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    How sewage surveillance is helping spot disease outbreaks early

    Widespread wastewater testing began during the COVID-19 pandemic. Now, public health officials are expanding their efforts to look for monkeypox, polio, even influenza. Is this the future of infectious disease monitoring?

    Worker in water treatment plant

    In the first few days of March 2020, Alexandria Boehm, PhD, Marlene Wolfe, PhD, and Krista Wigginton, PhD, all then at Stanford University, submitted a rapid proposal to the National Science Foundation to sample wastewater in the San Francisco Bay Area for evidence of SARS-CoV-2.

    “The program director reached out and said ‘Well, this is really interesting, but I don’t think the coronavirus is going to be an issue in the United States, so we’re not going to fund this proposal,’” Wolfe recalled recently with a laugh. A few weeks later, when it became clear that the coronavirus was, indeed, going to “be an issue,” the funding came through — on the same day that the Bay Area went into total lockdown.

    Boehm, Wolfe, and Wigginton then had to scramble to get back into the lab to develop sampling and testing protocols, as well as assemble an ad-hoc workforce to collect and test the samples, efforts that eventually led to the development of the Sewer Coronavirus Alert Network (SCAN), which continues to daily test nine wastewater treatment plants in Northern California. Last month, Boehm and Wolfe launched WastewaterSCAN, an effort to expand sewage surveillance to 300 sites across the country.

    Throughout the pandemic, state and local efforts to test wastewater for the presence of the coronavirus exploded, as health officials realized they could determine the presence of COVID-19 in their communities long before test results came in and hospitals filled up with patients. In late 2020, the Centers for Disease Control and Prevention (CDC) established the National Wastewater Surveillance System (NWSS) to provide a federal clearinghouse for wastewater testing results. Today, about 1,200 public utilities in all 50 states report their results to the CDC, says NWSS director Amy Kirby, PhD.

    While not all communities are represented — Kirby says the CDC is still trying to recruit utilities operators in small, rural areas — NWSS provides a fairly robust picture of the presence and prevalence of SARS-CoV-2 in communities across the nation.

    Public health officials now use the CDC’s data — and data from their own health departments or state, local, and academic partners — to set up mobile testing sites and vaccine clinics, to issue mask mandates (or cancel them), and to send out messages to their communities about risk levels and recommendations to mitigate personal risk.

    Now, as monkeypox and poliovirus — two viruses not detected in the United States in some time — make an appearance, public health officials are using the same infrastructure developed during the COVID-19 pandemic to test for these other infectious diseases.

    “The ability to monitor monkeypox at the very beginning of the outbreak in the United States really demonstrated how flexible and adaptable and useful the system can be,” says Wolfe, who is now an assistant professor in the Gangarosa Department of Environmental Health at Emory University in Atlanta. “The resources and the human capital and the amount of research that’s happened over the past two years from so many people in this field has been enormous. I really think that we’ve launched a new revolution in the way that we monitor infectious diseases.”

    A rather messy beginning

    That sewage surveillance is now an accepted part of the public health response belies the fact that widespread wastewater testing for pathogens is a fairly nascent technology — and that in the early days of the COVID-19 pandemic, multiple academic, state, and private laboratories were all just trying to figure out how to make it work.

    The Houston Health Department partnered with two academic labs — one at Baylor College of Medicine and another at Rice University — just to see if their testing yielded the same results. “We decided that we were going to sample our wastewater treatment plants and then we had Baylor and Rice separately analyze the data from each sample,” says Loren Hopkins, PhD, the chief environmental science officer for the City of Houston Health Department. “They each did triplicate testing on each sample, using different methods. … It was five weeks of really intense testing before we finally got the accuracy down and I thought, ‘Now I can use this.’”

    Houston still analyzes each wastewater sample twice, but now one test is conducted by the health department’s own lab, and the other by Rice. All results are posted on the Houston Health Department’s website, as well as sent to the CDC, which recently recognized the department as a National Wastewater Surveillance System Center of Excellence.

    At Stanford, the early days of sewage surveillance literally involved sending students and faculty to various public utilities in Northern California to pick up samples and bring them back to the lab for testing. As the technology evolved, Stanford partnered with Verily, a life sciences company in the Bay Area, to do the testing, with samples couriered or sent via FedEx or UPS to the lab each day.

    In the lab, scientists look for the genetic material of the coronavirus to determine whether it is present in the wastewater — and thus in the community. As time went on, they were able to look for specific variants by targeting the area of the genome that had a mutation specific to that variant, Wolfe says.

