A Scoring Tool to Predict Pulmonary Complications in Severe Leptospirosis with Kidney Failure

Rapid identification of patients likely to develop pulmonary complications in severe leptospirosis is crucial to prompt aggressive management and improve survival. The following article is a cohort study of leptospirosis patients admitted at the National Kidney and Transplant Institute (NKTI). Logistic regression was used to predict pulmonary complications and obtain a scoring tool. The Kaplan–Meir method was used to describe survival rates. Among 380 patients with severe leptospirosis and kidney failure, the overall mortality was 14%, with pulmonary hemorrhage as the most common cause. In total, there were 85 (22.4%) individuals who developed pulmonary complications, the majority (95.3%) were observed within three days of admission. Among the patients with pulmonary complications, 56.5% died. Patients placed on mechanical ventilation had an 82.1% mortality rate. Multivariate analyses showed that dyspnea (OR = 28.76, p < 0.0001), hemoptysis (OR = 20.73, p < 0.0001), diabetes (OR = 10.21, p < 0.0001), renal replacement therapy (RRT) requirement (OR = 6.25, p < 0.0001), thrombocytopenia (OR = 3.54, p < 0.0029), and oliguria/anuria (OR = 3.15, p < 0.0108) were significantly associated with pulmonary complications. A scoring index was developed termed THe-RADS score (Thrombocytopenia, Hemoptysis, RRT, Anuria, Diabetes, Shortness of breath). The odds of developing pulmonary complications were 13.90 times higher among patients with a score >2 (63% sensitivity, 88% specificity). Pulmonary complications in severe leptospirosis with kidney failure have high mortality and warrant timely and aggressive management.

Severe leptospirosis complicated with multiorgan dysfunction successfully managed with plasma exchange: a case report

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.

The concept of hemostasis disorders in severe leptospirosis

The purpose of the research to create a concept for diagnostics and therapy of hemostasis disorders of patients with severe leptospirosis.Patients and Methods. The study included 474 patients with severe serologically confirmed leptospirosis with a favorable outcome of the disease and 31 patients with fatal outcome (total 505 people). Variant of coagulopathy was determined by using a set of special methods for studying hemostasis. The influence of platelet concentrate transfusion, plasma exchange and various tactics of glucocorticoid therapy on patient survival and correction of hemostasis disorders was evaluated. Survival analysis was made using Kaplan-Meyer method with a Cox proportional intensity model. Relative risk (RR) was calculated with a 95% confidence interval (CI).Results: the use of early diagnosis of coagulopathy variants and the use of a differentiated therapy regimen in the choice of the variant of hemostasis disorder led to a decrease of mortality from 16.45% to 11.5% and decrease in the consumption of platelet concentrate and fresh frozen plasma.Conclusion: patients with severe leptospirosis develop a multivariate hemostatic pathology: isolated thrombocytopenia (38%) with thrombotic microangiopathy (20,5%), disseminated intravascular coagulopathy (37,1%), uremic coagulopathy (4,9%), hepatic coagulopathy (3,4%). Plasma exchange in thrombotic microangiopathy is pathogenetically justified. Also, plasma exchange is pathogenetically justified in order to reduce plasma volume in DIC syndrome with consumption coagulopathy and hepatic coagulopathy. The use of GCS in isolated thrombocytopenia can be effective and safe in both “medium doses” and in the form of “pulse therapy” if the following conditions are met: acute renal injury (AKI) III stage according to AKIN and the absence of renal replacement therapy (RRT). The main indication for platelet concentrate transfusion in severe leptospirosis is extremely severe thrombocytopenia (grade 4) with active life-threatening bleeding at the time of transfusion.

Comparative genome characterization of Leptospira interrogans from mild and severe leptospirosis patients

Leptospirosis is a zoonotic disease caused by spirochetes from the genus Leptospira. In Thailand, Leptospira interrogans is a major cause of leptospirosis. Leptospirosis patients present with a wide range of clinical manifestations from asymptomatic, mild infections to severe illness involving organ failure. For better understanding the difference between Leptospira isolates causing mild and severe leptospirosis, illumina sequencing was used to sequence genomic DNA in both serotypes. DNA of Leptospira isolated from two patients, one with mild and another with severe symptoms, were included in this study. The paired-end reads were removed adapters and trimmed with Q30 score using Trimmomatic. Trimmed reads were constructed to contigs and scaffolds using SPAdes. Cross-contamination of scaffolds was evaluated by ContEst16s. Prokka tool for bacterial annotation was used to annotate sequences from both Leptospira isolates. Predicted amino acid sequences from Prokka were searched in EggNOG and David gene ontology database to characterize gene ontology. In addition, Leptospira from mild and severe patients, that passed the criteria e-value < 10e-5 from blastP against virulence factor database, were used to analyze with Venn diagram. From this study, we found 13 and 12 genes that were unique in the isolates from mild and severe patients, respectively. The 12 genes in the severe isolate might be virulence factor genes that affect disease severity. However, these genes should be validated in further study.

The role of leptospiremia and specific immune response in severe leptospirosis

Leptospirosis can cause a high mortality rate, especially in severe cases. This multicenter cross-sectional study aimed to examine both host and pathogen factors that might contribute to the disease severity. A total of 217 leptospirosis patients were recruited and divided into two groups of non-severe and severe. Severe leptospirosis was defined by a modified sequential organ failure assessment (mSOFA) score of more than two or needed for mechanical ventilation support or had pulmonary hemorrhage or death. We found that leptospiremia, plasma neutrophil gelatinase-associated lipocalin (pNGAL), and interleukin 6 (IL-6) at the first day of enrollment (day 1) and microscopic agglutination test (MAT) titer at 7 days after enrollment (days 7) were significantly higher in the severe group than in the non-severe group. After adjustment for age, gender, and the days of fever, there were statistically significant associations of baseline leptospiremia level (OR 1.70, 95% CI 1.23–2.34, p = 0.001), pNGAL (OR 9.46, 95% CI 4.20–21.33, p < 0.001), and IL-6 (OR 2.82, 95% CI 1.96–4.07, p < 0.001) with the severity. In conclusion, a high leptospiremia, pNGAL, and IL-6 level at baseline were associated with severe leptospirosis.

