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Leptospirosis: an ignored cause of acute renal failure in Taiwan.

Leptospirosis, caused by a spirochete, is the most common zoonosis in domestic or wild animals. Animals excrete infected urine in soil or water and may cause human infections through abrased wound, mucosa, conjunctiva, or by swallowing contaminated water. Clinical presentations of leptospirosis are mostly subclinical. Five to ten percent of leptospirosis are fatal, causing fever, hemorrhage, jaundice, and acute renal failure (Weil's syndrome). Leptospirosis has been ignored as a cause of acute renal failure in Taiwan. We report two patients with leptospirosis who presented with high fever, abdominal pain, jaundice, and acute renal failure. Patient 1 died on day 12 of admission of multiple organ failure associated with pancytopenia, hypogammaglobulinemia, and reactive hemophagocytosis. Leptospirosis was recognized after death. Patient 2 was admitted with similar presentations 2 weeks later. Penicillin and doxycycline were given early in the course, and azotemia, jaundice, respiratory failure, and aseptic meningitis gradually improved. Renal biopsy showed interstitial nephritis. Several tubular clearance tests showed proximal tubular defect with severe bicarbonate wasting (FeHCO3- 20.9%) and incomplete type II renal tubular acidosis without affecting the distal nephron. After 80 days of treatment, this patient was discharged with recovery of conscious level and renal function. This is the first leptospirosis patient with detailed tubular functional and morphological studies of the kidney. Diagnosis of leptospirosis was made by microscopic agglutination test (MAT) for antibody to leptospira and by polymerase chain reaction (PCR) for leptospira DNA in blood and urine (interrogans serogroup australis in case 1 and Leptospira borgpetersenii serogroup ballum in case 2). Because active surveillance has resulted in 13 cases diagnosed as leptospirosis islandwide thereafter, underestimation and ignorance of leptospirosis as a cause of acute renal failure may occur in Taiwan. Therefore, an area with a low leptospirosis incidence may actually have a very high incidence. Leptospirosis should be suspected in febrile patients with jaundice and renal failure when pathogens cannot be identified by traditional culture for microorganisms.

Abdominal Pain↗

Evaluation of environmental risk factors for leptospirosis in dogs: 36 cases (1997-2002).

OBJECTIVE: To identify environmental risk factors for leptospirosis. DESIGN: Retrospective study. ANIMALS: 36 dogs with leptospirosis and 138 dogs seronegative for leptospirosis as determined by microscopic agglutination test for antibodies against Leptospira spp. PROCEDURES: Medical records of dogs evaluated for leptospirosis from 1997 though 2002 were identified. Owner address was used to geocode locations of dogs, and location-specific environmental risk factor data were obtained by use of a geographic information system. Risk of leptospirosis was estimated by odds ratios, controlling for potential confounding by dog age, sex, and breed. RESULTS: Leptospirosis in 19 of the 30 dogs in which an infecting Leptospira serovar could be identified was associated with Leptospira kirschneri serovar grippotyphosa infection. Dogs in which a diagnosis of leptospirosis was made, and dogs with leptospirosis caused by L kirschneri serovar grippotyphosa, were more likely to have addresses located in areas classified as rural in 1990 but urban in 2000. By use of information on recent urbanization and a logistic regression model, the status of 81.6% and 89.8% of dogs with leptospirosis and leptospirosis caused by serovar grippotyphosa, respectively, were correctly classified. Other environmental variables (proximity to streams, recreational areas, farmland, wetlands, areas subject to flooding, and areas with poor drainage; annual rainfall; and county cattle or pig population) did not significantly improve accuracy of classification. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs in periurban areas are at greater risk of leptospirosis. Vaccination of dogs in these areas to protect against leptospirosis should be considered.

Animals↗

Detection of dengue infection in patients investigated for leptospirosis in Barbados.

