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Pandemics start slowly — a few cases here, a few there — until suddenly people are sick or dying everywhere. Early detection by monitoring wastewater can help short-circuit that cycle.

It’s difficult to tell what is happening right now with highly pathogenic avian influenza A H5N1 (bird flu), which is rapidly spreading among cows and other mammals. The outbreak has raised concerns among virologists and epidemiologists that the current spread in mammals may allow the bird flu virus to adapt to mammalian physiology, pre-adapting it for sustained spread among humans, which could be catastrophic.

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In its current form, H5N1 is already quite dangerous for humans. Since 2003, outbreaks of bird flu among poultry have resulted in 880 documented cases of presumed transmission from birds to humans, with about 50% of cases resulting in death. These cases, however, have occurred mostly among people with close proximity to birds, such as those who had small backyard flocks and poultry farm workers.

If the H5N1 virus gains the ability for sustained human-to-human transmission, we could have another deadly pandemic on our hands.

These developments are of great concern to scientists like us who work on pandemic preparedness and response. We believe there is an urgent need to develop the capacity to rapidly detect and monitor the potential spillover of H5N1 into humans, including sustained human-to-human transmission. This will be challenging — if not impossible — by relying primarily on traditional public health surveillance approaches. A relatively novel tool, wastewater surveillance, demonstrated great potential during the Covid-19 pandemic for early detection and monitoring of that threat on a large scale, yet it remains vastly under-leveraged for H5N1 at this precarious moment.

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Our team established New York City’s community-based wastewater surveillance for SARS-CoV-2, analyzing the waste of 8.5 million New York City residents, as well as commuters and tourists who use bathrooms while in town and, yes, the waste of many NYC dogs, rats, birds, and other animals. This approach demonstrated the potential for the early detection of SARS-CoV-2 surges and outbreaks of emerging and reemerging infectious diseases. For example, our team documented the first evidence of the Omicron variant in the U.S., which was present in New York City wastewater 10 days before the first U.S. clinical case was identified via traditional surveillance.

When a case of acute flaccid paralysis caused by vaccine-derived poliovirus type 2 was reported in an unvaccinated person from Rockland County, N.Y., wastewater from there and surrounding counties showed the presence of poliovirus up to 25 days before and 41 days after the onset of symptoms in that patient, signaling the presence of a much broader outbreak than was previously appreciated.

This polio testing was done retrospectively, using stored wastewater samples tested after cases were detected via traditional public health surveillance, when the outbreak was well underway. If implemented earlier, however, wastewater surveillance could have detected this event more rapidly than traditional surveillance, giving public health authorities and the public more lead time to prepare and mobilize.

In many areas of the U.S., human waste flows from toilets through sewers into central municipal wastewater treatment facilities, where it can be sampled and tested for the presence and levels of pathogens. Yet pathogens circulating among animals are also present in residential sewers as a result of runoff into sewer sheds and other inflows, the presence of animals such as rats in sewers, or discarding large volumes of contaminated milk from dairy cows with H5N1 infection into the sewer system.

Wastewater surveillance systems exist throughout the U.S.; most are part of the National Wastewater Surveillance System, which is supported by the Centers for Disease Control and Prevention. This system is critical for national pandemic preparedness and response. While it has been used mostly for monitoring Covid-19, the potential exists for it to be on the lookout for a wider array of public health emergencies, including infectious disease threats like H5N1, industrial accidents, or bioterrorism. A recent preprint from U.S. researchers shows that community-based wastewater monitoring can detect animal contributions of H5N1 influenza, validating the use of wastewater surveillance for zoonotic diseases (infections that are spread between people and animals).

At this stage in the H5N1 situation, it is essential to rapidly detect spillover into the human population. Since community-based wastewater contains waste from both humans and animals, using community-based surveillance alone makes it impossible to rapidly detect and differentiate human outbreaks of H5N1 happening alongside animal outbreaks. Another limitation is that early in an outbreak, precisely when it is most important to detect, relatively few people are infected, and the concentration of the pathogen may be too low to detect.

To address these limitations, we initiated a pilot study of wastewater surveillance within New York City’s public health care system, a collaboration with NYC Health and Hospitals. As part of this work, we have been continuously monitoring wastewater at four H+H facilities for influenza and SARS-CoV-2, and have consistently found that we are able to detect surges in genome copies in hospital wastewater before surges in clinical cases are reported via traditional surveillance approaches. We have also monitored and detected mpox at different points when there were concerns about surges in cases of that infectious disease. (Technology developed by Sentinel Biotech, a company that two of us, J.D. and M.T., co-founded, is being used in this pilot.)

Wastewater from these facilities reflects activity from thousands of inpatients, outpatients, visitors, and employees. Routine testing of hospital-based wastewater may provide early detection and monitoring of potential infectious disease threats emergency rooms and hospitals are where very sick people show up first, and the wastewater samples are coming from fewer individuals. Also important, there is no animal waste present in hospital wastewater, meaning that the detection of any H5N1 and other zoonotic pathogens in hospital wastewater represents spillover activity in humans.

To be adequately prepared for the next pandemic, we believe it is critical for wastewater surveillance systems to be able to distinguish between human and animal contributions of infectious material in sewer systems. We are now actively developing genetic tests based on the H5N1 sequences the U.S. Department of Agriculture recently released that can be used for testing hospital wastewater in New York City. Data from these efforts, alongside traditional surveillance data, will offer vital opportunities to enhance early detection of H5N1 activity in humans under this current threat, as well as for future health crises.

We believe that more investment aimed at rapidly expanding the capabilities of wastewater surveillance is urgently needed for early detection and monitoring of a wider array of pathogens with pandemic potential than is currently under scrutiny. Wastewater surveillance is an ideal tool because of its low cost, ability to cover large populations, and capacity for early detection. In the short term, the responses of local, state, and national public health agencies should include immediate deployment of wastewater testing for H5N1.

Given that the most likely source of future pandemics will be from microbes circulating in the animal kingdom, the settings considered for wastewater surveillance for zoonotic pathogens like H5N1 should expand to include waste directly collected from facilities such as hospitals, large-scale emergency departments and outpatient health care providers, schools and universities, and nursing homes to enable more rapid and definitive detection and differentiation of animal outbreaks from human spillover activity leading to sustained community transmission.

Denis Nash is an infectious disease epidemiologist, professor of epidemiology at The City University of New York (CUNY) Graduate School of Public Health, and the executive director of the CUNY Institute for Implementation Science in Population Health. John Dennehy is a virologist, professor of biology at Queens College of CUNY, and co-founder and president of Sentinel Biotech LLC. Monica Trujillo is a professor of biology at Queensborough Community College of CUNY, and co-founder and chief technology officer Sentinel Biotech LLC. Leopolda Silvera is the deputy director of public and global health initiatives at NYC Health + Hospitals.

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