Department of Medical Microbiology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
RAK College of Dental Sciences, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates.
PLoS Negl Trop Dis. 2022 May 18;16(5):e0010409. doi: 10.1371/journal.pntd.0010409. eCollection 2022 May.
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.
严重的钩端螺旋体病具有挑战性，因为如果不进行适当的治疗，它可能会迅速发展并导致潜在的致命后果。了解钩端螺旋体感染的进展和病理生理学对于确定可能用于预测严重钩端螺旋体病的早期变化非常重要。本研究旨在了解 HP358 株问号钩端螺旋体在仓鼠模型中的发病动力学，并确定可作为预测严重钩端螺旋体病的生物标志物的早期参数。
方法/主要发现：雄性叙利亚仓鼠感染 HP358 株问号钩端螺旋体，感染后 24 小时、3 天、4 天、5 天、6 天和 7 天安乐死。采集血液、肺、肝和肾进行钩端螺旋体检测、血液学、血清生化和促炎与抗炎标志物的差异表达。研究宏观和微观器官损伤。HP358 株问号钩端螺旋体具有高度致病性，感染后 6-7 天内杀死仓鼠。肺部出血和器官血管充血是最早的病理变化。器官损伤和生化值变化先于血液学和免疫基因表达变化。
结论/意义：本研究揭示出血是严重钩端螺旋体病的最早表现，高水平的 IL-1β、CXCL10/IP-10、CCL3/MIP-α、中性粒细胞和低水平的淋巴细胞和血小板作为严重钩端螺旋体病的累积生物标志物组合。
