Leptospirosis

Leptospirosis is a globally important zoonotic disease that affects humans on all continents, in both urban and rural contexts, and in temperate and tropical climes. Leptospirosis is a disease of the environment; transmission depends on interactions between humans and mammalian reservoir hosts. A variety of infectious diseases that present as undifferentiated febrile syndromes, such as malaria, dengue and influenza, as well as viral hemorrhagic fevers can mimic leptospirosis. The importance of pulmonary hemorrhage as a lethal complication of leptospirosis has become more widely recognized. In contrast to textbook dogma, population-based studies indicate that there is a poor correlation between infecting leptospiral strain and clinical expression of disease. Genetic transformation of a Leptospira sp. has now been reported, which should allow for detailed analysis of a variety of leptospiral genes. Publication of the whole Leptospira genome is eagerly awaited. Following recent reports of a new, highly effective conjugate typhoid vaccine, new efforts to find leptospirosis vaccines should include the manufacture and testing of conjugate leptospiral lipopolysaccharide vaccines. Recent advances, particularly in epidemiology, molecular genetics and pathogenesis, are placing leptospirosis at the cutting edge of biomedical science.     

Leptospirosis in Kamphaeng Phet, Thailand

Leptospirosis, which is caused by pathogenic spirochetes of the genus Leptospira, is a zoonotic disease of global importance and an emerging health problem. We studied patients suspected of having leptospirosis in Kamphaeng Phet Province, Thailand. Of 106 patients with suspected leptospirosis evaluated at the provincial hospital, 69 (65%) were confirmed positive (titer > or = 1:800 or > or = 4-fold increase in titer) by microscopic agglutination testing. Seventy-seven percent (53) of the cases occurred during the rainy season (June through November). Sera reacted predominantly with Bratislava, Autumnalis, and Icterohaemorrhagiae serovars. The screening Leptospira Dip-S-Ticks test had poor sensitivity (32%) but a specificity of 100% compared with a Leptospira IgM enzyme-linked immunosorbent assay. Leptospirosis was found to be a frequently confirmed cause of morbidity in Kamphaeng Phet Province in those suspected of having the illness.     

Three cases of anicteric leptospirosis from Turkey: mild to severe complications

Leptospirosis is an acute generalized infectious disease, caused by spirochaetes, Leptospira interrogans. The severity of the disease ranges from an asymptomatic subclinical course to a fatal outcome. The three cases presented here were diagnosed serologically and had thrombocytopenia and acute renal failure as complication of anicteric leptospirosis. Our first case admitted with clinical presentation of pneumonia but clinical progress and laboratory findings made us to consider leptospirosis. The other two cases presented with aseptic meningitis were diagnosed as anicteric leptospirosis by the serological test results. One of the cases had fatal outcome but could not be strictly correlated with leptospirosis.     

Leptospirosis in the tropics and in travelers

Leptospirosis, caused by spirochetes of the genus Leptospira, has increasingly been recognized to affect travelers and residents in tropical settings. A zoonotic disease, leptospirosis is transmitted to humans through environmental surface waters contaminated by the urine of chronically infected mammals. Outcome of infection varies, ranging from acute febrile illness (including selfresolving undifferentiated fever) to aseptic meningitis to a fulminant syndrome of jaundice, oliguric renal failure, pulmonary hemorrhage, and refractory shock. Hospitalized cases have mortality rates as high as 25%. A recent clinical trial showed that third-generation cephalosporin is as effective as doxycycline and penicillin in the treatment of acute disease. Doxycycline is effective in preventing leptospirosis in travelers. No protective vaccine is currently available.     

Determinants of leptospirosis in Sri Lanka: Study Protocol

Background  

Leptospirosis is becoming a major public health threat in Sri Lanka as well as in other countries. We designed a case control study to determine the factors associated with local transmission of leptospirosis in Sri Lanka, in order to identify major modifiable determinants of leptospirosis. The purpose of this paper is to describe the study protocol in detail prior to the publishing of the study results, so that the readership will be able to understand and interpret the study results effectively.     

