Bridging wastewater and case surveillance reveals the hidden burden of the 2022 mpox outbreak dynamics

Transmission models of the 2022 global mpox outbreak relied on case data to infer transmission dynamics despite substantial underascertainment driven by barriers to testing and care. Wastewater-based surveillance (WBS) captures community viral shedding independent of healthcare access, yet how it can be integrated with case data to improve infection estimates remains unclear. We developed a compartmental model integrating case-notifications, wastewater viral-load, sexual network structure, and vaccination to evaluate how WBS complements case surveillance. Three model variants were fitted and validated using serological data: i) case-only, ii) wastewater-only and iii) combined. The case-only model reproduced incidence but not wastewater dynamics, whereas the wastewater-only model captured viral load trends but overestimated peak incidence. Joint calibration reconciled both data streams, yielding more precise estimates of infection burden, including a peak prevalence of 344 infections (95\% CrI: 230-494) and a cumulative incidence of 1,132 (95\% CrI: 943-1,349). Model-predicted seroprevalence aligned with that observed among sexual health clinic attendees, providing external validation. The wastewater-case model revealed infection underascertainment, time-varying contributions of sexual activity groups to wastewater signals and showed that wastewater lead-lag relationships depended on epidemiological and operational conditions. Together, these findings establish integrated wastewater-case modelling as a robust framework for epidemic reconstruction.