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Leptospirosis, a globally significant zoonotic disease caused by pathogenic Leptospira, continues to threaten the health and public safety of both humans and animals. Current clinical treatment of leptospirosis mainly relies on antibiotics but their efficacy in severe cases is controversial. Passive immunization has a protective effect in the treatment of infectious diseases. In addition, chicken egg yolk antibody (IgY) has gained increasing attention as a safe passive immunization agent. This study aimed to investigate whether hens produce specific IgY after immunization with inactivated Leptospira and the protective effect of specific IgY against leptospirosis. First, it was demonstrated that specific IgY could be extracted from the eggs of hens vaccinated with inactivated Leptospira and that specific IgY can specifically recognize and bind homotypic Leptospira with a high titre, as shown by MAT and ELISA. Next, we tested the therapeutic effects of IgY in early and late leptospirosis using a hamster model. The results showed that early specific IgY treatment increased the survival rate of hamsters to 100%, alleviated pathological damage to the liver, kidney, and lung, reduced leptospiral burden, and restored haematological indices as well as functional indicators of the liver and kidney. The therapeutic effect of early specific IgY was comparable to that of doxycycline. Late IgY treatment also enhanced the survival rate of hamsters and improved the symptoms of leptospirosis similar to early IgY treatment. However, the therapeutic effect of late IgY treatment was better when combined with doxycycline. Furthermore, no Leptospira colonization was observed in the kidneys, livers, or lungs of the surviving hamsters treated with specific IgY. Mechanistically, IgY was found to inhibit the growth and adhesion to cells of Leptospira. In conclusion, passive immunotherapy with specific IgY can be considered an effective treatment for leptospirosis, and may replace antibiotics regarding its therapeutic effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Leptospirosis is an infectious disease caused by pathogenic Leptospira spp., which could result in severe illnesses. Indirect contact with these pathogens is more common. Individuals could contract this disease through contact with contaminated water or during floods. In this case, we present the details of a 40-year-old male pig farmer who suffered from severe pulmonary hemorrhagic leptospirosis and multiple organ failure. The diagnosis of leptospirosis was confirmed through metagenomics next-generation sequencing (mNGS) while the patient received extracorporeal membrane oxygenation (ECMO) support, and antibiotic treatment was adjusted accordingly. The patient underwent comprehensive treatment and rehabilitation in the intensive care unit., Conclusion: This case illustrates the importance of early diagnosis and treatment of leptospirosis. While obtaining the epidemiological history, second-generation metagenomics sequencing was utilized to confirm the etiology. The prompt initiation of ECMO therapy provided a crucial window of opportunity for addressing the underlying cause. This case report offers valuable insights for diagnosing patients with similar symptoms., (© 2023. The Author(s).)

Leptospirosis is an infectious illness encountered mostly in tropical climates and has been of particular concern in Haiti after natural disasters. Heavy rainfalls and natural disasters in combination with scarce resources to control and identify clusters of infections make certain populations and countries vulnerable. In some cases, patients who contract this disease may need air medical transport to hospitals that have a higher level of care. In this case report, a trio of cases is highlighted from an outbreak that required air transport to transfer patients to a facility with the availability of an intensive care unit. The goal of highlighting these cases is to increase the awareness of physicians and air transport providers to the manifestation and treatment of this disease and to provide pearls to stabilize patients during transport., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Air Medical Journal Associates. Published by Elsevier Inc. All rights reserved.)

Leptospirosis is one of the most important zoonotic bacterial diseases worldwide, commonly affecting resource-poor populations and resulting in significant morbidity and mortality. This article provides an overview of the epidemiology, clinical manifestations, diagnosis and treatment of human leptospirosis., (© Royal College of Physicians 2022. All rights reserved.)

Background: Leptospirosis is a zoonotic spirochetal disease caused by Leptospira interrogans. The clinical presentation ranges from an asymptomatic state to a fatal multiorgan dysfunction. Neurological manifestations including aseptic meningitis, spinal cord and peripheral nerve involvement, cranial neuropathies and cerebellar syndrome are well recognized with varying frequencies among patients with this disease. Posterior reversible encephalopathy syndrome is a very rare occurrence in leptospirosis and only two cases are reported in the medical literature up to now. We report a case of posterior reversible encephalopathy syndrome in a patient with leptospirosis with rhabdomyolysis and acute kidney injury., Case Presentation: A 21 year-old male presented with fever and oliguric acute kidney injury with rhabdomyolysis. A diagnosis of leptospirosis was made and he was being managed according to the standard practice together with regular hemodialysis. The clinical condition was improving gradually. On day 8 of the illness, he developed headache and sudden painless complete bilateral vision loss followed by several brief generalized tonic clonic seizure attacks. Examination was significant for a Glasgow Coma Scale of 14/15, blood pressure of 150/90 mmHg and complete bilateral blindness. The findings of magnetic resonance imaging of the brain were compatible with posterior reversible encephalopathy syndrome. He was managed with blood pressure control and antiepileptics with supportive measures and standard treatment for leptospirosis and made a complete recovery., Conclusion: Posterior reversible encephalopathy syndrome, though very rare with leptospirosis, should be considered as a differential diagnosis in a patient with new onset visual symptoms and seizures, especially during the immune phase. Optimal supportive care together with careful blood pressure control and seizure management would yield a favourable outcome in this reversible entity.

