US - Dairy cows test positive for H5N1 avian flu in Texas, Kansas, Idaho, Michigan, New Mexico, Ohio, North Carolina, South Dakota, Colorado, Iowa, Minnesota, Wyoming, Oklahoma, California - March 24+ 10 confirmed human cases

[Treyfish]

Cornell scientists identify bird flu infecting dairy cows

By Melanie Greaver Cordova

Animal Health Diagnostic Center
April 2, 2024 FacebookTwitterEmailShare

Cornell virology experts are sequencing the bird flu virus that struck cows in the Texas panhandle last week, after work at Cornell and two other veterinary diagnostic laboratories found the highly pathogenic avian influenza (HPAI) virus in cattle samples, a first for this species.

Sequencing of the virus may help scientists understand why it jumped to cows and how future outbreaks may be prevented.

“When there is spillover of HPAI to a new species, especially to mammals, it is always concerning, as the virus may adapt and gain the ability to transmit between animals,” said Dr. Diego Diel, associate professor of virology in the Department of Population Medicine and Diagnostic Sciences and director of the Virology Laboratory at the Animal Health Diagnostic Center (AHDC).

HPAI is well-known for its ability to infect various animal species. It is fatal among birds, where it attacks the gastrointestinal tract and the nervous system. Since 2022, the HPAI outbreak has killed millions of commercial poultry and wild birds, and the virus has been detected in many wild carnivores such as foxes that feed on carcasses of dead birds and often suffer the same fate.

Currently there is no evidence that these mammalian species can transmit the virus to other animals, but its detection in ruminants is new. The USDA recently reported HPAI in a juvenile goat, but there were no previous reports of infection in cattle.

When assistant professor of practice Elisha Frye, D.V.M. ’10, first got the call about a disease outbreak of unknown origin among dairy herds in Texas from Will Leone ’07, D.V.M. ’11, a dairy producer and dairy production veterinarian, she advised him to send samples to the AHDC for immediate testing.

“The cows in Texas weren’t producing as much milk, and milk consistency was very different,” Frye said. The cows had mild respiratory signs, weren’t eating well and some had short-term, low-grade fevers.

Leone sent several types of samples to the AHDC, where Diel’s team conducted exploratory next generation sequencing (NGS) that detects viruses in a wide variety of species and samples, casting a wide net that gives scientists the ability to look for virtually anything.

Leone called Frye back a few days later with an update: Grackles and pigeons were found dead at the same facilities, alongside some farm cats. While samples from cows were being sequenced, tests from the birds and a cat performed in the Molecular Diagnostics Laboratory at the AHDC came back positive for HPAI. Analysis of the NGS data then detected influenza sequences in the nasal swabs and milk samples from the sick cows.

“Within five days of receiving the samples, we were able to identify HPAI in association with this outbreak in dairy cows,” Diel said. This was then confirmed by the National Veterinary Services Laboratory at the USDA.

The Cornell researchers detected the event around the same time as the Texas A&M Veterinary Medical Diagnostic Laboratory and the Iowa State Veterinary Diagnostic Laboratory.

When infected birds migrate through an area or farm, they can contaminate water or food sources with the virus. This is likely how the cows first encountered the virus. Whether all affected animals became infected through these sources or whether there was cow-to-cow transmission in herds is under investigation. Unlike birds, these cows did not die due to HPAI and recovered well.

......
“We will study how HPAI spilled over into dairy cows to understand why this outbreak happened,” Diel said. “There are a number of very important questions about its source and the risk of transmission to other animals and humans that need to be addressed.”

The AHDC is encouraging veterinarians to send samples from cows and other animals for any disease outbreak for testing. Instructions on how to submit samples is available here online.

https://news.cornell.edu/stories/2024/04/cornell-scientists-identify-bird-flu-infecting-dairy-cows

[Treyfish]

......“Thankfully, the case that has been identified of avian influenza in a human, that person is doing better and improving,” she said. “That person had a really minor illness. And the symptom that they complained of was conjunctivitis, which means just redness and irritation of the eyes. That’s not always really common with seasonal influenza, but it has been seen more in these avian influenza infections in people.”

Shuford said avian influenza typically spreads from birds to people, and this case is unusual since the spread was from another mammal species to a person.

“It’s an influenza virus. And so it’s spread often by breathing it in or by contacting the eyes, the nose or the mouth. There is also a potential that if somebody touches something and then touches their eyes, nose or mouth, that it could be passed that way,” she said......
https://www.texasstandard.org/storie...��

[Treyfish]

Sally Jo Sorensen
@sallyjos
·
2m
In #mnhouse #Agriculture committee at 1pm, MN Board of Animal Health will give an update on Highly Pathogenic Avian Influenza (#HPAI). Will be streaming on
@MNHouseInfo
HTV or YouTube channel, both HTV4 Here's the Board of Health slideshow #mnleg #mnfarms https://house.mn.gov/comm/docs/cSQNsaZhuUSM_CmtDn6iSw.pdf

[Mary Wilson]

Live - Minnesota House of Representatives

MN Board of Animal Health
Highly pathogenic Avian Influenza

https://www.house.mn.gov/live/4

(perhaps someone would please download this live video)

[Pathfinder]

COMMISSIONER MILLER CONFIRMS CAL-MAINE FOOD’S TEXAS POULTRY FACILITY TESTS POSITIVE FOR HPAI (4/2/2024)


AUSTIN – Today, Texas Agriculture Commissioner Sid Miller confirmed the Cal-Maine Foods, Inc. poultry facility in Farwell, Texas has received official notice of a positive test for H1N5. Due to United States Department of Agriculture (USDA) guidance for poultry infections, Cal-Maine will be required to depopulate 1.6 million laying hens and 337,000 pullets at their Farwell facility. This accounts for approximately 3.6% of the company's total flock as of March 2, 2024. Production at the facility has temporarily ceased as the Cal-Maine Foods, Inc. initiates protocols prescribed by the USDA.

