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Leptospirosis is an emerging illness presenting a broad range of clinical manifestations, ranging from asymptomatic or mild cases to severe and fatal outcomes. Early detection is crucial for effective treatment; however, similar clinical presentations in various febrile illnesses or co-infections, along with challenges in laboratory diagnostics, can lead to misdiagnosis and severe consequences. Identifying clinical predictors for severe forms of the disease is essential in mitigating complications and reducing mortality. Consequently, we conducted a retrospective case-control study to identify clinical markers indicative of severe disease in leptospirosis patients from the Transcarpathian region. The study focused on patients admitted with clinically suspected leptospirosis, involving a total of 51 diagnosed cases, with 13 resulting in severe outcomes and death. Categorical variables were analyzed using χ2, revealing a mean patient age of 50 years, predominantly male (n = 36, 70.5%). Oliguria emerged as a significant independent factor associated with mortality (odds ratio [OR], 13.5; 95% confidence interval [CI], 2.56–71.12; p = 0.001). Additionally, our analysis uncovered a noteworthy increase in leptospirosis notification rates in Transcarpathian compared to Ukraine, with 150 cases out of the total 433 in Ukraine. The highest notification rates were observed in Mukachevo District and Perechyn District. These findings highlight the importance of early recognition of key clinical markers, such as oliguria, which are critical for predicting severe outcomes in leptospirosis patients. The higher notification rates in Transcarpathian regions also underscore the need for enhanced surveillance, targeted public health interventions, and timely treatment to reduce mortality in endemic areas.

IntroductionLeptospirosis is a global zoonosis that affects more than one million people per year, with a lethality rate of approximately 15%. Chemokines are crucial in the immune response against Leptospira, recruiting leukocytes to the site of infection and regulating immune activity. In previous studies, we have shown that CCL2, CXCL5, and CCL8 are involved in the leptospirosis process, although the mechanisms are not understood. MethodsIn this study, we present the frequency of Leptospira serovars in human samples. We then evaluated the profile of various chemokines in sera from patients diagnosed with leptospirosis, assessing the possible correlation between them. Moreover, we evaluated the changes in the chemokine profile on different days after the first symptoms. The frequency of the Leptospira serovars in human samples is presented. Results and discussionThe main findings were that CCL5, CXCL5, and CXCL9 are highly expressed during leptospirosis, indicating a special role of these molecules in the immunity and pathogenesis of the disease. The correlation analysis of detected chemokines CXCL11, CXCL9, CCL3, and CCL2 helps to clarify the role of each cytokine in leptospirosis. The possible use of CCL5 as a biomarker for complementary diagnosis of the disease is suggested.

ABSTRACT 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.IMPORTANCELeptospirosis 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.

ABSTRACT: Leptospirosis is a zoonotic disease that must be studied on the One Health point of view. It is possible that there are particularities in the epidemiology of leptospirosis in Caatinga biome, where the environment is often unfavorable and challenges the adaptability of Leptospira spp. Overall, 100 dogs (47 shelter and 53 stray dogs) selected based on sampling calculation were used to evaluate the Leptospira spp. seroprevalence and associated factors. The microscopic agglutination test (MAT) was applied to detect anti-Leptospira spp. antibodies (cut-off titer 50). Risk factors were identified using the robust Poisson regression analysis. Twenty-four animals (24%; 95% CI = 15.6% - 32.4%) were seroreactive, antibody titers ranged from 50 to 200, and the reacting serogroups were Ballum (17%), Autumnalis (6%) and Djasiman (1%). The factors/categories associated with seropositivity were the environment where the animal stay/soil (prevalence ratio [PR] = 6.03; 95% CI for PR: 1.86 - 7.69; P < 0.001) and access to polluted water/yes (PR = 3.79; 95% CI for PR: 1.85 - 24.22; P = 0.011). The results suggested leptospirosis as a concern in the One Health context in stray and shelter dogs from the Caatinga biome despite the adverse conditions of this biome for the survive of Leptospira spp. on the environment. Moreover, despite being social and government issues, factors such as environment where the animal stay (soil) and access to polluted water must be carefully deemed and corrected to avoid the transmission of leptospires to animals and humans.

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.

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.

OBJECTIVES: Leptospirosis is a re-emergent zoonotic bacterial disease associated with renal and hepatic injury. In free-roaming cats in some regions, a high prevalence of Leptospira antibodies has been identified, and pathogenic leptospires have been detected in renal tissue, indicating that they may play a role in Leptospira epidemiology. The objective of this study was to determine the prevalence of Leptospira seroreactivity and urinary shedding of Leptospira DNA in free-roaming cats from northern California and southern Texas. A secondary objective was to compare the results of a point-of-care (POC) assay, designed to detect Leptospira antibodies, with the results of the microscopic agglutination test (MAT) when applied to serum samples from feral cats. METHODS: Specimens were obtained from free-roaming cats from northern California (n = 52; 2020) and southern Texas (n = 75; 2017). Leptospira quantitative PCR was performed on blood and urine specimens from Californian cats. Serum samples from Californian and Texan cats were subjected to MAT to categorize them as Leptospira antibody-positive or antibody-negative. The performance of the POC assay was assessed using the MAT as the gold standard. RESULTS: Leptospira DNA was not detected in the blood or urine of any cats tested. The results of the MAT were positive in 17.3% (n = 9) of Californian cats and 10.7% (n = 8) of Texan cats (P = 0.3). The median MAT titer was 1:100 (range 1:100-1:200) in Californian cats and 1:200 (range 1:100-1:800) in Texan cats. The POC assay was negative in all specimens. CONCLUSIONS AND RELEVANCE: Free-roaming cats in California and Texas are exposed to Leptospira species and may have the potential to act as sentinel hosts. No cats had evidence of current infection, as determined using PCR on blood and urine specimens. The POC test did not reliably detect anti-Leptospira antibodies in these cats. The role of cats in the maintenance or shedding of pathogenic leptospires requires further investigation.

The World Health Organization classifies leptospirosis as a significant public health concern, predominantly affecting impoverished and unsanitary regions. By using the Pensacola Bay System as a case study, this study examines the underappreciated susceptibility of developed subtropical coastal ecosystems such as the Pensacola Bay System to neglected zoonotic pathogens such as Leptospira. We analyzed 132 water samples collected over 12 months from 44 distinct locations with high levels of Escherichia coli (>410 most probable number/100 mL). Fecal indicator bacteria (FIB) concentrations were assessed using IDEXX Colilert-18 and Enterolert-18, and an analysis of water physiochemical characteristics and rainfall intensity was conducted. The LipL32 gene was used as a quantitative polymerase chain reaction (qPCR) indicator to identify the distribution of Leptospira interrogans. The results revealed 12 instances of the presence of L. interrogans at sites with high FIB over various land cover and aquatic ecosystem types. Independent of specific rainfall events, a seasonal relationship between precipitation and elevated rates of fecal bacteria and leptospirosis was found. These findings highlight qPCR's utility in identifying pathogens in aquatic environments and the widespread conditions where it can be found in natural and developed areas. HIGHLIGHTS The study utilized qPCR assays to detect pathogenic Leptospira in various aquatic ecosystems, revealing its presence in diverse habitats throughout the year, particularly in developed environments and smaller water bodies like streams and bayous.; Leptospira occurrence showed correlations with certain water quality parameters.; The research highlights the public health risks associated with Leptospira contamination in recreational water bodies, suggesting that relying solely on traditional fecal indicator bacteria may underestimate microbial risks.; The study emphasizes the efficacy of qPCR in detecting waterborne pathogens like Leptospira, supporting the “One Health” approach that advocates for multidisciplinary collaboration to address complex health issues at the intersection of human, animal, and environmental health.;

