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Clinical presentation of leptospirosis: a retrospective study of 34 patients admitted to a single institution in metropolitan France.

Leptospirosis has a highly variable clinical presentation, which may be related to different infecting serovars, host factors, or a combination of these. This study investigated retrospectively 34 consecutive patients with serologically confirmed leptospirosis admitted during the period 1992-2002. On admission, the most frequent symptoms were fever (100%), headache (75%), myalgia (55%), arthralgia (45%) and vomiting (39%). Pertinent laboratory findings included lymphopenia (85%), thrombocytopenia (75%), elevated liver enzymes (87%) and renal abnormalities (proteinuria, 77%; haematuria, 58%; elevated serum creatinine, 53%). The study confirmed the variable clinical and biological symptoms of leptospirosis, and indicated that lymphopenia is a common feature of leptospirosis cases.

Adolescent↗

Severe pulmonary haemorrhage accompanying hepatorenal failure in fulminant leptospirosis.

Leptospirosis is a re-emerging spirochetal zoonosis with a worldwide distribution affecting both animals and humans. The clinical syndromes may vary from a subclinical infection to a severe illness. Although it may potentially have a fulminant and fatal course, leptospirosis usually remains as an underdiagnosed cause of multiorgan failure. In this study, we report a patient with leptospirosis who presented with a fulminant course of diffuse alveolar haemorrhage and hepatorenal failure. His clinical condition deteriorated, despite appropriate antibiotic therapy and haemodialysis. However, he showed prompt clinical improvement when corticosteroids and plasma exchange were instituted in addition to the original therapy. We conclude that leptospirosis should be considered in any case presenting with pulmonary haemorrhage and hepatorenal failure. Plasma exchange and corticosteroids may be a choice of treatment in selected patients unresponsive to conventional therapy. Potential benefits of plasma exchange and corticosteroids may be based on a toxin- and/or cytokine-mediated pathogenesis of the disease.

Adult↗

Two methods for rapid serological diagnosis of acute leptospirosis.

Leptospirosis is a common and underdiagnosed zoonosis. Two rapid assays for serological diagnosis of acute leptospirosis in diagnostic laboratories, the immunoglobulin M (IgM)-dipstick assay and the indirect hemagglutination assay (IHA), were evaluated and compared with standard assays. Sera were examined from 104 patients admitted to a hospital for investigation in a leptospirosis diagnostic protocol. Specimens for serology were taken on days 1 and 4 of the patients' hospital stay. Antibodies were detected using an IgM-enzyme-linked immunosorbent assay (ELISA), microscopic agglutination test (MAT), an IgM-dipstick assay, and an IHA. Fifty-one patients were found to have leptospirosis. The sensitivity of the IgM-dipstick assay was 98%, its specificity was 90.6%, its positive predictive value was 90.9%, and its negative predictive value was 98%. The sensitivity of the IHA was 92.2%, its specificity was 94.4%, its positive predictive value was 95.9%, and its negative predictive value was 92.7%. The standard IgM-ELISA and MAT, were positive in the first samples tested from 67 and 55% of the cases, respectively, and the rapid IgM-dipstick assay and IHA were positive in 71 and 49%, respectively, in the first sample tested. Both rapid assays are highly sensitive and specific. Neither requires specialized equipment, and both are suitable for use in diagnostic laboratories.

Acute Disease↗

Application of multilocus variable-number tandem-repeat analysis for molecular typing of the agent of leptospirosis.

Leptospirosis is a worldwide-distributed zoonosis, endemic in tropical areas. Epidemiologic investigations of leptospirosis still rely on tedious serological identification tests. Recently, molecular typing systems based on variable-number tandem-repeat (VNTR) analysis have been described and have been used to identify Leptospira interrogans strains. Although L. interrogans is the most common Leptospira species encountered in human infections around the world, other pathogenic species, such as Leptospira kirschneri and Leptospira borgpetersenii, are also frequently associated with human leptospirosis. In this study, we aimed to extend multilocus VNTR analysis (MLVA) identification of strains to species other than L. interrogans. We designed primers for VNTR loci found in L. interrogans, L. kirschneri, and L. borgpetersenii. The discriminatory power of the redefined primers was evaluated on collection strains and then on clinical strains. We also carried out a retrospective study on 156 strains isolated from patients and animals from New Caledonia, an area of high endemicity in the South Pacific. Our results show that this simple PCR-based MLVA typing technique is a powerful methodology for the epidemiology of leptospirosis.