"This is absolutely devastating news for Cal-Maine and the entire Panhandle region which has already suffered so much already," Commissioner Miller said “Given this latest development, all producers must practice heightened biosecurity measures. The rapid spread of this virus means we must act quickly."

This news comes after the Center for Disease Control (CDC) confirmed a positive test of H5N1, a form of highly pathogenic avian influenza (HPAI), in a Texas dairy worker who had direct contact with cattle suspected of being infected. The individual became ill after interacting with cattle believed to be carrying the virus, exhibiting conjunctivitis as the primary symptom. This marks the second human case of H5N1 flu in the United States and the first associated with exposure to cattle, according to the CDC.

Yesterday, USDA confirmed five new H5N1 cases in dairy facilities, now totaling eleven across five states. HPAI has been found in dairy herds in Texas (7), Kansas (2), Michigan (1), and New Mexico (1). The presumptive positive test result from Idaho is still pending. Commissioner Miller said the Texas Department of Agriculture (TDA) will continue monitoring and providing guidance to producers and Texas consumers.

Commissioner Miller said consumers should be assured that rigorous safety measures and pasteurization protocols ensure that dairy products remain unaffected by HPAI. Dairies are required to destroy or divert milk from any sick cows.

The CDC has assured the public that the current health risk assessment for the U.S. general population remains low. However, individuals with close or prolonged, unprotected exposures to H5N1 are at higher risk of infection.

“The current risk to the public remains minimal,” Commissioner Miller emphasized. "It is important for us as an industry to maintain a high level of vigilance. State and national agencies will continue to provide updated guidance as developments warrant."

Cattle impacted by HPAI exhibit flu-like symptoms including fever and thick and discolored milk accompanied by a sharp reduction in milk production averaging between 10-30 pounds per infected cow. It is vital that dairy facilities nationwide practice heightened biosecurity measures to mitigate further spread.

Poultry may have no signs at all, mild respiratory signs like nasal discharge or sneezing, decreased feed consumption, ruffled feathers, and decreased egg production.

“Producers need to work with us and report cases right away,” added Commissioner Miller. “Transparency is going to be key to navigating and mitigating this outbreak. I encourage producers to work with state and national officials to report any symptomatic animals as soon as you identify them.”

Farmers are asked to notify their veterinarian if they suspect any animals are displaying symptoms of this condition.

For answers to frequently asked questions, the USDA has an FAQ sheet here.

For updated guidance as of March 27th, 2024, from the CDC click here.

###

https://www.texasagriculture.gov/News-Events/Article/9961/COMMISSIONER-MILLER-CONFIRMS-CAL-MAINE-FOOD-S-TEXAS-POULTRY-FACILITY-TESTS-POSI

[Lance]

https://www.cidrap.umn.edu/avian-inf...-cat-positives

Tests confirm avian flu on New Mexico dairy farm, probe finds cat positives


Lisa Schnirring


Today at 2:20 p.m.

Avian Influenza (Bird Flu)


The US Department of Agriculture (USDA) Animal and Plant Health Inspection Service yesterday announced that tests have now confirmed highly pathogenic avian influenza (HPAI) in a New Mexico dairy herd and that the virus has now been confirmed in five more Texas dairy herds.

Part of quickly evolving developments, the announcement came shortly after Texas health officials and the Centers for Disease Control and Prevention (CDC) announced the first human case, which involves a person from Texas who had contact with dairy cattle, highlighting the risk to farm workers.

And in another development, Texas officials yesterday said that cats showing illness signs in the dairy farm settings were also positive for the virus.

So far, the virus has now been confirmed on seven Texas farms, along with two in Kansas, and one each from New Mexico and Michigan. The USDA National Veterinary Services Laboratory in Ames, Iowa, is working to confirm a presumptive positive from a dairy herd in Idaho.

Cats tested positive in Texas farm sampling


Following yesterday's announcement of the first human H5N1 infection linked to dairy cow exposure, the Texas Department of State Health Services issued a health alert that urged health providers to be vigilant for people with symptoms from H5N1, especially those who have had contact with potentially infected animals.

It also noted that in March, investigators collected samples from several animals in Texas and Kansas. Wild birds, cats, and dairy cows were tested because they showed illness signs. "Further testing of these samples indicated the presence of avian influenza A(H5N1)," the TDSHS said. A press officer from the TDSHS confirmed in an e-mail that sick cats tested positive for the virus.

Wild birds on affected farms had earlier tested positive for H5N1, and evidence is growing that the virus may be spreading cow to cow. Investigations are still underway to sort out how the virus is spreading on farms, which includes identifying the extent of virus circulation in other animals or wildlife.

Cats are among the mammals previously known be contract H5N1, with infections reported in the United States, Poland, and South Korea.

