The latent threat of bird flu may be getting closer to boiling over.
This year has been marked by a series of worrying developments in the spread of the virus. Since April, at least 64 people have tested positive for the virus, the first cases in the United States aside from a single infection in 2022.
This year, herds of dairy cows in 16 states have been infected. The Centers for Disease Control and Prevention (CDC) on Wednesday confirmed the first serious case of bird flu in the country, a patient in critical condition in Louisiana. And California Governor Gavin Newsom declared a state of emergency this week due to the proliferation of outbreaks in cows and poultry.
“The traffic light is changing from green to amber,” said Peter Chin-Hong, a professor of medicine at the University of California, San Francisco, who studies infectious diseases. “A lot of signs are going in the wrong direction.”
No human-to-human transmission of bird flu has been documented, and the CDC maintains that the immediate risk to public health is low. But scientists are increasingly concerned, based on four key signals.
On the one hand, the avian flu virus -known as H5N1- has spread uncontrollably in animalsincluding cows that are often in contact with people. Furthermore, detections in wastewater show that the virus is leaving a wide mark, and not just in farm animals.
There are also several cases in humans where no source of infection has been identified, as well as research into the evolution of the pathogen, which has shown that the virus is evolving to better adapt to human receptors and will need fewer mutations to spread among the people.
Taken together, experts say, these indicators suggest that the virus has taken steps toward becoming the next pandemic.
“We’re in a very precarious situation right now,” says Scott Hensley, a professor of microbiology at the University of Pennsylvania.
Widespread circulation creates new routes of contagion
Since this bird flu outbreak began in 2022, the virus has spread in wild birds, commercial poultry, and wild mammals such as sea lions, foxes, and black bears. More than 125 million poultry have died from infections or been euthanized in the country, according to the US Department of Agriculture (USDA).
An unpleasant surprise came in March, when dairy cows began to get sick, eat less and produce discolored milk.
Research showed that the virus spread quickly and efficiently between cows, probably through raw milk, as infected cows excreted large amounts of the virus through their mammary glands. Apparently, raccoons and farm cats also became ill from drinking raw milk.
The more animals that become infected, the greater the chances of exposure for humans who interact with them.
“The more people who get infected, the more likely mutations are to occur,” says Jennifer Nuzzo, professor of epidemiology and director of the Pandemic Center at the Brown University School of Public Health. “I don’t like giving the virus a landing strip into a pandemic.”
Until this year, flu prevention efforts had not focused on cows.
“We didn’t think dairy cattle were a host for influenza, at least a significant host,” Andrew Bowman, a professor of veterinary preventive medicine at Ohio State University, told NBC News this summer.
But now, the virus has been detected in at least 865 cow herds in at least 16 states, as well as in raw (unpasteurized) milk sold in California and in domestic cats that drank raw milk.
“Right now, communities and consumers are directly at risk from raw milk and cheese products,” Chin-Hong said. “A year ago, or even a few months ago, that risk was lower.”
Cases without known source of exposure
Most human H5N1 infections have occurred among workers on poultry and dairy farms. But in several puzzling cases no source of infection has been identified.
The first was a hospitalized patient in Missouri who tested positive in August and recovered. Another was a child from California whose infection was reported in November.
Additionally, Delaware health officials this week reported a case of H5N1 in a person with no known exposure to poultry or livestock. But CDC testing could not confirm that the virus was bird flu, so the agency considers it a “probable” case.
In Canada, a teenager from British Columbia was hospitalized in early November after contracting the H5N1 virus with no known exposure to farm or wild animals. The virus’s genetic material suggested it was similar to a strain circulating in aquatic and poultry birds.
These inexplicable cases make some experts think.
“This suggests that the virus may be much more widespread and that more people could be exposed to it than we thought,” Nuzzo said.
Increased levels of bird flu in wastewater
To better understand the geography of the spread of bird flu, scientists monitor wastewater for fragments of the virus.
