So, in all, Missouri’s case count in the H5N1 outbreak will stay at one for now, and there remains no evidence of human-to-human transmission. Though both the household contact and the index case had evidence of an exposure, their identical blood test results and simultaneous symptom development suggest that they were exposed at the same time by a single source—what that source was, we may never know.
California and Washington
While the virus seems to have hit a dead end in Missouri, it’s still running rampant in California. Since state officials announced the first dairy herd infections at the end of August, the state has now tallied 137 infected herds and at least 13 infected dairy farm workers. California, the country’s largest dairy producer, now has the most herd infections and human cases in the outbreak, which was first confirmed in March.
In the briefing Thursday, officials announced another front in the bird flu fight. A chicken farm in Washington state with about 800,000 birds became infected with a different strain of H5 bird flu than the one circulating among dairy farms. This strain likely came from wild birds. While the chickens on the infected farms were being culled, the virus spread to farmworkers. So far, two workers have been confirmed to be infected, and five others are presumed to be positive.
As of publication time, at least 31 humans have been confirmed infected with H5 bird flu this year.
With the spread of bird flu in dairies and the fall bird migration underway, the virus will continue to have opportunities to jump to mammals and gain access to people. Officials have also expressed anxiety as seasonal flu ramps up, given influenza’s penchant for swapping genetic fragments to generate new viral combinations. The reassortment and exposure to humans increases the risk of the virus adapting to spread from human to human and spark an outbreak.
California’s infections bring the country’s total number of affected herds to 255 in 14 states, according to the USDA.
In a new release Thursday, California health officials worked to ease alarm about the human case, emphasizing that the risk to the general public remains low.
“Ongoing health checks of individuals who interact with potentially infected animals helped us quickly detect and respond to this possible human case. Fortunately, as we’ve seen in other states with human infections, the individual has experienced mild symptoms,” Tomás Aragón, director of California’s Department of Public Health, said. “We want to emphasize that the risk to the general public is low, and people who interact with potentially infected animals should take prevention measures.”
The release noted that in the past four months, the health department has distributed more than 340,000 respirators, 1.3 million gloves, 160,000 goggles and face shields, and 168,000 bouffant caps to farm workers. The state has also received 5,000 doses of seasonal flu vaccine earmarked for farm workers and is working to distribute those vaccines to local health departments.
Still, herd infections and human cases continue to tick up. Influenza researchers and other health experts are anxiously following the unusual dairy outbreak—the first time an avian influenza is known to have spilled over to and caused an outbreak in cattle. The more opportunities the virus has to spread and adapt to mammals, the more chances it could begin spreading among humans, potentially sparking an outbreak or even a pandemic.
Enlarge/ A warning sign outside a laboratory testing the H5N1 bird flu virus at The Pirbright Institute in Woking, UK, on Monday, March 13, 2023.
More than a month after a person in Missouri mysteriously fell ill with H5-type bird flu, investigators in the state are still identifying people who became ill after contact with the patient, raising questions about the diligence of the ongoing health investigation.
On September 6, Missouri’s health department reported the state’s first human case of H5-type bird flu, one that appears closely related to the H5N1 bird flu currently causing a nationwide outbreak among dairy cows. But the infected person had no known contact with infected animals—unlike all of the other 13 human cases identified amid the dairy outbreak this year. Those previous cases have all occurred in dairy- or poultry-farm workers. In fact, Missouri has not reported bird flu in its dairy herds nor recent poultry outbreaks.
Given the unexplained source of infection, health investigators in the state have been working to track the virus both backward in time—to try to identify the source—and forward—to identify any potential onward spread. The bird flu patient was initially hospitalized on August 22 but recovered and had been released by the time the state publicly reported the case.
In an update Friday, September 27, the Centers for Disease Control and Prevention relayed that Missouri officials have now identified four more health care workers who experienced mild respiratory illnesses after caring for the person with bird flu. None of the four workers were tested for flu at the time of their illnesses and all have since recovered.
Testing new cases for antibodies to H5N1
The four newly identified cases bring the total number of health care workers who fell ill after contact to six. Missouri investigators had previously identified two other health care workers who developed mild respiratory symptoms. One of those workers was tested for flu around the time of their illness—and tested negative. But the other, like the four newly identified cases, was not tested. That person has since submitted a blood sample to test for bird flu antibodies, which would indicate a previous infection.
In addition, a household contact of the bird flu patient also fell ill at the same time as the patient, suggesting a possible common source of the infection.