Genetic sequencing yields more information


Virologists are also looking for clues as genetic sequences in US ruminants and wild birds are uploaded to public databases.

Louise Moncla, PhD, assistant professor of pathobiology at the University of Pennsylvania School of Veterinary Medicine, yesterday said on X (formerly known as Twitter) that USDA scientists have rapidly sequenced full genomes and that she and her collaborators have added them to the Nextstrain visualization tool, which allows scientists to map the family tree of virus sequences.

She said sequences from the dairy cows nest with those from wild bird samples collected from Texas about the same time. However, the goat samples from Minnesota are most similar to a pheasant sequence from Colorado.

Moncla said none of the PB2 sequences have known adaptive markers, and the similarity of internal genes from wild bird and cattle sequences suggest direct transmission from wild birds.

The cases are unusual, because influenza A had never been reported in ruminants before, she said. "Following up on these cows, and keeping an eye on other species will be important going forward."

Who's most at risk on dairy farms?


Federal health officials have said the avian flu outbreaks in dairy herds and the new infection in Texas doesn't change its threat assessment, which is low for the public. They have also emphasized the safety of the nation's milk supply due to safety nets including pasteurization, while warning against drinking raw milk that can harbor pathogens.

In the latest Moos Room podcast, Joe Armstrong, DVM, a cattle production expert with the University of Minnesota, urged dairy farm operators at farms where the virus is confirmed or suspected to focus on those at greatest risk, especially if personal protective equipment is limited. The Moos Room podcast is part of University of Minnesota Extension outreach.

He said the most at-risk groups are anyone who works with raw milk, including those in milking parlors, employees who work with calves, and people who work with bulk tanks. He also said those with immunocompromised conditions, such as pregnancy, are at greater risk.

Armstrong also urged dairy operators to ensure that workers, including those from other countries who don't speak English as their first language, know the illness symptoms to report. "They may or may not be willing to seek medical help when they need it."

"If you are out there and you have employees who fit that description, you need to be advocating for them and watching out for them," Armstrong said. "Check in with them, make sure everything's OK. Make sure they understand what's happening."

[Michael Coston]

USDA Confirms HPAI Infection In Idaho Dairy Herd



Credit USDA




#17,982

Although we've known since last week that preliminary tests had indicated HPAI in an Idaho Dairy herd, this afternoon the USDA has confirmed those test results, making Idaho the 5th state with confirmed HPAI in cattle.

This announcement also indicates that confirmatory tests are being performed on additional samples submitted by Kansas, New Mexico, Ohio and Texas.

This afternoon CIDRAP news also reported that Texas has confirmed that three cats on affected farms tested positive for HPAI, and that evidence supporting cow-to-cow transmission continues to grow.

Excerpts from today's announcement from the USDA follow:

USDA Confirms Highly Pathogenic Avian Influenza in Dairy Herd in Idaho

Press Release

Contact:
APHISpress@usda.gov

WASHINGTON, April 2, 2024 – The U.S. Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS) has confirmed the detection of highly pathogenic avian influenza (HPAI) in a dairy herd in Idaho. APHIS shared on Friday, March 29 that its National Veterinary Services Laboratories (NVSL) in Ames, Iowa, was working to confirm presumptive positive test results from an Idaho herd; this announcement is a follow up to that information.

This marks the first known case of HPAI in cattle in Idaho. To date, USDA has confirmed the detection of HPAI in dairy herds in Texas (7) Kansas (2), Michigan (1), and New Mexico (1).

The NVSL is currently performing confirmatory tests on presumptive positive results from Kansas, New Mexico, Ohio and Texas. It is important to note that, while these samples are from cattle with at least some clinical signs in common with other cattle diagnosed with HPAI, the presence of HPAI should not be considered confirmed until the NVSL analysis is complete.

APHIS has created a landing pagewith recent announcements pertaining to HPAI detections in livestock, as well as biosecurity information and other resources. Going forward, APHIS will post confirmed detections of HPAI in livestock on that landing page by 4:00 p.m. ET each day.

APHIS continues to work closely with the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC), as well as state veterinary and public health officials, to investigate and diagnose the illness in dairy cows causing decreased lactation, low appetite, and other clinical signs.

USDA and federal and state partners will continue to share additional updates as information becomes available. APHIS has also prepared a Frequently Asked Questions document, which can be accessed hereas well as a document with recommendations for state animal health officials, veterinarians, and producers, which may be found here.

(Continue . . . )
.


https://afludiary.blogspot.com/2024/04/usda-confirms-infection-in-idaho-dairy.html

[Michael Coston]

CDC Summary Analyses of Genetic Sequences From HPAI Human Case In Texas


Flu Virus binding to Receptor Cells – Credit CDC




#17,983


The CDC this evening has released their analysis of the HPAI H5N1 virus sampled from the human case in Texas, and reports that it is largely similar to HPAI viruses collected from dairy cattle in Texas.

They do, however, report finding one well known `mammalian' mutation in the human sample; PB2-E627K.

Avian influenza in birds is predominantly a gastrointestinal malady, and is spread mostly via infected droppings. Birds run `hotter’ than mammals, which means avian flu viruses must adapt to lower temperatures found in the respiratory tract if they are to succeed in human or mammalian hosts.

PB2-E627K describes the swapping out of Glutamic acid (E) for Lysine (K) at position 627 in the PB2 protein, which allows the virus to replicate at lower temperatures found in the human respiratory tract.

