The management of leptospirosis

How to quickly identify patients who should be treated for leptospirosis is a challenge. The interest of polymerase chain reaction (PCR) assays is currently being evaluated and rapid tests which can be used outside of the specialised laboratory, have recently been developed. Leptospires are sensitive to many antibiotics and few clinical studies have been made to compare different treatment options. Doxycycline is standard therapy in early leptospirosis treatment and chemoprophylaxis. Intravenous penicillin has been considered the drug of choice in late and severe disease, although it is now challenged by ceftriaxone, which use is easier. Ciprofloxacin may be combined with standard therapy in uveitis. Adjunctive therapies proposed in the management of severe forms of leptospirosis and Jarisch–Herxheimer reactions, are reviewed.     

重组钩端螺旋体病DNA疫苗pVAX1/LipL21-LipL32诱导免疫应答反应的研究（英文）

目的选取致病性钩端螺旋体(简称钩体)中高度保守,同时是钩体外膜蛋白中含量最多的两个脂蛋白LipL32和LipL21构建成融合基因DNA疫苗pVAX1/LipL21-LipL32 ,观察在BALB/c小鼠中重组DNA疫苗诱导免疫应答反应的能力。方法采用连接引物PCR构建融合基因LipL21-LipL32 ,并将其插入真核表达载体构成重组DNA疫苗pVAX1/Li-pL21-LipL32 ,脂质体转染人胚肾细胞( HEK293细胞)后Western Blot验证重组DNA疫苗在真核细胞中的表达,并将其肌注BALB/c小鼠,用显微凝集试验( MAT)检测所产生的特异性抗体与问号钩体的凝集效价,用IL-10和TNF-β细胞因子试剂盒检测体液免疫和细胞免疫应答水平。结果 Western Blot分析显示重组DNA疫苗pVAX1/LipL21-LipL32在HEK293细胞中得到表达,小鼠动物实验结果显示重组DNA疫苗能有效地诱导机体的体液免疫和细胞免疫应答。结论成功构建钩体融合基因LipL21-LipL32重组DNA疫苗,所表达的融合蛋白能诱导特异的免疫应答反应,为进一步研究和发展新型的钩体病疫苗提供了实验基础。     

New Hypothesis for Cause of Epidemic among Native Americans, New England, 1616�C1619

In the years before English settlers established the Plymouth colony (1616–1619), most Native Americans living on the southeastern coast of present-day Massachusetts died from a mysterious disease. Classic explanations have included yellow fever, smallpox, and plague. Chickenpox and trichinosis are among more recent proposals. We suggest an additional candidate: leptospirosis complicated by Weil syndrome. Rodent reservoirs from European ships infected indigenous reservoirs and contaminated land and fresh water. Local ecology and high-risk quotidian practices of the native population favored exposure and were not shared by Europeans. Reduction of the population may have been incremental, episodic, and continuous; local customs continuously exposed this population to hyperendemic leptospiral infection over months or years, and only a fraction survived. Previous proposals do not adequately account for signature signs (epistaxis, jaundice) and do not consider customs that may have been instrumental to the near annihilation of Native Americans, which facilitated successful colonization of the Massachusetts Bay area.     

Antimicrobial Susceptibility of Leptospira spp. Isolated from Environmental,Human and Animal Sources in Malaysia

Leptospirosis is a zoonosis with worldwide distribution caused by pathogenic spirochetes of the genus Leptospira. The aim of this study was to evaluate the susceptibility of isolates obtained from different hosts. A total of 65 Leptospira isolates from humans (n = 1), zoonoses (rat, n = 60; dog, n = 1; swine, n = 1) and environment (n = 2) were tested against six antibiotics. All the isolates were resistant to trimethoprim and sulphamethoxazole and had high MIC toward chloramphenicol (MIC₉₀: 6.25 μg/ml). All except one environment isolate were sensitive to ampicillin, doxycycline and penicillin G.     

Coagulation disorders in patients with severe leptospirosis are associated with severe bleeding and mortality

Objective To determine the involvement of coagulation in bleeding and poor outcome in patients with severe leptospirosis. Methods In a prospective study, parameters of the coagulation system were measured on admission and during follow‐up in 52 consecutive patients with severe leptospirosis. Results All patients showed coagulation disorders, such as prolonged prothrombin time (PT) and activated partial thromboplastin time, marked procoagulant activity [thrombin–antithrombin (TAT) complexes, prothrombin fragment 1+2, D‐dimer], reduced levels of anticoagulant markers (protein C, antithrombin) and increased (anti‐) fibrinolytic activity [plasmin–antiplasmin (PAP) complexes, plasminogen activator inhibitor‐1]. These disorders were more pronounced in patients who died eventually. PT prolongation was associated with mortality (OR 1.4, 95% CI: 1.0–1.8, P = 0.04). Bleeding occurred in 31 subjects (60%). Of these, 24 had mild bleeding and seven had severe haemorrhages. Thrombocytopenia (platelets ≤100 × 10⁹/l) was significantly associated with clinical bleeding (OR 4.6, 95% CI: 1.3–16). A subanalysis of patients with and without severe bleeding revealed a more pronounced imbalance of the coagulation system in patients with severe bleeding, as reflected by a significant association with PT (OR 1.4, 95% CI: 1.0–1.8, P = 0.05) and the TAT/PAP ratio (OR 1.3, 95% CI: 1.0–1.6, P = 0.05), which is an indicator of the balance between coagulation and fibrinolysis. Overt disseminated intravascular coagulation (DIC) was found in 10 (22%) of the 46 patients for whom the score could be calculated. There was no significant association between DIC scores, bleeding diathesis or poor outcome. Conclusion The coagulation system was strongly activated in patients with leptospirosis. This was more pronounced in the deceased and in patients with severe bleeding than in than the survivors and in those without severe bleeding.     

