Severe Leptospirosis Research Articles

Severe Leptospirosis with Pulmonary hemorrhage; The role of intravenous hydrocortisone

Severe Leptospirosis with Pulmonary hemorrhage; The role of intravenous hydrocortisone

Renal Replacement Therapy in a Patient Diagnosed With Pancreatitis Secondary to Severe Leptospirosis.

In areas where the zoonotic disease leptospirosis is endemic, reduced morbidity and mortality is strongly linked to quick initiation of renal replacement therapy.

Leptospirosis: Malaysia Leptospirosis Research network experience

Background: Leptospirosis is a rat-borne bacterial infection caused by pathogenic Leptospira species has a global distribution affecting humans and a wide range of mammalian species. The disease is endemic in most tropical and subtropical regions, with risk influenced by flood, adventure travel, lack of sanitation and explosive population of rodent reservoirs. The first human case of severe leptospirosis was recognized in 1927 in Malaysia. Today at least 33,000 cases with 450 deaths have been recorded since its gazettement as a notifiable disease in 2010. Malaysia Leptospirosis research network (MyLepto) was formed in 2015 to understand the issues or challenges related to leptospirosis in Malaysia. One of the main objective of the MyLepto was to identify the rodent carrying and human infecting species and also to assess the gold standard techniques such as PCR and MAT in early diagnosis of the illness. Methods & Materials: For identifying the human infecting species, we performed lipL32 PCR and partial 16S rDNA (rrs) in patients clinically suspected for leptospirosis, while for rodents carrying strains, kidneys for small mammals trapped in hot spot and outbreak areas were cultured and confirmed by PCR. Results: For human, from a total of 165 patients, 92 (56%) were confirmed positive for leptospirosis through MAT (n = 43; 47%), PCR (n = 63; 69%) or both MAT and PCR (n = 14; 15%). The infecting Leptospira species determined by partial 16S rDNA (rrs) gene sequencing revealed two pathogenic Leptospira species namely L. interrogans (n = 44, 70%) and L. kirschneri (n = 17, 27%) and one intermediate species L. wolffii (n = 2, 3%). While for small mammals, an overall prevalence of 14.2% was detected comprising four species which include L. interrogans, L. kirschneri, L. borgpetersenii and L. weilii. Conclusion: The detection of similar species from rodents and human emphasizes the need for public health awareness on exposure to rodents.

Cardiac involvement in critically ill patients with leptospirosis: A prospective study using myocardial deformation imaging.

Myocardial inflammation often complicates leptospirosis, a re-emerging global zoonosis. Leptospirosis associated myocardial dysfunction is equivocal and the pattern of cardiac involvement may not differ from that of sepsis associated myocarditis. We prospectively compared cardiac involvement in 113 intensive care unit patients with severe leptospirosis to 31 patients with sepsis syndrome using a comprehensive assessment comprising of clinical presentation, electrocardiography, two-dimensional echocardiography (with global longitudinal strain calculation), and cardiac biomarker evaluation. Binomial logistic regression was performed to identify independent predictors of left ventricular systolic dysfunction in leptospirosis. Compared to sepsis syndrome, leptospirosis patients were younger, had higher body mass index measurements and were more likely to be smokers. Electrocardiography abnormalities were common and similar in both groups. Myocardial systolic dysfunction was common in both groups (leptospirosis: 55.86% vs sepsis syndrome: 51.61%, p=0.675) with subclinical left ventricular systolic dysfunction (characterized by abnormal global longitudinal strain and normal left ventricular ejection fraction) being most frequent followed by isolated right ventricular systolic dysfunction, isolated left ventricular systolic dysfunction, and bi-ventricular systolic dysfunction (leptospirosis: 31.43%, 18.42%, 13.16%, 10.53%, respectively; sepsis syndrome: 22.22%, 12.00%, 12.00%, 8.00%, respectively (p>0.05 for each comparator)). Leptospirosis patients had a trend towards greater troponin-T elevation (61.0% vs 40.0%, p=0.057). ST-segment elevation and elevated troponin were independent predictors of reduced left ventricular ejection fraction in leptospirosis. Cardiac involvement in leptospirosis appears to be similar to that of sepsis syndrome, with myocardial systolic dysfunction being common. As such, clinical vigilance pertaining to cardiac status is paramount in these high-risk patients.

The pre-activated immune response induced by LPS protects host from leptospirosis.

