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

Ethnopharmacological Relevance: Pastoralists in Nigeria mix Garcinia kola seed (GK), Khaya senegalensis stem bark (KS), and Vernonia amygdalina leaves (VA) to treat leptospirosis., Aim: To determine the in vitro and in vivo effect on single and combination therapy on Leptospira interrogans-infected mice., Materials and Methods: Evaluation of in vitro assay for anti-leptospiral motility of the extracts was carried out in triplicates. For the in vivo assessment, 40 adult male mice inoculated with Leptospira were randomly allocated into 8 groups of 5 mice each. Groups IV-IX were treated with 800 mg/kg b.w. of KS, GK, VA, KS + GK, KS + VA, GK + VA for 5 days. Group I was negative control, II was model control, and III was treated with penicillin (3.7 mg/kg b.w.) intramuscularly., Results: In vitro, at 90 min, all the extracts at 800, 400, and 200 mg/ml showed complete cessation of motility which was significantly (p < 0.05) different when compared to the negative control. A significant (p < 0.05) IC 50 of 0.18 mg/ml was recorded with GK when compared to KS (0.40 mg/ml), VA (0.25 mg/ml), and procaine penicillin (0.31 mg/ml). Mean packed cell volume, haemoglobin concentration, and mean corpuscular haemoglobin concentration decreased significantly (p < 0.05) in all infected groups and returned to almost pre-infection values. However, significant leucocytosis (p < 0.05) was observed in group II. AST and ALP showed a significant increase (p < 0.001). Histopathological evaluation showed the extracts to prevent the distortion of normal architecture of the selected organs., Conclusion: This study demonstrates the significant potential of Garcinia kola, Khaya senegalensis, and Vernonia amygdalina extracts singly and in combination to combat leptospirosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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

Leptospirosis is a widespread zoonosis in tropical regions and it is not frequently recognised in developed countries. We report a case of leptospirosis transmitted from a pet dog. A middle-aged woman was referred to our emergency department with a 7-day history of fever and diarrhoea. She presented with hypotension, tachycardia, grasping pain in the entire muscle and petechiae. A detailed medical interview revealed that her pet dog had been to the veterinarian 1 month earlier with similar symptoms. We treated her with intravenous antibiotics. The patient's diagnosis of leptospirosis was confirmed by serological testing and the detection of DNA in her urine. We contacted the veterinarian and shared the information. We found that the dog had suffered from leptospirosis based on serological testing. We emphasise the possibility of leptospirosis being transmitted from pet dogs. Persistent suspicion of leptospirosis will contribute to its diagnosis and improved public health., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Leptospirosis is an emerging infectious disease caused by pathogenic Leptospira spp. Humans and some mammals can develop severe forms of leptospirosis accompanied by a dysregulated inflammatory response, which often results in death. The gut microbiota has been increasingly recognized as a vital element in systemic health. However, the precise role of the gut microbiota in severe leptospirosis is still unknown. Here, we aimed to explore the function and potential mechanisms of the gut microbiota in a hamster model of severe leptospirosis. Our study showed that leptospires were able to multiply in the intestine, cause pathological injury, and induce intestinal and systemic inflammatory responses. 16S rRNA gene sequencing analysis revealed that Leptospira infection changed the composition of the gut microbiota of hamsters with an expansion of Proteobacteria. In addition, gut barrier permeability was increased after infection, as reflected by a decrease in the expression of tight junctions. Translocated Proteobacteria were found in the intestinal epithelium of moribund hamsters, as determined by fluorescence in situ hybridization, with elevated lipopolysaccharide (LPS) levels in the serum. Moreover, gut microbiota depletion reduced the survival time, increased the leptospiral load, and promoted the expression of proinflammatory cytokines after Leptospira infection. Intriguingly, fecal filtration and serum from moribund hamsters both increased the transcription of TNF-α , IL-1β , IL-10 , and TLR4 in macrophages compared with those from uninfected hamsters. These stimulating activities were inhibited by LPS neutralization using polymyxin B. Based on our findings, we identified an LPS neutralization therapy that significantly improved the survival rates in severe leptospirosis when used in combination with antibiotic therapy or polyclonal antibody therapy. In conclusion, our study not only uncovers the role of the gut microbiota in severe leptospirosis but also provides a therapeutic strategy for severe leptospirosis., Competing Interests: XX, XC, SZ, JL, WZ, YC No competing interests declared, (© 2024, Xie et al.)

