Pulmonary haemorrhage as the earliest sign of severe leptospirosis in hamster model challenged with Leptospira interrogans strain HP358

Severe leptospirosis is challenging as it could evolve rapidly and potentially fatal if appropriate management is not performed. An understanding of the progression and pathophysiology of Leptospira infection is important to determine the early changes that could be potentially used to predict the severe occurrence of leptospirosis. This study aimed to understand the kinetics pathogenesis of Leptospira interrogans strain HP358 in the hamster model and identify the early parameters that could be used as biomarkers to predict severe leptospirosis.

Methodology/Principal findings
Male Syrian hamsters were infected with Leptospira interrogans strain HP358 and euthanized after 24 hours, 3, 4, 5, 6 and 7 days post-infection. Blood, lungs, liver and kidneys were collected for leptospiral detection, haematology, serum biochemistry and differential expression of pro- and anti-inflammatory markers. Macroscopic and microscopic organ damages were investigated. Leptospira interrogans strain HP358 was highly pathogenic and killed hamsters within 6–7 days post-infection. Pulmonary haemorrhage and blood vessel congestion in organs were noticed as the earliest pathological changes. The damages in organs and changes in biochemistry value were preceded by changes in haematology and immune gene expression.

Conclusion/Significance
This study deciphered haemorrhage as the earliest manifestation of severe leptospirosis and high levels of IL-1β, CXCL10/IP-10, CCL3/MIP-α, neutrophils and low levels of lymphocytes and platelets serve as a cumulative panel of biomarkers in severe leptospirosis.

Author summary
As the severe form of leptospirosis could progress rapidly and be potentially fatal if not treated earlier, deciphering the pathophysiology kinetics of infection is crucial to determine the parameters of disease severity. To understand this, we challenged hamsters with the highly virulent Leptospira interrogans strain HP358. Pulmonary haemorrhage was observed as the earliest pathological change followed by liver and kidneys damages. The increased expression of IL-1β, CXCL10/IP-10, CCL3/MIP-α, high neutrophils and low lymphocytes and platelets production observed in the present study indicate that these parameters could serve as a cumulative panel of biomarkers in severe leptospirosis.