Leptospirosis is a globally distributed zoonotic disease caused by the pathogenic species of Leptospira, a genus of spirochete bacteria. Although this disease has a worldwide distribution, it is more common in the tropics due to its favorable transmission condition. In Malaysia, leptospirosis is an endemic disease. Occasional outbreaks have been reported and are mainly associated with forest and water activities, flood and crowded living environment [1–5].
The clinical presentation of leptospirosis varies from mild to severe, life-threatening and fatal outcomes. The symptoms are diverse, generally include fever and often shares presentations with other infectious diseases, such as malaria, dengue, and influenza. About 90% of leptospirosis is a subclinical or self-limited febrile illness, while the severe form is presented by sepsis and multiple organ failures . The most severe form of leptospirosis is Weil’s disease, seen in 5–15% of infected cases and typically involves multiple organs damages accompanied with jaundice, acute renal failure and hemorrhage and has a fatality rate of more than 10% [7, 8]. However, leptospirosis cases with lung involvement presenting with acute respiratory distress syndrome (ARDS) or severe pulmonary hemorrhage syndrome (SPHS) have the highest mortality rates of over 70% . The presentation of leptospirosis appears to be distinct in different geographical areas worldwide . This is particularly true as different geographical location may have different prevailing Leptospira species and serovars. The variations of intrinsic virulence among serovars and species have been asserted to partially explain the disease severity of mild and severe forms of leptospirosis . These differences may also lead to specific predictors of severe disease and mortality.
The two-extreme manifestation of leptospirosis which are mild/subclinical and severe illness with mortality cautions that the disease should not be taken lightly, and constant monitoring of patients is essential. For constant monitoring, it is important to determine the prognostic markers, but it is still not clear what factors that predict the transition from mild to severe/fatal illness. Several independent prognostic factors for fatal leptospirosis have been reported across the globe and these include older age, oliguria, hyperkalaemia, abnormal serum creatinine level, ARDS, pulmonary haemorrhage, elevated bilirubin level, hypotension, arrhythmia and altered mental status [8, 10, 11].
Earlier studies from Malaysia identified elevated levels of cytokines such as IL-6, IL17A and IL-22 as potential prognostic biomarkers with IL-17A as the independent predictor for leptospirosis associated fatalities . Another study conducted in a suburban area in Malaysia identified age above 70, clinical presentations suggestive of organ dysfunction and intensive care requirement as predictors for fatalities . Fish Low et al. (2020) reported hypocalcemia (calcium < 2.10 mmol/L), hypochloremia (chloride < 98 mmol/L), and eosinopenia (absolute eosinophil count < 0.040 × 109/L as clinical predictors for laboratory-confirmed leptospirosis when compared with clinically suspected leptospirosis cases . Analysis of a set of data for clinically diagnosed leptospirosis cases in a tertiary care hospital in Malaysia showed gastrointestinal tract (GIT) presentation as one of the predictors for severe illness, the study also found that GIT symptoms are significantly associated with age (20–40 yrs), poor sanitation and crowded living environment of the patients .
In the present investigation, we performed a multicentered observational study to identify factors predictive of severe leptospirosis. Determining the predictors at early stage of the disease could greatly reduce the severe illness development and thereby mortality.