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PubMed2002

Leptospirosis, water sports, and chemoprophylaxis.

Recreational activities, such as water sports and adventure travel, are emerging as an important risk factor for leptospirosis, a potentially fatal zoonosis. We report the clinical course of 2 patients who acquired leptospirosis through participation in water sports. Physicians caring for patients who participate in adventure travel involving water sports should be familiar with the risk factors for and diagnosis, prevention, and treatment of leptospirosis.

Adult↗
PubMed2003

Usefulness of serologic analysis as a predictor of the infecting serovar in patients with severe leptospirosis.

The diagnosis of leptospirosis is often made using the microscopic agglutination test (MAT), in which live antigens representing >20 serogroups undergo reaction with patient serum samples to detect agglutinating antibodies. Data derived from this assay are often used to infer the identity of the infecting leptospiral serovar or serogroup; however, paradoxical reactions and cross-reactions between serogroups are common. To evaluate the usefulness of this approach, data on culture-proven cases of leptospirosis that occurred in Barbados from January 1980 through December 1998 were reviewed. A total of 151 isolates of 4 serovars were identified. The sensitivity of MAT for the prediction of the infecting serovar was determined. Overall, the predominant serogroup at a titer of >or=100 correctly predicted 46.4% of all serovars isolated. If a titer of >or=800 was used as the cutoff, sensitivity decreased slightly to 44.4%. The overall specificity for all serogroups was 64.8%. Serologic analysis appeared to be of little value for the identification of the infecting serovar in individual cases of leptospirosis in humans. Presumptive serogroup reactivity data should be used only to gain a broad idea of the serogroups present at the population level.

Bacteriological Techniques↗
PubMed2006

Suburban leptospirosis: atypical lymphocytosis and gamma-delta T cell response.

Leptospirosis is a zoonotic disease associated with a changing global epidemiology. Recently, an increased incidence of canine leptospirosis in the northeastern United States and Canada has been associated with increasing rates of infection among reservoir hosts, such as skunks, raccoons, and squirrels, that are common in suburban settings. We describe a case of leptospirosis that provides new insight into the epidemiology, diagnosis, and pathogenesis of this disease acquired in the suburban setting. Atypical lymphocytosis corresponded to an expansion of gamma-delta T cells in peripheral blood.

Animals↗
PubMed1994

Leptospirosis complicated by a Jarisch-Herxheimer reaction and adult respiratory distress syndrome: case report.

Leptospirosis, severe infection due to Leptospira interrogans, is a potentially lethal disease that causes multiple organ failure. In addition to hepatic, renal, and CNS involvement, which are classic complications of leptospirosis, the disease may also be complicated by adult respiratory distress syndrome. Treatment with penicillin may precipitate a severe Jarisch-Herxheimer reaction. The mechanisms of Leptospira-induced toxicity remain obscure. We report a near-fatal case of leptospirosis in a patient who developed a JHR and respiratory failure immediately after initiation of therapy.

Drug Eruptions↗
PubMed1994

Leptospirosis in travelers.

Between 1987 and 1991 leptospirosis in 32 Dutch travelers was diagnosed. Infections were acquired predominantly in Thailand and other Southeast Asian countries. Contact with surface waters could be confirmed in all but one case. Fever, headache, and myalgia were the most common complaints. Signs included conjunctival injection and lymphadenopathy in 11 patients each, jaundice in 8, and nuchal rigidity in 3; renal function was impaired in 8. Leptospires were isolated from the blood or urine of nine patients. Thirty-one patients developed an antibody response. Classification of strains identified a variety of serogroups. Although only 14 patients received adequate treatment, all patients recovered completely. Since the number of patients with imported leptospirosis is increasing and the signs and symptoms of the disease are not specific, leptospirosis should be included in the differential diagnosis when a traveler returns from the Tropics with fever.

Asia, Southeastern↗
PubMed1990

Limulus lysate positivity and Herxheimer-like reactions in leptospirosis: a placebo-controlled study.

Jarisch-Herxheimer reactions are characteristic of some spirochetal diseases and have been reported in leptospirosis, but their pathogenesis and relationship to endotoxin remain unclear. Serial limulus amebocyte lysate assays (LAL) for endotoxin were performed on 40 patients with proven leptospirosis who were monitored for reactions after receiving either intravenous penicillin (24) or saline placebo (16). No Herxheimer-like reactions were observed, although 78% of patients had at least one positive LAL. Serum creatinine, serum bilirubin, and white blood cell counts were significantly higher (P less than .01) in simultaneously drawn LAL-positive specimens than in negative ones. Delayed hepatic clearance of endotoxin due to liver dysfunction may explain the high LAL positivity rate, since assay results correlated with severity of disease but not with the presence or absence of spirochetes. Fear of a Herxheimer-like reaction should not dissuade clinicians from administering antibiotics to patients with leptospirosis.

