Case Report: Refractory Acute Respiratory Distress Syndrome Supported by Extracorporeal Membrane Oxygenation due to Coinfection with Chlamydia pneumoniae and Leptospirosis in Reunion Island.

Infection with Leptospira spp. is common in Réunion, a tropical island in the Indian Ocean. However, respiratory coinfections between strains of Leptospira spp. and other microorganisms are rarely described. Here, we describe the first reported case of coinfection between Leptospira spp. and Chlamydia pneumoniae, responsible for refractory acute respiratory distress syndrome requiring extracorporeal membrane oxygenation with a favorable outcome. In a case of leptospirosis with severe respiratory illness, testing for respiratory coinfection, especially with atypical pathogens, could explain the seriousness of the clinical condition and lead to specific treatment.

Hematological and Hemostatic Alterations Associated With a Single Extracorporeal Renal Replacement Therapy in Dogs With Acute Kidney Injury Associated Leptospirosis: A Pilot Study.

Extracorporeal renal replacement therapy (ERRT) used in dogs with acute kidney injury (AKI) may be associated with hematological and hemostatic disorders. However, its characteristics are not fully described in dogs. The purpose of this pilot study was to characterize the impact of ERRT on hematological, hemostatic, and thromboelastometric parameters in dogs with AKI. We conducted a prospective observational single cohort study in 10 client-owned dogs with AKI associated leptospirosis undergoing ERRT. Results from the CBC, coagulation tests (prothrombin and activated partial thromboplastin times [aPTT]) and rotational thromboelastometry (TEM; intrinsic TEM [inTEM] and heparinase-based TEM [hepTEM]) were recorded before and after the first ERRT session. Blood abnormalities observed before the ERRT session included thrombocytopenia (10/10), anemia (8/10), leukocytosis (4/10), prolonged aPTT (4/10) and leukopenia (1/10). After ERRT, the platelet count decreased (-25%; P = .012) whereas leukocytes (+15%; P = .046) and aPTT (+24%; P = .006) increased. The clotting time (CT) on inTEM assay and the relative variation of CT based on inTEM and hepTEM profiles increased after the ERRT session (P = .037 and P = .048, respectively). Seven dogs, 2 dogs, and 1 dog were defined as having a normal, hypocoagulable, and hypercoagulable inTEM profile after ERRT, respectively. After ERRT, no hepTEM parameter was significantly different from before treatment. Platelet count, leukocytes, aPTT and CT were altered after the first ERRT session. Beyond the hemostatic abnormalities expected by the use of UFH, thrombocytopenia appears as the only hemostatic change after a single ERRT session in dogs with AKI.

Leptospirosis among Returned Travelers: A GeoSentinel Site Survey and Multicenter Analysis-1997-2016.

Leptospirosis is a potentially fatal emerging zoonosis with worldwide distribution and a broad range of clinical presentations and exposure risks. It typically affects vulnerable populations in (sub)tropical countries but is increasingly reported in travelers as well. Diagnostic methods are cumbersome and require further improvement. Here, we describe leptospirosis among travelers presenting to the GeoSentinel Global Surveillance Network. We performed a descriptive analysis of leptospirosis cases reported in GeoSentinel from January 1997 through December 2016. We included 180 travelers with leptospirosis (mostly male; 74%; mostly tourists; 81%). The most frequent region of infection was Southeast Asia (52%); the most common source countries were Thailand (N = 52), Costa Rica (N = 13), Indonesia, and Laos (N = 11 each). Fifty-nine percent were hospitalized; one fatality was reported. We also distributed a supplemental survey to GeoSentinel sites to assess clinical and diagnostic practices. Of 56 GeoSentinel sites, three-quarters responded to the survey. Leptospirosis was reported to have been most frequently considered in febrile travelers with hepatic and renal abnormalities and a history of freshwater exposure. Serology was the most commonly used diagnostic method, although convalescent samples were reported to have been collected infrequently. Within GeoSentinel, leptospirosis was diagnosed mostly among international tourists and caused serious illness. Clinical suspicion and diagnostic workup among surveyed GeoSentinel clinicians were mainly triggered by a classical presentation and exposure history, possibly resulting in underdiagnosis. Suboptimal usage of available diagnostic methods may have resulted in additional missed, or misdiagnosed, cases.