The annual incidence of leptospirosis in Barbados is approximately 13 severe cases/100,000. The peak incidence occurs in October to December of each year, coinciding with the months of heaviest rainfall. During the second half of 1995, an epidemic of dengue type 1 infection produced almost 1,000 laboratory-confirmed cases. During the same period, leptospirosis mortality was twice the average, suggesting that some cases of leptospirosis were being misdiagnosed and treated inappropriately. Sera from patients investigated for dengue or leptospirosis were analyzed retrospectively to determine the extent of misdiagnosis. During 1995 and 1996, 31 of 139 and 29 of 93 patients, respectively, were confirmed as having leptospirosis. Sera from the remaining leptospirosis-negative patients were tested for IgM antibodies to dengue virus. During 1995 and 1996, 48 of 108 patients and 21 of 64 patients, respectively, were found to have dengue. In 1997, sera from all patients investigated for leptospirosis were also tested prospectively for IgM antibodies to dengue: 38 of 92 leptospirosis-negative patients (41%) were dengue IgM-positive, while 2 of 25 leptospirosis cases also had serologic evidence suggesting acute dengue infection. A second large outbreak of dengue caused by serotype 2 occurred in 1997. During the 1995 and 1997 dengue epidemics in Barbados, dengue cases outnumbered leptospirosis cases investigated in the leptospirosis diagnostic protocol. During 1997, patients investigated but negative for dengue were also tested for anti-leptospiral IgM: 7.3% (19 of 262) were IgM-positive. Substantial misdiagnosis of both dengue and leptospirosis can occur and greater public awareness and clinical suspicion of the similar presentations of these two diseases are necessary.

Agglutination Tests↗

Antibiotics for treating leptospirosis.

BACKGROUND: Leptospirosis is a parasitic disease transmitted by animals. Severe leptospirosis may result in hospitalisation and about five per cent of the patients die. In clinical practice, penicillin is widely used for treating leptospirosis. OBJECTIVES: To evaluate the effectiveness and safety of antibiotics versus placebo or other antibiotic regimens in treating leptospirosis. We addressed the following clinical questions: a) Are treatment regimens with antibiotics more efficient than placebo for leptospirosis? b) Are treatment regimens with antibiotics safe when compared to placebo for leptospirosis? c) Which antibiotic regimen is the most efficient and safest in treating leptospirosis? SEARCH STRATEGY: Electronic searches and searches of the identified articles were combined. SELECTION CRITERIA STUDIES: Randomised clinical trials in which antibiotics were used as treatment for leptospirosis. Language, date, or other restrictions were not applied. PARTICIPANTS: Patients with clinical manifestations of leptospirosis. INTERVENTIONS: Any antibiotic regimen compared with a control group (placebo or another antibiotic regimen). DATA COLLECTION AND ANALYSIS: Data and methodological quality of each trial were independently extracted and assessed by two reviewers. The random effects model was used irrespective of significant statistical heterogeneity. MAIN RESULTS: Three trials met inclusion criteria. Allocation concealment and double blind methods were not clearly described in two. Of the patients enrolled, 75 were treated with placebo and 75 with antibiotics: 61 (81.3%) penicillin and 14 (18.6%) doxycycline. The patients assigned to antibiotics compared to placebo showed: a) Mortality: 1% (1/75) versus 4% (3/75); risk difference -2%, 95% confidence interval -8% to 4%. b) Duration of hospital stay (days): weighted mean difference 0.30, 95% confidence interval -1.26 to 1.86. c) Prolonged hospital stay (> seven days): 30% (7/23) versus 74% (14/19); risk difference -43%, 95% confidence interval -70% to -16%. Number needed-to-treat 3, 95% confidence interval 2 to 7. d) Period of disappearance of fever (days): weighted mean difference -4.04, 95% confidence interval -8.65 to 0.58. e) Leptospiruria: 5% (4/75) versus 40% (30/75); risk difference -46%, 95% confidence interval -88% to -3%. Number needed-to-treat 2, 95% confidence interval 1 to 33. REVIEWER'S CONCLUSIONS: Antibiotic regimens for treatment of leptospirosis is a form of care for which the evidence is insufficient to provide clear guidelines for practice. The randomised trials suggest that antibiotics could be a useful treatment for leptospirosis. Because of the questionable quality of two of the three trials, the indication for general use of antibiotics is uncertain. However, the evidence suggest that penicillin may cause more good than harm.

