Abstract:
Background: Leptospirosis is a neglected zoonotic disease which is a major challenge for clinicians and public
health professionals in tropical countries. The cytokine storm during the second (immune) phase is thought to be a
major contributory factor for the leptospirosis disease severity. We aim to summarize evidence for cytokine
response in leptospirosis at different clinical outcomes.
Methods: A systematic review was carried out to examine the cytokine response in leptospirosis patients using relevant
scientific databases. Reference lists of the selected articles were also screened. Quality of the selected studies was assessed
by using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.
Results: Of the 239 articles retrieved in the initial search, 18 studies fulfilled the selection criteria. India and Thailand have
produced the highest number of studies (17% each, n = 3). The majority were comparative cross-sectional studies (72%,
n = 13). Overall the quality of the selected studies was fair regardless of few drawbacks such as reporting of sample size
and the lack of adjustment for confounders. Microscopic agglutination test (67% - 12/18) and enzyme-linked
immunosorbent assay (50% - 9/18) were commonly used for the confirmation of leptospirosis and the measurement of
cytokines respectively. IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10 and TNF-α levels were found to be significantly higher in severe than
in mild leptospirosis. There were equivocal findings on the association between IL-1β, TNF-α and IL-10/TNF-α ratio and
disease severity.
Conclusions: Leptospirosis had a wide-range of elevated cytokines. However, prospective studies in-relation to the onset
of the symptom are required to better understand the pathophysiology of cytokine response in leptospirosis.
Keywords: Cytokines, Chemokines, MAT assay, ELISA, Severe leptospirosis, Weil’s disease
