Acute kidney injury and liver disease in an American bulldog with suspected leptospirosis.

A 6-year-old spayed female American bulldog was brought to a veterinary clinic with a 3-day history of vomiting, lethargy, anorexia, icterus, hemorrhagic diarrhea, and oliguria. The dog's clinical signs, complete blood (cell) count, serum biochemistry, urinalysis, and diagnostic imaging were indicative of acute kidney injury and acute hepatopathy consistent with leptospirosis. Treatment for leptospirosis was initiated but, due to the dog's lack of response and progression of clinical signs, euthanasia was ultimately elected after 3 d of hospitalization. The dog tested negative for Leptospira spp. on ELISA; urine, blood, and tissue PCRs; and immunohistochemistry. This case demonstrates that confirmation of leptospirosis can be challenging, even in an animal with the expected clinical presentation. Therefore, limitations of the diagnostic tests available, as well as the possibility of other, less likely differential diagnoses such as toxicosis, must be considered.

Lésion rénale aiguë et maladie hépatique chez un bouledogue américain avec leptospirose suspectée. Une femelle bouledogue américain stérilisée âgée de 6 ans a été présenté à une clinique vétérinaire avec une histoire d'une durée de 3 jours de vomissement, léthargie, anorexie, ictère, diarrhée hémorragique et oligurie. Les signes cliniques de la chienne, un comptage cellulaire sanguin complet, une biochimie sérique, une analyse d'urine et de l'imagerie diagnostique étaient indicateur de lésion rénale aiguë et d'hépatopathie aiguë compatibles avec la leptospirose. Un traitement pour la leptospirose a été instauré mais, étant donné l'absence de réponse de l'animal et la progression des signes cliniques, l'euthanasie a finalement été décidée après 3 jours d'hospitalisation. L'animal s'est avéré négatif par ELISA pour Leptospira spp.; l'urine, le sang et les tissus étaient également négatifs par PCR; et par immunohistochime. Ce cas illustre le fait que la confirmation de la leptospirose peut représenter un défi, même chez un animal avec la présentation clinique attendue. Ainsi, les limites des tests diagnostiques disponibles, de même que la possibilité d'autres diagnostics différentiels moins probables, tel qu'une toxicose, doivent être considérés.(Traduit par Dr Serge Messier).

A rare case of anti-DPPX encephalitis combined with neuroleptospirosis.

BACKGROUND: Neuroleptospirosis and anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis are both very rare and have only been reported in the form of respective case reports. There are no reports of anti-DPPX encephalitis combined with neuroleptospirosis in the literature. We reported the first case of neuroleptospirosis combined with elevated DPPX antibodies in serum and cerebrospinal fluid (CSF). CASE PRESENTATION: A previously healthy 53-year-old Chinese male farmer with a history of drinking raw stream water and flood sewage exposure was brought to the hospital due to an acute onset of neuropsychiatric symptoms. No fever or meningeal irritation signs were detected on physical examination. Routine laboratory investigations, including infection indicators, leukocyte and protein in CSF, electroencephalogram and gadolinium-enhanced magnetic resonance imaging of the brain, all revealed normal. While metagenomic next-generation sequencing (mNGS) identified the DNA genome of Leptospira interrogans in the CSF. Anti-DPPX antibody was detected both in blood and in CSF. A diagnosis of neuroleptospirosis combined with autoimmune encephalitis associated with DPPX-Ab was eventually made. He resolved completely after adequate amount of penicillin combined with immunotherapy. CONCLUSION: We highlight that in patients with acute or subacute behavioral changes, even in the absence of fever, if the most recent freshwater exposure is clear, physicians should pay attention to leptospirosis. Due to the low sensitivity of routine microscopy, culture, polymerase chain reaction and antibody testing, mNGS may have more advantages in diagnosing neuroleptospirosis. As autoimmune encephalitis can be triggered by various infections, neuroleptospirosis may be one of the causes of autoimmune encephalitis. Since neuronal antibody measurements themselves are not that common in neuroleptospirosis, future studies are needed to determine whether the detection of anti-DPPX antibodies is a rare event in leptospirosis. Early identification of autoimmune encephalitis and timely administration of immunotherapy may lead to a better outcome.