Anti-Bacterial Agents↗

An observational study to detect leptospirosis in Mumbai, India, 2000.

BACKGROUND: Leptospirosis is relatively uncommon in children. Following torrential rains and flooding an outbreak of leptospirosis was suspected in Mumbai. AIMS: To investigate the possibility of an outbreak of leptospirosis and describe the clinical illness. METHODS: From 24 July to 14 September 2000, children with a history of abrupt onset of high fever (>39 degrees C), who presented to our hospital, were admitted and tested serologically for anti-Leptospira antibodies by a quantitative enzyme linked immunosorbent assay (ELISA) test. An IgM titre of more than 20U/ml confirmed the diagnosis of leptospirosis. Clinical features in the confirmed leptospirosis and leptospirosis negative groups were analysed. RESULTS: Of 53 children screened, 18 (34%) had leptospirosis. In all 18, the disease was anicteric and responded well to intravenous penicillin. Four clinical features present at the time of admission were significantly associated with leptospirosis: a history of contact with flood water (18/18 v 16/35), conjunctival suffusion (5/18 v 1/35), abdominal pain (9/18 v 5/35), and skin rash (5/18 v 1/35). As the number of these four features concomitantly present increased, the chances of the child having leptospirosis also increased significantly. A history of contact with flood water had a sensitivity of 100%, and the presence of conjunctival suffusion, abdominal pain, and skin rash had a specificity of 97%, 86%, and 97%, respectively, for identifying children with leptospirosis. CONCLUSION: Leptospirosis should be suspected in febrile children with contact with flood water.

Age Distribution↗

Leptospirosis among patients presenting with dengue-like illness in Puerto Rico.

Leptospirosis is difficult to distinguish from dengue fever without laboratory confirmation. Sporadic cases/clusters of leptospirosis occur in Puerto Rico, but surveillance is passive and laboratory confirmation is rare. We tested for leptospirosis using an IgM ELISA on sera testing negative for dengue virus IgM antibody and conducted a case-control study assessing risk factors for leptospirosis, comparing clinical/laboratory findings between leptospirosis (case-patients) and dengue patients (controls). Among 730 dengue-negative sera, 36 (5%) were positive for leptospirosis. We performed post mortem testing for leptospirosis on 12 available specimens from suspected dengue-related fatalities; 10 (83%) tested positive. Among these 10 fatal cases, pulmonary hemorrhage and renal failure were the most common causes of death. We enrolled 42 case-patients and 84 controls. Jaundice, elevated BUN, hyperbilirubinemia, anemia, and leukocytosis were associated with leptospirosis (p < .01 for all). Male sex, walking in puddles, rural habitation, and owning horses were independently associated with leptospirosis. Epidemiological, clinical, and laboratory criteria may help distinguish leptospirosis from dengue and identify patients who would benefit from early antibiotic treatment.

Adolescent↗

Concurrent outbreak of leptospirosis and dengue in Mumbai, India, 2002.

This prospective study was undertaken to investigate the possibility of a concurrent outbreak of leptospirosis and dengue and to describe the clinical illnesses. From 20 June to 14 November 2002, children who presented to our hospital with a suspected diagnosis of leptospirosis or dengue were admitted. In every child with suspected leptospirosis, a screening latex agglutination test was carried out to detect anti-Leptospira antibodies. The diagnosis of leptospirosis was confirmed by a positive enzyme-linked immunosorbent assay (ELISA) test or microagglutination test. The diagnosis of dengue was confirmed by a positive IgM antibody capture ELISA test. Clinical features in the leptospirosis and leptospirosis-negative groups, and dengue and dengue-negative groups were analysed. Of 90 children screened, 15 (16.7 per cent) had leptospirosis. Two children with Weil's disease died and the remaining 13 responded well to intravenous penicillin. Five clinical features were significantly associated with leptospirosis, namely conjunctival suffusion (p=0.007), haemorrhage (p=0.020), abdominal pain (p=0.011), hepatosplenomegaly (p=0.044), and oedema (p=0.007). As the number of these five features concomitantly present increased, the chances of the child having leptospirosis also increased significantly (p<0.0001). Of 90 children screened, 16 (17.8 per cent) had dengue. All responded well to the treatment and went home. Two clinical features were significantly associated with dengue, namely arthralgia (p=0.020) and thrombocytopenia (p=0.001). If both these features were present, the chances of the child having dengue increased significantly (p=0.001). Our study shows that a concurrent outbreak of leptospirosis and dengue had occurred in the slums of Mumbai city.

