Virus World

Outbreaks of highly pathogenic H5N1 clade 2.3.4.4b viruses in farmed mink and seals combined with isolated human infections suggest these viruses pose a pandemic threat. To assess this threat, using the ferret model, we show an H5N1 isolate derived from mink transmits by direct contact to 75% of exposed ferrets and, in airborne transmission studies, the virus transmits to 37.5% of contacts. Sequence analyses show no mutations were associated with transmission. The H5N1 virus also has a low infectious dose and remains virulent at low doses.

This isolate carries the adaptive mutation, PB2 T271A, and reversing this mutation reduces mortality and airborne transmission. This is the first report of a H5N1 clade 2.3.4.4b virus exhibiting direct contact and airborne transmissibility in ferrets. These data indicate heightened pandemic potential of the panzootic H5N1 viruses and emphasize the need for continued efforts to control outbreaks and monitor viral evolution. In 2023, a highly pathogenic H5N1 virus caused an outbreak in mink. In the ferret model of influenza, the virus exhibits limited airborne transmissibility and high virulence. These findings indicate heightened pandemic potential of these viruses.

Published in Nature Comm. (May 15, 2024):

 https://doi.org/10.1038/s41467-024-48475-y 

Avian influenza (serotype H5N1) is a highly pathogenic virus that emerged in domestic waterfowl in 1996. Over the past decade, zoonotic transmission to mammals, including humans, has been reported. Although human to human transmission is rare, infection has been fatal in nearly half of patients who have contracted the virus in past outbreaks. The increasing presence of the virus in domesticated animals raises substantial concerns that viral adaptation to immunologically naive humans may result in the next flu pandemic. Wastewater-based epidemiology (WBE) to track viruses was historically used to track polio and has recently been implemented for SARS-CoV2 monitoring during the COVID-19 pandemic.

Here, using an agnostic, hybrid-capture sequencing approach, we report the detection of H5N1 in wastewater in nine Texas cities, with a total catchment area population in the millions, over a two-month period from March 4th to April 25th, 2024. Sequencing reads uniquely aligning to H5N1 covered all eight genome segments, with best alignments to clade 2.3.4.4b. Notably, 19 of 23 monitored sites had at least one detection event, and the H5N1 serotype became dominant over seasonal influenza over time. A variant analysis suggests avian or bovine origin but other potential sources, especially humans, could not be excluded. We report the value of wastewater sequencing to track avian influenza.

Preprint in medRxiv ( May 10, 2024):

https://www.medrxiv.org/content/10.1101/2024.05.10.24307179v1.full.pdf 

U.S. regulators confirmed that sick cattle in Texas, Kansas and possibly in New Mexico contracted avian influenza. They stressed that the nation’s milk supply is safe. A highly fatal form of avian influenza, or bird flu, has been confirmed in U.S. cattle in Texas and Kansas, the Department of Agriculture announced on Monday. It is the first time that cows infected with the virus have been identified. The cows appear to have been infected by wild birds, and dead birds were reported on some farms, the agency said. The results were announced after multiple federal and state agencies began investigating reports of sick cows in Texas, Kansas and New Mexico. In several cases, the virus was detected in unpasteurized samples of milk collected from sick cows. Pasteurization should inactivate the flu virus, experts said, and officials stressed that the milk supply was safe.

“At this stage, there is no concern about the safety of the commercial milk supply or that this circumstance poses a risk to consumer health,” the agency said in a statement. Outside experts agreed. “It has only been found in milk that is grossly abnormal,” said Dr. Jim Lowe, a veterinarian and influenza researcher at the College of Veterinary Medicine at the University of Illinois at Urbana-Champaign. In those cases, the milk was described as thick and syrupy, he said, and was discarded. The agency said that dairies are required to divert or destroy milk from sick animals....

USDA report (March 25, 2024):

https://www.aphis.usda.gov/aphis/newsroom/news/sa_by_date/sa-2024/hpai-cattle 

A new study highlights both the promise and the limitations of gene editing, as a highly lethal form of avian influenza continues to spread around the world.

Discovery means targeted solutions can be directed to avian flu viruses sooner to prevent spillover into humans, say scientists. Scientists have discovered that a gene present in humans is preventing most avian flu viruses moving from birds to people. The gene is present in all humans and can be found in the lungs and upper respiratory tract, where flu viruses replicate. It was already known to scientists, but the gene’s antiviral abilities are a new discovery. A six-year investigative study led by the MRC-University of Glasgow Centre for Virus Research found that the BTN3A3 gene is a powerful barrier against most avian flu viruses. Although relatively rare, some avian flu virus strains have periodically spilled over into humans. Two of the most recent H5N1 cases were reported in UK poultry farm workers in May this year. Human cases of H5N1 bird flu were first found in Hong Kong in 1997. Globally since 2003, 873 human H5N1 infections have been reported to the World Health Organization. Of those, 458 people died.

