Acute kidney injury due to Leptospira interrogans in 4 foals and use of renal replacement therapy with intermittent hemodiafiltration in 1 foal.

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.

Sequel and therapeutic modalities of leptospirosis associated severe pulmonary haemorrhagic syndrome (SPHS); a Sri Lankan experience.

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.

Tropical diseases in the ICU: A syndromic approach to diagnosis and treatment.

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.

Treatment of severe leptospirosis with therapeutic plasma exchange in a pediatric patient.

Ekinci F, Yildizdas RD, Horoz ÖÖ, Alabaz D, Tolunay I, 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.

Leptospirosis: Report from the task force on tropical diseases by the World Federation of Societies of Intensive and Critical Care Medicine.

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.

Efficacy of the Rabbit Polyclonal Anti-leptospira Antibody against Homotype or Heterotype Leptospira Infection in Hamster.

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.

Severe leptospirosis: treatment with intravenous corticosteroids and supportive care.

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.

Rodent-borne hemorrhagic fevers: under-recognized, widely spread and preventable - epidemiology, diagnostics and treatment.

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.

Potential benefits of plasma exchange by apheresis on the treatment of severe Icteric Leptospirosis: case report and literature review.

The role of plasmapheresis on the treatment of Leptospirosis has not been define, although it has already been used with beneficial effects in the reported case mentioned above, where was possible to contribute to the resolution of the toxic effects on the tubular renal cells. This case report show how plasma exchange prevents the multiorganic failure.

Lipotoxicidade na leptospirose humana: aspectos prognósticos e potencial efeito benéfico da administração de albumina / Lipotoxicity in human leptospirosis: prognostics aspects and potential beneficial effect of albumin administration

A leptospirose humana é uma doença infecciosa aguda de amplo espectro clínico e que cursa com alterações metabólicas e dislipidêmicas envolvendo colesterol total e frações, triglicerídeos e ácidos graxos não esterificados (AGNEs). Dentre os mecanismos celulares envolvidos na sua fisiopatologia encontram-se a inibição da enzima Na, K ATPase pela endotoxina GLP e a lipotoxicidade, ambos agravados pela redução dos níveis circulantes da albumina, molécula que exerce um papel fundamental na adsorção de moléculas lipídicas. Neste estudo observacional, determinamos as concentrações séricas de bilirrubina, creatinina e albumina e, pela técnica de cromatografia líquida de alta performance, a concentração sérica dos AGNEs de cadeia longa (C16: C18) de 27 pacientes com síndrome de Weil durante o período de internação hospitalar, dos quais cinco vieram a falecer. Verificamos correlações significantes (p<0,05) ao longo da internação hospitalar, nas concentrações séricas de marcadores bioquímicos de gravidade da doença (bilirrubina, creatinina e albumina), AGNEs, ácido oléico e ácido linoléico, e relação molar ácido oléico/albumina, com r (Pearson) de -0,7981, -0,7699, 0,9014, -0,8795 -0,9816, -0,9694, -0,9821, respectivamente. A relação molar ácido oléico/albumina e ácido oléico+linoléico/albumina foi significantemente mais elevada nos pacientes que faleceram (p<0,001), retornando aos valores semelhantes aos do grupo controle nos pacientes que evoluíram para a cura. Na análise por Curva Roc, a relação molar ácido oléico/albumina se mostrou um bom teste preditivo, com valor de corte 0,705 associado com maior especificidade e sensibilidade prognóstica. Nossos resultados sugerem que a utilização parenteral da albumina humana em pacientes com leptospirose pode ser uma potente ferramenta terapêutica nos casos mais graves ao interferir positivamente no resgate do equilíbrio bioquímico das relações molares ácido oléico/algumina e ácido oléico+linoléico/algumina.

Human leptospirosis is an acute infectious disease with a broad clinical spectrum. It courses with metabolic and dyslipidemic alterations, involving total cholesterol and fractions, triglycerides and nonesterified fatty acids (NEFAs). The cellular mechanisms involved in its pathogenesis include the inhibition of the enzyme sodium-potassium adenosine triphosphatase and lipotoxicity. Both mechanisms are aggravated by the reduction of serum levels of albumin, a molecule that plays a fundamental role in the absorption of lipid molecules. In this observational study, we determined the serum concentrations of bilirubin, creatinine and albumin, and, by High Performance Liquid Chromatography, the serum concentrations of long chain NEFAs (C16: C18) during the period of hospitalization of 27 patients with Weil's syndrome, five of whom progressed to death. Significant correlations were found between the length of hospitalization and serum concentrations of biochemical markers of severity (bilirubin, creatinine, albumin), NEFAs, oleic acid and linoleic acid, and the oleic acid: albumin molar ratio, with r (Pearson) of de -0,7981, -0,7699, 0,09014, -0,8795 -0,9816, -0,9694, -09821 respectively. The oleic acid: albumin molar ratio and oleic-plus-linoleic acid: albumin molar ratio were significantly higher in the patients who progressed to death, whereas in the cured patients this ratio decreased to levels that were similar to those found in the control group. Roc Curve analysis for the acid oleic: albumin molar ratio proved a good predictive test, with value of cutting 0.705 associated with greater specificity and prognostic sensitivity. Our results suggest that parenteral administration of human albumine may interfere positively in the rescue of biochemical balance of oleic acid: albumin molar ratio and oleic-plus-linoleic acid: albumin molar ratio and be a therapeutic tool for severe cases of leptospirosis.