Adult↗
PubMed2003

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

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

Acute Kidney Injury↗
PubMed1990

Long-term follow-up after leptospirosis.

Human leptospirosis is an infectious disease that is a substantial problem in the Third World, but it can occur in developed countries as well. Survivors of the acute disease are considered to recover without sequelae, though little literature exists on long-term follow-up among these patients. Eleven patients, at an average of 22 years after acute leptospirosis, were reevaluated for possible delayed sequelae. Results showed that liver and renal disease had resolved, but headache and ophthalmic sequelae persisted. Even though the number of patients involved in this study is small, it appears that the eyes, particularly the anterior chambers, may be the site of continuing morbidity after acute human leptospirosis. The pathogenesis for persistent headache is not known.

Acute Disease↗
PubMed2003

Field application of Lepto lateral flow for rapid diagnosis of leptospirosis.

The Lepto lateral flow assay for leptospirosis was evaluated at a primary health centre in the Andaman Islands, where leptospirosis is endemic. One hundred and seventeen suspected patients were included in the study; acute serum samples were collected from all of them and convalescent samples from 104. The standard criteria for diagnosis of leptospirosis were: (i) isolation of leptospires from blood, (ii) seroconversion in microscopic agglutination test (MAT) with a minimum titre of 100, (iii) a fourfold rise in titre in MAT or (iv) a MAT titre of 400 or more if only a single sample was available. The results of the lateral flow test were compared with these criteria. Lepto lateral flow had sensitivity of 52.9 % (37/70) in the first week of illness and 86 % (49/57) during weeks 2-4. The corresponding specificities were respectively 93.6 % (44/47) and 89.4 % (42/47). The sensitivity was 34.3 % (12/35) on days 2-3 of the illness, 63.3 % (14/22) on days 4-5 and 84.6 % (11/13) at the end of the first week. The test had a positive predictive value of 92.5 % (37/40) during the first week and 90.7 % (49/54) subsequently. Corresponding negative predictive values were respectively 57.1 % (44/77) and 84 % (42/50). Agreement of the results with the standard criteria was low during the first week, but high during weeks 2-4, with a kappa value of 0.7491. The positivity rates of the tests showed a logarithmic relationship with the MAT titres of samples (r(2) = 0.9271). All indices of validity and utility of lateral flow were similar to those of IgM ELISA and Lepto dipstick. The test can be performed at the bedside of the patient, as whole blood can also be used for testing.

Agglutination Tests↗
PubMed2003

Identification and evaluation of LPS antigen for serodiagnosis of uveitis associated with leptospirosis.

Leptospirosis is a widespread zoonotic disease that affects all mammals in different parts of the world. Though there are many commercial kits available for the diagnosis of systemic leptospirosis, the nature of the antigen has not been described. Therefore, identification of a specific antigen is important. Since ocular involvement in leptospirosis has been reported, there is a need to identify and characterize the leptospiral antigen for diagnosis of uveitis associated with past leptospiral infection (leptospiral uveitis) and for confirming the clinical diagnosis. Seven-day-old culture of Leptospira biflexa serovar Patoc was used for preparing the antigen. The present study included serum samples from 81 patients with clinical criteria for leptospiral uveitis, 15 cataract controls and 15 non-leptospiral uveitis controls. Serum samples were assayed by ELISA using our antigenic preparation and by a microscopic agglutination test (MAT) using 19 serovars. The antigen prepared had 280 micro g LPS ml(-1) and no detectable amount of protein. Silver-staining of SDS-PAGE for protein and LPS, dot blot and Western blot analysis and proteinase K and periodate treatment showed that LPS (13-21 kDa and 28 kDa) in our preparation was the relevant antigen for serodiagnosis. IgG antibodies showed reactivity in both leptospiral uveitis patients and controls. However, on the basis of IgM response to LPS, 48 % of the leptospiral uveitis patients were significantly positive compared with controls; 58 % of leptospiral uveitis patients and none of the controls were positive for MAT. When MAT and IgM ELISA results were considered together, 77 % were significantly positive. LPS is identified as a candidate antigen for serodiagnosis of leptospiral uveitis and has sensitivity and specificity of 48 and 90 %, respectively, in ELISA for IgM antibodies. Confirmation of clinical diagnosis with a specific laboratory test would help to initiate the most appropriate treatment for leptospiral uveitis.

Adult↗
PubMed2006

Polymerase chain reaction in comparison with serological tests for early diagnosis of human leptospirosis.