Abstract A growing number of studies have linked the incidence of leptospirosis with the occurrence of flood events. Nevertheless, the interaction between flood and leptospirosis has not been extensively studied to understand the influence of flood attributes in inducing new cases. This study reviews leptospirosis cases in relation to multiple flood occurrences in Kerala, India. Leptospirosis data were obtained for three years: 2017 (non-flood year) and two years with flooding—2018 (heavy flooding) and 2019 (moderate flooding). We considered the severity of flood events using the discharge, duration and extent of each flooding event and compared them with the leptospirosis cases. The distribution of cases regarding flood discharge and duration was assessed through descriptive and spatiotemporal analyses, respectively. Furthermore, cluster analyses and spatial regression were completed to ascertain the relationship between flood extent and the postflood cases. This study found that postflood cases of leptospirosis can be associated with flood events in space and time. The total cases in both 2018 and 2019 increased in the post-flood phase, with the increase in 2018 being more evident. Unlike the 2019 flood, the flood of 2018 is a significant spatial indicator for postflood cases. Our study shows that flooding leads to an increase in leptospirosis cases, and there is stronger evidence for increased leptospirosis cases after a heavy flood event than after a moderate flooding event. Flood duration may be the most important factor in determining the increase in leptospirosis infections.

Leptospirosis is a re-emerging zoonotic disease that has had an unprecedented impact on most health systems in the world. The spectrum of symptoms is variable and usually ranges from asymptomatic cases to severe manifestations involving multiple organ dysfunction accompanied by jaundice, hemorrhage, meningitis, and acute kidney injury that requires the need for intensive care assistance. Although early antibiotic treatment is usually effective, in severe cases, it may require renal replacement therapy, invasive mechanical ventilation, vasoactive support, and invasive hemodynamic monitoring, increasing the risk of death. In Latin America, the real burden of acute kidney injury in this condition is unknown and may be underestimated due to the rapid progression of the disease, similar to other vector zoonoses, and the low coverage of diagnostic tests in primary care, especially in rural regions. Therefore, below, we review the clinical aspects and describe the scientific, clinical, and therapeutic evidence of acute kidney injury attributed to Leptospira spp. and its relevance in patients with severe leptospirosis in Latin America.

Early laboratory confirmation is important for the accurate diagnosis and treatment of patient infected by leptospirosis. However, Microscopic agglutination test (MAT) as the gold standard for detection of human leptospirosis has many limitation and only available in reference laboratories. Therefore, many studies suggested LipL32 protein as a good candidate for development of leptospirosis detection kit because it is highly conserved and produced only in pathogenic Leptospira species. In this study, we aim to investigate the performance of our in-house ELISA using recombinant LipL32 to detect leptospirosis in Indonesia. Fourteen human sera were used in this study and the infection status were determine using MAT. The result showed that nine of eleven MAT positive sera were successfully recognized by LipL32 ELISA. The antibody binding to LipL32 was also confirm by immunoblot. There was one of three MAT negative sera has high OD above 0.5 in ELISA, but it showed negative reaction in immunoblot result. Overall, this study demonstrated that recombinant LipL32 protein can recognized antibody from human leptospirosis and can be used as a universal antigen to detect infection by any serovars of pathogenic leptospira.

Abstract Background Leptospirosis, an important zoonotic bacterial disease, commonly affects resource-poor populations and results in significant morbidity and mortality worldwide. The value of antibiotics in leptospirosis remains unclear, as evidenced by the conflicting opinions published. Methods We conducted a search in the PubMed, Web of Science, and Cochrane Library databases for studies. These studies included clinical trials and retrospective studies that evaluated the efficacy or safety of antibiotics for leptospirosis treatment. The primary outcomes assessed were defervescence time, mortality rate, and hospital stays. Subgroup analyses were performed based on whether there were cases involving children and whether there were cases of severe jaundice. Safety was defined as the prevalence of adverse events associated with the use of antibiotics. p scores were utilized to rank the efficacy of the antibiotics. Results There are included 9 randomized controlled trials (RCTs), 1 control trial (CT), and 3 retrospective studies (RS) involving 920 patients and 8 antibiotics. Six antibiotics resulted in significantly shorter defervescence times compared to the control, namely cefotaxime (MD, − 1.88; 95% CI = − 2.60 to − 1.15), azithromycin (MD, − 1.74; 95% CI = − 2.52 to − 0.95), doxycycline (MD, − 1.53; 95% CI = − 2.05 to − 1.00), ceftriaxone (MD, − 1.22; 95% CI = − 1.89 to − 0.55), penicillin (MD, − 1.22; 95% CI = − 1.80 to − 0.64), and penicillin or ampicillin (MD, − 0.08; 95% CI = − 1.01 to − 0.59). The antibiotics were not effective in reducing the mortality and hospital stays. Common adverse reactions to antibiotics included Jarisch–Herxheimer reaction, rash, headache, and digestive reactions (nausea, vomiting, diarrhea, abdominal pain, and others). Conclusions Findings recommend that leptospirosis patients be treated with antibiotics, which significantly reduced the leptospirosis defervescence time. Cephalosporins, doxycycline, and penicillin are suggested, and azithromycin may be a suitable alternative for drug-resistant cases. Systematic review registration PROSPERO CRD42022354938.

Purpose: Leptospirosis is a waterborne zoonotic disease prevalent in tropical regions, causing significant morbidity and mortality. It can involve any organ in its primary stage, and uveitis is its late complication. While advanced laboratory diagnosis is available only in tertiary care centers globally, a cost-effective bedside assessment of clinical signs and their scoring could offer a provisional diagnosis. Aim: To analyze the diagnostic potential of demographic and clinical signs in a large cohort of serologically confirmed leptospiral uveitis patients. Methods: In this retrospective study, demographic and clinical parameters of 876 seropositive leptospiral uveitis patients and 1042 nonleptospiral uveitis controls were studied. Multivariable logistic regression analysis with bootstrap confidence interval (CI) characterized the diagnostic predictors. The performance of the model was evaluated using the area under the receiver operating curve (AUROC). Results: Presence of nongranulomatous uveitis (odds ratio [OR] = 6.9), hypopyon (OR = 4.6), vitreous infiltration with membranous opacities (OR = 4.3), bilateral involvement (OR = 4), panuveitis (OR = 3.3), vasculitis (OR = 1.9), disc hyperemia (OR = 1.6), absence of retinochoroiditis (OR = 15), and absence of cystoid macular edema (OR = 8.9) emerged as predictive parameters. The AUROC value was 0.86 with 95% CI of 0.846–0.874. At a cut-off score of 40, the sensitivity and specificity were 79.5 and 78.4, respectively. Conclusion: The study demonstrates that ocular signs can serve as diagnostic predictors for leptospiral uveitis, enabling primary care ophthalmologists to make bedside diagnosis. This can be further confirmed by laboratory methods available at tertiary care centers.