The study found that some bird and swine flu viruses have a genetic mutation that allows them to escape the blocking effects of the BTN3A3 gene and infect people. By tracking the history of human influenza pandemics and linking resistance to the gene with key virus types, the researchers concluded that all human influenza pandemics, including the 1918 Spanish flu and the 2009 swine flu pandemics, were a result of BTN3A3-resistant strains.

The findings suggest that resistance to the gene could help determine whether flu strains have human pandemic potential or not. That may lead to testing of wild birds, poultry and other animals susceptible to flu viruses such as pigs, for BTN3A3-resistant viruses. “The antiviral functions of the [BTN3A3] gene appeared 40m years ago in primates,” said Prof Massimo Palmarini who led the study and is director of Glasgow’s virology research centre. “Understanding the barriers that block avian flu in humans means better targeted solutions and better control measures to prevent the spillovers. He said that if a gene-resistant virus was identified, “we can direct preventative measures to those viruses, sooner, to prevent the spillover [into humans]”.

Dr Rute Maria Pinto, the study’s lead author, said: “It’s pretty amazing, isn’t it? We are all fairly proud about the outcome. This gene had been identified before, and other functions were attributed to it, but we found that the gene is antiviral against avian flu. No one had found that before.” She said the discovery was expected to have immediate practical applications. “Now, when we find cases of bird flu, we can basically swab sick birds, carcasses or faeces and find out whether the virus can overcome the BTN3A3 gene, simply by looking at its sequence and determining if this virus is more or less likely to jump into humans. If the virus can in fact overcome BTN3A3 then stricter measurements should be put in place to prevent spillovers.” Pinto added: “As a scientist we are expected to find solutions to problems, to give back to the taxpayers that fund this [research], and to find something that can be used straight away is really impactful.” The study was also able to retrospectively identify increases in gene-resistant viruses ahead of previous human spillovers. Before the H7N9 bird flu virus outbreak, which first infected humans in China in 2013, the study found “an increased frequency of the BTN3A3-resistant genotype [in birds] in 2011-2012”. To date there have been almost 1,570 cases of H7N9 and at least 616 deaths. “I guess what these observations provide is a snapshot of what the frequency of the BTN3A3 resistant gene was at different period of times in the birds,” Palmarini said. “Because birds haven’t got BTN3A3, there is no evolutionary pressure to keep, or not, those traits.” He said certain mutations “might make the virus more or less fitter in the birds” but this had not yet been studied. Similarly, before the 2009 H1N1 swine flu pandemic, the study found H1N1 gene resistance in pigs occurring between 2002 and 2006. The swine flu pandemic is estimated to have killed between 150,000 and 575,400 people during the first year the virus circulated in humans.

Original publication in Nature (June 28):

 https://doi.org/10.1038/s41586-023-06261-8 

A dog in the Canadian province of Ontario has died of H5N1 bird flu after contact with wild birds, health officials say. It’s believed to be the first time that a dog has tested positive for the new strain of the virus. A statement from the Canadian Public Health Agency said a domestic dog in Oshawa, a city in Ontario, tested positive for avian influenza after chewing on a dead goose. The dog developed clinical signs of bird flu and died a few days later. “Both the dog and goose were tested for H5N1 highly pathogenic avian influenza (HPAI) virus, and both were positive,” said Dr. Scott Weese, the Director of the Centre for Public Health and Zoonoses at the University of Guelph. “Sequencing of the virus at the National Centre for Foreign Animal Diseases was performed and the virus from both the dog and goose were the same, and were consistent with the H5N1 strain that’s circulating in wild birds and domestic poultry,” he said. It’s believed to be the first time that a dog has been infected with the new strain of H5N1, which emerged in late 2021. In 2004, a dog in Thailand died of a previous strain of H5N1 after eating a duck which was infected with the virus. In December, a cat at a poultry farm in southern France also tested positive for the new strain of H5N1. The cat became sick and was euthanized on December 23. “Based on the current evidence in Canada, the risk to the general public remains low and current scientific evidence suggests that the risk of a human contracting avian influenza from a domestic pet is minor,” the government said in a statement. Nonetheless, pet owners have been advised to not give any raw meat from game birds or poultry to pets – such as dogs and cats – and to not let them eat or play with wild birds.

Dr. Weese called the case “concerning but not surprising” and “not a doomsday scenario.” “It’s concerning because any spillover into mammals raises concerns about continued adaptation of this virus to spread outside birds,” he said. “It’s not surprising because when you have millions of infected birds internationally, it’s inevitable that domestic and wild mammals will be exposed.” A wide range of animals in Canada have tested positive for bird flu during the past year, including foxes, seals, dolphins, black bears, wild mink, porpoises and skunks, according to the National Centre for Foreign Animal Diseases. The global spread of H5N1 clade 2.3.4.4b – and the recent spread to a growing number of mammals – has raised concern about the possibility of a future variant which could lead to human-to-human transmission. So far, only a few human cases have been found after contact with infected birds. “The global H5N1 situation is worrying given the wide spread of the virus in birds around the world and the increasing reports of cases in mammals, including in humans,” Dr. Sylvie Briand, a WHO official, said on February 24. “WHO takes the risk from this virus seriously and urges heightened vigilance from all countries.” Last week, Chile reported that more than 1,500 sea lions are believed to have died of H5N1 bird flu, which followed the deaths of at least 3,500 sea lions in neighboring Peru. Chile also reported its first human case of bird flu on March 29.

