Wastewater-based Disease Surveillance for Public Health Action (2023)

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1 Introduction Rapid detection of recognized or emerging infectious disease outbreaks is essential for timely public health response. The COVID-19 pandemic illuminated the strengths and limitations of the U.S. public health infrastructure, particularly the challenges to implementing widespread clinical testing, tracking asymptomatic infections, and anticipating community disease outbreaks. During the COVID-19 pandemic, wastewater surveillance1 gained traction as an additional epidemiological tool to monitor trends and anticipate disease incidence in communities. Wastewater surveillance systems collect samples of untreated municipal wastewater that are then 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 Box 1-1; Figure 1-1). 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. In the United States, 84 percent of households are connected to a wastewater treatment plant (U.S. Census, 2022). The sizes of communities served by an individual 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). 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 detects the genetic biomarkers of disease agents that have been discharged into a sewer. The measurement is inherently an indicator of the magnitude of the agent’s loading to wastewater, which can be interpreted to understand the prevalence of infection in a community. Wastewater surveillance can capture pre-symptomatic cases as well as infections across the spectrum of disease severity, including asymptomatic cases that may not   1 In this report and more broadly across the field of public health, “wastewater 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. The committee acknowledges that the word “surveillance” is a charged term also used in other contexts to describe careful watching by the police, although that use is not intended in this report. See Chapter 4 for a discussion about privacy considerations associated with implementing a national wastewater surveillance system. PREPUBLICATION COPY 7 

8 Wastewater-based Infectious Disease Surveillance for Public Health Action FIGURE 1-1 Components of a community-level wastewater surveillance system. Infected persons can shed biomarkers of infection (see Box 1-1) into the wastewater system through feces, urine, saliva, and other sources. Household wastewater is discharged into the sewer system and collected at the inflow to the wastewater treatment plant, where sampling occurs. The sample is then transported to a laboratory where it is analyzed, and the data are analyzed and published on internal- or external-facing dashboards. These data are then used by state, tribal, local, territorial, and national officials to support decision making on public health interventions, and the distribution of resources and support public communication. SOURCE: Adapted from https://www.cdc.gov/healthywater/surveillance/pdf/Wastewater- COVID-infographic-h.pdf. PREPUBLICATION COPY 

Introduction 9   BOX 1-1 What Is Actually Being Detected in Wastewater Surveillance? Theoretically, the actual pathogen—be it a virus, bacteria, parasite, or fungus—can be directly detected in wastewater, either by direct cultivation or following an enrichment step. In practice, this approach is limited by the low concentration and low viability of most pathogens in wastewater and the expense of direct isolation. Consequently, current pathogen detection is based on biomarkers—targets that are specific to a pathogen and amenable to detection independent of actual pathogen viability. The most commonly used biomarker is pathogen-specific nucleic acid, either RNA or DNA. Polymerase chain reaction (PCR) methods can be used to amplify targeted genetic fragments from known organisms, mitigating, at least in part, the challenge of low pathogen concentration in wastewater. Amplification can be highly specific and quantifiable and uses instrumentation and technical expertise that are widely available. Importantly, the amplification step can be modified as needed for new pathogens or variants, assuming targeted assays are available, and the end product can be sequenced for confirmation of pathogen identity or identification of genetic changes associated with a new variant. Genes encoding resistance to antibiotics can be detected in bacteria using the same amplification techniques. The distinction here is that key determinants of antibiotic effectiveness are being detected rather than the pathogen itself. Metagenomic sequencing methods enable the identification of previously unknown variants of known pathogens (Karthikeyan et al., 2022; see Chapter 2). These approaches do not require that the pathogen be viable. Additional approaches can directly detect other pathogen components, such as proteins and lipids, which can be used as biomarkers. Although methods based on these alternative biomarkers are less commonly used due to their relative inability to detect low concentrations, they may be required for certain infectious diseases (e.g., prion diseases) and may benefit from ongoing research to improve detection sensitivity. For uniformity in this report, the term “pathogen detection” (e.g., detection of SARS-CoV- 2) is used with the understanding that the actual detection is a pathogen-specific biomarker (e.g., an amplified segment of SARS-CoV-2) or, more broadly, biomarkers of microbial threats such as bacteria carrying genes encoding resistance to antibiotics.   result in an infected individual seeking medical care. However, interpretation of data may be confounded by variability in shedding levels and patterns, pathogen stability, and other factors. The concept of wastewater-based epidemiology first emerged in the 1940s (Paul and Trask, 1941; Paul et al., 1940). A variety of wastewater surveillance initiatives occurred in the 1990s, 2000s, and 2010s, including the use of surveillance in global polio eradication efforts (See Box 1-2), to detect prevalence of the flu, and monitor the use of pharmaceutical and illicit drugs (Safford et al., 2022). The experience of applying wastewater surveillance to poliovirus and coronavirus has highlighted the unique value of wastewater surveillance as well as potential limitations to its application. (See Chapter 2 for an in-depth discussion of how wastewater surveillance has been useful in the COVID-19 pandemic.) In the remainder of this chapter, the committee discusses the development of the National Wastewater Surveillance System (NWSS) and the motivation for this study. PREPUBLICATION COPY 