Objective: The Case Fatality Rate (CFR) of Leptospirosis in Semarang City has shown a tendency to increase from 2019 to 2022. In 2022, there were 30 cases reported, with 8 deaths (CFR 27%). The purpose of this study was to detect Leptospira sp. bacteria in rats and analyze the risk factors for leptospirosis in Semarang City. Methods: This study employed an observational approach with a Case-Control Study design. The research was conducted in Semarang City from November to December 2023. Non-random sampling techniques were used, specifically the total sampling method, resulting in a sample size of 45 case groups and 45 control groups. Bivariate analysis was performed using the Chi-square test, with a significance level set at

Leptospirosis has a complex transmission, involving rodents and many species of domestic and wild animals. Carrier animals spread leptospires, contaminating soil and water, the main sources of human infection. The risk of infection is modulated by socio-economic factors, environment and host animals and has changed, historically linked to agriculture but now prevalent in recreational environments. Leptospirosis also reveal gender-specific exposure patterns that determine infection risks. Emphasizing the interconnectedness of humans, animals, and the environment, the One Health approach highlights the ecosystem dynamics through which leptospires interact with hosts and abiotic factors, ensuring their survival and transmission.We advocate for integrating gender considerations into the ecosystem dynamics of complex zoonoses, such as leptospirosis, through a One Health perspective. This approach, yet to be fully explored, may enhance our understanding of the infection and its modulating factors. A scoping review of the literature was conducted across Embase and Pubmed databases to collect information on sex and gender-specific drivers, sources of infections, environmental drivers, and related risks of leptospirosis. Quantitative data were extracted from the articles selected according to a list of criteria, and analyzed to discern sex and gender disparities and identify primary drivers of leptospirosis. We confirmed that the excess of male leptospirosis cases described in many parts of the world is also present in Europe. Furthermore, we identified environmental and sociocultural drivers and hypothesized their interactions between and within human, animal, and environmental sectors. These interactions modulate direct and indirect exposure to Leptospira, heightening infection risks across the ecosystem. Based on our findings, utilizing leptospirosis as a model, we advocate for integrating One Health and gender approaches in public health practices to better plan and implement more effective and timely intervention measures.

ABSTRACTBackground The pathogenic Leptospira is maintained in renal tubules of certain animals, mostly rodents, and excreted in the urine which can contaminate the environment. It is necessary to detect pathogenic Leptospira in environmental samples. Knowing the survival of Leptospira in the environment (water and soil) can provide an overview of where and how they can be transmitted to humans.Objective Therefore, this study aimed to provide a systematic overview of pathogenic Leptospira presence in water and soil environment, the various species of pathogenic Leptospira that are harmful for human, and the ability to survive using a systematic review method.Methods The search process used four databases: PubMed, Science Direct, Scopus, and ProQuest. Furthermore, the articles sought were published from 2000 to July 2021, and 38 were analysed.Results The pathogenic Leptospira contamination in water was higher in urban areas, while soil samples were higher in rural areas. Various pathogenic Leptospira detected in the environment were L. alstonii, L. kmetyi, L. noguchii, and L. interrogans. Those pathogenic Leptospira can survive in water at 4–30°C and at pH < 7; in soil, it can survive at a humidity of < 20% and a pH < 6.Conclusion Urban and rural areas have the same risk for leptospirosis disease because pathogenic Leptospira (P1).

Leptospirosis is a bacterial disease that affects humans and animals and is caused by Leptospira. The recommended treatment for leptospirosis is antibiotic therapy, which should be given early in the course of the disease. Despite the use of these antibiotics, their role during the course of the disease is still not completely clear because of the lack of effective clinical trials, particularly for severe cases of the disease. Here, we present the characterization of L. interrogans Lsa45 protein by gel filtration, protein crystallography, SAXS, fluorescence and enzymatic assays. The oligomeric studies revealed that Lsa45 is monomeric in solution. The crystal structure of Lsa45 revealed the presence of two subdomains: a large α/β subdomain and a small α-helical subdomain. The large subdomain contains the amino acids Ser122, Lys125, and Tyr217, which correspond to the catalytic triad that is essential for β-lactamase or serine hydrolase activity in similar enzymes. Additionally, we also confirmed the bifunctional promiscuity of Lsa45, in hydrolyzing both the 4-nitrophenyl acetate (p-NPA) and nitrocefin β-lactam antibiotic. Therefore, this study provides novel insights into the structure and function of enzymes from L. interrogans, which furthers our understanding of this bacterium and the development of new therapies for the prevention and treatment of leptospirosis.

Leptospirosis is an emerging infectious disease caused by pathogenic Leptospira spp. Humans and some mammals can develop severe forms of leptospirosis accompanied by a dysregulated inflammatory response, which often results in death. The gut microbiota has been increasingly recognized as a vital element in systemic health. However, the precise role of the gut microbiota in severe leptospirosis is still unknown. Here, we aimed to explore the function and potential mechanisms of the gut microbiota in a hamster model of severe leptospirosis. Our study showed that leptospires were able to multiply in the intestine, cause pathological injury, and induce intestinal and systemic inflammatory responses. 16S rRNA gene sequencing analysis revealed that Leptospira infection changed the composition of the gut microbiota of hamsters with an expansion of Proteobacteria. In addition, gut barrier permeability was increased after infection, as reflected by a decrease in the expression of tight junctions. Translocated Proteobacteria were found in the intestinal epithelium of moribund hamsters, as determined by fluorescence in situ hybridization, with elevated lipopolysaccharide (LPS) levels in the serum. Moreover, gut microbiota depletion reduced the survival time, increased the leptospiral load, and promoted the expression of proinflammatory cytokines after Leptospira infection. Intriguingly, fecal filtration and serum from moribund hamsters both increased the transcription of TNF-α, IL-1β, IL-10, and TLR4 in macrophages compared with those from uninfected hamsters. These stimulating activities were inhibited by LPS neutralization using polymyxin B. Based on our findings, we identified an LPS neutralization therapy that significantly improved the survival rates in severe leptospirosis when used in combination with antibiotic therapy or polyclonal antibody therapy. In conclusion, our study not only uncovers the role of the gut microbiota in severe leptospirosis but also provides a therapeutic strategy for severe leptospirosis. [ABSTRACT FROM AUTHOR]

Equine leptospirosis can result in abortion, stillbirth, neonatal death, placentitis, and uveitis. Horses can also act as subclinical reservoir hosts of infection, which are characterized as asymptomatic carriers that persistently excrete leptospires and transmit disease. In this study, PCR and culture were used to assess urinary shedding of pathogenic Leptospira from 37 asymptomatic mares. Three asymptomatic mares, designated as H2, H8, and H9, were PCRpositive for lipL32, a gene specific for pathogenic species of Leptospira. One asymptomatic mare, H9, was culture-positive, and the recovered isolate was classified as L. kirschneri serogroup Australis serovar Rushan. DNA capture and enrichment of Leptospira genomic DNA from PCR-positive, culturenegative samples determined that asymptomatic mare H8 was also shedding L. kirschneri serogroup Australis, whereas asymptomatic mare H2 was shedding L. interrogans serogroup Icterohaemorrhagiae. Sera from all asymptomatic mares were tested by the microscopic agglutination test (MAT) and 35 of 37 (94.6%) were seropositive with titers ranging from 1:100 to 1:3200. In contrast to asymptomatic mares, mare H44 presented with acute spontaneous abortion and a serum MAT titer of 1:102,400 to L. interrogans serogroup Pomona serovar Pomona. Comparison of L. kirschneri serogroup Australis strain H9 with that of L. interrogans serogroup Pomona strain H44 in the hamster model of leptospirosis corroborated differences in virulence of strains. Since lipopolysaccharide (LPS) is a protective antigen in bacterin vaccines, the LPS of strain H9 (associated with subclinical carriage) was compared with strain H44 (associated with spontaneous abortion). This revealed different LPS profiles and immunoreactivity with reference antisera. It is essential to know what species and serovars of Leptospira are circulating in equine populations to design efficacious vaccines and diagnostic tests. Our results demonstrate that horses in the US can act as reservoir hosts of leptospirosis and shed diverse pathogenic Leptospira species via urine. This report also details the detection of L. kirschneri serogroup Australis serovar Rushan, a species and serotype of Leptospira, not previously reported in the US. [ABSTRACT FROM AUTHOR]

