Severe leptospirosis in tropical and non-tropical areas: A comparison of two french, multicentre, retrospective cohorts.

BACKGROUND: Leptospirosis is an anthropozoonosis that occurs worldwide but is more common in tropical regions. Severe forms may require intensive care unit (ICU) admission. Whether the clinical patterns and outcomes differ between tropical and non-tropical regions with similar healthcare systems is unclear. Our objective here was to address this issue by comparing two cohorts of ICU patients with leptospirosis managed in mainland France and in the overseas French department of Réunion, respectively. METHODOLOGY/PRINCIPAL FINDINGS: We compared two retrospective cohorts of patients admitted to intensive care for severe leptospirosis, one from Reunion Island in the Indian Ocean (tropical climate) and the other from metropolitan France (temperate climate). Chi-square and Student's t tests were used for comparisons. After grouping the two cohorts, we also performed multiple correspondence analysis and hierarchical clustering to search for distinct clinical phenotypes. The Réunion and Metropolitan France cohorts comprised 128 and 160 patients respectively. Compared with the Réunion cohort, the metropolitan cohort had a higher mean age (42.5±14.1 vs. 51.4±16.5 years, p<0.001). Severity scores, length of stay and mortality did not differ between the two cohorts. Three phenotypes were identified: hepato-renal leptospirosis (54.5%) characterized by significant hepatic, renal and coagulation failure, with a mortality of 8.3%; moderately severe leptospirosis (38.5%) with less severe organ failure and the lowest mortality rate (1.8%); and very severe leptospirosis (7%) manifested by neurological, respiratory and cardiovascular failure, with a mortality of 30%. CONCLUSIONS/SIGNIFICANCE: The outcomes of severe leptospirosis requiring ICU admission did not differ between tropical and temperate regions with similar healthcare access, practices, and resources, despite some differences in patient characteristics. The identification of three different clinical phenotypes may assist in the early diagnosis and management of severe leptospirosis.

Leptospirosis: predictores de mala evolución clínica en pacientes hospitalizados, 25 años de experiencia / Leptospirosis: predictors of poor outcomes in hospitalized patients, 25 years of experience

Introducción: La leptospirosis es una zoonosis que cons-tituye un problema emergente de salud pública. La insufi-ciencia renal, plaquetopenia y compromiso respiratorio se describen como predictores de mortalidad.Objetivos: Describir características clínicas, radiológicas y de laboratorio de individuos hospitalizados por leptos-pirosis y evaluar los predictores de mala evolución clínica (MEC).Materiales y métodos: Estudio de cohorte de inclusión ambispectiva de pacientes con leptospirosis internados en un hospital de la ciudad de Santa Fe entre 1997 y 2022. Se definió MEC como la admisión a Unidad de Cuidados Intensivos (UCI), requerimiento de asistencia respiratoria mecánica (ARM) y/o muerte. Se utilizaron las pruebas de Chi2, test T de Student o la U de Mann-Whitney, según co-rrespondiera. Se construyó una regresión logística binaria con las variables con p<0,05.Resultados: 101 pacientes, 87,1% (n=88) hombres, media-na de edad de 29 (RIC 20-44) años. La fiebre fue el síntoma más frecuente [83,2% (n=84)], seguido del compromiso di-gestivo [62,4% (n=63)]. Las alteraciones de laboratorio más frecuentes fueron: eritrosedimentación elevada [91,9% (n=79)] y leucocitosis [61% (n=61)]. Se observó MEC en el 25,7% (n=26). El 25,7% (n=26) fue admitido en UCI, el 13,9% (n=14) requirió ARM y el 5% (n=5) falleció. La presencia de plaquetopenia (OR=13,3, IC95% 2-80), las alteraciones en la radiografía de tórax (OR=33,5, IC95% 5-225) y la ausencia de cefalea (OR=6,8, IC95% 1-32) fueron predictores inde-pendientes de MEC.Conclusiones: En concordancia con la bibliografía, la afec-tación pulmonar y plaquetopenia son factores de riesgo para la mala evolución clínica. En nuestra serie, la cefalea constituyó un síntoma protector

