Laboratory diagnostic, epidemiological, and clinical characteristics of human leptospirosis in Okinawa Prefecture, Japan, 2003-2020.

BACKGROUND: Leptospirosis is considered an endemic disease among agricultural workers in Okinawa Prefecture, which is the southernmost part of Japan and has a subtropical climate, but data on the current status and trend of this disease are scarce. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a retrospective study of clinically suspected leptospirosis patients whose sample and information were sent to the Okinawa Prefectural Institute of Health and Environment from November 2003 to December 2020. Laboratory diagnosis was established using culture, nested polymerase chain reaction (PCR), and/or microscopic agglutination test (MAT) with blood, cerebrospinal fluid, and/or urine samples. Statistical analyses were performed to compare the epidemiological information, clinical features, and sensitivities of diagnostic methods among laboratory-confirmed cases. Serogroups and the species of Leptospira isolates were determined by MAT using 13 antisera and flaB sequencing. A total of 531 clinically suspected patients were recruited, among whom 246 (46.3%) were laboratory confirmed to have leptospirosis. Among the confirmed cases, patients aged 20-29 years (22.4%) and male patients (85.7%) were the most common. The most common estimated sources of infection were recreation (44.5%) and labor (27.8%) in rivers. Approximately half of the isolates were of the L. interrogans serogroup Hebdomadis. The main clinical symptoms were fever (97.1%), myalgia (56.3%), and conjunctival hyperemia (52.2%). Headache occurred significantly more often in patients with Hebdomadis serogroup infections than those with other serogroup infections. The sensitivities of culture and PCR exceeded 65% during the first 6 days, while the sensitivity of MAT surpassed that of culture and PCR in the second week after onset. PCR using blood samples was a preferable method for the early diagnosis of leptospirosis. CONCLUSIONS/SIGNIFICANCE: The results of this study will support clinicians in the diagnosis and treatment of undifferentiated febrile patients in Okinawa Prefecture as well as patients returning from Okinawa Prefecture.

A rare case of posterior reversible encephalopathy syndrome in a patient with severe leptospirosis complicated with rhabdomyolysis and acute kidney injury; a case report.

BACKGROUND: Leptospirosis is a zoonotic spirochetal disease caused by Leptospira interrogans. The clinical presentation ranges from an asymptomatic state to a fatal multiorgan dysfunction. Neurological manifestations including aseptic meningitis, spinal cord and peripheral nerve involvement, cranial neuropathies and cerebellar syndrome are well recognized with varying frequencies among patients with this disease. Posterior reversible encephalopathy syndrome is a very rare occurrence in leptospirosis and only two cases are reported in the medical literature up to now. We report a case of posterior reversible encephalopathy syndrome in a patient with leptospirosis with rhabdomyolysis and acute kidney injury. CASE PRESENTATION: A 21 year-old male presented with fever and oliguric acute kidney injury with rhabdomyolysis. A diagnosis of leptospirosis was made and he was being managed according to the standard practice together with regular hemodialysis. The clinical condition was improving gradually. On day 8 of the illness, he developed headache and sudden painless complete bilateral vision loss followed by several brief generalized tonic clonic seizure attacks. Examination was significant for a Glasgow Coma Scale of 14/15, blood pressure of 150/90 mmHg and complete bilateral blindness. The findings of magnetic resonance imaging of the brain were compatible with posterior reversible encephalopathy syndrome. He was managed with blood pressure control and antiepileptics with supportive measures and standard treatment for leptospirosis and made a complete recovery. CONCLUSION: Posterior reversible encephalopathy syndrome, though very rare with leptospirosis, should be considered as a differential diagnosis in a patient with new onset visual symptoms and seizures, especially during the immune phase. Optimal supportive care together with careful blood pressure control and seizure management would yield a favourable outcome in this reversible entity.

Blood Levels of Galectin-9, an Immuno-Regulating Molecule, Reflect the Severity for the Acute and Chronic Infectious Diseases.

