Pathology and Pathogenesis of Fatal Bordetella pertussis Infection in Infants
1Infectious Disease Pathology Branch and 2Office of the Director, Division of Viral and Rickettsial Diseases, and 3Meningitis and Vaccine‐Preventable Diseases Branch, Centers for Disease Control and Prevention, and 4Department of Pathology, Emory University School of Medicine, Atlanta, Georgia; 5Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles; and 6Department of Pathology, Texas Children’s Hospital and Baylor College of Medicine, Houston
Background.
Each year, Bordetella pertussis infection causes an estimated 294,000 deaths worldwide, primarily among young, nonvaccinated children. Approximately 90% of all deaths due to pertussis in the Unites States occur in young infants. These children often develop intractable pulmonary hypertension; however, the pathophysiologic mechanism responsible for this complication has not been well characterized, and there have been no detailed descriptions of the pathology of this disease since the 1940s.
Methods.Respiratory tissue samples obtained at autopsy from 15 infants aged 
4 months who had polymerase chain reaction– or culture‐confirmed B. pertussis pneumonia were evaluated by multiple histochemical stains, immunohistochemical evaluation, and electron microscopic examination.
Results.The pulmonary histopathologic examination of the samples revealed a descending infection dominated by necrotizing bronchiolitis, intra‐alveolar hemorrhage, and fibrinous edema. All samples had marked leukocytosis, and most showed luminal aggregates of abundant leukocytes in small pulmonary arteries, veins, and lymphatics. A novel immunohistochemical stain for B. pertussis revealed abundant extracellular bordetellae in cilia of the trachea, bronchi, and bronchioles, as well as intracellular bacteria and antigens in alveolar macrophages and ciliated epithelium.
Conclusions.Pertussis should be suspected in any infant death associated with marked leukocytosis, bronchopneumonia, or refractory pulmonary hypertension, particularly in children aged 4 months. The pathologic findings identified in the respiratory tracts of these children, in addition to recognized physiologic responses of the infant lung to hypoxia, suggest that B. pertussis pneumonia triggers a cascade of events that includes acute pulmonary vasoconstriction and pertussis toxin–mediated increases in circulating leukocyte mass. These responses ultimately compromise pulmonary blood flow, exacerbate hypoxemia, and create a vicious cycle of refractory pulmonary hypertension.
Received 28 November 2007; accepted 29 March 2008; electronically published 16 June 2008.
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Online publication date: 1-Jul-2009.
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The findings and conclusions in this article are those of the authors and do not necessarily reflect the views of the US Department of Health and Human Services.
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Presented in part: 96th Meeting of the United States and Canadian Academy of Pathology, San Diego, CA, March 2007 (abstract 1231); Pediatric Academic Societies’ 2007 Annual Meeting, Toronto, Canada, May 2007 (abstract 8220.12).