Introduction: Leptospirosis is an emerging zoonotic di-sease that poses a public health problem. Renal failu-re, thrombocytopenia, and respiratory involvement have been described as predictors of mortality.Objectives: To describe the clinical, radiological, and la-boratory characteristics of hospitalized individuals with leptospirosis and evaluate predictors of poor clinical outcomes (PCO).Materials and methods: A prospective cohort study was conducted including patients with leptospirosis admit-ted to a hospital in the city of Santa Fe between 1997 and 2022. PCO was defined as admission to the Intensive Care Unit (ICU), requirement for mechanical respiratory assistance (MRA), and/or death. The chi-square test, Student>s t-test, or Mann-Whitney U test were used as appropriate. A binary logistic regression was performed with variables having p<0.05.Results: Out of the 101 patients included, 87.1% (n=88) were male, with a median age of 29 (IQR 20-44) years. Fever was the most common symptom [83.2% (n=84)], followed by digestive involvement [62.4% (n=63)]. The most frequent laboratory abnormalities were elevated erythrocyte sedimentation rate [91.9% (n=79)] and leuko-cytosis [61% (n=61)]. PCO was observed in 25.7% (n=26) of patients, with 25.7% (n=26) admitted to the ICU, 13.9% (n=14) requiring MRA, and 5% (n=5) resulting in death. The presence of thrombocytopenia (OR=13.3, 95% CI 2-80), abnormalities in chest X-rays (OR=33.5, 95% CI 5-225), and absence of headache (OR=6.8, 95% CI 1-32) were predictors of PCO. Conclusions: Consistent with the literature, pulmonary involvement and thrombocytopenia are independent risk factors for poor clinical outcomes. In our series, the pre-sence of headache was a protective symptom

A lethal model of Leptospira infection in hamster nasal mucosa.

Leptospirosis is a fatal zoonosis caused by contact between skin or a mucosal surface and contaminated soil or water. Hamsters were infected by intraperitoneal injection fto establish experimental leptospirosis, which is not a natural route of infection. There are no reports of nasal mucosal infection in hamsters. In this study, infection of the nasal mucosa was performed to establish a model of natural infection. Both methods of infection can cause lethal models with similar symptoms in the later stages of infection, such as weight loss, blood concentration, increased neutrophils (GRAN), and decreased lymphocytes (LYM) in the blood, severe organ damage and liver function obstruction. The burden of Leptospira in the organs and blood was lower in the mucosal inoculation groups at 1 day after infection. However, mucosal infection induced a higher Leptospira burden in urine than intraperitoneal infection in the late stages of infection. After nasal mucosal infection, antibody levels were higher and lasted longer. These results indicated that the route of nasal mucosal infection is a good choice for studying leptospirosis in hamsters.

The Applicability of Commonly Used Severity of Illness Scores to Tropical Infections in Australia.

Many patients with leptospirosis, melioidosis, and rickettsial infection require intensive care unit (ICU) admission in tropical Australia every year. The multi-organ dysfunction associated with these infections results in significantly elevated severity of illness (SOI) scores. However, the accuracy of these SOI scores in predicting death from these tropical infections is incompletely defined. This retrospective study was performed at Cairns Hospital, a tertiary-referral hospital in tropical Australia. All patients admitted to ICU with laboratory-confirmed leptospirosis, melioidosis, and rickettsial disease between January 1, 1999 and June 30, 2020, were eligible for the study. The ability of Acute Physiology and Chronic Health Evaluation (APACHE) II, APACHE III, Simplified Acute Physiology Scores (SAPS) II, and Sequential Organ Failure Assessment (SOFA) scores to predict death before ICU discharge was evaluated. Overall, 18 (12.1%) of the 149 included patients died: 15/74 (20.3%) with melioidosis, 2/54 (3.7%) with leptospirosis and 1/21 (4.8%) with rickettsial disease. However, the APACHE II, APACHE III, SAPS II, and SOFA scores significantly overestimated the case-fatality rate of all the infections; the disparity between the predicted and observed mortality was most marked in the cases of leptospirosis and rickettsial disease. Commonly used SOI scores significantly overestimate the case-fatality rate of melioidosis, leptospirosis, and rickettsial infections in Australian ICU patients. This may be at least partly explained by the unique pathophysiology of these infections, particularly leptospirosis and rickettsial disease. However, SOI scores may still be useful in facilitating the comparison of disease severity in clinical trials that examine patients with these pathogens.