10 Wastewater-based Infectious Disease Surveillance for Public Health Action BOX 1-2 History of Wastewater Surveillance for Poliovirus Given the global vaccination campaign to eradicate polio, a single instance of poliovirus detection triggers the need for public health intervention. Wastewater surveillance has been a critical tool in tracking poliovirus because, in its absence, asymptomatic poliovirus shedding can remain undetected and allow community spread until detected through clinical cases of acute flaccid paralysis (which occurs in ≤0.5 percent of infections).2 Detection through wastewater triggers targeted screening of the community, which is more efficient and cost-effective than continuous large-scale population-based screening of individuals. Isolation of poliovirus from urban sewage was first reported in 1940 (Paul et al., 1940). Paul and Trask (1941) completed the first study using wastewater surveillance for poliovirus, and building on this study, Melnick (1947) used wastewater surveillance to understand transmission of polio in a population. Even though clinical surveillance of acute flaccid paralysis was considered the gold standard for polio surveillance, throughout the latter half of the 20th century, numerous studies reported the use of wastewater surveillance in addressing poliovirus outbreaks (Adu et al., 1998; Böttiger and Herrström, 1992; Gershy- Damet et al., 1987; Horstmann et al., 1973; Manor et al., 1999a,b; Marques et al., 1993; Pöyry et al., 1988; Thraenhart et al., 1977; van der Avoort et al., 1995; Zdrazílek et al., 1971). By the early 1990s, wastewater surveillance was used to effectively monitor and respond to polio outbreaks with targeted public health interventions and a robust vaccine campaign in Israel and the Palestinian Authority (Hovi et al., 2001; Manor et al., 1999b; Ranta et al., 2001). Since the early 2000s, systematic environmental surveillance for poliovirus has been performed in many countries that were endemic for polio or had risk of re-importation. The global polio eradication initiative has supported wastewater surveillance as a tool since 2013, starting in 5 countries and growing to more than 550 sites in 45 countries for routine wastewater surveillance (WHO, 2022). Wastewater surveillance continues to be an effective tool not only for fighting endemic poliovirus and re-importations but also for addressing vaccine-derived poliovirus outbreaks. The introduction and local spread of a type 2 vaccine- derived poliovirus in London was identified by wastewater surveillance (Wise, 2022; Klapsa et al., 2022). This virus was subsequently genetically linked to a strain implicated in a Jerusalem outbreak (Zuckerman et al., 2022) and a case of acute flaccid paralysis and wastewater detection in New York (Link-Gelles et al., 2022; Ryerson et al., 2022). DEVELOPMENT OF THE NATIONAL WASTEWATER SURVEILLANCE SYSTEM During the COVID-19 pandemic, broad interest in the potential usefulness of wastewater surveillance emerged. This led to the independent development of many local (e.g., sewershed and sub-sewershed; see Box 1-3) and hyperlocal (e.g., building or institution-based) wastewater surveillance efforts. As proof-of-concept was established for the feasibility and potential public health value of SARS-CoV-2 RNA detection and variant sequence identification, the   2 See https://www.cdc.gov/polio/what-is-polio/index.htm. PREPUBLICATION COPY 

