Determinants of Fatalities and Secondary Transmission in Laboratory Pathogen Incidents, 1900–2025

Abstract Objectives To identify biological, operational, and contextual risk factors associated with fatal and outbreak outcomes following accidental laboratory-associated incidents worldwide. Methods We analysed 1,126 laboratory-associated incidents reported globally between 1900 and 2025, including laboratory-acquired infections, personnel exposures, and accidental pathogen releases. Fatality and laboratory-associated outbreak (≥5 cases) were modelled separately. Multivariate logistic regression, classification and regression tree, and random forest models assessed associations across pathogen, personnel, procedural, facility, and regional variables. Performance was evaluated using stratified 5-fold cross-validation. Results Eighty-one fatalities (7.2%) and 148 outbreaks (13.1%) were identified. Fatal outcomes were strongly associated with pathogen risk group and class, particularly prions (OR 189.9) and RG4 pathogens (OR 32.4). Inadequate inactivation and leaks in wastewater or aerosols contributed to both outcomes. Personnel type was influential: microbiologists and technicians were more often associated with fatalities, whereas clinicians, researchers, students, and routine laboratory workers were more often associated with outbreaks. Higher containment facilities were protective in regression models. Random forest showed the strongest discrimination (AUCs of 0.814 for death and 0.799 for outbreak). Conclusions Mortality is primarily driven by pathogen virulence, whereas outbreaks reflect operational and contextual factors. Risk assessment frameworks should address severity and transmission as distinct but complementary domains.