Galectin-9 (Gal-9) is a ß-galactoside-binding lectin capable of promoting or suppressing the progression of infectious diseases. This protein is susceptible to cleavage of its linker-peptides by several proteases, and the resulting cleaved forms, N-terminal carbohydrate recognition domain (CRD) and C-terminal CRD, bind to various glycans. It has been suggested that full-length (FL)-Gal-9 and the truncated (Tr)-Gal-9s could exert different functions from one another via their different glycan-binding activities. We propose that FL-Gal-9 regulates the pathogenesis of infectious diseases, including human immunodeficiency virus (HIV) infection, HIV co-infected with opportunistic infection (HIV/OI), dengue, malaria, leptospirosis, and tuberculosis (TB). We also suggest that the blood levels of FL-Gal-9 reflect the severity of dengue, malaria, and HIV/OI, and those of Tr-Gal-9 markedly reflect the severity of HIV/OI. Recently, matrix metallopeptidase-9 (MMP-9) was suggested to be an indicator of respiratory failure from coronavirus disease 2019 (COVID-19) as well as useful for differentiating pulmonary from extrapulmonary TB. The protease cleavage of FL-Gal-9 may lead to uncontrolled hyper-immune activation, including a cytokine storm. In summary, Gal-9 has potential to reflect the disease severity for the acute and chronic infectious diseases.

Leptospira spp. in horses in southern Brazil: Seroprevalence, infection risk factors, and influence on reproduction.

Leptospirosis in horses is often associated with reproductive disorders. In the southern states of Brazil, horses are used for various jobs and cultural practices; nevertheless, serological surveillance for Leptospira is rare. Therefore, the objective of this study was to determine the seroprevalence of Leptospira spp. in horses in southern Brazil, as well as to identify the risk factors for infection and its impacts on reproduction. We performed microscopic agglutination tests for 12 serovars that corresponding 9 serogroup (Sejroe, Icterohaemorrhagiae, Australis, Pyrogenes, Pomona, Canicola, Grippotyphosa, Tarassovi and Ballum) in 595 samples from 60 herds. A brief history was obtained to analyze risk factors for reproductive disorders. A total of 45.9% of the tested horses were seropositive, of which the most frequent serogroups were Icterohaemorrhagiae (Icterohaemorrhagiae and Copenhageni serovars) and Ballum (Ballum serovar). Simple infections were found in 45.4% of seropositive animals, while mixed infections occurred in 54.6% of horses. There was a correlation between seropositivity and age and sex, that is, seropositivity was more frequent in animals over 6 years old and in females. There was no correlation between seropositivity and reproductive disorders. We conclude that there is a high seroprevalence of Leptospira spp. in southern Brazil with predominance of Icterohaemorrhagiae serogroup, mainly in older animals. Location, breeds, contact with dogs or other domestic animals are not risk factors, whereas gender is a risk factor. Reproductive disorders are not due to leptospirosis in the study region.

Clinical presentations and predictors of mortality for leptospirosis - A study from suburban area in Malaysia.

INTRODUCTION: Malaysia is endemic for leptospirosis with increasing incidence recorded over the years. Perak has recorded one of the highest incidence and mortality of leptospirosis since 2004. METHODS: This is a retrospective study of confirmed leptospirosis cases in Larut, Matang and Selama (LMS) district in Perak reported in 2016. The demographic, clinical presentation, laboratory result and clinical outcomes data were analysed and presented. RESULTS: Forty-two patients with confirmed diagnosis of leptospirosis were included into the study. Majority of patients were males and Malays. The case fatality rate was 14.3%. Patients with leptospirosis present with variable clinical presentations and are commonly seen with coinfection. Patients 70-year-old and older, have clinical presentations suggestive of organ dysfunction and require intensive care are associated with higher mortality. CONCLUSION: Leptospirosis is endemic in LMS district of Perak with high incidence and case fatality rate. The clinical presentation of leptospirosis is variable. Co-infection of leptospirosis with other acute febrile illness is common. Patients presenting with symptoms and signs of organ dysfunctions or require intensive care are associated with an increased odds of death.

Clinical and biochemical differences between hantavirus infection and leptospirosis: a retrospective analysis of a patient series in Belgium.

Objectives: Hantavirus infection and leptospirosis are infectious diseases transmitted by rodents. The clinical picture is nonspecific, often involving the kidneys but other organs can be affected too. Clinical and biochemical clues to make a difference between these two entities will be described.Methods: A retrospective analysis was performed on a database of patients presenting between January 2012 and September 2017 at the emergency department of the university hospital Leuven, Belgium. Patients were selected on the basis of a compatible clinical picture, biochemistry, and microbiological evidence. Presenting complaints and clinical examination were compared. Blood, taken at presentation, was used for hematological and biochemical analysis.Results: Sixteen patients with hantavirus infection and eight patients with leptospirosis were identified. All patients complained about general malaise and fever. Other frequent complaints were myalgia and a headache. Patients with leptospirosis often experienced photo- or sonophobia.Looking for neck stiffness and eye lesions might help to diagnose leptospirosis.Differences in biochemistry between viral and bacterial disease could be recognized; high C-reactive protein (CRP) and leukocytosis with left shift favor leptospirosis, elevated lactate dehydrogenase (LDH) favors viral infection. Abnormal liver function with raised total bilirubin is often seen in cases with leptospirosis.Conclusion: This study demonstrates some subtle clues that may help to differentiate between hantavirus infection and leptospirosis in patients presenting to a hospital in a nonendemic region of the world. Because of small number of patients, we could not identify significant clinical or biochemical tests. Serology remains the gold standard.