Age Distribution↗

Thrombocytopenia in the experimental leptospirosis of guinea pig is not related to disseminated intravascular coagulation.

BACKGROUND: Thrombocytopenia is commonly observed in severe leptospirosis. However, previous studies on coagulation alterations during leptospirosis resulted in inconsistent conclusions. Some findings showed that the prominent levels of thrombocytopenia observed in severe leptospirosis did not reflect the occurrence of disseminated intravascular coagulation (DIC) syndrome, while the others reached the conclusion that the hemorrhages observed in leptospirosis were due to DIC. The aim of this study is to elucidate whether DIC is an important feature of leptospirosis. METHODS: The leptospirosis model of guinea pig was established by intraperitoneal inoculation of Leptospira interrogans strain Lai. Hematoxylin and eosin (HE) staining, electron microscopy and immunohistochemistry staining were used to detect the pathologic changes. Platelet thrombus or fibrin thrombus was detected by HE, Martius Scarlet Blue (MSB) staining and electron microscopy. Hemostatic molecular markers such as 11-dehydrogenate thromboxane B2 (11-DH-TXB2), thrombomodulin (TM), thrombin-antithrombin III complex (TAT), D-Dimer and fibrin (ogen) degradation products (FDPs) in the plasma were examined by quantitative enzyme-linked immunosorbent assay (ELISA) to evaluate the hematological coagulative alterations in leptospirosis models. RESULTS: Pulmonary hemorrhage appeared in the model guinea pig 24 hours after leptospires intraperitoneal inoculation, progressing to a peak at 96 hours after the infection. Leptospires were detected 24 hours post-inoculation in the liver, 48 hours in the lung and 72 hours in the kidney by immunohistochemistry staining. Spiral form of the bacteria was initially observed in the liver, lung and kidney suggestive of intact leptospires, granular form of leptospires was seen as the severity increased. Platelet aggregation in hepatic sinusoid as well as phagocytosis of erythrocytes and platelets by Kupffer cells were both observed. Neither platelet thrombus nor fibrin thrombus was found in the liver, lung or kidney via morphological observation. Thrombocytopenia was observed in all infected guinea pigs of our experimental leptospirosis study. Analysis of hematologic molecular markers showed that 11-DH-TXB2 and TM in the plasma were elevated significantly. TAT that reflects the thrombin activation had a trend of decline after infection. Although D-dimer and FDPs increased statistically, the increasing may not bear clinical significance. CONCLUSION: Pathologic and hematological studies for experimental leptospirosis of guinea pig indicated that the thrombocytopenia found in guinea pigs did not correlate with the occurrence of DIC. The platelet aggregation and Kupffer cells phagocytosis might be the potential causes of thrombocytopenia in severe leptospirosis.

Animals↗

Clinical application of a polymerase chain reaction assay for diagnosis of leptospirosis in dogs.

OBJECTIVE: To evaluate the use of a polymerase chain reaction (PCR) assay on urine samples for diagnosis of leptospirosis in dogs. DESIGN: Prospective case study. ANIMALS: 132 dogs with clinical signs suggestive of leptospirosis and 13 healthy dogs. PROCEDURE: PCR testing was performed on urine samples to detect leptospiral DNA; results were compared with results of conventional criteria for the diagnosis of leptospirosis. RESULTS: Leptospirosis was diagnosed in 8 dogs via established criteria; all these dogs had positive results of PCR assay, including 1 dog with positive results before seroconversion developed. A positive PCR assay result was also obtained in 16 dogs that did not have a confirmed diagnosis of leptospirosis. In the 8 dogs that had a confirmed diagnosis of leptospirosis, serovars pomona (n = 3 dogs), grippotyphosa (2), canicola (2), and bratislava (1) were identified serologically. The remaining 121 dogs all had a diagnosis other than leptospirosis or were healthy. For PCR testing on urine, sensitivity was 100%, specificity was 88.3%, positive predictive value was 33%, and negative predictive value was 100%. CONCLUSIONS AND CLINICAL RELEVANCE: Positive PCR test results prior to seroconversion may have value in establishing an early diagnosis. Positive results in dogs that had signs consistent with leptospirosis despite failing to meet established criteria for leptospirosis raise questions regarding the sensitivity of serologic testing in diagnosis of leptospirosis. Serovars pomona, grippotyphosa, and canicola were most common.

