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Background: The high prevalence of leptospirosis in humans is of great public health concern, particularly in tropical and subtropical regions., Objective: This study aimed to determine the seroprevalence of leptospiral antibodies and the distribution of serovars in livestock breeders and farmers in Golestan province., Methods: Seventy samples of serum collected from farmers and ranchers suspected of leptospirosis were examined using an ELISA method for surveying Immunoglobulin M (IgM) anti-leptospiria. Also from samples, DNA was extracted and PCR was performed using by primers for 16s rRNA. Demographic properties of positive patients were analysed., Results: Chi-square statistical test shows a statistically significant difference between the gender and prevalence leptospirosis (p-value = 0.004). Also, by examining the age, it was shown that 68.57% of patients are in the middleaged rang. According to the results obtained from the study and investigation of blood serum IgM-and Immunoglobulin G (IgG) in people suspected of leptospirosis, 3 cases of the patients had IgM higher than 11 and were known to be positive for leptospirosis. Also, by examining the IgG level of patients, 5 cases had intermediate results, and 2 cases were found to be positive for IgG. The PCR results showed that 41.42% of patients tested positive for the 16s rRNA., Conclusion: Leptospirosis is a common disease among farmers, and in Golestan province, considering traditional farming methods, it is considered an important infectious disease. Therefore, health and safety measures should be expanded to control and prevent this disease. Also, by employing mechanised agricultural methods, the prevalence of leptospirosis in this region can be significantly reduced., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Scrub typhus and leptospirosis are re-emerging zoonotic infections with significant morbidity and mortality rates in India. Overlapping aetiological and epidemiological patterns indicate a high possibility of their co-infection in India, which can be a diagnostic challenge due to non-specific clinical features. A systematic search of the PubMed/MEDLINE, Scopus and Embase databases was conducted to identify relevant studies published through 31 August 2023. Studies reporting co-infection of scrub typhus and leptospirosis among the Indian population were included. Data extraction, quality assessment and statistical analysis were performed in accordance with established guidelines. Six studies met the inclusion criteria, comprising a total of 58 co-infection cases. Pooled prevalence of scrub typhus-leptospirosis co-infection among acute undifferentiated febrile illness patients was 3.7% (95% confidence interval [CI] 0.00 to 0.126). Among scrub typhus patients, the prevalence of co-infection with leptospirosis was 13.7% (95% CI 0.027 to 0.304). Significant heterogeneity was observed among the included studies, highlighting the need for cautious interpretation of prevalence estimates. This meta-analysis underscores the clinical importance of scrub typhus-leptospirosis co-infection in India and emphasizes the need for enhanced clinical awareness, improved diagnostic strategies and targeted research efforts to address this emerging infectious disease threat., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Terrestrial and aquatic environments contaminated with animal urine may contribute to the transmission of Leptospira, a causative agent of leptospirosis in humans and wild/domesticated animals. Although enormous amounts of work have been done decoding the ecophysiology, the factors governing the cell growth and virulence in Leptospires derived from environmental samples still remain elusive. Here, we show oxidation of a wide array of organic acids including acetoacetate by a new strain of Leptospira interrogans designated as KeTo, isolated from a sewage sample originating from a wildlife enclosure located at Mangalore, India. We further demonstrate the susceptibility of KeTo to ethyl ester of acetoacetate (ethyl acetoacetate, EA). A 4.7 Mbp genome of KeTo shared the highest relatedness to pathogenic L. interrogans RGA T (99.3%), followed by L. kirschneri 3522C T (91.3%) and other related species of Leptospira (80.8‒74.3%), and harbored genes encoding acetoacetyl-CoA synthetase and acetoacetate decarboxylase respectively involved in the acetoacetate utilization and acetone formation. In line with this, strain KeTo oxidized acetoacetate when supplied as a sole carbon. Aqueous EA suppressed biofilm formation (p < 0.0001) of KeTo in basal Ellinghausen-McCullough-Johnson-Harris (EMJH) medium. Similarly, significant inhibition in the growth/biofilm of Leptospira was recorded in semisolid EMJH with/without blood supplementation when exposed to volatile EA. The extent of ketone body oxidation and susceptibility to EA was found to vary with strain as evident through the analysis of L. interrogans serogroup Australis sv. Australis strain Ballico and L. interrogans serogroup Icterohaemorrhagiae sv. Lai Like strain AF61. In conclusion, our study demonstrated the ketone body metabolic ability and susceptibility to an esterified derivative of a major ketone body in the tested strains of L. interrogans. Molecular aspects governing EA-driven growth inhibition warrant further investigations to develop optimal therapeutics for leptospirosis., (© 2024. The Author(s).)

Bovine leptospirosis is a major reproductive disease. As cows can be leptospiral carriers both on the renal and genital tract, diagnosis can be challenging, with an underlying risk of misdiagnosis. Traditionally, the infection has been diagnosed by culturing or PCR from urine samples. Nevertheless, recent studies have suggested testing genital samples rather than urine, particularly for the diagnosis of genital colonization and reproductive disorders. The present study aimed to compare urine versus genital samples to detect leptospiral carriers in naturally infected cows with poor reproductive performance under field conditions. Five herds presenting >20 % of seroreactive animals against the Sejroe serogroup were selected. Of these, 106 cows with poor reproductive performance were studied, and urine, uterine fragment (UF), and cervicovaginal mucus (CVM) were obtained and tested by lipL32-PCR. A total of 73 (68.9 %) cows were infected; 64 of which (87.7 %) were diagnosed via positive genital samples (UF and/or CVM), while only 14 (19.2 %) by urine (p ≤ 0.001). Therefore, if the study had been limited to urine samples, as largely recommended, less than 20 % of the infected cows would have been detected, representing a huge misdiagnosis of the disease that could undermine the efficacy of control programs. In this context, the present study reinforces prior findings that testing genital samples, particularly CVM, is crucial to effectively diagnosing infected subfertile cows., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Precise and timely diagnosis is essential to prevent severe outcomes of leptospirosis in humans and animals. Existing diagnostic methods face challenges and limitations, underscoring the need for novel, field-applicable screening and diagnostic tests/assays. This study evaluates the diagnostic utility of a recombinant ErpY-like lipoprotein (rErpY-LIC11966) in a Latex Agglutination Test (LAT) for diagnosis of animal leptospirosis. The ErpY gene sequence from Leptospira interrogans serovar Pomona, excluding the signal peptide, was amplified, cloned into the pETite vector, and expressed in Escherichia coli. The expressed rErpY (∼16 kDa) was characterized by SDS-PAGE and Western blot using Leptospira-specific standard sera. To assess the diagnostic potential of rErpY, Ni-NTA affinity-purified protein was used to sensitize latex-coated beads (0.8 µm colour beads), which were then employed in the LAT for standardization and optimization with standard positive and negative sera. For evaluation, the rErpY-LAT was tested on serum samples from 177 suspected animal cases and compared to the microscopic agglutination test (MAT). It showed a relative diagnostic sensitivity of 90.6%, a specificity of 89.1%, and an overall accuracy of 90%. This study proposes rErpY-LAT as a field testing/screening diagnostic tool for preliminary serodiagnosis of leptospirosis, highlighting the potential of recombinant protein-based assays to address current diagnostic challenges., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Leptospirosis is a re-emerging worldwide zoonotic disease. Infected patients and animals often exhibit intestinal symptoms. Mounting evidence suggests that host immune responses to bacterial infection are closely associated with intestinal homeostasis. Our previous research has shown that the gut microbiota can protect the host from acute leptospirosis, while the specific bacterial metabolic mediators participating in the pathogenesis remain to be identified. Short-chain fatty acids (SCFAs) are metabolites produced mainly by the gut microbiota that play a role in immune regulation. However, whether SCFAs are the key to protecting the host against leptospirosis and the underlying regulatory mechanisms are unknown. In this study, our results showed that the SCFA butyrate is involved in ameliorating leptospirosis. The depletion of SCFAs by antibiotic cocktail treatment reduced survival time after Leptospira infection while supplementation with butyrate but not acetate or propionate significantly amelioration of leptospirosis. In vitro experiments showed that butyrate treatment enhanced the intracellular bactericidal activity mediated by reactive oxygen species (ROS) production. Mechanistically, butyrate functions as a histone deacetylase 3 inhibitor (HDAC3i) to promote ROS production via monocarboxylate transporter (MCT). The protection of butyrate against acute leptospirosis mediated by ROS was also proven in vivo . Collectively, our data provide evidence that the butyrate-MCT-HDAC3i-ROS signaling axis is a potential therapeutic target for acute leptospirosis. Our work not only interprets the microbial metabolite signaling involved in transkingdom interactions between the host and gut microbiota but also provides a possible target for developing a prevention strategy for acute leptospirosis., Importance: Leptospirosis is a worldwide zoonotic disease caused by Leptospira . An estimated 1 million people are infected with leptospirosis each year. Studies have shown that healthy gut microbiota can protect the host against leptospirosis but the mechanism is not clear. This work elucidated the mechanism of gut microbiota protecting the host against acute leptospirosis. Here, we find that butyrate, a metabolite of gut microbiota, can improve the survival rate of hamsters with leptospirosis by promoting the bactericidal activity of macrophages. Mechanistically, butyrate upregulates reactive oxygen species (ROS) levels after macrophage infection with Leptospira by inhibiting HDAC3. This work confirms the therapeutic potential of butyrate in preventing acute leptospirosis and provides evidence for the benefits of the macrophage-HDAC3i-ROS axis., Competing Interests: The authors declare no conflict of interest.

