Genomic Surveillance of Mpox through the Development of a Wastewater Intelligence Model and Data Analytics Platform

Project Summary A critical challenge in pandemic preparedness is the rapid identification of viral outbreak sources and tracking mutations that lead to new variants. Current public health surveillance methods, relying on resource-intensive laboratory testing of patient specimens, often yield incomplete data due to underreporting. The recent mpox outbreak in the Democratic Republic of the Congo—with over 22,000 suspected cases since January 2023 and the emergence of a new strain (clade 1b)—underscores the need for more effective surveillance tools. To address these limitations, we and others have developed wastewater approaches to screen municipal sewage for viral levels and variants. This method capitalizes on the shedding of pathogens like SARS-CoV-2 and mpox into sewer systems through bodily fluids, providing a comprehensive, real-time snapshot of community infection levels and viral evolution. Over the last five years, our team has built and implemented a comprehensive wastewater COVID-19 surveillance program that includes a community engagement responsive element and serves 2.4 million residents and 50 million annual tourists in Southern Nevada. In Summer 2022, we adapted this program to pilot a study tracking the clade IIb mpox outbreak in Las Vegas. Building on these achievements and developing novel reagents for clades I and II, we have a time-sensitive opportunity to test our central hypothesis: that enhanced wastewater surveillance, coupled with new computational tools, can enable rapid detection of mpox variants from both clades, facilitate assessment of antiviral drug efficacy, and inform strategic prioritization of vaccination sites. This high-risk, high-reward proposal extends our previous successful approaches with SARS-CoV-2, influenza, and drug use in wastewater, potentially breaking new ground in mpox research. Our proposal directly responds to the 2022 and 2024 mpox public health emergency of international concern declarations and aligns with NIAID's 2024 mpox research agenda. The identification of even a single mpox outbreak or treatment-resistant strain through our wastewater studies would significantly advance innovative research in genomic epidemiology and public health surveillance, potentially transforming our approach to managing emerging infectious diseases.