    In fact, a study published in July in Nature found that wastewater surveillance was able to accurately predict the omicron variant in San Diego 10 days before the first clinical detection.

    Such early warning signals can help determine public health interventions, but can also be used by clinicians. For instance, clinicians in Northern California were able to pivot early in the omicron wave to administer a certain type of monoclonal antibody treatment to patients, once it became clear from wastewater testing data that omicron was more prevalent than the delta variant, Wolfe says.

    Now that monkeypox and poliovirus have been identified as public health threats, scientists across the country are once again developing testing protocols for these two infectious agents.

    In New York, not long after a patient with paralytic polio was diagnosed in Rockland County, the New York State Department of Health began to test for the presence of poliovirus in wastewater. What they have found has been alarming: polio is, indeed, circulating not just in Rockland County but in surrounding counties and New York City, prompting public health officials to set up vaccine clinics and encourage those who are unvaccinated to get the shots. Vaccination against polio has declined in recent years, with 86.2% of New York City children having received the recommended three doses of vaccine. However, just 60.3% of the children in Rockland County, where the polio patient was identified, have received their vaccines.

    “For every one case of paralytic polio identified, hundreds more may be undetected,” said New York State Health Commissioner Mary T. Bassett, MD, MPH, in an August 12 press release. “The detection of poliovirus in wastewater samples in New York City is alarming, but not surprising. Already, the State Health Department — working with local and federal partners — is responding urgently, continuing case investigation and aggressively assessing spread. The best way to keep adults and children polio-free is through safe and effective immunization.”

    The future of disease detection?

    While the COVID-19 pandemic was the first time that wastewater surveillance had been used to detect the presence of a respiratory virus in a community, it certainly will not be the last. Already, the CDC is looking into using NWSS as a “multi-pathogen platform” to detect influenza and respiratory syncytial virus (RSV), as well as foodborne illnesses, monkeypox, and the emerging fungal pathogen Candida auris, Kirby says.

    Nationwide testing for poliovirus is not likely, as vaccination rates are fairly high in most communities. However, the CDC is in the process of identifying communities with low vaccination rates and will “work with the health departments in those communities to get wastewater surveillance in place,” Kirby says.

    Interest in wastewater surveillance for infectious diseases has remained high, not just among public health officials but also hospitals, doctor’s offices, and even individuals.

    “Public health officials have expressed to us that they find the [wastewater] data to be incredibly useful,” Wolfe says. “We’ve also seen clinicians and hospitals using this to predict surge capacity. … But we’ve also heard a lot of people saying, ‘You know, I look at your website to decide if I’m going to wear a mask when I go to the grocery store, even though it’s not required.’ Having policies is important, but we want to make sure that in the absence of public policies, that individuals also have good data in their hands to make their own decisions, because risk is much more than just how many cases are in the community.”

    In Houston, the public health department has seen a similar interest among individuals who want to make their own calculations around risk management. Officials there just finished a survey looking at how wastewater surveillance could better support schools, in which they surveyed school nurses, teachers, and even parents. “One thing that was really interesting is that the mothers, they want more data. There was a sentiment among the school staff that they thought all this information would be frightening, but the parents were like, ‘No, bring it on. We want to know what’s happening,’” Hopkins says.

    As the public becomes more comfortable with the results of wastewater testing, and public health officials rely on it to detect disease outbreaks early, efforts to ramp up the infrastructure to collect and test even more samples is growing. So far, WastewaterSCAN has enrolled 50 public utilities in the program, and has funding to scale up to 300.

    The CDC continues to do outreach to those communities that do not currently test to offer funding and resources. “We have 42 states now that are funded to do wastewater surveillance, up from 33 the year before,” Kirby says. “Unfortunately, we do have some communities that just don’t want to put any additional resources or time towards COVID surveillance, but as we expand to other targets, I’m hopeful that that will change.”

    Adds Wolfe: “Counting individual cases and taking care of individual patients who are sick is always going to be the cornerstone of infectious disease outbreak response. But we have the ability now to provide this population-level perspective, to have a system that is consistently running in the background that we can use not only to monitor for seasonal threats like flu and RSV, but also be prepared for emerging outbreaks like monkeypox. That will be an enormous boost to our public health infrastructure, especially as we see that with climate change, infectious diseases will continue to be a global threat.”