La importancia de interrogar el trabajo del paciente: a propósito de un caso de leptospirosis / Report of a case of leptospirosis: the importance of asking the patient about workplace factors

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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.

DISEASE COMPLEXITY IN A DECLINING ALASKAN MUSKOX (OVIBOS MOSCHATUS) POPULATION.

The muskox ( Ovibos moschatus ) population inhabiting the eastern North Slope (ENS) of Alaska, US declined dramatically during 1999-2006, whereas populations in western Alaska (WA) were stable or increasing. To understand morbidity and mortality factors contributing to the decline, Alaska Department of Fish and Game conducted pathologic investigations of carcasses from 2005 until 2008. Additionally, archived sera from both ENS and WA muskoxen collected during 1984-92, before the documented beginning of the ENS decline; sera collected during 2000, near the beginning of the decline; and contemporary sera (from live capture-release, adult females) collected during 2006, 2007, and 2008 were analyzed to determine whether prevalence of antibody to potential pathogens differed in the two areas or changed over time. The pathogens investigated were those that were believed could cause lameness or poor reproduction or adversely affect general health. Furthermore, trace mineral levels, hemograms, and gastrointestinal parasites were evaluated in live adult females captured 2006-08. Pathologic investigations identified several comorbid conditions, including predation, polyarthritis caused by or consistent with Chlamydophila spp. infection, hoof lesions, copper deficiency, contagious ecthyma, verminous pneumonia, hepatic lipidosis suggestive of negative energy balance, and bacterial bronchopneumonia due to Trueperella pyogenes and Bibersteinia trehalosi . Pathogens suspected to be newly introduced in the ENS muskox population on the basis of serologic detection include bovine viral diarrhea, respiratory syncytial virus, Chlamydophila spp., Brucella spp., Coxiella burnetii , and Leptospira spp., whereas parainfluenza virus-3 antibody prevalence has increased in the WA population. Although multiple disease syndromes were identified that contributed to mortality and, in combination, likely limited the ENS muskox population, further holistic investigations of disease agents, trace mineral status, and nutritional factors in conjunction with intensive demographic and environmental analyses would provide a better understanding of factors that influence Alaskan muskox populations.

[A Case of Leptospirosis in which the Causative Pathogen was Detected Using Cerebrospinal Fluid PCR Eight Days after Onset].

We report a patient with leptospirosis caused by infection with Leptospira interrogans serovar Rachmati. A 30-year-old Japanese man took part in a survival camp on Iriomote Island, Okinawa, from July 9 to July 15, 2014. During the camp, he swam in the river and kayaked. He developed a high fever and fatigue 7 days after completing his trip and was admitted to our hospital on July 22. On admission, he complained of a posterior cervical pain and a loss of appetite. Laboratory findings revealed granulocytosis, mildly elevated AST and ALT levels, elevated BUN and Cr levels, and a significantly elevated CRP level. No pathogenic bacteria were isolated from blood, urine, or cerebrospinal fluid cultures. We included leptospirosis in the differential diagnosis because of the patient's history of participating in a survival camp on Iriomote Island. Minocycline 200 mg, p.o. showed an excellent efficacy. The Leptospira flagellar gene FlaB was detected using a cerebrospinal fluid PCR. A microscopic agglutination test (MAT) during the convalescent stage demonstrated significant increases in antibodies against L. interrogans serovar Rachmati, confirming the diagnosis of leptospirosis. A medical history including occupation and recent travel history, and an adequate specimen sampling are crucial for the accurate and early diagnosis of leptospirosis.

A first report of leptospirosis after liver transplantation.

Leptospirosis has been rarely reported in solid organ transplant recipients. We report the first case to our knowledge of leptospirosis in a liver transplant recipient who developed jaundice and renal insufficiency. We describe his favorable clinical progression and discuss the possible mechanisms involved in the more benign disease course. We also review the previously published cases of leptospirosis in solid organ transplant recipients. Although this disease does not appear to present any particularities in this context, we highlight the importance of clinical suspicion in this setting, particularly after liver transplantation.