Changes in the H5N1 virus are 'concerning', according to the ECDC, and may suggest its potential to jump to humans is increasing. Mutations spotted in the H5N1 bird flu virus are “concerning” and may suggest the potential for avian influenza to jump to humans is increasing, according to the European Centre for Disease Control.  In a situation report published this week, the agency said that although the threat in Europe remains low for the general public, and low to moderate for those in frequent contact with birds, the risk assessments contain “high uncertainty” That’s because the increasing transmission of H5N1, including its introduction to the Americas and the spread in animals, has offered unprecedented opportunities for the virus to shift and reassort – a process where different strains of the same pathogen combine into something new.  “The expansion of mammal species identified infected with A(H5N1) viruses, as well as the detection of viruses carrying markers for mammalian adaptation in other genes such as the PB2 that correlated with increased replication and virulence in mammals, is of concern,” the ECDC said this week.  “Although the virus retained a preferential binding for avian-like receptors, several mutations associated to increased zoonotic potential were detected. The PB2 gene was recently identified in mink in Spain. H5N1 jumped from wild birds to thousands of farmed animals – within weeks, more than four per cent had died from haemorrhagic pneumonia. In total, 50,000 mink were culled. “In most of the mammalian cases where the virus has been sequenced, we have seen a specific mutation in the PB2 gene, which allows the virus to replicate at a different body condition,” Dr

Spread among captive mink could give the H5N1 strain opportunities to evolve and adapt to mammals. When mink at a big farm in Galicia, a region in northwestern Spain, started to die in October 2022, veterinarians initially thought the culprit might be SARS-CoV-2, which has struck mink farms in several other countries. But lab tests soon revealed something scarier: a deadly avian influenza virus named H5N1. Authorities immediately placed workers on the farm under quarantine restrictions. The more than 50,000 mink at the facility were killed and their carcasses destroyed. None of the farm workers became infected. But the episode, described in a paper in Eurosurveillance last week, has reignited long-smoldering fears that H5N1 could trigger a human pandemic. The virus is not known to spread well between mammals; people almost always catch it from infected birds, not one another. But now, H5N1 appears to have spread through a densely packed mammalian population and gained at least one mutation that favors mammal-to-mammal spread. Virologists warn that H5N1, now rampaging through birds around the world, could invade other mink farms and become still more transmissible. “This is incredibly concerning,” says Tom Peacock, a virologist at Imperial College London. “This is a clear mechanism for an H5 pandemic to start.” Isabella Monne, a veterinary researcher at the European Union’s Reference Laboratory for Avian Influenza in Italy, where the samples from Spain were sequenced, calls the finding “a warning bell....

As a new version of bird flu spread through North America this spring, scientists began finding the virus in red foxes, bobcats and other mammals.  Something was wrong with the foxes. That was what callers to the Dane County Humane Society in Wisconsin kept saying in April, as they reported fox kits, or young foxes, behaving in strange ways: shaking, seizing or struggling to stand. The kits, which were often lethargic and wandering by themselves, also seemed unusually easy to approach, showing little fear of humans. “We just kept getting calls,” said Erin Lemley, a wildlife veterinary technician at the humane society’s wildlife center. “And the foxes started coming in.” Some of the kits that were admitted for treatment were quiet and withdrawn, she said. Others stumbled around or had seizures, their heads ticcing, their eyes flicking rhythmically. After the staff ruled out rabies, low blood sugar and other potential causes, laboratory testing revealed a surprising culprit: a highly virulent strain of avian influenza. “It was not a fun surprise,” said Dr. Shawna Hawkins, a zoo and wildlife veterinarian at the University of Wisconsin-Madison.

A newly arrived bird flu is sweeping through wild bird populations in the United States, and that may mean trouble for poultry farmers who have been doing their best to control this flu outbreak in their flocks. Some 24 million poultry birds like chicken and turkeys have already been lost, either because they died from the virus or were killed to prevent its spread. But unlike a similar bird flu outbreak seven years ago, this one is unlikely to just burn itself out. That's because this particular flu virus seems capable of hanging around in populations of wild birds, which can pass the virus on to poultry farms. While chickens and turkeys with the virus quickly sicken and die, some waterfowl can remain healthy with the virus and carry it long distances. Scientists believe that wild migratory birds brought this virus to North America a few months ago. Since then, more than 40 wild bird species in more than 30 states have tested positive. This strain of bird flu virus has turned up in everything from crows to pelicans to bald eagles.  "It's somewhat surprising how widespread it is already in North America," says Jonathan Runstadler, an influenza researcher at Tufts University. "It's clearly able to persist and transmit from year to year in parts of Asia, Europe, Africa, and I don't think we should be surprised if that's going to be the case here." As the virus moves across the country, and potentially settles in for the long haul, it will encounter new animal species that could get infected. This pathogen will also get a chance to genetically mingle with the flu viruses that are already circulating in the U.S. "What that means for the virus in terms of how it evolves, how it changes, we just don't really know," says Richard Webby, a flu researcher at St. Jude Children's Research Hospital.