Background: Early diagnosis and detection of clinical deterioration of leptospirosis are challenges to all clinicians. This study aimed to report the characteristics and outcomes of patients admitted to the medical intensive care unit (MICU) for severe leptospirosis and to identify the clinical predictors of MICU admission., Methods: This was a 10-year retrospective study that included all patients diagnosed as leptospirosis, based on either serology or a Thai-Lepto score (TLS) of >4. All clinical characteristics and laboratory data were collected and compared between MICU cases and general ward cases. Binary logistic regression was applied to identify the independent factors for MICU admission., Results: Of the 68 patients who were diagnosed as leptospirosis based on inclusion criteria, 43 serologically-confirmed cases were subsequently analyzed. Fifty percent of the cases were admitted to the MICU and, compared with those admitted to the general ward, had higher Sequential Organ Failure Assessment (SOFA) score [10 (7-13) vs. 5 (2.2-5.6), p < 0.001]; higher TLS [7.5 (6.5-9.25) vs. 5.5 (3.5-6.5), p < 0.001]; lower mean arterial blood pressure (74.7 ± 15 mmHg vs. 84.2 ± 16.3 mmHg, p = 0.04); lower platelet count in ×10 3 cell/mm 3 [65 (52.8-105.8) vs. 159 (87.3-181.5), p = 0.008); higher total bilirubin level [4.4 (1.5-8.7) mg/dL vs. 1.2 (0.7-2.8) mg/dL, p = 0.01]; and required more inotropes and vasopressors (87% vs. 4.3%, p < 0.001), mechanical ventilator support (91.3% vs. 4.3%, p < 0.001), and renal replacement therapy (39.1% vs. 0%, p < 0.001). TLS, SOFA score, requirement for mechanical ventilation, and use of inotropes and vasopressors were the predictors of MICU admission. TLS > 6 and SOFA score >6 gave similar power to predict MICU admission., Conclusion: Among patients with leptospirosis, TLS, SOFA score, inotrope or vasopressor requirement, and mechanical ventilator support were the independent predictors of MICU admission. TLS > 6 and SOFA score >6 indicated the need for MICU admission., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Leptospirosis is caused by an infection with bacteria of the Leptospira species. These spirochetes are carried by a variety of wild and domestic animals. Humans can become infected with these bacteria; leptospirosis most commonly occurs in the tropics and subtropics. Military personnel are at risk of infection through deployment in the field., (2020.)

Objective: To describe a severe case of infection by Leptospira in a woman in the northwest of Mexico., Case Report: A 55-yearold woman from Sonora, México arrived at the Intensive Care Unit due to severe multiple organ failure primarily affecting the respiratory, renal and hepatic systems. Diagnostic tests were performed, and they were positive for anti-Leptospira antibodies, IgM and IgG; and spirochetes were observed on dark field microscopy and confirmed by Polymerase Chain Reaction (PCR). Doxycycline and platelet apheresis transfusion were used as treatment, which led to a very slow recovery., Conclusion: The information presented in this study may help in the identification of pathology caused by spirochetes. This case report is the first to present a case of severe leptospirosis in Sonora, México., (Copyright © 2020 by Academy of Sciences and Arts of Bosnia and Herzegovina.)

Four 2-month-old foals were presented to an equine hospital with acute kidney injury caused by Leptospira interrogans infection. Clinical signs were nonspecific and included lethargy, fever, and unwillingness to nurse. The most important hematologic and clinicopathologic findings were azotemia, anemia, thrombocytopenia, hyponatremia, and hypochloremia. The diagnosis was based on urinary real-time PCR, serology using a microscopic agglutination test, or both. The most important serovars involved were L. interrogans serogroup australis serovar Bratislava and Australis. Treatment consisted of IV fluid therapy and antimicrobial treatment. Renal replacement therapy with hemodiafiltration was performed in 1 of the foals. All foals survived to discharge. This report highlights the importance of early diagnosis and treatment in foals with acute kidney injury caused by L. interrogans infection., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Global Importance: Leptospirosis is the most widespread zoonosis worldwide. Mammals (eg, rats, horses, cows, pigs, dogs, cats and aquatic species, such as sea lions and northern elephant seals) can all be infected by leptospires. Infection in animals occurs through contact with urine or water contaminated with the bacteria. In people, the disease is acquired mainly from animal sources or through recreational activities in contaminated water., Practical Relevance: Literature on the clinical presentation of leptospirosis in cats is scarce, although it has been demonstrated that cats are susceptible to infection and are capable of developing antibodies. The prevalence of antileptospiral antibodies in cats varies from 4% to 33.3% depending on the geographical location. Urinary shedding of leptospires in naturally infected cats has been reported, with a prevalence of up to 68%. Infection in cats has been associated with the consumption of infected prey, especially rodents. Thus, outdoor cats have a higher risk of becoming infected., Clinical Challenges: Clinical presentation of this disease in cats is rare and it is not known what role cats have in the transmission of leptospirosis. Ongoing work is needed to characterise feline leptospirosis., Audience: This review is aimed at all veterinarians, both general practitioners who deal with cats on a daily basis in private practice, as well as feline practitioners, since both groups face the challenge of diagnosing and treating infectious and zoonotic diseases., Evidence Base: The current literature on leptospirosis in cats is reviewed. To date, few case reports have been published in the field, and information has mostly been extrapolated from infections in people and dogs. This review is expected to serve as a guide for the diagnosis and management of the disease in cats.

