal inhibitory concentration against leptospires. However, it became apparent from basic studies in vitro and in vivo that streptomycin showed the best bactericidal action against leptospires and that it was the most effective anti-leptospiral antibiotic. Gentamicin, tobramycin, and isepamicin are also effective as alternatives to streptomycin. Although penicillins, cephems, tetracyclines, and macrolides are also effective for the treatment of leptospirosis, when these antibiotics with inadequate bactericidal activity are used for the treatment of the disease, long-term therapy with sufficiently large doses may be required from an early stage of the disease until the appearance of antibodies.

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

Five cases of leptospirosis diagnosed from 1978 to 1996 were retrospectively reviewed. The five patients were male and their mean age was 34.2 years. Epidemiologic factors were found in the 5 patients. The 3 common clinical findings: fever, myalgia and jaundice were found in the 5 patients. Hepatorenal involvement was observed in 4 cases (80%), bleeding episodes in 4 patients (80%), cardiac involvement in 4 (80%); in none case was observed central nervous system involvement. In one case (20%) was observed septic shock with acute respiratory failure. The Leptospira serogroups identified were icterohaemorrhagiae in 3 cases and could not be determined in 2. All the patients were amelioration with antibiotic therapeutic. The epidemiologic, clinical, analytical and therapeutic aspects are discussed.

Three dogs from different locations with acute renal failure were hospitalized in autumn 1996 and 1997. Leptospira interrogans serovar pomona was detected by the microscopic agglutination test. All dogs recovered after antibiotic treatment. The importance of the development of vaccines adapted to emerging serovars in dogs should be addressed.

Leptospirosis is a ubiquitous, spirochetal zoonosis which presents with a broad clinical spectrum. Weil's syndrome, characterised by jaundice, renal failure and bleeding manifestations is the most severe form. A high index of suspicion for the diagnosis is required to institute therapy promptly. We describe a case of serologically confirmed Weil's syndrome with concomitant hepatitis B infection.

Twelve cases of leptospirosis followed by the Infectious Diseases Clinic of the Cukurova University Medical School, Adana, Turkey, between January 1994 and November 1995 are reported. Included are their clinical manifestation, laboratory findings and serotype. Nine men and three women with an average age of 40.4 years were studied. Symptoms, clinical manifestations, laboratory findings and treatment of the disease are evaluated. All of the patients had fever and chills and the following symptoms: nausea and vomiting (91.6%), lower back pain and myalgia (58.3%), headache (50%), epistaxis (16.6%) and confusion (25%). The predominant clinical findings were jaundice (91.6%), hepatomegaly (41.6%), dyspnea (25%), conjunctival suffusion (33%), and nuchal rigidity (33%). Diagnosis was based on dark-field examination of the blood, cerebrospinal fluid and urine specimens. Also, microscopic agglutination tests (MAT) were carried out for serodiagnosis. MAT showed L. interrogans serovar icterohaemorrhagiae in 11 cases and L. interrogans serovar grippomosocova in one case. There was cross reaction with L. biflexa patoc in all cases. Agglutinations were tested in the same specimens twice and confirmed in the Microbiology Laboratory of the Etlik Veterinary Research Institute in Ankara. All cases were treated with penicillin and doxycycline. In the end; 83.3% of the patients were cured and 16.6% died due to hepatorenal failure.

We conducted a retrospective analysis of 43 consecutive children (35 boys and 8 girls), 4-14 years of age and living in an urban area, who were hospitalized at the Instituto de Infectologia Emilio Ribas (Sao Paulo, Brazil) from January 1989 to December 1995 with an acute illness subsequently diagnosed as leptospirosis. Epidemiologic data indicated contact with contaminated water in most cases (88%). The patient sera reacted most strongly with Leptospira interrogans serovars copenhageni (45%) and icterohaemorrhagiae (32.7%). Jaundice was present in 70% of the patients, elevated transaminase levels in 56%, renal failure in 79%, meningitis in 23%, thrombocytopenia in 65%, and hemorrhagic manifestations in 11.6%. Three children had pulmonary hemorrhage with respiratory failure and one death occurred as a consequence of respiratory failure. We also observed that antimicrobial therapy reduced the extent of renal failure and thrombocytopenia. These data indicate that antibiotics benefit children with late, severe leptospirosis and that severe disease also occurs in children and should be considered in the differential diagnosis.