Leptospirosis is a worldwide zoonotic disease caused by serovars of Leptospira spp. that can infect a wide range of wild and domestic species, highlighting non-human primates (NHPs) as one of the most susceptible taxonomic groups. The aim of the present study was to determine the seroprevalence and potential risk factors associated with exposure to Leptospira spp. in captive NHPs in Spain. Between 2007 and 2021, sera were collected from 258 NHPs in 16 zoos and wildlife rescue centers (WRCs), and tested for antibodies to Leptospira spp. using the modified microagglutination test (MAT). Anti-Leptospira spp. antibodies were detected in 73 (28.3 %) of the 258 NHPs evaluated. Seropositivity was found in 61.0 % (25/41) of the species analyzed and in 87.5 % (14/16) of the sampled centers. Sera seropositive for six different serovars of Leptospira spp. were detected, with L. Grippotyphosa being the most prevalent. Seroprevalence was found to be significantly higher in Hominidae (61.8 %; P < 0.001) compared to other NHP families tested. To the author's knowledge, the present study is the largest serosurvey of Leptospira spp. conducted in NHPs in Europe and also reports for the first time exposure to Leptospira spp. in nine NHP species, expanding the host range for this zoonotic bacterium. Our results indicate high and widespread seropositivity of Leptospira spp. in NHPs kept in captivity in Spain, which may be of conservation and animal health concern. This study supports the need to include captive NHPs in monitoring programs to evaluate the exposure of these species to Leptospira spp. in captive centers., Competing Interests: Declaration of Competing Interest None of the authors of this study has a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of the paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Leptospirosis is a bacterial zoonosis that poses an increasing global public health risk. Pacific Island communities are highly vulnerable to leptospirosis outbreaks, yet the local drivers of infection remain poorly understood. We conducted a systematic review to identify the drivers of human Leptospira infection in the Pacific Islands. There were 42 included studies from which findings were synthesized descriptively. In tropical Pacific Islands, infections were a product of sociodemographic factors such as male gender/sex, age 20 to 60 years, Indigenous ethnicity, and poverty; lifestyle factors such as swimming, gardening, and open skin wounds; and environmental factors, including seasonality, heavy rainfall, and exposure to rodents, cattle, and pigs. Possible mitigation strategies in these islands include strengthening disease reporting standards at a regional level; improving water security, rodent control, and piggery management at a community level; and information campaigns to target individual-level drivers of infection. By contrast, in New Zealand, exposures were predominantly occupational, with infections occurring in meat and farm workers. Accordingly, interventions could include adjustments to occupational practices and promoting the uptake of animal vaccinations. Given the complexity of disease transmission and future challenges posed by climate change, further action is required for leptospirosis control in the Pacific Islands.

Leptospirosis is an infectious disease caused by the pathogenic Leptospira species through direct or indirect contact with infected animals. Due to protean clinical manifestation in the early stages, leptospirosis is often difficult to distinguish from other common acute febrile illnesses, such as dengue. Thus, this study aimed to investigate the prevalence of leptospirosis in suspected dengue patients whose serological diagnosis was negative. A total of 449 serum samples from patients (negative IgM-ELISA dengue) with fever, headache, myalgia, and nausea were tested. The Dual-Path Platform (DPP) rapid test developed by the Instituto de Tecnologia em Imunobiológicos Bio-Manguinhos in the city of Rio de Janeiro, Brazil was used for screening IgM antibodies against Leptospira in blood serum, and the microscopic agglutination test (MAT) was performed on samples positive in the DPP for leptospirosis, as well as on an equal number of negative samples. Results: The data obtained from the samples analyzed with the DPP assay showed 26 positive results (5.79%), of which 38.46% were male and 61.54% female, with a mean age of 41 years. We tested 52 samples using the MAT, including 26 reactive for IgM and 26 non-reactive in the DPP assay. Nine samples (17.31%) were reactive, and among them, six also showed reactivity in the DPP assay. Of the six samples reactive in both tests, 66.67% were female, living in urban areas in the city of Uberlândia, with a mean age of 50 years, being 50% white, 33.33% brown, and 16.67% black. The findings demonstrated that leptospirosis cases are underdiagnosed and undertreated in the study population and more attention needs to be paid for ruling out leptospirosis and other pathogens causing acute febrile illness in dengue-endemic areas.

Background: Leptospirosis, a global zoonotic disease, causes serious morbidity and mortality generally in low-income societies. This study aimed to investigate the prevalence of Leptospira serovars in cattle and high-risk human populations., Methods: This study investigated the presence of pathogenic Leptospira serogroups in the blood and kidney samples of cattle arriving at the Erzurum Meat and Milk Institution for slaughter between April and July, and between September and December 2022, and in the serum samples of humans. Kidney and serum samples from 289 cattle and serum samples from 100 individuals from at-risk occupational groups (58 farmers, 25 veterinarians and 17 butchers) were collected. As a control, 100 human blood samples were collected from civil servants who had no contact with animals. Microagglutination testing was used to investigate Leptospira serogroups in bovine sera, real-time polymerase chain reaction (PCR) for Leptospira DNA in kidney samples, and microagglutination testing and enzyme-linked immunosorbent assays for Leptospira antibodies in human blood serum samples., Results: Microagglutination test in 4.5% of cattle; Leptospira DNA was positive in 0.7%. Six strains of Leptospira interrogans , two of Bratislava, one of Pomana and one of Icterohaemorrhagiae were found in cattle, as well as one strain of Leptospira kirschneri Dadas. In humans, two Icterohaemorrhagiae, one Hebdomadis and one Dadas serovar were detected in both the risk group and the control group. Using ELISA, antibody positivity was found to be 14.0% in the risk group and 11.0% in the control group., Conclusion: The seroprevalence of Leptospira spp . in cattle in Erzurum, Türkiye, is relatively high. In this region, the risk of encountering Leptospira in the normal population is as high as in the risk group., Competing Interests: Conflict of Interest: None., (© Penerbit Universiti Sains Malaysia, 2024.)

The platypus ( Ornithorhynchus anatinus ) is an amphibious, egg-laying mammal of high conservation value that is found only in Australia. The zoonotic bacterium Leptospira interrogans serovar Hardjo was discovered in platypuses in prior studies, but little is known about its epidemiology. Samples in the Platypus Serum Bank were tested in 2023 and the results were combined with historical records. Antibodies against L. interrogans serovar Hardjo were found in 50% of 464 serum samples from 411 platypuses collected from 14 river basins in southeastern Australia between 1981 and 2012; prevalence remained high over three decades in the Shoalhaven River population. Seroprevalence increased with age, suggesting environmental exposure. Individual platypuses had persistent titres, some for six years. Seropositive females lactated, juveniles were recruited into the population, and there were no reports of clinical leptospirosis. Three necropsied platypuses were seropositive and had mild nephritis with leptospires in the renal tubules. The high seroprevalence, persistent titres, lack of disease, mild renal lesions, and renal colonisation suggest the platypus may be a maintenance host. Sympatric cattle had L. interrogans serovar Hardjo titres, but the spatial association with seropositive platypuses was statistically weak. Other mammalian wildlife species and sheep also have L. interrogans serovar Hardjo titres; therefore, a complex ecological network must be considered. A landscape-wide study is recommended to properly assess transmission pathways and confirm who is infecting whom.