Introduction 11   implementation of these systems expanded. Wastewater surveillance was deployed at several locations across the United States and internationally to forecast and monitor disease outbreaks (see Table 1-1) and was found to be effective in capturing information about both asymptomatic and symptomatic infections as well as in predicting outbreaks (see Chapter 2 for more detail). Recognizing the need for centralization and coordination of these efforts, the U.S. Centers for Disease Control and Prevention (CDC) launched the NWSS in partnership with the U.S. Department of Health and Human Services (HHS) in September 2020. The NWSS is the first national-level wastewater disease surveillance system in the United States, and it coordinates with state-, tribal-, local-, and territorial-level health departments to design and integrate wastewater surveillance data to inform public health decisions. The mission of the NWSS is to  offer technical assistance to public health departments and wastewater utilities implementing wastewater surveillance;  coordinate a centralized and standardized data portal for tracking of disease presence across the country;  establish working groups for health departments, public health laboratories, and wastewater utilities for knowledge sharing; and  strengthen epidemiological and laboratory capacity for wastewater surveillance at health departments (Kirby et al., 2021). BOX 1-3 Sewersheds and Sub-sewersheds A sewer network can have complex configurations depending upon the individual location. The geographic area serviced by a network of pipes (sewers) feeding into an individual wastewater treatment plant is termed its “sewershed.” Sewersheds can range in size from very small to very large. Wastewater treatment plants that submit samples to the National Wastewater Surveillance System serve populations that range in size from 100 to 4 million people, with a median of 45,000 people (A. Kirby, CDC, personal communication, 2022). The scale of a wastewater treatment plant and its sewershed are influenced by a number of factors including population size and density, geopolitical boundaries, topography, and technology. Some large urban areas are served by one or more large wastewater treatment plants (e.g., the Metropolitan Water Reclamation District of Greater Chicago operates three treatment plants that each collect and process wastewater from over a million people, along with four medium sized plants [CDPH et al., 2022]). Other urban areas are served by numerous smaller treatment plants; for example, Houston Water operates 39 wastewater treatment plants for its 2.2 million customers.a Thus, as demonstrated in these examples, wastewater surveillance sampling at treatment plant inflow can provide quite different levels of spatial detail. Within a sewershed there may be subareas, each serviced by a network of sewers, termed a “sub-sewershed.” An example is shown schematically in Figure 1-3-1 for Jefferson County, Kentucky (Holm et al., 2022b), which has five sewersheds (i.e., five individual wastewater treatment plants) and several additional sub-sewersheds illustrated by the individual shaded areas. Many sub-sewersheds can be sampled, as in this case, by sampling at individual manholes to large sewers (shown as circles) or at the location of pump stations (shown as squares). Pump stations are the locations of convergence of sewers in a sub-sewershed in PREPUBLICATION COPY 

12 Wastewater-based Infectious Disease Surveillance for Public Health Action order to pump the flow to greater elevation due to the topography of the service area. Spatial resolution in wastewater surveillance is discussed in more detail in Chapter 2. FIGURE 1-3-1 Map of sewersheds and sub-sewersheds used for SARS-CoV-2 in Jefferson County, Kentucky. NOTE: Triangles are wastewater treatment plants. Shaded areas represent sewersheds (delineated by heavy black borders) and sub-sewersheds. Circles are individual sub-sewershed sampling locations. SOURCE: Adapted from Holm et al. (2022b) with permission from the Royal Society of Chemistry. a See https://www.houstonpublicworks.org/houston-water. PREPUBLICATION COPY 