4-Methylcytosine DNA modification is critical for global epigenetic regulation and virulence in the human pathogen Leptospira interrogans.

In bacteria, DNA methylation can be facilitated by 'orphan' DNA methyltransferases lacking cognate restriction endonucleases, but whether and how these enzymes control key cellular processes are poorly understood. The effects of a specific modification, 4-methylcytosine (4mC), are even less clear, as this epigenetic marker is unique to bacteria and archaea, whereas the bulk of epigenetic research is currently performed on eukaryotes. Here, we characterize a 4mC methyltransferase from the understudied pathogen Leptospira spp. Inactivating this enzyme resulted in complete abrogation of CTAG motif methylation, leading to genome-wide dysregulation of gene expression. Mutants exhibited growth defects, decreased adhesion to host cells, higher susceptibility to LPS-targeting antibiotics, and, importantly, were no longer virulent in an acute infection model. Further investigation resulted in the discovery of at least one gene, that of an ECF sigma factor, whose transcription was altered in the methylase mutant and, subsequently, by mutation of the CTAG motifs in the promoter of the gene. The genes that comprise the regulon of this sigma factor were, accordingly, dysregulated in the methylase mutant and in a strain overexpressing the sigma factor. Our results highlight the importance of 4mC in Leptospira physiology, and suggest the same of other understudied species.

An Observational Study of Human Leptospirosis in Seychelles.

A 1-year population-based prospective study was launched in Seychelles, a country with one of the highest human incidence of leptospirosis worldwide, to describe the characteristic features of the epidemiology of the disease and highlight the most prominent risk factors. Diagnosis was based on the IgM enzyme-linked immunosorbent assay, microscopic agglutination test, and real-time PCR. A standardized questionnaire was administered to 219 patients aged ≥ 13 years consulting for acute febrile illness. The high incidence of leptospirosis in Seychelles was confirmed. The disease was particularly severe, as the case fatality rate was 11.8%. Leptospirosis was positively associated in univariate analysis with socio-professional and clinical variables including gardening/farming, oliguria, jaundice, conjunctivitis, history of hepatitis C virus infection, anemia, thrombocytopenia, and/or biological renal failure. Epidemiological analyses of the questionnaires highlighted a link of the disease with living in houses (versus apartment), the presence of animals around and in houses, gardening, and misuse of personal protective equipment. Multivariate analyses indicated that being a farmer/landscaper and having cattle and cats around the home are the most significant drivers of leptospirosis. Biological features most associated with leptospirosis were thrombocytopenia, leukocytosis, high values for renal function tests, and elevated total bilirubin. We report changes in behavior and exposure compared with data collected on leptospirosis 25 years ago, with indication that healthcare development has lowered case fatality. Continuous health education campaigns are recommended as well as further studies to clarify the epidemiology of human leptospirosis, especially the role of domestic animals.

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.

Elevated levels of IL-8 in fatal leptospirosis.

