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在普通狨猴(绢毛猴)中建立土拉弗朗西斯菌致死性吸入感染(兔热病)

Establishment of lethal inhalational infection with Francisella tularensis (tularaemia) in the common marmoset (Callithrix jacchus).

作者信息

Nelson Michelle, Lever Mark S, Savage Victoria L, Salguero Francisco Javier, Pearce Peter C, Stevens Daniel J, Simpson Andrew J H

机构信息

Biomedical Sciences, Defence Science and Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire, UK.

出版信息

Int J Exp Pathol. 2009 Apr;90(2):109-18. doi: 10.1111/j.1365-2613.2008.00631.x.

Abstract

Susceptibility and lethality studies of inhalational tularaemia were undertaken using the common marmoset (Callithrix jacchus) to determine its suitability as a non-human primate model. Pairs of marmosets were exposed to varying challenge doses of Francisella tularensis by the airborne route and monitored for up to 14 days postchallenge (p.c.). Lethal infection was achieved following a retained dose of less than 10 bacterial colony-forming units (CFU). However, precise LD(50) determination was not possible. The model was characterized using a target challenge dose of approximately 100 CFU. Increased core body temperature was the first indicator of disease, at approximately 2.5 days p.c. Overt clinical signs were first observed 12-18 h after the temperature increase. Significantly decreased activity was observed after approximately 3 days. All animals succumbed to infection between 4.5 and 7 days p.c. At postmortem examination, gross pathology was evident in the liver, spleen and lungs of all animals and high bacterial numbers were detected in all the organs assessed. Bacteraemia was demonstrated in all animals postmortem. Histopathological observations included severe suppurative bronchopneumonia, severe multifocal pyogranulomatous hepatitis, splenitis and lymphadenitis. Tularaemia disease progression in the common marmoset therefore appears to be consistent with the disease seen in humans and other animal models. The common marmoset may therefore be considered a suitable model for further studies of inhalational tularaemia.

摘要

利用普通狨猴(Callithrix jacchus)进行了吸入性兔热病的易感性和致死性研究,以确定其作为非人灵长类动物模型的适用性。将成对的狨猴通过空气传播途径暴露于不同剂量的土拉弗朗西斯菌,并在攻毒后(p.c.)长达14天进行监测。在保留剂量小于10个细菌菌落形成单位(CFU)后实现了致死性感染。然而,无法精确测定半数致死剂量(LD50)。该模型使用约100 CFU的目标攻毒剂量进行表征。核心体温升高是疾病的首个指标,约在攻毒后2.5天出现。在体温升高后12 - 18小时首次观察到明显的临床症状。约3天后观察到活动显著减少。所有动物在攻毒后4.5至7天内均死于感染。尸检时,所有动物的肝脏、脾脏和肺部均出现明显的大体病理学变化,在所有评估的器官中均检测到大量细菌。所有动物死后均证实有菌血症。组织病理学观察包括严重的化脓性支气管肺炎、严重的多灶性脓性肉芽肿性肝炎、脾炎和淋巴结炎。因此,普通狨猴的兔热病疾病进展似乎与人类和其他动物模型中所见的疾病一致。因此,普通狨猴可被认为是进一步研究吸入性兔热病的合适模型。

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