Background: Leptospirosis is a zoonosis caused by pathogenic species of bacteria belonging to the genus Leptospira. Most studies infer the epidemiological patterns of a single serogroup or aggregate all serogroups to estimate overall seropositivity, thus not exploring the risks of exposure to distinct serogroups. The present study aims to delineate the demographic, socioeconomic and environmental factors associated with seropositivity of Leptospira serogroup Icterohaemorraghiae and serogroup Cynopteri in an urban high transmission setting for leptospirosis in Brazil. Methods/Principal findings: We performed a cross-sectional serological study in five informal urban communities in the city of Salvador, Brazil. During the years 2018, 2020 2021, we recruited 2.808 residents and collected blood samples for serological analysis using microagglutination assays. We used a fixed-effect multinomial logistic regression model to identify risk factors associated with seropositivity for each serogroup. Seropositivity to Cynopteri increased with each year of age (OR 1.03; 95% CI 1.01–1.06) and was higher in those living in houses with unplastered walls (exposed brick) (OR 1.68; 95% CI 1.09–2.59) and where cats were present near the household (OR 2.00; 95% CI 1.03–3.88). Seropositivity to Icterohaemorrhagiae also increased with each year of age (OR 1.02; 95% CI 1.01–1.03) and was higher in males (OR 1.51; 95% CI 1.09–2.10), in those with work-related exposures (OR 1.71; 95% CI 1.10–2.66) or who had contact with sewage (OR 1.42; 95% CI 1.00–2.03). Spatial analysis showed differences in distribution of seropositivity to serogroups Icterohaemorrhagiae and Cynopteri within the five districts where study communities were situated. Conclusions/Significance: Our data suggest distinct epidemiological patterns associated with the Icterohaemorrhagiae and Cynopteri serogroups in the urban environment at high risk for leptospirosis and with differences in spatial niches. We emphasize the need for studies that accurately identify the different pathogenic serogroups that circulate and infect residents of low-income areas. Author summary: In this study, we investigated specific epidemiological patterns related to the Icterohaemorrhagiae and Cynopteri serogroups in urban environments at high risk for leptospirosis. Our results indicate that seropositivity for the Cynopteri serogroup increases with age. Seropositivity is also higher in places where houses have unplastered walls and where there are cats in the vicinity of the residences. Seropositivity for the Icterohaemorrhagiae serogroup also increases with age, and is more prevalent in men and in individuals exposed to work or who have contact with sewage. Spatial analysis reveals variations in the distribution of seropositivity for these serogroups within the five urban areas studied. We emphasize the importance of evaluating the epidemiological pattern for the different Leptospira serogroups, since each serogroup may be associated with different animal reservoirs. Our data suggest that the Icterohaemorrhagiae and Cynopteri serogroups present different epidemiological pattern, thus highlighting the need to understand the complex interactions between serogroups and reservoirs. These findings not only contribute to our understanding of the epidemiology of leptospirosis, but also have practical public health implications by helping to identify risk factors and thereby develop more effective preventive measures. [ABSTRACT FROM AUTHOR]

Background: In the last two decades, several rapid lateral flow immunoassays (LFIs) for the diagnosis of human leptospirosis were developed and commercialized. However, the accuracy and reliability of these LFIs are not well understood. In this study, we aimed to evaluate the accuracy of leptospirosis LFIs as well as the factors affecting the test efficiency using systematic review and meta-analysis. Methods and results: Original articles reporting the accuracy of human leptospirosis LFIs against microagglutination tests (MAT) or immunofluorescent assays (IFA) were searched from PubMed, Embase, and Scopus, and selected as per pre-set inclusion and exclusion criteria. A total of 49 data entries extracted from 24 eligible records published between 2003 and 2023 were included for meta-analysis. A meta-analysis was performed using STATA. The quality of the included studies was assessed according to the revised QUADAS-2. Only nine studies (32.1%) were considered to have a low risk of bias and no concern for applicability. Pooled sensitivity and specificity were calculated to be 68% (95% confidence interval, CI: 57–78) and 93% (95% CI: 90–95), respectively. However, the ranges of sensitivity (3.6 – 100%) and specificity (53.5 – 100%) of individual entries are dramatically broad, possibly due to the heterogeneity found in both study designs and LFIs themselves. Subgroup analysis demonstrated that IgM detection has better sensitivity than detection of IgG alone. Moreover, the test performance seems to be unaffected by samples from different phases of infection. Conclusions: The pooled specificity of LFIs observed is somewhat acceptable, but the pooled sensitivity is low. These results, however, must be interpreted with caution because of substantial heterogeneity. Further evaluations of the LFIs with well-standardized design and referent test will be needed for a greater understanding of the test performance. Additionally, IgM detection type should be employed when leptospirosis LFIs are developed in the future. Author summary: Several rapid lateral flow immunoassays (LFIs) for the diagnosis of leptospirosis, the most common bacterial infection transmitted from animals to humans, have been developed during the last two decades. The test accuracy, however, seems inconsistent among studies, raising questions about their reliability and applicability. Systematic review and meta-analysis were exploited to answer these questions. A total of 28 studies evaluating the human leptospirosis LFIs were included in this review. Major findings from our analysis include: i) the overall specificity of the LFIs is likely acceptable (93%), but the sensitivity is significantly low (68%); ii) substantial variation among studies was observed, alerting the reliability of this meta-analysis results; iii) the accuracy of the LFIs seems to be unaffected by samples collected from different phases of infection (acute vs. convalescent); and iv) IgM detection LFIs exhibit higher sensitivity as compared to IgG detection type. From our findings, we suggest that IgM detection LFIs should be focused on for future development. Also, in order to understand the performance of the LFIs better, other evaluation studies are still needed. [ABSTRACT FROM AUTHOR]

A growing number of studies have linked the incidence of leptospirosis with the occurrence of flood events. Nevertheless, the interaction between flood and leptospirosis has not been extensively studied to understand the influence of flood attributes in inducing new cases. This study reviews leptospirosis cases in relation to multiple flood occurrences in Kerala, India. Leptospirosis data were obtained for three years: 2017 (non-flood year) and two years with flooding—2018 (heavy flooding) and 2019 (moderate flooding). We considered the severity of flood events using the discharge, duration and extent of each flooding event and compared them with the leptospirosis cases. The distribution of cases regarding flood discharge and duration was assessed through descriptive and spatiotemporal analyses, respectively. Furthermore, cluster analyses and spatial regression were completed to ascertain the relationship between flood extent and the postflood cases. This study found that postflood cases of leptospirosis can be associated with flood events in space and time. The total cases in both 2018 and 2019 increased in the post-flood phase, with the increase in 2018 being more evident. Unlike the 2019 flood, the flood of 2018 is a significant spatial indicator for postflood cases. Our study shows that flooding leads to an increase in leptospirosis cases, and there is stronger evidence for increased leptospirosis cases after a heavy flood event than after a moderate flooding event. Flood duration may be the most important factor in determining the increase in leptospirosis infections. [ABSTRACT FROM AUTHOR]

