Nine farmworkers at two egg farms in Colorado have contracted mild cases of bird flu since mid-July while killing and disposing of millions of infected chickens, said public health officials on Thursday. These preliminary results again underscore the risk of exposure to infected animals, said theCenters for Disease Control(CDC), which added that the risk to the general population remains low.
TheColorado Department of Public Healthsaid that approximately 118 people have been tested for the avian flu virus and 10 cases have been confirmed nine on poultry farms since July 12 and one on a dairy farm in May. The national total, which includes three workers on dairy farms in Michigan and Texas, is 13 since April. In addition, a Colorado correctional inmate was infected with the H5N1 virus while culling an infected chicken flock in 2022.
All of the infected poultry workers were employed on egg farms in Weld County, northeast of Boulder six on one farm and three on the other. The CDC and the Colorado Department of Public Health jointly announced confirmation of the outbreak among workers on the second farm.
The three confirmed cases occurred in people who were working directly with infected poultry at a commercial egg layer operation that had reported an outbreak of H5 bird flu among poultry, said the CDC. All three people have mild illness and have been offered the antiviral drug oseltamivir for treatment. State and local officials continue to monitor poultry workers on farms with infected poultry.
According to the CDC, The risk to the general public from H5N1 [avian flu virus] remains low. Genetic tests show that the virus has not changed in ways that would make it more communicable, it said, and there have been no signs of unexpected increases in flu activity in Colorado or the rest of the country.
Highly pathogenic avian influenza has killed nearly 101 million birds in domestic flocks in 48 states since the disease appeared in the United States in February 2022. Some 172 dairy herds in 13 states have been diagnosed with H5N1 infections since late March. Fifty of them are in Colorado.
For weeks, the CDC has said people working with infected or potentially infected livestock should wear protective gear. For jobs like culling infected flocks, workers should wear water-resistant coveralls, masks, goggles, gloves, and boots, it says. Officials have acknowledged that it is difficult to assure compliance during prolonged physical labor in hot weather.
Historically, most human cases of bird flu infection have happened in people who are not wearing recommended personal protective equipment, said the CDC. Investigators will ask about the use of protective equipment on the Colorado farms, it said.
Just how deadly is the H5N1 avian flu? The virus, which is currently sweeping through U.S. dairy herds, rarely jumps to human beings, at least for now. But when it does the consequences can be grave: The World Health Organization reports that 52 percent of people known to be infected with H5N1 have died from the disease.
The figure has been widely cited in academic papers, public health communications, and media reports, where it can provoke apocalyptic visions. Bird flu pandemic could be 100 times worse than COVID, claimed one New York Post headline. An article in The Guardian leads with the WHOs enormous concern about the spread of H5N1, which, according to one lead scientist quoted, has an extraordinarily high human mortality rate.
The actual picture, while still alarming, is more complicated. The WHOs H5N1 mortality figure, an average of wildly different death rates from past outbreaks, doesnt factor in mild cases that went undetected. Even less certain is how lethal H5N1 would be if it evolves to spread not just from animals to humans, but also from person to person.
That genetic twist would likely diminish H5N1s virulence, experts predict, but no one can say how much less deadly it might become. And even a virus that kills far fewer than 52 percent of people would be devastating: As the world saw with the Covid-19 pandemic, even a death rate of 1 to 2 percent can be catastrophic.
But answering how lethal an H5N1 pandemic might be is no easy feat. A dive into that question reveals the ongoing challenges and, some experts say, failures of tracking the virus. And it offers a glimpse at the difficulty of communicating the risks and unknowns about an emerging pathogen.
Since the first human outbreak of H5N1 in Hong Kong in 1997, the disease has cropped up sporadically around the world, almost entirely infecting people who worked directly with poultry. Between Jan. 1, 2003 and May 3, 2024, the World Health Organization recorded 889 cases of H5N1 and 463 deaths. Dividing the total deaths by the number of cases results in what epidemiologists call a case fatality rate, or CFR, of 52 percent.
But CFRs are notoriously uncertain. The fundamental problem is that a case is not a tightly defined scientific concept, said Harvard epidemiologist Marc Lipsitch. These numbers are something we have to use because we dont have something better, but people in the business are aware that they are potentially deceptive.
When and where researchers look for cases can heavily bias CFRs. A virus that produces mild, undetected infections in 998 people, sends two people to the hospital, and then kills one of the hospitalized patients will have a CFR of 50 percent if public health authorities only manage to detect those two serious cases. But the true fatality rate would be one person in 1,000, or 0.1 percent.
During a 2003 H5N1 outbreak in Vietnam, a relative watches over a family member who has contracted the disease. Between Jan. 1, 2003 and May 3, 2024, the World Health Organization recorded 889 cases of H5N1 and 463 deaths. Visual: Paula Bronstein/Getty Images
Accurate CFRs are critically important in an outbreak because marshalling a public health response depends on understanding the diseases severity. For example, when H1N1, also known as swine flu, emerged in Mexico in the spring of 2009, tens of thousands of mild cases went undetected, causing health authorities to overestimate the severity of the disease. In a study published later that year, Lipsitch and an international group of researchers from organizations including the Centers for Disease Control and Prevention estimated that the actual case count among Mexican residents that spring was about 100 times higher than officially reported.
