Detection of a Single Measles Infection Using Untargeted Ultra-Deep Metagenomic Sequencing of Wastewater in Cook County, Illinois

AbstractMeasles is a contagious, vaccine-preventable viral disease that can be shed into wastewater by infected individuals. In September 2025, as part of an ongoing, nontargeted, ultra-deep metagenomic sequencing effort of wastewater in Cook County, Illinois, we detected measles reads from a facility serving more than 1 million people. Out of more than 900 million reads sequenced from wastewater collected on September 14, 2025, 43 matched measles virus genotype B3. Subsequent genomic analysis linked these reads to a confirmed measles infection that was present in the community on that day, demonstrating that untargeted metagenomics appeared to detect a single measles infection in a large municipal wastewater stream.