The illnesses are concerning, given the fear that H5N1 bird flu could begin spreading from human to human and spark a widespread outbreak or even a pandemic. However, it can’t be overlooked that a plethora of other respiratory viruses are around—and SARS-CoV-2 transmission was relatively high in Missouri at the time—it’s impossible to draw any conclusions at this point about whether the illnesses were bird flu infections.
But, the illnesses do clearly raise concern about the health investigation, which is being conducted by Missouri officials. “The slow trickle of info is the most concerning part,” infectious disease expert Krutika Kuppalli wrote on social media Friday. The CDC can get involved at the request of a state, but such a request has not been made. For now, the CDC is only providing technical assistance from Atlanta.
In its update today, the CDC emphasized that “to date, only one case of influenza A(H5N1) has been detected in Missouri. No contacts of that case have tested positive for influenza A(H5N1).” The agency added that blood testing results for H5 antibodies are pending.
A small study in Texas suggests that human bird flu cases are being missed on dairy farms where the H5N1 virus has taken off in cows, sparking an unprecedented nationwide outbreak.
The finding adds some data to what many experts have suspected amid the outbreak. But the authors of the study, led by researchers at the University of Texas Medical Branch in Galveston, went further, stating bluntly why the US is failing to fully surveil, let alone contain, a virus with pandemic potential.
“Due to fears that research might damage dairy businesses, studies like this one have been few,” the authors write in the topline summary of their study, which was posted online as a pre-print and had not been peer-reviewed.
The study authors, led by Gregory Gray, were invited to two undisclosed dairy farms in Texas that experienced H5N1 outbreaks in their herds starting in early and late March, respectively. The researchers had a previously approved research protocol to study novel respiratory viruses on dairy farms, easing the ability to quickly begin the work.
Rare study
“Farm A” had 7,200 cows and 180 workers. Illnesses began on March 6, and nearly 5 percent of the herd was estimated to be affected during the outbreak. “Farm B” had 8,200 cows and 45 workers. After illnesses began on March 20, an estimated 14 percent of the herd was affected.
The researchers first visited Farm A on April 3 and Farm B on April 4, collecting swabs and samples at each. Based on the previously approved protocol, they were limited to taking nasal swabs and blood samples from no more than 10 workers per farm. On Farm A, 10 workers provided nasal swabs and blood samples. On Farm B, only seven agreed to give nasal swabs, and four gave blood samples.
While swabs from cows, milk, a dead bird, and a sample of fecal slurry showed signs of H5N1, all of the nasal swabs from the 14 humans were negative. However, when researchers looked for H5N1-targeting antibodies in their blood—an indicator that they were previously infected—two of the 14, about 14 percent, were positive.
Both of the workers with previous infections, a man and a woman, were from Farm A. And both reported having flu-like symptoms. The man worked inside cattle corrals, close to the animals, and he reported having a cough at the time the samples were taken. The woman, meanwhile, worked in the cafeteria on the farm and reported recently recovering from an illness that included fever, cough, and sore throat. She noted that other people on the farm had similar respiratory illnesses around when she did.
The finding suggests human cases of H5N1 are going undetected. Moreover, managing to find evidence of two undetected infections in a sample of just 14 workers suggests it may not be hard to find more. The Centers for Disease Control and Prevention estimates that around 200,000 people work with livestock in the US.
Known infections in humans have all been mild so far. But experts are anxious that with each new infection, the wily H5N1 virus is getting new opportunities to adapt further to humans. If the virus evolves to cause more severe disease and spread from human to human, it could spark another pandemic.
Federal officials are also worried about this potential threat. In a press briefing Tuesday, Nirav Shah, the CDC’s principal deputy director, announced a $5 million effort to vaccinate farm workers—but against seasonal flu.
Shah explained that the CDC is concerned that if farm workers are infected with H5N1 and the seasonal flu at the same time, the viruses could exchange genetic segments—a process called reassortment. This could give rise to the pandemic threat experts are worried about. By vaccinating the workers against the seasonal flu, it could potentially prevent the viruses from comingling in one person, Shah suggested.
The US does have a bird flu-specific vaccine available. But in the briefing, Shah said that the use of that vaccine in farm workers is not planned for now, though there’s still active discussion on the possibility. The lack of severe disease and no documented human-to-human transmission from H5N1 infections both argue against deploying a new vaccine, Shah said. “There has to be a strong and compelling case,” he added. Shah also suggested that the agency expects vaccine uptake to be low among farm workers.