Animals↗

Macroscopic agglutination test for rapid diagnosis of human leptospirosis.

A commercially available slide agglutination test (SAT) for the diagnosis of human leptospirosis was evaluated by comparing it to an immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA) and to the microscopic agglutination test (MAT). For all 108 patients, leptospirosis was diagnosed on the basis of a fourfold or greater increase in titer by MAT (seroconversion), and all but 1 of 245 controls were MAT negative (titers, <1:100). Both SAT and the IgM ELISA failed to detect one case of infection (sensitivity, 99%). Only 3 of 145 blood donors and none of the 100 patients with other illnesses were SAT positive (specificity, 99%). The overall results were similar for the three tests; however, SAT and ELISA were statistically more sensitive as initial screening tests. For 22% of the patients, the diagnosis of leptospirosis was made earlier by SAT than by MAT. SAT detected 27 (44%) of 62 MAT-negative patients with the first serum sample. ELISA and SAT had very similar results. Follow-up of patients for 1 year after the onset of symptoms showed a decreasing rate of positivity by SAT from the third month on. The rate of positivity by ELISA decreased more slowly, to about 67% by the end of the study. By MAT all patients were persistently reactive. SAT and ELISA seem to be convenient methods for the rapid and early screening for leptospirosis and could replace the less sensitive MAT. ELISA gives less subjective results than SAT and provides information on IgM kinetics, but it can be performed only by the more sophisticated laboratories. SAT is inexpensive, can be performed more quickly and more easily than ELISA, and could be used by the less well equipped laboratories.

Adolescent↗

Utilization of exocellular mannan from Rhodotorula glutinis as an immunoreactive antigen in diagnosis of leptospirosis.

Previously, Rhodotorula glutinis was reported to produce a large amount of exocellular mannan, having a repeating unit of -->3)-D-Manp-(1-->4)-D-Manp-(1-->. Recently, we found that antigenic polysaccharides of Leptospira biflexa serovar patoc strain Patoc I have the same repeating unit and cross-react with antisera raised against extended strains of other leptospires (K. Matsuo, E. Isogai, and Y. Araki, Carbohydr. Res., in press). This structural identity and the difficulty of producing and isolating antigens led us to confirm the usefulness of Rhodotorula mannan as an immunoreactive antigen in a serological diagnosis of leptospirosis. In the present investigation, we confirmed the structural identity of an exocellular mannan isolated from R. glutinis AHU 3479 and tried to use it as an immunoreactive antigen in a serological diagnosis of leptospirosis. From its chemical analysis and (1)H- and (13)C-labeled nuclear magnetic resonance spectrometry, the Rhodotorula mannan was confirmed to consist of the same disaccharide units. Furthermore, such a preparation was shown to immunoreact to various sera from patients suffering with leptospirosis as well as to most rabbit antiserum preparations obtained from immunization with various strains of pathogenic leptospires. Therefore, the Rhodotorula mannan preparation is useful as an immunoreactive antigen in the serological diagnosis for leptospirosis.

Animals↗

Evaluation of a commercial latex agglutination assay for serological diagnosis of leptospirosis.

