Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Oklahoma Baboon Research Resource, Comparative Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Infect Immun. 2018 Oct 25;86(11). doi: 10.1128/IAI.00511-18. Print 2018 Nov.
Pertussis is a severe respiratory disease caused by The classic symptoms of pertussis include paroxysmal coughing with an inspiratory whoop, posttussive vomiting, cyanosis, and persistent coryzal symptoms. Infants under 2 months of age experience more severe disease, with most deaths occurring in this age group. Most of what is known about the pathology of pertussis in humans is from the evaluation of fatal human infant cases. The baboon model of pertussis provides the opportunity to evaluate the histopathology of severe but nonfatal pertussis. The baboon model recapitulates the characteristic clinical signs of pertussis observed in humans, including leukocytosis, paroxysmal coughing, mucus production, heavy colonization of the airway, and transmission of the bacteria between hosts. As in humans, baboons demonstrate age-related differences in clinical presentation, with younger animals experiencing more severe disease. We examined the histopathology of 5- to 6-week-old baboons, with the findings being similar to those reported for fatal human infant cases. In juvenile baboons, we found that the disease is highly inflammatory and concentrated to the lungs with signs of disease that would typically be diagnosed as acute respiratory distress syndrome (ARDS) and bronchopneumonia. In contrast, no significant pathology was observed in the trachea. Histopathological changes in the trachea were limited to cellular infiltrates and mucus production. Immunohistostaining revealed that the bacteria were localized to the surface of the ciliated epithelium in the conducting airways. Our observations provide important insights into the pathology of pertussis in typical, severe but nonfatal pertussis cases in a very relevant animal model.
百日咳是一种严重的呼吸道疾病,由 百日咳的典型症状包括阵发性咳嗽伴吸气性哮鸣、咳嗽后呕吐、发绀和持续的卡他症状。2 个月以下的婴儿患该病更严重,大多数死亡发生在这个年龄段。人类对百日咳病理学的了解大多来自对致命的人类婴儿病例的评估。狨猴百日咳模型为评估严重但非致命的百日咳的组织病理学提供了机会。狨猴模型重现了人类百日咳观察到的特征性临床体征,包括白细胞增多、阵发性咳嗽、黏液产生、气道重度定植和细菌在宿主之间传播。与人类一样,狨猴在临床表现上存在与年龄相关的差异,年幼的动物患更严重的疾病。我们检查了 5-6 周大的狨猴的组织病理学,发现与报告的致命人类婴儿病例相似。在幼年狨猴中,我们发现疾病高度炎症,集中在肺部,有典型的急性呼吸窘迫综合征(ARDS)和支气管肺炎的疾病迹象。相比之下,气管没有明显的病变。气管的组织病理学变化仅限于细胞浸润和黏液产生。免疫组化染色显示细菌定位于传导气道的纤毛上皮表面。我们的观察结果为典型、严重但非致命的百日咳病例在非常相关的动物模型中的百日咳病理学提供了重要的见解。