Short-course treatment with ceftriaxone for leptospirosis: a retrospective study in a single center in Eastern France.

Short-course (less than 7 days) antibiotic treatments have been rarely assessed in the management of leptospirosis. We analyzed the charts of patients hospitalized with confirmed and probable leptospirosis in a teaching hospital between 1994 and 2012. Of 89 patients with confirmed or probable leptospirosis, 21 patients (11 confirmed, 10 probable - 14 uncomplicated and 7 severe forms) admitted between 2001 and 2012 received ceftriaxone (1-2 g daily) for less than 7 days. Apyrexia was obtained within 2 days of treatment in all patients and no relapse was observed. These data support the hypothesis that short-course treatments of 3-6 days with ceftriaxone (1-2 g per day) may be an option in the treatment of uncomplicated and severe forms of leptospirosis responding quickly to therapy. This hypothesis deserves being confirmed in further clinical studies.

Duration of immunity of a multivalent (DHPPi/L4R) canine vaccine against four Leptospira serovars.

Despite effective vaccines against common Leptospira serovars, the development of new products with long duration of immunity is still important to protect dogs against leptospirosis. The results from four challenge studies performed one year after vaccination of dogs with a multivalent vaccine containing four Leptospira antigens are reported. Six week old dogs received two vaccinations, three weeks apart, and were challenged 367 days later. Clinical observations were recorded, while blood (culture, biochemistry and haematology), urine (culture) and liver and kidney (culture) samples were collected throughout the study or at necropsy. All control dogs remained seronegative until challenge, when they seroconverted. Antibody titres to Leptospira antigens were seen in vaccinated dogs 21 days after first vaccination and peaked three to six weeks after the second vaccination. Titres decreased in all studies over the following 12 months, until challenge when anamnestic responses were observed. In all studies control dogs demonstrated various abnormal clinical signs, while no vaccinated dogs were affected; differences between groups were only significant following L. bratislava challenge. Analysis of blood cultures showed all control and five of the 24 vaccinated dogs were Leptospira positive after challenge; all studies showed significant differences between treatment groups in mean number of days with positive cultures. Significant differences between vaccinated and control groups in mean number of days with positive urine cultures were also observed, with all non-vaccinated and one vaccinated dog Leptospira positive. The urine culture positive vaccinated dog also gave positive culture from kidney and liver samples. All except one control dog also showed positive Leptospira isolation from kidney or liver, with significant differences between vaccinated and control groups observed. The results demonstrate that administration of a new vaccine to six week old puppies induces immunity which is still effective up to one year later as demonstrated by challenge.

Controle da leptospirose em bovinos de leite com vacina autógena em Santo Antônio do Monte, Minas Gerais / Control of leptospirosis in dairy cattle with autogenous vaccine in Santo Antônio do Monte, MG, Brazil

Um surto de leptospirose foi observado em bovinos leiteiros em Santo Antônio do Monte, Minas Gerais. O rebanho apresentava reações positivas anti-leptospira sorovar Hardjo no teste de microaglutinação (MAT) e havia sido vacinado anteriormente com vacina experimental contendo a sorovariedade Hardjo. O MAT revelou 48,06% dos bovinos positivos para sorovariedade Hardjo genótipo Hardjobovis, 36,82% para sorovariedade Hardjo genótipo Hardjoprajitno. Os animais apresentavam aborto e mastite com presença de sangue no leite. A presente pesquisa teve como objetivos isolar as sorovariedades existentes a partir da urina de vacas sorologicamente positivas, elaborar uma vacina experimental com as sorovariedades isoladas no rebanho, avaliar a eficiência do programa de vacinação por um período de dois anos por meio da sorologia do rebanho. Foi isolada Leptospira spp. a partir da urina de duas vacas com sinais sugestivos da doença. As amostras isoladas foram identificadas pela sorologia com anticorpos monoclonais e seqüenciamento do gene 16S rRNA como pertencentes à espécie Leptospira interrogans, sorogrupo Sejroe, sorovariedade Hardjo e genótipo Hardjoprajitno. O uso da vacina autógena foi eficaz no controle da leptospirose no rebanho no período de dois anos. Os resultados da sorologia revelaram ausência de animais positivos na última prova realizada no rebanho.

