Positive states report new infections, negative states proclaim status w/o detail on requirements, and the balance "are underway" for 6 months!! What gives?? And does anyone care??
The two genotypes B3.13 and D1.1 both adapted to replication in mammalian cells. B3.13 with PB2-E627K and D1.1 with PB2-D701N have been detected in more than 20 dairy cow herds. My understanding is that at least PB2-E627K is a prerequisite for limited pig-to-pig transmission, that distinguishes this study from other studies where no pig-to-pig transmission was observed:
Thanks, for these updates, which I wasn't aware of. It's unfortunate that USDA's regulatory policy does not provide state or origin on sequences. The D1.1's have so far been confined to Nevada and Arizona, to my knowledge (2-3 separate introductions) with a larger cluster of isolates likely being the NV cases where several unique herds, but closely situated herds were diagnosed. AZ has been less forthcoming on any details surrounding their cases.
On the B3.13 PB2-E627K isolates, unofficially that has clustered with other isolates that were identified to California, so those may have developed in that state?
Of course we have no idea what genotypes may be present in undiagnosed herds where sampling is not taking place or where CT values are too weak to allow reliable sequencing...
Regarding whether any individual genotype has yet demonstrated the ability to transmit pig-to-pig, I think that question is somewhat academic, because any of these viruses are only a mutation away from that capability. It doesn't change the urgency for looking for non-endemic viruses in pigs, especially in herds at high risk for contact with H5-infected poultry, livestock, and wildlife. It's borderline malpractice to avoid testing pigs in contact with dairy or poultry herds because "the genotype doesn't contain PB2-E627K or D701N", so it's not a risk. Just do the swabbing and look for influenza by PCR, then sequence if it is there...
With at least three introductions into cows and both genotypes adapting to mammals that's a negative trend, not just individual occurrences. Although it's debatable if the virus is endemic or not.
A year ago I looked into the USDA Influenza A Swine Surveillance Program and it's been entirely insufficient for early detection of limited and asyptomatic outbreaks according to my very rough estimate:
I don't know if any measures like wastewater testing have been introduced since then, but the commercial incentives for farmers to report asymptomatic infections are minimal.
I expect limited pig-to-pig transmission in the proximity of affected herds, spillover from cows into several other species is well documented. I agree with you regarding the urgent need for increased general surveillance. It's just that detection of pig-to-pig transmission is more likely near dairy herds with PB2-E627K and PB2-D701N than anywhere else.
"Although we did not fully evaluate the direct effects of the E627K mutation in swine, the shedding and transmission profile shown for the 2 mammal isolates in this study indicate this adaptive mutation might have increased viral fitness through enhanced polymerase activity to enable transmission in an otherwise less susceptible host. (...) In contrast, we detected A/raccoon/WA/22 in the nasal cavity of inoculated pigs (4 of 15) and transmitted to contacts (2 of 5). Similarly, we detected A/redfox/MI/22 in the nasal cavity of inoculated pigs (5 of 15) and transmitted to a single contact."
Oh, don't get me wrong...I'm with you 100%! Every swine herd in the proximity of dairy and poultry outbreaks should be monitored and swabbed, symptoms or not (Yes, IAV is widely asymptomatic in swine). Especially when adaptive mutations are found in the outbreak isolates!
But we can't get states of origin on isolates or timely disclosure of the mutations (e.g. in 5 days), let alone nearby surveillance! We are totally set up for too little, too late due to political restrictions, excessive regulatory caution, and now likely inadequate staffing.
I assume the risk for pigs has increased dramatically compared to a few months ago, although there is no data for those exact strains in pigs yet. And I assume limited direct contact pig-to-pig transmission is occurring. But that's risk assessment, not scientific facts.
I find the issue of re-infection intriguing. It would be a perfect situation to create an Autogenous vaccine from within a positive herd and utilize it immediately in that same herd that was affected previously, instead of waiting for the next new grand drug/vaccine to gain approval.
We have so much to learn about the course of herd infection and immunity. I agree about post-infection vaccination. not sure how "autogenous" a vaccine would need to be. strains may be fairly cross protective, and conversely, the virus may "drift enough antigenically over time (like it does in pigs) that immunity won't hold regardless. How and where does the virus survive over time in herds? In replacement stock? Partially immune animals? Deep in the udder or lymphatics somewhere??
