Genotyping of Leptospira spp. in wild rats leads to first time detection of L. kirshneri serovar Mozdok in Serbia.

Introduction: This study aimed to investigate the prevalence and molecular characterization of Leptospira species in Belgrade, Serbia, an area where this disease is underexplored. Specifically, the study sought to employ molecular and multilocus sequence typing analyses to fill the gap in understanding the diversity and distribution of Leptospira species within the region. Methods: A comprehensive molecular analysis was conducted on kidney samples obtained from Norway rats (Rattus norvegicus) in the urban environment. The study utilized molecular diagnostic techniques including real-time PCR targeting the lipL32 gene and performing sequence-based typing schemes utilizing adk, icdA, lipL32, lipL41, rrs2, and secY genes. These methodologies were applied to ascertain the presence and characterize different Leptospira species and serovars, respectively. Results: The findings revealed the presence of two Leptospira species and three separate serovars in the Belgrade area. This study identified the presence of L. kirschneri serovar Mozdok in Serbia for the first time, a significant discovery previously undocumented in the region. This pioneering investigation sheds light on the molecular diversity and prevalence of Leptospira species in Serbia. Discussion: The study underscores the importance of employing molecular typing methods to gain insights into the epidemiology and characterization of Leptospira species. These findings significantly contribute to both local and global perspectives on leptospirosis epidemiology, providing vital insights for the development of effective control strategies and interventions. Summary: In our recent study, we explored the presence and performed molecular typing of the Leptospira species, the bacteria responsible for leptospirosis, in wild rats in Serbia. This was the first time such a study was conducted in the region. Leptospirosis is a serious disease that affects both animals and humans, often transmitted through contact with water contaminated by infected animals. Our focus was on understanding which types of Leptospira were present in these animals. Excitingly, we discovered a particular strain of Leptospira, known as L. kirshneri serovar Mozdok, for the first time in Serbia. This finding is significant because it sheds light on the presence and spread of different Leptospira serovars in Serbia. It also raises awareness about the potential health risks associated with this serovar, which was previously unknown in the area. Our work fits into a broader context of disease surveillance and public health. By identifying the types of Leptospira present in a specific region, we can better understand the risks to public health and take steps to prevent and control the spread of leptospirosis. This discovery is not just important for scientists studying infectious diseases; it has real implications for public health officials, veterinarians, and anyone concerned with preventing and treating leptospirosis. Our findings highlight the need for ongoing monitoring of Leptospira in wildlife and synanthropic fauna, to protect both animal and human health.

LIC_12757 from the pathogenic spirochaete Leptospira interrogans encodes an autoregulated ECF σE-type factor.

ECF (extracytoplasmic function) σ factors, members of the σ70-family, are the largest class of alternative σ factors which are stimulated in the presence of specific signals and direct RNA polymerase to transcribe a defined subset of genes. Thanks to them, bacterial pathogens can effectively reprogram their gene expression and, consequently, survive in the host and establish infection in a relatively short time. The number of ECF σ factors encoded within bacterial genomes is different depending on a given species and it reflects the likelihood that these bacteria will encounter harsh environmental conditions. The genome of L. interrogans, a zoonotic pathogen responsible for leptospirosis, is predicted to encode 11 ECF σE-type factors, but none of them have been characterized biochemically to date and their functions are still unknown. Here, we focused on one of the leptospiral ECF σ factors, namely LIC_12757, which was previously found to be up-regulated at elevated temperatures and may be related to the expression of clpB encoding an important L. interrogans virulence factor. We report cloning of the coding sequence of the LIC_12757 gene, its expression with the pET system and biochemical characterization of LIC_12757. By performing EMSA and in vitro transcription assays, we provide strong evidence that LIC_12757 indeed functions as a transcriptional factor that enables RNA polymerase to bind to the specific σE-type promoter and to initiate transcription. Interestingly, we demonstrate that LIC_12757 is autoregulated at the transcriptional level. Our study is a first step towards determining key aspects of LIC_12757 function in pathogenic Leptospira.

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.

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.

Risk of human leptospirosis in Colombia: spatiotemporal analysis and related hydroclimatic factors.

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

Feline leptospirosis prevalence worldwide: A systematic review and meta-analysis of diagnostic approaches.

Background and Aim: Leptospirosis in felids (domestic and wild cats) presents an ongoing challenge in our understanding. Numerous studies have reported the detection of Leptospira spp. in these feline populations, highlighting their potential as zoonotic carriers. This systematic review and meta-analysis aimed to provide insight into the global prevalence of leptospirosis in domestic and wild cats. Materials and Methods: We conducted extensive searches across five databases (PubMed, Scopus, Web of Science, Science Direct, and Google Scholar) following the Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols guidelines. Random-effect meta-analyses were performed using R software version 4.3.0 to estimate pooled prevalence rates. Subgroup meta-analyses were conducted based on continents, diagnostic methods, sample types, and wildcat genera. Results: A total of 71 articles on leptospirosis in domestic cats and 23 articles on leptospirosis in wild cats met the eligibility criteria. Our findings indicated a significantly higher pooled seroprevalence of leptospirosis in domestic cats compared with infection prevalence (9.95% [95% confidence interval (CI), 7.60%-12.54%] vs. 4.62% [95% CI, 2.10%-7.83%], p = 0.01). In contrast, no significant difference was observed in pooled seroprevalence and infection prevalence among wild cats (13.38% [95% CI, 6.25%-21.93%] vs. 2.9% [95% CI, 0.00%-18.91%], p = 0.21). A subgroup meta-analysis of domestic cats revealed significant differences in seroprevalence across continents, sample types, and diagnostic methods. On the contrary, wild cats had no significant differences in any of the subgroups. Conclusion: Leptospira spp. have evidently been exposed to both domestic and wild cats, highlighting their potential roles as reservoir hosts for leptospirosis. These findings highlight the importance of considering felids as a possible public health threat.

