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[Leptospirosis--epidemic, clinical and diagnostic aspects].

Leptospirosis is a major public health problem throughout the world. We studied 22 cases of leptospirosis. They were hospitalised between 1999-2003. Men were more affected than women and those with rural origin prevailed, too. The direct infection was more often found in these cases. These patients presented a large spectrum of signs and symptoms attributable to this spirochetal pathogen. The etiology was dominated by L. pomona, L. canicola, L. wolffi. Leptospirosis presented with 3 syndromes: Weil's syndrome, atypical pneumonia syndrome and aseptic meningitis. The adequate treatment was with penicillin or ampicillin i.v.

Adolescent↗

Leptospiral proteins expressed during acute & convalescent phases of human leptospirosis.

BACKGROUND & OBJECTIVES: The available serological techniques for the diagnosis of leptospirosis have less sensitivity during the early stage of the disease. Understanding of leptospiral proteins expressed during acute and convalescent phases of leptospirosis, would be help the develop of new serodiagnostic strategies. Therefore, the present study was carried out to identify (i) an antigen that is conserved among the various pathogenic leptospira; (ii) best protein antigen to which immune response can be identified in the acute phase; and (iii) best protein antigen which is present in convalescent sera which can be used for seroepidemiological studies. METHODS: Quantitative immunoblot analysis was performed using acute and convalescent phase human sera along with sera from normal healthy individuals and from patients with typhoid, malaria and hepatitis as the controls. All the samples were analyzed for the leptospiral protein recognition by using IgM and IgG immunoblots. Leptospiral cell fractionation was performed using triton X-114 and lysozyme and further the conservation of leptospiral proteins was also performed. RESULTS: In confirmed cases of leptospirosis, the IgG recognition in acute phase sera was 30.2, 39.5, 27.9, 55.8 and 27.9 per cent for the leptospiral proteins p32, p41/42, p58, p62 and p82 respectively. The IgG has considerably increased to 65.1, 55.8, 46.5, 67.4 and 48.8 per cent against the same proteins during convalescent phase. The IgM recognition was 32.6 , 32.6, 30.2 and 37.2 per cent for acute phase sera and 32.6, 37.2, 44.2 and 41.9 per cent for convalescent phase sera for the leptospiral proteins p14, p25, p32 and p41/42, respectively. Leptospiral proteins like p62 and p82 were recognized among all the control groups with 3.3-15.3 per cent for IgG recognition. INTERPRETATION & CONCLUSION: Leptospiral protein p32 was found to be highly sensitive and specific and could be useful for the development of newer techniques for diagnosis and seroepidemiological studies. Combination of p32 and p41/42 for IgG and p14, p25, p32, p41/42 for IgM would increase the sensitivity of these techniques further.

Antigens, Bacterial↗

Renal involvement in leptospirosis at Dr. Cipto Mangunkusumo and Persahabatan Hospitals.

AIM: To describe clinical pattern of ARF caused by leptospirosis and its related factors. METHODS: A cross-sectional study using medical record data of all leptospirosis cases admitted to Cipto Mangunkusumo and Persahabatan General Hospitals between January 1993 and December 1996. Patient identification included age, sex, and occupation. Clinical symptoms were described in details and followed by laboratory testing i.e. peripheral blood count, urinalysis, blood urea and creatinine, liver function test, and pancreatic enzymes assay. RESULTS: Seventy-five percent were men and the mean age was 38.3 years old. Sixty out of 68 (88.2%) patients had ARF as defined by an increase of plasma creatinine level of >1.5 mg/mL. The most common presenting symptoms in patients with ARF were fever (100%), nausea and vomiting (95.0%), muscle pain (88.1%) and jaundice (71.3%). The mean duration of fever 7.2 days. The most frequent laboratory abnormalities were increased erythrocyte sedimentation rate (100%), leukocytosis (90%) and increase total bilirubin level (87.5%). Only leukocytosis showed a significant difference between ARF and non-ARF patients (p=0,014). Leptospira bataviae was found in 95.6% of patients and 96.7% of ARF patients. Penicillin was given to 80.9% of patients with only 2 (2.9%) deaths. CONCLUSION: Although significant correlation cannot be established, we concluded that nausea, vomiting, muscle pain, jaundice, increased ESR and total bilirubin level should alert the physician about the possibility of renal involvement in leptospirosis patients with prolonged fever. Leptospira bataviae was an important virulent pathogen. Treatment with penicillin may significantly improve organ failure and was considered the drug of choice in managing leptospiral infection.