Or do new replacements keep getting infected as existing herd mates slowly clear infection, so that on a herd basis the infection never clears? In pigs, people practice "herd closures" to overcome that. Maybe that is not possible in large dairies... Herd basis immunity is fascinating!
Interesting points. All make sense. By "herd closures" I take it you mean the same as what I've always called a "closed herd": no bought in animals and use artificial insemination for breeding, yes?
I've been wondering for quite some time why my home area of southeast PA has fortunately remained negative while poultry houses there are positive.
Maybe because of the small herd demographic in general, replacements aren't as heavily relied upon(?).
Even more to that point, here in NC where I live now, I was told by state a legislator that the 1 herd, which was relatively large at about 1000 cows and positive in March 2024 (none since) had bought replacement animals in from Texas. I've been wondering why the normal vectors of service personnel (vets, nutritionists, etc) hadn't spread it. Additionally, 20 poultry houses here in NC were positive in 2024 and fortunately only 3 in January and then 1 in March (none since).
It is common knowledge that large dairy farms have high cull rates and often do not have enough in-house replacements. Hence buying replacements.
And it is west of the Mississippi where most bovines are affected by HPAI (whatever strain): the area of the nation that has the highest number of large herds (that need replacements the most).
Perhaps in states, like PA, NC, VT etc where there are some (but not dominated by) large herds - maybe the best definition of large herd is "X" replacement rate - but have avpreponderance of smaller herds (with either no replacements needed or below a certain threshold %) - even with poultry houses testing positive like in southeast PA - there is then no critical carrying capacity or density for the virus to become endemic in that area, even with wild fowl migratory routes..
I'm an east coast dairy vet for 30 years and freely admit i'm biased towards small herds for many reasons beyond HPAI. And I'll say something perhaps which is a Captain Obvious: the manner in which large dairy herds manage their cows to maximize production leads to cow "burn out" more quickly than smaller farms and the need for more replacements, thus keeping HPAI potentially entering such herds.
Also, many studies have shown that certified organic farms have relatively lower cull rates than conventional and I'd love to see data how they are doing in HPAI testing and clinical signs. But I don't think that's possible to ascertain, though valuable data it would be.
Just some "aha" moments that came to me from your response to my talking about autogenous vaccines.
Thank you for the many insights I glean from your detective work on this topic. It's why I subscribe 🙂
Your response raised many thoughts in my mind too voluminous to write currently. Would love to talk on the phone. In general I agree replacements are critical - and large herds bringing in lactating replacements raise the stakes even more. I just don't know where and how long this virus hides out post acute infection in herds - a really critical question for animal movements. PRRS and flu in pigs dies out with strict closure (no new animals added), especially if infection is spread to the entire herd early. we don't really see "carrier" animals as such. If true in cattle, the same concept should apply, but the herd has to truly "go negative", and the replacements (every time!) must remain negative. Or vaccine must be "sterilizing". So much to learn yet...and we also have to add in viral shift and drift...
As always, thank you for a very informative read on the situation, Dr. Korslund. The awesome Dr. Jetelina (who is also on this platform) put the risk of an H5N1 pandemic at around 8% around the beginning of the year when outbreaks in poultry were especially high. Do you have a number in mind for the probability of this occurring? Thanks!
I've never felt comfortable putting odds on that. I'm probably more concerned about the virus bouncing around in mammals after adaptation than I am about ongoing poultry outbreaks. Pigs and cats scare me a lot because of existing endemic viruses available for reassortment with H5N1 spillovers. But as for odds, 8% seems high...Even in pigs - the virus has to overcome endemic viruses that are already very adapted and providing some pre-existing non-specific immunity. Same is true in people. It takes the right combination of events for a truly genomically unique strain to hit a sufficiently susceptible population at a time when conditions are right to encourage spread. Then as it starts, another mutation or 2 needs to happen to pump the Ro at the right time. Thank God, I think we have a lot of near misses we likely never know about...
The trouble with H5N1 is the sheer # of chances it is getting to test fate. It's like buying a billion lottery tickets! Especially when the birds are moving and infected cattle are transferred between herds.
