Modeling epidemiological patterns of smallpox in Copenhagen in the 19th century after the introduction of the vaccine

In 1798, Jenners smallpox vaccine made it possible to prevent the deadliest of childhood diseases. In Denmark the vaccine was used from 1801, and by 1810 a mandatory 1-dose childhood vaccination program was instituted, free of charge. As proof of vaccination (or natural immunity) was required for church confirmation around age 13, about 90 % of children were vaccinated and smallpox disappeared from Copenhagen after 1808. After a 16-year "honeymoon period", it returned in 1824 with a new face: a milder disease in mostly young adults (1, 2). Here we investigate the effects of smallpox vaccination on the epidemic patterns through the post-honeymoon era (1824-1875). We accessed data from the hospital "Sokvaesthuset" where all smallpox cases, mild and severe, were hospitalized during 1824-1835 in order to contain the outbreak. We identified [~]3000 smallpox cases and four separate epidemics occurring during this period (1-3). We used a mechanistic model (SEIR) to assess factors playing a role in explaining the return of smallpox, and the changing age distribution. These factors included vaccination coverage, duration of immunity from vaccination and from natural infections, and the fate of the "lost generation" of persons born around 1800, too early to get vaccinated and too late to have been infected with smallpox. Our model tracks well the disappearance and return of smallpox in 1824, the interval between epidemic peaks, and the aging pattern. We propose vaccine waning after [~]20 years as the primary reason explaining the return of smallpox and the epidemic pattern. SignificanceSmallpox has played a major role in shaping modern medicine. Recently, it has received renewed attention due to fears of bioterrorism and the emergence of the closely related mpox. In this article, we use data from the carefully recorded smallpox outbreaks in Copenhagen in the 1800s to study its dynamics following vaccine rollout. We show that the vaccine likely induced a long-lived but finite immunity and that the "lost generation" who were neither vaccinated nor had contracted smallpox in childhood continued to be plagued by the disease in the following decades. The study is relevant for understanding how smallpox was eradicated and the role of vaccination in dealing with present epidemic threats.