The highly pathogenic avian influenza H5N1 virus that spilled from wild birds into US dairy cows late last year may have recently seeped from a dairy farm in Colorado to a nearby poultry farm, where it then infected five workers tasked with culling the infected chickens
In a press briefing Tuesday, federal officials reported that four of the avian influenza cases have been confirmed by the Centers for Disease Control and Prevention, while the fifth remains a presumptive positive awaiting CDC confirmation.
All five people have shown mild illnesses, though they experienced variable symptoms. Some of the cases involved conjunctivitis, as was seen in other human cases linked to the H5N1 outbreak in dairy cows. Others in the cluster of five had respiratory and typical flu-like symptoms, including fever, chills, sore throat, runny nose, and cough. None of the five cases required hospitalization.
The virus infecting the five people is closely related to the virus infecting the chickens on the poultry farm, which, in turn, is closely related to virus seen in infected dairy herds and in other human cases that have been linked to the dairy outbreak. The affected poultry farm is in Colorado’s northern county of Weld, which has also reported about two dozen outbreaks of avian influenza in dairy herds.
Dairy to poultry hypothesis
In one fell swoop, Colorado’s poultry farm outbreak has more than doubled the number of human avian influenza cases linked to the dairy cow spillover, bringing the previous tally of four cases to nine. While officials have previously noted instances where it appeared that H5N1 on dairy farms had moved to nearby poultry farms, this appears to be the first time such spread has led to documented human infections.
The link between the poultry farm cases and neighboring dairy farms is still just a hypothesis, however, Nirav Shah, the principal deputy director at the CDC, emphasized to reporters Tuesday. “It is a hypothesis that needs and requires a full investigation. But that is a hypothesis at this point,” he said of the link between the dairy farms and the poultry farm. So far, there is no direct evidence of a specific source of the poultry farm’s infection, and the route of infection is also unclear.
Throughout the outbreak of H5N1 on dairy farms, officials have noted that the primary way the virus appears to spread to new farms is via the movement of cows, people, and machinery between those facilities. There remains no evidence of human-to-human transmission. But milk from infected cows has been found to be brimming with high levels of infectious virus, and milk-contaminated equipment is a prime suspect in the spread.
In the press briefing Tuesday, Eric Deeble, acting senior advisor for H5N1 response with the US Department of Agriculture, noted the poultry are very susceptible to avian influenza and are easily infected. “It does not take much to introduce this into a flock,” Deeble said. The USDA is now working on a “trace-back” investigation on how the Colorado poultry farm was infected.
Searing spread
As for how the farm workers specifically became infected with the virus, health officials pointed to high temperatures that prevented workers from donning protective gear. The poultry farm is a commercial egg layer operation with around 1.8 million birds. Given the presence of bird flu on the premises, all 1.8 million birds need to be culled, aka “depopulated.” This is being carried out using mobile carts with carbon dioxide gas chambers, a common culling method. Workers are tasked with placing the birds in the chambers, which only hold a few dozen birds at a time. In all, the method requires workers to have a high degree of contact with the infected birds, going from bird to bird and batch to batch with the carts.
Amid this grim task, temperatures in the area reached over 100° Fahrenheit, and massive industrial fans were turned on in the facility to try to cool things down. Between the heat and the fans, the approximately 160 people involved in the culling struggled to use personal protective equipment (PPE). The required PPE for the depopulation involves a full Tyvek suit, boots, gloves, goggles, and an N95 respirator.
“The difficulty with wearing all that gear in that kind of heat, you can imagine,” said Julie Gauthier, executive director for field operations at the USDA’s Animal and Plant Health Inspection Service (APHIS). The industrial fans blowing large amounts of air made it yet more difficult for workers to keep goggles and respirators on their faces, she said.
The CDC and the USDA are both involved in further investigations of the poultry farm outbreak. CDC’s Shah noted that the team the agency deployed to Colorado included an industrial hygienist, who can work on strategies to prevent further transmission.
To date, at least 161 herds in 13 states have tested positive for avian influenza since the dairy outbreak was confirmed in March. Since January 2022, when US birds first tested positive for the H5N1 virus, 99 million birds in the US have been affected in 48 states, which involved 1,165 individual outbreaks.
The US government will pay Moderna $176 million to develop an mRNA vaccine against a pandemic influenza—an award given as the highly pathogenic bird flu virus H5N1 continues to spread widely among US dairy cattle.
The funding flows through BARDA, the Biomedical Advanced Research and Development Authority, as part of a new Rapid Response Partnership Vehicle (RRPV) Consortium. The program is intended to set up partnerships with industry to help the country better prepare for pandemic threats and develop medical countermeasures, the Department of Health and Human Services said in a press announcement Tuesday.