Leptospirosis: a zoonotic disease of global importance

In the past decade, leptospirosis has emerged as a globally important infectious disease. It occurs in urban environments of industrialised and developing countries, as well as in rural regions worldwide. Mortality remains significant, related both to delays in diagnosis due to lack of infrastructure and adequate clinical suspicion, and to other poorly understood reasons that may include inherent pathogenicity of some leptospiral strains or genetically determined host immunopathological responses. Pulmonary haemorrhage is recognised increasingly as a major, often lethal, manifestation of leptospirosis, the pathogenesis of which remains unclear. The completion of the genome sequence of Leptospira interrogans serovar lai, and other continuing leptospiral genome sequencing projects, promise to guide future work on the disease. Mainstays of treatment are still tetracyclines and beta-lactam/cephalosporins. No vaccine is available. Prevention is largely dependent on sanitation measures that may be difficult to implement, especially in developing countries.     

What role do coagulation disorders play in the pathogenesis of leptospirosis?

Leptospirosis is a zoonosis of worldwide distribution, spread by the urine of infected animals. It is a major public health problem, especially in developing countries, where circumstances for transmission are most favourable. The clinical picture varies from mild disease to a severe illness with haemostatic derangements and multiorgan failure eventually leading to death. Although the haemorrhagic complications of severe disease are serious, the pathophysiology is scarcely elucidated. The complex mechanisms involved in inflammation-induced coagulation activation are extensively studied in various infectious diseases, i.e. Gram-negative sepsis. Tissue factor-mediated coagulation activation, impairment of anticoagulant and fibrinolytic pathways in close concert with the cytokine network are thought to be important. But for human leptospirosis, data are limited. Because of the growing interest in this field, the impact of leptospirosis, and the availability of new therapeutic strategies, we reviewed the evidence regarding the role of coagulation in leptospirosis and provide suggestions for future research.     

Prevalence and carrier status of leptospirosis in smallholder dairy cattle and peridomestic rodents in Kandy, Sri Lanka

Leptospirosis is an important bacterial zoonotic disease globally and one of the notifiable diseases in Sri Lanka. Other than human leptospirosis, little information is available on leptospirosis in domestic and feral animals in Sri Lanka. Thus, this study attempted to determine the prevalence and carrier status of leptospirosis in smallholder dairy cattle and peridomestic rodents to understand the impact of the disease on public health in Kandy, Sri Lanka. Cattle and rodent samples were collected from the Yatinuwara and Udunuwara divisional secretaries in Kandy. Serum samples were analyzed for the presence of antileptospiral antibodies using microscopic agglutination test. DNA was extracted from cattle urine and rodent kidney tissue samples, in which polymerase chain reaction was carried out to detect the Leptospira flaB gene. The cattle in 19 (38.8%) of the 49 farms harbored antileptospiral antibodies. Out of 113 cattle serum samples, 23 (20.3%) were positive; 17 (73.9%) and 6 (26.1%) reacted with serogroups Sejroe and Hebdomadis, respectively. Out of the 74 rodent samples, 13 (17.5%) were positive; 8 (61.5%) and 4 (30.8%) had reactions to serogroups Javanica and Icterohaemorrhagiae, respectively. Leptospiral DNA was detected in one cattle urine sample and identified as Leptospira interrogans. This study revealed a high prevalence of leptospirosis in cattle and rodents in Kandy. These animals were infected with a wide array of leptospiral serogroups, which are consistent with the research findings observed in humans in Kandy. Overall, serological data indicate that relative to rodents, cattle may be a more significant reservoir for human transmission and a greater source of potential risk to local agricultural communities.     