There has been only one known human case

So far, the risk to humans seems low. But since related bird flu viruses have repeatedly jumped into people in the past, public health experts are watching for any signs of genetic changes that could make the virus able to move into humans. "We're concerned with any avian influenza virus that's circulating in domestic poultry or wild birds," says Todd Davis, an expert on animal-to-human diseases at the Centers for Disease Control and Prevention (CDC). "Because humans have no prior immunity to these viruses typically, if they were to be infected and spread the virus to other humans, then we could have another pandemic virus on our hands." This virus doesn't have genetic features previously associated with related bird flus that have infected humans. And the only person known to have contracted this particular bird flu virus was an elderly person in the United Kingdom who lived in close quarters with ducks; while some of the ducks got sick and died, their owner never had any symptoms. The CDC has been monitoring the health of more than 500 people in 25 states who were exposed to infected birds, says Davis. Although a few dozen people did develop flu-like symptoms, all were tested and none were positive for this virus.

Raptors could be especially hard hit

Wildlife experts have long known that highly pathogenic bird flus like this one were circulating in Europe and Asia. And they have worried about the possible threat these viruses might pose to American birds. Then, in December of 2021, chickens and other fowl got sick and started dying on a farm on the island of Newfoundland, Canada. Tests showed this deadly bird flu virus had made it across the Atlantic. "The very first moment it got to North America, it was a heads up to us," says Bryan Richards, the emerging diseases coordinator at the U.S. Geological Survey's National Wildlife Health Center. In January, government officials announced its arrival in the U.S. after a wigeon duck in South Carolina tested positive. The last time a dangerous bird flu entered the country, Richards says, "the number of instances where we picked that particular virus up in wild birds was very, very limited." In contrast, this latest bird flu virus is being detected in sick and dying birds all over. "This outbreak in the wild bird population is a lot more extensive than we saw in 2014 and 2015," says David Stallknecht, an avian influenza researcher with the University of Georgia. "Just a lot more birds appear to be affected." Waterfowl, and raptors that eat their dead bodies, are bearing the brunt of it. In Florida, for example, more than 1,000 lesser scaup ducks have succumbed to the virus. In New Hampshire, about 50 Canada geese died in a single event. In the Great Plains states, wildlife experts have seen mass die-offs in snow geese. "In addition, there's a host of other species, including black vultures and bald eagles and some of the other scavenging species, that were likely infected by consuming the carcasses of those waterfowl," says Richards. It remains to be seen how much of a toll this virus will take on American bird species. In Israel, when this virus hit an area where about 40,000 common cranes had gathered for the winter, "they lost a reported 8,000 of these birds over the course of a couple weeks," says Richards. "So when you start thinking about losing 20% of a specific population of wild birds, that's a pretty substantial impact."

Poultry farmers cull their flocks

Chickens and turkeys raised by the poultry industry have suffered the most deaths, and farmers are bracing themselves for even more. The bird flu that struck in 2014 and 2015 resulted in the deaths of more than 50 million birds and cost the industry billions of dollars. Back then, the greatest number of cases occurred in the month of April. "So I think I am kind of holding my breath this month," says Denise Heard, director of research programs for the U.S. Poultry & Egg Association. The virus has a number of ways to get from wild birds into poultry, says Heard. Since the last outbreak, the industry has worked to educate farmers about how to protect their flocks. "Wild migratory waterfowl are always flying over the top and when they poop, that poop gets on the ground," she says, explaining that the virus can then get tracked into bird houses on boots or inadvertently moved from farm to farm on vehicles. Heard says there currently seems to be less spread of the virus from farm to farm than was seen during the last major outbreak. Instead, there are more isolated cases popping up, perhaps because wild birds are bringing the viruses to farms and backyard flocks. If this virus sticks around in wild bird populations — which some scientists think is likely — poultry farmers may need to just learn to live with this problem. "I hope that this is not the case. I hope that in the U.S. this infection will die off soon, and the virus will go away again like it did in 2014," says Ron Fouchier, a virologist at Erasmus Medical Center in the Netherlands. "But there's no guarantee for that, as we've seen in Europe now that this virus has remained present for several years in a row." Since December, farmers in Europe have had to cull more than 17 million birds. "So that's very similar to the situation in the U.S.," says Fouchier. "And we are seeing massive die-offs in wild birds."

The emergence and global spread of the highly pathogenic H5N8 avian influenza virus (AIV), a pathogen that has caused continuous and ongoing outbreaks with massive mortality in both wild and farmed birds across Eurasia and Africa throughout 2020, represents a considerable public health concern — particularly considering the first human cases of H5N8 infection were first reported last December. In a Perspective, Weifeng Shi and George Gao discuss the emergence and zoonotic potential of the H5 AIV lineages. Shi and Gao argue that vigilant surveillance and rigorous infection control measures for these emerging viruses are critical to avoid further human spillovers that could result in new and devastating pandemics.

