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Clinical and Pathologic Changes in a Guinea Pig Aerosol Challenge Model of Acute Q Fever

机译:急性Q病豚鼠气溶胶激发模型的临床和病理变化

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Acute Q fever is a zoonotic disease caused by the obligate intracellular bacterium Coxiella burnetii and can manifest as a flu-like illness, pneumonia, or hepatitis. A need exists in Q fever research for animal models mimicking both the typical route of infection (inhalation) and the clinical illness seen in human cases of Q fever. A guinea pig aerosol challenge model was developed using C. burnetii Nine Mile phase I (RSA 493), administered using a specialized chamber designed to deliver droplet nuclei directly to the alveolar spaces. Guinea pigs were given 101 to 106 organisms and evaluated for 28 days postinfection. Clinical signs included fever, weight loss, respiratory difficulty, and death, with the degree and duration of response corresponding to the dose of organism delivered. Histopathologic evaluation of the lungs of animals infected with a high dose showed coalescing panleukocytic bronchointerstitial pneumonia at 7 days postinfection that resolved to multifocal lymphohistiocytic interstitial pneumonia by 28 days. Guinea pigs receiving a killed whole-cell vaccine prior to challenge with the highest dose of C. burnetii were protected against lethal infection and did not develop fever. Clinical signs and pathological changes noted for these guinea pigs were comparable to those seen in human acute Q fever, making this an accurate and valuable animal model of human disease.
机译:急性Q发烧是一种专一性的细胞内细菌 burnetii 引起的人畜共患疾病,可表现为流感样疾病,肺炎或肝炎。 Q发烧研究需要模仿人类感染Q烧的典型感染途径(吸入)和临床疾病的动物模型。使用 C开发了豚鼠气溶胶激发模型。九英里第一阶段(RSA 493),使用专门设计的腔室进行管理,该腔室旨在将液滴核直接传递到肺泡腔。给豚鼠10 1 至10 6 生物,并在感染后28天进行评估。临床体征包括发烧,体重减轻,呼吸困难和死亡,其反应程度和持续时间与所输送的生物剂量相对应。对被高剂量感染的动物的肺进行的组织病理学评估显示,感染后7天会合并全白细胞性支气管间质性肺炎,到28天时可分解为多灶性淋巴组织细胞性间质性肺炎。豚鼠在攻击前以最大剂量的C接受灭活的全细胞疫苗。 Burnetii 可以防止致命感染,并且不会发烧。这些豚鼠的临床体征和病理变化与人类急性Q发烧中观察到的相当,这使其成为一种准确而有价值的人类疾病动物模型。

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