Aim: To present the clinical features and review of literature of leptospiral uveitis., Methods: We present clinical features of patients with leptospiral uveitis with positive Leptospira IgM antibodies., Results: Twenty-six eyes of 24 patients, 11 males (45.8%), were included. The mean age was 37.5 ± 15.6 years. 91.7% had unilateral uveitis, 88.5% panuveitis, 11.5% anterior uveitis, 15.4% had hypopyon, 8% had cataract and 3.8% eyes had cystoid macular edema. Vitritis with characteristic vitreous membranes was an important feature. Retinal and choroidal vasculature were preserved on swept-source optical coherence tomography angiography. Mean presenting BCVA was logMAR0.49 ± 0.41, while final BCVA was logMAR0.04 ± 0.13. The mean duration for complete resolution of uveitis was 39.1 ± 15.5 days. 84.6% eyes achieved BCVA 6/6., Conclusion: Leptospiral uveitis is an under-reported entity. It may present as anterior uveitis or panuveitis. It must be included in the differential diagnosis of non-granulomatous uveitis. The visual prognosis is usually favorable even in severe cases.

Leptospirosis is a zoonotic disease with significant global impact and a challenging diagnosis. The utilization of adequately validated rapid tests is relevant for the opportune identification of the disease and for reduction in fatality rates. The present study analyzes the accuracy and reliability of the Dual Path Platform (DPP) assay -produced in Brazil by the Oswaldo Cruz Foundation (Fiocruz)- for diagnosing leptospirosis. Firstly, a serological panel was constructed in the Brazilian Reference Laboratory for Leptospirosis using samples routinely handled by reference laboratories of six Brazilian states. It consisted of 150 positive (according to MAT and IgM-ELISA) and 250 negative samples for leptospirosis. Subsequently, the panel samples were distributed to the reference laboratories for the performance of DPP assays in triplicate. Different measures were used in the assessment of diagnostic quality. Predictive values were estimated for different pre-test probability settings. Sensitivities varied between 67.33 % and 74.00 % and specificities between 93.20 % and 98.40 % in the states, and there were adequate agreements between them. Accuracies were lower for the samples of patients with less than 7 days of symptoms. In contexts of prevalence values up to around 25 %, positive and negative predictive values were around 90 %. However, in situations of high pre-test probabilities, NPVs were low. This study improves understanding of the use of DPP in diagnosing leptospirosis, particularly its application in healthcare settings. As long as the time of symptoms onset and clinical and epidemiological contexts are adequately considered for the interpretation of results, DPP is a valid option to be used in the leptospirosis diagnostic routine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In an integrated swine farm with 135 sows in Nagasaki Prefecture, premature births and stillbirths were observed in six sows in June and July 2023, and their etiology was investigated. Leptospiral flaB gene was detected in the kidney of one stillborn fetus and the placenta of its sow by nested PCR. Multilocus sequence typing revealed that the infecting strain was Leptospira interrogans ST118. In addition, leptospiral antigens were detected in lesions of the above tissues by immunohistochemical staining. The examined sow and several other sows in the farm had antibodies against serogroup Hebdomadis. These results suggested that L. interrogans serogroup Hebdomadis ST118 was the causative agent of premature births and stillbirths that occurred in this farm.

Leptospirosis and enteric fever are prevalent tropical acute bacterial febrile illnesses in Kelantan, Malaysia, that exhibit overlapping features and shared transmission dynamics, yet their spatial relationship remains understudied. This study aimed to analyze their spatial distribution, investigating potential interactions and intersecting patterns. A total of 212 laboratory-confirmed cases of enteric fever and 1106 of leptospirosis between 2016 and 2022, were retrieved from the national e-Notifikasi registry. Point pattern analysis revealed clustering of both diseases in the northern region, but leptospirosis was predominant in the south, exhibiting higher spatial risk. Seven co-infection cases were identified in overlapping hotspot areas. Spatial dependence between the diseases was identified within 4 km distance on average, with varying patterns over time and regions. Recognizing spatial dependence has implications for accurate diagnosis, timely intervention, and tailored public health strategies. The findings underscore the need for multi-disease interventions to address shared risk factors and co-infections in similar geographical contexts., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Zoonotic infections, characterized with huge pathogen diversity, wide affecting area and great society harm, have become a major global public health problem. Early and accurate prediction of their outbreaks is crucial for disease control. The aim of this study was to develop zoonotic diseases risk predictive models based on time-series incidence data and three zoonotic diseases in mainland China were employed as cases., Methods: The incidence data for schistosomiasis, echinococcosis, and leptospirosis were downloaded from the Scientific Data Centre of the National Ministry of Health of China, and were processed by interpolation, dynamic curve reconstruction and time series decomposition. Data were decomposed into three distinct components: the trend component, the seasonal component, and the residual component. The trend component was used as input to construct the Long Short-Term Memory (LSTM) prediction model, while the seasonal component was used in the comparison of the periods and amplitudes. Finaly, the accuracy of the hybrid LSTM prediction model was comprehensive evaluated., Results: This study employed trend series of incidence numbers and incidence rates of three zoonotic diseases for modeling. The prediction results of the model showed that the predicted incidence number and incidence rate were very close to the real incidence data. Model evaluation revealed that the prediction error of the hybrid LSTM model was smaller than that of the single LSTM. Thus, these results demonstrate that using trending sequences as input sequences for the model leads to better-fitting predictive models., Conclusions: Our study successfully developed LSTM hybrid models for disease outbreak risk prediction using three zoonotic diseases as case studies. We demonstrate that the LSTM, when combined with time series decomposition, delivers more accurate results compared to conventional LSTM models using the raw data series. Disease outbreak trends can be predicted more accurately using hybrid models., (© 2024. The Author(s).)

Leptospirosis is a widespread zoonosis caused by spirochaetes belonging to the pathogenic species of Leptospira , which are classified into more than 25 serogroups and 250 serovars. Vaccination can prevent the disease in dogs but offers incomplete efficacy because of a lack of cross-protection between serogroups. The aim of this study was to validate a robust recruitment and sampling process, with the objectives of isolating and typing circulating Leptospira pathogenic strains and then selecting those of proven virulence and pathogenicity for vaccine development. Blood and urine samples from dogs with clinical syndromes compatible with acute leptospirosis were sterilely collected and transported to a reference laboratory for a micro-agglutination test (MAT), PCR, and bacterial isolation. Isolated strains underwent molecular typing using RNA16S, variable-number tandem repeat (VNTR), and pulsed-field gel electrophoresis (PFGE). Subtyping was performed using core genome multilocus sequence typing (CgMLST). Among 64 included dogs, 41 had MAT and/or PCR results compatible with Leptospira infection, and 14 Leptospira strains were isolated. Based on molecular typing, 11 isolates were classified as L. interrogans serogroup Australis, serovar Bratislava, and 3 as serogroup Icterohaemorrhagiae, serovar Icterohaemorrhagiae. CgMLST subtyping revealed a diversity of clonal groups (CGs) distributed in several regional clusters. Besides validating a robust recruitment and sampling process, this study outlines the value of combining PCR and serological testing when suspecting leptospirosis and the usefulness of implementing molecular typing methods to identify circulating field strains. It also confirms the epidemiological importance of the Australis serogroup and allows for the collection of different highly pathogenic strains for vaccine development.

The Klaten Regency, Central Java Province, Indonesia, is a leptospirosis endemic area. The purpose of this study is to spatially describe the abiotic and biotic environmental factors that contributed to the incidence of leptospirosis in the Klaten Regency in 2018. This was a descriptive observational with a cross-sectional approach conducted in the Klaten Regency, Central Java, in 2019 with 59 respondents. The results revealed that the percentage of abiotic environmental factors such as poor waste disposal facilities, poor gutter conditions, rivers < 200 m, and flooding history, namely 35.6%, 41.2%, 54.2%, and 6.8%, respectively. The highest leptospirosis cases occurred in April 2018, with 325 mm of rainfall, an average temperature of 27 °C, an average humidity of 82.3%, and an altitude of 100-200 MASL (79.7%). Meanwhile, biotic factors included rat nest existence (100%), having pets at risk (32.2%), and ≥three types of vegetation (79.7%). The main result confirmed that all leptospirosis cases had rat nests throughout the respondent's house. This finding emphasizes the importance of rat pest control programs by establishing cross-sectoral collaboration with the Department of Agriculture and educating the public to also play a role in environmental cleanliness in controlling rats.