Perhaps overshadowed by the ongoing global COVID-19 pandemic, over the past year, H5N8 infections in both wildfowl and poultry have been identified in at least 46 countries across Europe, Asia, and Africa. While these outbreaks have led to the death or slaughter of many millions of birds worldwide, they’ve also notably resulted in at least one spillover event in Russia, where seven poultry farm workers tested positive for H5N8 virus. According to the authors, the rapid global spread of this AIV and its demonstrated ability to cross the species barrier, transmitting to humans, makes it a major concern to not only farming and wildlife security, but also global public health. Shi and Gao suggest that the surveillance of highly pathogenic AIVs in poultry farms, live markets, and wild birds must become a global priority.

Cited publication available in Science (May 21, 2021):

https://doi.org/10.1126/science.abg6302

Federal public health officials are turning to wastewater surveillance to help fill in the gaps in efforts to track H5N1 bird flu outbreaks in dairy cows. R eluctance among dairy farmers to report H5N1 bird flu outbreaks within their herds or allow testing of their workers has made it difficult to keep up with the virus’s rapid spread, prompting federal public health officials to look to wastewater to help fill in the gaps. On Tuesday, the Centers for Disease Control and Prevention is expected to unveil a public dashboard tracking influenza A viruses in sewage that the agency has been collecting from 600 wastewater treatment sites around the country since last fall. The testing is not H5N1-specific; H5N1 belongs to the large influenza A family of viruses, as do two of the viruses that regularly sicken people during flu season. But flu viruses that cause human disease circulate at very low levels during the summer months. So the presence of high levels of influenza A in wastewater from now through the end of the summer could be a reliable indicator that something unusual is going on in a particular area.

Wastewater monitoring, at least at this stage, cannot discern the sources — be they from dairy cattle, run-off from dairy processors, or human infections — of any viral genetic fragments found in sewage, although the agency is working on having more capability to do so in the future. CDC wastewater team lead Amy Kirby told STAT that starting around late March or early April, some wastewater collection sites started to notice unusual increases in influenza A virus in their samplings. Those readings stood out because by the last week of March, data the CDC tracks on the percentage of people seeking medical care for influenza-like illnesses suggested that the 2023-2024 flu season was effectively over. The increases were very site-specific, she said, and were not reflected in other areas. In fact, she called it “a very limited phenomenon. … The vast majority of our sites are not seeing this.” To date there has been little information in the public sphere about where infected cattle herds have been located. When the U.S. Department of Agriculture announces positive test results, it merely names the state in which the herd was located when the testing took place. Last week, the USDA reported that six additional herds — in Michigan, Idaho, and Colorado — had tested positive for H5N1, bringing the total to 42....

The avian influenza virus that has been infecting dairy cows and spreading alarm in the United States was expected to reach Germany this week. But that’s actually good news. A shipment of samples of the H5N1 virus from Cornell University virologist Diego Diel is destined for the Federal Research Institute for Animal Health in Riems, which has one of the rare high-security labs worldwide that are equipped to handle such dangerous pathogens in cattle and other large animals. There, veterinarian Martin Beer will use the samples to infect dairy cows, in search of a fuller picture of the threat the virus poses, to both cattle and people, than researchers have been able to glean from spotty data collected in the field. Six weeks into the outbreak that has spread to farms in nine U.S. states, the flow of data from those locations remains limited as public health officials sort out authorities and some farms resist oversight. “It’s incredibly difficult to get the right sample sets off the infected farms,” says Richard Webby, an avian influenza researcher at St. Jude Children’s Research Hospital. “It’s clearly a barrier to understanding what’s going on. … That’s why these experimental infections of cows are really going to be super informative.”

Tissue samples from a polar bear that was found dead have tested positive for the virus. A highly lethal form of bird flu that has been spreading across the world has now been detected in a dead polar bear in Alaska. It is the first known case in the Arctic animals, which are listed as threatened under the Endangered Species Act.

Why It Matters: The virus is a new threat for many wild mammals.

The infected polar bear provides further evidence of how widespread this virus, a highly pathogenic form of H5N1, has become and how unprecedented its behavior has been. Since the virus emerged in 2020, it has spread to every continent except for Australia. It has also infected an unusually broad array of wild birds and mammals, including foxes, skunks, mountain lions and sea lions. “The number of mammals reported with infections continues to grow,” Dr. Bob Gerlach, Alaska’s state veterinarian, said. In most cases, the virus has not caused mass die-offs in wild mammal populations. (South American sea lions have been one notable exception.) But it does represent a new threat for the already vulnerable polar bear, which is imperiled by climate change and the loss of sea ice. “The concern is that we don’t know the overall extent of what the virus may do in the polar bear species,” Dr. Gerlach said.

Background: The bear showed signs of disease.