Acute Kidney Injury↗

Risk factors for mortality in patients with leptospirosis during an epidemic in northern Kerala.

BACKGROUND: Epidemic leptospirosis is increasingly being reported from northern Kerala during the monsoon months. We investigated the risk factors for mortality during the 2002 epidemic. METHODS: Three hundred and forty patients suspected to have leptospirosis during the epidemic were studied by clinical examination, laboratory investigations and Leptospira serology (microscopic agglutination test). Two hundred and eighty-two seropositive cases were analysed for the clinical and laboratory profile, and risk factors for mortality using univariate and logistic regression analysis. RESULTS: Of the 282 seropositive cases, 58.9% were men. No significant association with occupational risk factors was seen; 62.9% had wounds on the feet. The majority had Weil syndrome with hepatic (69.8%) and renal (56.3%) involvement. Thrombocytopenia (65.8%) was common. Transient hyperglycaemia was observed in 10.3% of cases. Pulmonary haemorrhage (4.7%) and meningism (4.3%) were less common. Jaundice occurred in 46% of cases in the first week. The mortality rate was 6.03%. Hyperkalaemia (OR= 27.3), meningism (OR= 10.6), oliguria (OR=8.2), haemoptysis (OR= 5.4), bilirubin > 15 mg/dl (OR= 5.4), disorientation (OR=5), tachycardia (OR=4.1) and muscle tenderness (p=0.03) were the predictors of high mortality in univariate analysis. Only involvement of the lung and central nervous system were significant predictors of death in logistic regression. CONCLUSIONS: Leptospirosis is no more a mere occupational hazard in Kerala. Early occurrence of complications such as hepatitis mandates caution in the primary care setting. Lung and central nervous system involvement are significant predictors of mortality.

Adolescent↗

[Leptospirosis in the Republic of Mordovia].

Over 45 years, anthropurgic foci of Leptospira infection have been differently active in the Republic of Mordovia; in its population, the incidence of leptospiroses being greater than the average federal rates. The peak incidence of leptospirosis was observed at 10-11-year intervals: 1962-1963, 1971-1972, 1983, 1994-1995, 2001-2002 when outbreak and group morbidity were registered. There were 2.6- and 2.4-fold seasonal rises in morbidity in June to September with its peak in July-August, respectively. Cases of infection were notified in all the districts and towns of the republic, and in all landscape-environmental areas; group and outbreak incidence was found in 6 districts and environs of the town of Saransk in 1997-2002. Males aged 20-49 years are a group of risk for Leptospira infection; its incidence rates in age groups 0-14 and above 60 years are less than the average republican ones. Children (aged 0-14 years) and adolescents (aged 15-19 years) actively participate and determine outbreak and group mortality rates. Infection occurs most frequently while bathing in open water reservoirs, while using water from other water springs, going to the forest to pick mushrooms, berries, etc., while being engaged in laying in hay, fodder, and other feeds for animals. During registration of infection in Mordovia, the etiological pattern of human leptospirosis constantly changed, in 1992-2002 there were prevalent diseases caused by Grippotyphosa (60.96%), Canicola (7.12%), Seiroe (6.73%), Australis (6.54%), and Cynopteri (5.96%), in 1997-2002, the proportion of Australis (11.2%) increased and that of Canicola (4.7%) decreased. The leptospira serogroups Icterohaemorrhagiae, Tarassovi, Seiroe were prevalent animals. There was no correlation of the etiological environment of leptospiras isolated from agricultural animals and human beings in 1997-2002, which proves the leading role of natural leptospirosis foci and rodents as a source of infection.

Adolescent↗

Sero surveillance of leptospirosis among sewer workers in Pune.

