The Northeast region of the United States has more than 15,000 working dairies, each producing non-saleable waste milk.

Waste milk contains excess colostrum, transition milk, mastitic milk, or antibiotics. Many dairy producers feed waste milk to dairy calves, however, sometimes the amount of waste milk is in excess of what can be used resulting in it being disposed. Feeding waste milk to other species provides a viable option for dairy producers to use the product rather than waste it.

Option for pigs

For a pig, weaning is thought to be the most stressful time of its life, as it transitions from a completely liquid diet to a completely dry diet. Waste milk may serve to ease this transition to dry feed while keeping the pig hydrated.

Not quite 3 weeks ago the ECDC issued a guidance document (see  https://afludiary.blogspot.com/2024/06/ecdc-enhanced-influenza-surveillance-to.html - Enhanced Influenza Surveillance to Detect Avian Influenza Virus Infections in the EU/EEA During the Inter-Seasonal Period ) urging member nations to step up surveillance for potential human avian flu infections over the summer. 

As was reported in last year's analysis from the UKHSA (see  https://afludiary.blogspot.com/2024/06/ttd-time-to-detect-revisited.html - TTD (Time to Detect): Revisited ), there could be dozens of undetected cases of human H5N1 infection before public health would likely detect them, perhaps even hundreds. 

While the ECDC may only present  https://www.ecdc.europa.eu/sites/default/files/documents/ECDCStrategy-2024update2_0.pdf - non-binding recommendations  to member states, yesterday they reiterated the need for increased vigilance in the months ahead. 

Tasks that are only made tougher due to a recent spike in COVID cases across the country. 

Stay tuned. It could be a bumpy summer. 

Yesterday  https://www.paho.org/ - PAHO  (Pan American Health Organization), in conjunction with the WHO, released a public health risk assessment on the zoonotic spread of H5N1 in the Americas.  These types of assessments - while they can be useful - are only as good as the data used to make them. 

And unfortunately, surveillance and reporting continues to erode, both in the United States, and around the globe (see  https://afludiary.blogspot.com/2023/08/no-news-is-now-commonplace.html - No News Is . . . Now Commonplace ). 

Yesterday we learned that Oklahoma  https://afludiary.blogspot.com/2024/07/oklahoma-board-of-animal-health-hpai-h5.html - had become the 13th state to detect HPAI H5 in dairy cows , but this was based on samples collected last April, and only recently submitted to the USDA for testing. 

Testing of livestock remains largely voluntary (except for interstate transport of cattle), and no one really knows how widespread the virus is in cattle across the nation. 

Just over 18 months ago, in https://afludiary.blogspot.com/2022/12/flying-blind-in-viral-storm.html -  Flying Blind In The Viral Storm , we looked at the increasing willingness of many countries to delay, downplay, or hide reports of emerging infectious disease events, and it is arguably even more pervasive today. 

The overall risk in the general population of this event for the Region of the Americas to human health is classified as “Low” with a level of confidence in the available information of “Moderate”, for the following reasons:

Epidemiological and virological factors: 

Current epidemiological data indicate localized occurrences of avian influenza A(H5N1) clade 2.3.4.4b in dairy cattle herds within the United States of America, with spillover into humans and other mammals in direct contact. Virologically, the virus remains predominantly bound to avian-type receptors, limiting its transmissibility to humans via respiratory droplets or fomites, as demonstrated by recent studies. A substantial component of the risk of spread throughout the Region of Americas has, and will continue to be, predominantly from wild birds however, after introduction in cattle, the continuous transmission between the different states in the United States has evidenced other mechanisms of transmission (e.g., movement of cattle). Even with no further change in the virus there are likely to be additional outbreaks in mammals, and sporadic cases reported in humans. The recent global risk, given the same parameters, has been considered to be low by the World Health Organization (WHO), but requiring vigilance and ongoing monitoring (1-3).

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But, as the  https://www.who.int/news-room/speeches/item/who-director-general-s-opening-remarks-at-the-media-briefing---10-july-2024 - WHO warns : their ability to assess the risks is compromised by limited surveillance.

So while the risks are currently deemed to be `low', we can't afford to be lulled into complacency.  

Capacity for surveillance and response: 

The Region of the Americas benefits from robust pandemic preparedness initiatives led by Pan American Health Organization (PAHO), including the WHO Pandemic Influenza Preparedness (PIP) Framework and Preparedness and Resilience for Emerging Threats (PRET) initiative. PIP and PRET strengthens regional capacities for early detection, surveillance, vaccine deployment and response to zoonotic influenza outbreaks thereby mitigating the potential impact of localized influenza outbreaks and enhancing the region’s readiness to manage any potential spread (4).

 However, it is prudent for countries to enhance event-based surveillance mechanisms at the animal-human interface and continue to monitor influenza through its network of influenza-like illness (ILI) and severe acute respiratory infections (SARI) surveillance sites.

The available evidence supports a coordinated regional risk assessment of “low” for the general population and “low-to-moderate” for occupationally exposed individuals.