Leptospirosis is a febrile zoonosis of worldwide distribution. A latex agglutination assay was evaluated in two studies, the first using a panel of well-characterized sera from patients with leptospirosis and from patients with other disease states and the second, a prospective hospital-based study, evaluating sera from 186 consecutive patients admitted to hospital with acute febrile illness. The confirmed leptospirosis serum panel included paired acute- and convalescent-phase specimens from 40 cases, of which 34 gave positive latex tests (case sensitivity, 85%; 95% confidence interval [95% CI], 70 to 94%). The other diseases represented in the panel of 112 specimens from nonleptospirosis patients included autoimmune diseases, brucellosis, dengue, melioidosis, malaria, syphilis, toxoplasmosis, viral hepatitis, and a number of other viral infections. The specificity of latex agglutination using this panel was 81% (95% CI, 73 to 87%). Among the patients with acute febrile illness, there were 25 cases of leptospirosis and 161 patients with other diagnoses. The sensitivity and specificity of latex agglutination in this group were 88% (95% CI, 72 to 97%) and 98% (95% CI, 95 to 100%), respectively. In this evaluation, the two distinct groups of specimens gave similar results for sensitivity, but specificity was different in each study. The sensitivity and specificity observed for the hospital study were similar to those obtained in evaluations of other rapid tests in the same population. The results of this study suggest that multiple evaluations of new diagnostic assays should be performed, because performance characteristics may vary in different populations.

Antibodies, Bacterial↗

Pulmonary leptospirosis: an excellent response to bolus methylprednisolone.

BACKGROUND: This case series analyses the beneficial effect of methylprednisolone in pulmonary leptospirosis, which usually has an aggressive course and grave outcome. METHODS: 30 patients of pulmonary leptospirosis were evaluated. The initial 13 patients did not receive corticosteroids while the remaining 17 all received bolus methylprednisolone one gram intravenously for three days followed by oral prednisolone 1 mg/kg for seven days, on the basis of occasional case reports of benefit in pulmonary leptospirosis. APACHE III and lung injury scores of similar severity were considered while comparing outcomes in those who received methylprednisolone with those who did not. RESULTS: Dyspnoea and haemoptysis were the commonest symptoms in those with pulmonary manifestations. Overall mortality was 18% (3 of 17) in patients who received methylprednisolone, as compared with 62% (8 of 13 patients) in those who did not (p<0.02). In patients with established acute lung injury (ALI score >2.5), five of eight patients survived in the subgroup with corticosteroids (37% mortality) while only one of nine patients survived in the group that did not receive corticosteroids (89% mortality). Corticosteroids affected outcome only if given within the first 12 hours after the onset of pulmonary manifestations. Mortality seemed to correlate with the APACHE scores, and number of quadrants affected on chest radiographs, more than with blood gas pressures. CONCLUSIONS: Corticosteroids reduce mortality and change outcome significantly when used early in the management of pulmonary leptospirosis.

Adolescent↗

Determining risk for severe leptospirosis by molecular analysis of environmental surface waters for pathogenic Leptospira.

BACKGROUND: Although previous data indicate that the overall incidence of human leptospirosis in the Peruvian Amazon is similar in urban and rural sites, severe leptospirosis has been observed only in the urban context. As a potential explanation for this epidemiological observation, we tested the hypothesis that concentrations of more virulent Leptospira would be higher in urban than in rural environmental surface waters. METHODS AND FINDINGS: A quantitative real-time PCR assay was used to compare levels of Leptospira in urban and rural environmental surface waters in sites in the Peruvian Amazon region of Iquitos. Molecular taxonomic analysis of a 1,200-bp segment of the leptospiral 16S ribosomal RNA gene was used to identify Leptospira to the species level. Pathogenic Leptospira species were found only in urban slum water sources (Fisher's exact test; p = 0.013). The concentration of pathogen-related Leptospira was higher in urban than rural water sources (approximately 10(3) leptospires/ml versus 0.5 x 10(2) leptospires/ml; F = 8.406, p < 0.05). Identical 16S rRNA gene sequences from Leptospira interrogans serovar Icterohaemorrhagiae were found in urban slum market area gutter water and in human isolates, suggesting a specific mode of transmission from rats to humans. In a prospective, population-based study of patients presenting with acute febrile illness, isolation of L. interrogans-related leptospires from humans was significantly associated with urban acquisition (75% of urban isolates); human isolates of other leptospiral species were associated with rural acquisition (78% of rural isolates) (chi-square analysis; p < 0.01). This distribution of human leptospiral isolates mirrored the distribution of leptospiral 16S ribosomal gene sequences in urban and rural water sources. CONCLUSIONS: Our findings data support the hypothesis that urban severe leptospirosis in the Peruvian Amazon is associated with higher concentrations of more pathogenic leptospires at sites of exposure and transmission. This combined quantitative and molecular taxonomical risk assessment of environmental surface waters is globally applicable for assessing risk for leptospiral infection and severe disease in leptospirosis-endemic regions.