On the flip side, though, if researchers overlook fatal cases they will underestimate the lethality of a virus. For instance, research suggests that health authorities initially undercounted deaths in a 2003 SARS outbreak in Hong Kong because they didnt follow patients long enough to record everyone who died of the disease.
Like many experts, Peter Palese, a microbiologist at the Icahn School of Medicine at Mount Sinai in New York, thinks that the CFR of 52 percent for H5N1 calculated by the WHO likely overestimates the diseases severity. To meet the WHOs definition of an H5N1 case, the person must have had a fever and tested positive for the virus in a lab with the technical capacity to follow WHO protocols. Because many of the outbreaks have been in rural areas without sufficient testing capabilities, the case count is drawn almost exclusively from patients who were sick enough to be hospitalized. Meanwhile, said Palese, many milder infections likely went undetected, although the exact number of those silent infections is unknown.
It is not completely clear whether these high fatality rates are real, said Palese.
These numbers are something we have to use because we dont have something better, but people in the business are aware that they are potentially deceptive.
Outbreaks are like an iceberg where serious infections are immediately visible, but the larger numbers of mild infections are out of sight below the water line, said Malik Peiris, a virologist at the University of Hong Kong with extensive experience with H5N1. One of the best ways to get a more accurate case count, he said, is to test community members blood for antibodies against H5N1, which would indicate a previous infection: That gives you a much more accurate picture of the bottom of the iceberg.
Researchers have conducted dozens of such studies. But results from that research, said Peiris, are a bit mixed and somewhat confusing. While antibody studies of some H5N1 outbreaks find evidence of widespread mild infections, studies of other H5N1 outbreaks do not, even among people who worked closely with infected birds. Peiris described the disparity as rather puzzling.
Its possible, said Peiris, that antibody tests miss some cases. Type A influenza viruses such as H5N1 are characterized by the combination of two proteins on their surface: hemagglutinin, which can be one of 18 types numbered H1 to H18, and neuraminidase, numbered N1 to N11. Compared to the H1 and H3 proteins in the influenza A viruses responsible for seasonal flu, H5 proteins trigger a weaker response from the immune system, said Peiris: People may be getting mildly infected, but its not enough to elicit an antibody response.
Peiris and other experts described the current H5N1 outbreak in dairy farms as a prime opportunity to investigate how and where H5N1 is spreading as well as how we might contain it. But in many areas, farmers who are worried about the threat to their livelihood wont allow officials on site to test workers or animals.
As of July 18, H5N1 has been identified in 163 herds of dairy cattle in 13 states. But wastewater surveillance data showing spikes of Influenza A outside of flu season in some regions suggests that H5N1 could be circulating more widely, said epidemiologist Michael Osterholm, who heads the University of Minnesotas Center for Infectious Disease Research and Policy. Weve already missed a big chunk of potential worker infections, he said. Still, even now, antibody testing would give us a darn good picture of the number of human cases.
Thats the kind of thing we really need to get a handle on, Osterholm said. The absence of evidence is not evidence of absence.
Between March 2024 and now, H5N1 surveillance has entailed monitoring about 1,570 people who have been exposed to infected animals and testing at least 62 people, CDC spokesperson Jasmine Reed wrote in an email to Undark.
It is not completely clear whether these high fatality rates are real.
There have only been 11 reported cases of bird flu in humans in the U.S. since 2022, according to the CDC, with just five of those confirmed as H5N1. All cases have involved farmworkers who worked with infected animals. The agency is also providing technical assistance on an antibody testing by the Michigan Department of Health and Human Services that is looking for asymptomatic infections among people who worked with sick cows.
But, like many experts, Osterholm is worried that testing is wildly insufficient. More than 9 million cows produce milk across all 50 states, according to the U.S. Department of Agriculture. And the dairy farm industry employs more than 100,000 people.
While Michigan appears to be ground zero for the current outbreak, Osterholm said, I dont believe for a second thats really true. Michigans agriculture and health departments have just been more proactive about surveillance and testing, he said: Im convinced, quite honestly, that if they can get on more farms in more states, youll see this is much more widespread.
Accurately assessing the lethality and spread of H5N1 is crucial to predicting what could happen next.
For now, H5N1 has proven deadly, but still hard for humans to catch. If this were to become a pandemic virus, Osterholm said, it would have to go through major changes.
What those changes would mean for the virus lethality, though, is unclear.
H5N1 could develop the capability for person-to-person transmission in a few ways. In the process of replicating, viruses could acquire random mutations that make them better suited to a human host. In addition, different types of viruses can swap genes through a process called reassortment. So, if a human or other animal were infected with both a typical human flu virus and H5N1, those viruses could generate a new strain that was both deadly and easily transmitted.
Only a small set of avian influenza viruses have evolved to infect mammals, said Thomas Friedrich, a University of Wisconsin virologist who studies the evolution of pandemic viruses. To infect a host, viruses latch on to receptors on the surface of cells, Friedrich explained. The receptors H5N1 binds to in birds are configured differently from most of those in humans. People only have bird-type receptors deep in the lungs, said Friedrich, where infection is associated with severe disease.