We present the case of a man in his early 50s who presented with a history of fever, malaise and jaundice. Initial investigations showed liver and renal dysfunction with no discernible cause for the septic process. On starting intravenous antibiotics, the patient developed a septic-shock-like reaction requiring transfer to intensive care. A diagnosis of leptospirosis was eventually established through an extensive and thorough history leading to a stepwise approach to investigations. Treatment targeting leptospirosis was delivered with noticeable clinical improvement., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Leptospirosis is an important zoonotic infection worldwide. Diagnosis of leptospirosis is challenging given its nonspecific clinical symptoms that overlap with other acute febrile illnesses and limitations with conventional diagnostic testing. Alternative advanced diagnostics, such as microbial cell-free DNA (mcfDNA), are increasingly being used to aid in the diagnosis of infections and can be applied to pathogens with public health importance such as Leptospira , a nationally notifiable disease., Methods: The Karius Test uses plasma mcfDNA sequencing to detect and quantify DNA-based pathogens. This test offered through the Karius lab detected 4 cases of Leptospira santarosai during a 5-month period across the United States in 2021 and were clinically reviewed., Results: In our case series, 4 adolescents with recent travel to Central America (Costa Rica, n = 3 and Belize, n = 1) from April to August 2021 were diagnosed with leptospirosis. While a large workup was performed in all cases, mcfDNA testing was the first test to detect L. santarosai as the microbiological diagnosis in all cases., Conclusions: Results of the Karius Test enabled rapid, noninvasive diagnosis of leptospirosis allowing for targeted therapy. Use of mcfDNA can be utilized for diagnosis of pathogens where conventional testing is challenging or limited. This in turn can enable quick diagnosis for targeted treatment and potentially aid in supporting case definitions of reportable diseases of public health concern., Competing Interests: A.A.A. was an employee of Karius, Inc at the time the manuscript was prepared but no longer works for Karius, Inc. For the remaining authors, there are no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This study aimed to develop aptamers targeting LipL32, a most abundant lipoprotein in pathogenic Leptospira, to hinder bacterial invasion. The objectives were to identify high-affinity aptamers through SELEX and evaluate their specificity and inhibitory effects. SELEX was employed to generate LipL32 aptamers (L32APs) over 15 rounds of selection. L32APs' binding affinity and specificity for pathogenic Leptospira were assessed. Their ability to inhibit LipL32-ECM interaction and Leptospira invasion was investigated. Animal studies were conducted to evaluate the impact of L32AP treatment on survival rates, Leptospira colonization, and kidney damage. Three L32APs with strong binding affinity were identified. They selectively detected pathogenic Leptospira, sparing non-pathogenic strains. L32APs inhibited LipL32-ECM interaction and Leptospira invasion. In animal studies, L32AP administration significantly improved survival rates, reduced Leptospira colonies, and mitigated kidney damage compared to infection alone. This pioneering research developed functional aptamers targeting pathogenic Leptospira. The identified L32APs exhibited high affinity, pathogen selectivity, and inhibition of invasion and ECM interaction. L32AP treatment showed promising results, enhancing survival rates and reducing Leptospira colonization and kidney damage. These findings demonstrate the potential of aptamers to impede pathogenic Leptospira invasion and aid in recovery from Leptospira-induced kidney injury (190 words)., Competing Interests: Declaration of competing interest The authors have stated explicitly that there are no conflicts of interest in connection with this article., (Copyright © 2024 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

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., (© 2024. The Author(s).)

Background: Leptospirosis is a disease transmitted from animals to humans through water, soil, or food contaminated with the urine of infected animals, caused by pathogenic Leptospira species. Antibiotics are commonly prescribed for the management of leptospirosis. Despite the widespread use of antibiotic treatment for leptospirosis, there seems to be insufficient evidence to determine its effectiveness or to recommend antibiotic use as a standard practice. This updated systematic review evaluated the available evidence regarding the use of antibiotics in treating leptospirosis, building upon a previously published Cochrane review., Objectives: To evaluate the benefits and harms of antibiotics versus placebo, no intervention, or another antibiotic for the treatment of people with leptospirosis., Search Methods: We identified randomised clinical trials following standard Cochrane procedures. The date of the last search was 27 March 2023., Selection Criteria: We searched for randomised clinical trials of various designs that examined the use of antibiotics for treating leptospirosis. We did not impose any restrictions based on the age, sex, occupation, or comorbidities of the participants involved in the trials. Our search encompassed trials that evaluated antibiotics, regardless of the method of administration, dosage, and schedule, and compared them with placebo or no intervention, or compared different antibiotics. We included trials regardless of the outcomes reported., Data Collection and Analysis: During the preparation of this review, we adhered to the Cochrane methodology and used Review Manager. The primary outcomes were all-cause mortality and serious adverse events (nosocomial infection). Our secondary outcomes were quality of life, proportion of people with adverse events considered non-serious, and days of hospitalisation. To assess the risk of bias of the included trials, we used the RoB 2 tool, and for evaluating the certainty of evidence we used GRADEpro GDT software. We presented dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD), both accompanied by their corresponding 95% confidence intervals (CI). We used the random-effects model for all our main analyses and the fixed-effect model for sensitivity analyses. For our primary outcome analyses, we included trial data from the longest follow-up period., Main Results: We identified nine randomised clinical trials comprising 1019 participants. Seven trials compared two intervention groups and two trials compared three intervention groups. Amongst the trials comparing antibiotics versus placebos, four trials assessed penicillin and one trial assessed doxycycline. In the trials comparing different antibiotics, one trial evaluated doxycycline versus azithromycin, one trial assessed penicillin versus doxycycline versus cefotaxime, and one trial evaluated ceftriaxone versus penicillin. One trial assessed penicillin with chloramphenicol and no intervention. Apart from two trials that recruited military personnel stationed in endemic areas or military personnel returning from training courses in endemic areas, the remaining trials recruited people from the general population presenting to the hospital with fever in an endemic area. The participants' ages in the included trials was 13 to 92 years. The treatment duration was seven days for penicillin, doxycycline, and cephalosporins; five days for chloramphenicol; and three days for azithromycin. The follow-up durations varied across trials, with three trials not specifying their follow-up periods. Three trials were excluded from quantitative synthesis; one reported zero events for a prespecified outcome, and two did not provide data for any prespecified outcomes. Antibiotics versus placebo or no intervention The evidence is very uncertain about the effect of penicillin versus placebo on all-cause mortality (RR 1.57, 95% CI 0.65 to 3.79; I 2 = 8%; 3 trials, 367 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin or chloramphenicol versus placebo on adverse events considered non-serious (RR 1.05, 95% CI 0.35 to 3.17; I 2 = 0%; 2 trials, 162 participants; very low-certainty evidence). None of the included trials assessed serious adverse events. Antibiotics versus another antibiotic The evidence is very uncertain about the effect of penicillin versus cephalosporin on all-cause mortality (RR 1.38, 95% CI 0.47 to 4.04; I 2 = 0%; 2 trials, 348 participants; very low-certainty evidence), or versus doxycycline (RR 0.93, 95% CI 0.13 to 6.46; 1 trial, 168 participants; very low-certainty evidence). The evidence is very uncertain about the effect of cefotaxime versus doxycycline on all-cause mortality (RR 0.18, 95% CI 0.01 to 3.78; 1 trial, 169 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin versus doxycycline on serious adverse events (nosocomial infection) (RR 0.62, 95% CI 0.11 to 3.62; 1 trial, 168 participants; very low-certainty evidence) or versus cefotaxime (RR 1.01, 95% CI 0.15 to 7.02; 1 trial, 175 participants; very low-certainty evidence). The evidence is very uncertain about the effect of doxycycline versus cefotaxime on serious adverse events (nosocomial infection) (RR 1.01, 95% CI 0.15 to 7.02; 1 trial, 175 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin versus cefotaxime (RR 3.03, 95% CI 0.13 to 73.47; 1 trial, 175 participants; very low-certainty evidence), versus doxycycline (RR 2.80, 95% CI 0.12 to 67.66; 1 trial, 175 participants; very low-certainty evidence), or versus chloramphenicol on adverse events considered non-serious (RR 0.74, 95% CI 0.15 to 3.67; 1 trial, 52 participants; very low-certainty evidence). Funding Six of the nine trials included statements disclosing their funding/supporting sources and three trials did not mention funding source. Four of the six trials mentioning sources received funds from public or governmental sources or from international charitable sources, and the remaining two, in addition to public or governmental sources, received support in the form of trial drug supply directly from pharmaceutical companies., Authors' Conclusions: As the certainty of evidence is very low, we do not know if antibiotics provide little to no effect on all-cause mortality, serious adverse events, or adverse events considered non-serious. There is a lack of definitive rigorous data from randomised trials to support the use of antibiotics for treating leptospirosis infection, and the absence of trials reporting data on clinically relevant outcomes further adds to this limitation., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