Animals↗

Seasonality of canine leptospirosis in the United States and Canada and its association with rainfall.

A retrospective study was undertaken to describe seasonal patterns of leptospirosis diagnosed at veterinary teaching hospitals in the United States and Canada, and to determine if occurrence of cases (diagnoses) was associated with rainfall. The veterinary medicine database (VMDB) was searched for records of dogs in which a diagnosis of leptospirosis was made, and average monthly rainfall recorded at the city where each hospital is located was calculated from historical data. Time-series analysis was used to identify the variables that best described occurrence of cases of leptospirosis. Three-hundred and forty dogs were diagnosed with leptospirosis at 22 veterinary teaching hospitals between 1983 and 1998. Most cases (n = 184) were diagnosed between August and November during each year of the study. A significant correlation (r = 0.41) was detected between the number of cases of leptospirosis diagnosed and average rainfall recorded 3-months prior to diagnosis. The best-fitting (Akaike's corrected information criterion = 2.01) regression on the leptospirosis case series included cases diagnosed in the previous month and 12-months previously, and rainfall recorded 3 months previously. Leptospirosis has a seasonal distribution (late summer to fall), and rainfall can be used to predict the occurrence of leptospirosis. Leptospirosis can affect the health of dogs seriously and its prevalence is increasing, but the disease is preventable by vaccination.

Animals↗

Leptospirosis in Istanbul, Turkey: a wide spectrum in clinical course and complications.

Patients with high fever and multiorgan involvement were investigated for the determination of frequency, clinical course and complications of leptospirosis in Istanbul. Leptospirosis was determined in 22 cases among the 35 hospitalized patients that were pre-diagnosed as leptospirosis according to 'Probable Leptospirosis Diagnosis and Follow-up' form. Among the leptospirosis cases 19 were male and 16 were military staff. Mean age was 35.6 y. Dark field examination (DFE), latex agglutination test (LAG), ELISA IgM, leptospirosis culture (LC) and microscopic agglutination test (MAT) were performed to confirm the diagnoses. The most frequent initial symptoms and findings were fever, fatigue, headache, nausea-vomiting and increased muscle sensitivity. Jaundice was noted only in 2 cases. A 74-y-old female patient died after the recurrence of the disease with severe rhabdomyolysis and pulmonary failure. Sagittal sinus thrombosis, perimyocarditis and chronic renal failure were major complications in another 3 patients. ELISA IgM, LC, DFE, LAG and MAT tests were positive in 68, 72, 82, 100 and 100% of the patients, respectively. As a conclusion, diagnosis of leptospirosis is usually overlooked. Clinical awareness, use of probable leptospirosis diagnosis forms and the application of different laboratory methods in the diagnosis of suspected cases may offer the chance to diagnose the leptospirosis accurately.

Adult↗

Evaluation of the indirect hemagglutination assay for diagnosis of acute leptospirosis in Hawaii.