Environment↗

Use of doxycycline for leptospirosis after high-risk exposure in São Paulo, Brazil.

A clinical trial pilot study, double-blinded, randomized, and controlled with a placebo to assess the effectiveness of oral doxycycline (200 mg, single dose) in preventing leptospirosis after high exposure to potentially contaminated water was performed in São Paulo, SP, Brazil. Confirmed cases were defined as those with leptospira IgM antibody and symptoms; asymptomatic cases were those presenting with IgM antibodies but no symptoms; and suspected cases were individuals with symptoms but no IgM antibody. Forty subjects were given doxycycline and 42 were given placebo. In the drug-treated group there were 2 confirmed cases, 11 asymptomatic cases, and 6 suspected cases. In the placebo group there were 5 confirmed, 6 symptomatic, and 5 suspected cases. Even though we found a protective association of doxycycline for confirmed leptospirosis cases (RR = 2.3) and seroconversion only (RR = 2.0), the association was not statistically significant because of the small number of individuals enrolled in this pilot study. We observed that the 22% of the volunteers already had IgM antibodies to leptospirosis at the first sampling. Finally, the attack rate to confirmed, asymptomatic, and suspected cases of Leptospirosis was 8.5%, 22%, and 13%, respectively, in this population.

Adolescent↗

The association between serum potassium at hospital admission and the case-fatality rate of leptospirosis in men.

Severe leptospirosis affects predominantly males and presents a high susceptibility to hypokalemic acute renal failure. As hypokalemia and hyperkalemia induce severe complications, it is important to evaluate if the initial serum potassium is an independent risk factor for death in leptospirosis. The medical records of 1016 patients hospitalized with the diagnosis of leptospirosis were reviewed. The analysis was restricted to 442, according to the following criteria: male, 18 years or older, information about death or hospital discharge and recorded values of serum potassium, serum creatinine and duration of symptoms at admission. Potassium values lower than 3.5 mEq/L (hypoK), 3.5-5 mEq/L (normoK) and above 5 mEq/L (hyperK) were detected in 180, 245 and 17 patients, respectively. The death rate increased with serum potassium: 11.1% in the hypoK, 14.7% in the normoK and 47.1% in the hyperK group (p = 0.002). In a logistic regression model (normoK as referent), including age, creatinine and duration of symptoms, hypoK was not associated with increased death rate (odds ratio (OR) = 0.80; p > 0.1). On the other hand, hyperK showed a significant association with increased risk of death (OR = 3.95, p = 0.021). In conclusion, in this sample of men with leptospirosis initial serum potassium was positively and independently correlated with the risk of in-hospital death.

Adolescent↗

Evaluation of hemostasis disorders and anticardiolipin antibody in patients with severe leptospirosis.