Leptospirosis is an important global zoonosis caused by pathogenic Leptospira. It is estimated that more than 1 million people are infected by Leptospira each year, and the death toll is about 60,000. Some studies showed that delayed immune response was associated with severe leptospirosis, and TLR4 was very important in the control of leptospirosis. In this study, we aimed to explore the effect of the classical activator (LPS) of TLR4 on leptospirosis in susceptible and resistant hosts. The results showed that LPS pretreatment increased the survival rate of hamsters to 80%. And LPS pre-treatment also significantly reduced the leptospiral load and alleviated the pathological injury in organs of hamsters and mice. The result detected by ELISA in mice showed that the levels of TNF-α and IL-1β were increased in the LPS-treated group compared to the control group before infection. However, two days after infection, the level of cytokines in LPS group was down-regulated compared with that in control group. In addition, in vitro results showed that LPS pre-treatment enhanced the phagocytosis and bactericidal ability of macrophages on Leptospira. Collectively, our results indicated that the pre-activated immune response induced by LPS enhanced the ability of host against leptospirosis.

Circulating microtranscriptome profiles reveal distinct expression of microRNAs in severe leptospirosis.

Biomarkers to predict the severity of leptospirosis are still lacking. This study aimed to identify and validate microRNAs in patients with severe leptospirosis, that could potentially be used as biomarkers for predicting an unfavorable outcome. Serum samples were collected from participants with definite diagnosis of leptospirosis. The participants were divided into two groups, non-severe and severe leptospirosis, as defined by the Specific Organ Sequential Organ Failure (SOFA) Score of more than two in any organ. Microtranscriptome analysis was performed using the NanoString miRNA Expression Assay. The expression level of candidate miRNAs was then validated by quantitative RT-PCR. Based on the NanoString, the microtranscriptome profile of the severe group was significantly different from that of the non-severe group. Upregulation of miR155-5p, miR362-3p, miR502-5p, miR601, miR1323, and miR630 in the severe group were identified, and further investigated. A total of 119 participants were enrolled in the validation cohort. Serum miR155-5p and miR630 levels were significantly higher in the severe group compared to the non-severe group. The combined use of miR155-5p or miR-630 with serum bicarbonate levels had an AUC of 0.79 (95%CI; 0.69–0.89, p<0.001) in identifying the severity of the disease. This data provides the first evidence that the microtranscriptome profiles of patients with severe leptospirosis were different from the non-severe group. Serum miR155-5p and miR630 levels might be novel biomarkers for identifying severe leptospirosis.

Clinical characteristics, outcomes, and predictors of leptospirosis in patients admitted to the medical intensive care unit: A retrospective analysis

BackgroundEarly diagnosis and detection of clinical deterioration of leptospirosis are challenges to all clinicians. This study aimed to report the characteristics and outcomes of patients admitted to the medical intensive care unit (MICU) for severe leptospirosis and to identify the clinical predictors of MICU admission. MethodsThis was a 10-year retrospective study that included all patients diagnosed as leptospirosis, based on either serology or a Thai-Lepto score (TLS) of >4. All clinical characteristics and laboratory data were collected and compared between MICU cases and general ward cases. Binary logistic regression was applied to identify the independent factors for MICU admission. ResultsOf the 68 patients who were diagnosed as leptospirosis based on inclusion criteria, 43 serologically-confirmed cases were subsequently analyzed. Fifty percent of the cases were admitted to the MICU and, compared with those admitted to the general ward, had higher Sequential Organ Failure Assessment (SOFA) score [10 (7–13) vs. 5 (2.2–5.6), p < 0.001]; higher TLS [7.5 (6.5−9.25) vs. 5.5 (3.5−6.5), p < 0.001]; lower mean arterial blood pressure (74.7 ± 15 mmHg vs. 84.2 ± 16.3 mmHg, p = 0.04); lower platelet count in ×103 cell/mm3 [65 (52.8–105.8) vs. 159 (87.3–181.5), p = 0.008); higher total bilirubin level [4.4 (1.5–8.7) mg/dL vs. 1.2 (0.7–2.8) mg/dL, p = 0.01]; and required more inotropes and vasopressors (87% vs. 4.3%, p < 0.001), mechanical ventilator support (91.3% vs. 4.3%, p < 0.001), and renal replacement therapy (39.1% vs. 0%, p < 0.001). TLS, SOFA score, requirement for mechanical ventilation, and use of inotropes and vasopressors were the predictors of MICU admission. TLS > 6 and SOFA score >6 gave similar power to predict MICU admission. ConclusionAmong patients with leptospirosis, TLS, SOFA score, inotrope or vasopressor requirement, and mechanical ventilator support were the independent predictors of MICU admission. TLS > 6 and SOFA score >6 indicated the need for MICU admission.