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.

Leptospirosis is one of the neglected zoonosis, affecting human and animal populations worldwide. Reliable effective therapeutics and concerns to look for more research into the molecular analysis of its genome is therefore needed. In the genomic pool of the Leptospira interrogans many hypothetical proteins are still uncharacterized. In the current research, we performed extensive in silico analysis to prioritize the potential hypothetical proteins of L. interrogans serovar Copenhageni via stepwise reducing the available hypothetical proteins (Total 3606) of the assembly to only 15, based on non-homologous to homosapien, essential, functional, virulent, cellular localization. Out of them, only two proteins WP&#95;000898918.1 (Hypothetical Protein 1) & WP&#95;001014594.1 (Hypothetical Protein 2) were found druggable and involved in protein-protein interaction network. The 3 D structures of these two target proteins were predicted via ab initio homology modeling followed by structures refinement and validation, as no structures were available till date. The analysis also revealed that the functional domains, families and protein-protein interacting partners identified in both proteins are crucial for the survival of the bacteria. The binding cavities were predicted for both the proteins through blind and specific protein-ligand docking with their respective ligands and inhibitors and were found to be in accordance with the druggable sites predicted by DoGSiteScorer. The docking interactions were found within the active functional domains for both the proteins while for Hypothetical Protein 2, the same residues were involved in interactions with Cytidine-5'-triphosphate in blind and specific docking. Furthermore, the simulations of molecular dynamics and free binding energy revealed the stable substrate binding and efficient binding energies, and were in accordance to our docking results. The work predicted two unique hypothetical proteins of L. interrogans as a potential druggable targets for designing of inhibitors for them.Communicated by Ramaswamy H. Sarma.

Background: Leptospirosis is a zoonotic disease that afflicts both humans and animals. It progresses from flu-like symptoms to more severe hepatic and renal failure, and may also lead to aseptic meningitis. Individuals with autoimmune diseases (ADs) are potentially more susceptible to Leptospirosis. Thus far, limited data has documented the association between Leptospirosis and autoimmune disorders., Case Presentation: The patient had a definitive pathological diagnosis of Sjögren's syndrome (SS). Due to recurrent headaches, the patient sought consultation with a neurologist. Lumbar puncture revealed elevated white blood cells and protein levels in the cerebrospinal fluid, along with decreased glucose. Tuberculous meningitis was suspected. Radiographic imaging exhibited meningeal enhancement, ventricular enlargement, and hydrocephalus. The patient commenced treatment with anti-tuberculosis therapy and corticosteroids. Subsequently, high-throughput sequencing (HTS) of cerebrospinal fluid identified the presence of Leptospira interrogans. The patient was ultimately diagnosed with Leptospiral meningitis, and underwent antimicrobial and immunosuppressive therapy, resulting in stabilization of the condition and gradual symptom recovery., Conclusions: The case highlights the challenges in diagnosing and managing leptospirosis-related meningitis in the presence of ADs and emphasizes the importance of utilizing HTS for accurate pathogen detection. The potential correlation between leptospirosis and SS warrants further investigation, as does the need for multidisciplinary involvement in treatment strategies for such complex cases., (© 2023. The Author(s).)

