Saturday, May 25, 2024

CDC: Key Public Health Prevention Recommendations for HPAI A(H5N1)

Recommended PPE For Farmers 

 #18,083

Although the mantra from public health continues to be that the risk to public health from H5N1 remains low, the reality is we will likely only recognize any increased threat after it happens.  

Until then, it is prudent for those at a higher risk - such as dairy farmers - to take extra precautions in hopes that we never get to that point. 

While the CDC continues to churn out guidance, it really is up to state, tribal, local and territorial jurisdictions whether they will be promoted.  And so far - with a few notable exceptions - there has been a fair bit of resistance to these recommendations. 

The latest update from the CDC, posted yesterday, follows:


Key Public Health Prevention Recommendations for HPAI A(H5N1)

This document summarizes current key public health prevention recommendations for state, tribal, local, and territorial jurisdictions and provides links to resources for additional information on how to reduce the risk of infection and severe illness from highly pathogenic avian influenza (HPAI) A(H5N1) virus (hereafter “HPAI A(H5N1)”)

Background

  • HPAI A(H5N1) virus is widespread in wild birds worldwide and is causing outbreaks in poultry and U.S. dairy cows, with two recent human cases in U.S. dairy farm workers.
  • Since 1997, more than 900 sporadic human cases of HPAI A(H5N1) have been reported from 23 countries and more than 50% of these human cases have died.
  • CDC is working with the U.S. Department of Agriculture (USDA), the Food and Drug Administration (FDA), the Administration for Strategic Preparedness and Response (ASPR), public health and animal health officials in states, and other partners using a One Health approach to respond to the public health challenge posed by the multistate outbreak of HPAI A(H5N1) in dairy cows and other animals in the United States.
  • While CDC believes the current risk to the general public is low, some people (e.g., those who work with infected or presumed infected animals) are at greater risk of infection and CDC is monitoring for changes that might indicate the potential for increased transmission of the virus to humans or among humans.
  • CDC has recommended that state and local public health agencies monitor people with exposures to infected animals.
  • Information on the current HPAI A(H5N1) situation is available at H5N1 Bird Flu: Current Situation Summary

  • Protecting farm workers
Protecting farm workers

    Monitoring and testing farm workers
    • Monitor workers and other people with direct or close contact with cows, birds, or other domestic or wild animals infected, or potentially infected, with HPAI A(H5N1) viruses to rapidly identify any human cases, provide appropriate treatment, and prevent onward spread.
    • Monitoring is coordinated at the state or local level and should begin with first exposure and continue for 10 days past the last known exposure.
      • CDC will collect weekly aggregate monitoring reports from states and summarize information
    • To determine whether an illness is from HPAI A(H5N1) virus infection, testing of exposed symptomatic people is being done by state or local officials, and CDC conducts confirmatory testing when needed.
    Use of oseltamivir (generic or brand name Tamiflu™) for treatment and post-exposure prophylaxis of human infections


    This guidance is also available as a PDF.



    CDC Summary Analysis On Genetic Sequence From Michigan H5N1 Virus

    Credit NIAID
    Influenza A Virus


     #18,082

    Late yesterday the CDC published their genetic analysis of the virus that was sampled from the Michigan farm worker identified as infected with H5N1 earlier this week.  

    As expected this virus was classified as H5N1 clade 2.3.4.4b and closely aligned with genotype B3.13; nearly identical to the virus detected in dairy cattle and in the Texas human infection. 

    While the HA was identical to the Texas case, there was one notable difference in the PB2 gene. While the Texas case had the PB2 E627K mutation - which is known to enhance viral replication in mammals - the Michigan case did not. 

    Instead, the Michigan virus carried PB2 M631L, which has been detected in nearly all cattle samples (bur rarely in birds), and has been linked to increased replication (in mice) with the H10N7 virus. 

    I would note that Raj Rajnarayanan @RajlabN Assistant Dean of Research and Associate Professor, NYITCOM at Arkansas State University - posted the following on X/Twitter which identifies a second change to the PB2 (PB2 E362G) not mentioned in the CDC analysis. 

     

    No markers for antiviral resistance were detected, and the CDC concludes these results strongly support cow-to-human transmission.  