An outbreak of leptospirosis in dairy cattle was observed in Santo Antonio do Monte, Minas Gerais. The herd had positive reactions in anti-Leptospira serovar Hardjo agglutination test (MAT) and had been previously vaccinated with a vaccine containing serovars Hardjo. The MAT showed 48.06% of cattle positive for serovars Hardjo genotype Hardjobovis, 36.82% for serovars Hardjo genotype Hardjoprajitno. The animals had abortions and mastitis with blood in the milk. This study aimed to isolate the existing serovars from the urine of serologically positive cows, produce an experimental vaccine with the serovars isolated in the herd, evaluating the effectiveness of the vaccination program for a period of two years through the herd serology. Leptospira spp. was isolated from the urine of two cows with signs suggestive of the disease. The strains were identified by serology with monoclonal antibodies and 16S rRNA gene sequencing as belonging to the Leptospira interrogans species Sejroe serogroup Hardjo serovars and Hardjoprajitno genotype. Use of the autochthonous vaccine was effective in leptospirosis controlling in the herd in two years. The serology results showed the absence of positive animals in the last race held in the herd.

Successful treatment of septic shock and respiratory failure due to leptospirosis and scrub typhus coinfection with penicillin, levofloxacin, and activated protein C.

Leptospirosis and scrub typhus are common zoonoses and coinfection with both diseases has been reported sporadically, particularly in tropical and subtropical areas. A 53-year-old male presented with acute hypoxemic respiratory failure and septic shock due to leptospirosis and scrub typhus coinfection confirmed by serological assessments. Antibiotics, including intravenous penicillin and levofloxacin, were administered and human recombinant activated protein C was added because of a high risk of death due to septic shock with multiple organ failure. The patient's hemodynamics and hypoxemia substantially improved 4 days later and he had a complete recovery from the disease after 10 days of hospitalization. Coinfection of leptospirosis and scrub typhus may easily go unrecognized by physicians in febrile travelers or patients in the region where both diseases are endemic. In severe and critical cases of leptospirosis, scrub typhus, or coinfection with both, the use of APC in addition to appropriate antibiotic treatment and standard critical care might provide a greater chance for survival and a favorable outcome.

2010 ACVIM small animal consensus statement on leptospirosis: diagnosis, epidemiology, treatment, and prevention.

This report offers a consensus opinion on the diagnosis, epidemiology, treatment, and prevention of leptospirosis in dogs, an important zoonosis. Clinical signs of leptospirosis in dogs relate to development of renal disease, hepatic disease, uveitis, and pulmonary hemorrhage. Disease may follow periods of high rainfall, and can occur in dogs roaming in proximity to water sources, farm animals, or wildlife, or dogs residing in suburban environments. Diagnosis is based on acute and convalescent phase antibody titers by the microscopic agglutination test (MAT), with or without use of polymerase chain reaction assays. There is considerable interlaboratory variation in MAT results, and the MAT does not accurately predict the infecting serogroup. The recommended treatment for optimal clearance of the organism from renal tubules is doxycycline, 5 mg/kg p.o. q12h, for 14 days. Annual vaccination can prevent leptospirosis caused by serovars included in the vaccine and is recommended for dogs at risk of infection.

[Leptospirosis in children. Clinico-biological and therapeutic aspects for the cases hospitalised between 1992-2005]. / Leptospiroza la copil. Aspecte clinico-biologice si terapeutice pentru cazurile internate in perioada 1992-2005.

UNLABELLED: The aim of the study is that of showing the prevalence of the disease in childhood in our county. MATERIAL AND METHOD: We studied the observation files of the patients admitted in our unit in between 1992 and 2005 comprised in the 0-15 year old age bracket, noticing all the epidemiological, clinical and therapeutic aspects. RESULTS: In the above mentioned period, 16 patients from the 0-15 year old group (3.12% of all the patients suffering from leptospirosis) were admitted in our clinic. Male (93.75%) and suburban area (60%) were dominant; 11-15 year old group was represented in 87.5% cases; the prevalence was observed during the summer (11 cases) and during 1999 (6 cases); the meningeal signs were noticed in 5 cases and jaundice for 3 children; the most frequent agent was L. icterohaemorrhagiae--7 cases. The etiological treatment was performed for 14 cases with betalactamines for 7.4 days in average; no lethal cases were noticed. CONCLUSIONS: In the case of Iasi County, leptospirosis is a clinico-biological entity considered in the diagnosis of the jaundice, meningeal and febrile syndromes in children.

