I follow a lot of people. 1,878 as of this morning. I also don't engage in any other social media. Never have, never intend to. Pretty much every other social media domain is blocked at our firewall level. I only looked at twitter(as it was called at the time) in December of 2019, for the first time in my life, to try to get fast breaking COVID news, and have access to scientists who would be ahead of the knowledge curve.

I'm only really here for one reason. To get good info, synthesize it, and redistribute it, often in different words, when I think it'll be helpful. Despite some truly "delightful" DMs I've received recently, I have no ulterior motive. No one's forcing you to believe that, and I take it as a badge of honor to be blocked, so, knock yourself out if you're so inclined.

I'm asking everyone, particularly scientists, to be careful with your words. There's been palatable rising tensions here in 2024. Some of it has to do with science(H5N1, WHO airborne) some of it doesn't(politics), but it's real.

I have seen some truly awful H5N1 takes as things ramp up. Particularly this morning. Nuance matters. If you want to be a prognosticator, be clear. "I think" or "I believe" instead of launching into what you want to say.

Here's a few things I've seen that should be discussed carefully:

- Pasteurization is completely effective against H5N1.

Here's what the FDA says about that:

The FDA believes the pasteurization process is “very likely” to inactivate H5N1, though they acknowledged that no studies have been done to test that.

Here's someone who knows better:

“Daniel Perez, an influenza researcher at the University of Georgia, is doing his own test tube study of pasteurization of milk spiked with a different avian influenza virus. The fragile lipid envelope surrounding influenza viruses should make them vulnerable, he says. Still, he wonders whether the commonly used “high temperature, short time” pasteurization, which heats milk to about 72°C for 15 or 20 seconds, is enough to inactivate all the virus in a sample.”

- It's already spreading person to person across the US.

The only reference I can find that would lead to that conclusion would be this:

"Only one human case linked to cattle has been confirmed to date, and symptoms were limited to conjunctivitis, also known as pink eye. But Russo and many other vets have heard anecdotes about workers who have pink eye and other symptoms—including fever, cough, and lethargy—and do not want to be tested or seen by doctors. James Lowe, a researcher who specializes in pig influenza viruses, says policies for monitoring exposed people vary greatly between states. “I believe there are probably lots of human cases,” he says, noting that most likely are asymptomatic."

Or, perhaps in conjunction with this:

"The genetic sequence from the human case, which occurred on an unidentified farm in Texas, is sufficiently different from the cattle sequences that it can’t be easily linked to them, he said. The differences suggest that the individual was either infected in a separate event — maybe not via a cow, but through contact with infected wild birds — or that there might have been another line of viruses in cattle early on and it has since died out."

I don't want to belabor the point, and I don't want to call out anyone. I just felt the need, after scrolling through my timeline this morning, to point out that language matters. Be careful. Don't spread misinformation. If you want to prognosticate, go ahead, but be clear it's your opinion. Your magic internet points don't matter.

As pointed out by @HelenBranswell there's an early release of a paper from Iowa State with scientific details of the early part of this cattle H5N1 outbreak. To be quite honest, there's a lot in there that I can't really intelligently talk about as it's just out of my scientific comfort zone, but, I'm sure people who are more knowledgable will spring up to discuss it somewhere out there.

Some things I found interesting:

- From the cats in Texas that died "In total, >50% of the cats at that dairy became ill and died."

They were being fed milk from sick cows.

- "The HA sequences from the milk samples had 99.94% nucleotide identities with HA sequences from the cat tissues, resulting in a distinct subcluster comprising all 4 HA sequences, which clustered together with other H5N1 viruses belonging to clade 2.3.4.4b"

- "This case series differs from most previous reports of IAV infection in bovids, which indicated cattle were inapparently infected or resistant to infection (9). We describe an H5N1 strain of IAV in dairy cattle that resulted in apparent systemic illness, reduced milk production, and abundant virus shedding in milk. The magnitude of this finding is further emphasized by the high death rate (≈50%) of cats on farm premises that were fed raw colostrum and milk from affected cows; clinical disease and lesions developed that were consistent with previous reports of H5N1 infection in cats presumably derived from consuming infected wild birds (10–12). Although exposure to and consumption of dead wild birds cannot be completely ruled out for the cats described in this report, the known consumption of unpasteurized milk and colostrum from infected cows and the high amount of virus nucleic acid within the milk make milk and colostrum consumption a likely route of exposure. Therefore, our findings suggest cross-species mammal-to-mammal transmission of HPAI H5N1 virus and raise new concerns regarding the potential for virus spread within mammal populations."