Objective: To evaluate antimicrobial agents for treatment of models of acute and persistent leptospirosis caused by Leptospira interrogans serovar pomona., Design: Randomized trials comparing dosages and regimens of various antimicrobial agents for treatment of acute and persistent leptospirosis., Animals: 245 Golden hamsters to model acute leptospirosis and 121 mixed-breed swine to model persistent leptospirosis., Procedure: Hamsters and swine were inoculated with L interrogans serovar pomona. Antimicrobial agents were given to hamsters for 3 or 5 days after inoculation, with necropsy at 14 days after inoculation. Swine were treated for 1, 3, or 5 days beginning at 3 weeks after inoculation, and were necropsied 7 to 10 days after completion of antimicrobial agent treatment. Hamster tissue and swine tissue and urine specimens were examined by culture, fluorescent antibody testing, and histologic examination for presence of leptospires., Results: All untreated control hamsters became infected and manifested clinical signs and lesions of acute leptospirosis. Leptospires were not detected in hamsters treated with dihydrostreptomycin/penicillin G (25 mg/kg of body weight). Administration of ampicillin at all dosages reduced the number of hamsters infected, as confirmed at necropsy; the other agents tested required dosages greater than label recommendations to reduce the number infected. All untreated control swine became infected and shed leptospires in urine through the time of necropsy. Leptospires were not detected in kidneys or urine of swine treated with dihydrostreptomycin/penicillin G (25 mg/kg) for 1, 3, or 5 days, or in swine treated with oxytetracycline (40 mg/kg for 3 or 5 days), tylosin (44 mg/kg for 5 days), or erythromycin (25 mg/kg for 5 days). Treatment with ceftiofur and ampicillin was not effective in elimination of L interrogans serovar pomona in swine., Conclusions: Dihydrostreptomycin/penicillin G is effective for treatment of acute and persistent leptospirosis. Differences between the effectiveness of antimicrobial agents in the acute and persistent model of leptospirosis emphasize the importance of using the appropriate model for treatment evaluation. Antimicrobial agents evaluated for treatment of persistent leptospirosis in swine required the use of dosages above those recommended by the manufacturer., Clinical Relevance: Use of antimicrobial agents at extra-label dosages for treatment of persistent leptospirosis may cause residue problems in food animals; however, these regimens may be useful for treatment of breeding stock or animals destined for import/export.

The epidemiological distribution and clinical features of 12 cases of Weil's disease from Turkey, are reviewed. The disease is most common in male farmers from rural areas. Myalgia and jaundice were recorded in all patients. Signs included vomiting in 9 patients, haemorrhages in 6, and renal function was impaired in 6. Creatine phosphokinase levels were found above normal limits in 75% of the cases. Leptospires were demonstrated with dark-field microscopy in the blood of 9 and in the urine of 5 of these patients. The diagnosis was confirmed with microscopic agglutination test (MAT) as well as with ELISA. Ig M antibodies were detected in 11 (92%) of the patients and is an accurate marker for acute leptospirosis. Penicillin was used for therapy and the outcome was favorable in 10 patients. Two patients died. It should be kept in mind that leptospirosis is an extremely severe disease which requires appropriate examinations at the right moment.

The efficacy of dihydrostreptomycin in stopping the shedding of Leptospira hardjo subtype hardjobovis was studied in naturally infected cows. Blood and urine samples were collected from dairy cows kept on a farm where the farmer had contracted L hardjobovis infection. A microscopic agglutination test and an ELISA were used to determine specific antibody responses in serum. Polymerase chain reaction was used to detect bacterial shedding in urine. On the first sample collection date, 6 cows were seropositive, and 3 of those shed leptospires in the urine. These 3 cows were treated once with 25 mg of dihydrostreptomycin/kg of body weight. Within 1 week, the 3 cows stopped shedding leptospires. Six weeks later, 8 more lactating cows were found to be shedding leptospires. These cows were also treated once with dihydrostreptomycin, and they too stopped shedding leptospires within 1 week. From then on, the whole herd was examined weekly for a period of 2 months, and all cows Leptospira-positive by polymerase chain reaction were treated once with dihydrostreptomycin. Again, all cows stopped shedding leptospires in the urine within 1 week after treatment with dihydrostreptomycin. After a single treatment of the whole herd at the same time, new infections were not seen.

Leptospirosis is one of the commonest causes of diffuse alveolar haemorrhage. Despite good sensitivity to penicillin and current techniques of ventilation, there remains a considerable mortality which is particularly linked to the initial pulmonary disease at presentation. The authors describe a new case of a gravely ill patient with leptospirosis and sever hypoxaemia. There was diffuse alveolar haemorrhage and myositis thus a bolus of corticosteroids was used over the first 24 hours complementary to the traditional treatment.

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).

A predictable 6- to 7-day course of a fatal Leptospira interrogans serovar bataviae infection in experimentally infected mature 110- to 150-g hamsters was used to evaluate the therapeutic efficacy of conventionally used and newer antibiotics. Active drugs were ampicillin, bacampicillin, cyclacillin, piperacillin, mezlocillin, doxycycline, chlortetracycline, cefotaxime, and moxalactam. Cephalexin, cefadroxil, cefamandole, and cefoperazone showed little or no activity in preliminary studies. In delayed treatment studies, all nine active drugs prevented death of hamsters even when treatment was delayed until 1 to 2.5 days before expected time of death. Leptospires in kidneys of surviving animals could be demonstrated in one or more hamsters treated with doxycycline, chlortetracycline, cyclacillin, and piperacillin, but in none of the animals treated with ampicillin, bacampicillin, mezlocillin, cefotaxime, and moxalactam. The potential usefulness of newer penicillins and cephalosporins, as well as ampicillin, chlortetracycline, and doxycycline, for treatment of severe leptospirosis is reported.

A young New Hampshire man was recently treated for severe Weil's disease caused by serologically diagnosed Leptospira icterohemorrhagiae. In addition to severe renal failure and hepatic disease, his case featured marked thrombocytopenia with multiple evidences of bleeding. A course of steroid therapy was associated with improved platelet counts and amelioration of his hemorrhagic diathesis.