Severe sepsis due to severe falciparum malaria and leptospirosis co-infection treated with activated protein C.

Co-infection with falciparum malaria and leptospirosis is uncommon. The aim of this study is to report a case of severe sepsis secondary to dual infection with falciparum malaria and leptospirosis. The literature is also reviewed on the clinical course of such co-infections, and the possible mechanisms and treatment of patients with life-threatening malaria and leptospirosis with activated protein C. The patient was a 25-year old male admitted in the Respiratory Intensive Care Unit (RICU) with fever, haemolysis, acute renal failure, hepatitis, acute lung injury (ALI) and altered sensorium. A syndromic evaluation was done and investigations revealed falciparum parasitaemia. He was treated with parenteral artesunate, ceftriaxone and doxycycline, and adjunctive therapies as for severe sepsis. Infusion of activated protein C was started 20 hours after onset of organ dysfunction, and intensive haemodialysis was instituted. Over the next four days the patient became afebrile with progressive resolution of ALI, renal failure and hepatitis. His Leptospira serology (requested as part of the evaluation) was reported positive on day 5. Dual infections are common and under-recognized in the tropics. Failure to treat potential co-infections may lead to poor outcomes. Acute lung injury in falciparum malaria has high mortality rates and therapy as for severe sepsis may improve survival. Adjunctive therapies, including activated protein C, cannot replace source eradication.

Desarrollo de un método para determinar la concentración mínima inhibitoria en cepas de referencias de leptospiras / Development of a method to determine the minimum inhibitory concentration in reference strains from leptospiras

Se desarrolló un método para determinar la concentración mínima inhibitoria para las leptospiras, porque internacionalmente no existe un método estándar para medirla. Se utilizaron cepas de referencia, pertenecientes al complejo patogénico L. interrogans y L. biflexa frente a la penicilina, la ciprofloxacina, el cloranfenicol, la rifampicina, y la tetraciclina. La concentración mínima inhibitoria, fue definida como la menor concentración del antibiótico donde se observó la inhibición de la movilidad bacteriana por examen directo en campo oscuro. Los rangos fluctuaron para la penicilina desde 0,095 hasta 12-52 μg/mL, para la tetraciclina desde 0,156 hasta 3,13 μg/mL, para el cloranfenicol desde 0,08 hasta 12,52 μg/mL, para la rifampicina desde 0,08 μg/mL y hasta 1,56 μg/mL y para la ciprofloxacina desde 0,15 hasta 2,4 μg/mL. Los antibióticos que presentaron los valores más bajos fueron la ciprofloxacina, la rifampicina y la tetraciclina y el valor más elevado se obtuvo frente el cloranfenicol y la penicilina. En esta investigación fueron empleadas las cepas de los serogrupos que circulan más frecuentemente en Cuba. Este estudio permitirá en un futuro cercano, determinar la susceptibilidad antimicrobiana en cepas autóctonas aisladas de pacientes con leptospirosis, al nivel nacional(AU)

Following the course of human leptospirosis: evidence of a critical threshold for the vital prognosis using a quantitative PCR assay.

In order to follow the course of acute human leptospirosis, an ELISA microtiter plate hybridization method was developed for the quantitative determination of Leptospira spp. in biological samples after PCR. The biotin-labelled amplified product (331 bp from the rrs gene) was hybridized with a complementary capture probe covalently linked onto aminated polystyrene wells, and detected using a colorimetric reaction. The mean detection limit was 50 copies per 10 microl. In a prospective study of human leptospirosis cases, we obtained evidence that a density of 10(4) leptospires per ml of blood is a critical threshold for the vital prognosis of the patients. The practicability of the method makes it suitable for use in tropical areas for multicentric studies. Such studies could lead to a better knowledge of the natural history of the human disease. The method is also suitable for experimental evaluation of improved antibiotic treatments for leptospirosis.