Introduction 13   TABLE 1-1 Selected Examples of Ongoing Wastewater Surveillance Programs as of July 2022, Including Both Community and Institutional Scales Wastewater Surveillance Unique Aspects of the Program Program Missouri was one of the first states to initiate wastewater surveillance testing. This project is a collaborative effort among the Missouri Department of Health and Missouri Senior Services, the Missouri Department of Natural Resources, and the University of Missouri. This project tracks SARS-CoV-2 viral load in the wastewater of more than 100 participating community water systems across Missouri.a State Programs The program involves large-scale collaboration among multiple state agencies, the U.S. Environmental Protection Agency Office of Research and Development, and Ohio numerous universities. Wastewater treatment plants are sampled throughout the state. The state developed a public-facing dashboard that depicts trends in wastewater results. The city collects wastewater samples from the 39 wastewater treatment plants within the city, as well as at lift stations within the sewershed and individual facilities. The city uses the wastewater data, along with other data sources such as individual clinical Houston, Texas testing results and vaccination rates, to identify ZIP code-level “hot spots” for targeted public health intervention. The data are also used to monitor for early alerts of waves Local alongside other data such as emergency visits, general hospital bed use, and intensive Programs care unit bed use. The city quickly developed and implemented a wastewater surveillance program for SARS-CoV-2 by building off its existing opioid wastewater surveillance program. Tempe, Arizona The City of Tempe, in partnership with Arizona State University’s Biodesign Institute, generates and uses sewage data to inform city decisions and operational strategies. The privately funded Sewer Coronavirus Alert Network project is led out of Stanford University in collaboration with an industry partner. The project analyzes daily San Francisco primary settled solids from 11 wastewater treatment plants in the San Francisco Bay Bay Area, Area, serving approximately 10,000 to more than 1,000,000 people. Originally California focused on SARS-CoV-2, the project now reports the wastewater levels of a number Privately of pathogens.b Funded Programs The Rothberg Fund supports a SARS-CoV-2 wastewater surveillance program at New Haven, Connecticut’s wastewater treatment facility, with joint efforts by Yale New Haven, University and the New Haven Water Pollution Control Authority. Daily samples are Connecticut collected, and results are updated weekly. This facility serves 200,000 people in the area.c University of Under this ongoing program that started in May 2020, 340 buildings are monitored for California, San viral activity, and more than 200 wastewater samplers are situated across the campus.d Diego University Programs The university first analyzed samples for SARS-CoV-2 from utilities across the University of country and then began analyzing samples collected on campus. The university has Arizona, Tucson developed action levels for its campus wastewater surveillance program and used the wastewater data to prevent outbreaks. NOTE: Table includes both NWSS-funded community wastewater surveillance programs and privately funded programs. PREPUBLICATION COPY 

14 Wastewater-based Infectious Disease Surveillance for Public Health Action a See https://storymaps.arcgis.com/stories/f7f5492486114da6b5d6fdc07f81aacf. b See https://returntolearn.ucsd.edu/dashboard/index.html. c See https://www.yalecovidwastewater.com. d See http://wbe.stanford.edu. SOURCE: Adapted from EPA (2021) unless otherwise noted. Implementation The rapid expansion and coordination of wastewater surveillance across the United States was an emergency response to the COVID-19 pandemic. SARS-CoV-2 was first detected in the United States in January 2020, and several wastewater surveillance efforts were under way in the spring of 2020, with support from local and state funding, federal emergency response grants, nongovernmental organizations, and philanthropic partners. By September 2020, formal pilot wastewater surveillance sites were established in eight states as part of the NWSS. As of October 2022, the NWSS comprises more than 1,250 sampling sites, covering a population of more than 133 million individuals. In fiscal year (FY) 2022, CDC awarded funding to support wastewater surveillance programs across 42 states, 5 cities, and 10 tribes.3 To supplement jurisdiction-led wastewater surveillance programs, the NWSS provides testing capacity for an additional 500 sites through a commercial testing contract.4 The NWSS continues to expand to new sites (Kirby, 2022). A map of participating sites and the distribution of sites as of October 2022 is illustrated in Figure 1-2. As shown by the map, the geographic distribution of sites is generally clustered near major metropolitan areas with a paucity of sites across the southern and intermountain western United States. NWSS sites are based in 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. Implementation at NWSS-participating sites depends upon three primary entities—the health department, local wastewater utility, and analytical laboratory—to collect, test, and analyze samples and interpret the data (see Figure 1-1). Typically, local wastewater utilities collect, store, and distribute samples, which are used only for the NWSS and have no water quality regulatory implications. A public health, commercial, or academic laboratory partner analyzes the samples, and the public health department interprets the data to identify trends regarding infection prevalence within a community, integrate the wastewater data with other surveillance data, and determine the appropriate public health response. The multidisciplinary nature of a national wastewater surveillance system requires extensive collaboration between and across health departments, testing laboratories, and wastewater utilities. Historically, there has been limited collaboration between public health and wastewater departments (Clason, 2022), and active relationships across agencies rarely existed (McClary-Gutierrez et al., 2021).   3 See https://www.cdc.gov/healthywater/surveillance/wastewater-surveillance/progress/index.html and https://www.cdc.gov/budget/fact-sheets/covid-19/funding/index.html. 4 See https://sam.gov/opp/c68491abc61e4f6392b14d1e1abaf7c7/view.  PREPUBLICATION COPY 

