In early March, Dr. Blake Hanson and his colleagues at the Texas Epidemic Public Health Institute were preparing for a fire drill of sorts.
What if a virus with the potential to spark the next pandemic turned up in the wastewater they monitor? And what if that virus was the bird flu, H5N1, which has killed millions of animals and about half the nearly 900 people it has infected worldwide over the past two decades?
They gamed out this what-if exercise on a Monday. By Thursday of that same week, Hanson’s colleague, Dr. Michael Tisza, a molecular virologist and microbiologist at the Baylor College of Medicine in Houston, was ringing the alarm.
This time, it was not a drill.
“Mike had called me and said, ‘Hey, I think I found it,’” said Hanson, an epidemiologist at UTHealth Houston who uses big data methods and genomics to investigate infectious diseases.
That was March 7, about three weeks before the US Department of Agriculture announced that H5N1 had infected dairy cattle in Texas for the first time.
A different kind of wastewater monitoring
Over the past two years, as the idea of sampling sewer systems for the virus that causes Covid-19 and other pathogens has caught on across the country, the Texas Epidemic Public Health Institute — or TEPHI — took a different approach.
Rather than looking only for specific viruses, researchers there decided to use advanced techniques and computers to help sift through the vast soup of genetic material in their wastewater samples. By doing this, they’re able to find viruses they expect to see as well as ones they don’t know to look for.
“We can capture every known virus that that’s in the sample, and then the computational team will analyze the data comprehensively and see signals for many viruses, and that’s the benefit, I think, of what we’re doing relative to other sites,” said Dr. Anthony Maresso, a molecular virologist and microbiologist at the Baylor College of Medicine in Houston, who envisioned the system.
At least two other organizations have also been looking for signs of H5N1 in wastewater.
The WastewaterSCAN network, which is directed by researchers at Stanford and Emory Universities and Verily, recently posted a preprint study showing that it could detect the H5N1 virus in wastewater by looking for one specific part of the virus.
In addition to that early data, the team has since tested three additional sewer systems: one in North Carolina near a known H5N1 cattle outbreak, one in a California city that was having an unseasonably high number of human influenza A cases and one in a city in Hawaii where there are no dairy processing plants and no known cases of highly pathogenic avian influenza. In each case, the test correctly ruled in or out H5N1 infections. It was so successful that WastewaterSCAN plans to start using the test at all 190 wastewater sites it monitors.
The US Centers for Disease Control and Prevention also recently launched a dashboard showing sites where influenza A viruses are being detected at unusually high levels.
H5N1 is an A strain of the flu virus, like some types of seasonal flu. Detecting A strains now, in the offseason, is a reasonable proxy for H5N1, Maresso said, but it will be a less useful approach when seasonal influenza picks up again in the winter.
TEPHI’s system, on the other hand, could serve as a first alert for new viruses, the holy grail of pandemic prevention. Since the team started monitoring in 2022, they have found over 400 viruses in Texas wastewater.
Data at the flush of a toilet
Unlike taking a swab of a person’s — or a cow’s –—bodily secretions, wastewater monitoring is passive and doesn’t depend on getting permission to test or having a person come into a clinic or emergency room, care that may be out of reach for farmworkers. Researchers get data every time someone flushes a toilet or perhaps when wastewater systems treat agricultural waste, such as the permitted disposal of discarded milk.
The biggest drawback of wastewater monitoring is that it is difficult to pinpoint the source of the pathogen.
Since March 4, the date of the sample in which H5N1 was first detected by the TEPHI group, the researchers have found it all over the state, in the wastewater of nine cities in Texas and in 19 of the 23 sites they monitor. They did not name the cities they tested in the study but said they did notify local public health authorities and the CDC about their results.
Their findings were published recently as a preprint study, ahead of scrutiny by outside experts.
Source of the signal is still a mystery
“We don’t really know where it’s coming from,” said Dr. Eric Boerwinkle, dean of the UTHouston School of Public Health and director of TEPHI.
“We can all guess, and some people have their favorite ideas,” he said, noting that Texas is in the path of two major flyways for migratory birds and has a large agricultural industry that includes farmed birds and cows.
But H5N1 has been tearing through wild and commercially farmed bird flocks in the US since 2022, when the team started monitoring wastewater, and they haven’t seen it in any of their samples until now.
“Certainly, something that’s different now,” Tisza said, “is that it’s commonly infecting dairy cows.”
Only one person has tested positive for H5N1 in connection with the cattle outbreak. That person, a farm worker who had close contact with infected cows and developed a severe case of conjunctivitis, or redness and swelling of the eyes, but no breathing problems or congestion. He was treated with antiviral medications and has recovered, public health officials said.
The CDC says the current risk to public health is low, but it’s keeping a close eye on the situation.
The FDA recently tested 297 samples of dairy products purchased at grocery stores across the country. In expanded test results released Monday, the agency said, it found samples that were positive for dead fragments of the H5N1 bird flu virus in 15 of the 38 states where products were processed. About 1 out of every 5 samples had some traces of the virus, indicating that the outbreak might be more widespread than previously known.
TEPHI’s Maresso says they can’t rule out that what they are seeing is virus from milk that’s been poured down the drain or even asymptomatic human infections. He notes that they are not seeing an increase in flu cases in hospitals, which would alert them to severe infections.
“It would be maybe a more easily solvable puzzle if it was just one or two sites and we had some dairy or other processing plants right near that that plant where we’re sampling from. It would explain things. but we have essentially detected the signal on in nearly every site and certainly every city to this point,” Maresso said – even big cities in the state that aren’t near dairy farms.
As far as the direction of the Texas outbreak, whether it’s getting worse or going away, Tisza says, it’s hard to say. At first, he said, some cities his group monitors had a signal from H5N1 that was as strong as the one they see from seasonal influenza over the winter.
“But overall, it’s been only maybe about 25 percent of that signal,” he said.
“As far as the overall trajectory, it’s really kind of at a plateau right now. Not spiking up, not going away. So that in and of itself is interesting,” said Tisza, who notes that they’re keeping an eye on it. “And I’m sure you’ll hear from us again if there’s a big spike.”