Leptospirosis-associated meningitis in a patient with sjögren's syndrome: a case report.

BACKGROUND: Leptospirosis is a zoonotic disease that afflicts both humans and animals. It progresses from flu-like symptoms to more severe hepatic and renal failure, and may also lead to aseptic meningitis. Individuals with autoimmune diseases (ADs) are potentially more susceptible to Leptospirosis. Thus far, limited data has documented the association between Leptospirosis and autoimmune disorders. CASE PRESENTATION: The patient had a definitive pathological diagnosis of Sjögren's syndrome (SS). Due to recurrent headaches, the patient sought consultation with a neurologist. Lumbar puncture revealed elevated white blood cells and protein levels in the cerebrospinal fluid, along with decreased glucose. Tuberculous meningitis was suspected. Radiographic imaging exhibited meningeal enhancement, ventricular enlargement, and hydrocephalus. The patient commenced treatment with anti-tuberculosis therapy and corticosteroids. Subsequently, high-throughput sequencing (HTS) of cerebrospinal fluid identified the presence of Leptospira interrogans. The patient was ultimately diagnosed with Leptospiral meningitis, and underwent antimicrobial and immunosuppressive therapy, resulting in stabilization of the condition and gradual symptom recovery. CONCLUSIONS: The case highlights the challenges in diagnosing and managing leptospirosis-related meningitis in the presence of ADs and emphasizes the importance of utilizing HTS for accurate pathogen detection. The potential correlation between leptospirosis and SS warrants further investigation, as does the need for multidisciplinary involvement in treatment strategies for such complex cases.

Case Report: Leptospirosis Complicated by Persistent, Bilateral Sensorineural Hearing Loss.

The clinical manifestations of leptospirosis range from mild to life-threatening and can impact on multiple organ systems. A wide array of neurological manifestations of leptospirosis have been reported, although the pathophysiology of neuroleptospirosis remains incompletely understood. We present a case of leptospirosis complicated by bilateral sensorineural deafness, with nodular meningitis demonstrated in the internal auditory meatus on magnetic resonance imaging. The patient was treated with doxycycline, ceftriaxone, systemic and topical steroids, and hyperbaric oxygen therapy, with modest, but incomplete, improvement.

A 16-year-old man with leptospirosis and atypical disseminated intravascular coagulation: a case report.

BACKGROUND: Leptospirosis is known for its pulmonary form characterized by intra-alveolar hemorrhage, exhibiting a high mortality rate. Management by venous-venous extracorporeal membrane oxygenation has been reported in a small number of cases. CASE PRESENTATION: We report herein the case of a 16-year-old Caucasian male who was admitted with rapidly deteriorating respiratory and digestive complaints. He developed severe acute respiratory distress syndrome secondary to disseminated intravascular coagulation and intra-alveolar hemorrhage, requiring initiation of venous-venous extracorporeal membrane oxygenation. Initial infectious and immunological assessments were inconclusive, but repeat serology on the tenth day of admission confirmed a diagnosis of leptospirosis. The patient received multiple transfusions, and upon favorable response to treatment with corticosteroids and antibiotics, he was successfully weaned off venous-venous extracorporeal membrane oxygenation, which was discontinued after 12 days. CONCLUSION: Leptospirosis is a rare cause of severe acute respiratory failure following pulmonary hemorrhage. It is typically diagnosed by serology, with detectable IgM antibodies 5-7 days after the onset of symptoms. We report that early support with respiratory extracorporeal membrane oxygenation favors timely clearance of endobronchial clotting, parenchymal recovery, and prevention of ventilator-induced lung injury. Major hypofibrinogenemia, which did not seem to worsen during extracorporeal membrane oxygenation application, was managed by repeated transfusions. Further studies investigating the pathogenesis of this coagulopathy are required to further optimize the management of this rare and severe complication.

Fatal acute undifferentiated febrile illness among clinically suspected leptospirosis cases in Colombia, 2016-2019.