The aim of this study was to compare the sensitivity and specificity of polymerase chain reaction (PCR) using two primer pairs and combined with blood culture, immunoglobulin M enzyme-linked immunosorbent assay (IgM ELISA), microscopic agglutination test (MAT) and slide agglutination test (SAT) in the diagnosis of human leptospirosis. We analysed 124 serum samples: 60 from patients with confirmed leptospirosis, 20 from patients with other diseases and 44 from healthy individuals. Analysing the first serum sample collected during the first 3-8 days of disease, the sensitivities of the four tests MAT, IgM ELISA, SAT and PCR were, respectively, 69.0%, 79.3%, 72.4% and 62%. In subsequent samples, those same sensitivities were, respectively, 95.4%, 100%, 100% and 72.7% in samples collected from days 9 to 14 and 88.9%, 88.9%, 77.8% and 44.4% in those collected from days 15 to 42. The most specific method (at 100%) was PCR and the least specific (at 89.1%) was IgM ELISA. Although we found PCR to be less sensitive than the serological tests over the course of the disease, our data indicate that PCR was the most sensitive in those initial serum samples presenting no specific antibodies detectable by any of the serological methods tested. We also recommend that PCR can be used in combination with serological tests as we found that this improves the sensitivity of the diagnosis of leptospirosis in the first phase of the disease (93.1-96.5%).

Adult↗
PubMed2007

Rapid diagnostic tests for dengue and leptospirosis: antibody detection is insensitive at presentation.

OBJECTIVE: To determine the performance of rapid diagnostic tests for dengue and leptospirosis that rely on detecting antibodies that may not be produced when patients present for medical treatment. METHODS: We prospectively enrolled 723 patients with undifferentiated febrile illness presenting to rural hospitals in northern and northeastern Thailand over a 1-year period. We evaluated rapid antibody detection diagnostic tests for dengue and leptospirosis on these patients. RESULTS: Sensitivity of the tests was low at the acute visit (7.6-21.5%). Sensitivity at the convalescent visit ranged from 25.8% to 81.5% and was significantly higher than at the acute visit for all tests (chi(2), P < 0.001). CONCLUSIONS: Low sensitivity of the rapid tests at presentation suggests that their utility in the acute phase of dengue and leptospirosis is limited.

Adolescent↗
PubMed2006

Prognostic factors associated with severe leptospirosis.

Leptospirosis is an anthropozoonosis caused by Leptospira interrogans. It occurs worldwide and is endemic in French Polynesia. Leptospirosis is associated with a large variety of clinical symptoms. Most infections caused by leptospires are either sub-clinical or of very mild severity, but 5-10% of infections result in multiple organ damage, including kidney, liver and lung lesions. Among 71 patients hospitalised in Papeete for severe leptospirosis during a period of 2 years, the main risk-factors for a severe outcome were hypotension, oliguria and an abnormal chest auscultation at the first physical examination. Survival depends on rapid diagnosis and early appropriate management. Well-defined criteria may help physicians to improve the timely treatment of high-risk patients.

Humans↗
PubMed2001

Following the course of human leptospirosis: evidence of a critical threshold for the vital prognosis using a quantitative PCR assay.

In order to follow the course of acute human leptospirosis, an ELISA microtiter plate hybridization method was developed for the quantitative determination of Leptospira spp. in biological samples after PCR. The biotin-labelled amplified product (331 bp from the rrs gene) was hybridized with a complementary capture probe covalently linked onto aminated polystyrene wells, and detected using a colorimetric reaction. The mean detection limit was 50 copies per 10 microl. In a prospective study of human leptospirosis cases, we obtained evidence that a density of 10(4) leptospires per ml of blood is a critical threshold for the vital prognosis of the patients. The practicability of the method makes it suitable for use in tropical areas for multicentric studies. Such studies could lead to a better knowledge of the natural history of the human disease. The method is also suitable for experimental evaluation of improved antibiotic treatments for leptospirosis.

Adolescent↗
PubMed2006

Efficacy of macrolides and telithromycin against leptospirosis in a hamster model.

Human studies support the use of beta-lactams and tetracyclines in the treatment of leptospirosis. Additional agents from these and other classes of antimicrobials also have in vitro activity against Leptospira species, though corroborating in vivo data are limited or lacking. We evaluated the therapeutic efficacy of azithromycin, clarithromycin, and telithromycin in a lethal hamster model of leptospirosis using Leptospira interrogans serogroup Canicola serovar Portlandvere. A range of dosages for each antimicrobial was given to the infected animals on days 2 through 7 (5 days) of the 21-day survival model. All untreated control animals survived less than 10 days from infection. Ninety to 100% of doxycycline controls, treated for 5 days with 5 mg/kg of body weight of drug, survived to 21 days. Treatment with azithromycin (daily dose: 6.25, 12.5, 25, 50, 100, or 200 mg/kg) resulted in 100% survival at all evaluated doses. Animals receiving 20 mg/kg or more of clarithromycin (daily dose: 1, 5, 10, 15, 20, 40, 60, or 100 mg/kg) had improved survival. Ninety-eight percent of animals treated with telithromycin (daily dose: 1, 5, 10, 15, 20, or 40 mg/kg) survived. We conclude that all agents tested have demonstrated in vivo efficacy in treating acute leptospirosis. These results provide support for further evaluation of macrolide and ketolide antimicrobial agents in human trials.