Factors associated with severity and mortality in patients with confirmed leptospirosis at a regional hospital in northern Taiwan.

BACKGROUND/PURPOSE: The clinical, epidemiological, and laboratory factors associated with disease severity and mortality from confirmed leptospirosis patients in Taiwan are not well known. This retrospective study examined patients with suspected leptospirosis admitted to En-Chu-Kong Hospital, a regional teaching hospital in northern Taiwan. METHODS: From January 2002 to July 2014, 733 suspected cases were reported to the National Reference Laboratory, 57 of which were identified as laboratory and clinical confirmed. We analyzed the clinical, epidemiological, and laboratory factors associated with disease severity and mortality in 57 cases. RESULTS: The mean age was 59.1 ± 18.2 years, 74% were male, and 49% had occupational contact with soil. The major complications were pulmonary involvement (54%), shock (44%), ventilator support (32%), jaundice (32%), hemorrhage (30%), acute kidney injury (30%), meningitis (11%) and myocarditis (2%). Leptospira santarosai serova Shermani was present in 42 (74%) patients and 37 (58%) patients had severe leptospirosis. Sixteen (28%) patients had concomitant infections, including nine patients with bloodstream infection. The only independent predictor for severe leptospirosis was shock (OR 14.8, 95% CI 2.97-73.59). Eleven patients died (19%). Acute respiratory distress syndrome with severe pulmonary hemorrhage syndrome (6 patients) was present in 55% of the fatal cases. The factors independently related to mortality were prior steroid use (OR 20.2, 95% CI 1.9-217.5) and hemorrhage (OR 71.2, 95% CI 4.9 - >999.9). CONCLUSION: These results indicate that shock is a predictor of severe leptospirosis, and prior steroid use and hemorrhage are predictors of death from leptospirosis.

Zoonotic Pathogen Seroprevalence in Cattle in a Wildlife-Livestock Interface, Kenya.

A cross-sectional study was conducted to determine the seroprevalence of Brucella spp. and Leptospira spp. and risk factors of exposure in cattle in three zones with varying land use types and wildlife-livestock interactions. Five villages were selected purposively; two in areas with intensive livestock-wildlife interactions (zone 1), another two in areas with moderate livestock-wildlife interactions (zone 2) and one in areas where wildlife-livestock interactions are rarer (zone 3). Sera samples were collected from 1170 cattle belonging to 390 herds in all the zones and tested for antibodies against Brucella abortus and Leptospira interrogans serovar hardjo using ELISA kits. Data on putative risk factors for seropositivity of these pathogens in cattle were collected using a questionnaire. The overall apparent animal-level seroprevalence of brucellosis and leptospirosis was, respectively, 36.9% (95% CI 34.1-39.8) and 23.5% (95% CI 21.1-26.0). Brucella spp. seroprevalence was higher in zone 1 than in zones 2 and 3 (χ2 = 25.1, df = 2, P < 0.001). Zones 1 and 2 had significantly higher Leptospira spp. seroprevalence than zone 3 (χ2 = 7.0, df = 2, P = 0.029). Results of multivariable analyses identified animal sex (female) and zones (high interface area) as significant predictors (P < 0.05) of animal-level seropositivity of Brucella spp. For Leptospira spp., important predictors of animal-level seropositivity were animal sex (female), zones (moderate interface area) and herds utilizing a communal grazing reserve. The seroprevalences of Brucella spp. and Leptospira spp. in cattle were higher in areas with moderate to high wildlife-livestock interactions than those with rare interactions.

Raised levels of Il-6, Il-17a, and Il-22 in fatal leptospirosis.