The polar bear was found dead this past fall in far northern Alaska, near Utqiagvik. Swabs collected from the animal initially tested negative for the virus. But when experts conducted a more comprehensive work-up, performing a necropsy and collecting tissue samples from the bear, they found clear signs of inflammation and disease, Dr. Gerlach said. Last month, tissue samples from the bear tested positive for the virus, according to the Alaska Department of Environmental Conservation. The virus was ultimately identified in multiple organs, Dr. Gerlach said. “I think it would be a safe thing to say that it died from the virus,” he said. Alaska has previously reported infections in a brown bear and a black bear, as well as in several red foxes.

In June 2023, a fatal disease outbreak in cats occurred in Poland. Most cases tested in Poland (29 of 47) were positive for highly pathogenic avian influenza (HPAI) A (H5N1) virus. Genetic analyses revealed clade 2.3.4.4b with point mutations indicative of initial mammalian hosts adaptations. Cat viral sequences were highly similar (n = 21), suggesting a potential common infection source. To investigate possible infection routes, our group tested food samples from affected households. HPAI H5N1 virus was detected in one poultry meat sample.

Scientists identify three key changes needed to adapt the virus to mammals. The victims are varied, from thousands of sea lions off the coast of Peru to mink farmed for fur in Spain to grizzly bears in Montana and harbor seals in Maine. For months, the avian influenza virus that has been decimating birds across the world has also sickened and killed a menagerie of mammals, raising fears it might evolve to spread more efficiently between these animals, and ultimately between people. For that nightmare to unfold, however, the virus, a subtype known as H5N1, would have to undergo a major transformation, changing from a pathogen efficient at infecting cells in the guts of birds and spreading through feces-contaminated water into one adept at infecting human lung tissue and spreading through the air. So far, that has not happened. None of the few people who have caught the virus currently wiping out birds, called clade 2.3.4.4b, seems to have passed it on to other people. “This clade … is most of all and more than all previous clades an avian virus,” says virologist Martin Beer of the Friedrich Loeffler Institute. That is why it has spread so far and wide in birds, he says, and why it is so poor at infecting people. Beer and his colleagues in Berlin and Münster, Germany, have been using lung tissue taken from cancer patients undergoing surgeries, for instance, to see whether the virus can efficiently infect the human cells. So far, it cannot...

The government is investigating the source of contagion as well as others who were in contact with the patient. Chile has reported cases of the H5N1 bird flu since late last year. Chile detected the first case of bird flu in a human, the country’s health ministry reported on Wednesday. The case was detected in a 53-year-old man who presented severe influenza symptoms, according to a statement issued by the ministry, but they noted the patient was in stable condition. The government is also investigating the source of contagion as well as others who were in contact with the patient. Chile has reported cases of the H5N1 bird flu since late last year in wild animals. Recent cases in industrial farms caused the government to halt poultry exports. Industrial cases have also been detected in Argentina, but Brazil, the world’s largest exporter of poultry, remains free of the contagion. Chilean health authorities noted the virus can be transmitted from birds or marine mammals to humans, but there is no known human-to-human transmission. Earlier this year, Ecuador confirmed its first case of human transmission of bird flu in a nine-year-old girl. Global health officials have said risk of transmission between humans is low, but vaccine makers have been preparing bird flu shots for humans “just in case.”

H5N8 and H5N1 high pathogenicity avian influenza viruses (HPAIVs) caused outbreaks in poultry farms in Japan from November 2021 to May 2022. Hemagglutinin genes of these viruses belong to clade 2.3.4.4B and can be divided phylogenetically into the following groups: 20A, 20E, and 21E. In this study, we compared the infectivity and transmissibility of HPAIVs from three groups of chickens. Representative strains from 20A, 20E, and 21E groups are A/chicken/Akita/7C/2021(H5N8)(Akita7C), A/chicken/Kagoshima/21A6T/2021(H5N1)(Kagoshima6T), and A/chicken/Iwate/21A7T/2022(H5N1)(Iwate7T), respectively.

Fifty percent lethal dose of Akita7C in chickens (103.83 fifty percent egg infectious dose (EID50)) was up to seven times lower than those of Kagoshima6T and Iwate7T (104.50 and 104.68 EID50, respectively). Mean death times for Akita7C- and Kagoshima6T-infected chickens (3.45 and 3.30 days, respectively) were at least a day longer than that of Iwate7T (2.20 days). Viral titers of the trachea and cloaca of Iwate7T-infected chicken were the highest detected. The transmission rate of the Akita7C strain (100%) was markedly higher than those of the two strains (<50%). These data suggest that the infectivity and transmissibility of the Akita7C strain (H5N8) in chickens are higher than those of H5N1 viruses, providing fundamental information needed for formulating effective prevention and control strategies for HPAI outbreaks.