A prospective study was designed to evaluate disorders of hemostasis and levels of anticardiolipin antibodies (ACL) in 30 patients with severe leptospirosis and acute renal failure (ARF) (ARF was defined as serum creatinine > or =1.5 mg/dL). The patients had been admitted to the Walter Cantídio University Hospital, São José Infectious Diseases Hospital and General Hospital of Fortaleza, Ceará, from August 1999 to July 2001. They all were male, with a mean age of 32 +/- 14 years and with clinical and laboratory diagnoses of ARF leptospirosis. The time elapsed between onset of symptoms and the first hemorrhagic manifestation was 9 +/- 4 days. Bleeding was observed in 86% of the patients. Laboratory tests showed significantly high levels of urea (181 +/-95 mg/dl), fibrinogen, (515 +/- 220 mg/dl), prothrombin time (13.3 +/- 0.9 seconds) and low platelet counts (69 +/- 65 x 10(3)/mm3) on admission. There was no elevation in activated partial thromboplastin time or thrombin time. Levels of IgM and IgG ACL concentrations were significantly increased (p < 0.05) in leptospirosis patients when compared to control patients (28.5 +/- 32.4 vs. 11.5 +/- 7.9MPL U/ml and 36.7 +/- 36.1 vs. 6.5 +/- 2.5 GPL U/ml), respectively. Vasculitis, thrombocytopenia and uremia should be considered important factors for the pathogenesis of hemorrhagic disturbances and the main cause of death in severe leptospirosis.

Acute Kidney Injury↗

Seroepidemiology and occupational and environmental variables for leptospirosis, brucellosis and toxoplasmosis in slaughterhouse workers in the Paraná State, Brazil.

Leptospirosis, brucellosis and toxoplasmosis are widely-distributed zoonosis, being the man an accidental participant of their epidemiological chains. The aim of this paper was to make a seroepidemiological report and identify occupational and environmental variables related to these illnesses in 150 workers in a slaughterhouse in the Northern region of Paraná. For the diagnosis of leptospirosis a microscopical seroagglutination test was applied; for brucellosis, the tamponated acidified antigen test and the 2-mercaptoetanol tests were used, and for toxoplasmosis the indirect immunofluorescence reaction test. For each employee an epidemiological survey was filled, which investigated occupational and environmental variables which could be associated with these infections. Positive results for leptospirosis were found in 4.00% of the samples, for brucellosis in 0.66% of samples and toxoplasmosis in 70.00%. From the three diseases researched, only the results for leptospirosis suggest occupational infection.

Abattoirs↗

[Spatial distribution of leptospirosis in Rio Grande do Sul, Brazil: recovering the ecology of ecological studies].

Leptospirosis is an endemic disease in the State of Rio Grande do Sul, Brazil, and presents a broad diversity of exposure routes, reservoirs, etiological agents, and clinical features. The main objective of this work is to identify transmission areas and possible ecological components of leptospirosis transmission. This was accomplished through the aggregation of epidemiological data into spatial units that represent the State's socio-environmental diversity. The 1,274 confirmed leptospirosis cases that occurred in 2001 were georeferenced in the counties of residence. The county maps were overlaid on environmental units characterizing land use, altitude, and river basins. Incidence rates for each environmental class were calculated, along with their statistical significance, through GIS aggregation operations. The highest incidence rates were verified in coastal sedimentary areas with low altitude and predominantly agricultural land use. In these areas, most of the cases were associated with irrigated farming. The results suggest the existence of favorable ecological characteristics for leptospirosis transmission in places involving proliferation of peri-domiciliary rodents and intensive agricultural production. The article discusses the effects of data aggregation into environmental units, as well as strategies to control the endemic in the State.

Animals↗

[Spatial distribution of leptospirosis in the city of Rio de Janeiro, Brazil, 1996-1999].

Leptospirosis, one of the most widely disseminated zoonoses in the world, is endemic in Brazil and is characterized by outbreaks during seasons with the greatest rainfall. In 1996 the city of Rio de Janeiro experienced one of the largest urban epidemics in the country, shortly after heavy rainstorms in the month of February, with 1,732 reported cases and 51 deaths. The objective of this work was to describe the spatial distribution of leptospirosis in the city of Rio de Janeiro during the period 1996-1999. Data were from the National Information System for Reportable Diseases. The kernel ratio for cases and population generated a smoothed surface, which estimates the intensity of the leptospirosis incidence rate. In the resulting maps over the course of the study period, the sites with the highest leptospirosis intensity were not repeated, and the sites normally considered as having the highest risk -- slum areas and flooded areas -- were not always the most heavily affected. The techniques used can represent an important methodological acquisition for establishing territory-based surveillance.