That can help explain both why human infections with H5N1 viruses have tended to be very severe, he said. And why those viruses that infect those unfortunate humans have a hard time getting from that human to another one. To efficiently spread from person to person, the virus would need the ability to attach to human-type receptors in the upper respiratory tract. Once it takes hold there, talking, sneezing, coughing, and even breathing will then spew it into the world.
While it would probably only take a couple of genetic changes to get to that point, said Friedrich, we dont find a whole lot of evidence that bird viruses infecting humans are evolving toward the ability to bind those upper respiratory tract cells.
One theory for why, so far, H5N1 has not evolved to infect the upper respiratory tract in people is that the virus so successfully survives and replicates in the lower lungs that it outcompetes any mutations, said Friedrich. Data from his lab and others suggest that mutations that could bind with human-type receptors die off before taking hold.
Im convinced, quite honestly, that if they can get on more farms in more states, youll see this is much more widespread.
But that could change, he said, when the virus infects a species with both human-style and bird-style receptors. For example, researchers have pinpointed the start of the 2009 H1N1 pandemic to pigs, which can be infected with both human and bird flu. And a recent study in preprint that has not yet been peer-reviewed finds that cow udders can also contain both types of receptors and so could potentially become a mixing vessel for bird and flu viruses.
A new study published in the journal Nature suggests that may already be happening. A team of researchers from the U.S. and Japan found that H5N1 virus isolated from the milk of infected cows could bind with both human and bird receptors. Those results are controversial, however, as other researchers whove studied current strains of the virus concluded that it hasnt become more specific to humans.
In the last two years, H5N1 has spread to nonhuman mammals such as foxes, skunks, cats, mice, and marine mammals perhaps both because they are encountering more infected birds and because the virus has become better suited to mammalian hosts, said Friedrich. If the virus further evolved to infect the upper respiratory tract, rather than the lower lungs, of humans, researchers speculate that could make it less lethal, he said: But there is no hard-and-fast rule that viruses dont evolve to kill their host.
Like many researchers, Peiris is concerned that if H5N1 becomes a pandemic virus, the mortality rate would be much higher than that of Covid-19. He pointed to a recent CDC study showing that an H5N1 virus isolated from a person infected in a recent outbreak was lethal to ferrets, which he said are the best animal model for human severity and transmission.
An H5N1 pandemic would have catastrophic consequences, he said. I have no doubt about that.
There is one hopeful note. In early 2024, Peiris and his colleagues published a study suggesting that previous infection with the H1N1 swine flu may provide some protection against H5N1. In testing blood samples collected from a random sample of 63 adult blood donors, the researchers found that antibodies resulting from a previous infection of swine flu also reacted to the N1 protein in H5N1. While that immune response wouldnt block an infection entirely, it might mitigate its severity, said Peiris. The team is now studying that possibility in animal models.
For now, many public health experts remain frustrated by the lack of clear data on H5N1 especially following similar problems in the early days of the Covid-19 pandemic.
Public health authorities should be doing far more testing for evidence of H5N1 in agricultural workers, said Jennifer Nuzzo, who directs the Pandemic Center at the Brown University School of Public Health. But even if they did test more, said Nuzzo, there is a need for standardized protocols.
This is one of those things that we know we need to do, said Nuzzo, who spoke with Undark in June. Since then, the CDC has published such protocols for antibody testing, which would make studies easier to compare because researchers have used different methods in previous outbreaks. That has been an issue in the past, when, Nuzzo said, we jumped to very consequential conclusions based on these data that could very well be the product of a very biased study design.
While Nuzzo would like to see more farmworkers tested regularly, she acknowledges that its a hard-to-reach population. Farm owners arent always cooperative. And the workers, many of whom are undocumented, may also be reluctant to submit to testing that they view as a threat to their tenuous lives in the U.S. In the meantime, Nuzzo is adamant that farmworkers should be offered vaccination against the virus.
Amid the uncertainty, some public health experts suggest, the public conversation about H5N1 has become disconcertingly contradictory, with reassuring messages that risks are low juxtaposed against warnings of a brewing pandemic.
Communication about the threat of H5N1 often lacks nuance and perspective, said Osterholm. Figures like a 52 percent death rate, he said, do little to capture the profound unknowns about an ever-changing virus. At the same time, statements saying that theres little reason for the public to worry about H5N1 like recent pronouncements from the CDC appear to downplay the threat. For example, Nuzzo emphasized that the risk to farmworkers is not low.
Its true that the virus currently poses little risk to the general public, said Osterholm. But all that could change tonight.
Amid the uncertainty, some public health experts suggest, the public conversation about H5N1 has become disconcertingly contradictory.
Many health authorities view the flood of alarming and conflicting information on Covid-19 as an example of how not to communicate during a pandemic. Public guidance from the CDC was confusing and overwhelming, according to a 2022 internal review.
A common mistake was oversimplifying information, stripping out essential details and glossing over unknowns, said Nuzzo. That undermined peoples trust in advice that changed along with the evolving scientific information. You have to take people on the journey with you, she said. Because if you put a fairly high-consequence conclusion in front of them and dont kind of have anything to back it up, I think its natural that people are going to feel skepticism.