Haemophagocytic Lymphohistiocytosis with Leptospirosis: A Rare but Devastating Complication

Introduction. Secondary haemophagocytic lymphohistiocytosis (sHLH), often associated with an array of infections, malignancies, and autoimmune diseases, is rarely seen with leptospirosis, which carries a relatively poor prognosis even with modern state-of-the-art medical care. We describe a patient with leptospirosis complicated by sHLH who succumbed to illness following multiorgan dysfunction. Case Description. A 74-year-old farmer presented with high-grade, unsettling fever for a week. Muddy water exposure and suggestive symptoms prompted investigation and management in the line of leptospirosis (IV ceftriaxone was instituted, and later, MAT (microscopic agglutination test) became positive). Subsequently, he developed severe acute hypoxemia requiring mechanical ventilation and acute renal failure requiring renal replacement therapy. Bone marrow biopsy and markedly elevated serum ferritin and triglyceride levels done on day 10 (with unresolving fever, hepatosplenomegaly, and pancytopaenia) confirmed the diagnosis of HLH. The routine cultures, retroviral studies, CMV, dengue, hanta and mycoplasma antibodies, tuberculosis and COVID-19 PCR, and malaria screening were all normal. There was no improvement of hypoxemia following intravenous methylprednisolone. He died on day 15 despite escalating organ support. Conclusion. Leptospirosis is a common zoonotic disease in the tropics with significant morbidity and mortality. In the case of severe leptospirosis, overlapping clinical features with sHLH make the diagnosis of the latter challenging. No assessment tools are available to date to predict the risk of developing sHLH in a patient having leptospirosis. Outcome following sHLH due to leptospirosis still remains majorly ominous. A high index of suspicion and low threshold for specific investigations could possibly alter the outcome following such an occurrence.

Pica (Allotriophagy): An Underestimated Risk Factor for Severe Leptospirosis (Weil’s Diseases)? Report of a Leptospira Septic Shock Successfully Managed with ECMO

Leptospirosis is a zoonosis caused by infection with pathogenic strains of the bacterium Leptospira. The disease can be complicated by pulmonary hemorrhages and acute respiratory distress syndrome, with the mortality rate increasing to 51–100%. We report the case of a 37-year-old man who was admitted to the emergency department with a 6-day history of fever, weakness, vomiting and diarrhea, followed by jaundice. On admission, he presented leukocytosis, thrombocytopenia and acute liver and kidney injuries. His clinical course was critical, as it was immediately complicated by sepsis and severe respiratory failure, requiring haemodialysis, mechanical ventilation and broad-spectrum antibiotic therapy. In the following days, a veno-venous extracorporeal membrane oxygenation (VV-ECMO) was started due to a dramatic deterioration in respiratory function; 20 h later, it was switched to veno-arterial ECMO because of refractory cardiogenic shock. Hantavirus or Leptospira infection etiology was suspected, so penicillin G and methylprednisolone were initiated as an empirical therapy and subsequently confirmed after a laboratory diagnosis of leptospirosis. Although the clinical course was further complicated by hemorrhagic pneumonia, a gradual, full recovery occurred, and the patient was discharged from the hospital. After excluding other sources of contact with Leptospira-infected material, an unsuspected abnormal eating behavior was identified as the most probable cause of the patient’s Leptospira infection.

Pathogenesis of Pulmonary Hemorrhagic Syndrome in Human Leptospirosis

Based on a previous study and by incorporating new knowledge, the goal of our study was to understand more fully the pathogenesis of hemorrhagic pneumonia of severe human leptospirosis, highlighting the onset of capillary lesions by Leptospira itself and/or its antigenic/toxic products acting on the endothelium and binding to cadherins. Both events lead to loss of endothelial integrity, alter permeability, cause rupture, and open intercellular junctions, contributing to the hemorrhagic phenomena associated with severe leptospirosis.

Predictors of Severe Leptospirosis: A Multicentre Observational Study From Central Malaysia

Background: Leptospirosis is a re-emerging disease with vast clinical presentations ranges from subclinical or mild, to severe and fatal outcomes. Though leptospirosis can be managed well if diagnosed earlier, similar clinical presentations by several other febrile illnesses or co-infections often result in mis- or underdiagnosis, thereby lead to severe illness. Identification of clinical predictors for the severe form of the disease plays a crucial role in reducing disease complication and mortality. Therefore, we aimed to determine the clinical predictors associated with severe illness among leptospirosis patients from Central Malaysia through a prospective multicenter observational study. Methods: Data were collected from case records of 83 confirmed leptospirosis patients comprising of 33 severe and 50 mild. Statistical analysis was performed using χ2 and multivariable logistic regression test with Epi info software. Results: We identified mechanical ventilation, AKI, septic shock, creatinine level of >1.13mg/dL, ALT >50IU, AST >50IU, and platelet <150 x 109/L as factors associated with severe illness. AKI, ALT >50IU and platelet <150 x 109/L were defined as the independent factors for severity. Conclusions: Lungs, liver and kidney involvement, and septic shock were found as the prognostic factors for severe leptospirosis. AKI, high level of ALT and low level of platelets were found to be independent predictors of severity.