A method that first developed around polio elimination and matured during the COVID pandemic, is now being tested and used to track a much wider array of emerging disease threats. A unique symposium of scientists and public health experts at the Paris Sorbonne University last week looked at its promise and potential. 

In April 2020, French researchers at the Sorbonne and the Obepine research network,  [Observatoire Epidémiologique dans les Eaux Usées] realized that they could get an “early signal” of the trajectory of COVID-19 case incidence through wastewater surveillance. They began routine monitoring of some 200 large wastewater plants – an initiative that became a trend-setter in Europe and worldwide. 

Wastewater-based surveillance has long been used to track polio as well as a handful of other deadly, waterborne diseases, such as cholera and typhoid. However, the COVID-19 pandemic proved to be a turning point in wastewater-based epidemiology (WBE) – popularizing the method and introducing it to the mainstream of national surveillance programmes. 

Last week, a unique symposium at the Sorbonne University brought together about four dozen scientists from around the world to explore the approach, its challenges and potential to track other diseases beyond COVID, which can also circulate silently under the radar for weeks or months, before symptomatic cases begin to appear in human populations. 

The conference was led by the Sorbonne and Obepine with the 4EU+ university alliance, and the University of Paris-Pantheon, as well as the World Health Organization and the Geneva Health Forum (GHF). 

The conference is part of a series of symposiums developed in collaboration with the WHO on “lessons learnt from the COVID-19 Pandemic,” said Dr Antoine Flahault, director of the University of Geneva’s Global Health Institute and GHF chair. The first such conference Bern in 2023, addressed indoor air pollution; a third session is planned on drug and vaccine development.    

Dutch and French researchers developed first data on wastewater SARS-CoV2 concentrations and COVID disease

“The first data showing that SARS CoV2 levels in wastewater was related to COVID incidence rates in the population came from France and the Netherlands,” said Sorbonne virologist, Dr Vincent Marechal, who led the pioneering French research with the Obepine surveillance network. 

“We need to learn the lessons about what was done during the COVID 19 pandemic… to inform policies,” he said, discussing the goals of the event with Health Policy Watch.  

“We need to normalize the way to do analyses, to treat data. And we need ways to transfer these technologies to low and middle-income countries (LMICs),” he said.

“Although we are aware that this strategy cannot be used for all infections, the benefit/cost ratio is remarkable, particularly for detecting and monitoring epidemics in countries that do not have the logistical or economic means to carry out individual epidemiological monitoring of their populations.”

Roots in polio elimination – SARS-CoV2 pandemic triggered an explosion of interest

It’s a method that has been around for nearly a century – ever since the Yale University researcher Dr John Paul first documented the presence of poliovirus in sewage in Charleston, South Carolina in 1939. 

At the start of the global polio elimination campaign, monitoring wastewater for poliovirus gained traction as a way to identify the presence of virus early on. It was particularly effective since even among the vaccinated, symptomatic cases only occur in 1 out of every 200 people.  Use gradually expanded to include other deadly diseases, such as cholera and typhoid.

Following their 2020 identification of the link between COVID-19 incidence and wastewater concentrations of SARS-CoV2, the Obepine network spent two years monitoring the 200 French wastewater plants providing a regular data flow on the ebb and flow of the disease and its variants to the national and local governments, as well as to the public. 

The initiative, under the auspices of the French Ministry of Research and Innovation and the Ministry of Health, eventually became flagships in a broader EU-wide effort to monitor wastewater during the pandemic period. 

“Just one month of wastewater monitoring, covering about 40% of the population, and producing an incidence curve for the whole population, cost about €300,000,” Marechal remarked in a post-conference interview with Health Policy Watch. “In comparison population-based monitoring would have cost about €1.6 billion over the same period.” 

Post-pandemic, France’s own wastewater surveillance of COVID continues, but it has been taken over by the French Ministry of Health’s Sum’eau network, which is only monitoring about 54 wastewater plants. That, in Marechal’s view, is too small a sample from which to draw robust conclusions about COVID or to track prevalence of other new infections of concern like the mpox virus.