The public is much smarter than theyre given credit for, said Nuzzo, And I think people are hungrier for more information, not less.
In a recent study published in the journal Nature, scientists in the United States report the spillover of the highly pathogenic avian influenza (HPAI) H5N1 virus in cattle across several United States (US) regions. They further document the detailed symptomatic outcomes of the resulting disease in these bovine populations. Finally, they use a multidisciplinary approach incorporating epidemiological and genomic analyses to highlight that the virus's evolution confers the ability to allow for not only cow-to-cow transmission but also efficient multidirectional interspecies spillover, infecting birds, domestic cats, and even a raccoon in proximity to diseased cattle.
Study: Spillover of highly pathogenic avian influenza H5N1 virus to dairy cattle. Image Credit:Studio Romantic/ Shutterstock
Influenza A virus (IAV) H5Nx is a highly pathogenic avian influenza (HPAI) virus causing widespread respiratory illness and subsequent death in bird populations across Africa, Asia, Europe, and most recently North America. First discovered in China in 1996, the colloquially termed 'bird flu' has since evolved into eight clades and three neuraminidase subtypes, with the H5N1 subtype 2.3.4.4b being its most prevalent and epidemiologically relevant representative.
HPAI H5N1 is alarming, given its potential for spillover (cross-species infectivity). It has been reported to be transmitted from infected poultry populations into wild birds (2002), mammals (domesticated and wild), and even humans (2003). The World Health Organization (WHO) documented 860 human infections and more than 430 deaths since 2003 (fatality rate ~52.8%).
The virus poses significant threats to ecology, economy, and public health, having claimed more than 90 million bird lives in the United States (US) alone. The most recent H5N1-associated morbidity event was that of dairy cattle across Texas (TX), New Mexico (NM), Kansas (KS), and Ohio (OH) between January and March 2024. Understanding the epidemiological and genomic underpinnings of this event may allow researchers to elucidate the etiology (origin) of the disease and prepare for future outbreaks.
Influenza A Virus (H5N1/Bird Flu) Influenza A (H5N1/bird flu) virus particles (round and rod-shaped; red and yellow). Creative composition and colorization/effects by NIAID; transmission electron micrograph imagery is courtesy CDC. Scale has been modified/not to scale. Credit: CDC and NIAID
The present study documents the January-to-March 2024 morbidity event in American cattle across TX and its neighboring states. It uses a detailed multidisciplinary approach incorporating clinical, epidemiological, and phylogenomic investigations to elucidate the pathophysiology of the virus and the genetic underpinnings of its spillover potential.
Researchers first obtained samples for the clinic-epidemiological evaluation from nine farms across affected states TX (5 farms), NM (2), KS (1), and OH (1). Notably, the singular farm in OH was affected following the introduction of cattle (assumed to be healthy) from the first affected TX farm.
Data collection comprised nasal swabs, milk, blood buffy coats, and serum (n = 331). These samples were subjected to real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) and viral metagenomic sequencing. Additionally, tissue from birds (great-tailed grackles, rock pigeons) and mammals (cats and raccoons) found dead at infected farms were subjected to rRT-PCR analysis.
Virus-shedding investigations were conducted to elucidate the source and duration of viral transmissions following initial infections. Excised tissues from cows, dead birds, and mammals were subjected to histological examinations. Finally, phylogenomic analyses were conducted to isolate the etiological source of the viral strain and the genetic underpinnings of its substantial spillover.
Clinical-epidemiological investigations revealed multiple disease symptoms in cattle, notably decreased feed intake, mild respiratory distress, reduced rumination time, lethargy, dehydration, abnormal feces, and abnormal milk production (20-100% reduction in quantity, yellow color, and thick consistency). Symptoms persisted for 5-14 days. However, milk production remained reduced for up to four weeks.
All investigated rRT-PCR samples positively detected viral load, but virus shedding was the highest and most frequently detected in milk samples and mammary gland tissue. Notably, while virus shedding duration investigations detected viral loads in milk samples on days 3, 16, and 31 post-infection, infectious virus shedding was only observed on day 3.
"Histological examination of tissues from affected dairy cows revealed marked changes consistingof neutrophilic and lymphoplasmacytic mastitis with prominent effacement of tubuloacinar glandarchitecture which were filled with neutrophils admixed with cellular debris in multiple lobules inthe mammary gland. The most pronounced histological changes in the cat tissues consisted of mild to moderate multi-focal lymphohistiocytic meningoencephalitis with multifocal areas ofparenchymal and neuronal necrosis."
Phylogenomic analysis revealed that all recovered viral sequences aligned with a novel monophyletic reassorted substrain of H5N1 termed B3.13, first discovered in a Canada goose in Wyoming (25 January 2024). This lineage was most closely related to a sequence obtained from a deceased skunk in NM (23 February 2024). The similarity between viral genomes from investigated farms highlights circulation and cross-infectivity between their inhabitants, likely due to the transportation and introduction of animals between these farms.