Additional adaptations are needed to make an avian virus a genuine pandemic threat (some we know about, while others we may not), but PB2-E627K is an important one often look for.

I've reproduced the CDC's summary and some excerpts. Follow the link to read the full technical report.

Technical Update: Summary Analysis of Genetic Sequences of Highly Pathogenic Avian Influenza A(H5N1) Viruses in Texas

EspañolPrint


This is a technical summary of an analysis of the genomic sequences of viruses associated with an outbreak of highly pathogenic avian influenza (HPAI) A(H5N1) viruses in Texas. This analysis supports the conclusion that the overall risk to the general public associated with the ongoing HPAI A(H5N1) outbreak has not changed and remains low at this time. The genome of the virus identified from the patient in Texas is publicly posted in GISAID and has been submitted to GenBank.

April 2, 2024 – CDC has sequenced the influenza virus genome identified in a specimen collected from the patient in Texas who was confirmed to be infected with highly pathogenic avian influenza A(H5N1) [“HPAI A(H5N1)”] virus and compared these with HPAI A(H5N1) sequences from cattle, wild birds and poultry. The virus sequences are HA clade 2.3.4.4b HPAI A(H5N1) with each individual gene segment closely related to viruses detected in dairy cattle available from USDA testing in Texas.

While minor changes were identified in the virus sequence from the patient specimen compared to the viral sequences from cattle, both cattle and human sequences maintain primarily avian genetic characteristics and for the most part lack changes that would make them better adapted to infect mammals. The genome for the human isolate had one change (PB2 E627K) that is known to be associated with viral adaptation to mammalian hosts, and which has been detected before in people and other mammals infected with HPAI A(H5N1) virus and other avian influenza subtypes (e.g., H7N9), but with no evidence of onward spread among people.

Viruses can undergo changes in a host as they replicate after infection. Further, there are no markers known to be associated with influenza antiviral resistance found in the virus sequences from the patient’s specimen and the virus is very closely related to two existing HPAI A(H5N1) candidate vaccine viruses that are already available to manufacturers, and which could be used to make vaccine if needed. Overall, the genetic analysis of HPAI A(H5N1) viruses in Texas supports CDC’s conclusion that the human health risk currently remains low. More details are available in this technical summary below:

(SNIP)

The virus sequence was confirmed to be HA clade 2.3.4.4b HPAI A(H5N1) with each individual gene segment determined to be closely related to viruses detected in dairy cattle in Texas. The genotype was classified as B3.13 (1) and corresponds to the same genotype described by USDA for the virus detected in Texas cattle (2). This genotype contains PA, HA, NA and M gene segments from Eurasian wild bird lineages and PB2, PB1, NP and NS gene segments from American wild bird lineages. Other viruses with this genotype have been sporadically detected in wild birds, poultry and one skunk since November 2023 in the U.S. CDC’s real-time RT-PCR diagnostic test used for the detection of A(H5) virus in human samples has not been impacted by genetic changes in B3.13 genotype viruses

(SNIP)

Analysis of the other gene segments (PB2, PB1, PA, NP, M, NS) was also conducted. No known or suspected markers of reduced susceptibility to antiviral compounds that target the PA (i.e., baloxavir marboxil) or M2 (i.e., amantadine, rimantadine) were found.

In addition to the HA and NA, the RNA transcription and replication complex (PB2, PB1, PA, NP) also have species-specific determinants that impact efficient replication in humans and other mammals, particularly polymerase basic protein 2 (PB2). The PB1, PA and NP lacked markers of mammalian adaptation. The PB2 of the human specimen had a change of PB2 E627K compared to the PB2 genes of viruses available from USDA detections in Texas dairy cattle and typically found in A(H5N1) viruses circulating in wild birds. This mutation is, however, commonly found in humans and other mammals that are infected with HPAI A(H5N1) viruses and is understood to be associated with mammalian adaptation because it improves RNA polymerase activity and replication efficiency in mammalian cells; based on experimental studies in mice, guinea pigs and ferrets, it has the potential to impact pathogenesis or transmission in infected mammals (7-8).

Despite previous identification of PB2 E627K in human cases of HPAI A(H5N1) virus, there is no evidence of onward transmission among humans after infection with viruses containing this mutation. It is important to note that this substitution has not been seen in available PB2 genes from viruses circulating in wild birds and poultry or in the recently described cattle viruses detected in Texas, suggesting the mutation may have been acquired in the patient during the development of conjunctivitis. Viruses can undergo changes in a host as they replicate after infection, and it is not uncommon or surprising for HPAI A(H5N1) viruses to undergo this and other polymerase gene changes in infected patients (9). Additional data from A(H5N1) virus-infected animals from the premises where the person was likely exposed is needed to support this hypothesis.

The protein products from the M (M1 and M2) and NS (N1 and N2) genes lacked markers associated with mammalian adaptation. Collectively, epidemiologic, and viral genomic analyses indicate that this case represents a single zoonotic event and while the HA lacked changes likely to enhance transmission to mammals, it did acquire substitutions in PB2 likely to enhance replication in mammals, which illustrates that we have to remain vigilant and continue to characterize zoonotic viruses.

Overall, the genomic analysis of the virus from this human case does not change CDC’s risk assessment related to the HPAI A(H5) clade 2.3.4.4b viruses. The overall risk to human health associated with the ongoing HPAI A(H5) outbreaks in poultry and detections in wild birds and cattle remains low.

