Smallpox Re-Emergence Risk and Global Preparedness: A Comprehensive Review

Abstract

Smallpox, once a highly lethal infectious disease, was successfully eradicated in 1980 through global vaccination efforts. However, concerns regarding its potential re-emergence persist due to bioterrorism threats, declining population immunity, and advances in synthetic biology. This study reviews the historical significance, epidemiology, transmission dynamics, and current prevention strategies associated with smallpox. It also highlights the role of vaccination, ring vaccination, and case isolation in outbreak control, along with recent advancements in antiviral therapies such as tecovirimat. Despite these developments, several research gaps remain, including limited data on long-term immunity, vaccine safety, and real-world effectiveness of antiviral treatments. The study emphasizes the need for improved surveillance systems, safer vaccines, and strengthened global preparedness to mitigate future risks associated with smallpox and related orthopoxvirus infections.