Rats are major reservoirs for pathogenic Leptospira , the bacteria causing leptospirosis, particularly in urban informal settlements. However, the impact of variation in rat abundance and pathogen shedding rates on spillover transmission to humans remains unclear. This study aimed to investigate how spatial variation in reservoir abundance and pathogen pressure affect Leptospira spillover transmission to humans in a Brazilian urban informal settlement. A longitudinal eco-epidemiological study was conducted from 2013 to 2014 to characterize the spatial distribution of rat abundance and Leptospira shedding rates in rats and determine the association with human infection risk in a cohort of 2,206 community residents. Tracking plates and live-trapping were used to measure rat abundance and quantify rat shedding status and load. In parallel, four sequential biannual serosurveys were used to identify human Leptospira infections. To evaluate the role of shedding on human risk, we built three statistical models for: (1) the relative abundance of rats, (2) the shedding rate by individual rats, and (3) human Leptospira infection, in which "total shedding", obtained by multiplying the predictions from those two models, was used as a risk factor. We found that Leptospira shedding was associated with older and sexually mature rats and varied spatially and temporally-higher at valley bottoms and with seasonal rainfall (December to March). The point estimate for "total shedding" by rat populations was positive, i.e., Leptospira infection risk increased with total shedding, but the association was not significant [odds ratio (OR) = 1.1; 95% confidence interval (CI): 0.9, 1.4]. This positive trend was mainly driven by rat abundance, rather than individual rat shedding (OR = 1.8; 95% CI: 0.6, 5.4 vs. OR = 1.0; 95% CI: 0.7, 1.4]. Infection risk was higher in areas with more vegetative land cover (OR = 2.4; 95% CI: 1.2, 4.8), and when floodwater entered the house (OR = 2.4; 95% CI: 1.6, 3.4). Our findings indicate that environmental and hydrological factors play a more significant role in Leptospira spillover than rat associated factors. Furthermore, we developed a novel approach combining several models to elucidate complex links between animal reservoir abundance, pathogen shedding and environmental factors on zoonotic spillover in humans that can be extended to other environmentally transmitted diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Soni, Eyre, Souza, Diggle, Ko, Begon, Pickup, Childs, Khalil, Carvalho-Pereira, Pertile, Carvalho, Oliveira, Nery, Giorgi and Costa.)

Leptospirosis is an infectious neglected disease estimated to affect more than one million people worldwide each year. The Complement System plays a vital role in eliminating infectious agents. However, its precise role in leptospirosis remains to be fully understood. We investigated the importance of C3 in L. interrogans serovar Kennewicki strain Pomona Fromm (LPF) infection. Lack of C3 leads to decreased leukocyte number, impaired inflammatory response and failure to eliminate bacteria during the early stages of infection, which may cause interstitial nephritis later. These findings could be explained, at least in part, by the lower presence of local opsonins. Furthermore, antibody production against Leptospira was compromised in the absence of C3, highlighting the importance of CR2 in B lymphocyte proliferation and the adjuvant role of C3d in humoral immunity. Leptospires can be eliminated through the urine, and according to our study, the lack of C3 delays the elimination of LPF through urine during the early stages of the infection. These results strongly suggest the crucial role of C3 protein in orchestrating an appropriate inflammatory response against LPF infection and in effectively eliminating the bacteria from the body during the acute phase of leptospirosis., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2024 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Pathogenic Leptospira spp. causes leptospirosis in animals and humans globally, leading to systemic infections that can impact vital organs in affected animals. The purpose of this study was to evaluate kidney injury and to perform a retrospective analysis of leptospirosis infection in follow-up dog samples. The retrospective study collected epidemiological information obtained through paraclinical exams, immunohistochemistry (IHC), and molecular biology (qPCR) of cases from the Faculty of Veterinary Medicine from Timisoara between September 2016 and May 2023. No correlations were found between Leptospira infection and breed ( p = 0.714), gender or castration status ( p = 0.890), and anatomic pathology exam results ( p = 0.608). Significant associations were found in cases with high levels of azotemia ( p = 0.000) and immunological status (vaccinated vs. unvaccinated, p = 0.000), with the leptospirosis risk in unvaccinated animals calculated at OR = 85.500 (95%CI, 6.82-1071.26, p = 0.000). Retrospectively, leptospirosis was diagnosed in 27/65 cases (42%) using the IHC method, while the qPCR assay detected 29/65 cases (45%). This study demonstrates that qPCR is a robust and specific method for postmortem diagnosis of Leptospira spp. infection in dogs, offering higher specificity and reliability compared to traditional IHC methods, which showed 94.74% specificity in our study.

Hemoperfusion is a novel adjunct therapy that targets the dysregulated inflammatory events in severe sepsis. Previous studies have reported conflicting results on its efficacy and safety. This study was designed to assess the efficacy and safety of hemoperfusion among leptospirosis patients in septic shock and renal failure in terms of improvement in 28-day mortality, SOFA score, level of inflammatory markers, hemodynamics, and renal and pulmonary function. A total of 37 severe leptospirosis patients were enrolled and randomized into either standard medical therapy (SMT) alone, n = 20, or with hemoperfusion (HP), n = 17. Vital signs, urine output, vasopressor dose, PaO 2 /FiO 2 (P/F) ratio, and biochemical parameters of patients from each treatment arm were compared. The hemoperfusion group showed a 36.84% ( p = 0.017) risk reduction in 28-day mortality. Levels of procalcitonin, IL6, and lactate significantly decreased from baseline to day 7 in both groups. Statistically significant improvements in serum creatinine ( p = 0.04) and PF ratio ( p = 0.045) were observed in the hemoperfusion cohort. Intention-to-treat and per-protocol approaches showed that hemoperfusion increased the survival rate and decreased the mortality risk. This benefit for survival persisted even when patients were also receiving extracorporeal membrane oxygenation (ECMO), showing that hemoperfusion's benefits are independent of ECMO use. Hemoperfusion is a safe and effective adjunct therapy for managing severe sepsis. It promotes earlier renal and pulmonary function recovery and improves the survival of septic shock patients.

Leptospirosis, a notifiable endemic disease in Malaysia, has higher mortality rates than regional dengue fever. Diverse clinical symptoms and limited diagnostic methods complicate leptospirosis diagnosis. The demand for accurate biomarker-based diagnostics is increasing. This study investigated the plasma proteome of leptospirosis patients with leptospiraemia and seroconversion compared with dengue patients and healthy subjects using isobaric tags for relative and absolute quantitation (iTRAQ)-mass spectrometry (MS). The iTRAQ analysis identified a total of 450 proteins, which were refined to a list of 290 proteins through a series of exclusion criteria. Differential expression in the plasma proteome of leptospirosis patients compared to the control groups identified 11 proteins, which are apolipoprotein A-II (APOA2), C-reactive protein (CRP), fermitin family homolog 3 (FERMT3), leucine-rich alpha-2-glycoprotein 1 (LRG1), lipopolysaccharide-binding protein (LBP), myosin-9 (MYH9), platelet basic protein (PPBP), platelet factor 4 (PF4), profilin-1 (PFN1), serum amyloid A-1 protein (SAA1), and thrombospondin-1 (THBS1). Following a study on a verification cohort, a panel of eight plasma protein biomarkers was identified for potential leptospirosis diagnosis: CRP, LRG1, LBP, MYH9, PPBP, PF4, SAA1, and THBS1. In conclusion, a panel of eight protein biomarkers offers a promising approach for leptospirosis diagnosis, addressing the limitations of the "one disease, one biomarker" concept.