    That said,  we don't know the significance - or impact - of every amino acid substitution across the entire influenza A genome.  Multiple changes can work in concert to either enhance, or degrade the virus's biological fitness. 

    The full report from the CDC follows:



    Technical Update: Summary Analysis of the Genetic Sequence of a Highly Pathogenic Avian Influenza A(H5N1) Virus Identified in a Human in Michigan
     
    Updated May 24, 2024

    This is a technical summary of an analysis of the genomic sequence of the virus identified in the Michigan case of highly pathogenic avian influenza (HPAI) A(H5N1) virus infection. 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 Michigan (A/Michigan/90/2024) is publicly posted in GISAID (EPI_ISL_19162802) and has been submitted to GenBank.


    May 24, 2024 – CDC has sequenced the influenza virus genome identified in a conjunctival specimen collected from the person in Michigan who was identified to be infected with HPAI A(H5N1) virus and compared each gene segment with HPAI A(H5N1) sequences from cows, wild birds and poultry and the first human case in Texas. 

    The virus HA was identified as clade 2.3.4.4b with each individual gene segment closely related to genotype B3.13 viruses detected in dairy cows available from USDA testing. No amino acid changes were identified in the HA gene sequence from the Michigan patient specimen compared to the HA sequence from the case in Texas and only minor changes were identified when compared to sequences from cows. These data indicate viruses detected in both cows and the two human cases maintain primarily avian genetic characteristics and lack changes that would make them better adapted to infect or transmit between humans. 

    The genome of the human virus from Michigan did not have the PB2 E627K change detected in the virus from the Texas case, but had one notable change (PB2 M631L) compared to the Texas case that is known to be associated with viral adaptation to mammalian hosts, and which has been detected in 99% of dairy cow sequences but only sporadically in birds[i]. This change has been identified as resulting in enhancement of virus replication and disease severity in mice during studies with avian influenza A(H10N7) viruses[ii]

    The remainder of the genome of A/Michigan/90/2024 was closely related to sequences detected in infected dairy cows and strongly suggests direct cow-to-human transmission. Further, there are no markers known to be associated with influenza antiviral resistance found in the virus sequences from the Michigan 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 the HPAI A(H5N1) virus detected in a human in Michigan supports CDC’s conclusion that the human health risk currently remains low. More details of this and other viruses characterized in association with the dairy cow outbreak are available in a previous technical summary.

    [i] Thao-Quyen Nguyen, Carl Hutter, Alexey Markin, Megan Thomas, Kristina Lantz, Mary Lea Killian, Garrett M. Janzen, Sriram Vijendran, Sanket Wagle, Blake Inderski, Drew R. Magstadt, Ganwu Li, Diego G. Diel, Elisha Anna Frye, Kiril M. Dimitrov, Amy K. Swinford, Alexis C. Thompson, Kevin R. Snevik, David L. Suarez, Erica Spackman, Steven M. Lakin, Sara C. Ahola, Kammy R. Johnson, Amy L. Baker, Suelee Robbe-Austerman, Mia Kim Torchetti, Tavis K. Anderson Emergence and interstate spread of highly pathogenic avian influenza A(H5N1) in dairy cattle bioRxiv 2024.05.01.591751; doi: https://doi.org/10.1101/2024.05.01.591751

    [ii]Zhang X, Xu G, Wang C, Jiang M, Gao W, Wang M, Sun H, Sun Y, Chang KC, Liu J, Pu J. Enhanced pathogenicity and neurotropism of mouse-adapted H10N7 influenza virus are mediated by novel PB2 and NA mutations. J Gen Virol. 2017 Jun;98(6):1185-1195. doi: 10.1099/jgv.0.000770. Epub 2017 Jun 8. PMID: 28597818.

    Friday, May 24, 2024

    CDC Influenza A Wastewater Surveillance - May 18th

    #18,081

    The CDC has published an update of their influenza A wastewater surveillance dashboard, which they unveiled early last week.  Once again, this surveillance only checks for influenza A, and does not parse out novel flu subtypes like H5N1. 

    Although there are 689 wastewater treatment plants in their system, only 281 plants have submitted usable data over the past 2 weeks.  Last week, that number was cited as 218 WWTPs, although it appears that more reports were added over the past 7 days.