In an announcement of its own Tuesday, Moderna noted that it began a Phase 1/2 trial of a pandemic influenza virus vaccine last year, which included versions targeting H5 and H7 varieties of bird flu viruses. The company said it expects to release the results of that trial this year and that those results will direct the design of a Phase 3 trial, anticipated to begin in 2025.
The funding deal will support late-stage development of a “pre-pandemic vaccine against H5 influenza virus,” Moderna said. But, the deal also includes options for additional vaccine development in case other public health threats arise.
“mRNA vaccine technology offers advantages in efficacy, speed of development, and production scalability and reliability in addressing infectious disease outbreaks, as demonstrated during the COVID-19 pandemic,” Moderna CEO Stéphane Bancel said in the announcement. “We are pleased to continue our collaboration with BARDA to expedite our development efforts for mRNA-based pandemic influenza vaccines and support the global public health community in preparedness against potential outbreaks.”
US health officials have said previously that they were in talks with Moderna and Pfizer about the development of a pandemic bird flu vaccine. The future vaccine will be in addition to standard protein-based bird flu vaccines that are already developed. In recent weeks, the health department has said it is working to manufacture 4.8 million vials of H5 influenza vaccine in the coming months. The plans come three months into the H5N1 dairy outbreak, which is very far from the initial hopes of containment.
Botched response
The US is badly fumbling its response to the unprecedented outbreak, drawing criticism from US-based and international experts alike. Genetic analyses suggest that the virus has been spreading among the country’s dairy cattle since late last year. But, it wasn’t until months later, on March 25, that the US Department of Agriculture confirmed the first four infected herds in two states (Texas and Kansas). Since then, the outbreak has spread to around 140 herds in 12 states—at least.
Some farms are refusing to test, and experts expect that there is a significant number of undocumented herd infections, particularly given the widespread detection of inactivated H5N1 in the commercial milk supply. Further, of the 140 herds with documented infections, federal officials do not know how many are still actively infected rather than recovered. It is unclear if infected cows can become reinfected, and if so, how quickly after an infection.
While the risk to the general public is considered to be low currently, farm workers are at higher risk of contracting the infection. To date, there have been three confirmed infections among dairy farm workers—one in Texas and two in Michigan, which has had a uniquely robust response to the outbreak. Still, with hundreds to thousands of farm workers at risk of contracting the virus, only 53 people in the country to date have been tested for H5 influenza.
In a presentation in London last month, global health leader Seth Berkley said it was “shocking to watch the ineptitude” of the US response to the H5N1 outbreak. He, like other experts, questioned whether the US public health community has learned or improved from the failures of the COVID-19 pandemic.
Similar to problems during the pandemic, a key barrier to the H5N1 response is resistance from farmers and farm workers to partner with state and federal health officials. Federal agencies have limited authority within states, but they have announced an array of assistance programs for dairy farms, including compensatory funding and access to personal protective equipment for farm workers. They have also issued guidance and restrictions to tighten biosecurity measures. But there has been little voluntary participation on both fronts.
For instance, officials figured out early in the outbreak that movement of cattle, workers, and equipment between farms is the main way H5N1 is spreading among dairies. In April, the USDA required testing of a portion of cows prior to their movement across state lines. But movement within states is governed by states. In a survey last month, which captured data from 54 percent of affected farms at the time, more than 60 percent of farmers said they continued to move cattle off their infected farms after the onset of clinical signs of infection in their animals.
The more the virus expands its footprint across US dairy farms, adapts to its newfound mammalian host, and comes in contact with humans, the more and more chances it has to leap to humans and gain the ability to spread among us.
In HHS’s Tuesday announcement of the Moderna award, Dawn O’Connell, assistant secretary for Preparedness and Response, spoke to the growing concern that the H5N1 outbreak could spark another pandemic. “The award made today is part of our longstanding commitment to strengthen our preparedness for pandemic influenza,” O’Connell said. “Adding this technology to our pandemic flu toolkit enhances our ability to be nimble and quick against the circulating strains and their potential variants.”
The data confirms that H5N1 infections are significantly different from seasonal influenza viruses that circulate in humans. Those annual viruses make ferrets sick but are not deadly. They have also shown to be highly efficient at spreading via respiratory droplets, with 100 percent transmission rates in laboratory settings. In contrast, the strain from the Texas man (A/Texas/37/2024) appeared to have only a 33 percent transmission rate via respiratory droplets among ferrets.
