When the H5N1 bird flu virus jumps from animals into people, it hits a dead end. Missing the key genes that would help it infect humans, it isn’t causing a pandemic.
But if the virus suddenly changed into a dangerous new mutant, how would we know?
Experts say our cities have a valuable tool that can help us keep better tabs on the virus: sewage. While wastewater already is being tested for the presence of bird flu, the genetic sequence of the virus isn’t being studied — so we’re missing the chance to detect it before hospitals are flooded with the sick.
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“Sequencing wastewater is a very important task that can provide important information,” said Stanford University infectious disease expert Dr. Abraar Karan. “It is useful because it can tell us how the virus is evolving.”
If implemented, a “genomic surveillance” program would help health officials contain emerging hot spots and start a vaccination campaign, as well as encourage masking and other precautionary steps.
H5N1 has upended California’s dairy industry, the nation’s largest producer of milk, with a total of 733 dairies reporting infections since August 2024. Of these, 35 were discovered in the past month. Such widespread infections increase the opportunities for the virus to spread to dairy workers, according to infectious disease experts.
Genomic surveillance currently is too expensive and technically formidable to be harnessed into a large-scale, nationwide system, scientists agree.
But smaller research studies already have proven its potential. If targeted, or simplified, it could fend off the next pandemic, they say.
“Wastewater monitoring should be considered as a sentinel surveillance tool,” according to scientists with the University of Texas and Baylor College of Medicine, who deciphered the gene sequences of H5N1 samples in 10 cities throughout Texas. They published their results in a recent study in The New England Journal of Medicine.
Current testing looks for the prevalence of the virus in wastewater; it doesn’t look for specific mutations. And it doesn’t identify the source of the virus — whether it came from the stool of a person, an animal or an animal product, such as milk.
Genomic sequencing, which deciphers the entire viral genome, is more ambitious. It provides more information.
Experts are worried because H5N1, like seasonal flu viruses, constantly changes as it spreads. Viruses are engaged in an evolutionary arms race. Each iteration seeks to confer some sort of advantage, such as an ability to sidestep the immune system — or jump into new species.
The virus already has significantly changed since first identified in geese in 1996. In 2020, a new, highly pathogenic form emerged in Europe and spread quickly around the world. In the U.S. it has affected more than 100 million farmed birds, the worst bird flu outbreak in the nation’s history.
New mutations have eased its spread from birds into multiple other species, such as cows.
Since California’s first detection of the virus in dairies last summer, 38 people have become infected, almost all farm workers. In January, California’s state veterinarian placed a ban on poultry and dairy cattle exhibitions at fairs and shows.
In people, the illness is generally mild. But a few cases have been severe, and that worries experts. A teenager in Canada spent weeks in intensive care. Another case, involving a Louisiana man with underlying medical conditions, was fatal.
What’s puzzling is that, in both of these severe cases, the virus was not related to the virus that is circulating in cattle. Instead, it was linked to the virus found in birds.
Is there something about that particular genetic lineage that makes it more virulent or potentially transmissible between people? That’s what worries scientists.
So far, there’s been reassurance because the virus is unable to latch onto the cells in the human upper respiratory tract.
But if the virus evolves the ability to recognize the cell receptors in our upper airways, it would find a new home — and when we cough or sneeze, it could spread.
A single modification in the protein found on the surface of the virus currently circulating in dairy cows would allow for easier transmission among humans, according to a National Institutes of Health study published in December in the journal Science. However, additional genetic mutations would likely be required for the virus to spark a pandemic, researchers added.
Currently, there is limited visibility into where the virus is circulating. If people or animals don’t show symptoms, it can hide.
While milk is sampled, testing of dairy employees is largely voluntary, so the true extent of spread is unclear. Some farm owners have been reluctant to allow testing due to fears of financial loss; farmworkers, many of whom are undocumented, are unwilling to be tested due to concerns of losing work and possible immigration issues.
Wastewater offers an anonymous snapshot and an inside glimpse of the virus’s evolution.
There are challenges. Despite significant cost reductions in recent years, sequencing remains expensive and labor-intensive.
“You run into a lot of technical troubles,” said virologist Andrew Pekosz of the Johns Hopkins Bloomberg School of Public Health, who investigates the replication and disease potential of respiratory viruses.
The virus’s genome breaks into pieces in wastewater. And wastewater samples tend to be very diluted, so labs must create concentrations of the virus for processing, he said. And to get a close look at the virus, large pieces of the genome have to be “amplified,” increasing the number of copies of its DNA. To be accurate, the genome has to be “read” hundreds of times.
But there are ways that sequencing could be adapted to shine a bright light on emerging variants, Pekosz said.
For instance, sampling could be focused on smaller watersheds or “sewersheds” around dairies or high-risk communities, where the virus might be concentrated.
“You can target certain places, even a block or a building, if you wanted to do close surveillance on a certain area,” he said.
There could be technical shortcuts. It’s not necessary to sequence the entire viral genome, he said. Instead, scientists could focus on the protein that causes the greatest concern.
“That should give you a good amount of information,” Pekosz said.
While not perfect, he said, “it would help us understand: Are there any worrisome changes out there?”