Spatiotemporal assessment of pathogenic Leptospira in subtropical coastal watersheds.

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.

A case of leptospirosis in transcarpathia complicated with Jarisch-Herxheimer reaction.

A case report of Jarisch-Herxheimer (JHR) reaction on a 10th day of Leptospirosis caused by Leptospira Pomona. JHR occurs as a complication of an antibiotic treatment of various spirochetes and may lead to respiratory distress syndrome, renal failure, hepatic insufficiency, and multiple organ failure. This case represents a skin and cardio-vascular form of JHR with no lung involvement. The patient was treated with benzylpenicillin and low dexamethasone doses for 5th day of the disease with a shift to ceftriaxone and high doses of methylprednisolone. The fastest diagnosis of a sporadic zoonotic disease, early start of antibiotic therapy, and adequate doses of corticosteroids are key to the successful treatment of leptospirosis.

Bacterial community profiles within the water samples of leptospirosis outbreak areas.

Background: Leptospirosis is a water-related zoonotic disease. The disease is primarily transmitted from animals to humans through pathogenic Leptospira bacteria in contaminated water and soil. Rivers have a critical role in Leptospira transmissions, while co-infection potentials with other waterborne bacteria might increase the severity and death risk of the disease. Methods: The water samples evaluated in this study were collected from four recreational forest rivers, Sungai Congkak, Sungai Lopo, Hulu Perdik, and Gunung Nuang. The samples were subjected to next-generation sequencing (NGS) for the 16S rRNA and in-depth metagenomic analysis of the bacterial communities. Results: The water samples recorded various bacterial diversity. The samples from the Hulu Perdik and Sungai Lopo downstream sampling sites had a more significant diversity, followed by Sungai Congkak. Conversely, the upstream samples from Gunung Nuang exhibited the lowest bacterial diversity. Proteobacteria, Firmicutes, and Acidobacteria were the dominant phyla detected in downstream areas. Potential pathogenic bacteria belonging to the genera Burkholderiales and Serratia were also identified, raising concerns about co-infection possibilities. Nevertheless, Leptospira pathogenic bacteria were absent from all sites, which is attributable to its limited persistence. The bacteria might also be washed to other locations, contributing to the reduced environmental bacterial load. Conclusion: The present study established the presence of pathogenic bacteria in the river ecosystems assessed. The findings offer valuable insights for designing strategies for preventing pathogenic bacteria environmental contamination and managing leptospirosis co-infections with other human diseases. Furthermore, closely monitoring water sample compositions with diverse approaches, including sentinel programs, wastewater-based epidemiology, and clinical surveillance, enables disease transmission and outbreak early detections. The data also provides valuable information for suitable treatments and long-term strategies for combating infectious diseases.

Leptospiral LipL45 lipoprotein undergoes processing and shares structural similarities with bacterial sigma regulators.

Leptospirosis is a widespread zoonotic infectious disease of human and veterinary concern caused by pathogenic spirochetes of the genus Leptospira. To date, little progress towards understanding leptospiral pathogenesis and identification of virulence factors has been made, which is the main bottleneck for developing effective measures against the disease. Some leptospiral proteins, including LipL32, Lig proteins, LipL45, and LipL21, are being considered as potential virulence factors or vaccine candidates. However, their function remains to be established. LipL45 is the most expressed membrane lipoprotein in leptospires, upregulated when the bacteria are transferred to temperatures resembling the host, expressed during infection, suppressed after culture attenuation, and known to suffer processing in vivo and in vitro, generating fragments. Based on body of evidence, we hypothesized that the LipL45 processing might occur by an auto-cleavage event, deriving two fragments. The results presented here, based on bioinformatics, structure modeling analysis, and experimental data, corroborate that LipL45 processing probably includes a self-catalyzed non-proteolytic event and suggest the participation of LipL45 in cell-surface signaling pathways, as the protein shares structural similarities with bacterial sigma regulators. Our data indicate that LipL45 might play an important role in response to environmental conditions, with possible function in the adaptation to the host.

Accuracy of rapid lateral flow immunoassays for human leptospirosis diagnosis: A systematic review and meta-analysis.

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 reference 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.

Factors associated with differential seropositivity to Leptospira interrogans and Leptospira kirschneri in a high transmission urban setting for leptospirosis in Brazil.

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.

Neutralizing gut-derived lipopolysaccharide as a novel therapeutic strategy for severe 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-1ß, 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.

Molecular and serological diagnosis of multiple bacterial zoonoses in febrile outpatients in Garissa County, north-eastern Kenya.

