Department of Bacteriology, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Department of Pathology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.
Microbiology (Reading). 2014 Feb;160(Pt 2):418-428. doi: 10.1099/mic.0.072439-0. Epub 2013 Nov 20.
Leptospirosis is caused by pathogenic species of Leptospira. The aim of this study was to determine and characterize the pathogenicity of four dominant Leptospira isolates prevailing among rats in the Philippines. The isolates were Leptospira interrogans serovar Manilae strain K64, L. interrogans serovar Losbanos strain K37, L. interrogans serovar Ratnapura strain K5 and Leptospira borgpetersenii serovar Javanica strain K6. Pathogenicities were studied using hamsters, which reproduce severe human leptospirosis. The minimum lethal doses were 10(0) ( = 1) leptospires for K64, K37 and K5, and 10(1) leptospires for K6. Weight loss amongst the Leptospira-infected hamsters was observed from 1 day before death (K64-, K37- and K5-infected hamsters) to as much as 1 week before death for K6-infected hamsters. Similar and varied gross and microscopic lesions were observed amongst infected hamsters, even for strains belonging to the same species (i.e. L. interrogans). The most significant and common histopathological findings were congestion of the glomerulus, disarrangement of hepatic cords and erythrophagocytosis. Other findings were foamy splenic macrophages for K6, severe petechial pulmonary haemorrhage for K64, and hematuria and severe pulmonary congestion for K37. Immunostaining and culture revealed the presence of leptospires in different organs of the infected hamsters. Based on these results, Leptospira isolates from rats in the Philippines were shown to be highly virulent, causing pulmonary haemorrhage, severe hepato-renal damage and death in hamsters even at lower doses. The present findings on experimental leptospirosis support clinical data showing that patients with severe manifestations of leptospirosis, such as pulmonary haemorrhage, are increasing in the Philippines. These findings may serve as a basis to strengthen the early diagnosis and treatment of human leptospirosis.
钩端螺旋体病是由致病性钩端螺旋体引起的。本研究旨在确定和描述在菲律宾流行的四种主要的钩端螺旋体分离株的致病性。这些分离株是问号钩端螺旋体血清型 Manilae 株 K64、问号钩端螺旋体血清型 Losbanos 株 K37、问号钩端螺旋体血清型 Ratnapura 株 K5 和伯氏钩端螺旋体血清型 Javanica 株 K6。使用仓鼠研究了致病性,仓鼠可重现严重的人类钩端螺旋体病。K64、K37 和 K5 的最小致死剂量为 10(0) ( = 1) 钩端螺旋体,K6 的最小致死剂量为 10(1) 钩端螺旋体。K64-、K37-和 K5 感染的仓鼠在死亡前 1 天开始出现体重减轻,而 K6 感染的仓鼠在死亡前 1 周体重减轻。即使对于同一物种(即问号钩端螺旋体)的菌株,感染仓鼠的大体和微观病变也相似且多样。最显著和常见的组织病理学发现是肾小球充血、肝索排列紊乱和红细胞吞噬作用。其他发现包括 K6 的脾泡沫巨噬细胞、K64 的严重点状肺出血、K37 的血尿和严重肺充血。免疫染色和培养显示感染仓鼠的不同器官中有钩端螺旋体的存在。基于这些结果,菲律宾大鼠的钩端螺旋体分离株被证明具有高度的毒力,即使在较低剂量下,也能导致仓鼠发生肺出血、严重肝肾功能损害和死亡。本实验性钩端螺旋体病的发现支持临床数据,表明菲律宾严重表现的钩端螺旋体病(如肺出血)患者正在增加。这些发现可以为加强人类钩端螺旋体病的早期诊断和治疗提供依据。