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Introduction

Wastewater-based infectious disease surveillance describes the ongoing collection, analysis, and interpretation of and response to data related to the transmission of pathogens in wastewater for public health purposes. In wastewater surveillance systems, untreated municipal wastewater is sampled and analyzed for the presence of biomarkers of infection, most commonly pathogen deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) that are shed by infected persons (see Figure 1-1). The measurement is inherently an indicator of the magnitude of the agent’s loading to wastewater, which can be interpreted to understand the presence and increases or decreases in prevalence of infection in a community. Wastewater surveillance can capture pre-symptomatic and asymptomatic cases as well as infections across the spectrum of disease severity, regardless of people’s care-seeking behavior. During the COVID-19 pandemic, wastewater surveillance gained traction and was implemented rapidly as an additional epidemiological tool to monitor trends and anticipate disease incidence in communities.

Whereas clinical laboratory testing and health services track individual cases of infection, testing for a pathogen at a wastewater treatment plant (also known as community-level wastewater surveillance) provides aggregate data from an entire community sewershed (i.e., the community population consisting of homes, businesses, and other institutions that share a common sewer system or drainage area). It does not track or identify infectious disease for an individual person or household; rather, it detects the presence and changing quantities of a pathogen within the larger community. More focused sampling can take place within the sewershed at manholes or pump stations to capture information about disease in subsets

of the population (termed sub-sewershed sampling) or at facilities, such as hospitals or long-term care facilities.

In the United States, 84 percent of households are connected to a wastewater treatment plant (U.S. Census, 2022). The remaining unsewered population is not directly addressed by this epidemiological approach, although some members of this population regularly commute to sewered areas for work, school, or other activities.

WASTEWATER SURVEILLANCE IN THE UNITED STATES

Wastewater surveillance was implemented quickly across the country under emergency conditions during the COVID-19 pandemic, with independent development of many local and hyperlocal (e.g., building- or institution-based) initiatives. As proof-of-concept was established for the feasibility and potential public health value of SARS-CoV-2 RNA detection, the implementation of these systems expanded. Recognizing the need for centralization and coordination of these efforts, the U.S. Centers for Disease Control and Prevention (CDC) launched the National Wastewater Surveillance System (NWSS) in partnership with the U.S. Department of Health and Human Services (HHS) in September 2020. Through the NWSS, CDC coordinates with state-, tribal-, local-, and territorial-level health departments to design and integrate wastewater surveillance data to inform public health decisions.

The NWSS was the first national-level wastewater disease surveillance system in the United States and has been supported by $500 million in pandemic response funding over 4 years. As of April 2024, the NWSS was receiving data from more than 1,300 active sampling sites, covering a population of 130 million individuals (Figure 1-2).¹ This includes data collected through WastewaterSCAN, a privately funded wastewater surveillance initiative with over 180 sites across the nation in 2024.² The participation of most other sites is supported by CDC Epidemiology and Laboratory Capacity for Prevention and Control of Emerging Infectious Diseases (ELC) Cooperative Agreement grants provided to eligible health departments (i.e., state health departments, territories, and some large cities and counties). This cooperative agreement extends through fiscal year (FY) 2027.

Wastewater surveillance sampling sites are based in participating municipal wastewater systems; communities and populations that are unsewered are only captured in a wastewater surveillance system to the extent that individuals commute to a monitored sewershed for work, school, or other activities. The sizes of communities in the NWSS served by an individual

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¹ See https://www.cdc.gov/nwss/about.html.

² See https://data.wastewaterscan.org/publications/.

wastewater treatment plant can range widely, from very small plants that serve as few as 100 people to large plants that serve a few million people, with a median of approximately 45,000 people (A. Kirby, CDC, personal communication, 2022).

Implementation of wastewater surveillance depends upon three primary entities—the local wastewater utility, analytical laboratory, and health department—to collect, test, and analyze samples and interpret the data (see Figure 1-1). Typically, local wastewater utilities collect, package, and ship the samples, which are used only for infectious disease surveillance and have no water quality regulatory implications. A public health, commercial, or academic laboratory partner analyzes the samples and reports the data to CDC and the local public health jurisdiction. The public health department interprets the data to identify trends regarding infection prevalence within a community, integrates the wastewater data with other surveillance data, determines the appropriate public health actions, and communicates this information to the general public. The public health department must agree to the data sharing policies of the CDC to participate (see Chapter 4). The multidisciplinary nature of a national wastewater surveillance system requires extensive collaboration between and across health departments, testing laboratories, and wastewater utilities. These partnerships and the demands on the participating entities are discussed further in the committee’s Phase 1 report (NASEM, 2023).