Clinical manifestations of leptospirosis range from mild, common cold-like illness, to a life-threatening condition. The host immune response has been hypothesized to play a major role in leptospirosis outcome. Increased levels of inflammatory mediators, such as cytokines, may promote tissue damage that lead to increased disease severity. The question is whether cytokines levels may predict the outcome of leptospirosis and guide patient management. This study aimed to assess the association between Th1-, Th2-, and Th17-related cytokines with the clinical outcome of patients with leptospirosis. Different cytokine levels were measured in fifty-two plasma samples of hospitalized patients diagnosed with leptospirosis in Malaysia (January 2016-December 2017). Patients were divided into two separate categories: survived (n = 40) and fatal outcome (n = 12). Nineteen plasma samples from healthy individuals were obtained as controls. Cytokine quantification was performed using Simple Plex™ assays from ProteinSimple (San Jose, CA, USA). Measurements were done in triplicate and statistical analysis was performed using GraphPad software and SPSS v20. IL-6 (p = 0.033), IL-17A (p = 0.022), and IL-22 (p = 0.046) were significantly elevated in fatal cases. IL-17A concentration (OR 1.115; 95% CI 1.010-1.231) appeared to be an independent predictor of fatality of leptospirosis. Significantly higher levels of TNF-α (p ≤ 0.0001), IL-6 (p ≤ 0.0001), IL-10 (p ≤ 0.0001), IL-12 (p ≤ 0.0001), IL17A (p ≤ 0.0001), and IL-18 (p ≤ 0.0001) were observed among leptospirosis patients in comparison with healthy controls. Our study shows that certain cytokine levels may serve as possible prognostic biomarkers in leptospirosis patients.

Liver function assessment using indocyanine green plasma disappearance rate in a young male with icteric leptospirosis: a case report.

BACKGROUND: Leptospirosis is one of the leading global zoonotic causes of morbidity and mortality. It is induced by a pathogenic spirochete of the genus Leptospira. The icteric form of leptospirosis is characterized by pronounced hyperbilirubinemia and associated with significantly increased mortality. Conventional static liver function tests insufficiently assess hepatic damage and have limited prognostic value. Dynamic tests, such as indocyanine green plasma (ICG) clearance, more adequately reflect hepatic functional status. In this case report we describe the ICG plasma disappearance rates (ICG-PDR) in a patient with leptospirosis and massive hyperbilirubinemia, expanding our knowledge of liver dysfunction in icteric leptospirosis. CASE PRESENTATION: A 21-year-old Caucasian man presented with acute-onset jaundice, myalgia, fever and headaches. Laboratory tests upon admission revealed, most notably, acute kidney failure and hyperbilirubinemia of 17 mg/dl with mild elevation of aminotransferases. In the course of the following 4 days, total serum bilirubin increased to 54 mg/dl. The clinical outcome was favorable with intravenous ceftriaxone and doxycycline. Presumptive diagnosis of leptospirosis was later confirmed by PCR-based amplification of leptospiral DNA in the blood. ICG-PDR values, bilirubin as well as aminotransferases were recorded throughout hospitalization and a 3-month follow-up period. Initially dramatically reduced ICG-PDR (2.0%/min, normal range: 18-25%/min) rapidly normalized within 10 days, while bilirubin remained elevated up to week 7. Mild elevation of serum alanine aminotransferase was at its peak of 124 U/l by day 12 and reached close to normal levels by week 7 upon admission. CONCLUSIONS: Markedly diminished ICG-PDR values presented in this case report suggest severe liver function impairment in the acute phase of icteric leptospirosis. Prolonged elevation of serum bilirubin may not adequately reflect recovery of liver injury in this disease. ICG clearance appears to be a promising marker for the detection of hepatic dysfunction and recovery in icteric leptospirosis in addition to the static tests.

Heparin-Binding Protein Release Is Strongly Induced by Leptospira Species and Is a Candidate for an Early Diagnostic Marker of Human Leptospirosis.

BACKGROUND: Leptospirosis, caused by spirochetes of the genus Leptospira, is one of the most widespread zoonoses worldwide. Efficient diagnostic methods for early diagnosis of leptospirosis are still lacking, and acute disease presents with nonspecific symptomatology and is often misdiagnosed. The leptospires pathogenic processes and virulence mechanisms remain virtually unknown. In severe infections, hemostatic impairment is frequently observed, and pathophysiological complications often develop when the host response is modulated by the pathogen. The neutrophil heparin-binding protein (HBP) is an inflammatory mediator and potent inducer of vascular leakage. RESULTS: In this study, we found that leptospires and their secreted products induce the release of HBP from stimulated neutrophils through a controlled degranulation mechanism. We acknowledged 2 leptospiral proteins as able to induce HBP degranulation. These findings have clinical implications, as high levels of HBP were detected in serum from patients with leptospirosis, especially at the early phase of the disease. CONCLUSION: In conclusion, we describe a new mechanism by which the leptospirosis pathophysiological complications may arise, such as vascular leakage and edema formation. We also propose HBP as a new early screening biomarker for human leptospirosis.

