Severe pertussis infection

Abstract

We aimed to investigate the clinicopathological features of pertussis in children admitted to a tertiary-care university hospital in Brazil.This was a retrospective cohort study of all pediatric hospital admissions with pertussis from January 1, 2008 to December 31, 2014. We also reported the autopsy findings in children who died.Fifty-five patients admitted to the hospital over the study period had laboratorial confirmation of Bordetella pertussis infection, 17 (30.9%) needed pediatric intensive care unit (PICU) admission and 6 (10.9%) died. All patients who died were younger than 60 days old and unvaccinated for pertussis; 50% of them had coinfection with respiratory syncytial virus. Leukocyte count ≥40,000/mm3 at hospital admission was an independent risk factor for PICU admission. Mean heart rate during hospitalization ≥160 bpm was an independent risk factor for death. A cut-off point of 41,200 leukocytes/mm3 at hospital admission had sensitivity of 64.7% and specificity of 89.5% to predict PICU admission (area under the curve 0.75) and sensitivity of 100% and specificity of 81.6% to predict death (area under the curve 0.93). Autopsy showed medial thickening of small pulmonary arteries in 80% of patients who had pulmonary hypertension; intravascular aggregates of leukocytes or pulmonary thrombosis were not observed. Immunohistochemical staining of tissue samples obtained at autopsy identified B pertussis and respiratory syncytial virus in pulmonary and extra-pulmonary sites.Marked leukocytosis at presentation was associated with morbidity and mortality in children hospitalized with pertussis. Implementation of preventive strategies is crucial to diminish the incidence of the disease, especially in young unimmunized infants.

Histopathology of Bordetella pertussis in the Baboon Model

“…Infant baboons that were euthanized because of severe pertussis infection exhibited a pathology similar to that observed in fatal human cases of B. pertussis (7)(8)(9)16). In both hosts, subjects experienced descending disease, with pulmonary hemorrhage, edema, and fibrin deposits obstructing the terminal airways.…”

“…In contrast, 6-to 9-month-old (juvenile) baboons experience severe disease that lasts approximately 2 weeks, followed by a 2-to 3-week convalescence, resulting in a return to full health (10). We examined the histopathology of 5-to 6-week-old baboons that required euthanasia due to the severity of their disease following infection with B. pertussis, with the findings being similar to those reported for fatal human infant cases (7)(8)(9). 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.…”

“…Much of our understanding of pertussis pathology in humans is based on the histopathology of samples collected from fatal infant cases (7)(8)(9)16). Although this information provided a critical understanding of the pathology of the most severe cases of pertussis, it may not accurately reflect the pathology of the more common cases of pertussis in older infants and children that are severe but not fatal.…”

“…Much of what is known about the pathology of pertussis in humans is from the evaluation of fatal infant cases. Paddock et al and others evaluated the pathology of fatal pertussis cases and found that each child experienced a descending respiratory infection that was characterized by pulmonary hemorrhage and edema, necrotizing bronchiolitis, and bronchopneumonia with damaged mucosa, denuded epithelium, and cilium loss in the trachea (7)(8)(9). While the pathology of these cases provides important insights into the damage inflicted on the respiratory system, these cases represent the end-stage pathology of the most severe infections.…”

Association of Pertussis Toxin with Severe Pertussis Disease

“…Reports have described the identification of leukocyte thrombi in small pulmonary blood vessels and speculated that vascular occlusion caused by leukocytosis results in increased pulmonary arterial pressure and establishment of pulmonary hypertension [48,49]. However, this finding is not supported in other clinicopathological studies [16,50]. If leukocytosis does promote the onset of pulmonary hypertension, this may be one mechanism by which PT indirectly promotes this pathology.…”