- "Clinical IAV infection in cattle has been infrequently reported in the published literature. The first report occurred in Japan in 1949, where a short course of disease with pyrexia, anorexia, nasal discharge, pneumonia, and decreased lactation developed in cattle (17). In 1997, a similar condition occurred in dairy cows in southwest England leading to a sporadic drop in milk production (18), and IAV seroconversion was later associated with reduced milk yield and respiratory disease (19–21)."

- "An IAV-associated drop in milk production in dairy cattle appears to have occurred during >4 distinct periods and within 3 widely separated geographic areas: 1949 in Japan (17), 1997–1998 and 2005–2006 in Europe (19,21), and 2024 in the United States (this report). The sporadic occurrence of clinical disease in dairy cattle worldwide might be the result of changes in subclinical infection rates and the presence or absence of sufficient baseline IAV antibodies in cattle to prevent infection. Milk IgG, lactoferrin, and conglutinin have also been suggested as host factors that might reduce susceptibility of bovids to IAV infection (9). Contemporary estimates of the seroprevalence of IAV antibodies in US cattle are not well described in the published literature. One retrospective serologic survey in the United States in the late 1990s showed 27% of serum samples had positive antibody titers and 31% had low-positive titers for IAV H1 subtype-specific antigen in cattle with no evidence of clinical infections (24). Antibody titers for H5 subtype-specific antigen have not been reported in US cattle."

- "The genomic sequencing and subsequent analysis of clinical samples from both bovine and feline sources provided considerable insights. The HA and NA sequences derived from both bovine milk and cat tissue samples from different Texas farms had a notable degree of similarity. Those findings strongly suggest a shared origin for the viruses detected in the dairy cattle and cat tissues. Further research, case series investigations, and surveillance data are needed to better understand and inform measures to curtail the clinical effects, shedding, and spread of HPAI viruses among mammals. Although pasteurization of commercial milk mitigates risks for transmission to humans, a 2019 US consumer study showed that 4.4% of adults consumed raw milk >1 time during the previous year (29)"

(Is anyone monitoring these people, specifically?)

- "Ingestion of feed contaminated with feces from wild birds infected with HPAI virus is presumed to be the most likely initial source of infection in the dairy farms. Although the exact source of the virus is unknown, migratory birds (Anseriformes and Charadriiformes) are likely sources because the Texas panhandle region lies in the Central Flyway, and those birds are the main natural reservoir for avian influenza viruses (30)"

- "The mode of transmission among infected cattle is also unknown; however, horizontal transmission has been suggested because disease developed in resident cattle herds in Michigan, Idaho, and Ohio farms that received infected cattle from the affected regions, and those cattle tested positive for HPAI H5N1 (33)"

- "In conclusion, we showed that dairy cattle are susceptible to infection with HPAI H5N1 virus and can shed virus in milk and, therefore, might potentially transmit infection to other mammals via unpasteurized milk. A reduction in milk production and vague systemic illness were the most commonly reported clinical signs in affected cows, but neurologic signs and death rapidly developed in affected domestic cats. HPAI virus infection should be considered in dairy cattle when an unexpected and unexplained abrupt drop in feed intake and milk production occurs and for cats when rapid onset of neurologic signs and blindness develop. The recurring nature of global HPAI H5N1 virus outbreaks and detection of spillover events in a broad host range is concerning and suggests increasing virus adaptation in mammals. Surveillance of HPAI viruses in domestic production animals, including cattle, is needed to elucidate influenza virus evolution and ecology and prevent cross-species transmission."

https://wwwnc.cdc.gov/eid/article/30/7/24-0508_article

There's a new article on StatNews today from @HelenBranswell with a Q&A format about what we know, and don't know, at this point about this outbreak.

https://www.statnews.com/2024/04/30/h5n1-bird-flu-virus-cows-and-risk-to-people/

Wear a mask makes an early appearance, so that's a plus. There's some discussion of asymptomatic and presymptomatic spread.

Some quotes of note:

- "The U.S. Department of Agriculture has said few tests from the respiratory tracts of infected cows have come back positive — and those that did showed there wasn’t a lot of virus present. But there is at least some evidence that H5N1 is on occasion getting deep into the respiratory tracts of cows."

