Immunization is a cornerstone of global public health, preventing substantial morbidity and mortality worldwide. However, the long-term success of immunization programs depends not only on vaccine effectiveness but also on robust systems for monitoring and managing vaccine safety. Adverse Events Following Immunization (AEFIs), defined by the World Health Organization (WHO) as any untoward medical occurrence that follows immunization and does not necessarily have a causal relationship with vaccine use, remain an important challenge for vaccine safety surveillance and public confidence. This narrative review synthesizes evidence on the classification, biological and immunological mechanisms, clinical manifestations, surveillance, causality assessment, and public health management of AEFIs. Literature was identified through searches of PubMed/MEDLINE and Scopus, complemented by relevant grey literature from authoritative organizations, including WHO and the United States Centers for Disease Control and Prevention (CDC). The review considers evidence from both COVID-19 and non-COVID-19 vaccination programs, with emphasis on vaccine safety surveillance, pharmacovigilance, clinical assessment, and public health response. AEFIs were examined according to the WHO classification framework, comprising vaccine product–related, vaccine quality defect–related, immunization error–related, immunization anxiety–related, and coincidental events. Biological and immunological mechanisms range from expected innate inflammatory responses to rare immune-mediated and hypersensitivity reactions. Although most AEFIs are mild and self-limiting, rare serious events require timely recognition, investigation, and appropriate clinical management. Global vaccine safety monitoring capacity remains uneven, with substantial differences in reporting, surveillance infrastructure, diagnostic capacity, and health-system resources across settings. Strengthening pharmacovigilance, active and passive surveillance, healthcare worker training, causality assessment, and transparent risk communication is essential to ensure vaccine safety, sustain public confidence, and support the continued success of immunization programs worldwide.
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