Leptospirosis, one of the most important of neglected tropical diseases, is a common zoonosis in the tropics. Recent reports have demonstrated that pulmonary haemorrhage is one of the fatal complications of severe leptospirosis. In this report, we present a case of leptospirosis manifested with severe pulmonary haemorrhagic syndrome successfully treated with venovenous extracorporeal membrane oxygenation (VV-ECMO). A 39-year-old man who lives in Bangkok presented with fever, severe myalgia and haemoptysis. With rapid progression of acute respiratory failure in 6 hours, he was intubated and a litre of fresh blood was suctioned. Chest x-ray showed diffuse alveolar infiltrates compatible with ARDS, then mechanical ventilator with lung protective strategy was used. Diagnosis of leptospirosis with diffuse alveolar haemorrhage was made. Refractory hypoxaemia was not responsive to positive end-expiratory pressure (PEEP); thus, VV-ECMO was initiated on the first day. Other treatments included plasmapheresis, intravenous pulse methylprednisolone and intravenous antibiotics. The outcome of treatment was successful, and this patient was discharged to home on day 14 after admission., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Severe leptospirosis can have a case-fatality rate of over 50%, even with intensive care unit (ICU) support. Multiple strategies-including protective ventilation and early renal replacement therapy (RRT)-have been recommended to improve outcomes. However, management guidelines vary widely around the world and there is no consensus on the optimal approach., Methodology/principal Findings: All cases of leptospirosis admitted to the ICU of Cairns Hospital in tropical Australia between 1998 and 2018 were retrospectively reviewed. The patients' demographics, presentation, management and clinical course were examined. The 55 patients' median (interquartile range (IQR)) age was 47 (32-62) years and their median (IQR) APACHE III score was 67 (48-105). All 55 received appropriate antibiotic therapy, 45 (82%) within the first 6 hours. Acute kidney injury was present in 48/55 (87%), 18/55 (33%) required RRT, although this was usually not administered until traditional criteria for initiation were met. Moderate to severe acute respiratory distress syndrome developed in 37/55 (67%), 32/55 (58%) had pulmonary haemorrhage, and mechanical ventilation was required in 27/55 (49%). Vasopressor support was necessary in 34/55 (62%). Corticosteroids were prescribed in 20/55 (36%). The median (IQR) fluid balance in the initial three days of ICU care was +1493 (175-3567) ml. Only 2/55 (4%) died, both were elderly men with multiple comorbidities., Conclusion: In patients with severe leptospirosis in tropical Australia, prompt ICU support that includes early antibiotics, protective ventilation strategies, conservative fluid resuscitation, traditional thresholds for RRT initiation and corticosteroid therapy is associated with a very low case-fatality rate. Prospective studies are required to establish the relative contributions of each of these interventions to optimal patient outcomes., Competing Interests: The authors have declared that no competing interests exist.

A 47-year-old man with a recent history of wading in floodwaters presented with a 1-week history of cough, myalgia, conjunctival suffusion and decreasing urine output. The patient had uraemia, hypotension, leukocytosis, thrombocytopenia, elevated liver enzymes and oliguria. His condition quickly worsened with haemoptysis, and respiratory distress which subsequently required intubation and mechanical ventilation. Continuous renal replacement therapy was started together with haemoperfusion (HP). The patient initially required norepinephrine and this was discontinued after the first session of HP. He was referred for veno-venous extracorporeal membrane oxygenation (ECMO) due to severe hypoxia and pulmonary haemorrhage. Oxygenation and lung compliance improved, and serum creatinine levels continued to normalise with improved urine output. He was placed off ECMO, extubated and eventually discharged. Patient was diagnosed with severe leptospirosis, acute respiratory failure and acute kidney injury successfully treated with simultaneous ECMO and HP. Blood samples were positive for Leptospira spp. DNA via PCR assay., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The emergence of leptospirosis-associated severe pulmonary hemorrhagic syndrome (SPHS) with high case fatality has been reported from many countries. Understanding of clinical disease and sequel of SPHS needs larger studies with adequate numbers. The purpose of this study was to describe the characteristics and sequel by different therapeutic approaches for SPHS in Leptospirosis in Sri Lanka., Methods: This study was conducted at Teaching Hospital-Karapitiya (THK), Galle, Sri Lanka from June 2015 to December 2017. THK is the main tertiary care center for the Southern Province. All confirmed-cases of leptospirosis who presented during this period and were admitted to five medical units of THK were included in this study. SPHS was defined as a patient presenting; haemoptysis, arterial hypoxemia (Acute Lung Injury Score < 2.5), haemoglobin drop (10% from the previous value), or diffused alveolar shadows in the chest radiograph, without alternative explanation other than leptospirosis., Results: Of the 128 MAT confirmed cases of leptospirosis, 111 (86.7%) had acute kidney injury (AKI) whilst SPHS was seen in 80 (62.5%). Patients typically developed SPHS within the first week of illness, mostly on days 4 and 5. The case fatality rate of this study sample was 28.1% (n = 36), while for patients with SPHS, it was 41.5%. Most of the deaths (n = 19) were within the first 3 days of admission (on the same day 8, and within next 48 h 11). Among SPHS patients, 59 received therapeutic plasma exchange (TPE). The survival rate was higher (n = 35, 74.5%) when the TPE was performed within the first 48 h of detecting SPHS compared to patients in whom the procedure was done after 48 h (n = 5, 54.5%). Of the 19 leptosprosis patients with SPHS who did not receive TPE, 17 died (89.5%). However, the group of patients who received TPE was primarily the patients survived beyond day 3., Conclusions: We observed that during the study period, SPHS was common and the mortality rate was higher in the study area. The treatment modalities tested need further evaluation and confirmation.