The single-dose protocol of streptomycin treatment has been recommended to treat renal leptospirosis in bovines. However, treating genital infection remains a challenge. Recently, a protocol using three doses of streptomycin demonstrated effectiveness in the genital clearance of experimentally infected ewes. Therefore, the present study aimed to apply this three-dose protocol for genital infection treatment in naturally infected cows under field conditions. Thirty beef cows were diagnosed as positive by lipL32-PCR in their genital samples. Nucleotide sequences (n = 10) characterized them as Leptospira interrogans sg Sejroe, genetically related to Hardjoprajitno strains. After molecular diagnosis, 13 cows received a single dose of 25 mg/kg streptomycin. The other 17 cows were submitted to the three-dose protocol. The successful treatment rate of genital infection on the single streptomycin dose was 7/13 (53.8%), while the cows that received the three doses 16/17 were negative (94.1% of efficacy). Based on those results, we conclude that the standard treatment preconized for renal infection is not adequate for genital infection, and the three-dose protocol was successful in eliminating the carrier status of genital leptospirosis., Competing Interests: Declaration of Competing Interest We have no conflict of interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Leptospirosis is a zoonosis caused by spirochete "genus" leptospira. The clinical presentations of leptospirosis range from an influenza-like presentation of fever and myalgia, to severe forms. Leptospirosis can potentially lead to a misdiagnosis or delay in diagnosis when clinical similarities exist., Case Presentation: A 63-year-old man presented with fever, shock and thrombocytopenia followed by diffuse pulmonary hemorrhage. Peripheral blood Metagenomic Next-generation Sequencing (mNGS) reported Leptospira interrogans. The patient was treated with piperacillin-tazobactam (TZP) plus doxycycline and improved dramatically after 7 days., Conclusion: We conclude that leptospirosis can potentially lead to a misdiagnosis or delay in diagnosis. Correctly evaluation of thrombocytopenia in acute febrile illnesses facilitates the differential diagnosis of leptospirosis. mNGS can accurately detect Leptospira DNA during the early stage of the infection., (© 2023. The Author(s).)

We report the case of a female patient with a SARS-CoV-2 infection first diagnosed at 32 2/7 weeks of gestation, resulting in stillbirth at 33 5/7 weeks of gestation. Post partum the patient presented with severe and persistent haemolysis, mild thrombocytopaenia, renal insufficiency and proteinuria as well as elevated liver enzymes and jaundice. Further investigations revealed a positive IgM for Leptospira interrogans and proof of infection by PCR in the urine. The patient was treated with penicillin for 7 days and received a total of 23 units of red blood cells within 11 days. Haemolysis diminished over time and haemoglobin, proteinuria and transaminases normalised within 23 days after delivery. We suppose an acute leptospirosis as underlying cause for the haemolysis, mimicking pregnancy-associated thrombotic microangiopathy. Whether stillbirth was related to leptospirosis or SARS-CoV-2 infection remains unclear., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

While Leptospira are known to cause multi-system dysfunction, cardiac involvement is uncommon. We present a case febrile myocarditis diagnosed to have leptospirosis. The patient also had pancreatitis, jaundice and renal failure but recovered well with timely management.

Melioidosis and leptospirosis are two emerging tropical infections that share somewhat similar clinical manifestations but require different methods of management. A 59-year-old farmer presented to a tertiary care hospital with an acute febrile illness associated with arthralgia, myalgia and jaundice, complicated by oliguric acute kidney injury and pulmonary haemorrhage. Treatment was initiated for complicated leptospirosis but with poor response. Blood culture was positive for Burkholderia pseudomallei and microscopic agglutination test (MAT) for leptospirosis was positive at the highest titres of 1:2560, confirming a co-infection of leptospirosis and melioidosis. The patient made a complete recovery with therapeutic plasma exchange (TPE), intermittent haemodialysis and intravenous (IV) antibiotics. Similar environmental conditions harbour melioidosis and leptospirosis, making co-infection a very real possibility. Co-infection should be suspected in patients from endemic areas with water and soil exposure. Using two antibiotics to cover both pathogens effectively is prudent. IV penicillin with IV ceftazidime is one such effective combination.

Bacterial infections are one of the leading causes of morbidity, mortality, and healthcare complications in patients. Leptospirosis is found to be the most prevalent, re-emergent, and neglected tropical zoonotic disease worldwide. The adaptation to various environmental conditions has made Leptospira acquire a large genome (~4.6 Mb) and a complex outer membrane, making it unique among bacteria that mimic the symptoms of jaundice and hemorrhage. Sph2 is another important virulence factor that enhances hemolytic sphingomyelinase-capable of moving inside mitochondria-which increases the ROS level and decreases the mitochondrial membrane potential, thereby leading to cell apoptosis. In the present study, 25 suspected bovine serum samples were subjected to the Microscopic Agglutination Test (MAT) across the Mysuru region. Different samples, such as urine, serum, and aborted materials from the confirmed MAT-positive animals, were used for isolation and genomic detection by conventional PCR targeting virulence gene, Lipl32, using specific primers. Further, in vitro and in silico studies were performed on isolated cultures to assess the anti-leptospiral, anti-hemolytic, and sphingomyelinase enzyme inhibition using novel pseudopeptides. The microdilution technique (MDT) and dark field microscope (DFM) assays revealed that at a concentration of 62.5 μg/mL, the pseudopeptide inhibited 100% of the growth of Leptospira spp., suggesting its efficiency in the treatment of leptospirosis. The flow cytometry analyses show the potency of the pseudopeptide against sphingomyelinase enzymes using human umbilical vein endothelial cells (HUVECs). Thus, the present study demonstrated the efficacy of the pseudopeptide in the inhibition of the growth of Leptospira , and therefore, this can be used as an alternative drug for the treatment of leptospirosis.