Introduction 15   FIGURE 1-2 National Wastewater Surveillance System dashboard as of October 2022. SOURCE: https://covid.cdc.gov/covid-data-tracker/#wastewater-surveillance. At the national level, CDC provides funding support for these systems. CDC initially provided $2.5 million to support eight pilot NWSS sites, funded through the 2020 Coronavirus Aid, Relief, and Economic Security (CARES) Act.5 The number of sites was expanded through an additional $33 million provided through the Paycheck Protection Program. Initial funding for participating NWSS sites came from Epidemiology and Laboratory Capacity for Prevention and Control of Emerging Infectious Diseases (ELC) Cooperative Agreement grants provided by CDC to eligible health departments (i.e., state health departments, territories, and some large cities and counties).6 An additional $200 million in grants were made available from the ELC Enhancing Detection/Enhancing Detection Expansion program, supported by the Coronavirus Response and Relief Supplemental Appropriations Act of 2021.7 Finally, the NWSS was granted $384 million through the American Rescue Plan,8 starting in FY 2022 for use through 2025. In FY 2022, the NWSS supported wastewater surveillance initiatives in 42 states and 5 cities, with a total of $64 million in funding. The average amount awarded to each jurisdiction in FY 2022   5  Coronavirus Aid, Relief, and Economic Security Act of 2020, Public Law 116-136, 116th Cong., 2nd sess. (March 27, 2020). 6 All 50 states, 5 cities, 1 county, and 8 territories have been awarded ELC funding. See https://www.cdc.gov/ncezid/dpei/elc/elc-recipient-history.html. 7 Coronavirus Response and Relief Supplemental Appropriations Act of 2021, Public Law 116-260, 116th Cong., 2nd sess. (December 27, 2020). 8 American Rescue Plan Act of 2021, Public Law 117–2, 117th Cong., 1st sess. (March 11, 2021). PREPUBLICATION COPY 