Leptospirosis is a worldwide spirochetal zoonosis whose global incidence is increasing and is probably underestimated. Leptospirosis has long been associated with occupational contact with animals (rats and cattle) and has become in developed countries a pathology more related to recreational activities with exposure to fresh water (canoeing, swimming, canyoning) and to an environment contaminated by urine from leptospires excretory rodents. Leptospirosis should be one of the differential diagnoses to be considered when returning from travel to tropical areas, particularly Southeast Asia, and particularly during the rainy season. The clinical symptoms, particularly in the initial phase, are not specific and can limit to a flu-like syndrome or "dengue-like" making diagnosis often difficult. It is then necessary to look carefully for clinical (muscle pain, cough, conjunctival involvement, jaundice) and biological arguments (thrombocytopenia, cholestasis, rhabdomyolysis, frank elevation of CRP) that will help to diagnose leptospirosis and lead to quick antibiotic therapy before the progression to a severe icterohaemorrhagic (Weil's disease) or respiratory form associated with significant mortality. Treatment is based on injectable beta-lactams in severe forms (mainly cephalosporins) and amoxicillin, doxycycline or azithromycin in non-severe forms. Some atypical or delayed forms of leptospirosis occurring in the late immune phase of the disease are to know. Rapid diagnostic tools are currently being studied to improve diagnosis in remote areas and facilitate access to early treatment., (Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Thrombocytopenia is a well-known manifestation of acute tropical infectious diseases. The role of platelets in infections has received much attention recently because of their emerging activities in modulation of inflammatory responses, host defense, and vascular integrity. However, while many studies have addressed thrombocytopenia in tropical infections, abnormalities in platelet function have been largely overlooked. This is an important research gap, as platelet dysfunction may contribute to the bleeding tendency that characterizes some tropical infections. The development of novel platelet function assays that can be used in thrombocytopenic conditions (e.g., flow cytometry assays) has contributed to important new insights in recent years. In this review, the importance of platelets in tropical infections is discussed with special emphasis on the underlying mechanisms and consequences of thrombocytopenia and platelet dysfunction in these infections. Special attention is paid to malaria, a disease characterized by microvascular obstruction in which bleeding is rare, and to infections in which bleeding is common, such as dengue, other viral hemorrhagic fevers, and the bacterial infection leptospirosis. Given the importance of platelet function abnormalities in these infections, the development of affordable assays for monitoring of platelet function in low-resource countries, as well as pharmacologic interventions to prevent or reverse platelet function abnormalities, might improve clinical care and the prognosis of these infections., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Tropical infections form 20-30% of ICU admissions in tropical countries. Diarrheal diseases, malaria, dengue, typhoid, rickettsial diseases and leptospirosis are common causes of critical illness. Overlapping clinical features makes initial diagnosis challenging. A systematic approach involving (1) history of specific continent or country of travel, (2) exposure to specific environments (forests or farms, water sports, consumption of exotic foods), (3) incubation period, and (4) pattern of organ involvement and subtle differences in manifestations help in differential diagnosis and choice of initial empiric therapy. Fever, rash, hypotension, thrombocytopenia and mild derangement of liver function tests is seen in a majority of patients. Organ failure may lead to shock, respiratory distress, renal failure, hepatitis, coma, seizures, cardiac arrhythmias or hemorrhage. Diagnosis in some conditions is made by peripheral blood smear examination, antigen detection or detection of microbial nucleic acid by PCR. Tests that detect specific IgM antibody become positive only in the second week of illness. Initial therapy is often empiric; a combination of intravenous artesunate, ceftriaxone and either doxycycline or azithromycin would cover a majority of the treatable syndromes. Additional antiviral or antiprotozoal medications are required for some specific syndromes. Involving a physician specializing in tropical or travel medicine is helpful., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To characterize the transport of severely ill patients with extracorporeal respiratory or cardiovascular support., Methods: A series of 18 patients in the state of São Paulo, Brazil is described. All patients were consecutively evaluated by a multidisciplinary team at the hospital of origin. The patients were rescued, and extracorporeal membrane oxygenation support was provided on site. The patients were then transported to referral hospitals for extracorporeal membrane oxygenation support. Data were retrieved from a prospectively collected database., Results: From 2011 to 2017, 18 patients aged 29 (25 - 31) years with a SAPS 3 of 84 (68 - 92) and main primary diagnosis of leptospirosis and influenza A (H1N1) virus were transported to three referral hospitals in São Paulo. A median distance of 39 (15 - 82) km was traveled on each rescue mission during a period of 360 (308 - 431) min. A median of one (0 - 2) nurse, three (2 - 3) physicians, and one (0 - 1) physical therapist was present per rescue. Seventeen rescues were made by ambulance, and one rescue was made by helicopter. The observed complications were interruption in the energy supply to the pump in two cases (11%) and oxygen saturation < 70% in two cases. Thirteen patients (72%) survived and were discharged from the hospital. Among the nonsurvivors, there were two cases of brain death, two cases of multiple organ dysfunction syndrome, and one case of irreversible pulmonary fibrosis., Conclusions: Transportation with extracorporeal support occurred without serious complications, and the hospital survival rate was high.

Background: Leptospirosis is one of the most common zoonotic diseases worldwide. Infection occurs through contact with infected animals, or soil or water that has been contaminated by the urine of infected animals. Risk factors include occupational and recreational exposures, contact with floodwaters, and travel to areas with a high risk of leptospirosis, particularly tropical, developing countries. With climate change, flood-related outbreaks are becoming more common., Objective: This article aims to improve awareness of leptospirosis, and provide an update for general practitioners on its epidemiology, risk factors, clinical presentation, laboratory diagnosis, management and prevention., Discussion: Leptospirosis is sometimes misdiagnosed because clinical presentation can be non-specific and overlap with many other causes of acute febrile illnesses. In patients with risk factors for leptospirosis, a high index of clinical suspicion is important to ensure early diagnosis and treatment. Delays in treatment could increase the risk of severe complications, including pulmonary haemorrhage, acute renal failure and acute liver failure.

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

Ekinci F, Yıldızdaş RD, Horoz ÖÖ, Alabaz D, Tolunay İ, Petmezci E. Treatment of severe leptospirosis with therapeutic plasma exchange in a pediatric patient. Turk J Pediatr 2018; 60: 566-570. Leptospirosis is a common zoonotic disease caused by spirochetes of the genus Leptospira. Although it is mostly a tropical disease, some case reports have been published from temperate regions of the world. The disease presents with a wide spectrum; from asymptomatic self limited disease to a fatal illness characterized by multi-organ involvement. An 8-year-old girl presented with a 5-day history of fever, myalgia, fatigue, vomiting and diarrhea. She developed anuria, hypotension and became unconscious one day after admission and was referred to our pediatric intensive care unit for further evaluation and treatment. Initial physical examination revealed fever, jaundice, diffuse petecchiae on whole body, hepatomegaly and severe hypotension. Laboratory investigations showed elevated liver enzymes and bilirubin levels, elevated creatinine and creatine kinase levels and trombocytopenia. The diagnosis of Leptospirosis was detected by rapid IgM test and confirmed by microscopic agglutination test later. She was treated with mechanical ventilation, wide spectrum antibiotics, positive inotropic agents and penicillin G plus two days of continuous renal replacement therapy and five sessions of therapeutic plasma exchange performed daily. She recovered completely and was transferred to the pediatric ward on the 14th day of hospitalization. The exact role of therapeutic plasma exchange has not been well documented yet, it seems to have benefical effects on clinical and laboratory findings and survival as we observed in our patient and learned from experiences in adult patients presented as case reports.