We present the case of a young female landscaper who presented to an Australian tertiary hospital with persistent fevers and new pancytopenia. Extensive initial workup for her presenting illness did not identify a cause; however, a detailed history of her occupation revealed she worked heavily with soil on farms that had domestic livestock in addition to rodents. Hence, further serological testing for leptospirosis was performed, revealing a diagnosis of infection with Leptospira interrogans serovar Hardjo. Treatment covering leptospirosis was commenced, and she improved clinically, and her cell counts returned to normal. Pancytopenia is a rare manifestation of leptospirosis and has only been reported in a handful of case studies. We highlight that leptospirosis should be considered as a differential diagnosis in those with fever, and new pancytopaenia, particularly in patients with relevant risk factors for exposure., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Leptospirosis is the most common zoonosis frequently seen in the tropics and subtropics especially during the rainy season when humans wade in floods contaminated by the urine of infected rats in urban areas. Aside from direct toxicity of the leptospires, the role of an exuberant immune response to the pathogen leading to secondary organ damage has been recognized. Thus, our treatment protocol for patients with severe leptospirosis characterized by renal failure, acute liver injury, and lung hemorrhage now includes a short course of methylprednisolone and intravenous cyclophosphamide. In some patients, however, hemodynamic collapse and acute respiratory distress syndrome ensue, which may be due to the release of cytokines resulting from the dysregulated immune response. Blood purification in the form of hemoperfusion (HP) with neutral macroporous resin-adsorbing beads adsorbs cytokines and other inflammatory mediators leading to cardiovascular stability and stabilization of endothelial membranes. HP may be considered part of a multiorgan system therapeutic approach in diseases with reversible multiorgan failure that can lead to an improvement in patient survival., (© 2023 S. Karger AG, Basel.)

Background: Although most leptospirosis is mild, the severe form can cause multiple complications, with a fatality rate of over 50% even with ICU support. The clinical manifestations of leptospirosis vary depending on organs and tissues involved. Both cerebral artery and coronary artery can be damaged by leptospirosis. Although cerebral arteritis induced by leptospirosis has been reported, cerebral infarction caused by leptospirosis is rarely reported., Case Presentation: We report the case of a 79-year-old man admitted to intensive care unit (ICU) because of 3 days duration of fever, bloody sputum and dyspnea. Five days before he was admitted to hospital, he had harvested rice in flooded fields. After admission, leptospira interrogans DNA sequence was identified in bronchoalveolar lavage fluid (BALF) by next-generation sequencing (NGS). Microscopic agglutination test (MAT) showed the serum antibody of Mini serovars was 1,600 and Hebdomadis serovars was 800. On the eighth day of admission, the patient noted left hemiplegia. Cranial CT scan revealed low-density shadow in the right basal ganglia, so cerebral infarction was diagnosed. The patient's condition rapidly deteriorated and he died on the eleventh day of admission despite penicillin treatment, invasive mechanical ventilation and continuous renal replacement support., Conclusion: Neurologic leptospirosis manifested as cerebral occlusion, although rare, might be deadly and should not be ignored., (© 2022. The Author(s).)

Leptospirosis in ruminants presents as a chronic disease that causes several reproductive disorders leading to severe economic losses. The current recommended treatment can be efficient to eliminate the renal carrier state, however little is known about the effect of this drug in removing the genital carrier state and the hormonal influence on it. A total of 12 primiparous sheep experimentally infected with a strain of Leptospira santarosai serogroup Sejroe, FV52 strain, were used and distributed as group A (estrus; n = 5), group B (metaestrus; n = 4) and group C (control; n = 3). At D0, groups A and B were treated with streptomycin (25 mg/kg) single dose. Samples of cervicovaginal mucus (CVM) were collected on days 0, 3, and 35 post-treatment, while uterine fragment (UF) samples were collected on days 3 and 35, for PCR. Even after antibiotic treatment, all groups presented infected animals, at D3 and D35, with no significant difference between the treated and control groups. Based on these results, it was conducted a second protocol of treatment with streptomycin, IM (25 mg/kg) for three consecutive days, which was 100% effective to eliminate the genital carrier state; therefore, that protocol should be recommended., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