The present study highlights the potential of H5N1 viral spillover and cross-infectivity in both avian and mammalian hosts across farms in the US. The mammary gland was highlighted as the region with the highest viral replication, with infected milk representing the most likely transmission route. The novel substrain (B3.13) identified herein is alarming given its spillover potential (to domestic and wild bird populations and even other mammals cats, and raccoons).
While no human infections were reported from under-study farms, mild infections were reported during the study duration from other farms near the study area, highlighting the virus's zoonotic potential and the potential for a human pandemic.
According to guidelines from the CDC, it is crucial to wear the recommended personal protective equipment (PPE) when working directly or closely with sick or dead animals, such as animal feces, litter, raw milk, and other materials that might have the virus. The recommended PPE includes fluid-resistant coveralls, a waterproof apron, a NIOSH-approved respirator (e.g., N95), properly-fitted unvented or indirectly vented safety goggles or a face shield, head cover or hair cover, gloves, and boots.
Proper procedures for putting on and removing PPE, such as washing hands before and after using PPE and disinfecting reusable PPE after every use, are essential. Additionally, it is advised to shower at the end of the work shift, leave all contaminated clothing and equipment at work, and watch for symptoms of illness for ten days after working with potentially sick animals or materials.
THURSDAY, July 25, 2024 (HealthDay News) -- The bird flu is now jumping between species of mammals, a step that draws the virus closer to hopping into human beings, a new study warns.
Researchers have tracked transmission of avian influenza between dairy cows in herds, as well as from cows to cats and a raccoon.
This is one of the first times that we are seeing evidence of efficient and sustained mammalian-to-mammalian transmission of highly pathogenic avian influenza H5N1, said senior researcher Dr. Diego Diel, director of the Virology Laboratory at the Animal Health Diagnostic Center in the Cornell University College of Veterinary Medicine.
Still, genetic analysis of the virus did not reveal any mutations that would lead to enhanced transmissibility of H5N1 in humans, Diel said. The findings were published July 25 in the journal Nature.
However, mammal-to-mammal transmission does raise concerns that the virus might eventually adapt to spreading in humans, Diel said.
So far, 11 human cases have been reported in the United States, with the first dating back to April 2022, researchers said.
Four human cases are linked to cattle farms and seven to poultry farms, including an outbreak of six cases over the last few weeks in Colorado, researchers said.
These recent human cases contracted the same bird flu strain identified in the study as the one circulating in dairy cows, researchers said.
Luckily, all human cases to date have had mild symptoms, and the virus has not developed an ability to pass easily between humans.
The concern is that potential mutations could arise that could lead adaptation to mammals, spillover into humans and potential efficient transmission in humans in the future, Diel said in a Cornell news release.
For the study, researchers used genetic sequencing to track the viral strains that transmitted between cows when infected animals from Texas were moved to a farm with healthy cows in Ohio.
They also found that the virus was transmitted to cats, a raccoon and wild birds found dead on affected farms.
The cats and raccoon likely became infected from drinking raw milk from infected cows, researchers said.
More than 100 million cases of avian flu in poultry have been reported in the United States, and 168 dairy herds have been affected, the U.S. Centers for Disease Control and Prevention says.
Outbreaks in poultry have been reported in 48 states, and 13 states have had outbreaks in dairy cows.
More information
The U.S. Centers for Disease Control and Prevention has more about the bird flu.
SOURCE: Cornell University, news release, July 24, 2024
A new paper challenged two ideas about how the H5N1 bird flu behaves in cattle: that it always produces mild illness, and that asymptomatic animals don't spread disease.
Instead, the paper showed that cattle mortality was twice as high during outbreaks on two of the nine farms assessed, and almost a third of nasal swabs in asymptomatic animals were positive for the virus, as were half of urine samples.
The findings underscore "the need for robust measures to prevent and control the infection and further spread of HPAI [highly pathogenic avian influenza] H5N1 in dairy cattle," Kiril Dimitrov, DVM, PhD, of Texas A&M Veterinary Medical Diagnostic Laboratory in College Station, and co-authors wrote in Nature. "This would reduce the risk of the virus adapting in this new mammalian host species, thereby decreasing the pandemic risk to humans."
Dimitrov and colleagues studied nine farms -- five in Texas, two in New Mexico, one in Kansas, and one in Ohio -- that had outbreaks from February 11 to March 19.
The New York Times reported that 99 cows died during a 3-week outbreak on the Ohio farm, which is twice the normal mortality rate. The other increased mortality event occurred on a Texas farm, according to the paper.
The researchers found evidence of subclinical infection in some cows, with viral RNA detected in six of 19 nasal swabs and four of eight urine samples. Interestingly, animals with clinical illness shed virus at a lower frequency in nasal swabs and urine, they noted.
That has implications for the risk of spreading the virus between farms, as the researchers said epidemiologic and genomic data showed cow-to-cow transmission after apparently healthy cows from a Texas farm were transported to a farm in Ohio.
It's "possible that the virus infects through respiratory and/or oral routes replicating at low levels in the upper respiratory tract, from where it could disseminate to other organs via a short and low-level viremia," Dimitrov and colleagues wrote, notably to the mammary glands.
