Temporal, spatial, and methodological considerations in evaluating the viability of measles wastewater surveillance.

Measles is a highly transmissible disease of increasing concern due to waning vaccination contributing to a significant rise in measles cases, with 283 reported cases and 16 outbreaks in the U.S. as of November 7, 2024. Early identification of measles cases is thus critical to disease containment and control. Wastewater-based epidemiology (WBE) represents a potential strategy for the efficient identification of measles outbreaks. We investigated the suitability of WBE for measles outbreak identification by using a model-based approach to elucidate the relationship between measles shedding, wastewater concentration, and detectability. The model reveals conditions for effective detection, specifying the optimal timing, location, and methodology needed to achieve a specific probability of detection, including accounting for geographic variability of wastewater generation and measles case rates. Measles RNA shedding, primarily from urine, contributes an average of 8.72 log10 genome copies (GC) daily per infection into sewage. At the average U.S. wastewater treatment plant (WWTP), achieving a 50 % probability of detection requires approximately 78 cases per 100,000 people with a process limit of detection (PLOD) of 3.0 log10 GC/L. At a PLOD of 3.0 log10 GC/L, over half of all WWTPs in the world can detect a single hypothetical measles case at a 10 % probability of detection. However, achieving a 50-90 % detection rate is challenging, especially with a higher PLOD, except in areas with the highest measles cases. Some locations require case levels consistent with a complete lack of vaccination for feasible measles detection in wastewater. Future work exploring measles shedding, variable shedding behavior, and local case rates can enhance model predictions. Overall, this analysis suggests that WBE detection of measles in most locations remains challenging without a significant increase in case rates or technical improvements decreasing the PLOD.