“This suggests that A/Texas/37/2024-like viruses would need to undergo changes to spread efficiently by droplets through the air, such as from coughs and sneezes,” the CDC said in its data summary. The agency went on to note that “efficient respiratory droplet spread, like what is seen with seasonal influenza viruses, is needed for sustained person-to-person spread to happen.”
In the CDC’s study, researchers infected six ferrets with A/Texas/37/2024. The CDC’s data summary did not specify how the ferrets were infected in this study, but in other recent ferret H5N1 studies, the animals were infected by putting the virus in their noses. Ars has reached out to the agency for clarity on the inoculation route in the latest study and will update the story with any additional information provided.
All six of the infected ferrets developed severe disease and died. To test how well the virus could spread among the ferrets, the CDC scientists set up experiments to test transmission through direct contact and respiratory droplets. For the direct transmission test, three healthy ferrets were placed in the same enclosures with three experimentally infected ferrets. All three healthy ferrets became infected.
For the respiratory transmission test, three healthy ferrets were placed in enclosures next to enclosures containing the experimentally infected animals. The infected and uninfected ferrets shared air, but did not have direct contact with each other. Of the three healthy ferrets, only one contracted the H5N1 virus (33 percent). Additionally, that one respiratory transmission event seemed to have a one- to two-day delay compared with what’s seen in the same test with seasonal influenza viruses. This suggests further that the virus is inefficient at respiratory transmission.
The CDC called the overall results “not surprising.” Previous ferret experiments with H5N1 isolates—collected prior to the current bird flu outbreak among US dairy cows—have also found that H5N1 is often lethal to ferrets. Likewise, H5N1 isolates collected from Spain and Chile during the current global outbreak also found that the virus was inefficient at spreading via respiratory droplets among ferrets—with rates ranging from 0 percent to 37.5 percent.
For now, the findings don’t affect the CDC’s overall risk assessment for the general public, which is low. However, it does reinforce the risk to those who have contact with infected animals, particularly dairy and poultry farm workers.
To date, there have been four human cases of H5N1 in the US since the current global bird flu outbreak began in 2022—one in a poultry farm worker in 2022 and three in dairy farm workers, all reported between the beginning of April and the end of May this year. So far, the cases have been mild, the CDC noted, but given the results in ferrets, “it is possible that there will be serious illnesses among people,” the agency concluded.
The US government is nearing an agreement to bankroll a late-stage trial of Moderna’s mRNA pandemic bird flu vaccine, hoping to bolster its pandemic jab stockpile as an H5N1 outbreak spreads through egg farms and among cattle herds.
The federal funding from the government’s Biomedical Advanced Research and Development Authority, known as BARDA, could come as early as next month, according to people close to the discussions.
It is expected to total several tens of millions of dollars and could be accompanied by a commitment to procure doses if the phase-three trials are successful, they said.
Talks between the government and Pfizer over supporting the development of its mRNA vaccine targeting the H5 family of viruses are also ongoing. Pfizer, like Moderna, played a pivotal role in supplying mRNA vaccines for Washington’s jab rollout during the COVID-19 pandemic.
Bird flu has been detected on poultry farms in 48 states and in dairy cow herds across nine states as part of one of the worst outbreaks in recent history, according to the US Centers for Disease Control and Prevention. The CDC has also reported two cases affecting dairy workers in recent months, adding to concerns of the virus spreading in human populations.
US health authorities continue to classify the public health risk from bird flu as low, but their efforts to build up and diversify the pandemic vaccine stockpile have gathered pace. Federal health officials said last week that the government was moving ahead with plans to fill 4.8 million vials from its existing portfolio of protein-based bird flu vaccines and was in discussions with Moderna and Pfizer.
The possibility of contributing to the US pandemic vaccine stockpile also represents a commercial opportunity for the mRNA vaccine makers, whose market valuations have fallen significantly from pandemic highs. Moderna’s share price is up nearly 37 percent since the start of April.
Moderna has completed dosing of a mid-stage trial of its H5 pandemic flu vaccine, with interim data expected soon. Pfizer said in a statement on Wednesday that it “would be prepared to deploy the company’s capabilities to develop a vaccine for strategic stockpiles,” confirming that it had launched a phase-one trial for a pandemic flu vaccine last December.
Applications for BARDA grant funding for an mRNA-based pandemic flu vaccine closed in December last year, according to a project proposal seen by the Financial Times. But the bird flu outbreak has increased the urgency of talks, with federal officials acknowledging that the speed with which mRNA vaccines were designed and deployed during the COVID-19 pandemic showed their value compared with more traditional vaccine technology.