CDC plays an important role to facilitate the overall function and operation of the NWSS as a national system and supports its continued development. In addition to providing ELC funding for local, state, and tribal wastewater surveillance (including staff time, sample collection, and analysis), CDC aggregates data from participating wastewater surveillance sites across the country that are submitted from public health jurisdictions and/or analytical laboratories. CDC then shares the results with the public, health officials, and policy makers through a variety of mechanisms, including a public-facing data dashboard, summarized data briefs, and a restricted-access data dashboard for health departments (Data Collation and Integration for Public Health Event Response [DCIPHER]). The goal of the NWSS is for these data to be interpreted by public health officials and used to inform community health interventions, raise public awareness of disease transmission within communities, and track pathogen dynamics across the nation. At a national scale, the information can inform decisions on allocations of federal resources and other support to states; at state, local, and tribal levels, the information can inform decisions on public health actions.

In support of the NWSS, CDC collaborates and coordinates with other federal agencies, such as the U.S. Environmental Protection Agency, U.S. Department of Homeland Security, and the National Institutes of Health,

and coordinates communities of practice in conjunction with partners at the Water Environment Federation (WEF) and the Association of Public Health Laboratories (APHL). The communities of practice work to build capacity among the participating localities, host monthly meetings with cohorts of participants across jurisdictions to share experiences and keep health officials apprised of updates or program improvements, and facilitate connections among health departments that express a desire to share their data with one another. CDC also funds four NWSS Centers of Excellence—in California; Colorado; Houston, Texas; and Wisconsin—which provide additional expertise to assist with training, communication, and ongoing development of the NWSS. These Centers of Excellence complement an active research community that has helped facilitate the rapid evolution of wastewater epidemiology.

PHASE 1 REPORT

In late 2021, CDC charged the National Academies of Sciences, Engineering, and Medicine to appoint a committee of academic and public health experts to review community-level wastewater surveillance and its potential value toward understanding and preventing infectious disease in the United States. The committee’s work was divided into two parts. The first phase, released in early 2023, provided an assessment of the usefulness of community-level wastewater surveillance in the United States and its potential value for infectious disease beyond COVID-19. (See Box 1-1 for the committee’s complete Phase 1 statement of task.)

In its Phase 1 report (NASEM, 2023), the committee noted that wastewater surveillance has proved to be a valuable component of the nation’s emergency response to the COVID-19 pandemic and will remain a critical data source for public health action in responding to COVID-19. Notably, as at-home testing increased and clinical laboratory testing and reporting decreased over the course of the pandemic, wastewater surveillance for new variants and their spread assumed increasing importance. The report stated that the pandemic spurred tremendous innovation and technological advances in wastewater surveillance, and ongoing knowledge development can help address gaps and improve analytical methods and data interpretation, not only for COVID-19 but also for newly emergent and re-emerging infectious diseases.

Based on the experience with wastewater surveillance during COVID-19, the report concluded that wastewater surveillance is worthy of further development and continued investment. The committee presented a vision for a national wastewater surveillance system that is flexible, equitable, sustainable, integrated, and actionable, and recommended approaches to address ethical and privacy concerns and develop a more representative

wastewater surveillance system. In looking beyond COVID-19 toward additional microbial targets, the National Academies (NASEM, 2023) recommended three criteria to guide the NWSS in selecting among potential targets in its strategic allocation of effort and resources: (1) the public health significance of the threat, (2) the analytical feasibility for wastewater surveillance, and (3) the usefulness of community-level wastewater surveillance data to inform public health action. The report proposed a transparent process for prioritizing new targets and periodically re-evaluating their usefulness as scientific knowledge, technology, and infectious disease risks evolve.

The Phase 1 report emphasized the need for partnerships among federal agencies, nongovernmental organizations, academia, industry, wastewater utilities, and public health jurisdictions. The report highlighted the need to engage wastewater treatment plants as full partners to provide critical expertise and the value of close cooperation with researchers to further advance foundational knowledge needed for a robust surveillance system. The report also emphasized the importance of predictable and sustained federal funding moving forward (NASEM, 2023).