The present study investigates the public health impact of flooding on leptospirosis incidence after Storm Daniel in Thessaly, Greece, in September 2023. A notable increase in cases was observed, with seven cases of female patients and a mean age of 40.2 years, indicating a significant risk among working-age adults. From the end of September to the beginning of November 2023, a total of 35 patients from flood-prone areas presented to the Emergency Department of the Tertiary University Hospital of Larissa. Diagnosis of leptospirosis was established by meeting the criteria suggested by the national public health organisation (EODY)-compatible clinical course, epidemiological exposure, molecular and serologic confirmation by the detection of immunoglobulin M antibodies to leptospira spp. using a commercially available enzyme-linked immunosorbent assay and real-time quantitative PCR for the molecular detection of leptospira. The larger part (84.6%) of leptospirosis cases were associated with contact with floodwater. The majority of these patients (71.4%) were from the prefecture of Larissa, followed by 14.3% from the prefecture of Karditsa, 8.6% from the prefecture of Trikala, and 5.7% from the prefecture of Magnesia. Occupational exposure and urbanisation were key risk factors. The most prevalent clinical feature was rash (69.2%), followed by fever (61.5%) and myalgia (30.7%). The findings emphasise the need for robust public health strategies, improved sanitation, rodent control, and protective measures for sanitation workers. The data highlight the broader implications of climate change on public health and the necessity for ongoing surveillance and community education to mitigate future outbreaks.

Background: Leptospirosis and rickettsial infections are bacterial zoonoses prevalent in different geographical locations and presents with overlapping symptoms., Objective: To identify foetal outcomes in pregnant women diagnosed with rickettsial infections, including scrub typhus and leptospirosis, along with their associated factors., Methods: A comprehensive search was conducted in MEDLINE/PubMed, Scopus, CENTRAL (Cochrane), Web of Science, PsycINFO, Academic Search Premier, CINAHL, and Embase using defined search terms. Studies involving pregnant women with diagnosed leptospirosis and rickettsial infections, including scrub typhus, were selected. Two independent reviewers screened titles and abstracts using the Rayyan Web interface. Data extraction was performed in Microsoft Excel, with Zotero for reference management. Study quality was assessed using Joanna Briggs Institute Critical Appraisal tools. Data synthesis included narrative analysis., Results: Fifty-four studies were included: 22 on scrub typhus, 14 on rickettsial infection, 16 on leptospirosis, and 2 on all three infections. Of 176 scrub typhus cases, 53 resulted in foetal loss and 3 in neonatal death. Among 38 rickettsial infection cases, 4 had foetal loss. Out of 63 leptospirosis cases, 13 experienced foetal loss. Six maternal deaths occurred due to scrub typhus and one due to Rocky Mountain spotted fever., Conclusion: Leptospirosis and rickettsial infections, including scrub typhus, are important causes of pregnancy loss. Further research is needed to better understand and mitigate these risks in pregnant women., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: Globally, India has a high zoonotic disease burden and lacks surveillance data in humans and animals. Rodents are known reservoirs for many zoonotic diseases and their synanthropic behavior poses a great public health threat., Methods: In this study, trapped rodents/shrews from randomly selected villages within Puducherry, India, and their ectoparasites were screened for zoonotic pathogens, namely, Orientia tsutsugamushi, other pathogenic rickettsiae, Leptospira spp., Cryptosporidium spp., Coxiella burnetii and methicillin-resistant Staphylococcus aureus (MRSA) using conventional PCR. A total of 58 rodents/shrews were trapped from 11 villages. The species trapped were Suncus murinus (49/58, 84.48%), Rattus rattus (8/58, 13.79%) and Rattus norvegicus (1/58, 1.72%). All ectoparasites collected were identified as mites and its infestation rate was 46.55% (27/58)., Results: Real-time PCR targeting the 47 kDa gene of O. tsutsugamushi revealed positivity in one rodent and one shrew (3.45%) and two mite pools (7.41%). Conventional PCR targeting the 56 kDa gene revealed positivity in one shrew and two mite pools and the phylogenetic analysis of all three amplicons indicated the circulation of the Gilliam-related serotype. MRSA was detected in the alimentary tract of a shrew (1/32, 3.13%). Leptospira spp., Rickettsia, Cryptosporidium spp. and Co. burnetii tested negative., Conclusions: The detection of zoonotic pathogens within reservoir hosts and vectors poses a risk of transmission to humans. This study signifies the need for zoonotic pathogen surveillance in synanthropic rodents/shrews., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: Leptospirosis is an endemic zoonosis in tropical areas that is mainly related to rural activities; nevertheless, human leptospirosis (HL) outbreaks differ among regions. In Colombia, HL notifications are mandatory. Our objective was to determine the spatiotemporal distribution of HL in Colombia during 2007-2018 and its relationship with the main hydroclimatic variables., Methods: We determined the estimated incidence and lethality of HL according to department and year. The Bayesian spatiotemporal analysis of an autoregressive model (STAR) model included HL cases and hydroclimatic factors (average temperature, rainfall and relative humidity) for quarterly periods., Results: During the study period, 10 586 HL cases were registered (estimated incidence: 1.75 cases x 105) and 243 deaths by HL (lethality 2.3%). The STAR model found association of HL risk with temperature (RR:6.80; 95% CI 3.57 to 12.48) and space. Quindío and three other Amazonian departments (Guainía, Guaviare and Putumayo) had a positive relationship with a significant number of HL cases, adjusted for quarterly precipitation and humidity., Conclusion: Spatial analysis showed a high risk of HL in departments of the western Andean Colombian regions. By contrast, in the spatiotemporal model, a higher HL risk was associated with temperature and departments of the North Colombian Amazon regions and Quindío in the Colombian Andean region., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Pathogenic spirochetes of the genus Leptospira are the causative agent of leptospirosis, a widely disseminated zoonosis that affects humans and animals. The ability of leptospires to quickly cross host barriers causing infection is not yet fully understood. Thus, understanding the mechanisms of pathogenicity is important to combat leptospiral infection. Outer membrane proteins are interesting targets to study as they are able to interact with host molecules. Proteins containing leucine-rich repeat (LRR) domains are characterized by the presence of multiple regions containing leucine residues and they have putative functions related to host-pathogen interactions. Hence, the present study aimed to clone and express the recombinant protein encoded by the LIC11098 gene, an LRR protein of L. interrogans serovar Copenhageni. In silico analyses predicted that the target protein is conserved among pathogenic strains of Leptospira, having a signal peptide and multiple LRR domains. The DNA sequence encoding the LRR protein was cloned in frame into the pAE vector, expressed without mutations in Escherichia coli and purified by His-tag chromatography. Circular dichroism (CD) spectrum showed that the recombinant protein was predominantly composed of β-sheets. A dose-dependent interaction was observed with cellular and plasma fibronectins, laminin and the complement system component C9, suggesting a possible role of the protein encoded by LIC11098 gene at the initial stages of infection., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

This study aimed to explore sociocultural determinants that might contribute to the increased prevalence and incidence of leptospirosis, and how those determinants can also hinder health promotion interventions, particularly in rural areas of Sri Lanka. Even though several epidemiological studies have been conducted on leptospirosis in the Asia-Pacific region, the sociocultural background of this disease has not received sufficient attention. Therefore, through a qualitative study involving nine public health officials and 25 infected patients in five selected health administrative divisions, we demonstrate that a set of certain sociocultural determinants influence leptospirosis incidence and its prevalence. The thematic analysis generated six themes: a lack of knowledge of the causes and consequences of leptospirosis, false illness interpretations, a lack of readiness for the disease, poor economic conditions, social capital failure, and issues within the health system at the community level. Overall, results suggest that awareness programs aimed at demystifying false interpretations of leptospirosis lie at the center of any health promotion interventions at the community level., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

A simple IgG-specific ELISA for Leptospira spp. was compared with the microscopic agglutination test (MAT) to detect IgG antibody responses to a commercial vaccine in cattle. We used an enzyme-linked immunosorbent assay (ELISA) with sonicated Leptospira interrogans serovar copenhageni M 20. After initial vaccination, specific antibodies against Leptospira spp. were detected in 90 % of the animals by IgG-ELISA and 60 % by MAT, while after booster, antibodies were detected in 100 % and 80 % of the animals by IgG-ELISA and MAT, respectively. Both serological MAT and ELISA tests revealed interferences of vaccine antibodies. Disease diagnosis with ELISA and MAT methods should be made two and a half months and four months, respectively, after vaccination to avoid interference of vaccine antibodies. On the other hand, our results suggest that IgG-ELISA may be a useful method to assess the development of IgG antibodies induced by Leptospira vaccine., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024. Published by Elsevier B.V.)