To develop the macrophage migration inhibitory factor (MIF) directed therapeutic approach for the treatment of leptospirosis, we identified potential MIF inhibitors by screening 10 essential tautomerase inhibition classes of chemical compounds and 7 existing anti-inflammatory and anti-microbial drugs. Dopachrome tautomerase assay was performed to measure the anti-MIF activity of selected compounds. Among 17 chemical compounds, ibudilast, an anti-inflammatory agent showed the MIF tautomerase IC 50 value at a very lower concentration (9.5 ± 5.6 μM) which is considered similar to the IC 50 of standard MIF antagonist, ISO-1 (6.2 ± 3.8 μM) with non-significant cytotoxicity. The in vitro analysis of the therapeutic potential of MIF inhibitor revealed that ibudilast significantly reduced the leptospiral lipopolysaccharide (LPS) mediated expression of inflammatory mediators such as intercellular adhesion molecule (ICAM), p38 and p44/42 mitogen-activated protein kinase (MAPK), inflammatory cytokines, and decreased the reactive oxygen species (ROS) production, mitochondrial membrane potential (ΔΨ m ) loss and cell death of LPS treated THP-1 cells. In vivo analysis demonstrated that the administration of anti-MIF Ibudilast significantly reduced the histopathological changes, downregulates the pro-inflammatory cytokines, and protects the leptospiral BALB/c model from lethality by increasing the survival rate from 25% to 66%. Finally, the biocompatibility of the evaluated anti-MIF compound was explored by cytotoxicity, hemocompatibility, and cell death assay. Ibudilast showed no significant cytotoxicity and hemolytic activity was noticed even at the higher concentration of ≤50 μM and ≥250 μM, when compared with the positive control, 0.1% Triton X-100; no significant cell death was observed at ≤50 μM concentration of Ibudilast in THP-1 cells. From these lines of evidence, we propose that Ibudilast may be a great MIF targeting repurposing drug for reliable supportive treatment of severe leptospirosis., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Leptospirosis represents a public health problem in Panama, with an incidence rate of 1 in 100,000 inhabitants in 2014. Despite active surveillance and reports of outbreaks in the news, publications about human leptospirosis in Panama are scarce. The objective of this study was to describe the epidemiological and clinical features of leptospirosis in a cohort of patients admitted to the national reference hospital from January 2013 to December 2018. A total of 188 patients with suspected leptospirosis were identified, but only 56.9% (107 of 188) of the medical records could be retrieved. Microagglutination assays were completed in 45% (48 of 107) of the patients, confirming leptospirosis in 29.2% (14 of 48) of the patients. The most prevalent serogroup identified was Leptospira interrogans icterohemorrhagiae (4 of 14, 28.6%). The majority of patients with confirmed disease were middle-aged (36.4 ± 15.7 years), male (11 of 14, 78.6%), and symptomatic for 6.8 ± 0.7 days before admission. The predominant clinical presentation was fever (13 of 14, 92.9%), abdominal pain (7 of 14, 50%), and jaundice (8 of 14, 57.1%). Respiratory failure (8 of 14, 57.1%), elevated creatinine levels on admission (8 of 14, 57.1%), transfusion of blood-derived products (6 of 14, 42.9%), and required use of vasopressors (4 of 14, 28.6%) were common complications. Mortality was 28.6% (4 of 14). Empiric antibiotic therapy was initiated in almost all patients (10 of 12, 83.3%), and was appropriate in 90% (9 of 10) of them. Our study highlights the high prevalence of severe disease and reveals the diagnostic challenges concealing the true burden of leptospirosis in Panama. However, the small number of confirmed patients limits the generalization of these findings.

Leptospirosis, caused by pathogenic leptospira, is a neglected infectious disease that causes acute kidney injury, bleeding disorders, and even death. People can become infected with leptospirosis when they travel into epidemic areas. Except for vaccines and antibiotics, there are few reports of other drugs about prevention of leptospirosis. In this study, we show that the natural molecular compound, astragalus polysaccharides (APS), prevents against acute leptospirosis in hamsters. Pretreatment with APS improved the survival rate of hamsters with more minor organ damage and lower leptospira burden. After pretreatment with APS, the expression levels of leptospira-induced TLR2, TLR4, and TNF-α were enhanced. The priming effect of APS was studied in vitro. The data showed that leptospira-induced expressions of TNF-α and IL-1β were higher in APS-primed peritoneal macrophage, with enhanced glucose consumption and lactate production. Transcriptomic analysis revealed that pretreatment with APS down regulated respiratory chain and mitochondrial function, up regulated glycolysis related gene expressions. After pretreatment with glycolysis inhibitor (2-DG), the priming effect of APS in leptospira infection was inhibited. Our results indicated that pretreatment with natural molecular compound, APS, protected against acute leptospirosis in hamsters by priming effect through enhanced glycolysis., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Leptospirosis is an anthropozoonosis with polymorphic clinical symptoms and a high variability of severity, ranging from flu-like syndrome to severe acute kidney injury. This disease is highly incident in tropical regions but there is a trend towards increasing incidence in metropolitan France and in Reunion Island. The objective of this study was to describe the epidemiological, clinical, laboratory and therapeutic characteristics of the pediatric leptospirosis in metropolitan France and in Reunion Island., Patients and Methods: We performed a retrospective analysis of leptospirosis cases hospitalized in University hospitals where members of the Paediatric Nephrology Society work in France between January 2008 and December 2020, 6 centers reported leptospirosis cases, one center had one patient in consultation but lack of available data and 10 centers did not find any case., Results: A total of 21 cases were reported (mean age 13.4±3.4years), mostly boys (ratio 6:1). Out of 21 patients, 95% had fever, 71% were presenting with myalgia, 81% with thrombocytopenia, and 76% with gastrointestinal symptoms. Regarding kidney impairment, 18 patients (86%) had acute kidney injury, including 4 (19%) with oligoanuria, but none of them required acute dialysis. About 30% of patients had biological signs of tubulopathy including hypophosphatemia, hypokalemia, or tubular proteinuria. No death due to the disease occurred. The therapeutic management followed the current guidelines with the use of antibiotic therapy by amoxicillin or 3rd generation cephalosporins with symptomatic treatment. When there was biological control after exit, creatinine decreased., Discussion: In this multicenter retrospective study, we report 21 children with leptospirosis with a significant proportion of acute kidney injury, the outcome was favorable. Children do not seem to be at high risk of chronic kidney disease progression but nephrology follow-up has not been systematically carried out. Compared to studies performed in adults, the prognosis was better and hepatic impairment was rare. Compared to other pediatric studies, conjunctivitis was not a common symptom but kidney injury and survival appeared to be similar. Children were presenting with anicteric renal presentation. The casebook wasn't exhaustive and didn't include the other overseas territories, which account for the highest proportion of leptospirosis infection., Conclusion: Leptospirosis is an infection which may lead to multivisceral failure with kidney involvement conditioning the outcome. Despite a better prognosis in children, it remains important to quickly diagnose this infection in order to start appropriate antibiotic therapy and perform a kidney function monitoring., (Copyright © 2022. Published by Elsevier Masson SAS.)

Leptospirosis presents in a biphasic manner: an early leptospiraemic phase and a late immune phase. In its severe form, it presents with multi-organ failure, also known as Weil's disease. Stevens-Johnson syndrome (SJS) is an autoimmune hypersensitive reaction leading to diffuse fluid filled vesicle formation with detachment of skin and mucous membrane. Though SJS is triggered by different infections and drugs, its association with leptospirosis is not frequently reported. Here we present such a case.