- "While the contribution of respiratory transmission is still in question, there appears to be little doubt that a lot of spread is happening in milking parlors, where cows are strapped into the milking machines, and that in dairy cows, H5N1 seems to be primarily infecting mammary glands. The amount of virus in the udders of infected cows is off-the-charts high, making it easy to see how one cow’s infection soon becomes a herd’s problem."

- "Taylor noted another worry: H5N1, which is notorious for its ability to evolve, is being given a huge opportunity to adapt to bovine hosts. “The concern is if it becomes effective as a respiratory pathogen in cattle, it’s more likely to become effective as a respiratory pathogen in humans,” he said."

- "Sifford noted that cows in a herd without symptoms tested positive after cattle were moved into it from another herd whose remaining animals then went on to develop symptoms. The positive cows in the second herd haven’t developed symptoms, she said. “We are just getting underway with those studies to give us an idea of the opportunity for viremia either ahead of or after clinical signs,” she said. “So we should have more information about that in the coming weeks.”

One such study will be taking place in the high-containment laboratories at Kansas State University’s Center of Excellence for Emerging and Zoonotic Animal Diseases. Director Jürgen Richt said his group already has the necessary approvals and hopes to begin the research in mid-May."

- "Some uninfected cows will be housed with the infected animals to see whether they contract the virus, Richt said."

- "As to whether infected cows that have no symptoms are shedding virus in their milk, the evidence of viral traces in commercially purchased milk brings that question to the forefront. Farmers are supposed to discard milk from infected cows, which reportedly looks odd — yellowish and unusually thick. But PCR testing of commercially sold pasteurized milk has shown a substantial portion of samples were positive for RNA from H5N1, indicating the presence of either viral fragments or dead viruses. (The FDA said last week about one in five samples purchased in a cross-country survey tested positive.) So either some farmers aren’t following the recommendation, or some milk isn’t noticeably altered, or some cows that aren’t known to be sick are shedding the virus in their milk."

- "Kuiken is a bit pessimistic about whether, once the virus has found its way into a herd, transmission can be stopped: “You can’t not milk. And you probably can’t milk so well as to prevent cow-to-cow spread. I don’t think you can do it.” "

- "The CDC recommends that people working with or around cattle suspected or confirmed to be infected with H5N1 wear gloves, disposable fluid-resistant coveralls, vented safety goggles or a face shield, and an N95 respirator."

I would like to add to this that the CDC has recommendations for backyard flock owners since 2022 and I have yet to hear of anyone following it, even after bird flu has been found in their area. Recommendations, such as an N95, safety goggles and head to toe PPE, are pointless if no one follows them, or knows about them to begin with.

https://www.cdc.gov/flu/avianflu/h5/backyardflockowners.htm

- "Kuiken said the setup of many milking parlors is almost tailor-made to put workers in contact with viruses being shed in milk. That’s because there is typically a well — think of the area under the hoist in the garage where your car gets repaired — where workers are located while cows are being milked.

“So the milk worker is standing in a depressed area, and therefore his eyes are about at knee level — a little bit higher, maybe — with the cow. So very good for being inoculated, for eye infection,” he said."

- "Cook is also concerned about the possibility that the high pressure hoses that are used to spray down the parlors after milking may be aerosolizing virus that has fallen to the floor, making it easier for cows — and humans —to breathe in. He and other colleagues at the University of Wisconsin have begun deploying air monitoring devices into the milking parlors of affected farms to investigate the extent to which they can find genetic evidence of the virus in the air."

- "Farmers, who mostly haven’t been willing to have their cows tested, haven’t been keen to have their workers tested either."

Look, I know a lot of people are mad at the CDC about this, but, they can't raid farms and force people to test for a virus. I would sincerely like everyone who is calling for this to think it all the way through.

- "The World Health Organization appears to be concerned about the possibility of undetected human cases. Maria Van Kerkhove, acting head of the department of epidemic and pandemic preparedness, told STAT she’d like to see, among other things, studies looking for antibodies to H5N1 in the blood of farm workers and people who’ve been in contact with farm workers, to determine if there have been unreported cases and possibly even spread from those individuals to others."

People who don't want the CDC to test their workers for an active infection are really going to love the idea of the WHO coming in and testing their blood, right?