(Continue . . . )

[sharon sanders]

Raj Rajnarayanan
@RajlabN


20m
H5N1 Update | Avian Flu Clade 2.3.4.4b Looked at the newly uploaded Human Sequence (ID: 19027114) from Texas - PB2 contains E627K in addition to the mutations found in the dairy cattle and wild bird sequences uploaded earlier (used #Fluserver for mutational analysis)

Quote

Raj Rajnarayanan
@RajlabN

Mar 29

Avian Flu Clade 2.3.4.4b update Looked at newly uploaded sequences (GISAID) from Dairy Cattle and birds from Texas Dairy Cows, Blackbirds and Common Grackle have similar mutation pattern Likely source? 1/n
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Raj Rajnarayanan
@RajlabN
·
5m
.
@PeacockFlu
talked about host adaptation signatures in
@ScienceMagazine
H/T
@kakape

‘Incredibly concerning’: Bird flu outbreak at Spanish mink farm triggers pandemic fears
From science.org
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Raj Rajnarayanan
@RajlabN
·
3m
more on E627K host adaptation signature


Dynamic PB2-E627K substitution of influenza H7N9 virus indicates the in vivo genetic tuning and...
From pubmed.ncbi.nlm.nih.gov
3

[sharon sanders]

Technical Update: Summary Analysis of Genetic Sequences of Highly Pathogenic Avian Influenza A(H5N1) Viruses in Texas


Español
Print
This is a technical summary of an analysis of the genomic sequences of viruses associated with an outbreak of highly pathogenic avian influenza (HPAI) A(H5N1) viruses in Texas. This analysis supports the conclusion that the overall risk to the general public associated with the ongoing HPAI A(H5N1) outbreak has not changed and remains low at this time. The genome of the virus identified from the patient in Texas is publicly posted in GISAID and has been submitted to GenBank.

April 2, 2024 – CDC has sequenced the influenza virus genome identified in a specimen collected from the patient in Texas who was confirmed to be infected with highly pathogenic avian influenza A(H5N1) [“HPAI A(H5N1)”] virus and compared these with HPAI A(H5N1) sequences from cattle, wild birds and poultry. The virus sequences are HA clade 2.3.4.4b HPAI A(H5N1) with each individual gene segment closely related to viruses detected in dairy cattle available from USDA testing in Texas. While minor changes were identified in the virus sequence from the patient specimen compared to the viral sequences from cattle, both cattle and human sequences maintain primarily avian genetic characteristics and for the most part lack changes that would make them better adapted to infect mammals. The genome for the human isolate had one change (PB2 E627K) that is known to be associated with viral adaptation to mammalian hosts, and which has been detected before in people and other mammals infected with HPAI A(H5N1) virus and other avian influenza subtypes (e.g., H7N9), but with no evidence of onward spread among people. Viruses can undergo changes in a host as they replicate after infection. Further, there are no markers known to be associated with influenza antiviral resistance found in the virus sequences from the patient’s specimen and the virus is very closely related to two existing HPAI A(H5N1) candidate vaccine viruses that are already available to manufacturers, and which could be used to make vaccine if needed. Overall, the genetic analysis of HPAI A(H5N1) viruses in Texas supports CDC’s conclusion that the human health risk currently remains low. More details are available in this technical summary below:


Technical Summary:


Viral RNA extractions obtained from nasopharyngeal swab and conjunctival swab specimens collected from the patient were used as template to perform next generation sequencing using Illumina and Oxford Nanopore Technologies (ONT) platforms. Codon complete consensus sequence was successfully generated only from the conjunctival specimen and was assembled using CDC’s Iterative Refinement Meta Assembler (IRMA). Illumina and ONT yielded identical sequences at the consensus sequence level. In concordance with the rRT-PCR cycle threshold (Ct) values obtained from each specimen (i.e., approximately 18 for the conjunctival specimen and 33 for the nasopharyngeal sample), viral RNA from the nasopharyngeal sample failed to generate PCR amplicons suitable for sequencing. Notably, the patient reported only conjunctivitis with no respiratory or other symptoms, which likely resulted in lower viral RNA concentrations detected in the nasopharyngeal sample and is suggestive of a lack of respiratory infection in the patient.

The virus sequence was confirmed to be HA clade 2.3.4.4b HPAI A(H5N1) with each individual gene segment determined to be closely related to viruses detected in dairy cattle in Texas. The genotype was classified as B3.13 (1) and corresponds to the same genotype described by USDA for the virus detected in Texas cattle (2). This genotype contains PA, HA, NA and M gene segments from Eurasian wild bird lineages and PB2, PB1, NP and NS gene segments from American wild bird lineages. Other viruses with this genotype have been sporadically detected in wild birds, poultry and one skunk since November 2023 in the U.S. CDC’s real-time RT-PCR diagnostic test used for the detection of A(H5) virus in human samples has not been impacted by genetic changes in B3.13 genotype viruses.

