以非洲绿猴原发性肺鼠疫作为治疗效果评估模型。
Primary pneumonic plague in the African Green monkey as a model for treatment efficacy evaluation.
作者信息
Layton R Colby, Brasel Trevor, Gigliotti Andrew, Barr Edward, Storch Steven, Myers Leslie, Hobbs Charles, Koster Frederick
机构信息
Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
出版信息
J Med Primatol. 2011 Feb;40(1):6-17. doi: 10.1111/j.1600-0684.2010.00443.x. Epub 2010 Aug 16.
BACKGROUND
Primary pneumonic plague is rare among humans, but treatment efficacy may be tested in appropriate animal models under the FDA 'Animal Rule'.
METHODS
Ten African Green monkeys (AGMs) inhaled 44-255 LD(50) doses of aerosolized Yersinia pestis strain CO92. Continuous telemetry, arterial blood gases, chest radiography, blood culture, and clinical pathology monitored disease progression.
RESULTS
Onset of fever, >39°C detected by continuous telemetry, 52-80 hours post-exposure was the first sign of systemic disease and provides a distinct signal for treatment initiation. Secondary endpoints of disease severity include tachypnea measured by telemetry, bacteremia, extent of pneumonia imaged by chest x-ray, and serum lactate dehydrogenase enzyme levels.
CONCLUSIONS
Inhaled Y. pestis in the AGM results in a rapidly progressive and uniformly fatal disease with fever and multifocal pneumonia, serving as a rigorous test model for antibiotic efficacy studies.
背景
原发性肺鼠疫在人类中较为罕见，但可根据美国食品药品监督管理局的“动物规则”，在合适的动物模型中测试治疗效果。
方法
十只非洲绿猴吸入44 - 255半数致死剂量（LD50）的雾化鼠疫耶尔森菌CO92菌株。通过连续遥测、动脉血气分析、胸部X光摄影、血培养和临床病理学监测疾病进展。
结果
暴露后52 - 80小时，通过连续遥测检测到体温超过39°C发热，这是全身性疾病的首个迹象，也是开始治疗的明显信号。疾病严重程度的次要终点包括通过遥测测量的呼吸急促、菌血症、胸部X光成像的肺炎范围以及血清乳酸脱氢酶水平。
结论
非洲绿猴吸入鼠疫耶尔森菌会导致迅速进展且一致致命的疾病，伴有发热和多灶性肺炎，可作为抗生素疗效研究的严格测试模型。
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