BACKGROUND: Acute undifferentiated febrile illness is a common challenge for clinicians, especially in tropical and subtropical countries. Incorrect or delayed diagnosis of febrile patients may result in medical complications or preventable deaths. Common causes of acute undifferentiated febrile illness in Colombia include leptospirosis, rickettsioses, dengue fever, malaria, chikungunya, and Zika virus infection. In this study, we described the acute undifferentiated febrile illness in postmortem patients reported as suspected cases of leptospirosis through the national leptospirosis surveillance in Colombia, 2016-2019. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively analyze human fresh and formalin-fixed tissue samples from fatal suspected leptospirosis cases reported by the Public Health Laboratories in Colombia. Leptospirosis confirmation was made by immunohistochemistry, real-time polymerase chain reaction (PCR) in the tissue samples. In some cases, the serum sample was used for confirmation by Microagglutination test (MAT). Simultaneously, tissue samples were tested by PCR for the most common viral (dengue, Zika, and chikungunya), bacterial (Brucella spp., and Rickettsia spp.), and parasitic (malaria). Fresh tissue samples from 92 fatal suspected leptospirosis cases were reported to the National Reference Laboratory from 22/32 departments in Colombia. We confirmed leptospirosis in 27% (25/92) of cases. Other pathogens identified by real-time PCR were Brucella spp. (10.9%), Rickettsia spp. (14.1%), and dengue (2.2%). Dengue (6.9%), hepatitis (3.5%), and Yellow Fever cases (2.2%) were detected by the pathology. All patients were negative for chikungunya and Plasmodium spp. Most cases were classified as undifferentiated febrile illnesses (45.7%; 42/92). CONCLUSIONS/SIGNIFICANCE: This study underscores the importance of early and accurate recognition of leptospirosis to prevent mortalities. Moreover, it draws attention to the existence of other febrile syndromes in Colombia, including rickettsiosis and brucellosis, that currently lack sufficient human surveillance and regular reporting. Expanding laboratory surveillance to include viruses such as Hantavirus, Mayaro virus, Oropouche virus, and West Nile virus is crucial.

Coinfection of Malaria and Bacterial Pathogens among Acute Febrile Patients in Selected Clinics in Ghana.

Malaria remains the leading cause of acute febrile illness (AFI) in Africa despite successful control measures and programs. Acute febrile illnesses can be misdiagnosed as malaria as a result of the overlapping spectrum of nonspecific symptoms or may not be pursued because of limited diagnostic capabilities. This study investigated potential etiologies of AFIs in Ghana and determined the relationship between coinfection between malaria and Q fever, leptospirosis, and culturable bacteria in febrile patients. Participants were enrolled between July 2015 and December 2019 from four Ghanaian military treatment facilities. Of the 399 febrile participants, 222 (55.6%) males and 177 (44.6%) females were enrolled. Malaria was diagnosed in 275 (68.9%) participants. Malaria coinfection occurred with leptospirosis, Q fever, and blood-cultured bacteria in 11/206 (5.3%), 24/206 (11.7%), and 6/164 (3.7%) participants, respectively. Among the 124 malaria-negative samples, the positivity rates were 4.1% (3/74), 8.1% (6/74), and 3.6% (2/56) for leptospirosis, Q fever, and bacterial pathogens isolated from blood culture, respectively. The majority of documented clinical signs and symptoms were not significantly associated with specific diseases. Approximately 10% of malaria-positive participants also had evidence suggesting the presence of a bacterial coinfection. Therefore, even in the case of a positive malaria test, other pathogens contributing to febrile illness should be considered. Understanding the frequency of malaria coinfection and other etiological agents responsible for AFIs will improve diagnosis and treatment and better inform public health knowledge gaps in Ghana.

Clinical characteristics and outcomes of patients with leptospirosis complicated with acute pancreatitis: a systematic review.