Animals↗

Leptospirosis as a cause of acute respiratory failure: clinical features and outcome in 35 critical care patients.

Leptospirosis may have important complications, such as acute respiratory failure (ARF) associated or not with other organic dysfunction, with a high mortality rate. We report the characteristics and evolution of severe leptospirosis associated with ARF. During 10 years, 35 consecutive adult patients admitted in two general Intensive Care Units with severe leptospirosis and ARF, were followed up. Clinical characteristics, associated organic dysfunction and mortality were analyzed. Survivors were compared with non-survivors. The most frequent clinical manifestations were dyspnea, fever, myalgia, jaundice, hemoptysis and coughing. All patients presented ARF, needing mechanical ventilation, as well as other organic dysfunctions. The mortality rate was 51%. Non-survivors were older and had a higher incidence of organic dysfunction, mainly renal, cardiovascular and neurological failures, as well as a higher level of acidosis. In conclusion, leptospirosis should be considered as a cause of severe ARF and other associated organic dysfunctions.

Adult↗

A review of leptospirosis in farm animals in Portugal.

This paper presents a review of Leptospira infection in farm animals in Portugal which is based mainly on serological results obtained in the National Veterinary Research Laboratory between January 1987 and December 1993. Serum samples were tested by the microscopic agglutination test, at a minimum dilution of 1:100. Positive titres were obtained in 15.3% of the 9,543 bovine samples examined. Sejroe, Pomona, Hebdomadis, Tarassovi and Icterohaemorrhagiae were the principal serogroups which reacted in the tests. A total of 3,195 pigs were tested, of which 20.2% showed positive reactions. The main serogroups which reacted were Australis, Pomona, Cynopteri, Icterohaemorrhagiae and Autumnalis. Field observations on outbreaks of leptospirosis in pigs, along with data obtained from an experimental infection with serovar mozdok in pregnant gilts suggest that this serovar, rather than serovar pomona, may be causing Pomona group infections in pigs. Serum samples from 5,298 sheep were tested and 3.3% gave positive results. The predominant serogroups involved were Canicola, Pomona, Cynopteri, Sejroe and Icterohaemorrhagiae. From the 1,631 goats examined serologically, 5.0% gave positive results, mainly to serogroups Grippotyphosa, Canicola, Pomona, Icterohaemorrhagiae and Pyrogenes. Only 83 serum samples from horses were obtained, of which 43.4% showed positive titres. Serogroups Australis, Autumnalis, Cynopteri and Pyrogenes were those most commonly found. Serological evidence of leptospirosis in farm animals is widespread in Portugal, particularly in cattle and pigs. Leptospirosis in horses needs to be studied further. In an attempt to provide a general view on the occurrence of leptospirosis in these animal species in Portugal, the present results are compared with results obtained in previous studies and are complemented with both previous and recent bacteriological findings.

Agglutination Tests↗

Leptospirosis presenting with mania and psychosis: four consecutive cases seen in a military hospital in Turkey.

OBJECTIVE: To present the clinical features and the treatment alternatives of manic and psychotic symptoms in patients with leptospirosis. METHODS: Clinical observation and diagnosis of four cases with leptospirosis presenting with psychiatric symptoms. RESULTS: Leptospirosis diagnoses were established by recovery of the organism from culture, macroagglutination tests, and dark field microscopy in all cases. Leptospira ELISA-Ig M was also positive in all cases. Microagglutination tests were positive in case 1 and case 2. All of the cases were also screened for other possible medical, infectious, and neurological disorders that could account for their clinical symptoms. Patients were treated with a combination of antibiotics, antipsychotics and mood stabilizers. CONCLUSIONS: The presence of manic and psychotic symptoms with fever and high transaminase and/or CPK levels in high risk occupational groups during rainy periods should alert the physician to the possibility of leptospirosis. The psychiatric symptoms are sensitive to anti-psychotics and mood stabilizers but not to antimicrobial treatment, suggesting that the psychiatric picture may not be related to direct invasion of the central nervous system by the infectious agent.

Adult↗