The hemagglutinin (HA) gene codes for one of the two surface glycoproteins and is central to species specificity because it is responsible for virus attachment and fusion with host cells. Like the viruses detected in cattle, the analysis of the HA gene from the human specimen shows that it is closely related to HPAI A(H5) viruses in HA clade 2.3.4.4b recently detected in wild birds and poultry and lacks amino acid changes that improve recognition of mammalian receptors or fusion of the viral membrane with the host endosomal membranes. The HA is also the primary target of neutralizing antibodies elicited by infection or vaccination, and the HA of virus from the human specimen is very closely related to the A/Astrakhan/3212/2020-like pre-pandemic candidate vaccine virus (CVV) (IDCDC-RG71A) and the A/American wigeon/South Carolina/22-000345-001/2021-like CVV (IDCDC-RG78A), both of which are available to vaccine manufacturers (3). There are only four amino acid changes (L104M, L115Q, T195I, V210A) between the HA1 of the virus from the Texas case and A/Astrakhan/3212/2020-like CVV and only two changes (L115Q, T195I) compared to the A/American wigeon/South Carolina/22-000345-001/2021-like CVV. The changes are not in major antigenic epitopes strongly suggesting that antibodies elicited by A/Astrakhan/3212/2020-like and A/American wigeon/South Carolina/22-000345-001/2021-like vaccines would be expected to have good cross-reactivity – and therefore protection – against this virus.

The neuraminidase (NA) gene encodes the other surface protein of the virus. The major role of the NA is to release new progeny virions from an infected cell by enzymatically cleaving sialic acid receptors, which aids virus spread to uninfected cells within an infected host. The enzymatic activity of NA is inhibited by one class of antiviral drugs that are FDA-approved for treatment of influenza (i.e., NA inhibitors). Analysis of the N1 NA gene from the Texas human specimen showed that it did not have any known or suspected markers of reduced susceptibility to this class of antivirals, which includes oseltamivir. Furthermore, the NA has a full-length stalk which is consistent with viruses that naturally circulate in wild birds. In previous HPAI A(H5N1) virus outbreaks and zoonoses the NA stalk region often had deletions (e.g., a 20 amino acid deletion at positions 49–68 relative to A/goose/Guangdong/1/1996) that enhances replication and/or pathogenesis in terrestrial poultry and mice (4-6).

Analysis of the other gene segments (PB2, PB1, PA, NP, M, NS) was also conducted. No known or suspected markers of reduced susceptibility to antiviral compounds that target the PA (i.e., baloxavir marboxil) or M2 (i.e., amantadine, rimantadine) were found.

In addition to the HA and NA, the RNA transcription and replication complex (PB2, PB1, PA, NP) also have species-specific determinants that impact efficient replication in humans and other mammals, particularly polymerase basic protein 2 (PB2). The PB1, PA and NP lacked markers of mammalian adaptation. The PB2 of the human specimen had a change of PB2 E627K compared to the PB2 genes of viruses available from USDA detections in Texas dairy cattle and typically found in A(H5N1) viruses circulating in wild birds. This mutation is, however, commonly found in humans and other mammals that are infected with HPAI A(H5N1) viruses and is understood to be associated with mammalian adaptation because it improves RNA polymerase activity and replication efficiency in mammalian cells; based on experimental studies in mice, guinea pigs and ferrets, it has the potential to impact pathogenesis or transmission in infected mammals (7-8). Despite previous identification of PB2 E627K in human cases of HPAI A(H5N1) virus, there is no evidence of onward transmission among humans after infection with viruses containing this mutation. It is important to note that this substitution has not been seen in available PB2 genes from viruses circulating in wild birds and poultry or in the recently described cattle viruses detected in Texas, suggesting the mutation may have been acquired in the patient during the development of conjunctivitis. Viruses can undergo changes in a host as they replicate after infection, and it is not uncommon or surprising for HPAI A(H5N1) viruses to undergo this and other polymerase gene changes in infected patients (9). Additional data from A(H5N1) virus-infected animals from the premises where the person was likely exposed is needed to support this hypothesis.

The protein products from the M (M1 and M2) and NS (N1 and N2) genes lacked markers associated with mammalian adaptation. Collectively, epidemiologic, and viral genomic analyses indicate that this case represents a single zoonotic event and while the HA lacked changes likely to enhance transmission to mammals, it did acquire substitutions in PB2 likely to enhance replication in mammals, which illustrates that we have to remain vigilant and continue to characterize zoonotic viruses.

Overall, the genomic analysis of the virus from this human case does not change CDC’s risk assessment related to the HPAI A(H5) clade 2.3.4.4b viruses. The overall risk to human health associated with the ongoing HPAI A(H5) outbreaks in poultry and detections in wild birds and cattle remains low.

Note: HPAI A(H5) viruses, predominantly HPAI A(H5N1) clade 2.3.4.4b viruses, have been circulating globally in wild birds in the U.S. since late 2021. These viruses have caused outbreaks in commercial and backyard poultry, with spillover resulting in sporadic infections in mammals.