16 Wastewater-based Infectious Disease Surveillance for Public Health Action was approximately $900,000.9 In addition, the NWSS has provided funding to 10 tribal communities to develop wastewater surveillance capacity through the Tribal Public Health Capacity Building and Quality Improvement cooperative agreement.10 CDC also plays an important role in aggregating data and sharing the results from participating wastewater surveillance sites across the country. Data from the NWSS are communicated to the public, health officials, and policy makers through a variety of mechanisms, including a public-facing data dashboard, weekly summarized data briefs,11 a restricted-access data dashboard for health departments (Data Collation and Integration for Public Health Event Response [DCIPHER]), and weekly briefs for federal policy makers.12 The goal of the NWSS is for these data to be interpreted by public health officials and used to inform community health interventions, to raise public awareness of disease transmission within communities, and to track pathogen dynamics across the nation. CDC also coordinates Communities of Practice to build capacity among the participating localities and hosts monthly meetings with cohorts of participants across jurisdictions to share experiences and keep health officials apprised of updates or program improvements. As part of the federal support for the NWSS, CDC and HHS also convene the National Sewage Surveillance Interagency Leadership (NSSIL) Committee, in which additional federal agencies collaborate and coordinate to exchange information and discuss agency-specific roles and activities.13 CDC, U.S. Environmental Protection Agency, U.S. Department of Defense, U.S. Department of Homeland Security, U.S. Geological Survey (USGS), National Institutes of Health, and U.S. Department of Veterans Affairs support implementing sewage sampling and developing guidance documents for use by public health officials. CDC and USGS coordinate to provide surge capacity for wastewater testing when needed. Federal agencies also coordinate to prioritize federal research on wastewater sampling, analysis, and interpretation. Finally, NSSIL coordinates with several nongovernmental organizations, including the Association of Public Health Laboratories, the Association of State and Territorial Health Officials, the Water Environment Federation, and the Water Research Foundation (see Figure 1-3). Current Status and Future Outlook As the COVID-19 pandemic continues with ongoing monitoring of emerging variants and subvariants and possibly transitions from emergency response to endemic disease management, the application of wastewater surveillance as a public health tool will evolve. In particular, state, tribal, local, and territorial public health professionals; public utilities; and CDC are reviewing the usefulness of wastewater surveillance to inform public health decisions for SARS-CoV-2 as well as potential applications to other infectious pathogens. The surveillance system is also at a point of transition from an ad hoc collection of willing state and local participants seeking all useful information for local emergency pandemic response to a forward- looking national wastewater surveillance system that serves state, tribal, local, territorial, and   9 See https://www.cdc.gov/budget/fact-sheets/covid-19/funding/index.html. 10 See https://www.cdc.gov/tribal/cooperative-agreements/tribal-capacity-building-OT18-1803.html.  11 See https://www.cdc.gov/coronavirus/2019-ncov/covid-data/covidview/index.html. 12 See https://covid.cdc.gov/covid-data-tracker/#wastewater-surveillance. 13 See https://www.cdc.gov/healthywater/surveillance/wastewater-surveillance/federal-coordination-partnering- wastewater-surveillance.html. PREPUBLICATION COPY 

Introduction 17   national public health objectives simultaneously. Questions remain about what a standardized national wastewater surveillance system should look like, including ethical and privacy considerations; standard methodological approaches for data sampling, analysis, and interpretation; coordination or standardization among jurisdictions; and fundamental considerations of the technical feasibility of wastewater surveillance to monitor emerging diseases beyond COVID-19 in the United States. In addition, uncertainty remains around the use of wastewater surveillance to inform public health response, particularly how this form of disease monitoring can contribute to and complement traditional public health surveillance through clinical data and syndromic surveillance. FIGURE 1-3 National Wastewater Surveillance System Federal Partnering Framework. NOTES: APHL = Association of Public Health Laboratories; ASTHO = Association of State and Territorial Health Officials; CDC = U.S. Centers for Disease Control and Prevention; CSTE = Council of State and Territorial Epidemiologists; DHS = U.S. Department of Homeland Security; DoD = U.S. Department of Defense; EPA = U.S. Environmental Protection Agency; NACCHO = National Association of County and City Health Officials; NEHA = National Environmental Health Association; NIH = National Institutes of Health; NIST = National Institute of Standards and Technology; NSF = National Science Foundation; USGS = U.S. Geological Survey; VA = U.S. Department of Veterans Affairs; WEF = Water Environment Foundation; WRF = Water Research Foundation. SOURCE: https://www.cdc.gov/healthywater/surveillance/wastewater-surveillance/federal- coordination-partnering-wastewater-surveillance.html. PREPUBLICATION COPY 