Atypical case of hantavirus infection in Sri Lanka mimicking leptospirosis: a case report

BackgroundHantavirus infection is an emerging zoonotic infection which has two characteristic patterns of presentation: hantavirus pulmonary syndrome and hemorrhagic fever with renal syndrome. The clinical presentation of hantavirus infection closely mimics leptospirosis.Case presentationThis case report describes a previously apparently well 36-year-old Sri Lankan Sinhalese man who presented with an acute febrile illness with myalgia, with liver involvement in the form of transaminitis, cardiac involvement in the form of myocarditis, acute kidney injury, and pulmonary involvement. He was initially managed as severe leptospirosis with multiorgan dysfunction with antibiotics, steroids, and N-acetyl cysteine. A diagnosis of acute hantavirus infection was made subsequently. He made an uneventful recovery.ConclusionHantavirus infections need to considered in the differential diagnosis of patients presenting with acute febrile illness with multiorgan involvement. Larger studies are needed to evaluate the seroprevalence of hantavirus in Sri Lanka because it could be an emerging serious public health problem.

The Predictive Factors for Severe Leptospirosis Cases in Kedah.

Over the past decade, increased awareness about leptospirosis disease in developing and industrialized countries has resulted in increased numbers of leptospirosis cases being reported worldwide. About 5% to 15% of leptospirosis patients end up with severe forms of the disease. Complication due to leptospirosis requires monitoring, specific treatments, and intensive care admission, thus increasing the cost of treating severe leptospirosis cases. Currently, we have data on incident and mortality rates, but we do not have data on the number of patients with severe form of leptospirosis or how many patients have complications, and whether or not these complications were resolved. Therefore, we carried out this study to determine the predictive factors for severe leptospirosis cases in Kedah. We conducted a cross-sectional study. The data of patients diagnosed with leptospirosis were obtained from the surveillance unit, Kedah Health Department, through the e-notification system. These data were then sorted according to the hospitals where the patients were admitted. The patients’ medical records were collected, and their information was obtained using a checklist. A total of 456 confirmed leptospirosis cases were included in the study, with 199 patients classified as severe cases and 257 patients as mild cases, based on the Malaysian leptospirosis guidelines. Most patients were male (71.5%) with a mean SD age of 36.62 ± 20.75 years. The predictive factors for severe leptospirosis include abnormal lung sounds (OR: 3.07 [CI 1.58–6.00]), hepatomegaly (OR: 7.14 [1.10–45.98]), hypotension (OR: 2.16 [1.08–4.34]), leukocytosis (OR: 2.12 [1.37–3.29]), low hematocrit (OR: 2.33 [1.43–3.81]), and increased alanine aminotransferase (SGPT ALT) (OR: 2.12 [1.36–3.30]). In conclusion, knowing these predictive factors will help clinicians identify severe leptospirosis cases earlier and develop their treatment plans accordingly, to reduce the complications and death from severe leptospirosis.

Adjunctive treatment of leptospirosis with corticosteroids

Leptospirosis is one of the most globally widespread zoonosis caused by pathogenic spirochetes from genus Leptospira spp. Icteric leptospirosis is a severe form of the disease which affects 5-15% of patients with leptospirosis, is often rapidly progressive and has a high mortality rate. Early diagnosis of leptospirosis is crucial for initiation of adequate antimicrobial therapy in order to prevent the advent of complications and reduce mortality. Literature offers an increasing amount of evidence that early application of corticosteroids affects the course of the disease, prevents the onset of multiorgan failure, reduces mortality and reduces the duration of hospitalization. This paper is a case report of a patient with severe icteric leptospirosis who was treated with antimicrobial and corticosteroid therapy. The patient recovered fully, with no remaining morbidity after the severe disease.

Predictors of Mortality in Severe Leptospirosis

Predictors of Mortality in Severe Leptospirosis

Complete Genome Sequence of a Virulent Leptospira interrogans Serovar Copenhageni Strain, Assembled with a Combination of Nanopore and Illumina Reads.

Here, we present the complete genome sequence of a highly virulent Leptospira interrogans serovar Copenhageni strain isolated from a dog with severe leptospirosis. In this work, a gapless genome draft was assembled with a combination of Nanopore and Illumina data of relatively low coverage.