The two genotypes B3.13 and D1.1 both adapted to replication in mammalian cells. B3.13 with PB2-E627K and D1.1 with PB2-D701N have been detected in more than 20 dairy cow herds. My understanding is that at least PB2-E627K is a prerequisite for limited pig-to-pig transmission, that distinguishes this study from other studies where no pig-to-pig transmission was observed:
https://wwwnc.cdc.gov/eid/article/30/4/23-1141_article
"There are 8 Dairy Herds #H5N1 D1.1 with PB2 D701N"
https://bsky.app/profile/hlniman.bsky.social/post/3lmufumt3tc2i
"#H5N1 B3.13 Dairy Herds w/ PB2 E627K increased to 11"
https://bsky.app/profile/hlniman.bsky.social/post/3lmndm3esbs2p
Thanks, for these updates, which I wasn't aware of. It's unfortunate that USDA's regulatory policy does not provide state or origin on sequences. The D1.1's have so far been confined to Nevada and Arizona, to my knowledge (2-3 separate introductions) with a larger cluster of isolates likely being the NV cases where several unique herds, but closely situated herds were diagnosed. AZ has been less forthcoming on any details surrounding their cases.
On the B3.13 PB2-E627K isolates, unofficially that has clustered with other isolates that were identified to California, so those may have developed in that state?
Of course we have no idea what genotypes may be present in undiagnosed herds where sampling is not taking place or where CT values are too weak to allow reliable sequencing...
Regarding whether any individual genotype has yet demonstrated the ability to transmit pig-to-pig, I think that question is somewhat academic, because any of these viruses are only a mutation away from that capability. It doesn't change the urgency for looking for non-endemic viruses in pigs, especially in herds at high risk for contact with H5-infected poultry, livestock, and wildlife. It's borderline malpractice to avoid testing pigs in contact with dairy or poultry herds because "the genotype doesn't contain PB2-E627K or D701N", so it's not a risk. Just do the swabbing and look for influenza by PCR, then sequence if it is there...
With at least three introductions into cows and both genotypes adapting to mammals that's a negative trend, not just individual occurrences. Although it's debatable if the virus is endemic or not.
A year ago I looked into the USDA Influenza A Swine Surveillance Program and it's been entirely insufficient for early detection of limited and asyptomatic outbreaks according to my very rough estimate:
https://www.reddit.com/r/H5N1_AvianFlu/comments/1ddr1s2/comment/l88svgc/
I don't know if any measures like wastewater testing have been introduced since then, but the commercial incentives for farmers to report asymptomatic infections are minimal.
I expect limited pig-to-pig transmission in the proximity of affected herds, spillover from cows into several other species is well documented. I agree with you regarding the urgent need for increased general surveillance. It's just that detection of pig-to-pig transmission is more likely near dairy herds with PB2-E627K and PB2-D701N than anywhere else.
"Although we did not fully evaluate the direct effects of the E627K mutation in swine, the shedding and transmission profile shown for the 2 mammal isolates in this study indicate this adaptive mutation might have increased viral fitness through enhanced polymerase activity to enable transmission in an otherwise less susceptible host. (...) In contrast, we detected A/raccoon/WA/22 in the nasal cavity of inoculated pigs (4 of 15) and transmitted to contacts (2 of 5). Similarly, we detected A/redfox/MI/22 in the nasal cavity of inoculated pigs (5 of 15) and transmitted to a single contact."
https://wwwnc.cdc.gov/eid/article/30/4/23-1141_article
Oh, don't get me wrong...I'm with you 100%! Every swine herd in the proximity of dairy and poultry outbreaks should be monitored and swabbed, symptoms or not (Yes, IAV is widely asymptomatic in swine). Especially when adaptive mutations are found in the outbreak isolates!
But we can't get states of origin on isolates or timely disclosure of the mutations (e.g. in 5 days), let alone nearby surveillance! We are totally set up for too little, too late due to political restrictions, excessive regulatory caution, and now likely inadequate staffing.
I'm not very familiar with the details, but here is a recent B3.13 cow sequence with PB2-E627K from California:
https://bsky.app/profile/hlniman.bsky.social/post/3lq4idsvdb22a
Additionally PB2-K670R seems to indicate California, maybe not exclusively, I'm not sure:
https://bsky.app/search?q=K670R
I assume the risk for pigs has increased dramatically compared to a few months ago, although there is no data for those exact strains in pigs yet. And I assume limited direct contact pig-to-pig transmission is occurring. But that's risk assessment, not scientific facts.
I find the issue of re-infection intriguing. It would be a perfect situation to create an Autogenous vaccine from within a positive herd and utilize it immediately in that same herd that was affected previously, instead of waiting for the next new grand drug/vaccine to gain approval.