Leptospirosis causes a wide range of clinical outcomes, including organ failure and death. Early treatment significantly increases the chances of cure. Interleukin-8 (IL-8) is a chemoattractant cytokine for neutrophil and is associated with multiple organ failure. Research has indicated IL-8 to be raised in severe and fatal cases of leptospirosis, but its suitability as a prognostic biomarker has yet to be confirmed. This study aimed to evaluate the significance of IL-8 with the clinical outcomes of leptospirosis patients. Plasma IL-8 was measured in fifty-two samples from hospitalized patients and nineteen healthy controls. The comparisons were made between mild, severe-survived and fatal groups identified by clinical or laboratory findings. IL-8 was significantly higher in fatal (p = 0.01) compared to mild cases. IL-8 was also significantly higher in fatal (p = 0.02) when compared to survived cases of leptospirosis. IL-8 levels in the plasma of fatal leptospirosis cases were significantly elevated compared to survived cases and may serve as a potential prognostic biomarker in determining the possible outcome of leptospirosis patients.

Monoclonal antibodies against LipL32 confer prophylactic protection against lethal leptospirosis challenge in animal model.

Leptospirosis is a widespread zoonotic disease caused by pathogenic spirochetes of the genus Leptospira. The commercially available vaccines are bacterins that offer limited protection, short-term effect, and serovar-specific immunity. The development of novel immunization strategies is crucial to control the infection and decrease the chances of new outbreaks. In this study, purified monoclonal antibodies (mAbs) anti-LipL32 (1D9 and mAb3) were evaluated by their capacity to bind and neutralize the pathogen improving host survival. For that, an in vitro growth inhibition assay, and in vivo passive immunization were performed in animal model. Syrian hamsters were passively immunized by three different strategies. Hamsters immunized with mAb3 6 h prior to the lethal challenge showed a significantly higher survival rate of 61.1%, and a significant reduction in tissue damage in the lungs. Cumulatively, our results showed that anti-LipL32 mAbs inhibited the growth of L. interrogans in vitro, and that passive immunization offered significant protection in animal model when administered prior to infection.

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.

Severe leptospirosis in tropical Australia: Optimising intensive care unit management to reduce mortality.

BACKGROUND: Severe leptospirosis can have a case-fatality rate of over 50%, even with intensive care unit (ICU) support. Multiple strategies-including protective ventilation and early renal replacement therapy (RRT)-have been recommended to improve outcomes. However, management guidelines vary widely around the world and there is no consensus on the optimal approach. METHODOLOGY/PRINCIPAL FINDINGS: All cases of leptospirosis admitted to the ICU of Cairns Hospital in tropical Australia between 1998 and 2018 were retrospectively reviewed. The patients' demographics, presentation, management and clinical course were examined. The 55 patients' median (interquartile range (IQR)) age was 47 (32-62) years and their median (IQR) APACHE III score was 67 (48-105). All 55 received appropriate antibiotic therapy, 45 (82%) within the first 6 hours. Acute kidney injury was present in 48/55 (87%), 18/55 (33%) required RRT, although this was usually not administered until traditional criteria for initiation were met. Moderate to severe acute respiratory distress syndrome developed in 37/55 (67%), 32/55 (58%) had pulmonary haemorrhage, and mechanical ventilation was required in 27/55 (49%). Vasopressor support was necessary in 34/55 (62%). Corticosteroids were prescribed in 20/55 (36%). The median (IQR) fluid balance in the initial three days of ICU care was +1493 (175-3567) ml. Only 2/55 (4%) died, both were elderly men with multiple comorbidities. CONCLUSION: In patients with severe leptospirosis in tropical Australia, prompt ICU support that includes early antibiotics, protective ventilation strategies, conservative fluid resuscitation, traditional thresholds for RRT initiation and corticosteroid therapy is associated with a very low case-fatality rate. Prospective studies are required to establish the relative contributions of each of these interventions to optimal patient outcomes.

Severe leptospirosis in non-tropical areas: a nationwide, multicentre, retrospective study in French ICUs.