Bacterial zoonoses are diseases caused by bacterial pathogens that can be naturally transmitted between humans and vertebrate animals. They are important causes of non-malarial fevers in Kenya, yet their epidemiology remains unclear. We investigated brucellosis, Q-fever and leptospirosis in the venous blood of 216 malaria-negative febrile patients recruited in two health centres (98 from Ijara and 118 from Sangailu health centres) in Garissa County in north-eastern Kenya. We determined exposure to the three zoonoses using serological (Rose Bengal test for Brucella spp., ELISA for C. burnetti and microscopic agglutination test for Leptospira spp.) and real-time PCR testing and identified risk factors for exposure. We also used non-targeted metagenomic sequencing on nine selected patients to assess the presence of other possible bacterial causes of non-malarial fevers. Considerable PCR positivity was found for Brucella (19.4%, 95% confidence intervals [CI] 14.2-25.5) and Leptospira spp. (1.7%, 95% CI 0.4-4.9), and high endpoint titres were observed against leptospiral serovar Grippotyphosa from the serological testing. Patients aged 5-17 years old had 4.02 (95% CI 1.18-13.70, p-value = 0.03) and 2.42 (95% CI 1.09-5.34, p-value = 0.03) times higher odds of infection with Brucella spp. and Coxiella burnetii than those of ages 35-80. Additionally, patients who sourced water from dams/springs, and other sources (protected wells, boreholes, bottled water, and water pans) had 2.39 (95% CI 1.22-4.68, p-value = 0.01) and 2.24 (1.15-4.35, p-value = 0.02) times higher odds of exposure to C. burnetii than those who used unprotected wells. Streptococcus and Moraxella spp. were determined using metagenomic sequencing. Brucellosis, leptospirosis, Streptococcus and Moraxella infections are potentially important causes of non-malarial fevers in Garissa. This knowledge can guide routine diagnosis, thus helping lower the disease burden and ensure better health outcomes, especially in younger populations.

Utility of demographic and clinical signs as diagnostic predictors for leptospiral uveitis: A retrospective study.

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.

Acute kidney injury and liver disease in an American bulldog with suspected leptospirosis.

A 6-year-old spayed female American bulldog was brought to a veterinary clinic with a 3-day history of vomiting, lethargy, anorexia, icterus, hemorrhagic diarrhea, and oliguria. The dog's clinical signs, complete blood (cell) count, serum biochemistry, urinalysis, and diagnostic imaging were indicative of acute kidney injury and acute hepatopathy consistent with leptospirosis. Treatment for leptospirosis was initiated but, due to the dog's lack of response and progression of clinical signs, euthanasia was ultimately elected after 3 d of hospitalization. The dog tested negative for Leptospira spp. on ELISA; urine, blood, and tissue PCRs; and immunohistochemistry. This case demonstrates that confirmation of leptospirosis can be challenging, even in an animal with the expected clinical presentation. Therefore, limitations of the diagnostic tests available, as well as the possibility of other, less likely differential diagnoses such as toxicosis, must be considered.

Lésion rénale aiguë et maladie hépatique chez un bouledogue américain avec leptospirose suspectée. Une femelle bouledogue américain stérilisée âgée de 6 ans a été présenté à une clinique vétérinaire avec une histoire d'une durée de 3 jours de vomissement, léthargie, anorexie, ictère, diarrhée hémorragique et oligurie. Les signes cliniques de la chienne, un comptage cellulaire sanguin complet, une biochimie sérique, une analyse d'urine et de l'imagerie diagnostique étaient indicateur de lésion rénale aiguë et d'hépatopathie aiguë compatibles avec la leptospirose. Un traitement pour la leptospirose a été instauré mais, étant donné l'absence de réponse de l'animal et la progression des signes cliniques, l'euthanasie a finalement été décidée après 3 jours d'hospitalisation. L'animal s'est avéré négatif par ELISA pour Leptospira spp.; l'urine, le sang et les tissus étaient également négatifs par PCR; et par immunohistochime. Ce cas illustre le fait que la confirmation de la leptospirose peut représenter un défi, même chez un animal avec la présentation clinique attendue. Ainsi, les limites des tests diagnostiques disponibles, de même que la possibilité d'autres diagnostics différentiels moins probables, tel qu'une toxicose, doivent être considérés.(Traduit par Dr Serge Messier).

Prevalence, genetic diversity and eco-epidemiology of pathogenic Leptospira species in small mammal communities in urban parks Lyon city, France.