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.

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

Diagnostic accuracy of DPP Fever Panel II Asia tests for tropical fever diagnosis.

BACKGROUND: Fever is the most frequent symptom in patients seeking care in South and Southeast Asia. The introduction of rapid diagnostic tests (RDTs) for malaria continues to drive patient management and care. Malaria-negative cases are commonly treated with antibiotics without confirmation of bacteraemia. Conventional laboratory tests for differential diagnosis require skilled staff and appropriate access to healthcare facilities. In addition, introducing single-disease RDTs instead of conventional laboratory tests remains costly. To overcome some of the delivery challenges of multiple separate tests, a multiplexed RDT with the capacity to diagnose a diverse range of tropical fevers would be a cost-effective solution. In this study, a multiplex lateral flow immunoassay (DPP Fever Panel II Assay) that can detect serum immunoglobulin M (IgM) and specific microbial antigens of common fever agents in Asia (Orientia tsutsugamushi, Rickettsia typhi, Leptospira spp., Burkholderia pseudomallei, Dengue virus, Chikungunya virus, and Zika virus), was evaluated. METHODOLOGY/PRINCIPAL FINDINGS: Whole blood (WB) and serum samples from 300 patients with undefined febrile illness (UFI) recruited in Vientiane, Laos PDR were tested using the DPP Fever Panel II, which consists of an Antibody panel and Antigen panel. To compare reader performance, results were recorded using two DPP readers, DPP Micro Reader (Micro Reader 1) and DPP Micro Reader Next Generation (Micro Reader 2). WB and serum samples were run on the same fever panel and read on both micro readers in order to compare results. ROC analysis and equal variance analysis were performed to inform the diagnostic validity of the test compared against the respective reference standards of each fever agent (S1 Table). Overall better AUC values were observed in whole blood results. No significant difference in AUC performance was observed when comparing whole blood and serum sample testing, except for when testing for R. typhi IgM (p = 0.04), Leptospira IgM (p = 0.02), and Dengue IgG (p = 0.03). Linear regression depicted R2 values had ~70% agreement across WB and serum samples, except when testing for leptospirosis and Zika, where the R2 values were 0.37 and 0.47, respectively. No significant difference was observed between the performance of Micro Reader 1 and Micro Reader 2, except when testing for the following pathogens: Zika IgM, Zika IgG, and B pseudomallei CPS Ag. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that the diagnostic accuracy of the DPP Fever Panel II is comparable to that of commonly used RDTs. The optimal cut-off would depend on the use of the test and the desired sensitivity and specificity. Further studies are required to authenticate the use of these cut-offs in other endemic regions. This multiplex RDT offers diagnostic benefits in areas with limited access to healthcare and has the potential to improve field testing capacities. This could improve tropical fever management and reduce the public health burden in endemic low-resource areas.

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

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

Evolutionary insights into the emergence of virulent Leptospira spirochetes.

Pathogenic Leptospira are spirochete bacteria which cause leptospirosis, a re-emerging zoonotic disease of global importance. Here, we use a recently described lineage of environmental-adapted leptospires, which are evolutionarily the closest relatives of the highly virulent Leptospira species, to explore the key phenotypic traits and genetic determinants of Leptospira virulence. Through a comprehensive approach integrating phylogenomic comparisons with in vitro and in vivo phenotyping studies, we show that the evolution towards pathogenicity is associated with both a decrease of the ability to survive in the environment and the acquisition of strategies that enable successful host colonization. This includes the evasion of the human complement system and the adaptations to avoid activation of the innate immune cells. Moreover, our analysis reveals specific genetic determinants that have undergone positive selection during the course of evolution in Leptospira, contributing directly to virulence and host adaptation as demonstrated by gain-of-function and knock-down studies. Taken together, our findings define a new vision on Leptospira pathogenicity, identifying virulence attributes associated with clinically relevant species, and provide insights into the evolution and emergence of these life-threatening 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.

Efficacy and safety of antibiotics for treatment of leptospirosis: a systematic review and network meta-analysis.

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.

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).

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.

Prioritization of zoonoses of wildlife origin for multisectoral one health collaboration in Guyana, 2022.