Timely diagnosis of leptospirosis is important to ensure a favorable clinical outcome. The definitive serologic assay, the microscopic agglutination test (MAT), requires paired sera and is not useful for guiding early clinical management. The only screening test approved for use in the United States, the indirect hemagglutination assay (IHA), has not undergone extensive field evaluation. To assess the performance of the leptospirosis IHA in Hawaii, serum from patients evaluated for leptospirosis between 1992 and 1997 were tested with the IHA at the Hawaii State Laboratories Division and with the MAT at the Centers for Disease Control and Prevention. Leptospirosis was considered confirmed by a fourfold rise in MAT titer and/or a positive culture. A total of 92 (41%) of 226 specimens from 114 persons with confirmed leptospirosis were found positive by IHA. Only 18 (15%) of 119 specimens obtained within 14 days of onset were IHA positive, compared to 74 (69%) of 107 specimens collected more than 14 days after onset (P <0.001). Repeat testing ultimately resulted in 78 (68%) of the confirmed cases having at least one specimen found positive by IHA. Thirteen different presumptive infecting serogroups were identified among 251 specimens with an MAT titer of >/=200 and obtained from persons with confirmed or probable leptospirosis. Fifty (68%) of 73 specimens with Icterohaemorrhagiae as the presumptive infecting serogroup were found positive by IHA, compared to 44 (47%) of 93 specimens with Australis as the presumptive infecting serogroup (P, 0.01). The IHA test was positive for 3 (1%) of 236 specimens from 154 persons without leptospirosis. The sensitivity of the leptospirosis IHA in Hawaii was substantially below figures reported previously, particularly early in the course of illness, limiting its usefulness for diagnosing acute infection. Since the presumptive infecting serogroup affected IHA results and the prevalence of serovars varies with geography, the performance of the IHA should be assessed locally. More sensitive leptospirosis screening tests are needed in Hawaii.

Acute Disease↗

Increase of leptospirosis in dengue-negative patients after a hurricane in Puerto Rico in 1996 [correction of 1966].

Leptospirosis has rarely been reported in Puerto Rico, although in the period from 1948 to 1952, 208 cases of leptospirosis and an island-wide seroprevalence of antibody to Leptospira of 14% were documented. In Puerto Rico in October 1996, following rainfall and a period of flooding generated by Hurricane Hortense, serum specimens of 4 patients with suspected dengue fever that were negative for dengue tested positive for Leptospira-specific IgM antibodies in a dipstick assay. Subsequently, we used an island-wide dengue laboratory-based surveillance system to determine the increase in leptospirosis after hurricane-generated floods. All anti-dengue IgM-negative patients (n = 142) with disease onset from August 8 to October 6, 1996 from prehurricane and posthurricane groups were investigated for leptospirosis. Laboratory-confirmed leptospirosis cases were defined as microscopic agglutination test titers > or = 1 :400 to 1 or more serovars, or positive immunohistochemistry in autopsy tissues. Four (6%) of 72 prehurricane and 17 (24%) of 70 posthurricane patients had laboratory-confirmed cases of leptospirosis (relative risk [RR] = 4.4, 95% confidence interval [CI] = 1.6-12.4). The mean age of case-patients was 34 years (range = 13-64). Eighteen (86%) of 21 confirmed case-patients were males, including one patient who died (31 years old). Patients were located in 18 (38%) of 48 municipalities that submitted serum samples. Clinical features significantly associated with leptospirosis were eye pain (RR = 1.5, 95% CI = 1.3-1.9), joint pain (RR = 1.4, 95% CI = 1.1-1.6), diarrhea (RR = 1.7, 95% CI = 1.2-2.5), and jaundice (RR = 3.3, 95% CI = 1.5-7.2). This study demonstrates the utility of a dengue laboratory-based surveillance system for the detection of an increase of leptospirosis, which most likely would have gone unrecognized. Leptospirosis is treatable with antibacterial agents; knowledge of this diagnosis may significantly reduce morbidity and mortality.

Adolescent↗

Clinical distinction and evaluation of leptospirosis in Taiwan--a case-control study.