The rapid risk assessment will be reviewed should further epidemiological or virological information become available

The CDC has posted the following statement - which confirms much of  https://afludiary.blogspot.com/2024/07/colorado-locally-confirmed-hpai-cases.html - what we learned earlier today from the State of Colorado  - on the (now 4) confirmed human H5 infections among poultry workers from Weld County. 

A fifth presumed positive case will likely be confirmed later today. 

There are still no details provided on whether the workers wore PPEs, or have received antivirals, both of which should be standard procedure. 

https://www.cdc.gov/media/releases/2024/p-0715-confirm-h5.html - CDC Confirms Human Cases of H5 Bird Flu Among Colorado Poultry Workers

Press Release
For Immediate Release: July 14, 2024
Contact:  https://www.cdc.gov/coronavirus/2019-ncov/vaccines/about-vaccines/index.html - Media Relations
(404) 639-3286


July 14, 2024 – Four human cases of  https://www.cdc.gov/bird-flu/about/index.html - highly pathogenic avian influenza  (HPAI) A(H5) (“H5 bird flu”) virus infection in the state of Colorado have been confirmed by the Centers for Disease Control and Prevention (CDC). This includes all three presumptive-positive cases reported by that state on  https://cdphe.colorado.gov/press-release/colorado-state-health-officials-identify-possible-cases-of-avian-flu-in-colorado - Friday, July 12  and a fourth specimen that was later found to be presumptive-positive by the state on Friday. CDC also is aware of an additional (fifth) presumptive-positive case in Colorado that will be confirmed at CDC once the specimen arrives. All cases were in farm workers who were involved in the depopulation of poultry at a poultry facility experiencing an outbreak of HPAI H5N1 virus. 

A CDC team is on the ground in Colorado, supporting their assessment of the poultry outbreak and associated human cases. Given current information, CDC believes that the risk to the public from this outbreak remains low. These cases again underscore the risk of exposure to infected animals. There are no unexpected increases in flu activity otherwise in Colorado, or in other states affected by H5 bird flu outbreaks in cows and poultry.

1. Highly pathogenic avian influenza (HPAI) H5N1 virus is spread globally by wild birds

The circulating H5N1 clade (2.3.4.4b) has caused outbreaks on poultry farms and among backyard flocks, and die-offs among wild birds. Infections in mammals, including cattle and humans, triggered by viral spillover from birds highlights the potential for a pandemic, but the mechanisms of transmission are not fully known. https://www.cmaj.ca/content/196/25/E878?rss=1#ref-1 - 1 , https://www.cmaj.ca/content/196/25/E878?rss=1#ref-2 - 2  Evidence exists of viral reassortment and mammalian adaptation, https://www.cmaj.ca/content/196/25/E878?rss=1#ref-3 - 3  resulting in increased risk of transmission and disease among mammals.

2. As of June 12, 2024, no reported human cases of H5N1 have been acquired in Canada

Nearly 900 human cases of H5N1 have been reported globally since 2003, with a case fatality rate of 52%. https://www.cmaj.ca/content/196/25/E878?rss=1#ref-4 - 4  The clinical presentation may vary from mild to severe influenza. Dairy workers in the United States who recently became infected presented with hemorrhagic conjunctivitis. https://www.cmaj.ca/content/196/25/E878?rss=1#ref-2 - 2

3. Clinicians should ask about animal exposures in people presenting with influenza-like illness, conjunctivitis or, less commonly, meningoencephalitis

People with substantial exposure to livestock or wildlife may be at risk for infection. Currently, the risk to the general population is low, with no evidence of sustained person-to-person transmission. https://www.cmaj.ca/content/196/25/E878?rss=1#ref-3 - 3

4. Conventional laboratory-based testing may identify H5N1 HPAI as influenza A virus

Confirmatory testing is conducted at a provincial or national reference laboratory for suspected infections, which underscores the need to identify patients with exposure histories as soon as possible. https://www.cmaj.ca/content/196/25/E878?rss=1#ref-4 - 4  Nasopharyngeal and conjunctival swabs, if the patient has eye symptoms, should be collected, and public health should be informed of cases under investigation.

5. No vaccine currently exists for human use in Canada

Oseltamivir is the recommended antiviral for treatment and prophylaxis of HPAI infection. Oseltamivir should be administered as soon as possible to a person with a suspected infection, or after close contact with a confirmed case of HPAI.

As the investigation continues into recent avian flu infections in as many as five workers who culled Colorado poultry, officials today said that industrial fans in poultry barns where temperatures exceeded 104°F could have spread the virus through windblown feathers and through the air, potentially reducing the effectiveness of personal protective equipment (PPE).

Also, early genetic analysis suggests that the virus that infected the poultry and the workers is the same H5N1 genotype infecting dairy cattle, a useful clue for officials who are examining connections between the farms.

While we await further details, overnight several experts weighed in on Twitter/X, including Raj Rajnarayanan  https://x.com/RajlabN - @RajlabN  Assistant Dean of Research and Associate Professor, NYITCOM at Arkansas State University:

https://x.com/RajlabN/status/1812997153792610634">

https://x.com/PeacockFlu/status/1813135622938284356">

https://x.com/PeacockFlu/status/1813135622938284356">

Stay tuned.  

