Leptospirosis: a clinical and diagnostic challenge.

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.

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

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

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

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

Antibiotics for treatment of leptospirosis.

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; I2 = 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; I2 = 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; I2 = 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.

Use of Advanced Diagnostics for Timely Identification of Travel-associated Leptospira santarosai Infection in Four Adolescents Through Plasma Microbial Cell-free DNA Sequencing With the Karius Test.

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.

Case Report: Locally Acquired Leptospirosis in a Minnesota Boy and His Dog.

Leptospirosis affects numerous animal species, including domestic dogs, but documented transmission to humans is rare. Here, we describe epidemiologically linked cases in a 12-year-old Minnesota boy and his pet dog. While human leptospirosis is often thought of as a disease of tropical locations, this case report describes a rare documented example of local transmission in the northern United States, a region historically not perceived to be at high risk of Leptospira species transmission to humans. This case highlights an unusual presentation, with facial nerve palsy, underappreciated epidemiological risks, and diagnostic challenges of this reemerging infection.

Leptospirosis-associated meningitis in a patient with sjögren's syndrome: a case report.

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.

Case Report: Leptospirosis Complicated by Persistent, Bilateral Sensorineural Hearing Loss.

The clinical manifestations of leptospirosis range from mild to life-threatening and can impact on multiple organ systems. A wide array of neurological manifestations of leptospirosis have been reported, although the pathophysiology of neuroleptospirosis remains incompletely understood. We present a case of leptospirosis complicated by bilateral sensorineural deafness, with nodular meningitis demonstrated in the internal auditory meatus on magnetic resonance imaging. The patient was treated with doxycycline, ceftriaxone, systemic and topical steroids, and hyperbaric oxygen therapy, with modest, but incomplete, improvement.

Successful treatment with streptomycin of genital leptospirosis in naturally infected cows under field conditions.

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.

Case Report: Relapsing Leptospirosis in an Immunocompromised Host.

Leptospirosis is typically a self-limited febrile illness; when it occurs, meningitis usually develops early in the course. Here, we describe a patient who had engaged in freshwater activities in Kauai that was immunocompromised due to a history of mantle cell lymphoma, autologous hematopoietic cell transplant, and hypogammaglobulinemia. He developed leptospiral meningoencephalitis 11 weeks after illness onset and persistently detectable Leptospira DNA in blood and cerebrospinal fluid along with ongoing clinical illness, despite appropriate treatment.

Stillbirth and fulminant postpartum haemolysis: COVID-19 or leptospirosis or both?

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.

A rare case of severe leptospirosis infection presenting as septic shock in a non-endemic area: a case report and literature review.

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.

Hemoperfusion in Leptospirosis.

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.

Report of Weil's disease with a fatal course triggered by Jarisch-Herxheimer reaction.

Leptospirosis, a zoonotic disease characterized by a spectrum of influenza-like symptoms, can manifest as severe cases so called Weil's disease. Early diagnosis and treatment are crucial to avoid the potentially fatal course of the disease. Within 24 hours of the initial administration of antibiotics, patients may experience the Jarisch-Herxheimer reaction (JHR), characterized by chills, fever, hypotension, and impaired consciousness. The Okinawa Prefecture, where our hospital is situated, boasts the highest incidence rate of leptospirosis among all regions in Japan. This reports our encounter with the initial leptospirosis case after a period of 16 years within the Okinawa Prefecture. This case exhibited JHR and required the utilization of noradrenaline (NA). Despite evidence indicating that JHR does not correlate with mortality, we contend that diagnosis of Weil's disease necessitates admission to an intensive care unit (ICU) and vigilant monitoring for JHR, as it may result in impairment of general condition and fatal outcome, as observed in our case.

A case of severe leptospirosis with Jarisch-Herxheimer reaction presenting as respiratory failure.

Background: Leptospirosis is a widespread zoonotic disease caused by pathogenic Leptospira spp. The treatment of penicillin or tetracycline can cause a Jarisch-Herxheimer reaction (JHR), which can lead to acute respiratory distress syndrome (ARDS) and multi-organ failure in severe cases. The overall course of evolution and imaging features of a JHR exacerbation of leptospirosis have rarely been reported. Case presentation: We present a case of leptospirosis complicated by pulmonary alveolar hemorrhage and a Jarisch-Herxheimer reaction (JHR) that required respiratory and vasopressor support. This case demonstrates a well-defined course of evolution of JHR and the imaging features. Conclusions: Leptospirosis is easily misdiagnosed in some sporadic areas, and JHR complicates its management. Early diagnosis and appropriate treatment can reduce the mortality of severe leptospirosis with JHR.

Evaluating the Antimicrobial and Anti-Hemolytic Activity of Synthesized Pseudopeptide against Leptospiral Species: In Silico and In Vitro Approach.

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.

Double-trouble: A rare case of co-infection with melioidosis and leptospirosis from Sri Lanka.

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.

Leptospiral myocarditis and pancreatitis.

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.