• It is the first time that the specific IgY recognized and bound to Leptospira could be extracted from vaccinated hens. • Specific IgY can cure Leptospira- infected hamsters at either early or late stages. • Treatment with specific IgY protected Leptospira- infected hamsters from renal colonization. • Specific IgY was able to directly inhibit the growth of Leptospira. Leptospirosis, a globally significant zoonotic disease caused by pathogenic Leptospira , continues to threaten the health and public safety of both humans and animals. Current clinical treatment of leptospirosis mainly relies on antibiotics but their efficacy in severe cases is controversial. Passive immunization has a protective effect in the treatment of infectious diseases. In addition, chicken egg yolk antibody (IgY) has gained increasing attention as a safe passive immunization agent. This study aimed to investigate whether hens produce specific IgY after immunization with inactivated Leptospira and the protective effect of specific IgY against leptospirosis. First, it was demonstrated that specific IgY could be extracted from the eggs of hens vaccinated with inactivated Leptospira and that specific IgY can specifically recognize and bind homotypic Leptospira with a high titre, as shown by MAT and ELISA. Next, we tested the therapeutic effects of IgY in early and late leptospirosis using a hamster model. The results showed that early specific IgY treatment increased the survival rate of hamsters to 100%, alleviated pathological damage to the liver, kidney, and lung, reduced leptospiral burden, and restored haematological indices as well as functional indicators of the liver and kidney. The therapeutic effect of early specific IgY was comparable to that of doxycycline. Late IgY treatment also enhanced the survival rate of hamsters and improved the symptoms of leptospirosis similar to early IgY treatment. However, the therapeutic effect of late IgY treatment was better when combined with doxycycline. Furthermore, no Leptospira colonization was observed in the kidneys, livers, or lungs of the surviving hamsters treated with specific IgY. Mechanistically, IgY was found to inhibit the growth and adhesion to cells of Leptospira. In conclusion, passive immunotherapy with specific IgY can be considered an effective treatment for leptospirosis, and may replace antibiotics regarding its therapeutic effects. [ABSTRACT FROM AUTHOR]

Leptospirosis, one of the most common global zoonotic infections, significantly impacts global human health, infecting more than a million people and causing approximately 60,000 deaths annually. This mini-review explores effective treatment strategies for leptospirosis, considering its epidemiology, clinical manifestations, and current therapeutic approaches. Emphasis is placed on antibiotic therapy, including recommendations for mild and severe cases, as well as the role of probiotics in modulating the gut microbiota. Furthermore, novel treatment options, such as bacteriophages and newly synthesized/natural compounds, are discussed, and the findings are expected to provide insights into promising approaches for combating leptospirosis. [ABSTRACT FROM AUTHOR]

The World Health Organization classifies leptospirosis as a significant public health concern, predominantly affecting impoverished and unsanitary regions. By using the Pensacola Bay System as a case study, this study examines the underappreciated susceptibility of developed subtropical coastal ecosystems such as the Pensacola Bay System to neglected zoonotic pathogens such as Leptospira. We analyzed 132 water samples collected over 12 months from 44 distinct locations with high levels of Escherichia coli (.410 most probable number/100 mL). Fecal indicator bacteria (FIB) concentrations were assessed using IDEXX Colilert-18 and Enterolert-18, and an analysis of water physiochemical characteristics and rainfall intensity was conducted. The LipL32 gene was used as a quantitative polymerase chain reaction (qPCR) indicator to identify the distribution of Leptospira interrogans. The results revealed 12 instances of the presence of L. interrogans at sites with high FIB over various land cover and aquatic ecosystem types. Independent of specific rainfall events, a seasonal relationship between precipitation and elevated rates of fecal bacteria and leptospirosis was found. These findings highlight qPCR's utility in identifying pathogens in aquatic environments and the widespread conditions where it can be found in natural and developed areas. [ABSTRACT FROM AUTHOR]

Simple Summary: The expansion of human activities into natural areas increases contact between humans, domestic animals, and wildlife, which can facilitate the circulation of infectious agents between these species, leading to the emergence of zoonoses. Several studies have investigated the role of animals, including reptiles, as possible carriers of the Leptospira bacterium. This study aimed to detect the DNA of the bacterium in Kinosternon scorpioides turtles kept in captivity in a region of the Brazilian Amazon. Blood, cloacal fluid, cloacal lavage, and stomach lavage samples were collected from 40 turtles. Of these, 40% of the animals tested positive for Leptospira. Genetic analysis confirmed the identification of the bacteria, which could pose a risk to public health. Handling infected animals could increase the risk of transmitting the disease, especially considering that turtle meat is consumed in the region. This study is the first to detect Leptospira in the blood of chelonians, confirming exposure to the pathogen. Although the turtles showed no abnormal clinical signs, it is possible that the clinical signs are unknown in reptiles. In conclusion, captive K. scorpioides turtles have been exposed to Leptospira. Leptospirosis is a zoonosis of great importance for One Health. In this context, the Amazonian biome may harbor numerous hosts for Leptospira spp. that contribute to the maintenance of the pathogen in the environment. Some reptiles, such as chelonians, have been little studied in terms of their involvement with leptospires. The objective of this study was to detect Leptospira spp. DNA in Kinosternon scorpioides turtles kept in captivity in a region of the Brazilian Amazon. A total of 147 samples of blood (n = 40), cloacal fluid (n = 27), cloacal lavage (n = 40), and stomach (n = 40) were collected from 40 chelonians. After DNA extraction, the samples were subjected to amplification of a 331 base pair product of the 16S rRNA gene using the Lep1 and Lep2 primers. PCR products were Sanger sequenced, assembled, and subjected to online blast search and phylogenetic analysis. Of the animals tested, 40% (16/40, 95% confidence interval [CI]: 25–55) had at least one or two samples positive for Leptospira spp. Considering the total number of samples collected, 12.93% (19/147) were positive, being blood clots (27.5%; 11/40), followed by cloacal washings (10%; 4/40), cloacal fluid (11.11%; 3/27) and gastric washings (2.5%; 1/40). Of these, 11 samples were sequenced and showed 99% to 100% identity with Leptospira interrogans sequences, which was confirmed by phylogenetic analysis. This is the first study to detect pathogenic Leptospira DNA in chelonians in a region of the Brazilian Amazon. It has been concluded that K. scorpioides turtles in captivity have been exposed to pathogenic Leptospira. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Common cardiac arrhythmias seen in patients with leptospirosis are usually atrial fibrillation or first‐degree atrioventricular block, with bradyarrhythmia being rare in this group. It is essential to prioritize the examination of the patient's medical background, clinical symptoms, and comprehensive physical evaluation in order to promptly identify and address the patient's condition. Leptospirosis, a zoonotic disease that is widespread worldwide, has a significant impact on tropical areas and can affect various organs throughout the infection. During the initial stage, symptoms are typically non‐specific. Although cases of all three cardiac layers being affected have been reported, issues with the conduction system are especially significant in the early phase of the disease. The most frequent discoveries in these patients are atrial fibrillation or first‐degree atrioventricular block, with bradyarrhythmia being rare. We describe a 37‐year‐old male farmer who initially sought medical attention for general symptoms that had been deteriorating despite receiving outpatient treatment for 3 days for a presumed diagnosis of influenza. During his initial assessment, he exhibited sinus bradycardia, anemia, leukocytosis, elevated levels of direct and total bilirubin, and abnormal liver function test results. Through thorough history‐taking, physical examination, and laboratory analyses, a diagnosis of leptospirosis was conclusively established for him. Focusing on the patient's medical history, clinical manifestations, and thorough physical assessment is crucial for promptly diagnosing and treating patients. This becomes particularly significant for individuals who exhibit atypical symptoms, exemplified by our patient presenting with nonspecific indications and cardiac issues manifested as bradycardia. [ABSTRACT FROM AUTHOR]