Indeed, the paper confirmed that H5N1 has high tropism for mammary gland tissue in cows, which is "consistent with high expression of sialic acid receptors with an alpha 2,3 (avian-like receptor) and alpha 2,6 (human-like receptor) galactose linkage in these cells."
It also confirmed prior reports about key symptoms of the disease in cattle, including "decreased feed intake, decreased rumination time, mild respiratory signs (clear nasal discharge, increased respiratory rate, and labored breathing), lethargy, dehydration, dry/tacky feces or diarrhea, and milk with abnormal yellowish colostrum-like color, thick and sometimes curdled consistency."
Cattle often had an abrupt drop in milk production that could last for about a month, the researchers pointed out, but they generally recovered from their illness in 5 to 14 days, returning to their pre-outbreak health status.
The virus spread widely among other animals on or near the farm, including to cats, raccoons, and wild birds, which was confirmed by genomic analysis. "These observations highlight complex pathways underlying the introduction and spread of HPAI H5N1 in dairy farms, underscoring the need for efficient biosecurity practices and enhanced surveillance efforts in affected and non-affected farms," Dimitrov and co-authors concluded.
"The spillover of HPAI H5N1 into dairy cattle and evidence for efficient and sustained mammal-to-mammal transmission are unprecedented," they wrote. "This efficient transmission is concerning as it can lead to the adaptation of the virus, potentially enhancing its infectivity and transmissibility in other species, including humans."
Kristina Fiore leads MedPages enterprise & investigative reporting team. Shes been a medical journalist for more than a decade and her work has been recognized by Barlett & Steele, AHCJ, SABEW, and others. Send story tips to k.fiore@medpagetoday.com. Follow
Disclosures
The work was funded by the Animal Health Diagnostic Center at Cornell University, the Oklahoma Animal Disease Diagnostic Laboratory at Oklahoma State University, and Texas A&M Veterinary Medical Diagnostic Laboratory. It was supported in part by the USDA-National Institute of Food and Agriculture.
The authors reported no financial disclosures.
Primary Source
Nature
Source Reference: Caserta LC, et al "Spillover of highly pathogenic avian influenza H5N1 virus to dairy cattle" Nature 2024; DOI: 10.1038/s41586-024-07849-4.
ON JULY 14TH Americas Centres for Disease Control and Prevention (CDC) reported five new cases of the H5N1 avian flu virus in humans, bringing the total number of cases reported since April to nine. All five were involved in culling infected poultry in Colorado, and appear to have the same strain that has been spreading in dairy cows across the country since December. So far, there is no evidence the virus has adapted to spread between humans, a prerequisite for a flu pandemic. But things can change quicklythe more the virus circulates in animals that come in close contact with humans, the bigger the risk that a pandemic strain will emerge.
Should H5N1 go down this path, would the world be prepared? When SARS-CoV-2 emerged in 2019, humans had no natural immunity, drugs or vaccines. All three exist for H5N1, though how well any of them would work against a possible pandemic virus remains unclear.
Colorado health officials identified two more cases of the highly pathogenic H5N1 avian influenza bird flu in humans over the weekend, bringing the case count in the state to seven people who worked with inflected birds.
A worker at a northeast Colorado commercial egg layer in Weld County, where five other cases occurred, was confirmed sick on Friday. On Saturday, officials identified another presumptive positive case in a worker at a separate poultry farm in Weld County.
Another Colorado resident contracted the virus from infected cattle earlier this month.
The cluster of cases, comprising eight people in Colorado, accounts for most of the bird flu cases reported in humans in the country.
The recently infected workers were dealing directly with infected poultry and experienced mild symptoms such as pink eye and respiratory infection symptoms. Officials with the U.S. Department of Agriculture said last week that heat could have prevented proper use of personal protective equipment, exposing the workers to the virus.
Federal health officials have commissioned Moderna to develop a vaccine to protect people from an avian influenza that has been circulating in dairy cattle in recent months, according to reporting by the Iowa Capital Dispatch.
U.S. Department of Health and Human Services officials said July 3 the agency would devote about $176 million to the effort, with the hope that final clinical trials might commence next year.
This article first appeared in theColorado Newsline,a sistersite of the Nebraska Examiner in the States Newsroom network.
Colorado's state veterinarian yesterday issued a mandatory order for weekly bulk milk-tank testing for highly pathogenic avian influenza, as officials continue to battle the virus in dairy herds, with recent spillover to at least one large layer farm and workers culling the birds.
The order from state veterinarian Maggie Baldwin, DVM, applies to all dairy cow farms licensed by the Colorado Department of Public Health and Environment (CDPHE) and took effect yesterday.
It applies to all farms that aren't currently in quarantine and will apply to all affected farms that are released from quarantine. The samples will be collected by CDPHE-certified collection samplers and submitted to the Colorado State University Veterinary Diagnostic Laboratory.
With 49 outbreaks in dairy cattle reported by the state's agriculture department so far, Colorado by far has reported the most of any of the 13 affected states. The state has 105 licensed dairy facilities. Weld County has been the state's hardest hit area and is where the B3.13 genotype circulating in dairy cattle was recently confirmed at a massive layer farm.