July 11, 2024

Airborne transmission of bird flu via aerosolization of contaminated faeces from wild waterfowl does not play an important role in the infection of indoor-housed poultry. This is according to a risk analysis carried out by researchers of Wageningen Bioveterinary Research.

It's been more than 3 years since Anhui province has reported an H5N6 case ( https://afludiary.blogspot.com/2021/02/chinas-recent-resurgence-of-human-hpai.html - link ), but today Hong Kong's  https://www.info.gov.hk/gia/general/202407/25/P2024072500502.htm - CHP is reporting  on a fatal case (70, F) who fell ill following a visit to a live poultry market in the middle of June and died on July 8th. 

While getting reliable, and timely, reports out of China can be a challenge, this is only the 3rd case reported on the Mainland this year.  The  https://afludiary.blogspot.com/2024/06/who-wpro-reports-2nd-h5n6-case-in.html - other two cases were from Fujian Province , and all three have proved fatal. 

https://www.ecdc.europa.eu/sites/default/files/documents/Communicable-disease-threats-report-week-21-2024_0.pdf">

With the current evidence we should not assume that the risk of a mammalian outbreak is limited to clade B.3.13.

They not only confirmed that cattle are susceptible to a range of HPAI H5N1 viruses, they demonstrate that heat treatment at 56 °C for 30 minutes did not completely eliminate the infectivity of the tested AIV in milk.

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Once again we find that the deeper we look, the more we find. 

Yet in far too many places around the globe, Don't test, don't tell' continues to be the preferred option. 

As a result, we don't know how pervasive HPAI is in American cattle, and we know even less about what is going on with H5Nx in places like China, Asia, Russia, the Middle East, and Africa. 

There are some signs that governments and agencies are starting to take the threat more seriously (see  https://afludiary.blogspot.com/2024/07/colorado-orders-mandatory-statewide.html - Colorado Orders Mandatory Statewide Weekly Bulk-Tank Testing for HPAI  and  https://afludiary.blogspot.com/2024/07/ukhsa-raises-risk-assessment-on-hpai.html - UKHSA Raises Risk Assessment On HPAI H5N1 ), but in far too many places half-measures and bland reassurances remain the order of the day.

We may get lucky, and HPAI H5Nx may fizzle. But that is not its current trajectory, and we risk enormous damage by continuing to underestimate its future impacts. 

The state of Michigan has been rightfully lauded for having perhaps the most aggressive testing and monitoring program for farm workers exposed to HPAI in the country.  Through their efforts, two dairy workers were identified as having mild H5N1 infection (see  https://afludiary.blogspot.com/2024/05/michigan-announces-1st-human-h5n1.html - here  and  https://afludiary.blogspot.com/2024/05/cdc-statement-on-2nd-michigan-h5.html - here ). 

Michigan's MDARD also invited the USDA to investigate the spread of the H5 virus in farms (see  https://www.aphis.usda.gov/sites/default/files/hpai-h5n1-dairy-cattle-mi-epi-invest.pdf - Epidemiological investigation into the spread of H5N1 in Michigan ) which concluded the movement of livestock, farm equipment (including trucks), and personnel contributed to the spread of the H5N1 virus.

Other states have been far less cooperative, although Colorado recently asked the CDC to send  investigators after 9 people were infected by H5N1 across two poultry farms, and  https://afludiary.blogspot.com/2024/07/colorado-orders-mandatory-statewide.html - last week announced the most aggressive dairy cattle testing  in the nation. 

Grading on the curve, Michigan would appear to get an A+, but - as the following MMWR report illustrates - there were limitations to their surveillance as well. 

• Of the 23 known (now 26) infected dairies, only 20 appear to have provided employee lists. 

• Illnesses and/or symptoms were mostly self reported, and testing was voluntary. 

• Only symptomatic individuals were tested.

It is unknown how many other infected farms there might be in Michigan, and it is also possible that some individuals with minor symptoms - or an aversion to being tested - might not have responded to the daily texts. 

There is also often a narrow `window' where testing will reliably detect HPAI H5, particularly if  these workers were on already on prophylactic antivirals (not stated, but a common practice). 

Still, given that perfect is often the enemy of good, this is far-and-away the most comprehensive testing and surveillance program we've seen since HPAI H5 emerged in American dairy cattle, and it may be the best we can hope for. 

Given the anecdotal reports (see  https://afludiary.blogspot.com/2024/06/eid-journal-avian-influenza-ah5n1-virus.html - EID Journal: Avian Influenza A(H5N1) Virus among Dairy Cattle, Texas, USA ) of sick dairy workers who have refused to be tested, and the (likely large) number of unidentified infected herds across the nation, the known number of human infections is likely a significant undercount. 

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Two weeks ago the CDC held a COCA Call for clinicians to help them identify, treat, and report suspected novel flu infections (see  https://afludiary.blogspot.com/2024/07/cdc-coca-call-on-h5n1-for-clinicians.html - CDC COCA Call On H5N1 for Clinicians & Healthcare Centers Now Online ).

This presentation also included a  https://emergency.cdc.gov/coca/ppt/2024/071624_slides.pdf - 48-slide PDF file .  