    We know this because last Friday, 11 plants reported above average levels of influenza A, but a look back at that data set finds that number has increased to 21


    Screen shot of data for week ending 5/11 

    This week's data currently shows 14 WWTPs above average, but that number could rise as more data comes in, meaning comparisons to last week's numbers will need to wait until late next week. 


     Screen Shot of Data for Week Ending 5/18

    The CDC's update follows:|

    Influenza A Virus Wastewater Data

    Updated May 23, 2024

    Main Findings from Wastewater Surveillance

    During the two most recent weeks, (May 5, 2024–May 18, 2024), a total of 281 of 689 sites reported data meeting criteria for analysis for influenza A virus for both weeks or for either week, and 3 (1%) sites from 2 states were at a high level (>80th percentile compared to levels recorded at that site between October 1, 2023 and March 2, 2024).

    Wastewater and the Current Outbreak of Influenza A (H5N1) in birds, cattle, and other animals:Current wastewater monitoring methods detect influenza A viruses but do not determine the subtype. This means that avian influenza A(H5N1) viruses can be detected but would not be distinguished from other influenza A virus subtypes.

    Wastewater testing cannot determine the source of the influenza A virus. It could come from a human or from an animal (like a bird) or an animal product (like milk from an infected cow).

    Public health officials at CDC and state and local health departments are monitoring these data. For areas where influenza A virus levels in wastewater are high, CDC works with relevant partners to better understand the factors that could be contributing to these levels.

    Efforts to monitor influenza A virus activity using wastewater data are likely to evolve as the methodologies and interpretation are evaluated and refined.

    For the latest information on H5N1, and what you can do to protect yourself, visit H5N1 Bird Flu: Current Situation. For the latest information on influenza activity in people, visit the Weekly U.S. Influenza Surveillance Report.
    • Number of Wastewater Sites with Data Meeting Criteria for Analysis Reporting Current High Influenza A Levels in Recent Two Weeks: 3 (1% of Total Sites)
    • Number of Sites with Data Meeting Criteria for Analysis Reporting Influenza A Wastewater Data in Past Two Weeks: 281


    NIH: High H5N1 Influenza Levels Found in Mice Given Raw Milk from Infected Dairy Cows


    Colorized transmission electron micrograph of avian influenza A H5N1 virus
    particles (gold), grown in Madin-Darby Canine Kidney (MDCK) epithelial cells.
    Microscopy by CDC; repositioned and recolored by NIAID. Credit: CDC and NIAID


    #18,080

    Earlier today the New England Journal of Medicine (NEJM) published a correspondence from L. Guan et al. called Cow’s Milk and H5N1 Influenza Virus — Heat Inactivation which assesses both the effect of heat pasteurization of H5N1 contaminated milk, and the health impact (on mice) of consuming contaminated milk. 

    These studies suggest that pasteurization greatly reduces the risk of H5N1 infection, but refrigerated raw milk can contain dangerous levels of the virus for weeks

    All mice fed droplets of infected milk fell ill within a day, and researchers found `. . . high levels of virus in the animals’ nasal passages, trachea and lungs and moderate-to-low virus levels in other organs.'

    While humans are not mice, there is a pretty good chance that consuming raw, H5 contaminated milk, would be a very bad idea.  The NIH, which sponsored this research, published the following news release/summary describing the study in more detail. 

    High H5N1 Influenza Levels Found in Mice Given Raw Milk from Infected Dairy Cows

    May 24, 2024

    Mice administered raw milk samples from dairy cows infected with H5N1 influenza experienced high virus levels in their respiratory organs and lower virus levels in other vital organs, according to findings published in the New England Journal of Medicine. The results suggest that consumption of raw milk by animals poses a risk for H5N1 infection and raises questions about its potential risk in humans.