Objectives: Leptospirosis causes reversible multiple organ failure, and its mortality remains high. The aim of this study was to determine the mortality rate of leptospirosis in an ICU offering all types of organ support available nowadays and to compare it with mortality in bacterial sepsis., Design: Retrospective, descriptive, and single-center cohort study., Settings: The largest ICU of Reunion Island (Indian Ocean) in a teaching hospital., Patients: Consecutive patients hospitalized in ICU for leptospirosis from January 2004 to January 2015., Interventions: None., Measurements and Main Results: We report 134 cases of patients with leptospirosis hospitalized in ICU. The median age was 40 years (interquartile range, 30-52 yr), with a Simplified Acute Physiology Score II of 38 (27-50) and a Sequential Organ Failure Assessment score of 10 (8-12). Forty-one patients (31%) required mechanical ventilation and 76 (56%) required renal replacement therapy. The door-to-renal replacement therapy time was 0 (0-1) day after admission with a median urea of 25 mmol/L (17-32 mmol/L). Five patients required extracorporeal membrane oxygenation. The mortality rate was 6.0% (95% CI, 2.6-11.4). Among patients hospitalized for sepsis, the standardized mortality ratio of patients with leptospirosis with regards to Simplified Acute Physiology Score II was dramatically low: 0.40 (95% CI, 0.17 - 0.79)., Conclusions: The mortality of severe leptospirosis is lower than for other bacterial infection, provided modern resuscitation techniques are available. Prompt organ support ensures very low mortality rates despite high severity scores.

Leptospirosis is a potentially fatal zoo-anthroponosis caused by pathogenic species of Leptospira belonging to the family of Leptospiraceae, with a worldwide distribution and effect, in terms of its burden and risk to human health. The 'LeptoDB' is a single window dedicated architecture (5 948 311 entries), modeled using heterogeneous data as a core resource for global Leptospira species. LeptoDB facilitates well-structured knowledge of genomics, proteomics and therapeutic aspects with more than 500 assemblies including 17 complete and 496 draft genomes encoding 1.7 million proteins for 23 Leptospira species with more than 250 serovars comprising pathogenic, intermediate and saprophytic strains. Also, it seeks to be a dynamic compendium for therapeutically essential components such as epitope, primers, CRISPR/Cas9 and putative drug targets. Integration of JBrowse provides elaborated locus centric description of sequence or contig. Jmol for structural visualization of protein structures, MUSCLE for interactive multiple sequence alignment annotation and analysis. The data on genomic islands will definitely provide an understanding of virulence and pathogenicity. Phylogenetics analysis integrated suggests the evolutionary division of strains. Easily accessible on a public web server, we anticipate wide use of this metadata on Leptospira for the development of potential therapeutics.Database URL: http://leptonet.org.in.

Background: This study was conducted to investigate changes in the clinical pattern of leptospirosis over time, analyzing its clinical and laboratory presentations in a metropolitan city of Brazil., Method: This was a retrospective study including all patients with leptospirosis admitted to tertiary care hospitals in Fortaleza in the northeast of Brazil, between 1985 and 2015. Patients were divided into three groups according to the year of hospital admission: group I for the years 1985-1995, group II for 1996-2005, and group III for 2006-2015. Demographic, clinical, and laboratory data were compared between the groups., Results: A total of 507 patients were included. Their mean age was 37.3±15.9years and 82.4% were male. The mean time between symptom onset and admission was 7±4 days. There was a linear decrease in the levels of serum urea (190.1±92.7, 135±79.5, and 95.6±73.3mg/dl, respectively, p <0.0001) and creatinine (5.8±2.9, 3.8±2.6, and 3.0±2.5mg/dl, respectively, p <0.0001) in each decade, while levels of hemoglobin (10.31±1.9, 10.8±2.0, and 11.5±2.1g/dl, respectively, p <0.0001) and platelets (57.900±52.650, 80.130±68.836, and 107.101±99.699×10 9 /l, respectively, p<0.0001) increased. There was a tendency towards a linear decrease in mortality (22%, 14%, and 11.6%, respectively, p=0.060)., Conclusions: Leptospirosis showed significant changes over time in this region. The main changes point to a decrease in disease severity and complications, such as acute kidney injury. Mortality has decreased, being close to 11%., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Leptospirosis, caused by Leptospira, is one of the most important of neglected emerging zoonotic diseases that has important impacts on public health worldwide. Polyclonal antibody (pcAb) therapy is a potential method to process a series of pathogens for which there are limited determination of treatment, such as leptospirosis. First, we evaluated the efficacy of pcAb, derived from the sera of rabbits inoculated with Leptospira, against homotype (Leptospira interrogans serovar Lai) or heterotype (Leptospira interrogans serovar Autumnalis) Leptospira infection in a lethal hamster model. The pcAb treatment improved survival compared to the controls. The histopathology's of the infected kidney, liver and lung were also examined by hematoxylin and eosin staining. Using real-time quantitative PCR, we determined that most of the leptospires in the primary organs were almost completely removed by pcAb. In the second experiment, treatments, including antibiotic, pcAb, and combination, were started immediately after occurrence of the first serious sickness mouse in any group. No significant difference in survival rate between pcAb group and antibiotic group was found, but the combination therapy group significantly improved survival rate compared to the others (P<0.05). We conclude that the rabbit pcAb treatment may cure both the homotype and the heterotype lethal Leptospira infections in hamster, and combination therapy improved survival compared to antibiotic group in the late treatment of homotype leptospirosis., Competing Interests: The authors have declared that no competing interests exist.

