Pathology and pathogenesis of fatal Bordetella pertussis infection in infants.
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 <or=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 <or=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.
Paddock
Christopher D
CD
Infectious Disease Pathology Branch, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. cpaddock@cdc.gov
Sanden
Gary N
GN
Cherry
James D
JD
Gal
Anthony A
AA
Langston
Claire
C
Tatti
Kathleen M
KM
Wu
Kai-Hui
KH
Goldsmith
Cynthia S
CS
Greer
Patricia W
PW
Montague
Jeltley L
JL
Eliason
Mark T
MT
Holman
Robert C
RC
Guarner
Jeannette
J
Shieh
Wun-Ju
WJ
Zaki
Sherif R
SR
D001886:Bordetella pertussis / Q000302:isolation & purification*; D001996:Bronchopneumonia / Q000382:microbiology* / Q000473:pathology*; D015331:Cohort Studies; D003251:Constriction, Pathologic; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology; D000860:Hypoxia / Q000209:etiology; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D007964:Leukocytosis / Q000382:microbiology; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008297:Male; D011651:Pulmonary Artery / Q000473:pathology; D014917:Whooping Cough / Q000150:complications / Q000382:microbiology* / Q000473:pathology*