OBJECTIVES: Acute pancreatitis (AP) is a severe complication of leptospirosis. This review focuses on the current evidence of AP in patients with leptospirosis. METHODS: Data on clinical characteristics, biochemical parameters, diagnosis, complications, critical care, fluid management, operative management, and outcomes were analyzed. This study was registered in PROSPERO (CRD42022360802). RESULTS: We included 35 individual case reports and 4 case series involving 79 patients. Sex was reported for 48 (60.7%) patients; 38 (48.1%) were male and 10 (12.6%) were female. The patients' mean age was 45.13 (15-83 years). Acute kidney injury, thrombocytopenia, hypotension, and liver injury were the most common complications reported. Complete recovery was reported for 36 (45.5%) patients. Biochemical and radiological recovery was reported for 10 (12.6%) and 9 (11.3%) patients, respectively. Death was reported in 18 (22.7%) patients. CONCLUSION: A high degree of clinical suspicion and different modalities of investigations are essential in the diagnosis of AP in leptospirosis. AP can be easily missed in leptospirosis because both conditions share similar clinical presentations and complications. Because of the high prevalence of acute kidney injury, judicious fluid management and close monitoring are mandatory.

Leptospiral uveitis- "Transition 'from epidemic to endemic form" difficulties in laboratory confirmations.

Purpose: Leptospirosis is a waterborne zoonotic disease that primarily causes systemic illness, followed by uveitis. After heavy flooding in Madurai district, an epidemic outbreak of systemic and ocular leptospirosis occurred in 1994. Our data shows a transition to endemicity after each epidemic. Aim: The aim of this study is to report the clinical signs, epidemic outbreaks, and persistent endemicity of leptospiral uveitis, as well as the diagnostic dilemmas associated with it. Methods: A retrospective analysis of clinical signs was conducted using medical records of leptospiral uveitis patients over a period of 27 years (1994-2020) in a tertiary care eye hospital. The clinical workup of uveitis included a detailed clinical history, systemic, and ophthalmic examination. Microagglutination tests (MATs) was done at the Centers for Disease Control and Prevention (CDC) in Atlanta and later in our regional laboratory. Serum samples were collected from human systemic leptospirosis cases and a small group of animals in and around Madurai. Results: The first epidemic outbreak resulted in 200 seropositive patients. Subsequent epidemic outbreaks occurred in 1997, 1998, 2001, 2005, and 2012, with Madurai experiencing multiple outbreaks. However, the disease remained endemic, with 25-50 patients being observed per year in between the peaks. Ocular examination revealed acute non-granulomatous uveitis (94.9%), pan uveitis (59.8%), vitreous inflammatory reaction (55.4%), retinal vasculitis (29.5%), disc hyperemia (20.9%), and hypopyon. (16.2%). New serovars emerged every year, resulting in decreased sensitivity of the MAT. Over time, the MAT started to miss diagnoses. Conclusion: The persistent endemicity of leptospiral uveitis emphasizes the need for accessible diagnostic tests. The low performance of the MAT can be attributable to the use of an older panel. The incorporation of new isolates in the MAT by a national laboratory will improve the accuracy of diagnosis.

Stillbirth and fulminant postpartum haemolysis: COVID-19 or leptospirosis or both?

We report the case of a female patient with a SARS-CoV-2 infection first diagnosed at 32 2/7 weeks of gestation, resulting in stillbirth at 33 5/7 weeks of gestation. Post partum the patient presented with severe and persistent haemolysis, mild thrombocytopaenia, renal insufficiency and proteinuria as well as elevated liver enzymes and jaundice. Further investigations revealed a positive IgM for Leptospira interrogans and proof of infection by PCR in the urine. The patient was treated with penicillin for 7 days and received a total of 23 units of red blood cells within 11 days. Haemolysis diminished over time and haemoglobin, proteinuria and transaminases normalised within 23 days after delivery. We suppose an acute leptospirosis as underlying cause for the haemolysis, mimicking pregnancy-associated thrombotic microangiopathy. Whether stillbirth was related to leptospirosis or SARS-CoV-2 infection remains unclear.

Identifying risk factors and disease severity in leptospirosis: A meta-analysis of clinical predictors.

Leptospirosis is a bacterial zoonosis with a wide spectrum of clinical presentations. In order to identify potential risk factors and predictors of disease severity, a meta-analysis of the clinical features of severe and non-severe leptospirosis patients was conducted. PubMed was searched to collect studies on the difference in clinical characteristics of severe and nonsevere patients, and data were analyzed using Comprehensive Meta-Analysis V3 software. Results showed that patients with severe outcomes were more likely to have dyspnoea, oliguria, and hemorrhagic symptoms than nonsevere patients. Determining these predictors in the early stages of the disease could thus significantly reduce the development of severe cases and related mortality.

