The Variola Virus: The Threat of Reintroduction and Our Capacity to Respond

Abstract

Though eradicated in 1980, smallpox remains a top priority pathogen due to the threat of a deliberate or accidental reintroduction of the Variola major virus. This thesis represents a thorough assessment of this threat, grounded in the molecular virology and epidemiology of the virus. We evaluate the literature concerning the Variola virus and related countermeasures, engage with experts in the field, and assess our response capacity through a novel mathematical model. While large quantities of vaccines have been stockpiled, many innovative countermeasures with undetermined efficacies are being developed and acquired. Updated response plans and research directions are needed. We address several gaps in our knowledge concerning viral pathogenesis and countermeasure mechanisms, and our smallpox epidemic model with staged disease progression dynamics facilitates the assessment of mitigation strategies and interventions. We analyze for the first time the utility of adding antiviral intervention alongside vaccination in both contact tracing and mass response mitigation strategies. Our findings suggest future directions for countermeasure research and support the establishment of a new response plan based on the principles of mass response with vaccination alone. Altogether, this thesis presents a holistic assessment of the threat posed by a reintroduction of the Variola virus and our capacity to respond.