Концепция применения глюкокортикостероидов в терапии тяжелого лептоспироза

Концепция применения глюкокортикостероидов в терапии тяжелого лептоспироза

SAT-420 A CLINICAL SCORE TO PREDICT MORTALITY IN SEVERE LEPTOSPIROSIS

Leptospirosis is a zoonosis transmitted through contact with water or soil contaminated by urine from animal reservoirs. It is typically a mild acute febrile illness, however about 10% of patients progress to severe disease with a case fatality rate of 5-20%. This study aims to establish a clinical prediction tool that would predict the risk of progression to mortality in patients presenting to health care providers with signs and symptoms of leptospirosis. This is a retrospective case-control study on survivors and non-survivors due to severe leptospirosis admitted at our institution. Logistic regression was performed to identifysignificant predictors of mortality. A scoring system was generated and validated using the same patient population. A total of 383 patients were included in the study, 327 survivors and 56 (14.6%) non-survivors. Significant factors associated with mortality include history of hypertension (OR=3.72, 95%CI=1.16-8.91), diabetes (OR=15.46, 95%CI=4.58-52.21), presence of oliguria (OR=3.43, 95%CI=1.75-6.73), hemorrhage (OR=2.61, 95%CI=1.22-5.61), hypotension (OR=2.27, 95%CI=1.20-4.33), respiratory rate >20cpm (OR=1.87, 95%CI=1.06-3.31), crackles (OR=4.02, 95%CI=0.74-2.04), edema (OR=4.79, 95%CI=1.83-12.50), thrombocytopenia <100x103/uL (OR=3.80, 95%CI=2.11-6.83), prolonged partial thromboplastin time >45 seconds (OR=2.94, 95%CI=1.61-5.38), acidosis pH<7.30 (OR=5.11, 95%CI=2.60-10.05), atrial fibrillation (OR=11.62, 95%CI=4.48-30.14), and radiographic pulmonary congestion/edema (OR=3.78, 95%CI=1.82-7.81). A weighted scoring system was assigned and four risk categories of increasing severity and percent mortality was formed and can be used as an adjunct to guide clinical decision-making and prioritization of resources. Patients with score 0-2, mortality risk 2.42%, can be discharged with advice, or admit to a primary hospital. Patients with score 3-5, mortality risk 19.51%, can be referred or admitted to a tertiary hospital with an interim leptospirosis ward. Patients with a score of 6-8 and mortality risk 42.86%, recommend transfer to a more equipped ward with close monitoring for occurrence of complications, and possible transfer to the Intensive Care Unit (ICU). Lastly, patients with score >9 have a high mortality risk (81.82%), thus transfer to ICU. In conclusion, a clinical prediction score for mortality in severe leptospirosis is developed from the major prognostic risk factors, which may prove useful in triaging patients in the event of another leptospirosis outbreak.

Draft Genome Sequences of Leptospira interrogans Serovar Copenhageni Strains Isolated from Patients with Weil's Disease in Brazil.

Leptospirosis is a worldwide zoonosis caused by pathogenic species of Leptospira In Brazil, this disease is endemic, presenting epidemic potential in rainy seasons. Here, we announce the whole-genome sequences of two L. interrogans serovar Copenhageni strains isolated from blood samples from two icteric patients associated with severe leptospirosis in Brazil.

Leptospirosis-induced purpura: An atypical manifestation of Weil's disease.

Purpura is a rare but documented presenting feature of severe leptospirosis. We describe a case of Weil's disease characterized by predominating coagulopathy and hepato‐nephritis. We illustrate dynamic changes in cutaneous lesions.

Severe Leptospirosis with Pulmonary Hemorrhage; The Role of Intravenous Hydrocortisone

Leptospirosis is an endemic zoonosis caused by spirochetes of the genus Leptospira that typically occurs in tropical regions. Pulmonary hemorrhage which is the frequent cause of mortality in leptospirosis is either underdiagnosed or only discovered at autopsy. In this paper, we present a 23 year old male presenting with five days history of fever with anuria, dyspnea and hemoptysis. Leptospira IgM was positive. Chest Xray and HRCT scan showed diffuse bilateral infiltrates with pulmonary hemorrhage. Patient was treated with antibiotics, renal replacement therapy and steroids. However, methylprednisolone was unavailable thus, a high dose of hydrocortisone was used as an alternative. Leptospirosis has an immune phase which damages the endothelium affects organs like the liver, kidneys, heart, lungs and meninges. Immunomodulation with high-dose steroids may be used. Methylprednisolone is the ideal steroid given and is proven to weaken the inflammatory response and ameliorate the adverse effect of immune mediated response. In our case, a hydrocortisone equivalent of methylprednisolone was used which was unconventional but is cheaper and more available. Early recognition is important as administration of corticosteroid in addition to broad-spectrum antibiotics and early supportive care can lead to successful treatment, shortened hospital stays, reduction of morbidity and mortality. Thus, targeting the pulmonary involvement of leptospirosis with methylprednisolone equivalent hydrocortisone has demonstrated to be effective as evidenced by our patient’s response. Hence, it can be used to treat Leptospirosis with pulmonary hemorrhage at a lesser cost which is more practical to use in areas with limited resources.