Published in Viruses (jan. 17, 2023):

https://doi.org/10.3390/v15020265 

Wild carnivore species infected with highly pathogenic avian influenza (HPAI) virus subtype H5N1 during the 2021-2022 outbreak in the Netherlands included red fox (Vulpes vulpes), polecat (Mustela putorius), otter (Lutra lutra), and badger (Meles meles). Most of the animals were submitted for testing because they showed neurological signs. In this study, the HPAI H5N1 virus was detected by PCR and/or immunohistochemistry in 11 animals and was primarily present in brain tissue, often associated with a (meningo) encephalitis in the cerebrum. In contrast, the virus was rarely detected in the respiratory tract and intestinal tract and associated lesions were minimal. Full genome sequencing followed by phylogenetic analysis demonstrated that these carnivore viruses were related to viruses detected in wild birds in the Netherlands.

The carnivore viruses themselves were not closely related, and the infected carnivores did not cluster geographically, suggesting that they were infected separately. The mutation PB2-E627K was identified in most carnivore virus genomes, providing evidence for mammalian adaptation. This study showed that brain samples should be included in wild life surveillance programs for the reliable detection of the HPAI H5N1 virus in mammals. Surveillance of the wild carnivore population and notification to the Veterinary Authority are important from a one-heath perspective, and instrumental to pandemic preparedness. 

Published in Pathogens (Jan. 23, 2023):

https://doi.org/10.3390/pathogens12020168

In October 2022, an outbreak in Europe of highly pathogenic avian influenza (HPAI) A(H5N1) in intensively farmed minks occurred in northwest Spain. A single mink farm hosting more than 50,000 minks was involved. The identified viruses belong to clade 2.3.4.4b, which is responsible of the ongoing epizootic in Europe. An uncommon mutation (T271A) in the PB2 gene with potential public health implications was found. Our investigations indicate onward mink transmission of the virus may have occurred in the affected farm.

Published in Eurosurveillance (Jan. 18, 2023):

https://doi.org/10.2807/1560-7917.ES.2023.28.3.2300001

The CDC announced late Thursday that a person in Colorado has tested positive for an H5 bird flu virus — the first such recorded infection in the U.S.  The CDC did not reveal the neuraminidase subtype of the virus — the N portion of an influenza A virus’ name. The country is currently experiencing an unprecedented outbreak of H5N1 bird flu in both wild birds and in commercial poultry flocks. The man, described by Colorado health officials as being younger than 40 years old, experienced only fatigue; he is now in isolation and being treated with the flu antiviral oseltamivir. A statement from Colorado’s Department of Public Health and Environment said he is incarcerated at a state correctional facility and was culling poultry as part of a pre-release employment program. The CDC described the poultry outbreak as presumptively having been caused by H5N1. Michael Osterholm, director of the University of Minnesota’s Center for Infectious Diseases Research and Policy, was less sanguine, saying that while previous experience with H5N1 viruses suggests that human infections didn’t lead to sustained person-to-person spread, heightened surveillance is important. “Any time you’re dealing with H5N1, you sleep with one eye open,” he told STAT.

H5 viruses have long struck fear among scientists who study bird flu because of the economic damage they can wreak and their propensity to occasionally infect people. They are one of two subtypes — H7 viruses are the other — that can become highly pathogenic. That term refers to their deadliness when they infect birds. In the mid-aughts, H5N1 viruses decimated poultry flocks first in Southeast Asia and later into South Asia and North Africa. H5 viruses have also been seen to infect people from time to time, often with devastating consequences. Of just over 860 previously recorded human cases of H5N1 infection — from 19 countries — just over half have died. For a number of years, it was feared the virus might cause a potentially devastating pandemic. But when the first pandemic in decades finally occurred in 2009, it was caused by a mild swine flu virus, H1N1.  The CDC’s statement suggested it isn’t completely clear the Colorado man was actually infected. The test may have picked up virus that was “surface contaminant” — presumably virus picked up by a nose swab — that was present because of the man’s involvement in culling infected poultry. But the CDC said the individual meets the criteria as a positive case and had to be treated as such. “The appropriate public health response at this time is to assume this is an infection and take actions to contain and treat,” the statement said. The CDC statement also pointed out that the group of H5N1 viruses that are currently spreading throughout the U.S. and Europe are different from the H5N1 viruses that caused the earlier outbreaks in Asia and North Africa. This is only the second human infection caused by this clade of H5N1 viruses; the first was a man in the United Kingdom who was infected last December. His flock of poultry contracted the virus and the man tested positive for the virus, although he reportedly didn’t experience symptoms of illness.

More than 20 states have reported avian influenza in commercial and backyard farms.  A growing epidemic of bird flu across the East Coast and Midwest has led to more than 20 million birds dying or being destroyed since February, fueling a surge in egg and poultry prices. After circulating for months in Asia and Europe, highly pathogenic avian influenza (HPAI) has been detected in commercial and backyard farms in more than 20 states, according to the US Department of Agriculture. Individual farmers have been forced to cull hundreds of thousands -- sometimes millions -- of birds to check the spread of the disease.  Shell egg prices have jumped to $2.88 a dozen (up more than 50%) since Feb. 8, when the first case was identified in a commercial turkey flock in Indiana. No humans have tested positive in the US yet, but the economic toll could be major: The first US epidemic in 2015 cost the poultry industry more than $1.5 billion and caused egg prices to nearly double. Here's what you need to know about bird flu, including what the outbreak means for consumers, how the industry is combating it and if it poses a threat to humans.