Leptospirosis, a disease of significant economic impact on livestock and public health concern, may exhibit unique epidemiological characteristics in indigenous villages, particularly those located within semiarid climates such as the Caatinga biome in Brazil. This environment often presents conditions unfavorable for leptospire survival. This study conducted serological diagnoses of livestock in indigenous villages within the Caatinga biome, Northeastern Brazil. The survey was carried out in the Mãe Maria and Santa Helena indigenous villages, home to the Xukuru de Cimbres tribe, in the county of Pesqueira, Pernambuco State, Brazil, within the Caatinga biome. Blood samples were collected from cattle (n = 42), goats (n = 41), and sheep (n = 19). Out of the 102 samples tested, 73 (71.6%; 95% CI = 62.8% - 80.3%) were seroreactive (cut-off = 100). The seropositivity rates for cattle, goats, and sheep were 54.8%, 80.5%, and 89.5%, respectively. A statistically significant difference was observed in the proportion of seropositive animals between cattle and goats and cattle and sheep (P < 0.05). Icterohaemorrhagiae was identified as the most probable serogroup across all animal species. The study revealed that livestock in indigenous villages within the Caatinga biome are frequently exposed to leptospires. This finding underscores the importance of a One Health approach, emphasizing the need for comprehensive studies in areas where large human and animal populations coexist. Such studies are crucial for investigating zoonotic infections and for planning and implementing control measures against livestock-associated leptospirosis. [ABSTRACT FROM AUTHOR]

Background: Leptospirosis is a zoonotic disease. It is particularly prevalent in tropical countries and has major consequences for human and animal health. In Benin, the disease's epidemiology remains poorly understood, especially in livestock, for which data are lacking. Objectives: To characterise Leptospira seroprevalence and locally circulating serogroups in livestock from Cotonou and to estimate the prevalence of Leptospira renal carriage in cattle. Methods: We conducted a cross‐sectional study in February 2020 during which livestock were sampled at an abattoir and in an impoverished city district. We analysed blood samples from 279 livestock animals (i.e. cattle, sheep, goats and pigs) using the microscopic agglutination test. Additionally, samples of renal tissue from 100 cattle underwent 16s rRNA (rrs) real‐time PCR analysis. Results: For the 131 cattle, 85 sheep, and 50 goats tested, seroprevalence was 18% (95% confidence interval [CI] [12%, 26%]), 9% (95% CI [4%, 17%] and 2% (95% CI [0%, 9%]), respectively, and most of the seropositive animals were associated with 1:100 titres. All 13 pigs were seronegative. Leptospira DNA was found in the renal tissue of 10% (95% CI [5%, 18%]) of the cattle tested (n = 100). Leptospira borgpetersenii was the main species present (n = 7), but Leptospira interrogans (n = 2) and Leptospira kirschneri (n = 1) were also detected. Various serogroups (Canicola, Grippotyphosa, Sejroe, Icterohaemorrhagiae, Pomona, Pyrogenes, Australis and Autumnalis) were detected using microscopic agglutination test without a clear predominance of any of them. Conclusions: These results suggest that abattoir workers and people living in close contact with livestock in poor urban areas are exposed to the risk of Leptospira infection. [ABSTRACT FROM AUTHOR]

In the past 20 years in Switzerland, dogs with suspect acute leptospirosis frequently showed severe glomerular changes that had not been previously reported. These features were characterized by abundant extravasated erythrocytes and fewer neutrophils accompanied by marked fibrin exudation into the urinary space that was interpreted as an exudative glomerulonephritis (GN). This retrospective study describes this significant glomerular pathological change and investigates the association with leptospirosis. Tissues from 50 dogs with exudative GN, retrieved from 2 pathology archives in Switzerland were reviewed using hematoxylin and eosin, periodic acid-Schiff, phosphotungstic acid-hematoxylin, and Warthin and Starry stains. Clinical and postmortem data were collected for each case. Immunohistochemistry (IHC) and/or polymerase chain reactions were used as confirmatory tests for leptospirosis. While all 50 cases had clinical and pathological features supporting a diagnosis of leptospirosis, 37 cases were confirmed for the disease. Using a LipL32 antibody in addition to the OMV2177 antibody raised against the lipopolysaccharide of Leptospira interrogans serovar Copenhageni increased the detection rate of Leptospira by IHC in exudative GN from 24% to 62%. Signalment, seasonality, clinical signs, blood results, and pathological changes in dogs with exudative GN were similar to those reported for dogs without GN and confirmed infection by Leptospira spp.. Exudative GN was common among Swiss dogs with leptospirosis where it caused acute severe disease. Leptospirosis should be considered as a cause of this new pathologic feature by the pathologist. The pathogenesis remains unclear, but involvement of a geographic-specific serovar with unique virulence factors is suspected and warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: Leptospirosis is a neglected zoonosis which remains poorly known despite its epidemic potential, especially in tropical islands where outdoor lifestyle, vulnerability to invasive reservoir species and hot and rainy climate constitute higher risks for infections. Burden remains poorly documented while outbreaks can easily overflow health systems of these isolated and poorly populated areas. Identification of generic patterns driving leptospirosis dynamics across tropical islands would help understand its epidemiology for better preparedness of communities. In this study, we aim to model leptospirosis seasonality and outbreaks in tropical islands based on precipitation and temperature indicators. Methodology/Principal findings: We adjusted machine learning models on leptospirosis surveillance data from seven tropical islands (Guadeloupe, Reunion Island, Fiji, Futuna, New Caledonia, and Tahiti) to investigate 1) the effect of climate on the disease's seasonal dynamic, i.e., the centered seasonal profile and 2) inter-annual anomalies, i.e., the incidence deviations from the seasonal profile. The model was then used to estimate seasonal dynamics of leptospirosis in Vanuatu and Puerto Rico where disease incidence data were not available. A robust model, validated across different islands with leave-island-out cross-validation and based on current and 2-month lagged precipitation and current and 1-month lagged temperature, can be constructed to estimate the seasonal dynamic of leptospirosis. In opposition, climate determinants and their importance in estimating inter-annual anomalies highly differed across islands. Conclusions/Significance: Climate appears as a strong determinant of leptospirosis seasonality in tropical islands regardless of the diversity of the considered environments and the different lifestyles across the islands. However, predictive and expandable abilities from climate indicators weaken when estimating inter-annual outbreaks and emphasize the importance of these local characteristics in the occurrence of outbreaks. Author summary: Tropical islands are particularly vulnerable to leptospirosis outbreaks. Hot and rainy climate, abundance of reservoir species and outdoor lifestyle contribute to the high risk for human infection. These isolated areas also deal with difficulties associated with diagnosis because of low awareness of the medical staff, non-specific symptoms of leptospirosis and limited availability of laboratory testing. Leptospirosis remains poorly documented, and a better understanding of its dynamics and its climate drivers would help improve awareness and preparedness of the public health services. In this study, we provide a climate-based model of leptospirosis seasonal dynamics in 7 tropical islands. The use of climate variables from publicly available satellite data makes the model expandable to predict leptospirosis seasonal dynamics in other tropical islands where the disease is not routinely monitored. This study emphasizes the importance of rainfall and temperature in driving the seasonality of leptospirosis in tropical islands. However, climate alone did not appear to not be a sufficient indicator to predict interannual variations, suggesting that the risk of leptospirosis outbreaks must be refined, considering local specificities as the lifestyle and the very local environment. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is one of the global health challenges of the 21st century. Data regarding AMR mechanisms in Leptospira interrogans, the causative agents of leptospirosis, have been relatively limited. Therefore, our study aimed to identify resistance genes and explore potential resistance mechanisms specific to particular serovars. We conducted a comprehensive analysis of 98 Leptospira strains, representing 10 common serovars, using wholegenome sequencing (WGS) FASTA files. Employing the PATRIC tool from the Bacterial and Viral Bioinformatics Resource Center (BV-BRC), we scrutinized the genomes for AMR genes. Our investigation revealed 32 genes associated with AMR, with 20 key genes consistently prevalent across most strains. Notably, we identified unique efflux pump systems in serovar Pomona, indicating distinctive resistance mechanisms in this serovar. In summary, our findings shed light on the genetic landscape of AMR in Leptospira, uncovering both common and serovarspecific resistance elements. The presence of unique efflux pump systems in serovar Pomona introduces a novel dimension to our understanding of resistance mechanisms. These insights underscore the importance of tailored intervention strategies and collaborative efforts between human and veterinary healthcare professionals, as well as environmental scientists, to address the complex dynamics of leptospirosis and its implications for antibiotic resistance. [ABSTRACT FROM AUTHOR]