    Since 2003, H5N1 influenza viruses have circulated in 23 countries, primarily affecting wild birds and poultry with about 900 human cases, primarily among people who have had close contact with infected birds. In the past few years, however, a highly pathogenic avian influenza virus called HPAI H5N1 has spread to infect more than 50 animal species, and in late March, the United States reported a viral outbreak among dairy cows in Texas. To date, 52 cattle herds across nine states have been affected, with two human infections detected in farm workers with conjunctivitis. Although the virus has so far shown no genetic evidence of acquiring the ability to spread from person-to-person, public health officials are closely monitoring the dairy cow situation as part of overarching pandemic preparedness efforts.

    To assess the risk of H5N1 infection by consuming raw milk, researchers from the University of Wisconsin-Madison and Texas A&M Veterinary Medical Diagnostic Laboratory fed droplets of raw milk from infected dairy cattle to five mice. The animals demonstrated signs of illness, including lethargy, on day 1 and were euthanized on day 4 to determine organ virus levels. The researchers discovered high levels of virus in the animals’ nasal passages, trachea and lungs and moderate-to-low virus levels in other organs, consistent with H5N1 infections found in other mammals.

    In addition to the mice studies, the researchers also tested to determine which temperatures and time intervals inactivate H5N1 virus in raw milk from dairy cows. Four milk samples with confirmed high H5N1 levels were tested at 63 degrees Celsius (145.4 degrees Fahrenheit) for 5, 10, 20 and 30 minutes, or at 72 degrees Celsius (161.6 degrees Fahrenheit) for 5, 10, 15, 20 and/or 30 seconds. Each of the time intervals at 63℃ successfully killed the virus. At 72℃, virus levels were diminished but not completely inactivated after 15 and 20 seconds. The authors emphasize, however, that their laboratory study was not identical to large-scale industrial pasteurization of raw milk and reflect experimental conditions that should be replicated with direct measurement of infected milk in commercial pasteurization equipment.

    In a separate experiment, the researchers stored raw milk infected with H5N1 at 4℃ (39.2 degrees Fahrenheit) for five weeks and found only a small decline in virus levels, suggesting that the virus in raw milk may remain infectious when maintained at refrigerated temperatures.

    To date, the U.S. Food and Drug Administration concludes that the totality of evidence continues to indicate that the commercial milk supply is safe. While laboratory benchtop studies provide important, useful information, there are limitations that challenge inferences to real world commercial processing and pasteurization. The FDA conducted an initial survey of 297 retail dairy products collected at retail locations in 17 states and represented products produced at 132 processing locations in 38 states. All of the samples were found to be negative for viable virus. These results underscore the opportunity to conduct additional studies that closely replicate real world conditions. FDA, in partnership with USDA, is conducting pasteurization validation studies – including the use of a homogenizer and continuous flow pasteurizer. Additional results will be made available as soon as they are available.

    The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, funded the work of the University of Wisconsin-Madison researchers.

    ARTICLE:

    G Lizheng et al. Cow Milk Containing H5N1 Influenza Viruses—Heat Inactivation and Infectivity in Mice. The New England Journal of Medicine DOI: 10.1056/NEJMc2405495 (2024).

    WHO:

    NIAID Director Jeanne Marrazzo, M.D., and Lauren Byrd-Leotis, Ph.D., with NIAID’s Division of Microbiology and Infectious Diseases’ Viral Respiratory Diseases Section, are available to discuss the findings.

    WHO/ECDC On 1st H5N6 Human Infection of 2024



    #18,079

    Avian influenza reports out of China have become increasingly scarce,  but today the ECDC is reporting on China's 90th known human H5N6 infection, and the 1st of 2024.  The patient, described as a 52 year-old female living in Fujian Province, was hospitalized on April 22nd, and died 8 days later.

    While I've not seen this case mentioned China's weekly influenza report, or Hong Kong's Weekly avian influenza roundup, is does appear in the latest WHO Western Pacific Regional Office Avian Influenza Weekly Update Number 947, which provides following details.

    Human infection with avian influenza A(H5N6) virus

    Between 10 to 16 May 2024, one new case of human infection with avian influenza A(H5N6) virus was reported to WHO in the Western Pacific Region. The case was a 52-year-old female from Fujian Province in China with the date of onset on 13 April 2024. She was admitted to the hospital on 22 April and diagnosed on 24 April. The case passed away on 30 April.

    Before the onset of illness, the case had exposure to backyard poultry. All samples from close contact and environment have tested negative for influenza.

