Leptospirosis presents a significant health challenge in the Transcarpathian region of Ukraine, with higher incidence rates and mortality compared to national averages. We conducted a retrospective cohort study to investigate the effects of antibiotic and steroid treatments on outcomes in leptospirosis patients. Our analysis of clinical and laboratory data from a single center revealed that dexamethasone showed significant effects on various clinical variables, as did investigated antibiotics. Particularly, direct bilirubin levels emerged as a strong predictor of death. These findings provide valuable insights for clinicians in managing leptospirosis, aiding in outcome prediction and treatment decision-making not only in the Transcarpathian region but globally.

Leptospirosis, a disease primarily found in tropical regions, is a zoonotic illness transmitted through contact with the urine of animals, particularly rats [1]. Its clinical manifestations range from mild to severe, posing life-threatening consequences. Symptoms often mimic those of other infectious diseases, such as influenza [2]. Severe cases, affecting approximately 5% to 15% of individuals, manifest with acute renal failure, acute respiratory distress syndrome, pulmonary issues, hypotension, icterus, and altered mental status [3-7].

In the Transcarpathian region, leptospirosis persists as a prevalent zoonotic disease. Between 2005 and 2015, 420 cases were reported, with an incidence three times higher than the national average. The case fatality rate (CFR) for leptospirosis in Transcarpathia averages 12.5%, exceeding the national level of 9.8% [8-10].

Analysis reveals a significant increase in the notification rate of leptospirosis in Ukraine in 2023. This surge is primarily attributed to the rising incidence of leptospirosis in Transcarpathia, accounting for 150 cases out of the total 433 in Ukraine, and the Ivano-Frankivsk region, contributing 34 cases [11] (Figure 1).

Pathogenic Leptospira, responsible for the disease, are excreted in the urine of rats, with humans inadvertently becoming hosts and facing potentially life-threatening consequences [7]. Rats, however, remain immune to fatal infection, serving as natural reservoirs. Most human leptospiral infections are either mild or asymptomatic. Those who do develop the illness typically experience an abrupt onset of symptoms, including fever, rigors, myalgias, and headache [6, 9].

The disease unfolds in two phases [12]. The initial phase involves an acute febrile bacteraemia lasting 2 to 9 days, followed by a period of reduced or no fever and apparent improvement. The second phase, known as the “immune” phase, is characterised by renewed fever and the emergence of complications. Approximately 5%–15% of patients may progress to Weil’s disease, with pulmonary involvement being a notable feature (20%–70%) [7]. Pulmonary complications range from mild cough to severe symptoms like haemoptysis and Acute respiratory distress syndrome (ARDS), the latter carrying a high mortality rate of around 50% [13-15].

The role of corticosteroids in treating severe leptospirosis, especially in addressing pulmonary complications like ARDS, has been explored in a limited number of studies. The argument posits that multi-organ failure in leptospirosis may result from an overactive immune system rather than the direct effects of the pathogen [16]. Therefore, the use of therapeutic doses of steroids is considered to counteract immune activation, potentially reducing mortality and morbidity in severe leptospirosis cases [17]. However, the efficacy of corticosteroids remains uncertain due to the scarcity of studies.

This study aims to investigate the effects of antibiotic and steroid treatment on outcomes in patients diagnosed with leptospirosis within the Transcarpathian Region of Ukraine. Through a retrospective analysis of clinical and laboratory data from a single-center cohort, we aim to assess the impact of these treatments on patient morbidity and mortality rates. Additionally, we aim to explore potential associations between treatment regimens and clinical outcomes, thereby providing significant contributions to the understanding and management of leptospirosis in this geographical area.

2.1. Study design and diagnostic criteria

We conducted a retrospective single-center cohort study. All medical records were obtained from the Transcarpathian Regional Clinical Infectious Diseases Hospital, Ukraine. Confirmation of diagnosis was determined by the order of the Ministry of Health of Ukraine No. 905 of December 28, 2015. This includes fever or at least two of the following symptoms: chills, headache, myalgia, conjunctival hyperemia, skin and mucous membrane hemorrhages, rash, jaundice, myocarditis, meningitis, kidney failure, respiratory manifestations such as hemoptysis, and laboratory confirmation by Polymerase Chain Reaction (PCR) or MAT (Microscopic Agglutination Test).

Inclusion Criteria

Patients included in this study met the following criteria: diagnosed with leptospirosis according to the criteria outlined by the Ministry of Health of Ukraine; with medical records available at the Transcarpathian Regional Clinical Infectious Diseases Hospital; confirmed laboratory diagnosis by PCR or MAT; complete clinical and laboratory data for analysis; aged 18 years and older; and non-pregnant.

Exclusion Criteria

Patients were excluded from the study if they met any of the following criteria: incomplete medical records or missing key diagnostic information; incomplete or inconsistent laboratory confirmation results; history of receiving medications that could interfere with the study variables or outcomes; younger than 18 years old; or pregnant.

2.2. Patient Stratification and Grouping

We have grouped these patients into different groups for comparing clinical and laboratory data. Firstly, based on sex, males (n=27) and females (n=11). Secondly, based on steroid treatments, the majority received dexamethasone 8 mg per day (n=29), while a few received methylprednisolone 250 mg per day (n=2), and others included patients prescribed prednisolone 1 mg/kg/day or combination steroid types (n=4), with 3 patients not receiving steroids. Next, we grouped the patients based on antibiotic treatment into large groups, i.e. those treated with cephalosporins (n=17), benzylpenicillins (n=8), and others treated with carbapenems or macrolides (n=13). Finally, the patients were also grouped based on outcomes, i.e. 35 survivors and 3 non-survivors.

2.3. Statistical analysis

Power analysis was conducted to ascertain the appropriate sample size necessary to detect statistically significant effects or differences in our study variables, while maintaining a desired level of statistical power.

Quantitative variables following a non-normal distribution were described using the median (Me) and lower and upper quartiles (Q1 – Q3). Categorical data were described using absolute and relative frequencies. Comparisons of three or more groups on a quantitative variable with a distribution differing from normality were made using the Kruskal-Wallis test, with Dunn’s criterion and Holm correction applied as a post hoc method. The Wilcoxon test was employed for comparing quantitative variables following a non-normal distribution between two matched samples. The Mann-Whitney U-test was used to compare two groups on a quantitative variable with a distribution differing from normality. Frequencies in the analysis of multifield contingency tables were compared using Pearson’s chi-square test. ROC analysis was utilized to assess the diagnostic performance of quantitative variables in predicting a categorical outcome. The optimal cut-off value of the quantitative variable was estimated using Youden’s J statistic.

Statistical significance was determined at p < 0>