Wastewater surveillance predicts Mpox outbreak dynamics in a resource-limited urban setting

Wastewater-based surveillance (WBS) has emerged as a scalable approach for monitoring emerging pathogens, yet its capacity to function as an early-warning system for Mpox virus (MPXV) in rapidly urbanizing sub-Saharan African settings remains unresolved. We conducted weekly wastewater sampling at four facilities in the Kampala Metropolitan Area, Uganda, during the 2025 Mpox outbreak (February–September; n = 128 samples) and quantified MPXV DNA by real-time PCR. MPXV was detected at all sites (40.6–93.8% of weeks), demonstrating robust environmental detectability in a high-burden African city. However, temporal coupling between wastewater concentrations and clinical Mpox positivity was heterogeneous. After autocorrelation adjustment, concurrent correlations were generally weak and statistically underpowered. Lead–lag analyses revealed distinct site-dependent dynamics: the Bugolobi fecal sludge treatment facility exhibited a 3-week prospective signal (rs = 0.623), whereas high-connectivity Nakivubo wastewater inlets 1 & 2 and Naalya stabilization pond displayed concurrent or lagged patterns. No association persisted after false discovery rate correction. These findings show that WBS performance is not intrinsic to pathogen detection alone but emerges from the interaction between viral shedding, sewer network architecture, hydrological residence time, and health-seeking behaviour. Early-warning capacity is therefore a systems property of surveillance network design rather than a universal attribute of wastewater monitoring. Our results provide empirical evidence from sub-Saharan Africa that optimizing sewershed configuration and temporal resolution is essential before WBS can be operationalized as a predictive tool within national epidemic intelligence frameworks.