    To date, a total of 91 laboratory-confirmed cases of human infection with influenza A(H5N6) virus, including 36 deaths (CFR 40%), have been reported to WHO in the Western Pacific Region since 2014. The last case was reported from China, with an onset date of 25 November 2023.


    Today, the ECDC's  Communicable disease threats report, 18-25 May 2024, week 21 carries the following report.

    Avian influenza A(H5N6) – Multi-country – Monitoring human cases

    Overview:

    Update: A new fatal case of avian influenza A(H5N6) has been reported from Fujian Province in China. The patient was a woman in her 50s who had exposure to backyard poultry before the onset of symptoms on 13 April 2024.

    On 22 April, she was hospitalised and two days later diagnosed with avian influenza A(H5N6) infection. The patient died on 30 April 2024. No new cases have been detected among close contacts of the case. Samples from close contacts, poultry and environment tested negative.

    Summary: Since 2014, and as of 21 May 2024, 91 laboratory-confirmed cases, including 36 deaths (CFR: 40%), of human infection with influenza A(H5N6) virus have been reported, including six cases reported in 2023 and one case in 2024 (all from China). The cases were reported from China (90) and Laos (1).

    Sources: WHO Avian influenza weekly update Number 947

    ECDC assessment:

    Sporadic human cases of avian influenza A(H5N6) have been previously observed. No human-to-humantransmission has been reported to date. Sporadic zoonotic transmission cannot be excluded. The implementation of personal protective measures for people directly exposed to poultry and birds potentially infected with avian influenza viruses will minimise the remaining risk. The risk of zoonotic influenza transmission to the general public in EU/EEA countries is considered to be very low. 

    Actions:

    ECDC monitors avian influenza strains through its epidemic intelligence and disease network activities and collaborates with the European Food Safety Authority (EFSA) and the EU reference laboratory for avian influenza to identify significant changes in the epidemiology of the virus. ECDC works with EFSA and the EU reference laboratory to produce a quarterly report on the avian influenza situation. The most recent report was published in March 2024.

    Last time this event was included in the Weekly CDTR: 17 May 2024

    Maps and graphs

    Figure 1. Distribution of confirmed human cases of avian influenza A(H5N6) virus infection by year of onset and country, 2014 - 16 May 2024 (n=91)


    Getting reliable, and timely, information out of China on avian flu has always been difficult, but it has become even more challenging over the past few years.  Reports to the WHO are often delayed, and contain few details. 

    Although the steady decline in reported H5N6 cases since 2021 may indicate fewer actual infections, it is difficult to verify, given the lack of independent reporting in that country. 


    Preprint: Spillover of HPAI H5N1 Virus to Dairy Cattle Led to Efficient Intra - and Interspecies Transmission


    #18,078

    The above map is thought to under-represent the spread, and prevalence of HPAI H5N1 in dairy cattle, as many farmers, and some states, have been reluctant to aggressively test and report cases. Nor does this map indicate how many other animals (cats, raccoons, skunks, etc.) may have been infected by exposure to cattle or cattle products. 

    Similarly, we've seen a reluctance to actively test and report symptomatic human infections, which suggests the number of spillovers into humans may be higher than reported as well. 

    This newfound ability to infect, and efficiently spread between cattle has been attributed to a reassortment event - likely occurring sometime last year in an unknown host - where a novel genotype (B3.13) was generated, and began spreading in birds. 


    Nearly every `great leap forward' by HPAI H5 over the past 20+ years has been preceded by either a reassortment event - or the emergence of a new clade (see EID Journal: HPAI H5N8 In Migratory Birds - Qinghai Lake, 2016). 

    With so much diversity among H5 viruses circulating in the wild, these events are becoming more frequent. 

    Genotype B3.13 is the most recent reassortant to raise concerns, but it is unlikely to be the last. While evolution is rarely linear, B3.13 may become a stepping stone to H5's next `big evolutionary leap'. 

    Only time will tell. 

    Today we've a preprint from researchers at Cornell, Texas A&M, and the USDA which attempts to document and quantify just how big of a leap H5N1 has made as it has spread through American cattle.  And as they say in their wrap-up, it is unprecedented. 