Background: Leptospirosis is a bacterial infection which may cause multiple non-specific symptoms. Transmission of the disease can occur via rats or surface water infected by rats. The Netherlands have seen a record number of cases of leptospirosis in 2019. Diagnosis is often delayed and not always considered because of the variable clinical presentation of the disease. Surveillance of disease prevention concerning rat breeders is inadequate., Case Description: An 11-year-old girl visited the paediatrician with fever, myalgia and a headache followed by a stiff neck. Two days earlier she was bitten by one of her pet rats. Diagnostic testing confirmed a meningitis caused by leptospirosis-infection. The pet rats were found to be infected with leptospirosis. All rats were euthanized., Conclusion: Consider the diagnosis leptospirosis in patients with unexplained non-specific symptoms following rat exposure. Information regarding visits to tropical areas and animal exposure is vital. More awareness of zoonoses is needed among physicians and pet breeders.

Case Description: A 12-year-old sexually intact male zoo-managed Sumatran tiger (Panthera tigris sumatrae) was evaluated for a 3-day history of vomiting, hyporexia, and lethargy. Radiographs were supportive of gastrointestinal obstruction, and an exploratory laparotomy was performed., Clinical Findings: Diffuse tan foci were present on the liver parenchyma, and the tiger became icteric throughout the procedure. Hepatic histopathology and immunohistochemistry resulted in a diagnosis of leptospirosis. Serum microagglutination testing for Leptospira spp antibody titers were positive for L kirschneri serovar Grippotyphosa, rising from 1:400 to 1:3,200 in 2 days., Treatment and Outcome: The tiger was treated with antimicrobials, ursodiol, and mirtazapine, and increased biosecurity measures were instituted. Free-ranging wildlife on grounds were trapped, euthanized, and submitted for necropsy to screen for disease vectors. The tiger's urine was intermittently opportunistically collected from the enclosure and remained PCR assay negative for Leptospira spp until being positive once again on day 595. Although the tiger was without clinical signs at that time, antimicrobial therapy and increased biosecurity protocols were instituted a second time until urinary Leptospira shedding was confirmed to have stopped. By 1,071 days after initial presentation, the tiger remained nonclinical, with no additional urinary shedding episodes., Clinical Relevance: While domestic and nondomestic free-ranging felids have been reported as subclinical Leptospira spp carriers, this report indicates the clinical importance of leptospirosis when a tiger presents with generalized gastrointestinal signs and icterus. Due to the zoonotic potential, biosecurity measures are necessary. This patient had a clinically successful outcome with antimicrobial therapy and supportive care.

Leptospirosis, an underreported disease, is a highly prevalent spirochaetal zoonotic disease in both tropical and temperate climates. Symptoms can range from mild illness to potentially life-threatening infection. Laboratory tests are nonspecific. Microbiological confirmation is not widely available in endemic developing countries like Nepal. We need to rely on the serologic test, which has its own pitfalls in the initial days of illness. Here, we report a case of 56 years old female from the western region of Nepal who presented with fever, jaundice and anuria. She initially tested negative for leptospirosis but was later found to be positive in the second week of illness. Unlike the usual non-oliguric renal failure in leptospirosis, she presented with anuria requiring haemodialysis and subsequently had a good recovery with treatment. We highlight the importance of clinical suspicion and logical interpretation of serologic tests based on its timing from the onset of illness.

Background: Persistent leptospiruria in naturally infected dogs occurs despite appropriate antibiotic treatment., Hypothesis/objectives: To determine the frequency of persistent leptospiruria in naturally infected dogs and the association of persistent leptospiruria with different antibiotic treatments., Animals: Thirty-two dogs of varying age and breed diagnosed with leptospirosis via urine polymerase chain reaction assay (PCR)., Methods: A prospective observational study of dogs diagnosed with leptospirosis was undertaken to determine the frequency of persistent leptospiruria as determined by PCR. Clinical presentation of leptospirosis, antibiotic treatment, serum creatinine concentration, and outcome were recorded., Results: Fifteen of 32 dogs had a negative urine PCR on the first submission in the study, 5 of 15 received only an aminopenicillin. The remaining 17 dogs had a negative urine PCR on the second (n = 6 dogs), third (n = 5), fourth (n = 5), and eighth (n = 1) submissions. Acute kidney injury was reported in 32/32 dogs. Two of 32 dogs developed chronic kidney disease., Conclusions and Clinical Importance: Persistent leptospiruria is common despite treatment with antibiotics frequently recommended for treatment. Follow-up urine PCR to confirm clearance of the organism is recommended in all dogs. In dogs with persistent leptospiruria, chronic kidney disease can develop after acute kidney injury., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

Background: Leptospirosis is a common zoonotic infection caused by the spirochete Leptospira. The disease is more prevalent in the tropics, causing subclinical to severe illness leading to high morbidity and mortality., Case Presentation: A 77-year-old healthy Sri Lankan man presented to the Teaching Hospital Peradeniya with severe leptospirosis complicated with acute kidney injury, pulmonary hemorrhages, myocarditis, and severe thrombocytopenia. He was deteriorating despite treatment with intravenous antibiotics and methylprednisolone boluses. He made a dramatic improvement with two cycles of plasma exchange., Conclusion: Therapeutic plasma exchange is a life-saving treatment modality in severe leptospirosis with multiorgan failure., (© 2021. The Author(s).)