Background: Leptospirosis, an important zoonotic bacterial disease, commonly affects resource-poor populations and results in significant morbidity and mortality worldwide. The value of antibiotics in leptospirosis remains unclear, as evidenced by the conflicting opinions published. Methods: We conducted a search in the PubMed, Web of Science, and Cochrane Library databases for studies. These studies included clinical trials and retrospective studies that evaluated the efficacy or safety of antibiotics for leptospirosis treatment. The primary outcomes assessed were defervescence time, mortality rate, and hospital stays. Subgroup analyses were performed based on whether there were cases involving children and whether there were cases of severe jaundice. Safety was defined as the prevalence of adverse events associated with the use of antibiotics. p scores were utilized to rank the efficacy of the antibiotics. Results: There are included 9 randomized controlled trials (RCTs), 1 control trial (CT), and 3 retrospective studies (RS) involving 920 patients and 8 antibiotics. Six antibiotics resulted in significantly shorter defervescence times compared to the control, namely cefotaxime (MD, − 1.88; 95% CI = − 2.60 to − 1.15), azithromycin (MD, − 1.74; 95% CI = − 2.52 to − 0.95), doxycycline (MD, − 1.53; 95% CI = − 2.05 to − 1.00), ceftriaxone (MD, − 1.22; 95% CI = − 1.89 to − 0.55), penicillin (MD, − 1.22; 95% CI = − 1.80 to − 0.64), and penicillin or ampicillin (MD, − 0.08; 95% CI = − 1.01 to − 0.59). The antibiotics were not effective in reducing the mortality and hospital stays. Common adverse reactions to antibiotics included Jarisch–Herxheimer reaction, rash, headache, and digestive reactions (nausea, vomiting, diarrhea, abdominal pain, and others). Conclusions: Findings recommend that leptospirosis patients be treated with antibiotics, which significantly reduced the leptospirosis defervescence time. Cephalosporins, doxycycline, and penicillin are suggested, and azithromycin may be a suitable alternative for drug-resistant cases. Systematic review registration: PROSPERO CRD42022354938. [ABSTRACT FROM AUTHOR]

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. Author summary: This study aims to discern whether there are variations in the clinical manifestations and outcomes of severe Leptospirosis between tropical and non-tropical regions with comparable healthcare infrastructures. Conducted in France, the research scrutinizes the distinctions in patient characteristics, clinical presentations, and prognoses between a tropical area and a temperate one. The analysis reveals minimal discrepancies in patient profiles and clinical patterns across these regions. Additionally, no statistically significant differences were observed regarding the duration of intensive care unit (ICU) or hospital stays, as well as ICU or hospital mortality rates, between the tropical and non-tropical locales. The findings suggest that the clinical features and outcomes of individuals afflicted with severe leptospirosis exhibit substantial uniformity across tropical and temperate regions endowed with similar healthcare resources. This study contributes valuable insights into the understanding of leptospirosis, highlighting the consistency in disease presentation and prognosis irrespective of climatic distinctions, given comparable healthcare capabilities. [ABSTRACT FROM AUTHOR]

Leptospirosis is an anthropozoonotic disease, which remains under diagnosed in most of the regions of our country due to the lack of awareness, atypical presentation and lack of proper diagnostic facility and set up. Diagnosis usually depends on Microscopy, Culture and Serological tests like ELISA, MAT (Microscopic agglutination test). MAT is the gold standard diagnostic test but it requires live Leptospires and it can only be done in a reference laboratory. Hence, ELISA is the most preferred cost-effective serological method and is genus specific with both sensitivity and specificity of 95%. Aim of the present study is to estimate the seroprevalence of Leptospirosis among suspected Acute Febrile illness (AFI) cases presented to Government General Hospital Kurnool. The study was conducted from August 2023 to March 2024 on 260 AFI cases. Detection of IgM antibody was done by using Recombilisa Leptospira IgM ELISA kit. Out of 260 clinically suspected cases of Leptospirosis, 30 (11.53%) were positive. Majority of cases belonged to 21-40 years age group. Seroprevalence was found to be higher in Males (14.1%) as compared to Females (8.5%). A high seroprevalence of Leptospirosis was noted in AFI cases, so a programmatic approach for prevention, control and management of such emerging zoonotic diseases through NOHP-PCZ (National One Health Program for Prevention and Control of Zoonoses) will be a very useful step towards achieving optimal health. [ABSTRACT FROM AUTHOR]

Background and Aim: Microscopic agglutination test (MAT) for the diagnosis of leptospirosis requires live cultures and is serovar-specific, while polymerase chain reaction (PCR) requires expensive equipment and sample preparation. The rLipL32 protein is conserved and can be used for the production of immunoglobulin G (IgG) anti-rLipL32 antibody, which can be used as a biomarker for leptospirosis diagnosis. This study aimed to produce and characterize an IgG anti-rLipL32 antibody as a biomarker for leptospirosis diagnosis. Materials and Methods: Escherichia coli rLipL32 was cultured and analyzed by PCR and sequencing. Cultures were used for rLipL32 protein expression and purification and the rLipL32 protein was analyzed by sodium dodecyl sulfatepolyacrylamide gel electrophoresis (SDS-PAGE). The rLipL32 protein was used to produce anti-rLipL32 serum and was analyzed by enzyme-linked immunosorbent assay (ELISA). Serum was purified to obtain IgG anti-rLipL32 antibody and characterized by SDS-PAGE and western blotting. Results: PCR was able to amplify the LipL32 gene from E. coli rLipL32, and sequencing analysis showed 99.19% similarity with pathogenic Leptospira. SDS-PAGE analysis showed a 32-kDa band. ELISA results showed an increase in OD in antirLipL32 serum compared to preimmune serum. Western blotting results showed that the IgG anti-rLipL32 antibody was able to bind and cross-reacts with pathogenic Leptospira serovar but not with E. coli or Staphylococcus aureus. Conclusion: IgG anti-rLipL32 antibody has high specificity and sensitivity against Leptospira pathogens. These findings suggest that IgG anti-rLipL32 antibody is a promising biomarker for the diagnosis of leptospirosis. [ABSTRACT FROM AUTHOR]

