Abstract
BackgroundParameters predicting the evolution of leptospirosis would be useful for clinicians, as well as to better understand severe leptospirosis, but are scarce and rarely validated. Because severe leptospirosis includes septic shock, similarities with predictors evidenced for sepsis and septic shock were studied in a hamster model.Methodology/Principal FindingsUsing an LD50 model of leptospirosis in hamsters, we first determined that 3 days post-infection was a time-point that allowed studying the regulation of immune gene expression and represented the onset of the clinical signs of the disease. In the absence of tools to assess serum concentrations of immune effectors in hamsters, we determined mRNA levels of various immune genes, especially cytokines, together with leptospiraemia at this particular time-point. We found differential expression of both pro- and anti-inflammatory mediators, with significantly higher expression levels of tumor necrosis factor α, interleukin 1α, cyclo-oxygenase 2 and interleukin 10 genes in nonsurvivors compared to survivors. Higher leptospiraemia was also observed in nonsurvivors. Lastly, we demonstrated the relevance of these results by comparing their respective expression levels using a LD100 model or an isogenic high-passage nonvirulent variant.Conclusions/SignificanceUp-regulated gene expression of both pro- and anti-inflammatory immune effectors in hamsters with fatal outcome in an LD50 model of leptospirosis, together with a higher Leptospira burden, suggest that these gene expression levels could be predictors of adverse outcome in leptospirosis.
Highlights
Leptospirosis is the most widespread zoonosis occurring worldwide with possible fatal outcomes [1]
We used a hamster model of leptospirosis to evaluate if immune genes were differentially expressed between individuals and if their expression levels could help forecast the outcome of the disease
We found that hamsters that later died from leptospirosis had significantly higher expression levels of both pro- and antiinflammatory mediators compared to survivors
Summary
Leptospirosis is the most widespread zoonosis occurring worldwide with possible fatal outcomes [1]. Though most often an endemic disease, epidemics have been associated with particular meteorological events [2,3,4] or clusters of cases related to occupations or leisure activities [5,6,7,8] It is notably highly prevalent in tropical areas, but some of the clusters of cases have been reported in temperate countries [7,8]. Validated prognostic factors to help forecast the evolution of a leptospirosis are scarce. They would be valuable for clinicians to decide whether their patients should only be treated with antibiotics, kept at the hospital in a standard unit or directed to an intensive care unit. Because severe leptospirosis includes septic shock, similarities with predictors evidenced for sepsis and septic shock were studied in a hamster model
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