BACKGROUND: Leptospirosis is the most widespread zoonosis. Leptospirosis remains underreported in Taiwan because of ignorance and the broad spectrum of clinical manifestations. Acute renal failure (ARF) is a prominent feature of leptospirosis. This investigation conducted a case-control study to obtain information to distinguish leptospirosis from other conditions with similar presentations. METHODS: Leptospirosis surveillance was performed at Chang Gung Memorial Hospital, Taiwan, between September 2000 and December 2001. Suspected clinical cases were included in the sample and investigated. Diagnosis was confirmed with four-fold or greater increase of microscopic agglutination test (MAT) titer in paired sera; positive immunoglobulin M (IgM) dipstick with single MAT > or =400; or isolation of leptospira. Cases were classified as excluded based on confirmed etiology other than leptospirosis or negative paired serologic test. RESULTS: Twenty-two confirmed cases and 21 excluded cases of leptospirosis were identified from among 169 suspected cases. An outbreak was observed during the flooding from Typhoon Nali. L. shermani, the most common serovar in Taiwan, was identified in 78.5% of confirmed cases. In the confirmed group, mean age was 44 +/- 14.5 (21-66) yrs similar to that of the excluded group, with male predominance (86.4 vs. 57.1%, p<0.05). The most common presentations in the confirmed group were fever (95.5%), ARF (86.4%), myalgia (72.7%) and jaundice (63.6%). Ten patients were infected through occupational or recreational exposure, and in six patients, the infection was associated with flooding. The most distinct presentations of leptospirosis cases compared with excluded cases were increased incidence of hemorrhagic diathesis (odds ratio (OR): 10, p=0.04), myalgia (OR: 8.0, p=0.02), bilateral enlarged kidneys (OR: 7.5, p=0.0004), risk factor exposure (OR: 6.9, p=0.005), sterile pyuria (OR: 6.3, p=0.017), hypokalemia (OR: 5.0, p=0.035) and thrombocytopenia (OR: 4.8, p=0.04). Hospitalization days correlated well with levels of peak creatinine (Cr) (p=0.0362) and platelet nadir (p=0.0039) reached. Penicillin treatment was followed by rapid symptoms and renal function improvement. CONCLUSIONS: Prompt recognition of the characteristic presentations of leptospirosis, followed by timely antibiotic treatment, can dramatically save the patients even with severe multiple organ damage.

Adult↗

[Changes in the epidemiology of human leptospirosis in the Slovak Republic].

BACKGROUND: The epidemiologic patterns of infectious diseases are liable to change in the course of time. References to such changes in leptospirosis are very rare and of low systematic value. OBJECTIVES: The study is aimed at the detection of changes in the epidemiology of leptospirosis within the 20 years in Slovakia. METHODS: Basic epidemiologic characteristics of leptoospirosis were compared within two chronological periods. 598 registered cases were analyzed during the first period (1970-1976), and 200 cases of leptospirosis were analysed during the second period (1986-1991). MAIN RESULTS: The second period yielded a decrease in total incidence to approximately 50% (yearly average was 0.9/10(5) of the population). At the same time the cyclic character of morbidity has almost entirely disappeared. The incidence of leptospirosis has significantly decreased in the group of population between 40 and 59 years of age, thus causing a particular shift in morbidity towards the younger population. Cases of leptospirosis caused by L. tarassovi and L. canicola ceased to occur, however one case of infection caused by L. hardjo has been registered in the Slovak population. A significant decrease in the incidence of diseases caused by the Sejroe group serovars was detected, especially in housewives, retired people, industrial and agricultural workers. In contrast to the latter, the proportion of leptospirosis cases caused by L. icterohaemorrhagiae/copenhageni increased particularly in pupils and students, as well as those caused by L. pomona in slaughter-house workers. Consequently, the most dominating disease is represented by field fever (L. gripotyphosa), the second highest incidence is ascribed to Weil disease (L. icterohaemorrhagiae/copenhageni), while the incidence of infections caused by the group of Sejroe serovars dropped from the first to the fourth place. The possible reasons of these changes are presented. No changes in the incidence of leptospirosis according to sex and seasonal occurrence were registered. CONCLUSION: The results of this study are in accordance with the current knowledge of the development of epidemiologic signs of infectious diseases, including leptospirosis. The results provide a pattern of the current situation in the field of leptospirosis epidemiology in the territory of Slovakia and emphasize the importance of systematic surveillance enabling the assessment of appropriate measures suppressing these infections. (Fig. 7, Ref. 7.).

Adolescent↗

Leptospirosis in children in Mumbai slums.