Animals↗
PubMed2001

Leptospirosis.

Leptospirosis is a worldwide zoonotic infection with a much greater incidence in tropical regions and has now been identified as one of the emerging infectious diseases. The epidemiology of leptospirosis has been modified by changes in animal husbandry, climate, and human behavior. Resurgent interest in leptospirosis has resulted from large outbreaks that have received significant publicity. The development of simpler, rapid assays for diagnosis has been based largely on the recognition that early initiation of antibiotic therapy is important in acute disease but also on the need for assays which can be used more widely. In this review, the complex taxonomy of leptospires, previously based on serology and recently modified by a genotypic classification, is discussed, and the clinical and epidemiological value of molecular diagnosis and typing is also evaluated.

Animals↗
PubMed1994

Detection of leptospires in urine by PCR for early diagnosis of leptospirosis.

We tested urine samples from patients at different stages of current leptospirosis and thereafter to determine whether use of the PCR for detection of leptospires in urine can be a valuable alternative to culturing. The procedure of DNA extraction and subsequent PCR applied to 15 freshly voided urine samples proved to be twice as sensitive as culturing. Overall, we were able to detect leptospires in approximately 90% (26 of 29) of the urine samples. Urine and serum samples were obtained from seven patients, before the eighth day of illness. Although it is generally assumed that leptospiruria starts approximately in the second week of illness, we were able to detect leptospires in all of these early urine samples. In contrast, only two of seven corresponding serum samples gave positive PCR results, which suggests that PCR analysis of urine can be more successful for early diagnosis of leptospirosis than PCR analysis of serum. Urine samples from six patients who had been treated with antibiotics at the time of illness were positive by PCR, implying that the patients were still shedding leptospires in their urine despite treatment. Some of these samples were even taken years after the infection, indicating that shedding of leptospires in urine may last much longer than is generally assumed. We conclude that detection of leptospires in urine with PCR is a promising approach for early diagnosis of leptospirosis and may also be useful in studying long-term shedding.

Acute Disease↗
PubMed2003

Evaluation of four commercially available rapid serologic tests for diagnosis of leptospirosis.

Four rapid tests for the serologic diagnosis of leptospirosis were evaluated, and the performance of each was compared with that of the current standard, the microscopic agglutination test (MAT). The four rapid tests were a microplate immunoglobulin M (IgM)-enzyme-linked immunosorbent assay (ELISA), an indirect hemagglutination assay (IHA), an IgM dipstick assay (LDS), and an IgM dot-ELISA dipstick test (DST). A panel of 276 sera from 133 cases of leptospirosis from four different geographic locations was tested as well as 642 sera from normal individuals or individuals with other infectious or autoimmune diseases. Acute-phase sera from cases (n = 148) were collected or=15 days after onset (median = 29.1). By a traditional method (two-by-two contingency table), the sensitivities for detection of leptospirosis cases were 93.2% by LDS, 92.5% by DST, 86.5% by ELISA, and 79.0% by IHA. Specificity was 98.8% by DST, 97% by ELISA and MAT, 95.8% by IHA, and 89.6% by LDS. With a latent class analysis (LCA) model that included all the rapid tests and the clinical case definition, sensitivity was 95.5% by DST, 94.5% by LDS, 89.9% by ELISA, and 81.1% by IHA. The sensitivity and specificity estimated by the traditional methods were quite close to the LCA estimates. However, LCA allowed estimation of the sensitivity of the MAT (98.2%), which traditional methods do not allow. For acute-phase sera, sensitivity was 52.7% by LDS, 50.0% by DST, 48.7% by MAT and ELISA, and 38.5% by IHA. The sensitivity for convalescent-phase sera was 93.8% by MAT, 84.4% by DST, 83.6% by LDS, 75.0% by ELISA, and 67.2% by IHA. A good overall correlation with the MAT was obtained for each of the assays, with the highest concordance being with the DST (kappa value, 0.85; 95% confidence interval [CI], 0.8 to 0.90). The best correlation was between ELISA and DST (kappa value, 0.86; 95% CI, 0.81 to 0.91). False-positive LDS results were frequent (>or=20%) in sera from individuals with Epstein-Barr virus, human immunodeficiency virus, and periodontal disease and from healthy volunteers. The ease of use and significantly high sensitivity and specificity of DST and ELISA make these good choices for diagnostic testing.

Humans↗