PURPOSE: To report the incidence, risk factors, clinical presentation, and outcome predictors of severe leptospirosis requiring intensive care unit (ICU) admission in a temperate zone. METHODS: LEPTOREA was a retrospective multicentre study conducted in 79 ICUs in metropolitan France. Consecutive adults admitted to the ICU for proven severe leptospirosis from January 2012 to September 2016 were included. Multiple correspondence analysis (MCA) and hierarchical classification on principal components (HCPC) were performed to distinguish different clinical phenotypes. RESULTS: The 160 included patients (0.04% of all ICU admissions) had median values of 54 years [38-65] for age, 40 [28-58] for the SAPSII, and 11 [8-14] for the SOFA score. Hospital mortality was 9% and was associated with older age; worse SOFA score and early need for endotracheal ventilation and/or renal replacement therapy; chronic alcohol abuse and worse hepatic dysfunction; confusion; and higher leucocyte count. Four phenotypes were identified: moderately severe leptospirosis (n = 34, 21%) with less organ failure and better outcomes; hepato-renal leptospirosis (n = 101, 63%) with prominent liver and kidney dysfunction; neurological leptospirosis (n = 8, 5%) with the most severe organ failures and highest mortality; and respiratory leptospirosis (n = 17, 11%) with pulmonary haemorrhage. The main risk factors for leptospirosis contamination were contact with animals, contact with river or lake water, and specific occupations. CONCLUSIONS: Severe leptospirosis was an uncommon reason for ICU admission in metropolitan France and carried a lower mortality rate than expected based on the high severity and organ-failure scores. The identification in our population of several clinical presentations may help clinicians establish an appropriate index of suspicion for severe leptospirosis.

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.

Leptospirosis in the elderly: the role of age as a predictor of poor outcomes in hospitalized patients.

Background: The aim of this study was to investigate factors associated with poor outcomes among elderly hospitalized patients with leptospirosis. Methods: This is a retrospective cohort study with leptospirosis patients admitted to three tertiary hospitals in Fortaleza, Brazil, from January 1985 to July 2017. Patients were divided into two groups: elderly (age ≥60 years) and young (age <60 years). A comparison of demographical, clinical and laboratory data, treatment and outcomes was executed in order to investigate differences between groups. Results: A total of 507 hospitalized patients were included, with mean age 38 ± 15 years. Elderly group presented lower incidence of myalgia, vomiting, and dyspnea, as well as, higher medium systolic blood pressure. Elderly also manifested higher frequency of AKI (85.9 vs. 74.7%, p = 0.05), hemodialysis requirement (54.7 vs. 37.0%, p = 0.007) and death (32.8 vs. 12.2%, p < 0.001). In multivariate analysis, age ≥60 years was a predictor of hemodialysis requirement (p = 0.008, OR = 2.049, 95% CI = 1.207-3.477) and death (p < 0.001, OR = 3.520, 95% CI = 1.940-6.386). Conclusion: Leptospirosis in the elderly is associated with less hemodynamic impairment and higher frequency of AKI. Advanced age was also a predictor of poor outcomes, such as hemodialysis requirement and death, mostly due to kidney involvement.

Sequel and therapeutic modalities of leptospirosis associated severe pulmonary haemorrhagic syndrome (SPHS); a Sri Lankan experience.

BACKGROUND: The emergence of leptospirosis-associated severe pulmonary hemorrhagic syndrome (SPHS) with high case fatality has been reported from many countries. Understanding of clinical disease and sequel of SPHS needs larger studies with adequate numbers. The purpose of this study was to describe the characteristics and sequel by different therapeutic approaches for SPHS in Leptospirosis in Sri Lanka. METHODS: This study was conducted at Teaching Hospital-Karapitiya (THK), Galle, Sri Lanka from June 2015 to December 2017. THK is the main tertiary care center for the Southern Province. All confirmed-cases of leptospirosis who presented during this period and were admitted to five medical units of THK were included in this study. SPHS was defined as a patient presenting; haemoptysis, arterial hypoxemia (Acute Lung Injury Score < 2.5), haemoglobin drop (10% from the previous value), or diffused alveolar shadows in the chest radiograph, without alternative explanation other than leptospirosis. RESULTS: Of the 128 MAT confirmed cases of leptospirosis, 111 (86.7%) had acute kidney injury (AKI) whilst SPHS was seen in 80 (62.5%). Patients typically developed SPHS within the first week of illness, mostly on days 4 and 5. The case fatality rate of this study sample was 28.1% (n = 36), while for patients with SPHS, it was 41.5%. Most of the deaths (n = 19) were within the first 3 days of admission (on the same day 8, and within next 48 h 11). Among SPHS patients, 59 received therapeutic plasma exchange (TPE). The survival rate was higher (n = 35, 74.5%) when the TPE was performed within the first 48 h of detecting SPHS compared to patients in whom the procedure was done after 48 h (n = 5, 54.5%). Of the 19 leptosprosis patients with SPHS who did not receive TPE, 17 died (89.5%). However, the group of patients who received TPE was primarily the patients survived beyond day 3. CONCLUSIONS: We observed that during the study period, SPHS was common and the mortality rate was higher in the study area. The treatment modalities tested need further evaluation and confirmation.