As we've seen previously from the UKHSA (see  https://afludiary.blogspot.com/2024/06/ttd-time-to-detect-revisited.html - TTD (Time to Detect): Revisited ), identifying community spread of a novel virus could take weeks, and only come after dozens or even hundreds of people had been infected. 

Our ability to detect H5 cases in the community depends not only on a bit luck, but also on how hard we are actually looking.

And right now, in far too many places, we barely appear to be looking at all.

A new paper challenged two ideas about how the H5N1 bird flu behaves in cattle: that it always produces mild illness, and that asymptomatic animals don't spread disease.

Instead, the paper showed that cattle mortality was twice as high during outbreaks on two of the nine farms assessed, and almost a third of nasal swabs in asymptomatic animals were positive for the virus, as were half of urine samples.

See how a manure lagoon works and why farmers want to build even more of them

While the total number of dairy farms reporting HPAI hovers just above 170, and only 4 dairy workers (and 9 poultry workers) have been diagnosed with the new bovine strain (B3.13) of the virus, there are  reasons to believe the scope of this outbreak is larger than those numbers would suggest. 

• First,  https://afludiary.blogspot.com/2024/03/curious-reports-of-unknown-disease-in.html - cattle were reportedly falling ill in Texas  (and other states) for months before the first diagnosis - last March - of HPAI H5N1.  

• Second,  https://www.bovinevetonline.com/news/industry/message-ag-industry-about-h5n1 - we're repeatedly heard  that farm owners - and farm workers - have been less-than-receptive to testing of cattle, or personnel.  Testing of cattle (except prior to interstate transport) remains largely optional. 

• Third, we've seen numerous anecdotal reports of sick cattle workers who were never tested, including in last month's  https://afludiary.blogspot.com/2024/06/eid-journal-avian-influenza-ah5n1-virus.html - EID Journal: Avian Influenza A(H5N1) Virus among Dairy Cattle, Texas, USA .

Testing of exposed farm workers, when it is done, is generally limited to symptomatic individuals only.  The CDC justifies this decision by citing  https://afludiary.blogspot.com/2024/07/cdc-updates-on-seroprevalence-genetic.html - a recent (small) seroprevalence study in Michigan , which tested 35 farm workers and found no neutralizing or HI antibodies specific to avian influenza A(H5N1) virus.

That said,  https://afludiary.blogspot.com/2024/06/cdc-summary-of-h5n1-seroprevalence.html - we've seen a number of seroprevalence studies  on (various) HPAI H5N1 strains over the years that have found limited evidence of asymptomatic (or very mild) infection with H5 avian influenza. 

Of course getting people to voluntarily submit to a serological study (which may involve multiple blood draws over time), can be difficult.  Language barriers, the migratory aspects of farm work, and a general distrust of the government are additional hurdles. 

All of which brings us to a preprint - published on the MedRxiv website yesterday -  which among other things, reports finding a small number (n=2) of H5 seropositive farm workers among a small cohort (n=14) that were tested across two farms in Texas. 

They also report several mutations associated with increased spillover potential in cattle. 

It is worth noting these researchers used Microneutralisation (MN) assay rather than Haemagglutination Inhibition (HAI) testing. Both are viewed as the gold standard for antibody testing, but the MN assay's superior sensitivity can be more prone to detecting cross-reacting antibodies from previous influenza A virus infections or vaccinations.

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From  https://www.kff.org/ - KFF Health News :

https://kffhealthnews.org/news/article/bird-flu-undetected-farmworkers-testing-contagious-mammals/ - Bird Flu Cases Are Going Undetected, New Study Suggests. It’s a Problem for All of Us.

By  https://kffhealthnews.org/news/author/amy-maxmen/ - Amy Maxmen  JULY 31, 2024

A new study lends weight to fears that more livestock workers have gotten the bird flu than has been reported.
 
“I am very confident there are more people being infected than we know about,” said Gregory Gray, the infectious disease researcher at the University of Texas Medical Branch who led the study,  https://www.medrxiv.org/content/10.1101/2024.07.27.24310982v1 - posted online Wednesday  and under review to be published in a leading infectious disease journal. “Largely, that’s because our surveillance has been so poor.”

As bird flu cases go underreported, health officials risk being slow to notice if the virus were to become more contagious. A large surge of infections outside of farmworker communities would trigger the government’s flu surveillance system, but by then it might be too late to contain.

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Richard Webby, director of the World Health Organization Collaborating Center for Influenza at St. Jude Children’s Research Hospital in Memphis, Tennessee, said the results confirmed his suspicions that the 13 human bird flu cases reported this year by the CDC were an undercount.

“Maybe what we see isn’t exactly the tip of the iceberg, but it’s certainly not the whole story,” Webby said.

           https://kffhealthnews.org/news/article/bird-flu-undetected-farmworkers-testing-contagious-mammals/ -  (Continue . . . ) 

I can't say that I'm particularly surprised by these findings, but they should serve as a wake-up call. 

It has been more than 4 months since the first (belated) detection of HPAI H5 in cattle, and sad to say, we continue to treat HPAI H5 as more of an agricultural economic problem than as a potential public health threat.  