A retrospective 5-year study in Moldova of acute renal failure due to leptospirosis: 58 cases and a review of the literature.

BACKGROUND: Renal involvement [as acute renal failure (ARF)] is a prominent feature of both mild and severe leptospirosis-a re-emerging infectious disease. Few large series describe in detail clinical and laboratory features of cases with ARF and their outcome. METHODS: We performed a retrospective analysis (1997-2001) of all consecutive, serological confirmed leptospirosis cases with ARF (n=58, 53 male, age 44+/-13 years, rural residents=31%, animal contact=88%. RESULTS: Clinical manifestations (>50% prevalence): oliguria 95%, fever and jaundice 93%, nausea and vomiting 83%, haemorrhagic diathesis 80%, headache, hepatomegaly 76%, myalgias, abdominal pain 70%, hypotension 62%, disturbed consciousness 50%. A pattern of multiple organ failure (MOF) was frequent: ARF together with hepatic failure in 72%, respiratory failure in 38%, circulatory failure in 33%, pancreatitis in 25% and rhabdomyolysis in 5% of cases. Renal dysfunction: 35% of cases had a renal K(+)-wasting defect and 43% a FE(Na)(+)>1% and low-osmolarity urine despite volume depletion. Haematuria was encountered in 12 and mild proteinuria in 10 subjects. Outcome: 26% deaths, 64% normal hepatic and renal function at 90 days from presentation (however 29% maintained the initial tubular defect), 10% persistent mild renal failure. All deceased patients had, beside ARF, at least two other organ failures, affected consciousness, and haemorrhagic diathesis vs a prevalence for the above features of only 34, 33, and 72%, respectively, in the survivors group (P<0.05). CONCLUSIONS: Leptospirosis presenting with ARF is a severe disease, frequently leading to MOF and to death in one-third of the patients. In particular, the haemorrhagic diathesis and cerebral involvement are markers for unfavourable patient and renal outcomes.     

Leptospirosis in Germany, 1962-2003

Epidemiologic trends of human leptospirosis in Germany were investigated by analyzing national surveillance data from 1962 to 2003 and by conducting a questionnaire-based survey from 1997 to 2000. After a steady decrease of leptospirosis incidence from 1962 to 1997, surveillance data indicate an increase in disease incidence to 0.06 per 100,000 (1998-2003). Of 102 laboratory-confirmed cases in humans from 1997 to 2000, 30% were related to occupational exposures. Recreational exposures were reported in 30% (including traveling abroad in 16%), whereas residential exposure accounted for 37% of the cases. Direct contact with animals, mostly rats and dogs, was observed in 31% of the cases. We conclude that recent changes in transmission patterns of leptospirosis, partially caused by an expanding rat population and the resurgence of canine leptospirosis, may facilitate the spread of the disease in temperate countries like Germany. Preventive measures should be adapted to the changing epidemiology of leptospirosis.     

flaB-PCR在钩端螺旋体病检测中应用

目的 探讨flaB-PCR对组织标本中钩端螺旋体检测的可行性，为钩端螺旋体流行病学调查提供一种快速、有效的技术手段。方法 根据黄疸出血型钩体赖株高度保守序列flaB设计一对引物，用PCR方法对实验动物标本及疫区动物标本中的钩端螺旋体DNA进行flaB基因片断扩增，扩增产物用琼脂糖凝胶电泳进行检测。结果 该引物可特异性扩增钩端螺旋体DNA，而对本实验所用其它细菌均不扩增。肾组织中含10条钩端螺旋体经flaB-PCR扩增后，琼脂糖凝胶电泳可以目测到扩增产物。26份人工感染钩端螺旋体的动物脏器标本，flaB-PCR扩增阳性10份，阳性率38．46％；细菌分离阳性2份，阳性率7．69％。2种方法比较差异有统计学意义（X^2=6．93，P〈0．01）。疫区70份蛙肾标本。分离细菌8株，阳性检出率11．43％；flaB-PCR扩增产物琼脂糖凝胶电泳阳性14份，阳性检出率20％。细菌分离阳性的标本flaB-PCR均为阳性。结论 flaB-PCR灵敏、特异、快速，是钩端螺旋体检测的有效方法，可用于钩体病疫情监测和流行病学调查。