Disentangling the influence of reservoir abundance and pathogen shedding on zoonotic spillover of the Leptospira agent in urban informal settlements.

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.

Serosurvey of Leptospira spp. in captive non-human primates in Spain.

Leptospirosis is a worldwide zoonotic disease caused by serovars of Leptospira spp. that can infect a wide range of wild and domestic species, highlighting non-human primates (NHPs) as one of the most susceptible taxonomic groups. The aim of the present study was to determine the seroprevalence and potential risk factors associated with exposure to Leptospira spp. in captive NHPs in Spain. Between 2007 and 2021, sera were collected from 258 NHPs in 16 zoos and wildlife rescue centers (WRCs), and tested for antibodies to Leptospira spp. using the modified microagglutination test (MAT). Anti-Leptospira spp. antibodies were detected in 73 (28.3 %) of the 258 NHPs evaluated. Seropositivity was found in 61.0 % (25/41) of the species analyzed and in 87.5 % (14/16) of the sampled centers. Sera seropositive for six different serovars of Leptospira spp. were detected, with L. Grippotyphosa being the most prevalent. Seroprevalence was found to be significantly higher in Hominidae (61.8 %; P < 0.001) compared to other NHP families tested. To the author's knowledge, the present study is the largest serosurvey of Leptospira spp. conducted in NHPs in Europe and also reports for the first time exposure to Leptospira spp. in nine NHP species, expanding the host range for this zoonotic bacterium. Our results indicate high and widespread seropositivity of Leptospira spp. in NHPs kept in captivity in Spain, which may be of conservation and animal health concern. This study supports the need to include captive NHPs in monitoring programs to evaluate the exposure of these species to Leptospira spp. in captive centers.

Drivers of human Leptospira infection in the Pacific Islands: A systematic review.

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

Study on Seroprevalence and Leptospiral Antibody Distribution Among Livestock Breeders and Farmers in Golestan Province.

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

Leptospirosis in the Platypus (Ornithorhynchus anatinus) in Australia: Who Is Infecting Whom?

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

Effective Management of Leptospirosis: A Case Report of Combined Doxycycline and Ceftriaxone Therapy.

Leptospirosis is a bacterial infection caused by the pathogen Leptospira. The disease is primarily transmitted through contact with animals (mainly rats) or through exposure to contaminated water or soil. Underdeveloped countries and places with poor housing and sanitation are at higher risk. Leptospirosis often presents with nonspecific symptoms, making it difficult to diagnose. This can delay the initiation of appropriate treatment. In the case presented, the patient had a history of cough, high fever, and a rash over various parts of the body. This combination of respiratory symptoms, systemic fever, and dermatological manifestations led to the suspicion of an infection. Initial blood examinations revealed a significantly increased white blood cell (WBC) count, indicating an infection. Further enzyme-linked immunosorbent assay (ELISA) testing was confirmed by active immunoglobulin M (IgM) antibodies specific to leptospira species, followed by a chest X-ray scan. The antibiotics doxycycline (for seven days) and ceftriaxone (two weeks) were used to treat the leptospirosis. The patient was also given antipyretics to bring down fever and antitussive agents to suppress the cough. Hydration and breathing exercises were also given high priority in healing from this illness. After treatment, the patient did very well, he sweated less before dawn, the rash started to go away, and finally, even coughing was controlled. Further blood tests have shown that now the WBC is in the normal range and the IgM antibody level has dropped. In other words, the infection has been eradicated. For detailed information, refer to the case study "A Moral Call," which argues that early treatment and intervention are critical in managing leptospirosis. Getting this severe infection with early antibiotic therapy and nursing care gives people a chance for complete recovery from their illness. There must be more studies into this disease's long-term effects and how to prevent it when the risk group is more significant.

Efficacy of Adjunct Hemoperfusion Compared to Standard Medical Therapy on 28-Day Mortality in Leptospirosis Patients with Renal Failure and Shock: A Single-Center Randomized Controlled Trial.