Information continues to be released  https://gisaid.org/resources/gisaid-in-the-news/highly-pathogenic-avian-influenza-outbreak-in-the-united-states/ - piecemeal, and at a glacial pace. 

While H5N1 remains a long-shot for becoming a pandemic, we do ourselves few favors by turning a blind eye, and hoping for the best. 

The bovine B3.13 genotype currently affecting cattle has infected at least 13 American farm workers since March, but so far it has only produced mild illness in humans.  The concern, of course, is that could change over time. 

Yesterday, in  https://afludiary.blogspot.com/2024/08/preprint-bovine-h5n1-influenza-virus.html - Preprint: Bovine H5N1 Influenza Virus Binds Poorly to Human-type Sialic Acid Receptors , we looked at a study which reassuringly found the B3.13 genotype continues to bind preferentially to avian receptor cells. 

Today we have a study which finds that the bovine B3.13 genotype doesn't replicate in lung tissues as well as earlier (A/Vietnam/1203/2004), more pathogenic (in humans), H5N1 variants.  

It also doesn't appear to illicit as strong of an immune response, both of which may help explain it current mild presentation. 

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While this study is reassuring, influenza's superpower is its ability to continually reinvent itself, either slowly through antigenic drift, or rapidly via antigenic shift (reassortment).   

The current `mild' presentation of bovine (B3.13) H5N1 could change overnight with one or two `key' mutations, or reassortment with a more `humanized' virus.  

Or not.  Flu viruses are famously unpredictable. 

While we are watching H5N1 in the Americas, we could easily be blindsided by another genotype or clade from elsewhere in the world, or even a different subtype altogether (i.e. H5N6, H5N2, H3N8, H10Nx, etc).

The point being, that whether H5N1 (and bovine B3.13 in particular) has the `right stuff' to spark a pandemic is unknowable, but history tells us that another novel flu will emerge. 

And when that inevitably happens, we'd better be prepared for it.  

Prior to 2021, North America only had one brush with HPAI H5; an avian epizootic that began in December of 2014 and eventually infected poultry in 15 states.  

That H5Nx virus, however, was ill-suited for long-term carriage in wild and migratory birds, and disappeared the following summer (see http://afludiary.blogspot.com/2016/07/pnas-enigma-of-disappearing-hpai-h5-in.html -  PNAS: The Enigma Of Disappearing HPAI H5 In North American Migratory Waterfowl).

It now persists (at low levels) in wild birds even through the summer months, and new waves of infection are expected when migratory birds return from their high latitude nesting places this fall. 

Today FAO/WHO/WOAH issued a joint statement - based on data as of July 18, 2024 - indicating that the threat from HPAI H5N1 to general public remains low, although the risks for occupationally exposed persons ranges from low to moderate depending on the risk mitigation measures in place.

This is essentially the same level of risk we've seen from the CDC and the ECDC. 

Earlier this week the journal Nature published a report on multiple detections of the recent (2022-2023) H3N2 human seasonal flu virus circulating in pigs, a result of reverse zoonosis.  

This type of spillover is a concern since it not only poses a risk to swine production, it could also lead to the emergence of new (and potentially more dangerous) swine variant viruses. 

Influenza viruses evolve via two well established routes; Antigenic drift & Antigenic Shift (reassortment).

• Antigenic drift causes small, incremental changes in the virus over time. Drift is the standard evolutionary process of influenza viruses, and often come about due to replication errors that are common with single-strand RNA viruses (see https://www.youtube.com/watch?v=ug-M1nIhfIA&t=2s -   https://www.youtube.com/watch?v=ug-M1nIhfIA&t=2s - NIAID Video: Antigenic Drift ) or due to  https://afludiary.blogspot.com/2019/05/j-gen-virology-mutations-in-pb2-and-ha.html - host adaptation . 
• Shift occurs when one virus swap out chunks of their genetic code with gene segments from another virus.  This is known as reassortment. While far less common than drift, shift can produce abrupt, dramatic, and sometimes pandemic inducing changes to the virus (see  https://www.youtube.com/watch?v=DdFCx8jbesQ - NIAID Video: How Influenza Pandemics Occur ).

In either case, most mutations/reassortments are evolutionary failures.

They die out quickly because they are not as biologically `fit’ as the parental virus they must compete with. Only rarely does a mutation convey enough of an evolutionary advantage to allow it to become `fixed' in a host, and potentially transmitted onward.

While reassortment gets most of our attention due to its ability to change a virus radically overnight, antigenic drift - over years or decades - can eventually produce more `pandemic ready' viruses as well. 

As a result the H5N1 viruses circulating in the United States or Europe today are genetically distinct from the H5N1 viruses of the past, and even those currently circulating in Peru, Japan, or the Middle East.

Since 2020 a new clade 2.3.4.4b H5N1 virus became dominant, and it - and its variants - have shown an enhanced ability to spill over into mammals around the globe (see  https://afludiary.blogspot.com/2023/11/eid-journal-highly-pathogenic-avian.html - here ,  https://afludiary.blogspot.com/2023/11/eid-journal-hpai-ah5n1-virus-clade.html - here ,  https://afludiary.blogspot.com/2023/11/two-eid-journal-dispatches-on-h5n1-in.html - here,  and  https://afludiary.blogspot.com/2023/11/emerg-microb-inf-high-number-of-hpai-h5.html - here ).   One  https://afludiary.blogspot.com/2024/08/preprint-enhanced-replication-of.html - genotype (B3.13)  has spilled over into American Dairy cows.