“In our case, the Health Ministry said that we should be doing research, while they took over the more routine monitoring function,” he said. “Although in my opinion, it is a mistake to split these two functions.”

Method still being used widely for COVID tracking 

Elsewhere in  Europe and beyond, institutions in dozens of countries continue to track SARS-CoV2 in wastewater samples  – albeit with varying degrees of intensity and a diversity of scientific and institutional approaches. 

There are at least a few testing sites in most major countries of Europe, Asia and the Americas, a handful of African nations and Saudi Arabia. About 31 countries, mostly in Europe and North America, but also including Turkey and India, publicly report data, according to a WHO dashboard that follows trends in wastewater surveillance. 

And a detailed WHO technical guidance explains how to conduct wastewater surveys – although ‘guidance’ in WHO parlance is not a formal “guideline” that sets an international standard.  

It’s not surprising that such monitoring, to date, is the most common in middle- and high-income settings, where formal wastewater treatment systems made sampling easy, said Marechal. 

But in the same way that the method has been used to track polio, typhoid and cholera, it’s important to develop cost-effective methods whereby the science of wastewater-based epidemiology (WBE)  can be effectively deployed for more endemic and emerging diseases in developing countries.

What pathogens can be monitored most easily? 

Post-Covid, mpox is another virus that became the focus of significant WBE tracking in developed countries such as Canada.  Gastro-intestinal viruses, such as noroviruses or rotaviruses are among those other pathogens that can be easily monitored in wastewater, Marechal said. 

“It also works for most major flu viruses, flu A, B, RSV (respiratory syncytial virus), and it can be used for AMR (anti microbial resistance),” Marechal added. 

While flu is not necessarily as deadly, an “early signal” about prevalence from wastewater can alert doctors about the onset of flu season, who then may be quicker to examine and diagnose the virus in their patients, he pointed out. Even more significantly, such a system can also provide critical signals early on of a flu epidemic or pandemic. 

There is also promise that measles outbreaks might be identifiable early through wastewater samples, he said. Although the science around that is not yet well developed, his team of  researchers have obtained promising results in the context of an ongoing study with the Institut Pasteur in Guinea. 

“A field that is much more difficult, arboviruses, dengue, zika, and chikungunya,” Marechal observed. While the surge in dengue virus makes this a worldwide concern, there are challenges in monitoring through wastewater because “the amount of viruses excreted is much lower than flu or COVID.” 

Deadly endemic diseases such as marburg virus and Ebola also pose special challenges. These viruses may first spread in more isolated rural areas of low-income countries where wastewater is not collected in large concentrations. Also, both marburg and Ebola are highly symptomatic in those infected, so the contribution that wastewater detection may make to early detection and tracking is comparatively lower, than, say polio.  

Applications in low- and middle-income countries  

While not used routinely in low- and middle-income countries, wastewater monitoring of diseases has paid big dividends in the global polio elimination campaign, where only one in every 200 cases is symptomatic and the costs of human, blood-based screening would be exorbitant.  

Wastewater monitoring was dubbed the “silent hero” that helped public health officials track and ultimately halt a 2021-22 outbreak of wild poliovirus type1 in Malawi and Mozambique, triggered by a strain imported from Pakistan. 

More recently, a polio outbreak in war-torn Gaza was first identified through wastewater samples in mid-July, leading to the launch of a massive vaccine booster campaign. 

“The value of wastewater surveillance….is highlighted by the investments made by the Global Polio Eradication Campaign program and WHO, and there are now thousands of sites where wastewater science is conducted for poliovirus, often from informal surge networks,” said Nicholas Grassly of Imperial College, London. 

For typhoid, as well, the use of such informal networks has been “really key,” Grassly said, because of the close correlation between wastewater levels of the virus and human cases.

In addition, blood-based surveillance of typhoid in the kinds of low-income settings where it typically occurs is very limited. Linked to that, the uptake of typhoid vaccines has been slow, he said.  

“So the question here is, can we use wastewater detection of Salmonella typhi (typhoid bacteria) to motivate and monitor the introduction of typhoid conjugate vaccines, having to sample from informal sewage networks, drainage channels, rivers? 