Cardiac Involvement in Leptospirosis – An Unusual Manifestation

Cardiovascular involvement by Leptospira is unusual. We report a case of a 29-year-old male sanitation worker who was diagnosed with leptospirosis (PCR testing for Leptospira spp. was positive in blood and urine). He had no classical clinical findings, and the presence of shock was the main worrisome finding. Within 24 hours of admission, the emergence of chest pain led us to consider cardiac involvement, which was demonstrated by diffuse supra-ST segment elevation, elevated troponin and NT-proBNP and an echocardiogram showing mildly left ventricular ejection fraction (LVEF 48–50%). There are several reports of cardiovascular involvement in severe leptospirosis but most patients are asymptomatic. In this case, the main key to diagnosis of perimyocarditis was the new onset of chest pain.

Hemostatic derangement in leptospirosis: A prospective cross-sectional study.

Context:Coagulation abnormalities have been observed among leptospirosis patients. However, coagulopathy in severe leptospirosis has not been further characterized.Aims:The aim of this study was to evaluate conventional coagulation and rotational thromboelastometry (ROTEM®) parameters in leptospirosis patients.Settings and Design:This prospective cross-sectional comparative study included patients presenting to a tertiary hospital in Sri Lanka with clinically and serologically confirmed leptospirosis (14 severe and 6 mild), dengue (6), sepsis (5), and 6 healthy individuals.Subjects and Methods:Blood samples were collected between the 3rd and 10th days of illness for prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), fibrinogen, lupus anticoagulant, factors VII and VIII, D-dimer, platelet count, and ROTEM.Statistical Analysis Used:ANOVA post hoc comparison using Bonferroni was applied to compare groups.Results:PT and aPTT were prolonged in leptospirosis patients and were corrected with normal plasma. TT was not significantly prolonged in leptospirosis. Fibrinogen was significantly elevated in severe leptospirosis (P = 0.001) and sepsis (P = 0.001) compared with healthy controls and dengue. Thirty percent of leptospirosis patients had thrombocytopenia (17% in mild and 36% in severe). No significant differences were seen in inTEM clotting time (CT) and exTEM CT in leptospirosis when compared to the other three groups. inTEM clot formation time (CFT) and exTEM CFT in dengue were significantly higher compared to severe (P = 0.001) and mild (P = 0.005) leptospirosis. inTEM maximum clot firmness (MCF) (P = 0.001) and exTEM MCF (P = 0.001) were significantly lower in dengue than in leptospirosis. Only one patient with leptospirosis had bleeding manifestations.Conclusions:Abnormalities in conventional coagulation parameters occur in leptospirosis. However, ROTEM parameters in leptospirosis are not significantly altered.

Relationship Between the Prevalence of Blood Groups and Severity of Leptospirosis: A Case-Control Study.

Introduction:The correlation between the prevalence and severity of leptospirosis with blood groups has not been investigated so far, but several studies have been conducted to link the infectious diseases with blood groups. The aim of this study was to investigate the prevalence of blood type in patients with leptospirosis and its association with disease severity.Methods:This is a case-control study performed on hospitalized patients with the diagnosis of leptospirosis in Mazandaran province, Iran, in 2018. The control group was selected from among the families of patients. Blood groups (ABO and Rh) and severity of the disease were assessed. Data were analyzed by SPSS 22.Results:A total of 300 people (150 in the case and 150 in the control) enrolled in the study. The mean age was 44.35 ± 15.39 years and 81.3% were men. The highest frequency of blood type in both groups was O+, A+, and B+, respectively. There was a statistically significant difference in the frequency of blood groups (P = .037). Comparison between severity of disease and blood types (ABO, Rh) showed no significant difference (P > .05).Conclusions:According to our study, O+ was the most common among patients with leptospirosis. The frequency of O in patients was significantly higher than in the control group, but there was no significant relationship between leptospirosis and Rh. The prevalence of this blood type was higher in people with a severe form of the disease. Finally, there is no statistically significant difference between the severity of the disease and ABO and Rh.