Integrating measles wastewater and clinical whole-genome sequencing enables high-resolution tracking of virus evolution and transmission

ABSTRACT Measles outbreaks have surged globally in recent years, but current surveillance systems have limited capacity to monitor measles virus (MeV) transmission and evolution at population scale. Although MeV can be detected in wastewater, the public health potential of wastewater genomic surveillance for MeV remains largely unexplored. Here, we deploy sensitive, low-cost MeV wastewater genomic surveillance combining virus concentration, whole-genome amplicon sequencing, and bioinformatic analysis alongside routine clinical genomic surveillance during the 2024-25 outbreak in South Africa. Integrated phylogenetic analyses of wastewater and clinical MeV genomes revealed previously undetected interprovincial spread and transmission links not captured by standard N450 sequencing. Our findings demonstrate that wastewater-integrated whole-genome surveillance expands the coverage and resolution of routine MeV monitoring and provides a scalable tool to advance measles control and elimination efforts.