The occurrence of leptospirosis has defied epidemiology even when using different analysis technologies at local geographical levels. This cross-sectional and descriptive study sought to identify spatial correlations between social and environmental risk factors and leptospirosis in Belém in the State of Pará from 2007 to 2013. Epidemiological data were obtained from the Information System for Notifiable Diseases of the Pará State Department of Public Health and the environmental, demographic and cartographical data from the Brazilian Institute of Geography and Statistics. Men aged 20 to 39 of unknown profession and mixed ethnicity were the most affected. Laboratory diagnosis (82%) and hospital care (67.22%) confirmed satisfactory access to the Unified Health System. Numerical Kriging indicated the highest concentrations of the disease in the Guamá and Jurunas neighborhoods in lower lying areas near canals. The Buffer technique showed higher concentrations of the disease in areas with no domestic solid garbage collection service (26%), sewage (22%), piped water (38%), with unpaved roads (20%) and street flooding (65%). The Moran technique revealed a direct spatial correlation between these variables (p = 0.01543). The general trend showed the decrease of the disease.

Leptospirosis. Leptospirosis is the first worldwide anthropozoonosis with an incidence of 1 000 000 cases per year. It is more frequently encountered in tropical areas but also can be diagnosed in tempered places. In France, the most exposed people are athletes in fresh water (canoeing, rafting, caving...) and agricultural workers. The peak incidence occurs in late summer. After transcutaneous or mucosal penetration, Leptospira can cause direct tissue injury by invasion, or indirect injury by toxinic and/or immunological mechanism. Also called summer flu, the clinical presentation is variable: it ranges from simple flu-like illness to septic shock with multiple organ dysfunction syndrome, with varying degrees of fever, headache or myalgia. Conjunctival suffusion is also very evocative. Biology can show thrombocytopenia, lymphopenia, cholestasis, elevated liver enzymes, renal failure, hematuria and proteinuria. Mortality occurs very rarely if organ failures (renal failure, pulmonary edema lesions ...) are undertaken by adequate therapy. The diagnosis is usually based on serology (micro-agglutination test), repeated 15 days after the first test. A first negative serology is not sufficient to rule out the diagnosis. PCR detection is also available and can facilitate the diagnosis of leptospirosis. A vaccine is available but it only protects against serogroup Icterohaemorrhagiae. It is recommended for professional expositions, but there is no consensus for leisure activities., Competing Interests: M. de Laroche déclare n’avoir aucun lien d’intérêts. S. Jauréguiberry déclare des liens d’intérêts ponctuels (travail scientifique, rapports d’expertise, activités de conseil, prise en charge lors de congrès) avec les entreprises Guilin et Sigma Tau.

Background: Leptospirosis is a health problem worldwide. Its most severe form is a classic model of sepsis, provoking acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI), with associated mortality that remains unacceptably high. We previously demonstrated that early initiation of sustained low-efficiency dialysis (SLED) followed by daily SLED significantly decreases mortality. However, the mode of clearance can also affect dialysis patient outcomes. Therefore, the objective of this study was to compare the effects of SLED with traditional (diffusive) clearance, via hemodialysis, and SLED with convective clearance, via hemodiafiltration (SLEDf), in patients with severe leptospirosis., Methods: In this prospective study, conducted in the intensive care unit (ICU) from 2009 through 2012, we compared two groups-SLED (n = 19) and SLEDf (n = 20)-evaluating demographic, clinical, and biochemical parameters, as well as serum levels of interleukins, up to the third day after admission. All patients received dialysis early and daily thereafter., Results: During the study period, 138 patients were admitted to our ICU with a diagnosis of leptospirosis; 39 (36 males/3 females) met the criteria for ARDS and AKI. All patients were on mechanical ventilation and were comparable in terms of respiratory parameters. Mortality did not differ between the SLEDf and SLED groups. However, post-admission decreases in the serum levels of interleukin (IL)-17, IL-7, and monocyte chemoattractant protein-1 were significantly greater in the SLEDf group. Direct bilirubin and the arterial oxygen tension/fraction of inspired oxygen ratio were significantly higher in the SLED group. We identified the following risk factors (sensitivities/specificities) for mortality in severe leptospirosis: age ≥ 55 years (67%/91%); serum urea ≥ 204 mg/dl (100%/70%); creatinine ≥ 5.2 mg/dl (100%/58%); Acute Physiology and Chronic Health Evaluation II score ≥ 39.5 (67%/88%); Sequential Organ Failure Assessment score ≥ 20.5 (67%/85%); and inspiratory pressure ≥ 31 mmHg (84%/85%)., Conclusions: The mode of dialysis clearance might not affect outcomes in severe leptospirosis.

Objective: To alert clinicians to the climatic conditions that can precipitate outbreaks of the rodent-borne infectious diseases most often associated with flooding disasters, leptospirosis (LS), and the Hantavirus-caused diseases, hemorrhagic fever with renal syndrome (HFRS) and Hantavirus pulmonary syndrome (HPS); to describe the epidemiology and presenting clinical manifestations and outcomes of these rodent-borne infectious diseases; and to recommend both prophylactic therapies and effective control and prevention strategies for rodent-borne infectious diseases., Design: Internet search engines, including Google®, Google Scholar®, Pub Med, Medline, and Ovid, were queried with the key words as search terms to examine the latest scientific articles on rodent-borne infectious disease outbreaks in the United States and worldwide to describe the epidemiology and presenting clinical manifestations and outcomes of LS and Hantavirus outbreaks., Setting: Not applicable., Participants: Not applicable., Interventions: Not applicable., Main Outcome Measure: Rodent-borne infectious disease outbreaks following heavy rainfall and flooding disasters., Results: Heavy rainfall encourages excessive wild grass seed production that supports increased outdoor rodent population densities; and flooding forces rodents from their burrows near water sources into the built environment and closer to humans., Conclusions: Healthcare providers should maintain high levels of suspicion for LS in patients developing febrile illnesses after contaminated freshwater exposures following heavy rainfall, flooding, and even freshwater recreational events; and for Hantavirus-caused infectious diseases in patients with hemorrhagic fevers that progress rapidly to respiratory or renal failure following rodent exposures.