Leptospirosis is a common tropical febrile illness which may manifest with the hepatorenal syndrome and systemic hemorrhagic manifestations. Pituitary apoplexy is a rare but life-threatening condition characterized by a hemorrhage within the pituitary gland or a pituitary adenoma. Apoplexy is very rarely associated with some inducing events such as infectious diseases such as dengue hemorrhagic fever, Hantaan virus, Puumala virus have also been reported to cause pituitary apoplexy. We present the first case of pituitary apoplexy in a patient who was being treated for leptospirosis and discuss the possible mechanisms of apoplexy in the scenario presented. We also review other reports of infectious causes that may result in pituitary apoplexy., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Leptospirosis is an underdiagnosed bacterial infection with nonspecific symptoms, hence, a diagnostic challenge. Identifying a case of leptospirosis in Switzerland is uncommon. Although kidney complications are frequent in severe forms, including tubular dysfunction, observing this complication is rare in our country. We report the case of a patient with leptospirosis and kidney dysfunction, which was notable for proximal tubulopathy. This case report describes the diagnosis and management of this patient's tubular dysfunction., Case Presentation: A 34-year-old Caucasian male known for alcohol and drug abuse presented to our emergency department suffering from severe pain in the lower limbs, jaundice, and fever with flu-like symptoms. Physical examination was not contributory. Blood tests showed cytopenia, elevated inflammatory markers, acute kidney injury, and altered liver function tests with predominant cholestasis. Urinalysis showed proteinuria and significant glycosuria without concomitant hyperglycemia. Leptospirosis was suspected and confirmed by both positive serum polymerase chain reaction and elevated immunoglobulin M for Leptospira interrogans. The patient was treated with intravenous amoxicillin-clavulanate and doxycycline for 7 days. After antibiotic treatment, symptoms disappeared, and kidney dysfunction completely resolved., Conclusion: Our case focuses on the description of leptospirosis-related acute kidney injury with proximal tubular dysfunction, which is a rare finding in Switzerland., (© 2021. The Author(s).)

Background: Leptospirosis is a zoonotic illness caused by pathogenic spirochetes of the genus Leptospira. The disease spectrum ranges from a mild influenza-like presentation to a more serious Weil's syndrome. Leptospirosis rarely presents as a primary neurological syndrome. We report two cases of Leptospira borgpetersenii serovar Tarasssovi presenting as aseptic meningitis in Sri Lanka., Case Presentation: We describe case reports of two patients presenting as symptomatic aseptic meningitis due to neuroleptospirosis. Both patients had significant neurological involvement at presentation in the absence of common clinical features of leptospirosis. These patients were initially managed as bacterial or viral meningitis and leptospirosis was suspected due to a history of exposure to contaminated water. Subsequently, they were diagnosed to have neuroleptospirosis by positive Leptospira serology and both patients gained full recovery., Conclusion: Our report highlights the importance of considering leptospirosis as a differential diagnosis in patients with aseptic meningitis in endemic settings. Obtaining a detailed occupational and recreational history is helpful in diagnosing neuroleptospirosis promptly. We report the association of Leptospira borgpetersenii serovar (sv.) Tarassovi (strain bakeri) in causing aseptic meningitis, which has not been reported to the best of our knowledge.

Leptospirosis, caused by pathogenic Leptospira species, is an essential but neglected zoonosis. There are more than 300 serovars of pathogenic Leptospira, while inactivated bacteria offers only short-term serovar-specific protection. Leptospirosis treatment is mainly dependent on the use of antibiotics. However, the side effects of antibiotics and the risk of antibiotic resistance remain major problems. Thus, alternative agents which are fewer side effects on humans and efficient in leptospirosis would be welcome. Many studies have reported that polysaccharides could be used as immunostimulants in treating infection and cancer. In this study, we examined the protective effect of polysaccharides isolated from Iris against leptospirosis. To our knowledge, it is the first time to report Iris polysaccharides (IP) as an immunostimulant in treating infection. The results showed that IP treatment significantly increased the survival rate of hamsters challenged by a lethal dose of leptospires. Besides, the tissue injury and leptospiral load were reduced in IP-treated infection group compared with the untreated infection group at 4 days post-infection (p.i.). Intriguingly, IP treatment sustained intense immune response at 4 days p.i. analyzed by qPCR. The results exhibited that the gene expression of TLR2 and TLR4 was significantly increased in the group coinjected with IP and leptospires than in the infected controls. And the expression of IL-1β and TNF-α were also up-regulated after IP treatment, except the expression of IL-1β in the kidney. Our results not only broaden the medicinal value of Iris, but also provide a competent candidate for the control of Leptospira infection., (Copyright © 2021. Published by Elsevier Ltd.)

Chronic leptospirosis usually occurs during sublethal doses infection of susceptible animal and reservoir host, which typical symptom is interstitial nephritis, and leptospira urine, contaminating the environment and threatening other susceptible animals and humans. Dipotassium glycyrrhizinate (DG) is a replacement for glycyrrhizic acid, which exhibits anti-inflammation, immunomodulation effects. This study is to investigate whether DG relieves leptospira-induced nephritis. In vitro, DG inhibited the leptospira-induced transcription levels of IL-1β, IL-6, TNF-α, RANTES, MCP-1 and iNOS, and protein levels of IL-1β and TNF-α, and downregulated NF-κB and MAPK pathway in TCMK-1 cells. In vivo, DG attenuated the kidney histopathological change and downregulated the expression of IL-1β and TNF-α, as well as reduced kidney leptospiral burden. In summary, DG alleviated leptospira-induced inflammation through inhibitory NF-κB and MAPK pathway, and DG decreased the renal colonization of leptospires in mice., (Copyright © 2021. Published by Elsevier Ltd.)