A novel Fas-binding outer membrane protein and lipopolysaccharide of Leptospira interrogans induce macrophage apoptosis through the Fas/FasL-caspase-8/-3 pathway.

Leptospira interrogans is the major causative agent of leptospirosis, an emerging, globally spreading zoonotic infectious disease. The pathogen induces macrophage apoptosis, but the molecular basis and mechanism remain unknown. In the present study, we found that L. interrogans caused apoptosis of phagocytosis-inhibited macrophages, and the product of the L. interrogans LB047 gene (Lep-OMP047) was the unique protein captured by mouse and human Fas proteins. The recombinant expressed Lep-OMP047 (rLep-OMP047) strongly bound mouse and human Fas proteins with equilibrium association constant (KD) values of 5.20 × 10-6 to 2.84 × 10-9 M according to surface plasmon resonance measurement and isothermal titration calorimetry. Flow-cytometric examination showed that 5 µg rLep-OMP047 or 1 µg lipopolysaccharide of L. interrogans (Lep-LPS) caused 43.70% or 21.90% early apoptosis in mouse J774A.1 macrophages and 28.41% or 15.80% for PMA-differentiated human THP-1 macrophages, respectively, but the apoptosis was blocked by Fas-antagonizing IgGs, Fas siRNAs, and caspase-8/-3 inhibitors. Moreover, Lep-OMP047 was significantly upregulated during infection of macrophages. Lep-LPS promoted the expression and cytomembrane translocation of Fas and FasL in macrophages. The JNK and p38 MAPK but not ERK signaling pathways, as well as the transcription factors c-Jun and ATF2 but not CHOP, mediated Lep-LPS-induced Fas/FasL expression and translocation. TLR2 but not TLR4 mediated Lep-LPS-induced JNK/p38 MAPK activation. Therefore, we demonstrated that a novel Fas-binding OMP and LPS of L. interrogans induce macrophage apoptosis through the Fas/FasL-caspase-8/-3 pathway.

Leptospirosis among Returned Travelers: A GeoSentinel Site Survey and Multicenter Analysis-1997-2016.

Leptospirosis is a potentially fatal emerging zoonosis with worldwide distribution and a broad range of clinical presentations and exposure risks. It typically affects vulnerable populations in (sub)tropical countries but is increasingly reported in travelers as well. Diagnostic methods are cumbersome and require further improvement. Here, we describe leptospirosis among travelers presenting to the GeoSentinel Global Surveillance Network. We performed a descriptive analysis of leptospirosis cases reported in GeoSentinel from January 1997 through December 2016. We included 180 travelers with leptospirosis (mostly male; 74%; mostly tourists; 81%). The most frequent region of infection was Southeast Asia (52%); the most common source countries were Thailand (N = 52), Costa Rica (N = 13), Indonesia, and Laos (N = 11 each). Fifty-nine percent were hospitalized; one fatality was reported. We also distributed a supplemental survey to GeoSentinel sites to assess clinical and diagnostic practices. Of 56 GeoSentinel sites, three-quarters responded to the survey. Leptospirosis was reported to have been most frequently considered in febrile travelers with hepatic and renal abnormalities and a history of freshwater exposure. Serology was the most commonly used diagnostic method, although convalescent samples were reported to have been collected infrequently. Within GeoSentinel, leptospirosis was diagnosed mostly among international tourists and caused serious illness. Clinical suspicion and diagnostic workup among surveyed GeoSentinel clinicians were mainly triggered by a classical presentation and exposure history, possibly resulting in underdiagnosis. Suboptimal usage of available diagnostic methods may have resulted in additional missed, or misdiagnosed, cases.

A case of post-leptospirosis autoimmune epilepsy presenting with sleep-related hypermotor seizures.