The jabs from GSK, Sanofi, and CSL Seqirus, which make up the US government’s existing pandemic vaccine portfolio, provide immunity to the current strain of bird flu, according to laboratory testing, but rely on a more time-intensive manufacturing process using egg- and cell-based cultures.
The US health department, Moderna, and Pfizer declined to comment on the potential funding.
Four backyard alpacas in southern Idaho have tested positive for highly pathogenic avian influenza (HPAI) H5N1, marking the first time bird flu has been detected in members of the fleecy camelid family, according to the US Department of Agriculture.
On Tuesday, the USDA announced that the agency’s National Veterinary Services Laboratories confirmed the infection on a farm in Jerome County on May 16. While the infections are a first for the spitting llama relatives, the USDA said they weren’t particularly surprising. The alpacas were in close contact with HPAI-infected poultry on the farm, which were “depopulated” this month. Of 18 alpacas on the affected farm, only four were found to be infected. There were no deaths documented, according to a report the USDA submitted to the World Organization for Animal Health.
Genomic sequencing indicates that the H5N1 virus infecting the alpacas (B3.13) matches both the virus currently circulating among US dairy cows and the virus that infected birds on the farm.
The finding does not increase the threat of H5N1 to the general public, but it again highlights the virus’s alarming ability to readily spread to mammals. The USDA has documented hundreds of cases of H5N1 in a wide range of mammals since May 2022, when the outbreak strain began spreading in North America. In March, the USDA announced the unprecedented outbreak among dairy cows. But the agency has found the virus spreading in mink, raccoons, foxes, cats, seals, bears, mountain lions, bottlenose dolphins, goats, and coyotes, among other animals. With each new species and infection, H5N1 gains new opportunities to adapt to better infect and spread among mammals. And as the virus jumps to mammals in close contact with humans, the risk increases that the virus will have the opportunity to adapt to spread among humans.
The USDA and state officials continue to identify H5N1 in dairy herds. According to the latest data on the USDA’s tracking site, at least 66 dairy herds in nine states have been infected.
Researchers at the University of Wisconsin-Madison squirted raw H5N1-containing milk from infected cows into the throats of anesthetized laboratory mice, finding that the virus caused systemic infections after the mice were observed swallowing the dose. The illnesses began quickly, with symptoms of lethargy and ruffled fur starting on day 1. On day 4, the animals were euthanized to prevent extended suffering. Subsequent analysis found that the mice had high levels of H5N1 bird flu virus in their respiratory tracts, as well their hearts, kidneys, spleens, livers, mammary glands, and brains.
“Collectively, our data indicate that HPAI [Highly Pathogenic Avian Influenza] A(H5N1) virus in untreated milk can infect susceptible animals that consume it,” the researchers concluded. The researchers also found that raw milk containing H5N1 can remain infectious for weeks when stored at refrigerator temperatures.
Bird flu has not historically been considered a foodborne pathogen, but prior to the unexpected outbreak of H5N1 in US dairy cows discovered in March, it had never been found at high levels in a food product like milk before. While experts have stepped up warnings against drinking raw milk amid the outbreak, the mouse experiment offers some of the first data on the risks of H5N1 from drinking unpasteurized dairy.
Before the mouse data, numerous reports have noted carnivores falling ill with H5N1 after eating infected wild birds. And a study from March in the journal Emerging Infectious Diseases reported that over half of the 24 or so cats on an H5N1-infected dairy farm in Texas died after drinking raw milk from the sick cows. Before their deaths, the cats displayed distressing neurological symptoms, and studies found the virus had invaded their lungs, brains, hearts, and eyes.
While the data cannot definitely determine if humans who drink H5N1-contaminated raw milk will suffer the same fate as the mice and cats, it highlights the very real risk. Still, raw milk enthusiasts have disregarded the concerns. PBS NewsHour reported last week that since March 25, when the H5N1 outbreak in US dairy cows was announced, weekly sales of raw cow’s milk have ticked up 21 percent, to as much as 65 percent compared with the same periods a year ago, according to data shared by market research firm NielsenIQ. Moreover, the founder of California-based Raw Milk Institute, Mark McAfee, told the Los Angeles Times this month that his customers baselessly believe drinking H5N1 will give them immunity to the deadly pathogen.
