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

Abstract

Background 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.

Impaired functions of human monocyte-derived dendritic cells and induction of regulatory T cells by pathogenic Leptospira

“…These observations are in line with our findings, as we observed decreased T cell proliferation and induction of Tregs in response to PTGS2 -expressing MoDCs-P. Moreover, previous studies demonstrated an upregulation of PTGS2 expression in the blood and target organs of hamsters infected with pathogenic leptospires [ 32 , 33 ]. Additionally, prior research has shown that the combination of PGE2 and IL-10 production can convert naïve CD4 + T cells into Tregs [ 34 – 36 ].…”

A Paternal Fish Oil Diet Preconception Reduces Lung Inflammation in a Toxicant-Driven Murine Model of New Bronchopulmonary Dysplasia

“…At the time of necropsy the whole lung was quickly removed from the chest cavity and immediately photographed. This photograph was used to assess lung hemorrhaging via gross analyses (e.g., coagulation of blood at the surface of the lung or discoloration) as previously described [ 48 , 49 ]. Next, the right lobe of the lung was excised from the whole lung and weighed.…”

Leptospirosis, An Unusual Differential of Diffuse Alveolar Haemorrhage (DAH) in a Non-Tropical ITU- A Case Report

“…Diffuse severe patchy bilateral ground glass opacities, pulmonary consolidative changes, peribronchovascular nodules and peri bronchial thickening. 10 . This patient, who even though had a severe pulmonary involvement, did not have the same severity of involvement of other organs such as kidney or liver which again is an unusual picture when we consider Weil's disease 11,12 .…”

“…A delay in diagnosis and treatment may lead to increased disease severity and mortality 8 . In this case report, we present a 25-year-old gentleman who had pulmonary hemorrhage as the earliest sign of severe leptospirosis without severe renal or hepatic involvement, which is a rare occurrence by itself 10,11 .…”