This clade has also greatly expanded its host range in birds (see  https://afludiary.blogspot.com/2022/07/defra-unprecedented-order-shift-in-wild.html - DEFRA: The Unprecedented `Order Shift' In Wild Bird H5N1 Positives In Europe & The UK ).

At the same time, we are seeing far fewer, and often less severe, human infections from HPAI H5N1.  While the `right' reassortment could conceivably spark a pandemic, the $64 question remains; is HPAI H5 - in general - evolving towards becoming a bigger pandemic threat over time?

We've a preprint today that attempts to answer that question using large-scale computational modeling of H5 Influenza variants.  This in silico analysis by researchers at the University of North Carolina at Charlotte, finds reasons to believe it is. 

In this study, we computationally model 1,804 protein complexes consisting of various H5 isolates from 1959 to 2024 against 11 HA1-neutralizing antibodies. This study shows a trend of weakening of the binding affinity of existing antibodies against H5 isolates over time, indicating that the H5N1 virus is evolving immune escape of our medical defenses.

We also found that based on the wide variety of host species and geographic locations in which H5N1 was observed to have been transmitted from birds to mammals, there is not a single central reservoir host species or location associated with H5N1's spread.

These results indicate that the virus is well on its way to moving from epidemic to pandemic status in the near future. This study illustrates the value of high-performance computing to rapidly model protein-protein interactions and viral genomic sequence data at-scale for functional insights into medical preparedness.

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While we are concentrating primarily on the bovine B3.13 H5N1 virus right now, the reality is there are multiple subtypes, numerous clades and subclades, and hundreds of genotypes of HPAI H5 circulating - often outside of our view - all around the world.  

Any one of them is potentially only a few mutations, or a single fortuitous reassortment, away from cracking the code to make it more transmissible in humans. 

That may take years to happen, and it is even possible there is  https://afludiary.blogspot.com/2014/07/are-influenza-pandemic-viruses-members.html - some unknown `species barrier'  that protects us.  But HPAI H5 has time on its side, and an enormous (and growing) array of genetic material to tinker with, which gives it an edge. 

And if HPAI H5 ultimately fails, well . . .  there are a plethora of avian, swine, and canine flu viruses with zoonotic potential in the wings (see  https://www.cdc.gov/pandemic-flu/php/national-strategy/influenza-risk-assessment-tool.html - CDC IRAT List ).  

Any of which could leap ahead of the queue without warning. 

While occasional neurological involvement with H5N1 infection has been reported over the past 20 years, prior to 2020 it was considered a fairly unusual occurrence.

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And as we've discussed previously, even minor genetic variations between viruses can produce vastly different characteristics (see  https://afludiary.blogspot.com/2012/04/differences-in-virulence-between.html - Differences In Virulence Between Closely Related H5N1 Strains ).  

While we may be comforted by the lack of severe H5N1 infection in the United States, the virus continues to rapidly evolve, making past performance no guarantee of future results. 

Assuming this pattern holds - and a novel H5 or H7 virus doesn't intervene - then we might expect to see an H2 or H3 virus emerge next.  

This reassortant is concerning since its HA comes from the  https://afludiary.blogspot.com/2023/03/china-guangdong-cdc-reporting-1-h3n8.html - H3N8 virus which has spilled over into humans at least 3 times  in recent years, its  https://afludiary.blogspot.com/2024/07/frontiers-phylogenetic-and-mutational.html - NA comes from the H10N3 virus  which has also infected humans, and its  https://afludiary.blogspot.com/2024/06/who-india-reports-2nd-h9n2-case.html - internal genes are from the H9N2 virus,  which has infected > 130 people over the past 2 decades.

The fact that it has now been found in Northern China suggests it may have been carried in by migratory birds.  In addition to this novel H3N3 virus, this survey found many of the `usual suspects'  (H3, H5, H7, H9, etc.) among the 6,000 samples analysed. 

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Although we get very little in the way of real-time reporting on avian flu out of China, their scientists  continue to publish excellent (albeit, often belated) reports in the scientific journals.  

The overarching message from these reports is that avian influenza viruses continue to expand - both in range and variety - across China, and that some of these viruses pose legitimate public health risks. 

While most will end up as evolutionary failures, we need to pay attention, because it only take one over-achiever to send us down the pandemic path again.

#18,265

Overnight the Indian media has been filled with excited - and in some cases, inconsistent -  https://economictimes.indiatimes.com/news/india/human-case-of-bird-flu-detected-in-odisha-heres-what-are-the-symptoms-and-precautions-you-should-follow/articleshow/112853808.cms?from=mdr - reports  of 1 or more human infections with `bird flu' (subtypes mentioned are H1N1 & H9N2) detected in the Puri district of Odisha, which  https://timesofindia.indiatimes.com/india/odisha-to-cull-20000-birds-in-response-to-avian-flu-outbreak/articleshow/112823703.cms - is currently dealing with an H5N1 outbreak in poultry.  