Hemoperfusion is a novel adjunct therapy that targets the dysregulated inflammatory events in severe sepsis. Previous studies have reported conflicting results on its efficacy and safety. This study was designed to assess the efficacy and safety of hemoperfusion among leptospirosis patients in septic shock and renal failure in terms of improvement in 28-day mortality, SOFA score, level of inflammatory markers, hemodynamics, and renal and pulmonary function. A total of 37 severe leptospirosis patients were enrolled and randomized into either standard medical therapy (SMT) alone, n = 20, or with hemoperfusion (HP), n = 17. Vital signs, urine output, vasopressor dose, PaO2/FiO2 (P/F) ratio, and biochemical parameters of patients from each treatment arm were compared. The hemoperfusion group showed a 36.84% (p = 0.017) risk reduction in 28-day mortality. Levels of procalcitonin, IL6, and lactate significantly decreased from baseline to day 7 in both groups. Statistically significant improvements in serum creatinine (p = 0.04) and PF ratio (p = 0.045) were observed in the hemoperfusion cohort. Intention-to-treat and per-protocol approaches showed that hemoperfusion increased the survival rate and decreased the mortality risk. This benefit for survival persisted even when patients were also receiving extracorporeal membrane oxygenation (ECMO), showing that hemoperfusion's benefits are independent of ECMO use. Hemoperfusion is a safe and effective adjunct therapy for managing severe sepsis. It promotes earlier renal and pulmonary function recovery and improves the survival of septic shock patients.

Zoonotic outbreak risk prediction with long short-term memory models: a case study with schistosomiasis, echinococcosis, and leptospirosis.

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

Spatial Interaction Between Leptospirosis and Enteric Fever in Kelantan, Malaysia: A 2016-2022 Notification Registry Analysis.

Leptospirosis and enteric fever are prevalent tropical acute bacterial febrile illnesses in Kelantan, Malaysia, that exhibit overlapping features and shared transmission dynamics, yet their spatial relationship remains understudied. This study aimed to analyze their spatial distribution, investigating potential interactions and intersecting patterns. A total of 212 laboratory-confirmed cases of enteric fever and 1106 of leptospirosis between 2016 and 2022, were retrieved from the national e-Notifikasi registry. Point pattern analysis revealed clustering of both diseases in the northern region, but leptospirosis was predominant in the south, exhibiting higher spatial risk. Seven co-infection cases were identified in overlapping hotspot areas. Spatial dependence between the diseases was identified within 4 km distance on average, with varying patterns over time and regions. Recognizing spatial dependence has implications for accurate diagnosis, timely intervention, and tailored public health strategies. The findings underscore the need for multi-disease interventions to address shared risk factors and co-infections in similar geographical contexts.

Diagnostic Pathways of Leptospira spp. in Dogs with Kidney Injury.

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

Foetal outcome of Leptospira and Rickettsial infections during pregnancy: a systematic review.

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

Determination of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and systemic immune-inflammation index in dogs with leptospirosis.

Leptospirosis is a globally distributed zoonosis with multisystemic involvement in canine species, capable of causing a pulmonary hemorrhagic syndrome (LPHS) in the most severe cases. In humans, the neutrophil to lymphocyte ratio (NLR), platelets to lymphocytes (PLR) and systemic immune-inflammation index (SII) have been described as predictors of morbidity and mortality in various pathologies, but no such studies have been developed for canine leptospirosis. Hence, we aimed to assess the usefulness of NLR, PLR and SII in dogs affected with leptospirosis, focusing on those that died or survived after hospitalization, whether or not they developed LPHS. The leptospirosis group was composed by 36 dogs while the control group consisted of 32 healthy dogs. The NLR, associated with inflammation, demonstrated a threefold or greater increase in all leptospirosis groups compared to the control group (median 2.44 ± 1.66) (developing or not LPHS). Dogs that died (median 67.78 ± 158.67), developed LHPS (median 85.17 ± 143.77), or both developed LHPS and died (median 67.78 ± 155,14) had a lower PLR in comparison to the control group (median 101,82 ± 53,75) and the rest of groups, but no statistically significant differences were observed (p > 0.05). The SII was higher in leptospirosis-affected dogs that survived (median 1356,92 ± 2726,29) and statistically significant differences were observed in those who did not develop LPHS (median 1770,41 ± 2630,77; p < 0.05) compared to the control group (median 555,21 ± 313,26). Our data shows that NLR may be used as inflammation indicator, while more studies are needed for PLR and SII in canine leptospirosis.