Outbreaks at two large layer farms in Weld County have recently been linked to seven H5N1 infections in cullers, who are working in barns in heat wave conditions, which make it difficult for personal protective equipment (PPE) to provide optimal protection.
The US Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS) today added one more confirmation in another herd from Colorado to its list of affected dairy farms, raising the national total to 169 from 13 states.
In its latest updates, APHIS also reported one more outbreak at a poultry farm, a commercial table egg pullet facility in Weld County.
Also, APHIS reported detections in three live bird markets in Florida's Miami-Dade County, which together have nearly 800 birds.
Since H5N1 was first detected in US poultry in early 2022, more than 100 million bird losses have been reported across 48 states, according to APHIS.
Raw milk from cows infected with the H5N1 bird flu has been shown to contain very high levels of the virus, making it quite risky for people to consume.
With FDA data showing some 4.4% of Americans drank raw milk at least once a year, and 1% drank it once a week or more, millions of Americans may be at risk of contracting the virus.
The question is, would an H5N1 infection from raw milk look like a typical influenza infection to most doctors, or would its symptoms be different? And would doctors be testing for influenza?
On that first question, Andrew Pekosz, PhD, professor of molecular microbiology and immunology at Johns Hopkins University Bloomberg School of Public Health in Baltimore, said it's likely an H5N1 infection from raw milk "would be primarily a respiratory infection based on what happens to other animals that either ingest H5N1-containing milk, or what we see with predatory birds and other carnivores who get infected by eating an H5N1-infected bird."
"In those animals, the infection is in the lungs, but also spreads to a lot of other organs, which is what leads to the death of the animal," Pekosz told MedPage Today in an email.
Those animals include cats; in April, data published in the CDC's Emerging Infectious Diseases showed that more than half of 24 domestic cats fed raw milk from sick cows on a dairy farm in north Texas in mid-March became sick and died.
The cats had signs of systemic influenza infection, including lots of nasal discharge, depressed mental state, and stiff body movements, the researchers reported at the time.
If the infection looks like a typical, or possibly more severe, influenza infection, would a doctor or hospital even test for influenza, let alone search for the H5N1 strain?
Pekosz said emergency departments and healthcare professionals have received communications from health authorities, such as CDC Health Alert Network advisories, to be aware of potential H5N1 infections.
"However, it is not something that is high on most healthcare providers' lists of pressing concerns, so it is possible a case could initially be missed, particularly if it's not a severe infection," he added.
James Lawler, MD, MPH, an infectious diseases expert at the University of Nebraska Medical Center's Global Center for Health Security in Omaha, agreed that it would be easy to miss cases of H5N1 infections from raw milk.
"If we do have sporadic cases popping up every now and then, given the state of surveillance in our public health system, we're probably not going to find it," Lawler told MedPage Today. "If a 20-year-old shows up to an emergency department with severe pneumonia in July, many places will not test that person for flu."
"I'm really concerned about people who are consuming raw milk," he added. "I think there's a high likelihood that we're having even more human cases and those are going undetected."
While most human cases in the recent cattle outbreak have been tied to large dairy farms, and a key route of transmission among cows appears to be contaminated equipment, any cattle exposed to wild birds could potentially become infected, experts said. Also, companion animals that drink H5N1-contaminated raw milk -- and interact with humans -- may pose a risk.
Lawler said, ideally, animal caretakers who sell raw milk should recognize that milk from an animal with symptoms "shouldn't be put into the supply chain." However, cows early in infection, or with latent infection, or those that are only mildly symptomatic "still have high amounts of virus in their milk" and thus pose a risk to the supply chain.
While Lawler acknowledged that the chances of H5N1 evolving to efficiently spread between humans remains low, the stakes are high if it does gain that advantage -- and the more chances it has to spread in mammals, and in humans, the more likely that adaptation is to happen, he said.
Cow mammary glands are a particularly problematic substrate because they contain both "flavors" of sialic acid receptors that the virus uses to bind to host cells, he said: alpha 2,3, which is common in birds; and alpha 2,6, which is common in human upper airways.
Humans also have alpha 2,3 receptors, but these are deeper down in the lungs, Lawler said, which is a likely reason H5N1 has been particularly lethal (with greater than 50% mortality) in historic human cases, as it causes severe pneumonia.
Letting the virus persist in cows "means you're potentially allowing the virus to select for strains that can bind to both, and that would be a potentially dangerous virus," he said.
"All these things are concerning, and I'm pretty disappointed in the lack of a sense of urgency we've seen from the federal government and some state agencies as well," Lawler said. "We seem to be relying on hope as our strategy."
"We're continuing the messaging that this is low risk, and I would argue that it's not," he added. "Risk is the product of threat, and then vulnerability and consequence. While the threat is low -- the probability that this virus is going to mutate into something that transmits efficiently between humans is probably still low -- the problem is, if that happens, then our vulnerability and the consequences of that event would be incredibly high."
Kristina Fiore leads MedPages enterprise & investigative reporting team. Shes been a medical journalist for more than a decade and her work has been recognized by Barlett & Steele, AHCJ, SABEW, and others. Send story tips to k.fiore@medpagetoday.com. Follow
Less than a year ago, the Centers for Disease Control and Prevention funded a disease prediction center at Northeastern University called EPISTORM: The Center for Advanced Epidemic Analytics and Predictive Modeling Technology.
