Monkeypox is a zoonotic infection prevalent throughout central and west Africa, and is a prototype for studying the transmission dynamics of emerging zoonoses. In the aftermath of the global smallpox eradication campaign, monkeypox was studied intensively to determine its potential to fill the niche left vacant by smallpox. Monkeypox appeared to spill over frequently into human populations, and exhibited limited human-to-human transmission, but early studies concluded that it posed little threat of becoming an endemic human pathogen. A recent upsurge in monkeypox cases has re-ignited interest in fundamental questions about monkeypox dynamics, including: What protection remains from historical smallpox vaccination? As this protection wanes, could monkeypox emerge as an endemic pathogen of humans? How frequently does monkeypox spill over from its animal reservoir into human populations? We address these questions using statistical and modeling analyses of historical and contemporary data sets for monkeypox in the Democratic Republic of Congo (DRC).

Results/Conclusions

By analyzing of the age distribution of monkeypox cases over time, combined with data on historical vaccine coverage, we estimate that smallpox vaccination retains >95% protective efficacy against monkeypox more than 20 years after the vaccines were administered. Integrating this result with demographic data, we project the decline of population immunity to monkeypox through coming decades. Building on past studies of human-to-human transmissibility, we translate these trends into projections for the increase in the effective reproductive number (R_eff) for monkeypox as population immunity wanes. From the year 2020 onwards, the 95% confidence interval for R_eff includes values greater than one, indicating the potential for endemic circulation of monkeypox among humans. Accounting for on-going societal and demographic changes in the DRC makes this outcome more likely, as would possible adaptation of the virus to human hosts. Finally, we analyze seroprevalence data to obtain estimates of total case incidence in the human population. Using a new method derived from stochastic outbreak models, we extract the cases caused by spillover transmission from the wildlife reservoir, enabling us to estimate the per capita risk of infection as roughly 0.1% per year. These methods have potential to elucidate cross-species spillover transmission for many zoonotic pathogens.