A rare case of severe leptospirosis infection presenting as septic shock in a non-endemic area: a case report and literature review.

BACKGROUND: Leptospirosis is a zoonosis caused by spirochete "genus" leptospira. The clinical presentations of leptospirosis range from an influenza-like presentation of fever and myalgia, to severe forms. Leptospirosis can potentially lead to a misdiagnosis or delay in diagnosis when clinical similarities exist. CASE PRESENTATION: A 63-year-old man presented with fever, shock and thrombocytopenia followed by diffuse pulmonary hemorrhage. Peripheral blood Metagenomic Next-generation Sequencing (mNGS) reported Leptospira interrogans. The patient was treated with piperacillin-tazobactam (TZP) plus doxycycline and improved dramatically after 7 days. CONCLUSION: We conclude that leptospirosis can potentially lead to a misdiagnosis or delay in diagnosis. Correctly evaluation of thrombocytopenia in acute febrile illnesses facilitates the differential diagnosis of leptospirosis. mNGS can accurately detect Leptospira DNA during the early stage of the infection.

Demographic and clinical risk factors associated with severity of lab-confirmed human leptospirosis in Colombia, 2015-2020.

BACKGROUND: Leptospirosis is a common zoonoses and is a major global public health threat. Most cases are mild, typically presenting as a non-specific acute febrile illness. However, leptospirosis can have life-threatening manifestations, including pulmonary hemorrhage syndrome, and acute kidney injury. In Colombia, notification and lab-confirmation of suspected human cases are mandatory. However, little is known about the demographic and clinical factors associated with severe leptospirosis, which could help to reduce clinical complications and mortality. Our aim was to identify risk factors associated with severe leptospirosis, intensive care unit (ICU) admission, and mortality in lab-confirmed cases in Colombia, 2015-2020. METHODS AND FINDINGS: We analyzed 201 lab-confirmed human leptospirosis cases by microagglutination test. We used a logistic regression to identify the demographic and clinical risk factors associated with severe leptospirosis, admission to ICU, and death. Most leptospirosis confirmed cases occurred in men (85.6%); the mean age was 36.7 years. We classified severe cases (43.3%) by clinical manifestations as renal (29.9%) and liver (27.4%) failure, multiple-organ failure (24.4%), septic shock (24.4%), Weil syndrome (18.4%), pulmonary hemorrhage (18.4%), and meningitis (2.5%), admitted to the ICU (30.3%), and fatal (8.5%). Clinical conditions associated with severe leptospirosis were dyspnea (OR: 5.54; 95% CI: 1.46 to 20.98), tachycardia (OR:9.69; 95% CI: 15.96 to 58.8), and rash (OR: 10.25; 95% CI: 25.01 to 42.08). CONCLUSIONS: We identified demographic characteristics and clinical symptoms associated with severe leptospirosis in Colombia. We hope these results can support clinicians in providing timely treatment to leptospirosis patients to avoid preventable medical complications or deaths.

Leptospirosis-Induced Myocarditis and Arrhythmias.

Cardiac manifestations in leptospirosis usually involve atrial arrhythmias, conduction abnormalities, and nonspecific ST-T changes, while left ventricular dysfunction is rare. We present the case of a 45-year-old male without a pre-existing cardiovascular history who developed atrial fibrillation and atrial and ventricular tachycardia, in addition to new-onset cardiomyopathy in the setting of fulminant leptospirosis infection.

Hemoperfusion in Leptospirosis.