“It’s a very different system to what we would have in a high income country, but it is possible, and what we’re seeing is that the emergence of data to show that the prevalence of detection of salmonella type in the environment does correlate with clinical incidence of disease.”

Moving ahead, WBE-based sampling to identify the spillover of zoonotic diseases into human populations, early on, as well as pockets of drug resistant pathogens also hold great potential for low- and middle income settings  – where both risks are growing, often without adequate surveillance, conference panelists also noted.

“Antimicrobial resistance is one of the major, if not the major, pandemic disease that we have now affecting global health, while wastewater monitoring is probably one of the most appropriate and efficient ways to cope with this problem,” remarked Alfonos Zecconi, of the University of Milan. 

Surveillance for zoonotic spillover, meanwhile, is the focus of a new grant by the Bill and Melinda Gates Foundation in Africa and Asia, Grassly said. Their grant will support the piloting of methods for early detection of zoonotic infections in human wastewater.  

“Can we use waste water surveillance to estimate the extent of zoonotic infection and associated risk factors and look for evidence of human transmission and genetic adaptation – potentially providing an early warning of threats?” Grassly asked. 

“If we can do that, then we can implement risk mitigation activities, not only in public health, but across sectors, and also start to develop those medical countermeasures that we might need, including vaccines and diagnostics.” 

Brazil: standardizing a diagnostic ‘kit’ for wastewater surveillance 

Beyond the research questions, rolling out surveillance methods more widely  involves numerous challenges for LMICs, even in countries such as Brazil with a strong research tradition and considerable experience in waste water testing,  said Maria Aguiar Oliveira, of the Fiocruz Institute. 

Fiocruz is working with the Ministry of Health to establish formal guidelines for wastewater surveillance, which would be integrated into the existing National Public Health Laboratory Network. 

Fiocruz also is developing a standardized diagnostic kid for wastewater sampling of viral  pathogen samples so that results from different testing sites are comparable.

“One of the biggest challenges is how to compare the results because everywhere, each group is using a different target, different sampling and so on,” Aguiar Oliveira observed, noting that wastewater sampling also requires entirely different tools and targets, as compared to diagnostics for human populations. 

“We have been designing and validating a kit, a molecular panel, and the idea is from viral concentration to viral detection to have the single product that we can scale up in a very reasonable price to all of our networks – because we are a nonprofit public institution.”

Such harmonization of best practices in sampling and analysis can both improve the reliability of results – as well as bringing costs down making the technique even more accessible, pointed out Marechal. 

“We need to normalize the way to make analyses, to treat data,” he said. “We can find money to set up research projects. What we need is money for sustainable monitoring, for years on end,” he says.

“Efforts must be made to produce high-quality, standardized data that can be integrated into robust epidemiological models with dynamic mapping of outbreaks. This is essential if we are to have early warning systems, and if we are to detect changes in the trajectory of an epidemic, upwards or downwards, as quickly as possible.”

Who owns sewage? 

Along with the technical and cost issues, key questions of public trust, individuals’ right to privacy and data ownership also shadow WBE research. 

The thorny dilemmas are illustrated by one study in Missouri, which tracked a novel SARS spike sequence variant to a commercial building of just 30 people in the period of January 2022-23, notes Marechal. 

“The mutations in the spike gene and elsewhere resembled those subsequently found in omicron variants,” reports the paper by researchers at the Universities of Missouri and Wisconsin, published in Lancet Microbe in April 2024. 

In that case, the pinpointing of the variant to just one building did not lead to any particular policy action – but what if an even more dangerous virus had been found in wastewater in the same location?  

“The question is twofold,” said Marechal.  “Would you even be allowed to do that in France – I’m not sure.  And if you did, while it was not the case in Missouri, are you allowed to impose lockdowns or individual confinements as a result? This example prompts a lot of reflection on the legal and ethical framework for WBE work.” 