Background: Leptospirosis is the most widespread zoonosis in the world. Cardiac involvement is a frequent complication of leptospirosis although significant left ventricular dysfunction is rare. We report a case of fatal leptospira myocarditis leading to cardiogenic shock on the second day of illness. This early occurrence of myocarditis is not previously reported., Case Presentation: A 36-yr-old previously healthy Sri Lankan male who takes care of a horse presented to the medical casualty ward with a one day history of fever, arthralgia and severe myalgia. He developed hypotension on the second day of illness. Electrocardiogram showed sinus tachycardia with ST segment depression in lateral leads which evolved in to rapid atrial fibrillation in the subsequent days. 2D echocardiogram showed dilated cardiac chambers with severe global hypokinesia and an ejection fraction of 20%. His renal and liver functions were within normal limits. He developed multi organ dysfunction syndrome and refractory shock, later in the course of illness. Leptospirosis was confirmed by positive leptospira IgM and negative IgG. Patient died on the fifth day of illness despite optimal medical treatment with intravenous penicillin, meropenem, levofloxacin, inotropes and supportive care in the intensive care unit., Conclusions: We describe a rare and unusual early complication of leptospirosis which has not been reported before. It is important to bear in mind that leptospirosis could present as myocarditis during the early phase of illness.

Leptospirosis is a global disease of animals, which can have a major economic impact on livestock industries and is an important zoonosis. The current knowledge base is heavily biased towards the developed agricultural economies. The disease situation in the developing economies presents a major challenge as humans and animals frequently live in close association. The severity of disease varies with the infecting serovar and the affected species, but there are many common aspects across the species; for example, the acute phase of infection is mostly sub-clinical and the greatest economic losses arise from chronic infection causing reproductive wastage. The principles of, and tests for, diagnosis, treatment, control and surveillance are applicable across the species.

Leptospirosis is a widespread and potentially fatal zoonosis that is endemic in many tropical regions and causes large epidemics after heavy rainfall and flooding. Infection results from direct or indirect exposure to infected reservoir host animals that carry the pathogen in their renal tubules and shed pathogenic leptospires in their urine. Although many wild and domestic animals can serve as reservoir hosts, the brown rat (Rattus norvegicus) is the most important source of human infections. Individuals living in urban slum environments characterized by inadequate sanitation and poor housing are at high risk of rat exposure and leptospirosis. The global burden of leptospirosis is expected to rise with demographic shifts that favor increases in the number of urban poor in tropical regions subject to worsening storms and urban flooding due to climate change. Data emerging from prospective surveillance studies suggest that most human leptospiral infections in endemic areas are mild or asymptomatic. Development of more severe outcomes likely depends on three factors: epidemiological conditions, host susceptibility, and pathogen virulence (Fig. 1). Mortality increases with age, particularly in patients older than 60 years of age. High levels of bacteremia are associated with poor clinical outcomes and, based on animal model and in vitro studies, are related in part to poor recognition of leptospiral LPS by human TLR4. Patients with severe leptospirosis experience a cytokine storm characterized by high levels of IL-6, TNF-alpha, and IL-10. Patients with the HLA DQ6 allele are at higher risk of disease, suggesting a role for lymphocyte stimulation by a leptospiral superantigen. Leptospirosis typically presents as a nonspecific, acute febrile illness characterized by fever, myalgia, and headache and may be confused with other entities such as influenza and dengue fever. Newer diagnostic methods facilitate early diagnosis and antibiotic treatment. Patients progressing to multisystem organ failure have widespread hematogenous dissemination of pathogens. Nonoliguric (high output) renal dysfunction should be supported with fluids and electrolytes. When oliguric renal failure occurs, prompt initiation of dialysis can be life saving. Elevated bilirubin levels are due to hepatocellular damage and disruption of intercellular junctions between hepatocytes, resulting in leaking of bilirubin out of bile caniliculi. Hemorrhagic complications are common and are associated with coagulation abnormalities. Severe pulmonary hemorrhage syndrome due to extensive alveolar hemorrhage has a fatality rate of >50 %. Readers are referred to earlier, excellent summaries related to this subject (Adler and de la Peña-Moctezuma 2010; Bharti et al. 2003; Hartskeerl et al. 2011; Ko et al. 2009; Levett 2001; McBride et al. 2005).

Leptospirosis is recognized as a zoonotic disease that is emerging worldwide. Severe manifestations are associated with high morbidity and mortality rates and may therefore pose an important risk to public health, especially in certain high prevalence areas like Taiwan. The severe pulmonary form of leptospirosis is a lesser known entity and is characterized by intra-alveolar hemorrhage and can lead to acute respiratory failure with resistant hypoxemia, which leads to high mortality rates despite maximally invasive mechanical ventilation and adequate treatment. We herein present a case of severe leptospirosis complicated by massive pulmonary hemorrhage, which was successfully managed by extra corporeal membrane oxygenation.

Background: Leptospirosis has a mortality rate of 5-20%. Poor prognostic factors are older age; oliguria; elevated potassium, creatinine and/or bilirubin levels; and altered mental status. We conducted this retrospective study to analyse the predictors of mortality among Indian patients with leptospirosis., Methods: Clinical, biochemical, demographic and treatment related data (time between onset of symptoms and commencement of leptospira specific antibiotics) of 101 leptospirosis patients were reviewed. Predictors identified by univariate analysis were analysed by multivariable Cox regression for survival analysis., Results: Prominent clinical features were: fever (101/101, 100%), jaundice (62, 62.4%), vomiting (42, 41.6%), oliguria (35, 34.7%), cough (18, 17.8%) and dyspnoea (10, 10.0%). Common complications were acute kidney injury (22, 21.8%), cardiovascular collapse (13, 12.9%), haemorrhages (10, 10.0%), meningitis (7, 6.9%), acute respiratory distress syndrome and pancreatitis (5, 5.0% each). Seventeen patients died (16.8%). Univariate predictors of mortality were older age, delayed antibiotic therapy, higher bilirubin, aspartate aminotransferase, alkaline phosphatase, leucocyte count and aspartate/alanine aminotransferase ratio (AAR). Only AAR (HR 1.208, 95% CI 1.051-1.388) and number of days the patient was symptomatic before access to specific antibiotic therapy (HR 1.304, 95% CI 1.081-1.574) remained significant predictors after Cox regression., Conclusions: Multivariate analysis showed high AAR and delayed antibiotic therapy might be associated with fatality., (© The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Leptospirosis is a zoonotic infection endemic in Hawai'i. This review discusses the incidence of documented human cases in Hawai'i and current recommendations for diagnosis, prevention, and treatment of leptospirosis.