Leptospirosis (LTPS) is a bacterial infection that affects humans, often with mild or no symptoms. It is estimated that approximately 10 % of patients with LTPS may experience multi-organ dysfunction, including renal abnormalities. In regions where LTPS is widespread, a considerable number of instances involving acute kidney injury (AKI) and chronic kidney disease (CKD) of unknown etiology (CKDu) have been reported. Additionally, studies have shown a correlation between kidney graft dysfunction in patients with stable kidney transplants after LTPS. These findings indicate that exposure to LTPS may increase the likelihood of kidney transplantation due to the onset of both acute and chronic kidney injuries. Simultaneously, it poses a potential risk to the stability of kidney grafts. Unfortunately, there is limited scientific literature addressing this issue, making it difficult to determine the negative impact that LTPS may have, such as its role as a risk factor for the need of kidney transplantation or as a threat to individuals who have undergone kidney transplants. This study aims to shed light on the immune mechanisms triggered during LTPS infection and their importance in both kidney damage and allograft dysfunction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Leptospirosis, an underdiagnosed zoonotic disease in India, was studied retrospectively in Madhya Pradesh, Central India. Between 2018 and 2019, 2617 samples from patients with hepatitis-related symptoms were collected. Of these, 518 tested negative for hepatitis and other tropical viral diseases under the VRDL project were analyzed for leptospira IgM using ELISA. 68 (13.12%) were positive for leptospirosis. Common symptoms included fever (97.45%) and jaundice (42.27%), with renal involvement in 30.88% of cases. Higher incidence was observed in the 31-60 age group, especially during monsoon and post-monsoon seasons. The study highlights the need for increased clinician awareness and inclusion of leptospirosis in screening panels to differentiate tropical illnesses in India., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the research work reported here., (Copyright © 2024 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Introduction: Leptospirosis and dengue are two significant public health concerns in tropical and subtropical regions, often resulting in severe forms of disease and fatality. This study addresses the pressing public health issues of leptospirosis and dengue in the Dakshina Kannada district of Karnataka, India. Both diseases pose significant health risks and are relatively understudied in this region, making it essential to investigate their prevalence and clinical presentations for targeted healthcare planning., Aim: The primary aim is to determine the frequency of leptospirosis and dengue among febrile illness cases to understand the epidemiological patterns and assess co-infection rates in Dakshina Kannada., Method: Between 2020 and 2021, serum samples suspected of leptospirosis were tested using IgM ELISA (n = 1629) and the Microscopic Agglutination Test (MAT) (n = 92) for leptospirosis, while dengue was tested using NS1Ag and IgM antibodies ELISA (n = 1415). Data were collected through medical records and patient interviews. Seasonal trends, gender, and age distributions were analyzed., Result: The study found a significant prevalence of leptospirosis (21 %) and dengue (10 %) among febrile illness cases in the study area, with a 1.3 % co-infection rate. Clinically, fever was common to both diseases, but leptospirosis also frequently exhibited symptoms such as abdominal pain, myalgia, and jaundice. MAT screening revealed a predominance of anti-leptospiral antibodies against the Djasiman, Pyrogenes, Hurstbridge, Hebdomadis, and Grippotyphosa serogroups in Dakshina Kannada., Conclusion: The study highlights the urgent need for focused public health interventions, improved diagnostic tools, and targeted epidemiological studies to manage these diseases. The findings underscore the necessity of enhancing diagnostic capabilities and public health awareness, particularly considering the significant health risks posed by leptospirosis and dengue in the region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Infection and invasion are the prerequisites for developing the disease symptoms in a host. While the probable mechanism of host invasion and pathogenesis is known in many pathogens, very little information is available on Leptospira invasion/pathogenesis. For causing systemic infection Leptospira must transmigrate across epithelial barriers, which is the most critical and challenging step. Extracellular and membrane-bound proteases play a crucial role in the invasion process. An extensive search for the proteins experimentally proven to be involved in the invasion process through cell junction cleavage in other pathogens has resulted in identifying 26 proteins. The similarity searches on the Leptospira genome for counterparts of these 26 pathogenesis-related proteins identified at least 12 probable coding sequences. The proteins were either extracellular or membrane-bound with a proteolytic domain to cleave the cell junction proteins. This review will emphasize our current understanding of the pathogenic aspects of host cell junction-pathogenic protein interactions involved in the invasion process. Further, potential candidate proteins with cell junction cleavage properties that may be exploited in the diagnostic/therapeutic aspects of leptospirosis will also be discussed. KEY POINTS: • The review focussed on the cell junction cleavage proteins in bacterial pathogenesis • Cell junction disruptors from Leptospira genome are identified using bioinformatics • The review provides insights into the therapeutic/diagnostic interventions possible., (© 2024. The Author(s).)

Introduction: Leptospirosis and melioidosis are common in tropical and temperate climates and can be acquired by exposure to contaminated water and soil. However, concomitant leptospirosis and melioidosis infection is rarely described in the literature. We report a case of leptospirosis-melioidosis coinfection and systematically review the literature., Case Presentation: A 42-year-old male presented with fever associated with chills and rigor, dull aching pain in the right thigh, myalgia, progressive breathlessness, and dry cough for 10 days. At presentation, he was tachypneic and had tachycardia, and oxygen saturation was 46% in room air. Chest radiography and computed tomography scan showed interstitial involvement. Magnetic resonance imaging for thigh pain revealed right femur osteomyelitis. Leptospira serology was positive, and blood culture grew Burkholderia pseudomallei, confirming the diagnosis of melioidosis. Thus, a diagnosis of presumptive leptospirosis based on modified Faine's criteria and systemic melioidosis was made. He received doxycycline and intravenous meropenem and improved., Results: We performed a systematic review to understand the spectrum of leptospirosis-melioidosis coinfection. We identified only nine cases of coinfection described in literature. Only one patient had septic arthritis, and our case is the only one presenting with osteomyelitis. Serology diagnosed leptospirosis, whereas melioidosis was confirmed by blood culture in most patients. The majority of coinfected patients developed some complications, and six died., Conclusions: Leptospirosis-melioidosis coinfection is rarely reported in the literature. Physicians should maintain a high index suspicion of leptospirosis-melioidosis coinfection in patients presenting with acute febrile illness following exposure to soil or freshwater, particularly in tropical and endemic regions., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Manoj Kumar Panigrahi, Shakti Kumar Bal, Tara Prasad Tripathy, Akshaya Moorthy, Swadesh Kumar Mohanty, Ashoka Mahapatra, Sourin Bhuniya.)

The Omp85 family of outer membrane proteins are ubiquitously distributed among diderm bacteria and play essential roles in outer membrane (OM) biogenesis. The majority of Omp85 orthologs are bipartite and consist of a conserved OM-embedded 16-stranded beta-barrel and variable periplasmic functional domains. Here, we demonstrate that Leptospira interrogans encodes four distinct Omp85 proteins. The presumptive leptospiral BamA, LIC11623, contains a noncanonical POTRA4 periplasmic domain that is conserved across Leptospiraceae. The remaining three leptospiral Omp85 proteins, LIC12252, LIC12254 and LIC12258, contain conserved beta-barrels but lack periplasmic domains. Two of the three 'noNterm' Omp85-like proteins were upregulated by leptospires in urine from infected mice compared to in vitro and/or following cultivation within rat peritoneal cavities. Mice infected with a L. interrogans lic11254 transposon mutant shed tenfold fewer leptospires in their urine compared to mice infected with the wild-type parent. Analyses of pathogenic and saprophytic Leptospira spp. identified five groups of noNterm Omp85 paralogs, including one pathogen- and two saprophyte-specific groups. Expanding our analysis beyond Leptospira spp., we identified additional noNterm Omp85 orthologs in bacteria isolated from diverse environments, suggesting a potential role for these previously unrecognized noNterm Omp85 proteins in physiological adaptation to harsh conditions., (© 2024. The Author(s).)