An outbreak of leptospirosis among Peruvian military recruits

Acute undifferentiated febrile illnesses are common in tropical developing countries but are difficult to diagnose on clinical grounds alone. Leptospirosis is rarely diagnosed, despite evidence that sporadic cases and epidemics continue to occur worldwide. The purpose of this study was to diagnose an outbreak of acute undifferentiated febrile illness among Peruvian military recruits that developed after a training exercise in the high jungle rainforest of Peru. Of 193 military recruits, 78 developed an acute febrile illness with varied manifestations. Of these, 72 were found to have acute leptospirosis by a microscopic agglutination test (MAT). An enzyme-linked immunosorbent assay using Leptospira biflexa antigen was insensitive for the detection of anti-leptospiral IgM antibodies compared with the MAT (20 of 72, 28%). This outbreak of acute undifferentiated febrile illness among Peruvian military recruits was due to leptospirosis. High clinical suspicion, initiation of preventative measures, and performance of appropriate diagnostic testing is warranted in similar settings to identify, treat, and prevent leptospirosis.     

Antimicrobial therapy of leptospirosis

PURPOSE OF REVIEW: Leptospirosis is an important but often overlooked zoonotic disease that can cause significant morbidity and mortality. The optimal antimicrobial treatment for this disease has not been established. This review summarizes the most recent literature pertaining to the use of antimicrobial agents in the treatment of leptospirosis. RECENT FINDINGS: Leptospira are highly susceptible to a wide variety of antimicrobials in vitro. Despite this, it is not clear what the best choice of antimicrobial agents is for human disease. Based on the best available literature, the current choices of treatment for leptospirosis include penicillin, doxycycline, cefotaxime, ceftriaxone and azithromycin. Penicillin has long been considered the treatment of choice. Doxycycline is a reasonable alternative, but concerns exist regarding its use in all patients. Recent trials have demonstrated that cefotaxime and ceftriaxone are also acceptable agents. For a variety of reasons, these may be the preferred agents at this time. Azithromycin appears promising for the treatment of less severe disease. Another option for treating leptospirosis is the fluoroquinolone antimicrobials, although adequate human trials are lacking to fully support their use. SUMMARY: Leptospirosis is an important cause of morbidity and mortality worldwide. Despite this, the optimal treatment is not fully defined.     

Urban Leptospirosis in Africa: A Cross-Sectional Survey of Leptospira Infection in Rodents in the Kibera Urban Settlement,Nairobi, Kenya

Leptospirosis is a widespread but under-reported cause of morbidity and mortality. Global re-emergence of leptospirosis has been associated with the growth of informal urban settlements in which rodents are thought to be important reservoir hosts. Understanding the multi-host epidemiology of leptospirosis is essential to control and prevent disease. A cross-sectional survey of rodents in the Kibera settlement in Nairobi, Kenya was conducted in September–October 2008 to demonstrate the presence of pathogenic leptospires. A real-time quantitative polymerase chain reaction showed that 41 (18.3%) of 224 rodents carried pathogenic leptospires in their kidneys, and sequence data identified Leptospira interrogans and L. kirschneri in this population. Rodents of the genus Mus (37 of 185) were significantly more likely to be positive than those of the genus Rattus (4 of 39; odds ratio = 15.03). Questionnaire data showed frequent contact between humans and rodents in Kibera. This study emphasizes the need to quantify the public health impacts of this neglected disease at this and other urban sites in Africa.     

Molecular characterization of virulent Leptospira interrogans serogroup Icterohaemorrhagiae isolated from Cavia aperea

Leptospirosis is a worldwide zoonotic infection caused by pathogenic Leptospira. Synanthropic rodents are recognized carriers of leptospires; however, the role of wild rodents in the epidemiology of the disease is still incipient. In this work, we describe Leptospira strain isolated from Cavia aperea (Brazilian guinea pig). The isolated strain was characterized by partial rpoB gene sequencing, variable-number tandem-repeats and histopathological analysis. The strain was identified as Leptospira interrogans, serogroup Icterohaemorrhagiae and caused clinical signs of leptospirosis in the hamster model, attesting to its virulence. In conclusion, these findings could be useful for elucidating the epidemiological role of C. aperea in leptospirosis.     

