“Am I going to be the next case of a bird to mammalian spillover event?” Hill, an ecologist who studies how diseases jump between animals, recalls thinking. “The odds are low, but your imagination will take you there. It’s not out of the question.”
Hill knows better than most. She is among a small army of researchers racing to gather crucial data amid an unprecedented outbreak of H5N1, a highly contagious form of bird flu, to find answers to questions many of us would prefer not to consider. Among them: If bird flu can rage unchecked across the globe and adapts itself to infect cats, skunks, cows, and seals, if it can get into our milk supply, then why are human infections so rare? And what might it take for that to change?
Answering those questions has become more urgent in the last few weeks. Since arriving on the Atlantic Coast via migratory birds in late 2021, the virus has killed tens of thousands of wild birds and hundreds of seals. The scope of the pandemic on Massachusetts beaches, Hill said, is far worse than at any time since its arrival. In April, scientists discovered it had jumped to cows and made its way into the nation’s milk supply. Chillingly, scientists at the University of Arizona recently said the spillover into cows likely occurred in December and the virus has been quietly spreading unchecked through the nation’s livestock farms since.
Public health officials have downplayed the immediate threat to human health, noting human infections are rare and viral fragments found in milk have likely been inactivated by pasteurization. The Centers for Disease Control and Prevention closely followed more than 6,000 people who had been exposed to the virus between 2022 and 2023; only one was infected.
But some local epidemiologists are sounding alarms. Dr. Nahid Bhadelia, founding director of the Boston University Center on Emerging Infectious Diseases, is among a growing chorus of disease experts who warn the federal government is moving too slowly. As of last week, only 25 people in the entire country had been tested for the virus, federal health officials said at a briefing — an effort Bhadelia said is far too anemic given the shape-shifting superpowers of the virus and the consequences of it adapting to human-to-human transmission.
“We have a small window, and we’re not taking advantage of it by increasing our testing to get a true understanding of how widespread this virus is,” Bhadelia said. “We have to figure out how it’s transmitting, how it’s evolving, and stop the transmission so we don’t get to a position where we have to think about how we do a broader response for this in humans. We’re not doing enough.”
The growing list of mammals known to have contracted the virus, she said, should serve as a warning.
Since 1996, when H5N1 was first identified in waterfowl in China, the virus has spread to the Middle East, Africa, Europe, and the United States and infected more than 48 mammal species including tigers, leopards, domestic cats and dogs, minks, pigs, seals, donkeys, horses, and cows.
Though human cases are extremely rare, they can be lethal: Of 887 confirmed human cases since 1996, more than half the people — 463 — died. To date, there has been no observed human-to-human transmission, a viral feature that would be necessary to spark a global human pandemic. But the apparent infection of a farm worker in Texas through contact with a cow last month — the first known case of a mammal infecting a human — takes it one step closer.
Infected birds are known to have the virus in their saliva and feces, and most previous cases of human infection are believed to have occurred when individuals got the virus on their hands and then touched their eyes, nose, or mouth. The virus can also be inhaled when airborne.
The good news is that scientists such as Hill and her collaborators, Wendy Puryear and Jonathan Runstadler, virologists at Cummings School of Veterinary Medicine at Tufts University, have developed and refined powerful tools to foster collaboration and avert calamity.
To better understand the phenomenon of spillover, to document how the virus is changing, and to track its global progression, they have spent the last decade compiling vast libraries of genetic samples from dead and infected animals, uploading them to shared databases. The most widely used database, GISAID, contains more than 188,333 genetic sequences associated with more than 31,095 individual viral samples.
“We monitor these sequences for specific, known mutations that are linked to adaptation or a high likelihood of spillover in mammals,” Hill said.
When novel mutations are discovered, said Hill, scientists at labs around the world inject the sequences into mice, ferrets, ducks, and other lab animals and document the impact. Are the viruses deadlier? Does the mutation shift the impact from a gastrointestinal to respiratory transmission? Scientists have not determined how the virus is spreading among cows, though some speculate milking machinery is somehow “aerosolizing” the virus, allowing it to spread through droplets in the air.
Andy Pekosz, a virologist at Johns Hopkins Bloomberg School of Public Health who studies influenza, said he and others are closely watching for mutations in key areas that are needed for spillover into humans.
First, H5N1 would likely need to better glom onto receptors on the surface of human cells, which differ from those found in birds, so that it can inject its DNA into human cells.
Secondly, the avian virus in its current form has difficulty commandeering the cellular machinery needed to reproduce itself once it gets inside humans cells.
Body temperature is another important obstacle. Birds, Pekosz notes, “run hot,” with an average body temperature of 102 to 104 degrees Fahrenheit. The upper respiratory tract of humans is around 91.5 degrees Fahrenheit. That small difference can have a big impact on the ability of the virus to replicate.
“We have evidence from lots of different infections of mammals that each of these three things can change,” if the correct mutations occur in the viral DNA, Pekosz said. “Fortunately, we haven’t seen all three of those things change at the same time.”
BU’s Bhadelia worries federal officials aren’t doing enough to prevent a mutation from getting a foothold in humans. One reason there is less spillover into humans than into other mammal species, she suggests, may be that other mammals are much more likely to come into contact with infected birds than humans. Now that the virus appears to be endemic on American farms, that will probably no longer be the case.
Bhadelia said widespread testing is needed both for farm animals and dairy and farm workers. Others have suggested farm workers should be equipped with eye goggles, masks, and other protective gear.
The USDA, Bhadelia notes, is attempting to strike a delicate balance between protecting the agricultural industry and maintaining trust with farm owners to ensure access to continued monitoring, and the larger public health threat. But that caution may come at a cost. Each new infection in a human host represents an opportunity for the virus to potentially gain new mutations that better optimize it for survival in its new home.
“If I were a betting person,” she said. “I would guess that there are already other farm workers who may have been infected.”
Globe correspondent Alex Viveros contributed to this report
Adam Piore can be reached at [email protected].
Rachel Carter is a health and wellness expert dedicated to helping readers lead healthier lives. With a background in nutrition, she offers evidence-based advice on fitness, nutrition, and mental well-being.