In 2017, highly fatal canine leptospirosis emerged in Sydney, Australia. Based on results of microscopic agglutination testing (MAT), serovar Copenhageni appeared to be the most common causative serovar. Prior to this, no clinical cases had been reported since 1976. In a serosurvey of healthy dogs in Australian shelters in 2004, 2.4% of 431 New South Wales dogs had serological evidence of exposure to Copenhageni, the most prevalent serovar. The aim of this study was to estimate the current prevalence of Leptospira exposure and associated serovars in healthy Sydney dogs, previously unvaccinated against Leptospira. Serum samples from 411 healthy dogs in leptospirosis hotspots and neighbouring suburbs were collected before vaccination. MAT for 23 serovars was performed at the WHO Leptospirosis Reference Laboratory in Queensland, Australia. The overall seroprevalence was 4.1% (17/411) with low titres (1/50–1/200) detected. Eleven dogs were from known leptospirosis hotspots. Eight dogs were known to hunt rodents. One dog had been in contact with a leptospirosis positive dog 1 year prior. Serovar Topaz was the most prevalent serovar (n = 5) followed by serovars Australis (n = 4), Copenhageni (n = 4), Djasiman (n = 2), Cynopteri (n = 1), Javanica (n = 1), Medanensis (n = 1), and Pomona (n = 1). In conclusion, serological evidence of exposure of dogs in Sydney to Leptospira is low, but apparently has increased since 2004. Positive titres to serovars not previously reported to cause disease in dogs could be due to low virulence of those serovars or cross‐reactivity with other serovars. [ABSTRACT FROM AUTHOR]

Background: Leptospirosis is a reemerging zoonosis affecting humans and animals worldwide in tropical and subtropical countries. The study was conducted to estimate the seroprevalence of leptospirosis in high-risk occupational groups (cattle farm workers, poultry farm workers, and slaughterhouse workers) in the state of Gujarat and to determine related risk factors for leptospirosis. Methods: Using an interview-guided questionnaire, a cross-sectional study was conducted involving 123 people in high-risk occupational groups (namely, cattle farm workers, poultry farm workers, and slaughterhouse workers) from five districts of the state of Gujarat, India. The participants' serum samples were screened for antileptospiral antibodies by using Immunoglobulin G (IgG) and Immunoglobulin M (IgM) enzyme-linked immunosorbent assays (ELISAs) followed by a microscopic agglutination test (MAT). The Chi-square (χ²) test and odds ratio were calculated using IBM SPSS Statistics for Windows, version 22 (IBM Corp., Armonk, N.Y., USA) to ascertain the associated risk factors. Results: Regarding demographic information, this study included 104 men and 19 women in high-risk occupational groups. The overall seroprevalence of antileptospiral antibodies in these high-risk workers was 46.3%. The seroprevalence was the highest among poultry farm workers (56.6%), followed by cattle farm workers (54.5%) and slaughterhouse workers (25.6%). The MAT in combination with IgM is adequate for the serological diagnosis of leptospirosis, but we have also employed IgG ELISA to understand the chronic infection in these high-risk occupational groups as exposure was both past and present. Tests were conducted for antibodies against various Leptospira serovars in the major serogroups; frequent serovars included Hurstbridge, Panama, Javanica, Tarassovi, Copenhageni, Pomona, and Weaveri, among others. The significant (P < 0.05) risk factors associated with leptospirosis in these high-risk occupations reported to be living in field areas, the presence of livestock in the neighborhood, working in slaughterhouses, drinking water from natural water resources, contact with animals such as dogs or livestock, and wounds during occupational practice. Conclusion: Considering the high seroprevalence of leptospirosis, high-risk occupational groups should be regularly screened for potential development of the fatal disease. Hurstbridge was found to be the most prevalent serovar in the studied population, followed by Panama, Javanica, and Tarassovi. [ABSTRACT FROM AUTHOR]

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Rodent-borne zoonoses pose great threat to human as well as animal health and productivity. Leptospira is one among the major pathogens harboured by rats and is neglected worldwide leading to their misdiagnosis and underdiagnosis. Rapid urbanisation favours exposure of humans and domestic animals to rodent reservoirs, resulting in increased transmission of the bacterium. The present study was conducted to identify the occurrence of Leptospira spp. in rats in Thrissur district, Kerala. A total of 100 peri-domestic rats (66 Rattus norvegicus and 34 R. rattus) were collected during summer and monsoon seasons. This included 50 rats each during summer and monsoon seasons from households rearing animals and paddy fields. Seroprevalence of leptospirosis was determined by microscopic agglutination test (MAT) and renal carriage of the organism was determined by isolation and polymerase chain reaction (PCR) of organism from kidney samples. The MAT of serum samples revealed seroprevalence of 10 per cent in summer and 28 per cent in monsoon. The predominant serovars detected during summer were Australis and Javanica. However, Bataviae and Gryppotyphosa were the predominant serovars during monsoon. There was significant difference in seroprevalence of Leptospira between summer and monsoon seasons. The EMJH semisolid media was inoculated with kidney dissected out from rats and 16 isolates were obtained. The isolates were subjected to PCR targeting 16S rRNA, lipl 21, lipl 32 and lipl 41 genes. A total of five isolates obtained during summer and 11 during monsoon were confirmed to be pathogenic leptospires. The results of the present study show the occurrence of Leptospira spp. in rats and its significant difference during both seasons. This will help to adopt proper interventions for effective prevention and control of the disease in endemic areas like Kerala. [ABSTRACT FROM AUTHOR]

Leptospirosis is a neglected zoonotic disease that commonly affects cattle, pigs, horses, and dogs in many countries. Infection in dogs is usually subclinical, but acute cases of leptospirosis may occur along with systemic failure, which may become fatal. After recovery from an acute infection, dogs may become asymptomatic carriers and shed pathogenic leptospires through urine for long periods of time. Here, a study of ten different cases of leptospirosis is presented, showing the relevance of dogs as asymptomatic carriers of pathogenic Leptospira. The diagnosis was confirmed via isolation and further serological and genetic identification. Four Leptospira isolates (LOCaS28, 31, 34, and 46) were obtained from the kidneys and urine samples of 58 dogs destined for destruction (6.89%) at a Canine Control Center in Mexico City. No spirochetes were observed in the urine samples of those Leptospira-positive dogs examined under dark-field microscopy, and no clinical signs of disease were observed either. Six additional isolates were obtained: two came from asymptomatic carrier dogs (CEL60 and UADY22); another isolate came from an asymptomatic dog that was a pack companion of a clinically ill dog with fatal leptospirosis (AGFA24); and finally, three isolates were taken from dogs that died of leptospirosis (LOCaS59, Citlalli, and Nayar1). Nine out of the ten isolates were identified as being from the serogroup Canicola via cross-absorption MAT using reference strains and specific antisera, and their identity was genetically confirmed as Canicola ST34 via multi-locus sequencing typing (MLST). In contrast, the isolate Nayar1 was identified as serovar Copenhageni ST2. Interestingly, the asymptomatic dogs from which Leptospira isolates were recovered consistently showed high antibody titers in the microscopic agglutination test (MAT), revealing values of at least 1:3200 against serogroup Canicola and lower titer values against other serogroups. Isolates showed different virulence levels in the hamster model. Taken as a whole, all these findings confirmed that dogs may act as asymptomatic carriers of pathogenic leptospires and possibly spread them out to the environment, thus representing an active public health risk. The results also showed that the Canicola ST34 clone is the most prevalent Leptospira serovar in dogs in Mexico, and finally that the old-fashioned MAT is a good alternative for the detection of presumptive Leptospira asymptomatic carrier dogs. [ABSTRACT FROM AUTHOR]