In silico analysis and functional characterization of a leucine-rich repeat protein of Leptospira interrogans.

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 ß-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.

Complexities of Severe Leptospirosis: A Case With Acute Hypoxic Respiratory Failure, Acute Kidney Injury, and Hyponatremia.

Leptospirosis, an acute zoonotic infection caused by spirochetes of the genus Leptospira, poses significant health risks worldwide. Transmission occurs through contact with infected animals' urine, blood, or tissue. This case report examines a 44-year-old man with severe leptospirosis, presenting as Weil's disease, characterized by acute hypoxic respiratory failure and acute kidney injury (AKI) secondary to rhabdomyolysis, complicated by severe hyponatremia. The case underscores the diagnostic and management challenges associated with leptospirosis, highlighting the importance of interdisciplinary collaboration and comprehensive diagnostic evaluation.

Murine C3 of the complement system affects infection by Leptospira interrogans.

Leptospirosis is an infectious neglected disease estimated to affect more than one million people worldwide each year. The Complement System plays a vital role in eliminating infectious agents. However, its precise role in leptospirosis remains to be fully understood. We investigated the importance of C3 in L. interrogans serovar Kennewicki strain Pomona Fromm (LPF) infection. Lack of C3 leads to decreased leukocyte number, impaired inflammatory response and failure to eliminate bacteria during the early stages of infection, which may cause interstitial nephritis later. These findings could be explained, at least in part, by the lower presence of local opsonins. Furthermore, antibody production against Leptospira was compromised in the absence of C3, highlighting the importance of CR2 in B lymphocyte proliferation and the adjuvant role of C3d in humoral immunity. Leptospires can be eliminated through the urine, and according to our study, the lack of C3 delays the elimination of LPF through urine during the early stages of the infection. These results strongly suggest the crucial role of C3 protein in orchestrating an appropriate inflammatory response against LPF infection and in effectively eliminating the bacteria from the body during the acute phase of leptospirosis.

Tropical Co-infection in a Tertiary Care Center in South India: A Case Report.

Tropical co-infections, characterized by overlapping clinical manifestations and the potential for diagnostic confusion, pose significant challenges in the management of febrile illnesses in endemic regions. This case report presents a 33-year-old male with a five-day history of fever, gastrointestinal symptoms, and dry cough, ultimately diagnosed with co-infections of dengue, leptospirosis, and Salmonella paratyphi A. This case underscores the challenges posed by the overlapping clinical features of endemic tropical diseases, emphasizing the necessity for comprehensive diagnostic strategies and tailored treatment protocols in managing febrile illnesses in endemic regions. Clinicians must also consider serological cross-reactivity when interpreting diagnostic tests, as it can complicate the identification of co-infections and impact treatment decisions, necessitating vigilance and an integrated approach in clinical practice.

Leptospirosis Incidence Post-Flooding Following Storm Daniel: The First Case Series in Greece.

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

Gut microbiota-derived butyrate improved acute leptospirosis in hamster via promoting macrophage ROS mediated by HDAC3 inhibition.