Leptospirosis is a bacterial infection caused by the pathogen Leptospira. The disease is primarily transmitted through contact with animals (mainly rats) or through exposure to contaminated water or soil. Underdeveloped countries and places with poor housing and sanitation are at higher risk. Leptospirosis often presents with nonspecific symptoms, making it difficult to diagnose. This can delay the initiation of appropriate treatment. In the case presented, the patient had a history of cough, high fever, and a rash over various parts of the body. This combination of respiratory symptoms, systemic fever, and dermatological manifestations led to the suspicion of an infection. Initial blood examinations revealed a significantly increased white blood cell (WBC) count, indicating an infection. Further enzyme-linked immunosorbent assay (ELISA) testing was confirmed by active immunoglobulin M (IgM) antibodies specific to leptospira species, followed by a chest X-ray scan. The antibiotics doxycycline (for seven days) and ceftriaxone (two weeks) were used to treat the leptospirosis. The patient was also given antipyretics to bring down fever and antitussive agents to suppress the cough. Hydration and breathing exercises were also given high priority in healing from this illness. After treatment, the patient did very well, he sweated less before dawn, the rash started to go away, and finally, even coughing was controlled. Further blood tests have shown that now the WBC is in the normal range and the IgM antibody level has dropped. In other words, the infection has been eradicated. For detailed information, refer to the case study "A Moral Call," which argues that early treatment and intervention are critical in managing leptospirosis. Getting this severe infection with early antibiotic therapy and nursing care gives people a chance for complete recovery from their illness. There must be more studies into this disease's long-term effects and how to prevent it when the risk group is more significant., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Timande et al.)

Tropical co-infections, characterized by overlapping clinical manifestations and the potential for diagnostic confusion, pose significant challenges in the management of febrile illnesses in endemic regions. This case report presents a 33-year-old male with a five-day history of fever, gastrointestinal symptoms, and dry cough, ultimately diagnosed with co-infections of dengue, leptospirosis, and Salmonella paratyphi A . This case underscores the challenges posed by the overlapping clinical features of endemic tropical diseases, emphasizing the necessity for comprehensive diagnostic strategies and tailored treatment protocols in managing febrile illnesses in endemic regions. Clinicians must also consider serological cross-reactivity when interpreting diagnostic tests, as it can complicate the identification of co-infections and impact treatment decisions, necessitating vigilance and an integrated approach in clinical practice., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Simon et al.)

Leptospirosis is a bacterial disease of worldwide distribution with relevant implications for animal and human health. Different large wild carnivore species can act as reservoirs of this zoonotic pathogen. This study aimed to evaluate the circulation of Leptospira spp. in free-ranging wolves (Canis lupus) from southern Europe. A total of 281 kidney samples of wolves from Spain and Italy were collected between 2017 and 2023. The presence of Leptospira DNA was analysed by real-time PCR and phylogenetic analyses were carried out using a Bayesian approach. The overall prevalence was 3.2 % (9/281; 95 %CI: 1.1-5.3). Leptospira DNA was detected in nine of the 180 wolves from Spain (5.0 %; 95 %CI: 1.8-8.2), but not in the Italian wolf population (0 %; 0/101). Molecular analyses revealed high homology between the sequences obtained in the present study and isolates of Leptospira interrogans and Leptospira borgpetersenii from different rodent and domestic ungulate species. Our results provide evidence of a low and spatially heterogeneous circulation of this pathogen in wolf populations of southern Europe. The detection of zoonotic Leptospira species in this survey supports the need to consider wolf populations in monitoring programs for leptospirosis with a One Health approach., Competing Interests: Declaration of Competing Interest None of the authors of this study has a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of the paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Leptospirosis is a zoonosis with global public health impact, particularly in poor socio-economic settings in tropical regions. Transmitted through urine-contaminated water or soil from rodents, dogs, and livestock, leptospirosis causes over a million clinical cases annually. Risk factors include outdoor activities, livestock production, and substandard housing that foster high densities of animal reservoirs. This One Health study in southern Chile examined Leptospira serological evidence of exposure in people from urban slums, semi-rural settings, and farm settings, using the Extreme Gradient Boosting algorithm to identify key influencing factors. In urban slums, age, shrub terrain, distance to Leptospira -positive households, and neighborhood housing density were contributing factors. Human exposure in semi-rural communities was linked to environmental factors (trees, shrubs, and lower vegetation terrain) and animal variables ( Leptospira -positive dogs and rodents and proximity to Leptospira -positive households). On farms, dog counts, animal Leptospira prevalence, and proximity to Leptospira -contaminated water samples were significant drivers. The study underscores that disease dynamics vary across landscapes, with distinct drivers in each community setting. This case study demonstrates how the integration of machine learning with comprehensive cross-sectional epidemiological and geospatial data provides valuable insights into leptospirosis eco-epidemiology. These insights are crucial for informing targeted public health strategies and generating hypotheses for future research.

Leptospirosis is a significant zoonosis worldwide, with disease severity ranging from a mild non-specific illness to multi-organ dysfunction and hemorrhage. The disease is caused by pathogenic bacteria of the genus Leptospira , which are classified into pathogenic and saprophytic clades. Bacterial binding to host molecules and cells, coordinated by adhesin proteins, is an important step in pathogenesis. While many leptospiral adhesins have been identified, the vast majority have not been characterized in vivo . Herein, we present an overview of the current methodologies and successes in identifying adhesins in Leptospira , including known biological roles in vivo . We will also identify and discuss potential areas for future research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Surdel and Coburn.)

Background: Both dengue and Leptospira infections are endemic to tropical and subtropical regions, with their prevalence increasing in recent decades. Coinfection with these pathogens presents significant diagnostic challenges for clinicians due to overlapping clinical manifestations and laboratory findings. This case report aims to elucidate two clinical scenarios where the coinfection of dengue and leptospirosis complicates the disease course, creating a diagnostic conundrum., Case Presentation: We present the clinical scenarios of two Bangladeshi males, aged 25 and 35 years, who were admitted to our hospital with acute febrile illness. The first patient exhibited hepatic and renal involvement, while the second presented with symptoms initially suggestive of meningoencephalitis. Both cases were initially managed under the presumption of dengue infection based on positive serology. However, further evaluation revealed coinfection with Leptospira, complicating the disease course. Both patients received appropriate treatment for dengue and antibacterial therapy for leptospirosis, ultimately resulting in their recovery., Conclusion: These case scenarios underscore the critical importance for clinicians in regions where dengue and Leptospira are endemic to consider both diseases when evaluating patients presenting with acute febrile illness., (© 2024. The Author(s).)

Introduction: Leptospirosis is a globally transmitted zoonotic disease caused by Leptospira spp., a highly mobile, obligate aerobic, spiral-shaped bacteria. Described first by Adolf Weil in 1886, leptospirosis in Germany is rare, leading to a delayed diagnosis due to diverse symptoms. Most cases are mild, but severe forms, like Weil's disease, cause life-threatening complications such as fever, jaundice, hemoptysis, and acute kidney injury (AKI). The aim of this work was to provide a literature review of leptospirosis with renal manifestation based on a case report., Case Presentation: We report the case of an 81-year-old male patient with initially unclear oliguric AKI, bilateral pulmonary infiltrates, and jaundice. After excluding common AKI causes, the expanded patient history suggested possible rat contact in his chicken coop. Finally, we serologically identified an infection with Leptospira spp. by positive IgM, proving that the illness was compatible with classical Weil's disease. The patient underwent temporary hemodialysis and antibiotic treatment with intravenous penicillin G for 2 weeks. Under therapy, the AKI, hyperbilirubinemia, and clinical condition of the patient improved. The patient was discharged after 2 weeks. In the following controls, slightly impaired kidney function was observed, indicating a progress of his chronic kidney disease (CKD)., Conclusion: Although leptospirosis is rare, there are some cases with a fulminant course. Impairment of renal function often correlates with severity of the disease requiring antibiotic treatment. In some cases, AKI progresses to CKD demonstrating the need to raise awareness for leptospirosis., (© 2024 S. Karger AG, Basel.)

Leptospirosis, an acute zoonotic infection caused by spirochetes of the genus Leptospira, poses significant health risks worldwide. Transmission occurs through contact with infected animals' urine, blood, or tissue. This case report examines a 44-year-old man with severe leptospirosis, presenting as Weil's disease, characterized by acute hypoxic respiratory failure and acute kidney injury (AKI) secondary to rhabdomyolysis, complicated by severe hyponatremia. The case underscores the diagnostic and management challenges associated with leptospirosis, highlighting the importance of interdisciplinary collaboration and comprehensive diagnostic evaluation., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Maqbool et al.)