New article from StatNews again today, this time titled "Pasteurization inactivates H5N1 bird flu in milk, new FDA and academic studies confirm"

https://www.statnews.com/2024/05/01/bird-flu-pasteurization-inactivates-h5n1-in-milk/

I think the take home message in the article is:

"On Wednesday, the agency reported results from testing of a further 201 products, which included cottage cheese and sour cream, in addition to milk. Any PCR-positive samples were then injected into embryonated chicken eggs, to see whether any active virus could be grown — the gold standard test for assessing the viability of an influenza virus. None of the samples produced viable, replicating virus, Prater said."

"In addition, several samples of retail powdered infant formula as well as other powdered milk products. All PCR results from these products were negative. The agency did not disclose when it plans to make its full analysis, including which products were purchased from which states, available to the public."

"Bolstering the FDA’s data, academic researchers at the Ohio State University and St. Jude Children’s Research Hospital told STAT Tuesday night that their own study of 58 PCR-positive milk samples taken from Texas, Kansas, and eight other states in the Midwest also failed to turn up any evidence that H5N1 can survive the pasteurization process."

Catching up on my reading today and there's 4 new articles from StatNews.com that fit in this thread.

First, making the case for expanded wastewater surveillance:

https://www.statnews.com/2024/05/01/h5n1-bird-flu-hospital-wastewater-surveillance/

@HelenBranswell with another article about the USDA obfuscating data by labeling genomic sequences with simply "USA" and "2024":

https://www.statnews.com/2024/05/02/bird-flu-in-cows-h5n1-virus-changes-missing-data/

This one discusses a preprint

"The authors suggest the spillover event that started the spread in cattle may have happened in early December. The first detection that something was amiss with some cattle herds in the Texas panhandle dates to late January, but it took until March 25 before USDA confirmed the presence of H5N1 in a Texas herd."

https://www.biorxiv.org/content/10.1101/2024.05.01.591751v1.full.pdf+html

"Our genomic analysis
and epidemiological investigation showed that a reassortment event in wild bird populations preceded a5
single wild bird-to-cattle transmission episode. The movement of asymptomatic cattle has likely played a
role in the spread of HPAI within the United States dairy herd. Some molecular markers in virus populations
were detected at low frequency that may lead to changes in transmission efficiency and phenotype after evolution in dairy cattle. Continued transmission of H5N1 HPAI within dairy cattle increases the risk for
infection and subsequent spread of the virus to human populations."

The politics of public health is the topic of the next one, which is depressing:

https://www.statnews.com/2024/05/02/bird-flu-testing-dairy-state-politics-in-congress/

"Republican lawmakers have one big message on the avian flu outbreak in cows: Calm down."

No comment from me as I couldn't even get through it without having to take a walk.

And, finally, a little more info about the preprint paper from above and the recent data dump from the USDA:

https://www.statnews.com/2024/05/02/bird-flu-virus-in-cows-four-months-before-h5n1-outbreak-confirmed/

""These data support a single introduction event from wild bird origin virus into cattle, likely followed by limited local circulation for approximately 4 months prior to confirmation by USDA,” the authors wrote."

"In the last few years, H5N1 has spread from wild birds to a variety of carnivorous mammals, including foxes, bears, and seals, but in each of those instances, the virus has hit a dead end. The outbreak in dairy cows represents one of the first times that this bird flu virus has demonstrated the ability to efficiently transmit between mammals, said Thomas Mettenleiter, a virologist who served as the director of the Friedrich Loeffler Institut — Germany’s leading animal disease research center — from 1996 until he stepped down last year. The other instance was a number of outbreaks at mink farms in Spain and Finland in 2022 and 2023, respectively."

Another article from @HelenBranswell today. This time with an interesting Q&A with the head of the CDC's influenza division.

https://www.statnews.com/2024/05/03/bird-flu-why-h5n1-keeping-awake-cdc-top-flu-scientist/

"It sounds like your team that was ready to go didn’t go. And it sounds like from what you’re telling me that CDC is very much in the back seat on this one. That it’s the states or local authorities who are running this.

They have the authority, right? CDC does not have the authority to go into a state. We have to have an invite from state public health.

Have any states invited CDC in?

No. Not officially yet. We’re speaking to these partners if not once a day, more than that."