Leptospirosis is a re-emerging worldwide zoonotic disease. Infected patients and animals often exhibit intestinal symptoms. Mounting evidence suggests that host immune responses to bacterial infection are closely associated with intestinal homeostasis. Our previous research has shown that the gut microbiota can protect the host from acute leptospirosis, while the specific bacterial metabolic mediators participating in the pathogenesis remain to be identified. Short-chain fatty acids (SCFAs) are metabolites produced mainly by the gut microbiota that play a role in immune regulation. However, whether SCFAs are the key to protecting the host against leptospirosis and the underlying regulatory mechanisms are unknown. In this study, our results showed that the SCFA butyrate is involved in ameliorating leptospirosis. The depletion of SCFAs by antibiotic cocktail treatment reduced survival time after Leptospira infection while supplementation with butyrate but not acetate or propionate significantly amelioration of leptospirosis. In vitro experiments showed that butyrate treatment enhanced the intracellular bactericidal activity mediated by reactive oxygen species (ROS) production. Mechanistically, butyrate functions as a histone deacetylase 3 inhibitor (HDAC3i) to promote ROS production via monocarboxylate transporter (MCT). The protection of butyrate against acute leptospirosis mediated by ROS was also proven in vivo. Collectively, our data provide evidence that the butyrate-MCT-HDAC3i-ROS signaling axis is a potential therapeutic target for acute leptospirosis. Our work not only interprets the microbial metabolite signaling involved in transkingdom interactions between the host and gut microbiota but also provides a possible target for developing a prevention strategy for acute leptospirosis. IMPORTANCE: Leptospirosis is a worldwide zoonotic disease caused by Leptospira. An estimated 1 million people are infected with leptospirosis each year. Studies have shown that healthy gut microbiota can protect the host against leptospirosis but the mechanism is not clear. This work elucidated the mechanism of gut microbiota protecting the host against acute leptospirosis. Here, we find that butyrate, a metabolite of gut microbiota, can improve the survival rate of hamsters with leptospirosis by promoting the bactericidal activity of macrophages. Mechanistically, butyrate upregulates reactive oxygen species (ROS) levels after macrophage infection with Leptospira by inhibiting HDAC3. This work confirms the therapeutic potential of butyrate in preventing acute leptospirosis and provides evidence for the benefits of the macrophage-HDAC3i-ROS axis.

Leptospirosis and melioidosis coinfection presenting as acute respiratory distress syndrome and osteomyelitis: Case report and systematic review.

INTRODUCTION: Leptospirosis and melioidosis are common in tropical and temperate climates and can be acquired by exposure to contaminated water and soil. However, concomitant leptospirosis and melioidosis infection is rarely described in the literature. We report a case of leptospirosis-melioidosis coinfection and systematically review the literature. CASE PRESENTATION: A 42-year-old male presented with fever associated with chills and rigor, dull aching pain in the right thigh, myalgia, progressive breathlessness, and dry cough for 10 days. At presentation, he was tachypneic and had tachycardia, and oxygen saturation was 46% in room air. Chest radiography and computed tomography scan showed interstitial involvement. Magnetic resonance imaging for thigh pain revealed right femur osteomyelitis. Leptospira serology was positive, and blood culture grew Burkholderia pseudomallei, confirming the diagnosis of melioidosis. Thus, a diagnosis of presumptive leptospirosis based on modified Faine's criteria and systemic melioidosis was made. He received doxycycline and intravenous meropenem and improved. RESULTS: We performed a systematic review to understand the spectrum of leptospirosis-melioidosis coinfection. We identified only nine cases of coinfection described in literature. Only one patient had septic arthritis, and our case is the only one presenting with osteomyelitis. Serology diagnosed leptospirosis, whereas melioidosis was confirmed by blood culture in most patients. The majority of coinfected patients developed some complications, and six died. CONCLUSIONS: Leptospirosis-melioidosis coinfection is rarely reported in the literature. Physicians should maintain a high index suspicion of leptospirosis-melioidosis coinfection in patients presenting with acute febrile illness following exposure to soil or freshwater, particularly in tropical and endemic regions.

Recombinant outer membrane protein Lipl41 from Leptospira interrogans robust immune responses in mice model.

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