This video-illustrated case report concerns a 49-year-old woman who presented with sleep-related hypermotor seizures. The antecedent history of leptospirosis, high frequency of new-onset seizures, presence of an unclassified anti-neuronal antibody, and dramatic response to steroids strongly supported post-infectious immune-mediated pathogenesis in our patient. To the best of our knowledge, post-leptospirosis autoimmune epilepsy presenting as sleep-related hypermotor seizures has not hitherto been reported. [Published with video sequence on www.epilepticdisorders.com].

Seroepidemiology of leptospirosis among febrile patients in a rapidly growing suburban slum and a flood-vulnerable rural district in Mozambique, 2012-2014: Implications for the management of fever.

OBJECTIVE: Leptospirosis is one of the most widespread zoonoses in the world and is caused by spirochetes of the genus Leptospira. In Mozambique, the disease is largely ignored and its epidemiology is unknown. The objective of this study was to investigate the occurrence of leptospirosis in febrile patients. METHODS: This cross-sectional study was performed between July 2012 and September 2015 among febrile patients. A total of 373 paired serum samples were drawn from febrile patients; 208 were from Caia District Hospital (rural setting) in Sofala Province and 165 were from Polana Caniço General Hospital (suburban setting) in Maputo City. Samples were initially screened using an in-house ELISA for IgM and IgG antibodies. Double positive samples were confirmed using a microagglutination test (MAT). RESULTS: Of the 373 febrile patients, five (1.3%) had acute leptospirosis (MAT ≥400) and 38 (10.2%) had a presumptive infection (IgM-positive/MAT <400). While most of the patients with a presumptive infection lived in the rural setting (84.2%, 32/38), the majority of patients with acute infections (60%, 3/5) and with negative results (60.3%, 199/330) lived in the suburban setting (p=0.000). Contact with rodents was significantly higher in patient with acute leptospirosis (100%, 5/5) than in those with a presumptive infection (39.5%, 15/38) or negative results (41.8%, 138/330) (p=0.031). Four out of the five patients (80%) with acute leptospirosis were treated with antimalarial drugs although malaria results were negative. The prevailing serogroup, according to MAT results, was Australis (40%; 4/10), followed by Icterohaemorrhagiae (30%, 3/10). CONCLUSIONS: This study found that leptospirosis is prevalent among Mozambicans, and most cases are misdiagnosed as malaria.

Continuous Excretion of Leptospira borgpetersenii Ballum in Mice Assessed by Viability Quantitative Polymerase Chain Reaction.

Rodents are the main reservoir animals of leptospirosis. In this study, we characterized and quantified the urinary excretion dynamics of Leptospira by Mus musculus infected with 2 × 108 virulent Leptospira borgpetersenii serogroup Ballum. Each micturition was collected separately in metabolic cages, at 12 time points from 7 to 117 days post-infection (dpi). We detected Leptospira in all urine samples collected (up to 8 per time point per mouse) proving that Leptospira excretion is continuous with ca. 90% live L. borgpetersenii Ballum, revealed by viability quantitative polymerase chain reaction. Microscopic visualization by Live/Dead fluorescence confirmed this high proportion of live bacteria and demonstrated that L. borgpetersenii Ballum are excreted, at least partly, as bacterial aggregates. We observed two distinct phases in the excretion dynamics, first an increase in Leptospira concentration shed in the urine between 7 and 63 dpi followed by a plateau phase from 63 dpi onward, with up to 3 × 107Leptospira per mL of urine. These two phases seem to correspond to progressive colonization of renal tubules first, then to stable cell survival and maintenance in kidneys. Therefore, chronically infected adult mice are able to contaminate the environment via urine at each micturition event throughout their lifetime. Because Leptospira excretion reached its maximum 2 months after infection, older rodents have a greater risk of contaminating their surrounding environment.

High level of IL-10 expression in the blood of animal models possibly relates to resistance against leptospirosis.

Leptospirosis is a severe zoonosis which immunopathogenesis is poorly understood. We evaluated correlation between acute form of the disease and the ratio of the anti-inflammatory cytokine IL-10 to the pro-inflammatory TNF-α and IL-1ß expression during the early phase of infection comparing resistant mice and susceptible hamsters infected with two different species of virulent Leptospira. The IL-10/TNF-α and IL-10/IL-1ß expression ratios were higher in mouse compared to hamster independently of the Leptospira strain, suggesting a preponderant role of the host response and notably these cytokines in the clinical expression and survival to leptospirosis. Using an IL-10 neutralization strategy in Leptospira-infected mouse model, we also showed evidence of a possible role of this cytokine on host susceptibility, bacterial clearance and on regulation of cytokine gene expression.