Leptospirosis is an important occupational disease affecting people coming in contact with animals and their discharges. The occurrence of infection in ones workplaces is linked to the environment to which the worker is exposed and the adaptability of the organism in that working environment. Rodents usually abound in underground sewers and are carriers of leptospira. The urine of rodents and other animals present in that area is likely to contaminate these sewers. Leptospira are excreted in the urine of infected animals. Thus sewer workers are at a potential risk of leptospirosis. The prevalence of leptospirosis in these workers could thus indirectly predict the presence of the disease in animals in a particular geographical niche. Total seventy-eight sewer workers from 5 different municipal wards in Pune were examined to find out the evidence of past infection with leptospira using microagglutination test (MAT). The prevalence rate was found to be 16.6%. The serovars to which antibodies were detected include autumnalis (38.4%), pyrogenes (23.0%), canicola (15.3%) and pomona (15.3%). Evidence of leptospiral infection was found to be maximum in sewer workers in the areas of the city that were infested with rodents and stray animals.

Animals↗

Leptospirosis: an emerging health problem in Thailand.

Leptospirosis is an emerging health problem in Thailand, with dramatic increases in reported incidence since 1996. The annual number of reported leptospirosis cases increased from 398 cases in 1996 to 14,285 cases in 2000. In 2001, 2002, and 2003, the number of reported cases decreased, but still remained high at 10,217, 6,864, and 4,958 cases, respectively. The epidemiological characteristics of leptospirosis in Thailand include a peak incidence in September and October in association with the rainy season. A vast majority of the cases (90%) were reported in the Northeast region. The case fatality rate was as high as 4.4%, having a predominant association with male farmers aged 15 to 45 years. Outpatient cases were approximately 9 times more common than admitted cases, with an apparent recent shift in the pattern of infecting serovars among reservoir animals and humans.

Adolescent↗

Indirect immunoperoxidase test for the diagnosis of leptospirosis.

Leptospirosis is a widespread zoonotic disease that affects all mammals, including humans, in different parts of the world. Clinical recognition of leptospirosis is challenging, and the definitive serologic diagnosis assay, the microscopic agglutination test (MAT), is time-consuming and difficult to conduct. In this study, an indirect immunoperoxidase (IIP) test to detect Leptospira-specific antibodies in human serum samples was developed. The efficacy of the IIP was compared with the indirect immunofluorescent assay (IFA) and MAT. A total of 368 human serum samples were analyzed by MAT, IFA, and IIP. Using a MAT titer of > or = 1:100 as the gold standard, the sensitivities for the detection of Leptospiral antibodies at a titer of 1:200 were 94.7% by IFA and 93.6% by IIP; specificities were 95.3% by IFA and 94.9% by IIP; and accuracies were 95.1% by IFA and 94.6% by IIP. With a titer of 1:400, the sensitivity, specificity, and accuracy were 86.2%, 98.9%, and 95.7% by IFA, respectively; whereas, for the IIP, the sensitivity was 85.1%, specificity 98.5%, and accuracy 95.1%. A further evaluation of this test with 80 unknown-febrile-disease sera was also included. We found that the sensitivity and specificity of this test were 100% and 76.8%, respectively. Therefore, the IIP test is a potentially valuable tool for the diagnosis of leptospirosis.

Agglutination Tests↗

A test strip IgM dot-ELISA assay using leptospiral antigen of endemic strains for serodiagnosis of acute leptospirosis.

A test strip IgM dot-ELISA assay for the detection of leptospire-specific IgM antibodies in human sera was developed. Antigen dotted on a nitrocellulose paper strip was the pool sonicated antigen prepared from three predominant reactive Leptospira serovars currently in endemic area, i.e., Bratislava, Sejroe and Pyrogenes. The ability of the test to diagnose acute leptospiral infection was assessed by testing 343 single serum samples from 96 laboratory-confirmed leptospirosis case patients with positive result in the standard microscopic agglutination test (MAT), 55 serum samples from patients with various diseases other than leptospirosis, and 192 serum samples from healthy individuals. Using the results of the MAT as a gold standard, the sensitivity and specificity of the test strip IgM dot-ELISA assay were 98.96 and 93.93 per cent, respectively. The assay offered relatively high negative predictive values (99.57%) thus making the assay ideally suited for rapid screening. The stability of the test strip was assessed with a panel of five positive and five negative control sera after storage at 4 degrees C and -20 degrees C at different times. The results showed a good performance of the test strip at both storage temperatures for up to one year. In conclusion, the test strip IgM dot-ELISA assay was sufficiently sensitive for use as a screening test for serodiagnosis of acute leptospirosis. The assay was simple, inexpensive, and easy to perform for both a single test format and a large number of specimens. However, further studies are still needed to improve the stability of the test strip and assay reagents at ambient temperature, and to make the assay more rapidly and more user friendly.