We have so much to learn about the course of herd infection and immunity. I agree about post-infection vaccination. not sure how "autogenous" a vaccine would need to be. strains may be fairly cross protective, and conversely, the virus may "drift enough antigenically over time (like it does in pigs) that immunity won't hold regardless. How and where does the virus survive over time in herds? In replacement stock? Partially immune animals? Deep in the udder or lymphatics somewhere??
Or do new replacements keep getting infected as existing herd mates slowly clear infection, so that on a herd basis the infection never clears? In pigs, people practice "herd closures" to overcome that. Maybe that is not possible in large dairies... Herd basis immunity is fascinating!
Interesting points. All make sense. By "herd closures" I take it you mean the same as what I've always called a "closed herd": no bought in animals and use artificial insemination for breeding, yes?
I've been wondering for quite some time why my home area of southeast PA has fortunately remained negative while poultry houses there are positive.
Maybe because of the small herd demographic in general, replacements aren't as heavily relied upon(?).
Even more to that point, here in NC where I live now, I was told by state a legislator that the 1 herd, which was relatively large at about 1000 cows and positive in March 2024 (none since) had bought replacement animals in from Texas. I've been wondering why the normal vectors of service personnel (vets, nutritionists, etc) hadn't spread it. Additionally, 20 poultry houses here in NC were positive in 2024 and fortunately only 3 in January and then 1 in March (none since).
It is common knowledge that large dairy farms have high cull rates and often do not have enough in-house replacements. Hence buying replacements.
And it is west of the Mississippi where most bovines are affected by HPAI (whatever strain): the area of the nation that has the highest number of large herds (that need replacements the most).
Perhaps in states, like PA, NC, VT etc where there are some (but not dominated by) large herds - maybe the best definition of large herd is "X" replacement rate - but have avpreponderance of smaller herds (with either no replacements needed or below a certain threshold %) - even with poultry houses testing positive like in southeast PA - there is then no critical carrying capacity or density for the virus to become endemic in that area, even with wild fowl migratory routes..
I'm an east coast dairy vet for 30 years and freely admit i'm biased towards small herds for many reasons beyond HPAI. And I'll say something perhaps which is a Captain Obvious: the manner in which large dairy herds manage their cows to maximize production leads to cow "burn out" more quickly than smaller farms and the need for more replacements, thus keeping HPAI potentially entering such herds.
Also, many studies have shown that certified organic farms have relatively lower cull rates than conventional and I'd love to see data how they are doing in HPAI testing and clinical signs. But I don't think that's possible to ascertain, though valuable data it would be.
Just some "aha" moments that came to me from your response to my talking about autogenous vaccines.
Thank you for the many insights I glean from your detective work on this topic. It's why I subscribe 🙂
Your response raised many thoughts in my mind too voluminous to write currently. Would love to talk on the phone. In general I agree replacements are critical - and large herds bringing in lactating replacements raise the stakes even more. I just don't know where and how long this virus hides out post acute infection in herds - a really critical question for animal movements. PRRS and flu in pigs dies out with strict closure (no new animals added), especially if infection is spread to the entire herd early. we don't really see "carrier" animals as such. If true in cattle, the same concept should apply, but the herd has to truly "go negative", and the replacements (every time!) must remain negative. Or vaccine must be "sterilizing". So much to learn yet...and we also have to add in viral shift and drift...
As always, thank you for a very informative read on the situation, Dr. Korslund. The awesome Dr. Jetelina (who is also on this platform) put the risk of an H5N1 pandemic at around 8% around the beginning of the year when outbreaks in poultry were especially high. Do you have a number in mind for the probability of this occurring? Thanks!
I've never felt comfortable putting odds on that. I'm probably more concerned about the virus bouncing around in mammals after adaptation than I am about ongoing poultry outbreaks. Pigs and cats scare me a lot because of existing endemic viruses available for reassortment with H5N1 spillovers. But as for odds, 8% seems high...Even in pigs - the virus has to overcome endemic viruses that are already very adapted and providing some pre-existing non-specific immunity. Same is true in people. It takes the right combination of events for a truly genomically unique strain to hit a sufficiently susceptible population at a time when conditions are right to encourage spread. Then as it starts, another mutation or 2 needs to happen to pump the Ro at the right time. Thank God, I think we have a lot of near misses we likely never know about...
The trouble with H5N1 is the sheer # of chances it is getting to test fate. It's like buying a billion lottery tickets! Especially when the birds are moving and infected cattle are transferred between herds.
Always appreciate your thorough responses! Your expertise is so valuable, now and always. Thank you!