"There has been a single human case in Texas. Has anybody done serology testing around that individual? That would be an obvious place to start, would it not?

I don’t know that that was consented to. You have to have consent from people to follow up. Certainly it was something that was on our radar for what we would like to have and request, but to my knowledge, serology was not performed. (A report on the case published Friday in the New England Journal of Medicine confirmed Dugan’s belief. The infected person and his contacts would not consent to have blood drawn.)"

After a peaceful weekend in the woods and some reflection, I decided I am not going to live blog all of the articles that come out about H5N1 any further. I think a lot of it is distraction. That said, I would still like to keep up on the science, and I'm sure other people would, too.

So here's a new story on an article discussing how cows might be a "mixing vessel" for influenza that digs into the receptor types. It "found that tissue from the mammary gland contains abundant receptors of the kind to which avian flu viruses like H5N1 can attach. But brain and respiratory tract tissues contained far fewer of this type of receptor."

https://www.statnews.com/2024/05/06/bird-flu-spread-study-of-h5n1-virus-infection-in-cows/

https://www.biorxiv.org/content/10.1101/2024.05.03.592326v1.full.pdf+html

"Human IAVs24 preferentially bind SA-α2,6 (human receptor), whereas avian IAVs have a preference for α2,325
(avian receptor). The avian receptor can further be divided into two receptors: IAVs isolated26 from chickens generally bind more tightly to SA-α2,3-Gal-β1,4 (chicken receptor), whereas27 IAVs isolated from duck to SA-α2,3-Gal-β1,3 (duck receptor). We found all receptors were28 expressed, to a different degree, in the mammary gland, respiratory tract, and cerebrum of beef29
and/or dairy cattle. The duck and human IAV receptors were widely expressed in the bovine30 mammary gland, whereas the chicken receptor dominated the respiratory tract. In general, only31 a low expression of IAV receptors was observed in the neurons of the cerebrum. These results32 provide a mechanistic rationale for the high levels of H5N1 virus reported in infected bovine33
milk and show cattle have the potential to act as a mixing vessel for novel IAV generation."

The paper has some salient, and interesting facts. It's always amazing to me what research comes out of these types of situations, and what assumptions that were made previously don't hold up to scrutiny.

"Here we evaluate the expression of IAV receptors in situ in the mammary gland, respiratory114 tract and cerebrum of cattle, which typically has been considered less susceptible to IAV115 infection5 . Strikingly, was the finding that both the human- (SA-α2,6) and the duck receptors116 (SA-α2,3-Gal-β1,3) were highly expressed in the mammary glands, whereas no expression of117 the chicken receptor (SA-α2,3-Gal-β1,4) was detected. A previous study showed that co-expression118 of both the human- and avian receptors can enhance the receptor binding of H5N1119 isolated from ducks (clade 2.1.1) in vitro23. Combined these findings support the hypothesis120 that the high viral load seen in milk from cows infected by HPAI H5N1 virus belonging to121 clade 2.3.4.4b are due to local viral replication, because these viruses have high affinity for this122 receptor24. Additionally, the avian receptor has been found to be highly expressed in the human123 cornea and conjunctiva25 which may explain the report that conjunctivitis was the dominating124 clinical sign of a person presumably infected by dairy cows in Texas 7."

"The transmission route(s) and the pathogenesis of H5N1 in cows remain unclear,126 and it’s not known if the virus enters the mammary gland by an ascending infection or127
systemically by the blood supply.

...

Suggestions by the USDA that only some udder quarters may be133 involved in infection does, however, argue against a viremic source27."

"The investigation of the IAV receptor distribution in the respiratory tract also135
revealed some novel findings. In the upper respiratory tract and upper part of the lower136 respiratory tract (trachea, bronchi, and bronchioles), the chicken receptor (SA-α2,3-Gal-β1,4)137 was expressed on the surface of the respiratory epithelium, whereas a lack of - or very limited138 expression - of the human and duck receptors was detected. This pattern is the opposite to what139 we found in the mammary gland. The lack of expression of the human receptor in the upper140 respiratory tract of cattle contrasts with findings in humans25,28 and swine22,25 and supports the141 perception that bovines are highly resistant to infection with influenza A viruses of human and142
swine origin when exposed by the respiratory route1,29. In the lung alveolar cells, however, all143 three receptors were abundantly expressed, similar to what has been found in pigs and144
humans22,25,28."