Leptospirosis in Franche-Comté (FRANCE): clinical, biological, and therapeutic data.

OBJECTIVES AND METHOD: We report the patient data in 77 cases of leptospirosis confirmed by PCR and/or serology (micro-agglutination), observed between 1994 and 2008 at the Besançon teaching hospital. Our aim was to compare the epidemiological, clinical, biological, and therapeutic characteristics of leptospirosis in the Franche-Comté region, to those reported in other regions. RESULTS: The median age was 42years and 95% were male patients. Leptospirosis acquisition was likely related to aquatic leisure activities (50.6%), professional exposure (28.6%), building maintenance works (11.7%), or unknown (9.1%). Forty-eight cases were uncomplicated and 29 were severe presentations of leptospirosis. Among severe cases, eight patients had to be managed in an intensive care unit, and one patient died. L. grippotyphosa and L. icterohaemorrhagiae were the main serogroups involved. Age above 50years and serogroup L. icterohaemorrhagiae were positively associated with clinical severity. The outcome was favorable for 15 patients treated with ceftriaxone for less than 7days. CONCLUSIONS: We recommended conducting clinical trials aiming at validating short courses of ceftriaxone to treat leptospirosis.

O uso da talidomida como terapia adjuvante na leptospirose experimental / The use of thalidomide as adjuvant therapy in experimental leptospirosis

A leptospirose é uma zoonose de importância global, causada por leptospiras patogênicas. Seu tratamento é limitado quando iniciado após quatro dias do surgimento de sintomas, portanto, novas terapias adjuvantes são necessárias. Objetivo. Testar a droga imunomoduladora talidomida como terapia adjuvante à ampicilina no modelo de tratamento tardio da leptospirose experimental em hamsters. Métodos. 60 hamsters foram infectados via intraperitoneal por Leptospirainterrogans cepa L1-130, e foram separados em grupos: nenhum tratamento (NONE), talidomida (TAL), ampicilina (AMP) e ambos (AMP-TAL)...

Leptospirosis is a zoonosis of global importance, caused by pathogenic leptospira. His treatment is limited when started after four days of onset of symptoms, increasing the risk of morbidity and mortality, so new adjuvant therapies are needed.Objectives.To test the immunomodulatory drug, thalidomide, as an adjuvant therapy to antibiotics in experimental leptospirosis. Methods. Hamsters were infected by Leptospirainterrogans strain L1-130, and groups were assigned based on no treatment (NONE), thalidomide only (TAL), ampicillin only (AMP) or both (AMP-TAL). Thalidomide was administered via a gastric tube: 50 mg/kg in linseed oil and 2 ml/kg for three days. Ampicillin was administered intramuscularly at the rate of 100 mg/kg/bid for six days. Treatment was started two days after the onset of symptoms (experiment 1) and immediately after detection of the first death (experiment 2). Results. Experiment 1: all hamsters from the groups AMP and AMP-TAL...

Detecção de Espécies Reativas de Oxigênio no sangue periférico de pacientes com leptospirose grave / Detection of Reactive Oxygen Species in peripheral blood patients with severe leptospirosis

Leptospirose é uma zoonose que pode levar a graves complicações, como a síndrome de Weil e a síndrome pulmonar hemorrágica, porém os mecanismos patogênicos que levam ao desenvolvimento das formas graves da doença ainda são desconhecidos. Após a penetração no indivíduo, as leptospiras invadem a corrente sanguínea e se disseminam para os órgãos. Dessa forma, a leptospirose apresenta características semelhantes as da sepse, doença que tem o estresse oxidativo como um dos principais responsáveis pelo seu agravamento. Entretanto, pouco se sabe sobre o envolvimento do estresse oxidativo na leptospirose. O presente estudo teve como objetivo avaliar se a produção de espécies reativas de oxigênio (ROS) e os níveis do antioxidante glutationa (GSH) estão relacionados com as manifestações clínicas mais graves de pacientes hospitalizados com leptospirose. A produção de ROS e os níveis de GSH foram avaliados nas amostras de sangue de doze pacientes e nove indivíduos saudáveis através dos ensaios de quimioluminescência e de absorbância, respectivamente. Nós observamos que os níveis de ROS estavam aumentados (p=0.0012) e os de GSH diminuídos (p=0.0002) nos pacientes quando comparados com os indivíduos saudáveis. Dentre os pacientes, a diminuição de GSH estava correlacionada com a trombocitopenia (r=0.63) e com elevados níveis de creatinina (r= -0.64), enquanto que a produção de ROS estava fortemente correlacionada com os níveis elevados de potássio sérico (r=0.8). A compreensão da importância biológica de ROS e do GSH na leptospirose faz-se necessária, pois uma investigação mais detalhada pode levar ao desenvolvimento de terapias adjuvantes focadas no estresse oxidativo.

Leptospirosis is a zoonotic disease that causes severe manifestations such as Weil’s disease and pulmonary hemorrhage syndrome, however the underlying mechanisms that lead to the development of severe forms are not clear. Leptospires penetrate through skin, reach the bloodstream and disseminate to the organs. Thus, leptospirosis and sepsis have similar characteristics. Although there is vast literature demonstrating that oxidative stress play an important role in the severity of sepsis, none is known about it in leptospirosis. The aim of this study was to evaluate whether reactive oxygen species (ROS) production and antioxidant reduced glutathione (GSH) levels are related to complications in patients hospitalized with leptospirosis. ROS production and GSH levels were measured in blood samples of twelve patients and nine healthy controls using chemiluminescence and absorbance assays. We found that ROS production was higher (p=0.0012) and GSH levels were lower (p=0.0002) in leptospirosis patients compared with healthy individuals. Among patients, GSH depletion was correlated with thrombocytopenia (r=0.63) and elevated serum creatinine (r= -0.64), while a strong positive correlation was observed between ROS production and elevated serum potassium (r=0.8). Additional investigation of the biological significance of ROS production and GSH levels is warranted as they may guide the development of novel adjuvant therapies for leptospirosis targeting oxidative stress.

Leptospirosis.

Leptospirosis has recently been classified as an emerging disease because of large clusters of cases resulting from exposure during recreational activities and natural disasters. In addition to their involvement in the prevention, diagnosis, and treatment of leptospirosis in animals, veterinarians serve an important role in public health by providing guidance and information on risk factors and prevention and control measures.

Prevention and treatment of leptospirosis.

Leptospirosis is a common zoonosis acquired by exposure to body fluids, to tissues of infected animals, or to contaminated soil or fresh water. Large outbreaks of leptospirosis have occurred following excess rainfall or in tourists following exposure to fresh water during adventure activities. Prevention may be achieved through the use of protective clothing or by changes in animal husbandry. Immunization is not widely used in human populations but has a role in agriculture. Oral administration of doxycycline (Periostat , CollaGenex) once-weekly can give short-term protection in high-risk environments. The disease in humans has a broad range of symptoms. Treatment may be symptomatic or may require administration of antibiotics, such as doxycycline or penicillin.