Antagonista de opioides para o tratamento do prurido associado à colestase. Relato de caso / Opiate antagonist therapy for the cholestasis pruritus. Case report

JUSTIFICATIVA E OBJETIVOS: Pacientes com lep­tospirose podem desenvolver colestase, levando à queixa de prurido. Existem vários tratamentos propostos para o prurido, porém nenhum deles é satisfatoriamente efetivo. O objetivo deste artigo foi relatar o emprego de um antagonista opioide para o tratamento de prurido associado à 3 colestase em paciente com leptospirose.RELATO DO CASO: Paciente do sexo masculino, 51 anos, apresentou quadro de leptospirose, referindo dentre 11 as principais queixas prurido intenso. A queixa manteve-se até o quarto dia de internação, quando se optou pelaprescrição de um antagonista opioide, levando à remissão completa do quadro. CONCLUSÃO: O sucesso da terapia no caso apresentado soma-se a outros relatos da literatura que demonstram evidências de que os antagonistas opioides são bem tolerados e rêduzem significativamente o prurido associado à colestase.

In LipL32, the major leptospiral lipoprotein, the C terminus is the primary immunogenic domain and mediates interaction with collagen IV and plasma fibronectin

LipL32 is the major leptospiral outer membrane lipoprotein expressed during infection and is the immunodominant antigen recognized during the humoral immune response to leptospirosis in humans. In this study, we investigated novel aspects of LipL32. In order to define the immunodominant domains(s) of the molecule, subfragments corresponding to the N-terminal, intermediate, and C-terminal portions of the LipL32 gene were cloned and the proteins were expressed and purified by metal affinity chromatography. Our immunoblot results indicate that the C-terminal and intermediate domains of LipL32 are recognized by sera of patients with laboratory-confirmed leptospirosis. An immunoglobulin M response was detected exclusively against the LipL32 C-terminal fragment in both the acute and convalescent phases of illness. We also evaluated the capacity of LipL32 to interact with extracellular matrix (ECM) components. Dose-dependent, specific binding of LipL32 to collagen type IV and plasma fibronectin was observed, and the binding capacity could be attributed to the C-terminal portion of this molecule. Both heparin and gelatin could inhibit LipL32 binding to fibronectin in a concentration-dependent manner, indicating that the 30-kDa heparin-binding and 45-kDa gelatin-binding domains of fibronectin are involved in this interaction. Taken together, our results provide evidence that the LipL32 C terminus is recognized early in the course of infection and is the domain responsible for mediating interaction with ECM proteins.

Fiebre amarilla: la enfermedad recurrente: a propósito de un caso / Yellow fever: the recurrent disease: a purpose of a case

La fiebre amarilla es una enfermedad infecciosa producida por arbovirus que origina compromisos hepático, hemorrágico y renal, frecuentemente fatales. Tiene dos patrones de transmisión, el urbano, generalmente epidémico y el selvático de presentación esporádica o pequeños brotes. Esta enfermedad es una de las grandes plagas de la historia de la humanidad; durante siglos azotó a los habitantes y colonizadores del Africa y la América tropical. A mediados de este siglo la enfermedad disminuyó su incidencia con las campañas de erradiación del vector y la introducción de la vacunación en 1934. Actualmente se informan entre 1000 y 3000 casos anuales, un 10 por ciento de los cuales tiene lugar en Centro y Sudamérica. No existen antivirales efectivos disponibles para esta enfermedad. La fiebre amarilla es difícil de identificar durante las etapas tempranas, ya que puede confundirse fácilmente con malaria, fiebre tifoidea, fiebre viral hemorrágica, leptospirosis y hepatitis viral. El tratamiento es sintomático y de sostén. La fiebre amarilla puede prevenirse con la vacunación. El caso que se presenta a continuación es un paciente masculino de 19 años que consulta por presentar fiebre, evacuaciones líquidas, cefalea y epistaxis, teniendo antecedentes apidemiológicos y familiares importantes, el cual fue tratado desde el comienzo de su ingreso como un Síndrome Icterohemorrágico, al no tener un diagnóstico bien establecido, el cual se obtuvo al egresado el paciente mediante resultados serológicos positivos para fiebre amarilla (1,2).