References

1. GenoFLU. GitHub – USDA-VS/GenoFLU: Influenza data pipeline to automate genotyping assignment
2. United States of America – Influenza A viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) – Follow up report 44. https://wahis.woah.org/#/in-review/4451?fromPage=event-dashboard-url
3. World Health Organization. 2024. Genetic and antigenic characteristics of zoonotic influenza A viruses and development of candidate vaccine viruses for pandemic preparedness. February 2024. https://cdn.who.int/media/docs/default-source/influenza/who-influenza-recommendations/vcm-northern-hemisphere-recommendation-2024-2025/202402_zoonotic_vaccinvirusupdate.pdf?sfvrsn=70150 120_4
4. Stech O, Veits J, Abdelwhab EM, Wessels U, Mettenleiter TC, Stech J. 2015. The Neuraminidase Stalk Deletion Serves as Major Virulence Determinant of H5N1 Highly Pathogenic Avian Influenza Viruses in Chicken. Sci Rep 5:13493.
5. Naguib MM, Arafa AS, El-Kady MF, Selim AA, Gunalan V, Maurer-Stroh S, Goller KV, Hassan MK, Beer M, Abdelwhab EM, Harder TC. 2015. Evolutionary trajectories and diagnostic challenges of potentially zoonotic avian influenza viruses H5N1 and H9N2 co-circulating in Egypt. Infect Genet Evol 34:278-91.
6. Zhou H, Yu Z, Hu Y, Tu J, Zou W, Peng Y, Zhu J, Li Y, Zhang A, Yu Z, Ye Z, Chen H, Jin M. 2009. The special neuraminidase stalk-motif responsible for increased virulence and pathogenesis of H5N1 influenza A virus. PLoS One 4:e6277.
7. Bortz E, Westera L, Maamary J, Steel J, Albrecht RA, Manicassamy B, Chase G, Martínez-Sobrido L, Schwemmle M, García-Sastre A. Host- and strain-specific regulation of influenza virus polymerase activity by interacting cellular proteins. mBio. 2011 Aug 16;2(4):e00151-11. doi: 10.1128/mBio.00151-11. PMID: 21846828; PMCID: PMC3157893.

1. Min JY, Santos C, Fitch A, Twaddle A, Toyoda Y, DePasse JV, Ghedin E, Subbarao K. Mammalian adaptation in the PB2 gene of avian H5N1 influenza virus. J Virol. 2013 Oct;87(19):10884-8. doi: 10.1128/JVI.01016-13. Epub 2013 Jul 17. PMID: 23864613; PMCID: PMC3807384.

1. Le QM, Sakai-Tagawa Y, Ozawa M, Ito M, Kawaoka Y. Selection of H5N1 influenza virus PB2 during replication in humans. J Virol. 2009 May;83(10):5278-81. doi: 10.1128/JVI.00063-09. Epub 2009 Mar 4. PMID: 19264775; PMCID: PMC2682078.

Last Reviewed: April 2, 2024

https://www.cdc.gov/flu/avianflu/spotlights/2023-2024/h5n1-analysis-texas.htm

[sharon sanders]

This is NOT about the H5N1 avian influenza strain but provides some interesting information about PB2 E627K:

J Gen Virol
. 2014 Apr;95(Pt 4):779-786.
doi: 10.1099/vir.0.061721-0. Epub 2014 Jan 6.

The PB2 E627K mutation contributes to the high polymerase activity and enhanced replication of H7N9 influenza virus

Hong Zhang ¹, Xuyong Li ², Jing Guo ², Li Li ¹, Chong Chang ¹, Yuanyuan Li ², Chao Bian ³, Ke Xu ¹, Hualan Chen ², Bing Sun ^{3 1}
Affiliations expand

• PMID: 24394699
• DOI: 10.1099/vir.0.061721-0

Abstract


Human infection by H7N9 influenza virus was first identified in China in March 2013. As of 12 August 2013, a total of 135 documented cases with 44 fatalities had been reported. Genetic and laboratory analyses of the novel H7N9 viruses isolated from patients indicate that these viruses possess several polymerase gene mutations previously associated with human adaptation and potential pandemic capabilities. However, the function of these mutations in the emergence and pathogenicity of the viruses is not well known. In this study, we demonstrate that the PB2 E627K mutation, which occurs in over 70 % of the H7N9 patient isolates, promotes the replication of H7N9 virus by enhancing PB2 polymerase activity and enhances virulence in mice. Our results show the PB2 E627K mutation has played an important role in this H7N9 influenza outbreak and in the pathogenicity of the H7N9 virus.

https://pubmed.ncbi.nlm.nih.gov/24394699/

[Mary Wilson]

Largest US fresh egg producer halts production at Texas plant after bird flu found in chickens

Published 5 hours ago•Updated 4 hours ago

By The Associated Press and NBCDFW Staff

The largest producer of fresh eggs in the United States said Tuesday that it has stopped production at a Texas plant after bird flu was found in chickens there.

Ridgeland, Mississippi-based Cal-Maine Foods, Inc. said in a statement that approximately 1.6 million laying hens and 337,000 pullets, about 3.6% of its total flock, were destroyed after the infection, avian influenza, was found at the facility in Parmer County, Texas. ...

The company said there is no known bird flu risk associated with eggs that are currently in the market and no eggs have been recalled. Miller echoed the statement, saying the risk to the public is minimal. ...

Cal-Maine sells the majority of its eggs in the Southwestern, Southeastern, Midwestern and mid-Atlantic regions of the United States, the company said.

https://www.nbcdfw.com/news/local/texas-news/avian-flu-found-in-chicken-eggs-in-texas/3504517/

[Treyfish]

Ohio dairy cattle test positive for bird flu

The Ohio Department of Agriculture says cattle in Wood County tested positive. Test result awaiting confirmation from U.S. Department of Agriculture

Erin Glynn
Columbus Dispatch

The cattle that tested positive came to a dairy operation in Wood County from Texas on March 8. State officials were notified when the cattle began exhibiting symptoms similar to herds infected with bird flu in other states. Most sick cows recover within a few days, according to the Ohio Department of Agriculture.