In normal times, the Centers for Disease Control and Prevention and the Food and Drug Administration strongly discourage drinking raw milk. Without pasteurization, it can easily be contaminated with a wide variety of pathogens, including Campylobacter, Cryptosporidium, E. coli, Listeria, Brucella, and Salmonella.
Fortunately, for the bulk of Americans who heed germ theory, pasteurization appears completely effective at deactivating the virus in milk, according to thorough testing by the FDA. Pasteurized milk is considered safe during the outbreak. The US Department of Agriculture, meanwhile, reports finding no H5N1 in retail beef so far and, in laboratory experiments, beef patties purposefully inoculated with H5N1 had no viable virus in them after the patties were cooked to 145°F (medium) or 160°F (well done).
Enlarge/ A glass of fresh raw milk in the hand of a farmer.
To drink raw milk at any time is to flirt with dangerous germs. But, amid an unprecedented outbreak of H5N1 bird flu in US dairy cows, the risks have ratcheted up considerably. Health experts have stepped up warnings against drinking raw milk during the outbreak, the scope of which is still unknown.
Yet, raw milk enthusiasts are undaunted by the heightened risk. The California-based Raw Milk Institute called the warnings “clearly fearmongering.” The institute’s founder, Mark McAfee, told the Los Angeles Times this weekend that his customers are, in fact, specifically requesting raw milk from H5N1-infected cows. According to McAfee, his customers believe, without evidence, that directly drinking high levels of the avian influenza virus will give them immunity to the deadly pathogen.
Expert Michael Payne told the LA Times that the idea amounts to “playing Russian roulette with your health.” Payne, a researcher and dairy outreach coordinator at the Western Institute for Food Safety and Security at UC Davis, added, “Deliberately trying to infect yourself with a known pathogen flies in the face of all medical knowledge and common sense.”
Much remains unknown about the biology of avian influenza in cattle. Until March 25, when the US Department of Agriculture confirmed the virus in a dairy herd in Texas, cattle were generally considered virtually resistant to H5N1. But since then, the USDA has tallied 42 herds in nine states that have contracted the virus. Epidemiological data so far suggests that there has been cow-to-cow transmission following a single spillover event and that the 42 outbreak herds are connected by the movement of cattle between farms.
The limited data on the cows so far suggests that the animals largely develop mild illness from the infection and recover in a few weeks. Their mammary glands are the primary target of the virus. A preprint published earlier this month found that cows’ udders are rife with the molecular receptors that bird flu viruses latch onto to spark an infection. Moreover, the glands contain multiple types receptors, including ones targeted by human flu viruses as well as those targeted by bird flu viruses. Thus, dairy cows could potentially act as a mixing vessel for the different types of flu viruses to reassemble into new, outbreak-sparking variants.
With the virus apparently having a field day in cows’ udders, researchers have found raw milk to be brimming with high levels of H5N1 viral particles—and those particles appear readily capable of spilling over to other mammals. In a case study last month, researchers reported that a group of about two dozen farm cats developed severe illness after drinking milk from H5N1-infected cows. Some developed severe neurological symptoms. More than half the cats died in a matter of days.
Deadly virus
Data on flu receptors in the two animals may explain the difference between cows and cats. While the cow’s mammary gland had loads of multiple types of flu receptors, those receptors were less common in other parts of the cow, including the respiratory tract and brain. This may explain why they tend to have a mild infection. Cats, on the other hand, appear to have receptors more widely distributed, with infected cats showing viral invasion of the lungs, hearts, eyes, and brains.
Raw milk devotees—who claim without evidence that drinking raw milk provides health benefits over drinking pasteurized milk—dismiss the risk of exposure to H5N1. They confidently argue—also without evidence—that the human digestive system will destroy the virus. And they highlight that there is no documented evidence of a human ever becoming infected with H5N1 from drinking tainted milk.
The latter point on the lack of evidence of milkborne H5N1 transmission is true. However, the current outbreak is the first known spillover of highly pathogenic avian influenza (HPAI) to dairy cow mammary glands. As such, it presents the first known opportunity for such milk-based transmission to occur.
Before pasteurization became routine for commercial milk production, raw milk was a common source of infections, serving up a cornucopia of germs. According to the FDA, in 1938, milkborne outbreaks accounted for 25 percent of all foodborne disease outbreaks. In more recent times, milk has been linked to less than 1 percent of such outbreaks. The Centers for Disease Control and Prevention notes that areas where raw milk was sold legally between 1998 and 2018 had 3.2 times more outbreaks than areas where the sale of raw milk was illegal.