PHASE 2 STUDY AND CONTEXT

As the nation transitions from COVID-19 pandemic emergency response to endemic disease management with ongoing monitoring of emerging SARS-CoV-2 variants, the addition of new pathogen targets at some sites, and heightened awareness of potential pandemic risks, the application of wastewater surveillance as a public health tool also continues to evolve. In Phase 2 of the study (see Box 1-1), CDC asked the National Academies for a detailed assessment of opportunities and barriers in wastewater surveillance for the prevention and control of infectious diseases in the United States as it considers the future of the NWSS beyond COVID-19. CDC requested that the committee define specific characteristics for sampling, testing, and data analysis in the development of a robust, integrated national wastewater surveillance program and identify significant technical limitations and research and development needs. In its analysis, the committee considered approaches and methods used within NWSS, WastewaterSCAN, and other smaller programs where information was readily available. In this report, more attention was directed to NWSS, because it encompasses nearly all current community wastewater-based surveillance sites in the United States. Additionally, the NWSS is managed by the sponsor of this study. The committee focused on technical feasibility and scientific issues; although assessing the return on investment is also important, the question of the cost-effectiveness of wastewater surveillance in terms of the value of information provided is beyond the committee’s charge.

To address its Phase 2 statement of task, the committee held six information-gathering meetings between April and October 2023. These discussions served as the initial basis for the committee’s deliberations, which were further informed by a review of relevant literature and the committee’s collective expertise. Knowing that wastewater surveillance was developed under emergency conditions and the science of wastewater epidemiology is rapidly evolving, the committee approached its task envisioning what should be accomplished in the next 5–8 years to increase the utility of wastewater surveillance in the United States at a national scale. Although many of the committee’s recommendations can be acted upon sooner, the committee recognized that substantial research and development may

be needed to support decisions on the evolution of national wastewater surveillance.

The committee’s vision and recommendations were developed assuming stable continued financial support for national wastewater surveillance and related research and development. In early conversations about the statement of task, CDC staff clarified that the intent of the task to “identify resources for supporting wastewater surveillance” was for the committee to recommend other partners or programs that could provide needed expertise, capabilities, and tools—not who should provide funding for the program. However, it is important to acknowledge the budget uncertainty for wastewater surveillance that lies ahead. Only late in the committee process did it

become evident that NWSS funding was facing sharp cuts. The President’s Budget for FY 2025 (OMB, 2024) released in March 2024 included only $20 million for the NWSS, down from approximately $125 million/year during the pandemic, although local, state, and tribal programs can continue to use available funds previously allocated through ELC cooperative agreement grants for wastewater surveillance through FY 2027. The committee was not asked to restructure the NWSS under significantly reduced funding. Instead, the committee addressed its charge by laying out a vision toward a robust, integrated national wastewater-based infectious disease surveillance program with increased utility for the prevention and control of infectious diseases (see Box 1-1). As described in this report, achieving this vision and building a system that helps communities address endemic disease outbreaks while also ensuring a well-functioning wastewater surveillance system that is ready for the next pandemic will require much from CDC and substantial federal investment in research and analysis.

REPORT STRUCTURE

This report describes the state of wastewater surveillance sampling, testing, and data analysis and issues that should be addressed to improve the usefulness of data for public health response for a variety of pathogens and determinants of antimicrobial resistance. Chapters 2 through 5 focus on endemic pathogens, which are known to be present in the United States but may have regional, seasonal, or year-to-year variability in their prevalence, leading to outbreaks of concern to communities or the nation, while Chapter 6 addresses emerging pathogens and antimicrobial resistance of concern. Chapter 2 reviews trade-offs among sampling strategies. In Chapter 3, the committee evaluates the state of analytical methods and quality control and recommends areas for improvement. Chapter 4 reviews the tools available for data analysis, integration, and interpretation. Chapter 5 discusses the potential expansion of endemic targets for community-level wastewater surveillance. Finally, Chapter 6 addresses wastewater surveillance strategies (i.e., sampling, analytical methods, and data analysis and interpretation) for emerging outbreaks and pandemic threats, including those that are previously known outside the United States or in animal populations as well as truly unknown pathogens.