Antigens, Bacterial↗

Mild, self-resolving acute leptospirosis in an HIV-infected patient in the Peruvian Amazon.

We report a case of acute, self-resolving leptospirosis presenting in a HIV-positive patient from the Peruvian Amazon. The patient presented with an undifferentiated acute febrile illness that resolved without treatment, diagnosed retrospectively as leptospirosis by serology and real-time polymerase chain reaction. Five months later, he was admitted because of a febrile illness with jaundice, hepatosplenomegaly, peripheral edema, and oral candidiasis. Because of the clinical suspicion of AIDS, stored sera of the previous admission were tested, and HIV seropositivity was confirmed, proving that the condition was present at the first admission. Acute leptospirosis in HIV coinfection is not inevitably severe, and there is probably a wide variation in clinical manifestations similar to what occurs in immuno-competent hosts.

Adult↗

Unusual clinical manifestations of leptospirosis.

Leptospirosis has protean clinical manifestations. The classical presentation of the disease is an acute biphasic febrile illness with or without jaundice. Unusual clinical manifestations may result from involvement of pulmonary, cardiovascular, neural, gastrointestinal, ocular and other systems. Immunological phenomena secondary to antigenic mimicry may also be an important component of many clinical features and may be responsible for reactive arthritis. Leptospirosis in early pregnancy may lead to fetal loss. There are a few reports of leptospirosis in HIV-infected individuals but no generalisation can be made due to paucity of data. It is important to bear in mind that leptospiral illness may be a significant component in cases of dual infections or in simultaneous infections with more than two pathogens.

Humans↗

Laboratory diagnosis of leptospirosis.

Leptospirosis is a worldwide zoonosis caused by pathogenic Leptospira species, for which humans are accidental hosts. It is endemic in the tropical urban areas including our country, where seasonal epidemics are becoming increasingly common. Laboratory tests are necessary to confirm the diagnosis of clinically suspected leptospirosis due to its varied symptomatology. Moreover, leptospirosis must always be considered during the differential diagnosis of other tropical febrile illnesses. Laboratory analysis depends on the samples available and temporal stage of the illness. A confusing array of laboratory tests is described for the detection of this spirochete and antibodies. The conventional tests include direct microscopy, culture and the most widely used reference standard method -the microscopic agglutination test. In addition a variety of newer serological tests and those based on molecular techniques have been described. This review has attempted to describe the basis of these techniques and discussed the relative advantages and drawbacks of these assays with special emphasis on the selection of the most appropriate specimen and test, and the correct interpretation of the test result.

Bacteriological Techniques↗

Seroprevalence and risk factors associated with leptospirosis in dogs.

This study was done to determine the seroprevalence and risk factors of leptospirosis in dogs. From March to September 2004, a total of 210 dogs were randomly selected from the Small Animal Hospital, Faculty of Veterinary Medicine, Chiang Mai University. Dog sera were collected from the cephalic vein and kept at -20 degrees C until submitted to the National Institute of Health for a Microscopic Agglutination Test (MAT). Risk factors were analysed using logistic regression modelling. The prevalence of Leptospira antibodies was 11% (23/210). The most prevalent Leptospira serogroups were Bataviae 5.2% (11/210), Canicola 2.4% (5/210), Australis 1.4% (3/210), Icterohaemorrhagiae 1.4% (3/210), Ballum 0.5% (1/210), Djasiman 0.5% (1/210), Javanica 0.5% (1/ 210), Mini 0.5% (1/210), and Sejroe 0.5% (1/210). Risk factors, including signalment, environment and health status, were not significantly associated with leptospirosis antibodies. However, playing in sewage, staying outdoors >50% of the time, and consumption raw meat increased the risk of leptospirosis antibodies in dogs.

