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Histopathology of Bordetella pertussis in the Baboon Model
Lindsey I Zimmerman1, James F Papin2, Jason Warfel1
1Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Insights
This study reveals baboons with pertussis (whooping cough) develop lung inflammation similar to human infant cases. The baboon model offers insights into severe, nonfatal pertussis pathology.
Area of Science:
- Infectious Diseases
- Pathology
- Animal Models
Background:
- Pertussis, caused by *Bordetella pertussis*, is a severe respiratory illness, particularly in infants.
- Human infant pertussis pathology is primarily studied from fatal cases.
- A baboon model offers a unique opportunity to study severe, nonfatal pertussis histopathology.
Purpose of the Study:
- To investigate the histopathology of severe but nonfatal pertussis in a baboon model.
- To compare baboon pertussis pathology with findings from fatal human infant cases.
- To understand the inflammatory response and bacterial localization in the baboon airway.
Main Methods:
- Utilized a baboon model to study pertussis.
- Examined histopathology in 5- to 6-week-old baboons.
- Employed immunohistostaining to localize *Bordetella pertussis*.
Main Results:
- Baboon pertussis recapitulates human clinical signs, including coughing and airway colonization.
- Juvenile baboons exhibited severe lung inflammation, resembling acute respiratory distress syndrome (ARDS) and bronchopneumonia.
- Tracheal pathology was limited to inflammation and mucus, while bacteria localized to the ciliated epithelium.
Conclusions:
- The baboon model effectively mimics severe, nonfatal human pertussis.
- Findings provide crucial insights into the lung-centric inflammatory pathology of pertussis.
- This model is valuable for studying the disease mechanisms and potential interventions for pertussis.
Abstract:
Pertussis is a severe respiratory disease caused by Bordetella pertussis 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.
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