“In recent months we’ve seen detections in many more places and much more frequently,” says Amy Lockwood, head of public health partnerships at Verily, a company that provides wastewater testing services to the CDC and a program called WastewaterSCAN.
Earlier this month, about 19% of sites in the CDC’s National Wastewater Monitoring System — across at least 10 states — reported positive detections.
It is not possible to know whether the virus fragments found come from animal or human sources. Some could come from wild bird droppings entering storm drains, for example.
“We don’t think any of this is indicative of human-to-human transmission now, but there is a lot of H5 virus out there,” said Peggy Honein, director of the CDC’s Division of Infectious Diseases Preparedness and Innovation.
Lockwood and Honein pointed out that detections of wastewater have occurred mainly in places where dairy products are processed or near poultry farms, but in recent months mysterious outbreaks have appeared in areas without these types of agricultural facilities.
“We’re starting to see it in more and more places where we don’t automatically know what the source may be,” Lockwood said. And he added: “We are immersed in a very big numbers game.”
One mutation away?
Until recently, scientists who study viral evolution thought that H5N1 would need a handful of mutations to spread easily among humans.
But research published this month in the journal Science found that the version of the virus circulating in cows could bind to human receptors after a single mutation. (The researchers were only studying virus proteins, not the entire infectious virus.)
“We do not want to assume that this discovery will cause a pandemic. “We just want to point out that the risk increases as a result,” said Jim Paulson, co-author of the study and professor of Molecular Medicine at Scripps Research.
On the other hand, in recent months scientists have identified worrying elements in another version of the virus, which was found in the Canadian teenager who became seriously ill. Samples of the virus showed signs of mutations that could make it more susceptible to spreading between people, Hensley said.
A CDC spokesperson said it’s unlikely the virus had those mutations when the teen was exposed.
“The mixture of changes in this virus most likely occurred after a prolonged infection of the patient,” the spokesperson said.
The agency’s research does not suggest that “the virus is adapting to transmit easily between humans,” the spokesperson added.
The viral strain in the first serious case of bird flu in the United States, announced Wednesday, belonged to the same lineage as the Canadian teenager’s infection.
Demetre Daskalakis, director of the National Center for Immunization and Respiratory Diseases, said the CDC is testing a sample from that patient to determine if it has any mutations of concern.
Hensley, for his part, said he worries that flu season could offer the virus a shortcut to evolution. If someone is infected with a seasonal flu virus and a bird flu virus, they can exchange fragments of genetic code.
“There is no need for mutation: the genes are simply exchanged,” said Hensley, who added that he hopes farmworkers get flu vaccines to limit these opportunities.
Future tests and vaccines
Experts say much can be done to better track the spread of bird flu and prepare for a possible pandemic. Some of that work has already begun.
On Tuesday, the USDA expanded bulk testing of milk to a total of 13 states, representing about 50% of the national supply.
Nuzzo says this effort cannot be accelerated as needed.
“We have taken too long to generalize the analysis of bulk milk. “This is how we are detecting most outbreaks on farms,” he said.
At the same time, Andrew Trister, Verily’s chief medical and scientific officer, said the company is working to improve its wastewater testing in hopes of identifying worrisome mutations.
The USDA has also authorized field trials to vaccinate cows against H5N1. Hensley said his lab has tested a new mRNA vaccine in calves.
For humans, the federal government has two bird flu vaccines in stock, although they would need authorization from the Food and Drug Administration.
Nuzzo said health authorities should offer vaccines to farmworkers.
“We should not wait for farmworkers to die before acting,” he said.
Additionally, scientists are developing new mRNA vaccines against H5N1. This type of vaccine, which was first used against Covid-19, can be adapted more quickly to specific viral strains and can also be scaled up more quickly.
Hensley’s lab reported in May that an mRNA vaccine candidate offered protection against the virus in ferrets during preclinical testing. Another candidate in development by the CDC and Moderna has also shown promising results in ferrets, which are often used as a human model to study the flu.
“Now we just have to go through the clinical trials,” Hensley said.