While emerging diseases may also flourish in marginalized communities with less access to hygiene, sanitation and healthcare, the rights of religious and ethnic minorities, migrants and people with diverse sexual orientations also must be respected, underlined Jean Baptiste Guyonnet, of Panthéon Assas University.

So action on a disease risk discovered through wastewater data would be carefully evaluated through the lens of the “proportionality” of the risk versus any measures that might be considered, and the harm they could do to those communities.  

Building trust 

But the best way to minimize ethical risk is by partnering directly with the affected community, stressed Talia Glickman, of the Canadian Water Network, “for a community informed, if not a community led response.”  

She cited one example from Canada’s Ontario Province response to the global mpox outbreak of 2022-2023 – which WHO had declared a global health emergency and hit hardest a men having sex with men. 

When provincial authorities decided to start monitoring wastewater for mpox infections in mid-2022, they reached out to the Gay Men’s Sexual Health Alliance (GMSH). 

“In particular with mpox being monitored in the wastewater, there was a need to discuss the communication of potentially sensitive data and what those impacts would be on this particular equity deserving population,” said Glickman. “As we all know, there were a lot of uncomfortable parallels to early days of the HIV pandemic…. And so the GMSH were able to coordinate regular meetings between community-based organizations, public health authorities, researchers and policymakers, which helped ensure timely feedback and collaboration.

“The bottom line is that moral obligation, I think when you’re collecting that data, you have an obligation to communicate it back to the affected communities,” Glickman said. 

“This sort of cross sector coordination… improved the speed, the quality of the response, and it made Ontario’s response to mpox one of the most effective mpox responses in the world…. And it provides a great example of integrating all those activities into wastewater monitoring.”

Ethical research principles offer good guidance 

United States law doesn’t require, or prohibit, very much in terms of research on wastewater, added Natalie Ram, of the University of Maryland. 

However, researchers funded by the federal government are entitled to special legal protections that allow them to protect the confidentiality of their research subjects or related data – e.g. say from law enforcement.  

“But ethical practice can impose a much better guiding framework,” added Ram. “Public health only works when we have public trust. And so public trust is a necessary predicate for successful monitoring and implementation, uptake of community responses. 

“Wastewater surveillance gives us a lot of raw data, and we might not need people’s consent to get it right, but if you want to use it ethically, as we heard earlier this morning, you’ve got to have a plan for what to do with that data. And if you go to the community and say, oh, we’ve been spying on your wastewater all of this time, surprise, now go get a vaccine, that’s not going to go very well. You have to have buy-in from the community, and support. 

“And that gets all the more important as the watersheds get smaller because then they can become very population specific. 

Integrating into policy decision-making 

Amidst this plethora of legal and ethical questions, WHO has not been in a rush to set down strict, prescriptive guidelines on exactly how countries should manage wastewater surveillance. 

Part of that is likely related to the unsettled legal issues around privacy and the ownership of data on wastewater pathogens – which so far lacks a global standard of consensus upon which WHO could build a guideline standard. 

But that also reflects the changing role of WHO in the global health scene, said Dr Chikwe Ihekweazu, WHO’s assistant director general for Health Emergency Intelligence and Surveillance Systems, at a closing session of the Paris event. 

“Thirty years ago, …the world would wait for WHO to come up with guidance, and everyone would be paralyzed until it does,” Ihekweazu observed.

So now we’re in a different world; when there’s an opportunity, there are lots of initiatives driving it forward, and our role is changing. We have to think together, and respect the opportunity that academia provides, digital surveillance systems offer, countries offer, regional bodies offer, financing bodies offer, philanthropic organizations offer, and see how we can make the best use of the various skills, resources and expertise that we all bring to the table. 

So …it’s a good problem to have. We’re not in a position of absolute scarcity; we have a problem of making the most efficient use of the expertise and resources that we all bring to the table. And it’s a humbling position to be in, and maybe that’s why this meeting is so important with the players in the room.

Image Credits: WHO , Kando , Naughton et al, January 2023, US CDC Mpox wastewater data, Uzzell et al, 2024/PLOS Neglected Tropical Diseases, Eric Comte, The Rivers Trust , Eric Comte .