It isn't at all clear whether any of these cases have actually tested positive for avian influenza - or of what subtype - although samples have reportedly been sent to Pune for further analysis. 

India has previously reported  https://afludiary.blogspot.com/2024/06/who-india-reports-2nd-h9n2-case.html - 2 H9N2 cases  (2019 & 2024), https://www.who.int/emergencies/disease-outbreak-news/item/human-infection-with-avian-influenza-a%28h5n1%29-%EF%BD%B0-india -  1 case of H5N1  in 2021, and was the apparent source of  https://afludiary.blogspot.com/2024/05/australia-victoria-reports-imported.html - an exported case of H5N1  (in a child) who traveled to Australia last March.  Over the years there have been other suspected cases, but none were officially confirmed. 

While the facts of these suspected cases are (for now) uncertain, it is clear something is going on, as  https://x.com/HFWOdisha - Odisha's Directorate of Health  has issued a barrage of documents over the past few hours pertaining to the investigation, and their response. 

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In the past few hours these directives have been issued, both marked Top Most Urgent.  The second one references `suspected human cases'. 

Up until a couple of months ago, rodents had never been included in the  https://www.aphis.usda.gov/livestock-poultry-disease/avian/avian-influenza/hpai-detections/mammals - USDA's list of mammalian wildlife  infected with H5N1 (see  https://afludiary.blogspot.com/2024/06/usda-adds-house-mouse-to-mammals.html - USDA Adds House Mouse To Mammals Affected by H5N1) . Since early June we've seen nearly 100 rodents (house mouse, deer mice) added to the list, and they now comprise over 25% of all of the confirmed mammals on the list. 

Over the past few months we've also  https://afludiary.blogspot.com/2024/07/usda-adds-4-new-species-deer-mice.html - seen the addition  of domestic cats (n=37), prairie voles (n=1), and desert cottontails (n=1) to the list. HPAI H5 continues to expand its host range in mammals, and surveillance likely only picks up a small fraction of these spillover events.   

Earlier this month, in  https://afludiary.blogspot.com/2024/08/nature-decoding-rna-viromes-in-shrew.html - Nature: Decoding the RNA Viromes in Shrew Lungs Along the Eastern Coast of China , we looked at a study that found a wide range of zoonotic viruses - including HPAI H5N6 - in shrews.  Previously, in 2015's  https://afludiary.blogspot.com/2015/05/taking-hpai-to-bank-vole.html - Taking HPAI To The Bank (Vole) , we looked at that species' susceptibility to both H5N1 and H7N1.

While they haven't gotten the attention they probably deserve, rodents - which are often abundant around poultry and dairy farms - likely contribute to the spread of HPAI viruses (see 2016's  https://www.tandfonline.com/doi/full/10.1080/01652176.2017.1325537 - The role of rodents in avian influenza outbreaks in poultry farms: a review ).

All of which makes it less-than-surprising that researchers have now reported finding HPAI H5N1 in wild rats in Egypt.  Given recent detections in deer mice in the U.S., it is probably safe to assume this is not a rare occurrence. 

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What that will look like a year or two from now is anyone's guess. 

Preprint: Highly Pathogenic Avian Influenza H5 Virus Exposure in Goats and Sheep (in Pakistan)

A little over 5 months ago, in  https://afludiary.blogspot.com/2024/03/minnesota-boah-statement-on-hpai-h5n1.html - Minnesota BOAH Statement On HPAI H5N1 Infected Goat Kids , we looked at the first known detection of HPAI H5Nx in goats.  A few days later we saw the first reports of  https://afludiary.blogspot.com/2024/03/usda-statement-on-hpai-in-dairy-cattle.html - cattle infected with H5N1 in Texas  - which  https://www.aphis.usda.gov/livestock-poultry-disease/avian/avian-influenza/hpai-detections/hpai-confirmed-cases-livestock - has now spread to at least 14 states  - and along the way, we've also seen  https://afludiary.blogspot.com/2024/05/usda-hpai-h5n1-detected-in-alpacas.html - reports of H5N1 in Alpacas . 

Six months ago, the conventional wisdom was that cattle, goats, alpacas, and other livestock were largely immune to influenza A infection (see 2019's  https://www.mdpi.com/1999-4915/11/6/561 - Influenza A in Bovine Species: A Narrative Literature Review ), although it wasn't considered impossible.

With in excess of 190 herds now affected in the United States (undoubtedly an undercount, due to a lack of mandatory testing), we now know that HPAI can and does affect dairy cattle.  And while it has only been reported in the United States, it seems likely that other outbreaks have gone undetected around the globe. 

Today we have a preprint (see link below) that finds high levels of antibodies to H5, H7, and H9 influenza A viruses in goats and sheep in Pakistan, all of which is highly suggestive of past infection.

One has to assume that if it has appeared in goats, cattle, and alpacas in North America, and in goats and sheep half-a-world away in Pakistan, it could be spilling over (unnoticed) in other places as well. 

But of course, we can't know that if we aren't willing to look.  

