Frick Ondraya M, Livingston Virginia A, Whitehouse Chris A, Norris Sarah L, Alves Derron A, Facemire Paul R, Reed Douglas S, Nalca Aysegul
Veterinary Medicine Division, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD 21702, USA.
Naval Medical Research Center, Undersea Medicine Department, Silver Spring, MD 20910, USA.
Pathogens. 2021 May 13;10(5):597. doi: 10.3390/pathogens10050597.
Tularemia is a severe, zoonotic infection caused by the Gram-negative bacterium . Inhalation results in a rapid, severe bacterial pneumonia and sepsis, which can be lethal. Because the cynomolgus macaque is the accepted nonhuman primate model for tularemia, we conducted a natural history study of pneumonic tularemia by exposing macaques to target inhaled doses of 50, 500, or 5000 colony forming units (CFU) of subsp. tularensis SCHU S4. Two animals within the 50 CFU group (calculated doses of 10 and 11 CFU) survived the challenge, while the remainder succumbed to infection. Exposure of cynomolgus macaques to aerosolized SCHU S4 resulted in fever, anorexia, increased white blood cell counts, lymphopenia, thrombocytopenia, increased liver enzymes, alterations in electrocardiogram (ECG), and pathological changes typical of infection with , regardless of the challenge dose. Blood pressure dropped during the febrile phase, particularly as temperature began to drop and macaques succumbed to the disease. ECG analysis indicated that in 33% of the macaques, heart rate was not elevated during the febrile phase (Faget's sign; pulse-temperature disassociation), which has been reported in a similar percentage of human cases. These results indicated that infection of cynomolgus macaques with aerosolized results in similar disease progression and outcome as seen in humans, and that cynomolgus macaques are a reliable animal model to test medical countermeasures against aerosolized .
兔热病是由革兰氏阴性菌引起的一种严重的人畜共患感染病。吸入该病菌会导致快速、严重的细菌性肺炎和败血症，可能会致命。由于食蟹猕猴是公认的兔热病非人灵长类动物模型，我们通过让猕猴吸入目标剂量为50、500或5000个土拉弗朗西斯菌亚种SCHU S4菌落形成单位（CFU），开展了肺型兔热病的自然史研究。50 CFU组中的两只动物（计算剂量为10和11 CFU）在此次挑战中存活下来，而其余动物均死于感染。无论挑战剂量如何，将食蟹猕猴暴露于雾化的SCHU S4中都会导致发热、厌食、白细胞计数增加、淋巴细胞减少、血小板减少、肝酶升高、心电图（ECG）改变以及土拉弗朗西斯菌感染的典型病理变化。在发热阶段血压下降，尤其是当体温开始下降且猕猴死于该病时。心电图分析表明，33%的猕猴在发热阶段心率未升高（法热氏征；脉搏-体温解离），在类似比例的人类病例中也有此报道。这些结果表明，雾化的土拉弗朗西斯菌感染食蟹猕猴会导致与人类相似的疾病进展和结果，并且食蟹猕猴是测试针对雾化土拉弗朗西斯菌的医学对策的可靠动物模型。