Background and Objectives: Leptospirosis is an infectious zoonotic disease that can result in severe complications. It is widespread, especially in hot and humid climates such as the northern region of Iran. The immune responses to leptospirosis are multifaceted. Lipl41 is an outer membrane protein that is expressed during infection and is highly conserved among pathogenic species. This makes it a good candidate for diagnosis and induction of specific immune responses. The aim of the present study was to evaluate immune responses against recombinant Lipl41 in mice., Materials and Methods: After immunizing of different groups of mice with recombinant Lipl41 (rLipl41), the levels of specific antibodies and cytokine profiles interferon-gamma/interleukin-4 (IFN-γ/IL-4) were measured., Results: The results revealed that rLipl41 showed a significant increase in antibody levels compared with the control groups (P< 0.05). Although the level of IL-4 in the groups that received Lipl41 was similar to that in the other control groups, the IFN-γ levels showed a significant increase (P<0.05)., Conclusion: It has been concluded that recombinant Lipl41 protein could strongly stimulate specific immune responses and be considered a potential candidate for vaccine development and diagnostic research., (Copyright© 2024 The Authors. Published by Tehran University of Medical Sciences.)

This study examines household pets as potential epidemiological links between environments contaminated with pathogenic leptospires and humans in Santa Fe, Argentina. The aims of our study were: (a) to characterize the habits and exposure to environmental sources of leptospirosis in the population of dogs and cats attending to municipal spay and neutering campaigns in Santa Fe, Argentina, (b) to assess the seroprevalence of anti-Leptospira antibodies in asymptomatic dogs and cats, (c) to evaluate factors that could increase seropositivity, and (d) to identify spatial clusters of seropositive dogs and cats in the capital city of Santa Fe. From May to November 2022, a cross-sectional serosurvey was conducted during municipal spaying/neutering campaigns. Eligible household dogs and cats were over 6 months old, apparently healthy, and not vaccinated against leptospirosis in the past 6 months. We used microagglutination test (MAT) to assess anti-Leptospira antibodies using a panel of 10 reference strains. We used generalized linear mixed effects models (GLMM) to examine individual and census tract-level risk factors for seropositivity, and local Moran's I statistic for spatial clusters. Results showed higher leptospiral antibody prevalence in dogs (18.2 %) than cats (3.6 %, p = 0.002). Dogs with street access had higher likelihood of being seropositive (OR: 3.8, 95 % CI: 1.2; 11.9), and areas with chronic poverty showed an elevated risk of presenting seropositive animals (RR: 4.0, 95 % CI: 1.1; 14.4). Spatial analysis didn't reveal significant seropositivity clusters among census tracts. These findings shed light on widespread Leptospira seropositivity in pets in this endemic region. Understanding seroprevalence and risk factors can guide public and veterinary health strategies, emphasizing increased leptospirosis vaccination for dogs in vulnerable areas and promoting responsible pet care., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Leptospirosis is an infectious disease with a worldwide distribution, which represents a major challenge in animal production across developing countries, mainly in tropical areas. Horses are particularly susceptible to the disease, presenting manifestations ranging from subclinical to the development of uveitis that compromises the visual health of the animals. In recent years, serological studies have been carried out in equid populations from America, demonstrating high exposure. For this reason, the aim of this study was to demonstrate microbiologically and molecularly the presence of the members of the genus Leptospira in urine samples from equids in an endemic state of leptospirosis in Mexico, and to detect the serological presence of anti-Leptospira antibodies in the sampled animals. For this reason, blood and urine samples were collected from 28 horses and one mule from three localities in the state of Veracruz, Mexico. Urine samples were inoculated in Ellinghausen-McCullough-Johnson-Harris (EMJH) medium, and the recovered isolates were typed using a short Multi Locus Sequence Typing scheme. Amplifications of the expected size were subjected to sequencing, and the recovered sequences were compared with those of reference deposited in GenBank using the BLAST tool. To identify their phylogenetic position, we performed a phylogenetic reconstruction using the maximum likelihood method. Additionally, Microscopic Agglutination test was performed on the serum samples to identify anti-Leptospira antibodies. We recovered 16 urine isolates which tested positive for the presence of Leptospira DNA. The phylogenetic reconstruction and the MLST analysis confirmed the presence of several genotypes of Leptospira interrogans and Leptospira santarosai. An overall serological frequency of 97.1 % was detected. Our results represent the first record of the presence of Leptospira through bacteriological isolates in equids from Mexico., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

This study evaluates the diagnostic efficacy of urinary biomarkers, Neutrophil Gelatinase-Associated Lipocalin (uNGAL), and Kidney Injury Molecule-1 (uKIM-1), in identifying Acute Kidney Injury (AKI) in dogs affected with leptospirosis or babesiosis. Acute kidney injury was diagnosed based on the increase in serum creatinine levels above 0.3 mg/dL within 48 h and dogs were categorized according to AKI grades based on International Renal Interest Society guidelines. Traditional biomarkers (serum creatinine and blood urea nitrogen) and novel biomarkers like urinary NGAL and urinary KIM-1 levels were measured and compared to concentrations obtained in control dogs. Statistical analysis assessed significant differences (P < 0.01) across AKI grades, specifically noting elevated urinary NGAL and KIM-1 in IRIS grade I AKI (P < 0.001). The study highlights the diagnostic significance of urinary NGAL and KIM-1 as early indicators of renal damage, particularly valuable in non-azotemic AKI cases, offering promising markers for early AKI diagnosis in veterinary clinical settings. These biomarkers demonstrate clinical utility and underscore their potential for improving AKI management in veterinary medicine. Further validation studies involving larger cohorts and diverse etiologies of AKI are needed to confirm the diagnostic accuracy and clinical utility of urinary NGAL and KIM-1 in veterinary practice., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Leptospirosis is a zoonotic disease of global significance, contributing to morbidity and mortality worldwide. It is endemic to tropical regions, with outbreaks during monsoons. The disease manifestations are similar to that of other febrile illness such as dengue, malaria hence often misdiagnosed and underreported. The zoonoses if undetected, progresses to cause severe life-threatening complications also known as Weil's disease. Routine diagnostic tests are based on the detection of antibodies in patient serum and are not accurate during the initial phase of the infection. Therefore, it is necessary to detect novel biomarkers that can be used in early detection of leptospirosis. Circulating miRNAs are known to be promising biomarkers for various diseases including cancer, tuberculosis, influenza; hence in this study the potential of miRNAs as biomarkers for leptospirosis was evaluated. A total of 30 leptospirosis cases were screened for the differential expression of 10 miRNA by RT-qPCR assay. The differential expression was calculated by relative quantification using healthy individuals as controls. Among the 10 miRNA,3 miRNA, miR-28-5p, miR-302c-3p and miR-302a-3p were reported to exhibit a significant trend of upregulation. Further their role in immune pathways and biological processes was investigated by KEGG analysis and Gene Ontology. The 3 miRNAs were observed to target various immune response pathways, thus confirming their role in host immune response. Based on the results obtained in this study, miR-28-5p, miR-302c-3p and miR-302a-3p can be considered as potential biomarkers for the detection of leptospirosis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gillaine Vail Pinto, Praveen Rai, Shama Prakash Kabekkodu, Indrani Karunasagar, Ballamoole Krishna Kumar has patent pending to Intellectual Property India. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Leptospirosis is a common but underdiagnosed zoonosis. We conducted a 1-year prospective study in La Guaira State, Venezuela, analyzing 71 hospitalized patients who had possible leptospirosis and sampling local rodents and dairy cows. Leptospira rrs gene PCR test results were positive in blood or urine samples from 37/71 patients. Leptospira spp. were isolated from cultured blood or urine samples of 36/71 patients; 29 had L. interrogans, 3 L. noguchii, and 4 L. venezuelensis. Conjunctival suffusion was the most distinguishing clinical sign, many patients had liver involvement, and 8/30 patients with L. interrogans infections died. The Leptospira spp. found in humans were also isolated from local rodents; L. interrogans and L. venezuelensis were isolated from cows on a nearby, rodent-infested farm. Phylogenetic clustering of L. venezuelensis isolates suggested a recently expanded outbreak strain spread by rodents. Increased awareness of leptospirosis prevalence and rapid diagnostic tests are needed to improve patient outcomes.