Experiencia en el tratamiento de la leptospirosis / Experience in the leptospirosis treatment

Se realizó un estudio descriptivo longitudinal retrospectivo de los pacientes confirmados con leptospirosis en el período comprendido entre 1994-1995 en el Hospital General Docente “Aleida Fernández Chardiet” de Güines. Se observó que el 84,3 porciento de las pacientes ingresados evolucionaron satisfactoriamente a la terapéutica con penicilina, el tratamiento alternativo con tetraciclina ocupo el segundo lugar, seguido por la estreptomicina, que se utilizó en pacientes alérgicos a la penicilina y a la tetraciclina o con insuficiencia hepática, siendo el resultado satisfactorio, sugiriendo el uso de la estreptomicina como tratamiento alternativo en esta enfermedad. La morbilidad fue de un 5 porciento. La causa de los fallecidos fue por el síndrome de Weil, confirmados por necropsia. Se encontró un promedio de estadía de cuatro días disminuyendo los costos hospitalarios, se demostró la importancia del diagnóstico y tratamiento precoz de esta enfermedad en los cuatro días de la aparición de los síntomas y signos, ya que esto disminuye las posibilidades de complicaciones (AU)

[The clinical use of blood ultrafiltration in leptospirosis patients with acute kidney and liver failure]. / Klinicheskoe primenenie ul'trafil'tratsii krovi u bol'nykh leptospirozom s ostroi nedostatochnost'iu pochek i pecheni.

The use of ultrafiltration of blood in clinical settings in the treatment of patients with leptospirosis presenting with acute renal failure permits enhancing a detoxicating effect due to elimination with the ultrafiltrate of up to 30% of products of nitrogenous metabolism. This allows the water balance to be corrected, homeostasis, the functional activity of the cardiovascular, respiratory systems to be stabilized. Therapeutic effectiveness is enhanced that is evidenced by a 20% decline in the incidence of complications and in case-fatality rate in grave forms of leptospirosis.

Treatment and outcome of dogs with leptospirosis: 36 cases (1990-1998).

OBJECTIVE: To characterize serologic and clinical features and outcome of dogs with leptospirosis that were treated conservatively (i.e., medical management alone) or with hemodialysis. DESIGN: Retrospective study. ANIMALS: 36 dogs with leptospirosis. PROCEDURE: History; results of physical examinations, ultrasonography, and serologic, hematologic, and serum biochemical analyses; time to resolution of azotemia; and outcome were obtained from medical records. Dogs were treated conservatively (n = 22) or with hemodialysis (14). RESULTS: Between 1990 and 1998, amount of rainfall was positively correlated with number of cases of leptospirosis identified per year. Serum antibodies against 6 Leptospira serovars were measured, and titers were highest to Leptospira pomona in 16 (44%) dogs, L bratislava in 9 (25%) dogs, and L hardjo in 1 (3%) dog. Eight (22%) dogs had equally high titers to L pomona and L bratislava, 1 (3%) had equally high titers to L grippotyphosa and L canicola, and 1 (3%) had high titers to L grippotyphosa, L pomona, L canicola, and L bratislava. During initial evaluation, all dogs were azotemic. Thirty (83%) dogs survived, including 12 of 14 (86%) dogs treated with hemodialysis and 18 of 22 (82%) treated conservatively. Serum creatinine concentration was similar in both groups after resolution of clinical signs. CONCLUSIONS AND CLINICAL RELEVANCE: Infection with L pomona and L bratislava was recognized as a cause of leptospirosis in dogs, and resulted in development of acute renal failure with various degrees of azotemia. Prognosis for dogs with mild to moderate azotemia was good with conservative treatment, whereas treatment with hemodialysis appeared to improve prognosis for dogs with severe azotemia.

Diagnosis and treatment of leptospirosis in the primary care setting.

Leptospirosis is an infectious illness that usually develops 1 to 2 weeks after indirect or direct exposure to the urine of infected animals. Infection occurs through open cuts, absorption through intact mucous membranes, and drinking contaminated water. The typical presentation is a flulike syndrome of sudden onset that tends to resolve within 2 weeks. A mild immunologic phase usually presents as an aseptic meningitis. A more severe immunologic phase (Well's syndrome) can result in jaundice, renal failure, adult respiratory distress syndrome, disseminated intravascular coagulation, and death. Laboratory tests take too long to replace clinical diagnosis, which is imperative so that antibiotic therapy can begin before the fourth day of illness. Although leptospirosis is more common in tropical climates, detection in the continental United States is increasing. Early, accurate detection and treatment in the primary care setting are vital for limiting life-threatening complications.