Variability in the Diagnostic Criteria for Severe Pertussis: A Systematic Review

Pertussis, or whooping cough, can be life threatening in infants, yet the concept of severe pertussis remains poorly defined in the literature. Lack of standardization may impair research and public health interventions.

To assess the variability in terminology and criteria used to define severe pertussis in the published literature.

A systematic review of the literature drawn from PubMed and Web of Science databases was performed. Studies involving infants with pertussis that provided a definition for severe pertussis and published from database inception to April 2025 were included without language restrictions. Study characteristics and detailed definitions of severe pertussis were extracted. Variations in terminology and criteria used across definitions were described.

Of the 914 unique studies identified, 133 underwent full-text review, and 78 were included in the study, encompassing 49 observational studies, 22 case reports, 3 case-control studies, and 4 reviews; no randomized clinical trials were included. Five different terms used to define severe pertussis were identified: severe (44 of 78 studies [56%]), malignant (12 of 78 studies [15%]), critical (9 of 78 studies [12%]), fatal (9 of 78 studies [12%]), and fulminant (4 of 78 studies [5%]). Across studies, 22 different criteria were used to define clinical severity, which were classified into 3 categories (ie, clinical, biological, and outcome). The most commonly reported criteria included respiratory failure (40 of 78 studies [51%]), pulmonary hypertension (30 of 78 studies [38%]), leukocytosis (28 of 78 studies [36%]), death (29 of 78 studies [37%]), and intensive care unit admission (29 of 78 studies [37%]).

This systematic review revealed substantial heterogeneity in the definition of severe pertussis in the literature. A consensus-based definition of severe pertussis is urgently needed to improve the understanding of its pathophysiology and to enhance clinical management, clinical research, and public health decision-making.