18 Wastewater-based Infectious Disease Surveillance for Public Health Action MOTIVATION FOR THE STUDY 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 has been divided into two parts as described in Box 1-4. The first phase, which is the focus of this report, provides an assessment of the usefulness of current community-level wastewater surveillance in the United States and its potential value for infectious disease beyond COVID-19. As explained in the statement of task, in the context of this study, “community-level” wastewater surveillance includes “sampling at wastewater treatment plants” and does not include “local surveillance at neighborhood or institutional scales.” However, in committee discussions with the sponsor, hyperlocal sampling at specifically designated sentinel sites, such as likely points of entry of infectious disease, was deemed to be within the scope of the study because the intent of these sites is to provide data of value to the nation (see also Chapter 3). In addition, a few examples of sub-sewershed and institutional-scale surveillance are included in the report to accurately portray the range of wastewater surveillance efforts that took place during the COVID-19 pandemic, and to highlight lessons learned that may be applicable to community-scale efforts. The committee was not asked to assess non-infectious agents or surveillance in global settings. The Phase 2 study (see Box 1-4) will offer a detailed technical evaluation and needs assessment for an ongoing national wastewater surveillance program. To address its Phase 1 statement of task, the committee held two information-gathering meetings. Speakers were selected to complement the broad and interdisciplinary experiences of the committee members, in particular representing perspectives from utility, public health, and ethics stakeholder groups engaged in wastewater surveillance. 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. REPORT STRUCTURE This report describes the usefulness of a robust community-level wastewater surveillance system for the United States and highlights approaches for integrating wastewater surveillance data into a public health response for a variety of pathogens. Chapter 2 provides a retrospective assessment of how wastewater surveillance was used in understanding and informing the public health response during the COVID-19 pandemic, including early challenges that were encountered. Chapter 3 describes a vision for a national wastewater disease surveillance system, including key characteristics of a robust system. Chapter 4 discusses strategies for implementing the committee’s vision for a national wastewater-based infectious disease surveillance system beyond COVID-19, discussing future challenges and strategies to collaborate across federal, state, and local jurisdictions. PREPUBLICATION COPY 

Introduction 19   BOX 1-4 Statement of Task Phase 1 An ad hoc committee of the National Academies of Sciences, Engineering, and Medicine will review community-level wastewater-based disease surveillance and its potential value toward prevention and control of infectious diseases in the United States. The committee will: 1. Describe wastewater-based disease surveillance and how it differs from other approaches to disease surveillance and other wastewater monitoring for contaminants. 2. Review how wastewater-based surveillance has been useful in understanding COVID-19 in communities and informing local public health decisions. 3. Examine the potential value of specific applications of wastewater-based disease surveillance for understanding and preventing disease and illness beyond COVID-19 and factors that may limit its application in the United States. 4. Describe the general characteristics of a robust, integrated approach for national use of wastewater-based disease surveillance. 5. Discuss broad approaches to increase the public health impact of wastewater surveillance in the United States and the most effective strategies for federal, state, and local coordination to achieve national implementation of wastewater surveillance for an array of diverse infectious disease health indicators. For the purpose of this study, community-level wastewater-based disease surveillance implies sampling at wastewater treatment plants and does not include local surveillance at neighborhood or institutional scales. To inform the study, the committee will briefly review ongoing and planned U.S. federal, state, local, tribal, and territorial efforts as well as international case examples for implementing wastewater-based disease surveillance. The committee’s report will include conclusions and recommendations on wastewater-based surveillance in federal, state and local public health efforts in the prevention and control of infectious diseases. Applications of wastewater-based surveillance for non-infectious agents, in global settings, and for facility-level surveillance are outside the scope of this review, but the committee may identify these for future evaluation. Phase 2 The committee will conduct an in-depth study of opportunities and barriers relevant to increasing the use and utility of wastewater surveillance for the prevention and control of infectious diseases in the United States. Specifically, the committee will: 1. Define specific characteristics for development and implementation of a robust, integrated wastewater-based infectious disease surveillance program and discuss technical constraints and opportunities associated with wastewater sampling, testing, and data analysis, including: PREPUBLICATION COPY 

20 Wastewater-based Infectious Disease Surveillance for Public Health Action  Methods and/or quality criteria, including genomics and sequencing, to detect pathogens, including strain- or variant-specific methods. Methods for discovery of unknown emerging pathogens can also be considered.  Data reporting, data analysis, and data interpretation for detecting emerging threats to public health and estimating disease incidence and prevalence, including data integration with other surveillance data for improving predictive models. 2. Identify significant technical limitations that could impact the feasibility of using wastewater surveillance as a platform for generating data for indicators of public health status and risk. 3. Describe the research, development, and information sharing needed to meet emerging needs and increase impact of wastewater surveillance for improving public health in the United States. 4. Identify resources for supporting wastewater surveillance.   PREPUBLICATION COPY