Evaluation of the EIE-IgM-Leptospirose assay for the serodiagnosis of leptospirosis

Access to low-cost, effective diagnosis for leptospirosis is urgently needed in developing countries. The EIE-IgM-Leptospirose, a kit produced for public health laboratories in Brazil, was shown to have a sensitivity of 76% (77 of 102 patients) and 100% (102 of 102 patients) during acute and convalescent-phase leptospirosis, respectively, and a specificity of 93-100% (total healthy and patient control subjects evaluated, 486). These findings indicate that the assay will be useful for diagnosis of this emerging infectious disease in Brazil and other developing countries.     

绵阳市1963～1997年钩端螺旋体病疫情及流行菌株变化分析

本文报告了四川绵阳市 35年钩端螺旋体病 (下称钩体 )疫情及流行菌株情况 ,年平均发病率 4.73/10万 ,年平均死亡率 0 .0 79/10万 ,钩体病的性别、年龄、职业及季节分布与国内报道相一致。35年中发生 5次局部暴发流行 ,4次以黄疽出血型为主 ,一次以七日热型为主。从病人血分离到 49株钩体菌 ,分属七群 10个血清型 ,从动物体内分离到菌株 174株 ,证实啮齿类动物为主要传染源。     

Leptospirosis misdiagnosed as pulmonary-renal syndrome

A case of leptospirosis complicated by diffuse alveolar hemorrhage, acute renal failure, and apparent hemoglobinuria was initially diagnosed and managed as a pulmonary-renal syndrome. However, renal biopsy findings were normal. Leptospirosis may manifest with severe lung injury characterized by diffuse alveolar hemorrhage, acute respiratory distress syndrome, and acute renal failure and be accompanied by high mortality rates. Leptospirosis should be considered in patients with features of pulmonary-renal syndrome, particularly in regions known to be endemic for leptospirosis. A history of potential exposure to Leptospira is an important diagnostic clue, and empiric antimicrobial therapy should be considered.     

绵阳市1963～1997年钩端螺旋体病疫情及流行菌株变化 …

本文报告了四川绵阳市３５年钩端螺旋体病（下称钩体）疫情及流行菌株情况,年平均发病率４．７３／１０万,年平均死亡率０．０７９／１０万,钩体病的性别、年龄、职业及季节分布与国内报道相一致。３５年中发生５次局部暴发流行,４次以黄疸出血型为主,一次以七日热型为主。从病人血分离到４９株钩体菌,分属七群１０个血清型,从动物体内分离到菌株１７４株,证实啮齿类动物为主要传染源。     

Duplex PCR-hybridization based detection of pathogenic Leptospira in environmental water samples obtained from endemic areas in northeast region of Thailand

Leptospirosis, a major health problem worldwide, is known to be endemic in the northeastern part of Thailand with the risk of infection by exposure to pathogenic Leptospira in contaminated aquatic environment. A method based on PCR-hybridization detection of pathogenic Leptospira in water was established. The method included filtration of water sample through membrane filters of two pore sizes, DNA extraction from filters using a guanidine thiocyanate extraction method, a duplex-PCR assay with two primer pairs, and hybridization with a synthetic LipL32 DNA probe. The duplex-PCR allowed detection of two products of 279 bp for LipL32 gene and 430 bp for 16S rRNA gene. In water samples artificially seeded with serovar bratislava, at least 10(3) cells could be analyzed by PCR-agarose gel electrophoresis and 1-10 cells by PCR-Southern blot hybridization. The protocol was applied to the detection of pathogenic Leptospira in environmental waters collected from endemic areas in the northeast region of Thailand. Of 100 water samples analyzed, 23 samples were positive for pathogenic Leptospira with PCR performed with Southern blot hybridization only, but none was detected by PCR-agarose gel-electrophoresis. However, PCR performed with the chemiluminescent LipL32 probe using the Fluorescein ULS labeling facilitated the detection of low numbers of pathogenic Leptospira in water. This method should prove useful for monitoring of pathogenic Leptospira pollution in environmental waters, and has the potential to become a valuable tool to the surveillance of leptospirosis in endemic areas, thus leading to enhanced public health protection.     