OBJECTIVE: There is limited data available on symptomatic leptospirosis in Indian children. We report an outbreak of leptospirosis that occurred in children living in slums following heavy rainfall and flooding. This hospital-based prospective study was conducted from July to August 2001. METHODS: Diagnosis of acute leptospirosis was suspected by following the Indian Leptospirosis Society working definition for leptospirosis. Diagnosis was confirmed by detecting anti-Leptospira antibodies, using either a Leptospira genus-specific latex agglutination assay or a dipstick assay or by a macroscopic slide agglutination test. RESULT: Thirty (32%) out of 93 children admitted had acute leptospirosis. Fever, bodyache, chills, abdominal pain, headache, vomiting, cough, hepatosplenomegaly, edema and crepitations were the common presenting signs and symptoms. Twenty - two children had anicteric leptospirosis and 8 had Weil disease. Response to penicillin treatment was good in all except in one child with Weil disease who died of renal failure within 3 hours of admission. CONCLUSION: Leptospirosis has emerged as an infectious disease in Mumbai. During monsoon, parents should ensure that their child does not have contact with the contaminated flood water.

Child↗

An open, randomized, controlled trial of penicillin, doxycycline, and cefotaxime for patients with severe leptospirosis.

BACKGROUND: Leptospirosis is an important cause of fever in the rural tropics. Since 1996, there has been a marked increase in the incidence of leptospirosis in northeastern Thailand. Although leptospirosis generally is susceptible to antibiotics, there is no consensus regarding the optimal treatment for severe leptospirosis. METHODS: An open-label, randomized comparison of parenteral cefotaxime, penicillin G sodium (hereafter known as "penicillin G"), and doxycycline for the treatment of suspected severe leptospirosis was conducted. The study involved 540 patients admitted to 4 hospitals in northeastern Thailand. RESULTS: A total of 264 patients (48.9%) had leptospirosis confirmed by serologic testing or culture. The overall mortality rate was 5%. There were no significant differences between the antibiotics with regard to associated mortality, defervescence, or time to resolution of abnormal findings of laboratory tests either among all study participants or among the subgroup of patients with confirmed leptospirosis. A total of 132 patients had rickettsial infection diagnosed, and, for these patients, treatment with doxycycline was superior to treatment with penicillin G. CONCLUSIONS: Doxycycline or cefotaxime is a satisfactory alternative to penicillin G for the treatment of severe leptospirosis.

Adolescent↗

Leptospirosis leads to dysregulation of sodium transporters in the kidney and lung.

Leptospirosis is a public health problem worldwide. Severe leptospirosis manifests as pulmonary edema leading to acute respiratory distress syndrome and polyuric acute renal failure (ARF). The etiology of leptospirosis-induced pulmonary edema is unclear. Lung edema clearance is largely affected by active sodium transport out of the alveoli rather than by reversal of the Starling forces. The objective of this study was to profile leptospirosis-induced ARF and pulmonary edema. We inoculated hamsters with leptospires and collected 24-h urine samples on postinoculation day 4. On day 5, the animals were killed, whole blood was collected, and the kidneys and lungs were removed. Immunoblotting was used to determine expression and abundance of water and sodium transporters. Leptospirosis-induced ARF resulted in natriuresis, lower creatinine clearance, and impaired urinary concentrating ability. Renal expression of the sodium/hydrogen exchanger isoform 3 and of aquaporin 2 was lower in infected animals, whereas that of the Na-K-2Cl cotransporter NKCC2 was higher. Leptospirosis-induced lesions, predominantly in the proximal tubule, were responsible for the polyuria and natriuresis observed. The polyuria might also be attributed to reduced aquaporin 2 expression and the attendant urinary concentrating defect. In the lungs, expression of the epithelial sodium channel was lower, and NKCC1 expression was upregulated. We found that leptospirosis profoundly influences the sodium transport capacity of alveolar epithelial cells and that impaired pulmonary fluid handling can impair pulmonary function, increasing the chance of lung injury. Greater knowledge regarding sodium transporter dysregulation in the lungs and kidneys can provide new perspectives on leptospirosis treatment.

Acute Kidney Injury↗