Age-patterns of severity of clade I mpox in historically endemic countries

BackgroundThe last two years have seen mpox emerge as a notable pandemic threat. The global 2022-23 outbreak of clade II mpox caused over 93,000 cases worldwide, while the 2023-24 epidemic of the more severe clade I virus in the Democratic Republic of Congo (DRC) has caused over 14,000 cases and over 650 deaths thus far. Of particular concern is that both case incidence and mortality in the DRC outbreak are concentrated in children. However, quantification of age variation in severity for clade I infections has been lacking to date. MethodsUsing Bayesian binomial regression models, we analysed data from systematically reviewed clade I outbreaks to estimate case fatality ratios (CFR) by age, smallpox vaccination status and over time. We compared model predictive performance using leave-one-out cross-validation and compared our findings to the ongoing DRC outbreak. FindingsThe CFR had a near-reciprocal relationship with age, declining from 9.7% (95% credible interval: 6.9%-13.0%) among 5-year-olds to 1.2% (95%CrI: 0.3%-3.7%) by age 30. Accounting for vaccination status in addition to age did not improve model fit, but posterior parameter estimates suggest substantial vaccine-protection against death. Reanalysis incorporating cases from the ongoing DRC outbreak suggested less steep declines in severity with age and a protective effect of vaccination against death of 64% (95%CrI: - 3.4%-95.6%) and reduction in severity over time. InterpretationWe provide estimates of the mpox clade I CFR in historically endemic settings by vaccine status, and find the highest risk of death in the youngest children. FundingWellcome, NIHR, MRC, Community Jameel