Spatial and statistical analysis of leptospirosis in Thailand from 2013 to 2015.

This study analyzes the temporal pattern and spatial clustering of leptospirosis, a disease recognized as an emerging public health problem in Thailand. The majority of those infected are farmers and fishermen. Severe epidemics of leptospirosis in association with the rainy reason have occurred since 1996. Still, an understanding of the annual variation and spatial clustering of the disease is lacking. Data were collected from the Center of Epidemiological Information, Bureau of Epidemiology, Ministry of Public Health, covering the nationwide incidence of leptospirosis during the period 2013-2015. Clustering techniques, including local indicators of spatial association and local Getis-Ord Gi* statistic, were used for the analysis and evaluation of the annual spatial distribution of the disease. Both these statistics revealed similar results for the areas with the highest clustering patterns of leptospirosis. Specifically, there were persisting hotspots in north-eastern and southern parts of Thailand over the three years covered by the study. This outcome suggests that healthcare resources should be allocated to the areas characterized by leptospirosis clustering.

Evaluation of different strategies to promote a protective immune response against leptospirosis using a recombinant LigA and LigB chimera.

Leptospirosis is a zoonosis of worldwide distribution, caused by infection with pathogenic Leptospira species. The vaccines that are currently available are bacterins, with limited human use, that confer short-term, serovar-specific immunity. Lig proteins are considered to be the best vaccine candidates to date. Here, we aimed to construct a recombinant Lig chimera (LC) comprised of LigAni and LigBrep fragments, and to evaluate it as subunit or DNA vaccine using different administration strategies. Vaccines were formulated with 50 µg of recombinant LC associated with different adjuvants or with 100 µg of pTARGET/LC. Four-week-old hamsters received two doses of vaccine with different strategies and were challenged with 5 × DL50Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130. The immune response generated by Lig chimera conferred 100% protection to hamsters treated with at least one dose of recombinant LC. Despite the high levels of antibodies that vaccinated animals produced, a sterilizing immunity was not achieved. The lack of a sterilizing immunity could indicate the importance of a mixed humoral and cellular immune response. The present study generated insights that will be useful in the future development of improved subunit vaccines against leptospirosis.

Acute respiratory distress syndrome in leptospirosis.

PURPOSE: Acute Respiratory Distress Syndrome is a major complication of leptospirosis, leading to the majority of fatalities. METHODS: Retrospective, descriptive and single-center cohort study. The primary outcome was the Standardized Mortality Ratio (SMR) for ARDS in leptospirosis based on the quartiles of the SAPS2 score in the reference population of 1683 patients hospitalized for ARDS. The second outcomes were to determine the risk factors of mortality of ARDS in leptospirosis and to describe the cases requiring Extracorporeal Membrane Oxygenation (ECMO). RESULTS: Of 172 leptospirosis patients from January 2004 to October 2017, 39 (23%) presented a moderate or severe ARDS with a mortality rate of 23% (9 cases). Among patients with ARDS, the SMR with regards to Simplified Acute Physiology Score II was 0.49 (CI95%: 0.21; 0.96). Risk factors associated with mortality found by bivariate analysis were Severity Acute Physiology Score II (p = 0.01), Sequential Organ Failure Assessment (p = 0.01), base excess (p = 0.002), kaliemia (p = 0.004), bilirubinemia (p = 0.01) and level of aspartate aminotransferase (p = 0.01). Eight patients underwent ECMO for refractory ARDS and six survived. CONCLUSIONS: Leptospirosis can induce serious but transient ARDS with a better prognosis than that of other causes of ARDS. Several patients have been successfully treated with ECMO.