What is bird flu?

Bird flu is caused by avian influenza Type A viruses, which spread naturally among waterfowl and can infect wild birds, domestic poultry and other animals, though rarely humans. There are more than a dozen strains of bird flu, which are classified as either "low pathogenic" or "highly pathogenic," depending on their ability to spread disease and kill poultry.   The strain bombarding the US right now, Eurasian H5N1, is considered highly pathogenic.

How is bird flu transmitted?

The main source of infection is migratory waterfowl, such as ducks and geese. "They get infected but don't get sick," Denise Derrer, public information director for the Indiana State Board of Animal Health, told CNET. "Then they shed the virus in their droppings or wherever the land." That means the spread could peak in a few weeks, when spring migration reaches its high point, and not abate until June, when the birds settle into their summer breeding grounds. How the virus gets from barn to barn is still not entirely clear, which makes it hard to get a grip on the situation, according to Dr. Yuko Sato, a professor at Iowa State's school of veterinary medicine. "There's no concluded study on how it's coming in," Sato told NPR. "We can identify some weak links -- for example, people tracking it in." 

Where have bird flu outbreaks been detected?

The current strain of H5N1 was first reported in Asia and Europe. In the UK, eggs can no longer be labeled free-range because hens have been cooped up for months to avoid infection. Since the USDA confirmed the first US case in a wild duck in South Carolina in mid-January, infections have been reported in commercial farms and backyard flocks in Connecticut, Delaware, Illinois, Indiana, Iowa, Kansas, Kentucky, Maine, Maryland, Massachusetts, Michigan, Minnesota, Missouri, Nebraska, North Carolina, North Dakota, New Hampshire, New York, Ohio, South Dakota, Wisconsin and Wyoming.  As a result, more than 20 million egg-laying hens, poultry chickens and turkeys have been or will soon be "depopulated," or killed, with more infections detected nearly every day. On March 31 alone, infections were detected in five states.

Among the worst outbreaks:

Normally, bird flu viruses do not spread easily from person to person. But if this does happen, it could trigger a pandemic. Researchers from the MDC and RKI have now explained in the journal Nature Communications what makes the leap from animals to humans less likely. Whenever people suddenly become infected with a bird flu virus such as H5N1, H7N9, and H5N6, the World Health Organization (WHO) has to assess the risk: Are these the first signs of a pandemic? Or is it just a few dozen or hundred cases that have only arisen through close contact with infected poultry? Researchers led by Professor Matthias Selbach from the Max Delbrueck Center for Molecular Medicine (MDC) have now found another piece of the puzzle that may be important in this initial assessment. In a paper published in Nature Communications, the researchers explain that avian influenza A viruses (IAVs) are unable to transform infected human cells into effective virus factories, because they do not produce enough of the matrix protein M1 following infection. The virus requires this protein, however, to export its many copies of its genetic material from the cell nucleus—a prerequisite for building new viruses.

Not all flu is the same—the name refers to a large family of viruses. Each member of this family is named after two prickly growths on the virus's surface: hemagglutinin (H), which enables the virus to infect human and animal cells where it can multiply, and neuraminidase (N), which helps the virus's offspring to extract themselves from the infected cell. In waterfowl, there are 16 known hemagglutinin subtypes and nine known neuraminidase subtypes. That results in at least 144 possible combinations that are constantly changing and adapting to new hosts—like chickens, for example, but also mammals including horses, pigs, and humans. Such new virus variants are often more dangerous than seasonal flu, because the human immune system has never encountered them before. Some people find themselves defenseless, while the immune system of others reacts so violently that the person's own resistance damages the body. In the worst case scenario, a pandemic could cost millions of lives. The Spanish flu of 1918, for example, claimed more than 50 million victims. Researchers around the world are therefore trying to understand the rules that determine when there is the possibility of a pandemic, and when there is not.

Why are human cells bad factories for bird flu? "Hemagglutinin in humans and birds has a slightly different chemical structure, for example, which makes it more difficult for an avian influenza virus to infiltrate a human cell than a bird's cell," explains Selbach. Boris Bogdanow, a Ph.D. student in Selbach's research group and the lead author of the current study, focused his research specifically on what other natural species barriers exist in flu viruses. But the devil is in the detail, so Bogdanow performed more in-depth analyses to take a closer look at the protein distribution. In doing so, he came across the matrix protein M1, much larger quantities of which were produced in the lung cells infected with the human virus. The M1 protein is responsible, among other things, for exporting the replicated viral RNA from the nucleus of the infected cells and then assembling it with other newly produced viral proteins to form flu virus offspring. Could it be, then, that the viral RNA of bird flu viruses in human cells remains trapped in the cell nucleus because too little M1 protein is present?....

Published in Nature Communications (04 December 2019):

https://doi.org/10.1038/s41467-019-13520-8