Age Factors↗

Retrospective serosurvey of leptospirosis among patients with acute febrile illness and hepatitis in Egypt.

The epidemiologic status of leptospirosis in Egypt has not been well defined because of difficulties in disease diagnosis. A retrospective study was conducted to detect leptospiral antibodies among undiagnosed acute febrile illness (AFI) and hepatitis cases. Approximately 16% of both AFI (141/886) and acute hepatitis (63/392) cases showed seroreactivity to Leptospira IgM by ELISA and microscopic agglutination test (MAT). Canicola, Djasiman, Grippotyphosa, Pyrogenes, Icterohemorrhagiae, and Pomona were the most commonly reactive serovars among patients with AFI. Djasiman, Grippotyphosa and Icterohemorrhagiae were the most reactive among patients with acute hepatitis. This study represents the first systematic report of Leptospira associated with patients with AFI and hepatitis in Egypt. Physicians need to have increased awareness about the importance of leptospirosis in the differential diagnosis of AFI and acute hepatitis in Egypt. In addition, laboratory capacity should be developed at fever hospitals to diagnose leptospirosis.

Adolescent↗

[Serum nitric oxide as an additional criterion for evaluating the course of leptospirosis].

The blood level of nitric oxide (NO) was studied during an infectious process in 107 patients with leptospirosis. The content of NO was estimated from the level of the final stable nitrogen cycle metabolite--nitrite was estimated by the Griss reaction. Infectious toxic shock (57%), disseminated intravascular coagulation syndrome (31%), respiratory distress syndrome (36%), and acute renal and hepatic failure (76%) were observed in the examinees. A combination of 3-4 of the above abnormalities was noted in 49% of the patients. There were elevated blood nitrite levels at the onset of the disease in patients with leptospirosis with signs of infectious toxic shock (15.3+/-2.79 micromol/l). In patients with a poor or complicated rehabilitative period, the high levels of nitrite were retained or its concentration repeatedly increased at weeks 3-4 of the disease. It has been shown that the measurements of blood nitrite levels may be used as an additional diagnostic criterion for evaluating the course of leptospirosis.

Adult↗

[Creatine phosphokinase in leptospirosis].

Leptospirosis is a widely-distributed infectious disease, that usually presents with fever, headache and myalgia. Organ involvement could have very different severity degree. We evaluate 21 patients with leptospirosis looking for prognostic and diagnostic value of myalgia and/or elevated creatine-phosphokinase serum levels. Myalgia was recorded in nearly all patients (91%). Creatine-phosphokinase levels above normal limits were seen in 37% of cases, either in severe forms of leptospirosis with organ involvement or in mild forms of disease. We conclude that creatine-phosphokinase elevated levels could be of early diagnosis interest but they are not solely seen in the more severe forms of the disease.

Adolescent↗

[The mechanisms maintaining epidemic foci of leptospirosis].

24,419 samples of blood serum, collected in the Azerbaijan SSR among different professional groups of the population, have been tested for leptospirosis. The comparison of the results with those obtained in the natural foci of leptospirosis and in the foci of this infection appearing as a consequence of human activities has made it possible to come to the conclusion that the epidemic foci of leptospirosis are maintained due to the existence of foci among cattle. The cases of contamination among persons professionally linked with large cattle breeding complexes have been found to exceed those among persons working at farms of a nonindustrial type.

Age Factors↗

[Leptospirosis in children: a not infrequent disease (author's transl)].

A total of 14 cases of leptospirosis in children aged from 5 to 15 years, hospitalized in the Paris region, are reported. The polymorphe character of the disease is pointed out. The necessity for respecting a rigorous chronological order when requesting complementary examinations, which could confirm the diagnosis, is stressed. Domestic animals, team-mates, and while swimming at week-ends or during holidays, are potential sources or means of infection in the young. This justifies searching for leptospirosis in cases of unexplained fever, a pseudo-influenza syndrome, a meningitis which is mainly of the lymphocytic type, or more rarely, in cases of jaundice. Leptospirosis should be a disease well-known by the pediatrician.

Adolescent↗