This H5N1 strain of bird flu, among the deadliest forms according to the Associated Press, has been found in dairy cows in Texas, Kansas, Idaho, New Mexico and Michigan.

State and federal publ
https://www.dispatch.com/story/news/...u/73186058007/

[Treyfish]

Highly Pathogenic Avian Influenza Detected in Ohio Dairy Herd

Wood County operation received cows from a Texas dairy that later confirmed HPAI


PUBLISHED ON APRIL 2, 2024
REYNOLDSBURG, Ohio — The Ohio Department of Agriculture (ODA) has received a presumptive positive test result of highly pathogenic avian influenza (HPAI) in an Ohio dairy cattle herd and is awaiting confirmation from the United States Department of Agriculture’s (USDA) National Veterinary Services Laboratory (NVSL).

The dairy operation in Wood County received cows on March 8, 2024, from a Texas dairy, which later reported a confirmed detection of HPAI. Ohio’s animal health officials were notified when the livestock began showing clinical signs compatible with sick, lactating dairy cows in other states.....


https://www.morningagclips.com/highl...hio-dairy-herd

[Michael Coston]

USDA: Testing Recommendations Of Influenza A In Cattle






#17,985

The USDA has published an interim guidance document on the testing of cattle for influenza A. Since cattle were presumed unlikely hosts for HPAI up until a little more than a week ago, this guidance is subject to change as more is learned about the threat.

The high points from this 5-page document include:

• Testing remains voluntary
• The criteria for testing is fairly narrow, with only symptomatic dairy cows currently eligible for testing

Due to its length, I've only reproduced some excerpts. Follow the link to read the document in its entirety. I'll have a brief postscript after the break.

Version.2024.04.01

Please note: This situation is evolving rapidly. Check back frequently for updated versions.

Testing Recommendations for Influenza A in Cattle

BACKGROUND: The Animal and Plant Health Inspection Service, Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDC), State Animal Health and Public Health Officials, and National Animal Health Laboratory Network (NAHLN) laboratories are continuing to investigate an illness among dairy cows that is causing decreased lactation, low appetite, and other symptoms. APHIS has confirmed highly pathogenic avian influenza (HPAI) H5N1 in bovine-origin samples associated with the illness.

This document provides APHIS’ current recommendations regarding testing of affected or exposed cattle. This is a rapidly evolving situation and new information is being received, reviewed, and analyzed constantly to inform and adjust recommendations accordingly.

APHIS will share new information with our valued partners and stakeholders as soon as it is available. At this time, APHIS is not requiring testing. Testing may be done on a voluntary basis and is a tool producers may use to help manage this disease or reduce the risk of introducing the disease. APHIS may fund some testing as outlined below.

TESTING AFFECTED CATTLE (Cattle that meet the Case Profile)

New suspect cases:

Dairy farms and other cattle herds with an active event: cows must be exhibiting clinical signs; there may be dead/sick birds, cats, or other mammals. All would be eligible for reimbursement by APHIS through NAHLN or Unexplained Morbidity/Mortality Event (UME) funding; please see specifics as outlined below.

Working Case Profile:

• Sudden drop in feed intake with concurrent decreased rumination and rumen motility.
• Subsequent marked drop in herd level milk production. More severely affected cows may have thickened milk that almost appears like colostrum or may have essentially no milk.
• Changes in manure - most reporting indicates tacky to dry manure in affected cattle.

A FAD/EP number is required prior to testing to qualify for reimbursement. Although the HPAI (H5N1) virus itself is a foreign animal disease (FAD), we are considering this as an emerging disease in cattle. APHIS encourages states and industry to use the established FAD/Emerging Disease investigation process to investigate credible reports of HPAI (H5N1) virus in dairy cattle (and beef cattle or other domestic livestock species).

APHIS will fund the NAHLN laboratory influenza PCR testing for up to 20 mammals (no more than two samples per mammal) and unlimited birds per premises. If lactating, one sample must be milk/mammary tissue. Samples must go to a NALHN laboratory approved to test for avian influenza.

(SNIP)

Retrospective cases:

Herds with no clinical signs, but had a previous event that meets the case profile (see above for definition) since November 1, 2023:

APHIS is working to gather as much information as possible to help improve the understanding of this event. As such retrospective testing can provide insight into the movement of this virus as well as performance of serological assays for potential future use. Banked or retained milk/tissue. APHIS is willing to fund influenza testing on banked samples from cattle and other mammals on the premises that match the case profile.

(SNIP)

UNAFFECTED CATTLE - Movement Testng for (Influenza A)

APHIS does not reimburse for movement testing.

At this time, we strongly recommend minimizing movement of cattle as much as possible, with special attention to evaluating risk and factoring that risk into movement decisions. Do not move sick or exposed animals.

Based on our current information, it appears the virus has an affinity to replicate in mammary tissue. We have yet to identify animals with confirmed virus replication in tissues other than mammary tissue and milk.

(Continue . . .)


This is, as stated, a rapidly evolving situation - and while it might be desirable to cast a wider testing net - it takes time to gear up to deal with a new threat. As it is, it is taking up to a week to confirm test results.

Hopefully, this outbreak is limited to producing dairy cows, but we won't know that for sure until wider testing can be arranged.

Stay tuned.

https://afludiary.blogspot.com/2024/04/usda-testing-recommendations-of.html