In a Q&A document, the Food and Drug Administration notes that it does “not know at this time if HPAI A (H5N1) viruses can be transmitted through consumption of unpasteurized (raw) milk and products (such as cheese) made from raw milk from infected cows.” However, the agency goes on, because of that lack of data and the potential for infection, the FDA recommends halting all sales of raw milk and raw milk products from H5N1 infected or exposed cattle. In general, the agency recommends against consuming raw milk.
Globally, as of March 28, there have been 888 cases of H5N1 reported in humans in 23 countries. Of those 888 cases, 463 were fatal. That represents a 52 percent fatality rate; however, it’s possible that there are asymptomatic or undiagnosed cases that could alter that rate. In the US, only one human so far is known to have been infected with H5N1 in connection with the dairy cow outbreak—a farm worker who developed pink eye. The man had no respiratory symptoms and recovered. He did not consent to further follow-up, and researchers did not get consent to test the man’s household contacts to see if they, too, were infected.
The US Department of Agriculture this week posted an unpublished version of its genetic analysis into the spillover and spread of bird flu into US dairy cattle, offering the most complete look yet at the data state and federal investigators have amassed in the unexpected and worrisome outbreak—and what it might mean.
The preprint analysis provides several significant insights into the outbreak—from when it may have actually started, just how much transmission we’re missing, stunning unknowns about the only human infection linked to the outbreak, and how much the virus continues to evolve in cows. The information is critical as flu experts fear the outbreak is heightening the ever-present risk that this wily flu virus will evolve to spread among humans and spark a pandemic.
But, the information hasn’t been easy to come by. Since March 25—when the USDA confirmed for the first time that a herd of US dairy cows had contracted the highly pathogenic avian influenza H5N1 virus—the agency has garnered international criticism for not sharing data quickly or completely. On April 21, the agency dumped over 200 genetic sequences into public databases amid pressure from outside experts. However, many of those sequences lack descriptive metadata, which normally contains basic and key bits of information, like when and where the viral sample was taken. Outside experts don’t have that crucial information, making independent analyses frustratingly limited. Thus, the new USDA analysis—which presumably includes that data—offers the best yet glimpse of the complete information on the outbreak.
Undetected spread
One of the big takeaways is that USDA researchers think the spillover of bird flu from wild birds to cattle began late last year, likely in December. Thus, the virus likely circulated undetected in dairy cows for around four months before the USDA’s March 25 confirmation of an infection in a Texas herd.
This timeline conclusion largely aligns with what outside experts previously gleaned from the limited publicly available data. So, it may not surprise those following the outbreak, but it is worrisome. Months of undetected spread raise significant concerns about the country’s ability to identify and swiftly respond to emerging infectious disease outbreaks—and whether public health responses have moved past the missteps seen in the early stages of the COVID-19 pandemic.
But another big finding from the preprint is how many gaps still exist in our current understanding of the outbreak. To date, the USDA has identified 36 herds in nine states that have been infected with H5N1. The good news from the genetic analysis is that the USDA can draw lines connecting most of them. USDA researchers reported that “direct movement of cattle based upon production practices” seems to explain how H5N1 hopped from the Texas panhandle region—where the initial spillover is thought to have occurred—to nine other states, some as far-flung as North Carolina, Michigan, and Idaho.
Enlarge/ Bayes factors for inferred movement between different discrete traits of H5N1 clade 2.3.4.4b viruses demonstrating the frequency of movement.
Enlarge/ Putative transmission pathways of HPAI H5N1 clade 2.3.4.4b genotype B3.13 supported by epidemiological links, animal movements, and genomic analysis.
Putative transmission pathways of HPAI H5N1 clade 2.3.4.4b genotype B3.13 supported by epidemiological links, animal movements, and genomic analysis. [/ars_img]The bad news is that those lines connecting the herds aren’t solid. There are gaps in which the genetic data suggests unidentified transmission occurred, maybe in unsampled cows, maybe in other animals entirely. The genetic data is clear that once this strain of bird flu—H5N1 clade 2.3.4.4 genotype B3.13 —hopped into cattle, it could readily spread to other mammals. The genetic data links viruses from cattle moving many times into other animals: There were five cattle-to-poultry jumps, one cattle-to-raccoon transmission, two events where the virus moved from cattle to domestic cats, and three times when the virus from cattle spilled back into wild birds.
“We cannot exclude the possibility that this genotype is circulating in unsampled locations and hosts as the existing analysis suggests that data are missing and undersurveillance may obscure transmission inferred using phylogenetic methods,” the USDA researchers wrote in their preprint.