Background: The human population in Guyana, located on the South American continent, is vulnerable to zoonotic diseases due to an appreciable reliance on Neotropical wildlife as a food source and for trade. An existing suboptimal health surveillance system may affect the effective monitoring of important zoonotic diseases. To effectively address this deficit, a One Health zoonotic disease prioritization workshop was conducted to identify nationally significant zoonoses. Methods: Prioritization of zoonotic diseases was conducted for the first time in Guyana & Caribbean region using literature review, prioritization criteria and a risk prioritization tool in combination with a consultative One Health workshop. This involved multisectoral experts from varied disciplines of social, human, animal, and environmental health to prioritize zoonotic diseases using a modified semi-quantitative One Health Zoonotic Disease Prioritization (OHZDP) tool. The inclusion and exclusion criteria were applied to pathogen hazards in existence among wildlife in Guyana during the hazard identification phase. Results: In total, fifty zoonoses were chosen for prioritization. Based on their weighted score, prioritized diseases were ranked in order of relative importance using a one-to-five selection scale. In Guyana, this zoonotic disease prioritization method is the first significant step toward bringing together specialists from the fields of human, animal, and environmental health. Following discussion of the OHZDP Tool output among disease experts, a final zoonotic disease list, including tuberculosis, leptospirosis, gastroenteritis, rabies, coronavirus, orthopoxvirus, viral hemorrhagic fevers, and hepatitis were identified as the top eight priority zoonoses in Guyana. Conclusions: This represents the first prioritization of nationally significant zoonotic diseases in Guyana and the English-speaking Caribbean. This One Health strategy to prioritize these eight zoonoses of wildlife origin is a step that will support future tracking and monitoring for disease prevalence among humans and wildlife and can be used as a decision-making guide for policymakers and stakeholders in Guyana.

Tracking potential Leptospira sources following human cases of leptospirosis: A One Health approach applied to an ecosystem in Brittany, France.

Pathogenic Leptospira can cause leptospirosis: a widespread, potentially fatal bacterial zoonosis whose risk is mediated by the soil and water features, animal host distributions, meaning the local ecosystem. When human cases of leptospirosis occur, it is challenging to track down their source because ecosystem-level epidemiological knowledge on Leptospira is needed. Between 2016 and 2019 in a focal riparian ecosystem, the human population experienced an outbreak and successive cases of leptospirosis attributable to L. kirschneri and L. interrogans. The epidemiological investigation was carried out using the One Health approach, as described in international health guidelines. As a first step in this process, we investigated leptospiral carriage in the main animal hosts found in the region. We sampled 143 nutrias, 17 muskrats, and 10 Norway rats using convenient trapping. DNA was extracted from their kidneys, lungs, and urine and subjected to real-time PCR (RT-PCR) targeting the Leptospira 16S rDNA and lfb1 genes. In the farms along the river's stretch of interest, we sampled serum from 439 cattle and used a microscopic agglutination test to detect the presence of antibodies against Leptospira. Urine samples were concomitantly obtained from 145 cattle and were used in two analyses: RT-PCR targeting the Leptospira 16S rDNA gene and Leptospira culturing. We found th, wt rodents were the most likely source of the L. interrogans behind the human cases. The cattle tested negative for Leptospira DNA but positive for antibodies against the serogroups implicated in the human cases. We failed to identify the potential source of the L. kirschneri responsible for several human cases of leptospirosis. Our results call for further clarification of the Leptospira maintenance community, which may comprise known maintenance hosts, such as rodents, as well as taxa not commonly considered to be maintenance hosts but that can still spread Leptospira. The resulting research network will collaboratively conduct future eco-epidemiological surveys to illuminate the leptospirosis risks faced by humans and animals within ecosystems.

Identification of Dominant Leptospira Serogroups among Leptospirosis Cases and Their Clinical Outcomes: A Prospective Hospital-Based Study in Mangaluru, India.

Leptospirosis is a reemerging zoonotic disease of worldwide significance, endemic to the southern region of India, with clinical manifestations similar to other febrile illnesses; hence, it is often misdiagnosed and underreported. Inadequate information about the disease burden and the regional circulating serogroups contributes to its neglected disease status. This study aimed to identify the infecting Leptospira serogroup in the coastal region of Mangaluru and study the clinical symptoms and outcome among leptospirosis patients. Serum samples were collected from 30 patients with confirmed leptospirosis admitted to a tertiary care center in Mangaluru and screened by microscopic agglutination test (MAT) for the infecting serogroup. The clinical profile of these cases was reviewed, and data regarding epidemiological factors such as age, sex, complications, and mortality were recorded. The MAT identified a higher occurrence of serogroup Bataviae (n = 7, 43.75%) and serogroup Australis (n = 5, 31.25%) compared with other serogroups screened in this study population. Patients were aged 16 to 65 years, with a predominance of males. The clinical presentation of leptospirosis ranged from a mild febrile illness to multiorgan failure. Fever (n = 29, 96%) was the common clinical presentation, followed by myalgia, nausea, and abdominal pain. Acute kidney injury, acute respiratory distress syndrome, and multiple organ dysfunction syndrome were the common complications observed. Determining the circulating serogroup is necessary to understand the epidemiology and diversity of Leptospira serogroups among animals and humans to strategize appropriate preventive measures.