Estimating the burden of leptospirosis in Sri Lanka; a systematic review.

BACKGROUND: Although the assessment of disease burden should be a priority for allocating resources, leptospirosis is grossly underestimated despite its true burden in Sri Lanka. This study aimed to assess the morbidity and mortality of leptospirosis based on routine surveillance data, hospital reported data and scientific publications from Sri Lanka. METHOD: A systematic review was carried out, and Pub Med, MEDLINE®, BIOSIS Previews, Zoological Record, Web of Science Core Collection, Current Contents Connect, KCI-Korean Journal Database, BIOSIS Citation Index, Data Citation Index, SciELO Citation Index and Google Scholar databases were searched. Quarterly epidemiological bulletin (QEB), indoor morbidity & mortality returns (IMMR) and hand searches of local literature were performed in local libraries. Forty-two relevant full texts, 32 QEBs, and 8 IMMR were included in the full text review. Adjustments were made for under diagnosis, underreporting and chance variability. RESULTS: The estimated annual caseload of leptospirosis in Sri Lanka from 2008 to 2015, was 10,423, and the cumulative annual incidence of leptospirosis that required hospitalization was 52.1 (95% CI 51.7-52.6) per 100,000 people. The estimated number of annual deaths due to leptospirosis was approximately 730 (95% CI 542-980), with an estimated pooled case fatality ratio of 7.0% (95% CI 5.2-9.4). The most common organs involved were the kidney, liver and heart, with median rates of 48.7, 30, and 14.2%, respectively. CONCLUSION: Our systematic review shows gross underestimation of the true leptospirosis burden in the national statistics of Sri Lanka, and the hospitalization rates estimated in our study were compatible with the total burden estimate of 300·6 (95% CI 96·54-604·23) per 100,000 people published previously.

Epidemiology of Human Leptospirosis in French Guiana (2007-2014): A Retrospective Study.

Leptospirosis is a worldwide zoonotic bacterial infection with a rising incidence. French Guiana is mostly covered by Amazonian rain forest. Despite a potentially favorable environment, leptospirosis has been barely studied in French Guiana. The objective of this study was to describe the current trends of leptospirosis epidemiology in French Guiana. A cross-sectional study was performed in the two main hospitals of French Guiana. Cases of leptospirosis from 2007 to 2014 were retrospectively identified with a systematic screening of serological and polymerase chain reaction results to classify them as confirmed, probable, or excluded cases. Medical files were reviewed to collect epidemiological data. Among the 72 included patients, 55 (76.4%) cases were confirmed and 17 (23.6%) were probable. The median age was 39 years (range: 16-82 years) and the M/F sex ratio 6.2. Sixty-two (86.1%) patients required hospitalization, including 12 (16.7%) in the intensive care unit. Three (4.2%) patients died. The monthly distribution of cases was correlated with rainfall (P = 0.004) and moisture (P = 0.038). Professional exposure was frequently identified (especially gold mining and construction). Among 16 different serogroups identified by microagglutination test, Icterohaemorrhagiae was the most frequent (38.0%). This study revealed an epidemiology close to that observed in Brazilian regions, and professional and climatic risk factors. The high diversity of serogroups may reveal a complex environmental reservoir requiring further investigations. Only 20% of leptospirosis patients were suspected as such on hospital admission, thus emphasizing the need to inform local physicians.