Rodents are recognized as the main reservoirs of Leptospira spp. Rats, in particular, serve as hosts for the widely predominant Leptospira interrogans serovar Icterohaemorrhagiae, found worldwide. Several studies have shown the importance of other reservoirs, such as mice or hedgehogs, which harbor other leptospires' serovars. Nevertheless, our knowledge of circulating Leptospira spp. in reservoirs other than rats remains limited. In this context, we proposed an eco-health approach to assess the health hazard associated with leptospires in urban green spaces, where contacts between human/small mammals and domestic animals are likely. We studied the prevalence, the diversity of circulating strains, and epidemiology of pathogenic Leptospira species in small terrestrial mammal communities (rodents and shrews), between 2020-2022, in two parks in Lyon metropolis, France. Our study showed a significant carriage of Leptospira spp. in small terrestrial mammals in these parks and unveiled a global prevalence rate of 11.4%. Significant variations of prevalence were observed among the small mammal species (from 0 to 26.1%), with Rattus norvegicus exhibiting the highest infection levels (26.1%). We also observed strong spatio-temporal variations in Leptospira spp. circulation in its reservoirs. Prevalence seems to be higher in the peri-urban park and in autumn in 2021 and 2022. This is potentially due to differences in landscape, abiotic conditions and small mammal communities' composition. Our study suggests an important public health relevance of rats and in a lesser extent of other rodents (Apodemus spp., Clethrionomys glareolus and Mus musculus) as reservoirs of L. interrogans, with rodent species carrying specific serogroups/serovars. We also emphasize the potential hazard associated between the shrew Crocidura russula and L. kirschneri. Altogether, these results improve our knowledge about the prevalence of leptospirosis in an urban environment, which is an essential prerequisite for the implementation of prevention of associated risks.

Domestic dogs in indigenous Amazonian communities: Key players in Leptospira cycling and transmission?

BACKGROUND: Leptospirosis is the world's most common zoonotic disease. Mitigation and control rely on pathogen identification and understanding the roles of potential reservoirs in cycling and transmission. Underreporting and misdiagnosis obscure the magnitude of the problem and confound efforts to understand key epidemiological components. Difficulties in culturing hamper the use of serological diagnostics and delay the development of DNA detection methods. As a result, especially in complex ecosystems, we know very little about the importance of different mammalian host species in cycling and transmission to humans. METHODOLOGY/PRINCIPAL FINDINGS: We sampled dogs from five indigenous Kichwa communities living in the Yasuní National Park in the Ecuadorian Amazon basin. Blood and urine samples from domestic dogs were collected to assess the exposure of these animals to Leptospira and to identify the circulating species. Microscopic Agglutination Tests with a panel of 22 different serovars showed anti-leptospira antibodies in 36 sampled dogs (75%), and 7 serogroups were detected. Two DNA-based detection assays revealed pathogenic Leptospira DNA in 18 of 19 dog urine samples (94.7%). Amplicon sequencing and phylogenetic analysis of 16S rRNA and SecY genes from 15 urine samples revealed genetic diversity within two of three different Leptospira species: noguchii (n = 7), santarosai (n = 7), and interrogans (n = 1). CONCLUSIONS/SIGNIFICANCE: The high prevalence of antibodies and Leptospira DNA provides strong evidence for high rates of past and current infections. Such high prevalence has not been previously reported for dogs. These dogs live in the peridomestic environment in close contact with humans, yet they are free-ranging animals that interact with wildlife. This complex web of interactions may explain the diverse types of pathogenic Leptospira observed in this study. Our results suggest that domestic dogs are likely to play an important role in the cycling and transmission of Leptospira. Future studies in areas with complex ecoepidemiology will enable better parsing of the significance of genotypic, environmental, and host characteristics.

Nucleotide-induced ClpC oligomerization and its non-preferential association with ClpP isoforms of pathogenic Leptospira.

Bacterial caseinolytic protease-chaperone complexes participate in the elimination of misfolded and aggregated protein substrates. The spirochete Leptospira interrogans possess a set of Clp-chaperones (ClpX, ClpA, and ClpC), which may associate functionally with two different isoforms of LinClpP (ClpP1 and ClpP2). The L. interrogans ClpC (LinClpC) belongs to class-I chaperone with two active ATPase domains separated by a middle domain. Using the size exclusion chromatography, ANS dye binding, and dynamic light scattering analysis, the LinClpC is suggested to undergo nucleotide-induced oligomerization. LinClpC associates with either pure LinClpP1 or LinClpP2 isoforms non-preferentially and with equal affinity. Regardless, pure LinClpP isoforms cannot constitute an active protease complex with LinClpC. Interestingly, the heterocomplex LinClpP1P2 in association with LinClpC forms a functional proteolytic machinery and degrade ß-casein or FITC-casein in an energy-independent manner. Adding either ATP or ATPγS further fosters the LinClpCP1P2 complex protease activity by nurturing the functional oligomerization of LinClpC. The antibiotic, acyldepsipeptides (ADEP1) display a higher activatory role on LinClpP1P2 protease activity than LinClpC. Altogether, this work illustrates an in-depth study of hetero-tetradecamer LinClpP1P2 association with its cognate ATPase and unveils a new insight into the structural reorganization of LinClpP1P2 in the presence of chaperone, LinClpC to gain protease activity.

Leptospira infection and carrier survey on rats from wet market areas in Kuala Lumpur, Malaysia.