Leptospira borgpetersenii from free-living white-eared opossum (Didelphis albiventris): First isolation in Brazil

Leptospirosis is a zoonotic disease that occurs all over the world, caused by bacteria of the genus Leptospira. Marsupial and didelphidae families are considered susceptible to infection caused by a wide range of Leptospira serovars for which they serve as reservoirs. Thirty-three free-living white-eared opossums (Didelphis albiventris) were captured in Southern Brazil and bodily fluids were collected. From the urine samples it was possible to obtain an isolate identified as Leptospira borgpetersenii by rpoB gene sequencing and belonging to serovar Castellonis by Multilocus Variable-Number Tandem-Repeat Analysis. This is the first report of the isolation of Leptospira spp. from the white-eared opossum in Brazil. In addition, the new strain was also virulent in the hamster model of lethal leptospirosis. The microscopic agglutination test (MAT) was used for detecting the presence of antibodies against Leptospira spp. in white-eared opossum, human, cattle and canine sera using a panel of 59 Leptospira strains that included the new isolate. The inclusion of the new strain in the MAT battery increased the MAT sensitivity for canine sera. These findings suggest that the white-eared opossum is an important reservoir of pathogenic Leptospira spp.     

Leptospirosis presenting as ascending progressive leg weakness and complicating with acute pancreatitis

Leptospirosis is a spirochetal bacterial infection of great public health importance. It has a broad spectrum of clinical manifestations which goes from subclinical infection and self-limited anicteric febrile illness (80-90% of all cases) to icteric leptospiropirosis known as Weil's disease. This is a severe disease characterized by hemorrhage, acute renal failure and jaundice. It is uncommon for leptospirosis to present itself as a primary neurological disease. Additionally, acute pancreatitis is an unusual gastrointestinal manifestation. We report a case of leptospirosis presenting as ascending progressive leg weakness and complicating with acute pancreatitis in an adult patient treated at Hospital Universitário, Universidade Federal de Santa Catarina. The diagnosis was confirmed through ELISA-IgM antibody testing positive for leptospirosis. After antibiotic therapy and support treatment for a few weeks, total resolution of severe manifestations was achieved. Rare and unusual presentations of leptospirosis should be kept in mind in relevant epidemiological scenario.     

Rapid serological assays for leptospirosis are of limited value in southern Vietnam

Leptospirosis, although ubiquitous and potentially lethal, is often not diagnosed. The seroprevalence of anti-Leptospira antibodies and the utility of two rapid tests for the serodiagnosis of the disease were studied in Binh Thuan, an area in southern Vietnam with favourable conditions for Leptospira. In an initial survey, blood samples from 44 patients with undifferentiated fever and 83 healthy subjects were each examined for anti- Leptospira antibodies using three tests: an ELISA; a latex card-agglutination test (Dri Dot); and a lateral-flow assay (LeptoTek Lateral Flow). In the ELISA, samples from 35% of the healthy subjects and 40% of the febrile patients were found to have titres of anti- Leptospira IgM of at least 1:80. Only one of the 13 patients checked again, in ELISA, 3 weeks later, showed the marked increase in IgM titre that is indicative of acute leptospirosis. In the initial survey, although the positive results of the lateral-flow assay, applied to whole blood and serum, showed a good agreement with those of the ELISA (kappa = 0.743), the results of the lateral-flow assay were often indeterminate. The card-agglutination test was more specific. The overall agreement between the results of the rapid tests and those of the ELISA was generally poor. When the samples classified as 'indeterminate' in the lateral-flow assay were considered positive, the maximum kappa-value for this assay applied to whole blood was only 0.512. In conclusion, it appears that high seroprevalences of anti- Leptospira IgM and low incidences of acute leptospirosis limit the diagnostic value of the rapid tests that were investigated. The lateral-flow assay is not specific enough. The card-agglutination test is possibly better but, because of the low incidence, its sensitivity could not be evaluated adequately in the present study.