Leptospirosis is the most common zoonosis frequently seen in the tropics and subtropics especially during the rainy season when humans wade in floods contaminated by the urine of infected rats in urban areas. Aside from direct toxicity of the leptospires, the role of an exuberant immune response to the pathogen leading to secondary organ damage has been recognized. Thus, our treatment protocol for patients with severe leptospirosis characterized by renal failure, acute liver injury, and lung hemorrhage now includes a short course of methylprednisolone and intravenous cyclophosphamide. In some patients, however, hemodynamic collapse and acute respiratory distress syndrome ensue, which may be due to the release of cytokines resulting from the dysregulated immune response. Blood purification in the form of hemoperfusion (HP) with neutral macroporous resin-adsorbing beads adsorbs cytokines and other inflammatory mediators leading to cardiovascular stability and stabilization of endothelial membranes. HP may be considered part of a multiorgan system therapeutic approach in diseases with reversible multiorgan failure that can lead to an improvement in patient survival.

Transcriptome landscape reveals the chronic inflammatory response in kidneys affected by the combinatory effect of leptospirosis and nephrotoxic injury.

Leptospirosis can cause chronic kidney damage, putting patients at risk of additional kidney injury due to other factors that can lead to renal failure. To understand the combined effect, the transcriptome profiles of kidneys of mice with adenine-induced and chronically Leptospira-infected kidneys were analysed. Chronic inflammation and T-helper 17 immune responses were activated and a high-level expression of Indoleamine 2,3-dioxygenase 1 protein was found. The results indicate that the combination may predispose patients to chronic inflammation, kidney function disruption, and symptoms seen in progressive chronic kidney disease (CKD). Furthermore, immunometabolic regulation may contribute to renal injury caused by chronic leptospirosis with secondary nephrotoxic injury. This study identified several significantly disrupted genes that could serve as potential targets for the diagnosis or treatment of CKD. Our work provides insight into the combined effect of leptospirosis and secondary kidney damage and the molecular basis for rapid progression of CKD.

Incidence of acute pancreatitis among patients with leptospirosis requiring extracorporeal membrane oxygenation (ECMO): a descriptive study.

BACKGROUND: Acute pancreatitis (AP) is an infrequently reported manifestation of leptospirosis. It is more commonly seen in patients with acute respiratory distress syndrome. Despite novel modalities such as extracorporeal membrane oxygenation (ECMO), the mortality rate remains high and whether this is associated with the lung injury caused by the inflammation in AP remains unclear. OBJECTIVES AND METHODS: A descriptive study was conducted at a tertiary hospital in the Philippines. Primary outcome was defined as the presence or absence of AP. Secondary outcomes were defined as 28-day mortality rate, length of hospital stay, ECMO days, renal replacement therapy (RRT) days, days on mechanical ventilation, presence of local complications of AP and development of nosocomial infections. RESULTS: A total of 27 patients were included in the study, and 88.89% (n=24) were men. The mean age for all patients was 33.59±10.22 years. Out of the 27 patients, 19 (70.37%) were diagnosed with AP. Among these 19 patients, one (5.26%) had necrotising pancreatitis and two (10.52%) developed local complications of pancreatitis. Six patients (31.58%) died among those who developed AP, while one (12.50%) died among those who did not. The duration of hospital stay, ECMO, RRT, mechanical ventilation and development of nosocomial infections was also higher in the group who presented with AP. CONCLUSION: AP is an under-reported complication of leptospirosis. Our study demonstrated a higher mortality and morbidity in patients with leptospirosis who developed AP.

Leptospirosis during the COVID-19 pandemic: a case report.

Since SARS-CoV-2 disease (COVID-19) has been labeled as a pandemic, it took the spotlight in the differential diagnosis for patients presenting with acute respiratory and systemic symptoms. Leptospirosis is one of the most common zoonoses in the world, yet it is mainly a disease of differential diagnosis for places that do not have it as an endemic. Due to the high burden of COVID-19 on the healthcare field, patients suffering from other infections may have been inadvertently neglected. COVID-19 infection can mimic other infectious diseases and can confuse physicians in their search for a confirmatory diagnosis. Nonetheless, it is very crucial to broaden the differential diagnosis and keep diseases like leptospirosis within the differential diagnosis despite its rarity, especially in patients presenting with unexplained systemic infectious symptoms. This is a unique case of a patient who presented with dyspnea, jaundice and change in urine color who was suspected to be COVID-19 positive. After a detailed investigation, the patient was diagnosed with leptospirosis instead of COVID-19 and was treated with plasmapheresis and antibiotics accordingly.