BACKGROUND OBJECTIVES: Leptospirosis is an important zoonotic infection that has caused significant mortality and morbidity worldwide. This disease is endemic in Malaysia and as a developing tropical country, leptospirosis is concerning as it threatens Malaysian public health and the country's economic sectors. However, there is limited information on leptospirosis in Malaysia, especially regarding leptospiral seroepidemiology among carriers in Malaysia. Therefore, more epidemiological information on the source of the disease and reservoir are needed for better disease control and source intervention. The objectives of this study are to gather information on Leptospira infection and the carrier status of rats captured from selected wet markets of Kuala Lumpur metropolitan city in Malaysia. METHODS: Live rat trappings were performed in four major wet markets in Kuala Lumpur, namely, Pudu, Chow Kit, Datuk Keramat, and Petaling Street. Animal samplings were performed for 12 months in 2017, where blood and kidney samples were collected and tested for anti-leptospiral antibodies via Microscopic Agglutination Test (MAT) and pathogenic Leptospira screening via Polymerase Chain Reaction (PCR) amplification offlaB gene. RESULTS: MAT showed that 34.7% (n = 50/144) of the captured rats were positive for anti-leptospiral antibody of which the most prominent serovar was Malaya followed by a local strain, IMR LEP 175. In parallel, 50 rats were also positive for pathogenic Leptospira DNA. INTERPRETATION CONCLUSION: This study showed that there are persistent Leptospira infections among rats in Kuala Lumpur wet markets and these rats are important reservoir hosts for the bacteria.

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

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

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

Metagenomic next-generation sequencing for diagnosing severe leptospirosis in a patient suspected COVID-19: A case report.

Leptospirosis is a zoonotic and neglected waterborne disease caused by the pathogenic helical spirochetes. Early diagnosis of leptospirosis remains challenging due to non-specific symptoms and the limited availability of rapid point-of-care diagnostic tests. Herein, we present a case where a patient suspected of having COVID-19 was diagnosed with leptospirosis using metagenomic next-generation sequencing (mNGS). This case highlights the potential of mNGS to diagnose leptospirosis in the context of the COVID-19 pandemic.

Seroprevalence of leptospirosis among stray dogs in Bosnia and Herzegovina.

Leptospirosis is a (re) emerging zoonosis that occurs worldwide. This study aimed to assess seroprevalence of leptospirosis and to identify the most common reactive serovars and risk factors for seropositivity in apparently healthy stray dogs of unknown vaccination status in the Sarajevo region of Bosnia and Herzegovina. Positive microscopic agglutination test titres (≥ 1:25) were detected in 3.87% (156/4028) of samples and most of the sera reacted against one serovar (85.9%). Dogs were most commonly reactive to Canicola (40.4%) and Hardjo (33.3%), followed by Pomona (15.4%) Tarassovi (14.7%), Icterohaemorrhagiae (8.3%), Grippotyphosa (5.8%), Bratislava (1.3%) and Saxkoebing (0.6%). Dogs older than one year had higher odds of seropositivity compared to younger dogs. The seropositivity was higher in spring and autumn than in summer. These results advocate for the need of a control strategy for this zoonosis in the country, which should include sero-surveillance, monitoring, and the inclusion of additional serovars in the testing.

Inter-species Transcriptomic Analysis Reveals a Constitutive Adaptation Against Oxidative Stress for the Highly Virulent Leptospira Species.

Transcriptomic analyses across large scales of evolutionary distance have great potential to shed light on regulatory evolution but are complicated by difficulties in establishing orthology and limited availability of accessible software. We introduce here a method and a graphical user interface wrapper, called Annotator-RNAtor, for performing interspecies transcriptomic analysis and studying intragenus evolution. The pipeline uses third-party software to infer homologous genes in various species and highlight differences in the expression of the core-genes. To illustrate the methodology and demonstrate its usefulness, we focus on the emergence of the highly virulent Leptospira subclade known as P1+, which includes the causative agents of leptospirosis. Here, we expand on the genomic study through the comparison of transcriptomes between species from P1+ and their related P1- counterparts (low-virulent pathogens). In doing so, we shed light on differentially expressed pathways and focused on describing a specific example of adaptation based on a differential expression of PerRA-controlled genes. We showed that P1+ species exhibit higher expression of the katE gene, a well-known virulence determinant in pathogenic Leptospira species correlated with greater tolerance to peroxide. Switching PerRA alleles between P1+ and P1- species demonstrated that the lower repression of katE and greater tolerance to peroxide in P1+ species was solely controlled by PerRA and partly caused by a PerRA amino-acid permutation. Overall, these results demonstrate the strategic fit of the methodology and its ability to decipher adaptive transcriptomic changes, not observable by comparative genome analysis, that may have been implicated in the emergence of these pathogens.

Leptospira-specific immunoglobulin Y (IgY) is protective in infected hamsters.

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.