Pathogens: Susceptibility of Synanthropic Rodents to H5N1 Subtype HPAI Viruses

Previously, in 2015's  https://afludiary.blogspot.com/2015/05/taking-hpai-to-bank-vole.html - Taking HPAI To The Bank (Vole) , we looked at that species' susceptibility to both H5N1 and H7N1, while more recently - in  https://afludiary.blogspot.com/2024/08/nature-decoding-rna-viromes-in-shrew.html - Nature: Decoding the RNA Viromes in Shrew Lungs Along the Eastern Coast of China  - we looked at a study that found a wide range of zoonotic viruses - including HPAI H5N6 - in shrews. 

A lot seems to depend upon both the host species, and the subtype/clade of the infecting influenza virus. Some rodents may develop mild, even asymptomatic, infection while others may quickly succumb to the virus. 

Up until two months ago, rodents had never been included in the  https://www.aphis.usda.gov/livestock-poultry-disease/avian/avian-influenza/hpai-detections/mammals - USDA's list of mammalian wildlife  infected with H5N1 (see  https://afludiary.blogspot.com/2024/06/usda-adds-house-mouse-to-mammals.html - USDA Adds House Mouse To Mammals Affected by H5N1) .

Since early June we've seen nearly 100 rodents (house mouse, deer mice) added to the list, and they now comprise nearly 25% of all of the confirmed mammals on the list. We've also seen  https://afludiary.blogspot.com/2024/07/usda-adds-4-new-species-deer-mice.html - the recent addition  of domestic cats (n=53), prairie voles (n=1), and desert cottontails (n=1) to that list.

And just last week, in  https://afludiary.blogspot.com/2024/08/vet-quarterly-hpai-virus-h5n1-clade.html - Emer. Microbe & Inf.: HPAI Virus H5N1 clade 2.3.4.4b in Wild Rats in Egypt during 2023 , we a surprisingly high percentage of wild rats testing positive for H5 antibodies in Egypt. 

All of which brings us to a new study, published today in Pathogens, where researchers challenged several rodent species (house mice, brown rat, black rat) with two (older 2010, 2007) HPAI H5N1 viruses, and found they are both susceptible to the virus and could potentially play a role it its evolution and spread. 

• Six months ago cattle, goats, and alpacas weren't considered susceptible hosts,  https://afludiary.blogspot.com/2024/05/usda-hpai-h5n1-detected-in-alpacas.html - now they are .  

• Last week, we saw evidence that sheep may be susceptible as well (see  https://afludiary.blogspot.com/2024/09/preprint-highly-pathogenic-avian.html - Preprint: Highly Pathogenic Avian Influenza H5 Virus Exposure in Goats and Sheep (in Pakistan) ).

• Although long suspected,  https://afludiary.blogspot.com/2024/09/preprint-highly-pathogenic-avian.html - blowflies are now considered plausible `mechanical' vectors  of HPAI viruses

• In 2020 the USGS found long-term (up to 7 months) survival of influenza A viruses in wetlands in both Alaska and Minnesota (see  https://afludiary.blogspot.com/2020/09/proc-royal-society-b-influenza-viruses.html - Proc. Royal Society B: Influenza A Viruses Remain Viable For Months In Northern Wetlands - USGS ) 

• Last May, in  https://afludiary.blogspot.com/2024/05/viruses-assessment-of-survival-kinetics.html - Viruses: Assessment of Survival Kinetics for Emergent Highly Pathogenic Clade 2.3.4.4 H5Nx Avian Influenza Viruses  we looked at the survivability of 5 different HPAI H5 clade 2.3.4.4b viruses collected between 2014 and 2021, in a laboratory environment at 3 different temperatures (measured in days).

• And while still controversial, we've seen a number of studies suggesting long-distance airborne spread of avian flu viruses, including 2019's  https://afludiary.blogspot.com/2019/08/nature-airborne-transmission-may-have.html - Nature: Airborne Transmission May Have Played A Role In Spread Of U.S. 2015 HPAI Epizootic  and 2022's  https://afludiary.blogspot.com/2022/06/eid-journal-hpai-h5n8-clade-2344b-virus.html - HPAI (H5N8) Clade 2.3.4.4b Virus in Dust Samples from Poultry Farms, France, 2021 .

The CDC has now released a statement on the  https://afludiary.blogspot.com/2024/09/missouri-dhss-human-h5-bird-flu-case.html - Missouri H5 case  (see below).  Given the lack of occupational exposure - and no known exposure to animals - the epidemiological investigation into this case will be of extreme interest. 

We should get more information on the full subtype, and hopefully complete genomic sequencing, sometime next week.

As we've seen previously from the UKHSA (see  https://afludiary.blogspot.com/2024/06/ttd-time-to-detect-revisited.html - TTD (Time to Detect): Revisited ), identifying community spread of a novel virus could take weeks, and only come after dozens or even hundreds of people had been infected. 

While this is hopefully an isolated case, the fact that it was only confirmed 2 weeks after the patient was hospitalized (and now released), illustrates how difficult it can be to detect novel flu viruses like HPAI H5N1 in real-time. 

As we've seen, detecting H5 cases in the community often requires a bit of luck, but the harder we look, the earlier we are apt to identify cases.