Purpose of Review: In the past years, the importance of studying leptospirosis in a translational context has become more evident. This review addresses recent findings in the study of leptospirosis infection, focusing on those applicable to public health, or that will affect management and diagnosis of cases of leptospirosis., Recent Findings: We review here recent findings regarding translational aspects of leptospirosis research. Briefly, PCR or a combination of serology and PCR seem to have a higher sensitivity than the current gold standard (microagglutination test). More clinical trials are needed to determine the best treatment for mild and severe leptospirosis. Dendritic cells and γδ T cells seem to have an important role in the immune response to leptospirosis. Environmental assessment is emerging as a very useful tool., Summary: In order to understand leptospirosis, multiple aspects need to be considered, including host, pathogen and environment. In this review, we will address newer diagnostics, current advances in immunology and treatment and the growing role of environmental assessment.

Leptospirosis, caused by a spirochete of genus Leptospira, is considered the most widespread zoonosis in the world. It has a global distribution with a higher incidence in the tropics and subtropics, ranging from 10 to 100 human cases per 100,000 individuals. Leptospirosis is considered an "emerging" zoonosis due to increased contact between animals and humans and the resulting human encroachment into wildlife habitat. Climate change and its associated environmental shifts can affect the degree of transmission of leptospirosis. Surveillance for leptospirosis is important for early detection of cases because early treatment is crucial to decrease morbidity and mortality. In June 2012, the Council of State and Territorial Epidemiologists approved reinstatement of leptospirosis as a Nationally Notifiable Condition. Reinstatement of national surveillance will facilitate the assessment of the incidence, geographic distribution, trends, and risk factors associated with human cases and the identification of outbreaks and potential new animal reservoirs., (Published by Elsevier Ltd.)

This review presents an overview of the most important rodent-borne hemorrhagic fever pathogens directly transmitted from rodents to humans, namely Leptospira and hantaviruses, together with the New- and Old-World arenaviruses. These zoonotic diseases frequently share clinical symptoms, transmission routes and other epidemiological features and often have an emerging pattern. Differential diagnostics could benefit from a syndrome-based approach grouping these pathogens. In this review extensive descriptions of the epidemiology, clinical symptoms, diagnostics and treatment are provided including a practical overview, listing clinical features, diagnostics and risk factors for each selected rodent-borne hemorrhagic fever pathogen.

Leptospirosis is a common zoonotic infection worldwide and is recognized as an emerging public health problem. Although commonly thought of as a tropical disease, incidence in temperate climates is increasing, with recent outbreaks in the United States and Germany, among other countries. The disease presents with symptoms ranging from fever, headache, nausea, and vomiting to life-threatening multiorgan failure characterized by acute liver failure, nephritis, pulmonary hemorrhage, meningitis, and cardiac arrhythmia. We describe a case of an otherwise healthy 28-year-old man who had just returned from a 2-month trip to Southeast Asia. He presented to our emergency department twice after his return with the complaint of fever and malaise. Initially, he was treated with symptomatic measures and discharged home with malaria smears and blood cultures pending. On his final presentation before admission, he presented with severe fatigue, myalgia, acute renal failure, and marked thrombocytopenia. After several days, inpatient testing revealed the patient's leptospira antibody titer was markedly positive. Given the nonspecificity of patient symptoms, early diagnosis of leptospirosis can be challenging. Diagnostic uncertainty may lead to delay in recommended intravenous antibiotic treatment. We present a case of severe leptospirosis treated exclusively with supportive measures and intravenous corticosteroids., (Copyright © 2013 Elsevier Inc. All rights reserved.)

In leptospirosis, severe pulmonary hemorrhagic syndrome has replaced Weil's disease as the main cause of mortality, with rates of up to 75%. Four men, all farmers, were admitted to the intensive care unit between August 2009 and July 2010 with a diagnosis of acute respiratory distress syndrome. All patients presented with fever, hemoptysis, bilateral pulmonary infiltrates in chest radiographs, and thrombocytopenia and had compatible epidemiological history with leptospirosis; 3 patients had anemia, 3 had renal failure, 2 had increased creatine kinase, whereas bilirubin was slightly increased in only 1 patient. Leptospirosis was diagnosed serologically in all cases. Empirical therapy with ceftriaxone was administered immediately to all patients, while implementation of ARDSnet protective mechanical ventilation approach combined with an early goal-directed hemodynamic approach led to a relatively low mortality rate (25%). Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology Score II and Sepsis-Related Organ Failure Assessment scoring systems were unable to predict the outcome of the patients with leptospirosis-associated severe pulmonary hemorrhagic syndrome.

This study presents a Brazilian goat herd with reproductive failure over 2009-2010, in which there were abortions (22/50; 44%), embryonic resorption (6/50; 12%) and neonatal deaths (2/50; 4%). A diagnosis of leptospirosis was made, based on serology (microscopic agglutination test - MAT), bacterial culture, and polymerase chain reaction (PCR). Antibiotic therapy, specific vaccination protocols and changes in management practices were instigated. One year after the outbreak, diagnostic methods were repeated and reproductive performance re-analysed. Soon after the outbreak, 61/125 (48.8%) of the goats were seropositive for Leptospira. Pure isolates of Leptospira were not obtained, but Leptospira PCR testing was positive in 48/50 (96%) urine samples. After 1 year only 4.2% were seropositive and the occurrence of reproductive problems decreased roughly 10-fold, although five goats (10.4%) remained PCR-positive. A broad-based management approach, including serological and molecular diagnostic methods, vaccination, antibiotic treatment, and alteration of some environmental aspects, were critical to the control of this outbreak, thereby minimising subsequent reproductive failures and economic losses., (Copyright © 2012 Elsevier Ltd. All rights reserved.)