Considered a National Weather Service for epidemic threats, the center was designed to help detect and prepare the United States for the next outbreak of infectious disease, especially in rural areas.
Now, EPISTORM researchers find themselves on the front lines of the bird flu outbreak.
Also known as H5N1, bird flu has been detected in 169 livestock herds on dairy farms in 13 states since March 25, according to the U.S. Department of Agriculture.
The spread to cows is of particular concern to scientists, who say any extension to mammal species creates more opportunities for the respiratory virus to evolve into a strain more dangerous to people.
To help mitigate the outbreak, EPISTORM researchers have produced risk maps highlighting potential hot spots on farms based on the cows travel across state lines, says Alessandro Vespignani, director of Northeasterns Network Science Institute, Sternberg Family Distinguished Professor and head of EPISTORM.
We correctly identified the potential for outbreaks in Colorado, Minnesota, Iowa, Wyoming and Oklahoma, Vespignani says.
The USDA has required testing of dairy cows moved between states since late April, a few weeks after the CDC reported a human infection linked to dairy cattle in Texas which is believed to be the first cow-to-human transmission of H5N1.
The federal health agency says that as of July 3, four people have been infected with bird flu after contact with sick dairy cows, while published reports say seven poultry farm workers in Colorado have contracted H5N1 just this month.
The CDC says from 1997 through late April 2024, 909 people across the globe were reported to have H5N1, 52% of whom died. Since 2022, seven people succumbed after contracting bird flu.
Severity profile: Unknown
The current viruses lack some of the changes observed in prior bird flu viruses, Vespignani says. We have to be very careful crying wolf too much because we dont want to continually say we are on the verge of a new pandemic.
We need to be honest and say we dont know. We dont know what the severity profile of the disease will be, he says.
Vespignani also called for continued testing in farm workers and their families to monitor the potential asymptomatic spread of H5N1.
The more human cases we have, the higher the risk that the virus will pick up the mutation that will make it more adapted to humans and human-to-human transmission, Vespignani says.
The infections reported this month in Colorado are the largest bird flu outbreak to date.
Bird flu, also known as highly pathogenic avian influenza, has affected more than 100 million poultry birds in the U.S. since January 2022. The first human case of H5N1 in the U.S. was reported three months later in a person in Colorado who had been culling infected birds, the CDC says.
Even if this doesnt trigger a human pandemic, it is in the interest of everybody to understand what is going on in farms, where the virus is causing economic harm through the culling of flocks, Vespignani says.
Thats why the epidemic experts community is monitoring (the virus) very carefully, he says.
Human cases of H5N1 in the U.S. have been mild so far, with pink eye or conjunctivitis being a major complaint associated with the respiratory virus. No hospitalizations have been reported.
More testing is needed
We arent doing enough testing, says Sam Scarpino, director of AI + Life Sciences at the Institute for Experiential AI at Northeastern and a member of the EPISTORM innovation center, which is supporting public stakeholders in detecting and preparing the U.S. for the next outbreak of disease.
We just have no idea how many people have been potentially infected by the virus in the past months, Scarpino says.
Public health officials most likely missed some bird flu cases in humans, Scarpino says, adding that he guesses the number could range from 50 to 100.
We know we havent missed thousands because we would see them in the emergency department, he says.
Active surveillance of wastewater by the CDC and private companies such as WW Scan does not indicate spikes in any type of influenza, including bird flu, Scarpino says.
Mammals can be infected with H5N1 if they are exposed to environments contaminated with the virus or if they eat infected birds. Most cows recover with supportive treatment, but avian flu is associated with high mortality in birds, according to the American Veterinary Medical Association.
Follow the evolution of the virus
Scarpino and Vespignani said theyd like to see increased blood testing and group or pool testing of farm workers, their families and co-workers.
We need to know the landscape of transmission, Vespignani says. We need to follow the evolution of the virus. Its in the interest of everybody to understand whats going on, what is the level of spreading on the farms.
We know that so far it has been mostly in dairy cattle. It will be important to understand if there is spillover in meat cattle, he says.
The way we prevent larger outbreaks is by monitoring, carefully isolating people as soon as they get the infection from animals, limiting the number of human cases as much as we can, Vespignani says. He says hes not worried about the food chain as long as people drink pasteurized instead of raw milk.
Farm workers, especially those working around sick animals, can help avoid contracting H5N1 by wearing personal protective equipment, Vespignani says.
Published reports say workers at the egg farm in Colorado where the latest outbreak among humans occurred might not have been wearing heavy and cumbersome PPE due to temperatures in the 100-degree range.
If a farm worker dies, its going to be a preventable death and tragically unnecessary, Scarpino says.
Tests for the public?
The CDC says federal officials are meeting with commercial labs about the possibility of making commercial H5 testing available.
Ten of those licenses are currently in place, and several more are in progress, the CDC says.
Testing is the way we get information in public health, Vespignani says. It is crucial that we have situational awareness.
