Will a re-emergence of ancient infectious diseases pose a new risk to humanity in the coming millennia?

Infectious diseases including smallpox, the black plague, cholera, and others have been responsible for the loss of millions of lives over the past millennia, prior to the development of effective treatment strategies during the recent century. Throughout history, epidemics and pandemics are known to have occurred intermittently throughout the world for over 2,500 years. During the 20th century, many of the causative infectious agents were identified, the evolution of vaccines and antimicrobials were developed, resulting in treatment strategies and public health measures that brought about the resolution and presumed virtual eradication of some of the infectious agents. Cholera is transmitted via the fecal-oral route, and outbreaks continue to occur, with the most recent epidemic in Haiti following the massive earthquake of 2010 despite the development of effective vaccines and supporting public health measures. While smallpox was deemed to have been eradicated by the WHO, the recent discovery of Alaskapox, a novel strain of orthopoxvirus that is genetically similar to ‘old-world’ smallpox claimed its first fatality in January 2024. The bubonic plague also continues to reappear in clusters, most recently in rural Oregon in the USA in early 2024. Thus, the emergence of variants of these and other devastating ancient diseases continues to require diligence in establishing and delivery of public health measures and therapeutic options to ensure the plagues of former millennia remain in the history books and not in the community during the present and future generations.