    Given its size (43 page-PDF), and technical nature, I've only posted some excerpts.  Follow the link to read the preprint in its entirety. 

    I'll return with a brief postscript after the break.
    From birds to mammals: spillover of highly pathogenic avian influenza H5N1 virus to dairy cattle led to efficient intra- and interspecies transmission
    Leonardo C Caserta, Elisha A. Frye, Salman L. Butt, Melissa A Laverack, Mohammed Nooruzzaman, Lina M. Covalenda, Alexis Thompson, Melanie Prarat Koscielny, Brittany Cronk, Ashley Johnson, Katie Kleinhenz, Erin E Edwards, Gabriel Gomez, Gavin R. Hitchener, Mathias Martins, Darrell R. Kapczynski, David L. Suarez, Ellen Ruth Alexander Morris, Terry Hensley, John S. Beeby, Manigandan Lejeune, Amy Swinford, Francois Elvinger, Kiril M Dimitrov,Diego G. Diel
    doi: https://doi.org/10.1101/2024.05.22.595317


    Preview PDF

    Abstract

    Infections with the highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b virus have resulted in the death of millions of domestic birds and thousands of wild birds in the U.S. since January, 2022. Throughout this outbreak, spillovers of the virus to mammals have been frequently documented.
    Here, we report the detection of HPAI H5N1 virus in dairy cattle herds across several states in the U.S. The affected cows displayed clinical signs encompassing decreased feed intake, altered fecal consistency, respiratory distress, and decreased milk production with abnormal milk. Infectious virus and RNA were consistently detected in milk collected from affected cows. Viral staining in tissues revealed a distinct tropism of the virus for the epithelial cells lining the alveoli of the mammary gland in cows.
    Analysis of whole genome sequences obtained from dairy cows, birds, domestic cats, and a racoon from affected farms indicated multidirectional interspecies transmissions.
    Epidemiologic and genomic data revealed efficient cow-to-cow transmission after healthy cows from an affected farm were transported to a premise in a different state. These results demonstrate the transmission of HPAI H5N1 clade 2.3.4.4b virus at a non-traditional interface and to a new and highly relevant livestock species, underscoring the ability of the virus to cross species barriers.

              (SNIP) 


    Figure 6. Model of spillover and spread of HPAI H5N1 genotype B3.13 into dairy cattle. A reassortment event in an unknown host species led to the emergence of H5N1 genotype B3.13 which circulated in wild birds and mammals before infecting dairy cattle. Following spillover of H5N1 into dairy cattle, the virus was able to establish infection and efficiently transmit from cow-to-cow (intraspecies transmission) and from cow to other species, including wild (great tailed grackles) and peridomestic birds (pigeons) and mammals (cats and raccoons) (interspecies transmission). Spread of the virus between farms occurred by the movement of cattle between farms, and likely by movement wild birds and fomites including personnel, shared farm equipment and trucks (feed, milk and/or animal trucks).
    (SNIP)

    The ability of HPAI H5N1 clade 2.3.4.4b to cross species barriers has been evident and spillover into mammalian species has been reported throughout the current global outbreak 23,43. Prior to the detection in cattle, however, most mammalian species were considered dead-end hosts,given that virus tropism for the central nervous system commonly resulted in fatal encephalitis 44,45.

    Our epidemiological investigation combined with genome sequence - and geographical dispersal  analysis provides evidence of efficient intra- and inter-species transmission of HPAI H5N1 genotype B3.13. Soon after apparently healthy lactating cattle were moved from Farm 1 to Farm 3, resident animals in Farm 3 developed clinical signs compatible with HPAI H5N1 providing evidence to suggest that non-clinical animals can spread the virus. 
    Analysis of the genetic relationship between the viruses detected in Farms 1 and 3, combined with phylogeographical  modeling indicate that the viruses infecting cattle in these farms are closely related, supporting the direct epidemiological link and indicating long-range viral dispersal and efficient cattle-to-cattle transmission.
    The results from the phylogenomic and phylogeographical analyses in both sites of Farm 2 and on Farms 5, 6 and 7 also indicate regional long-range farm-to-farm spread of the virus.In these cases, fomites such as shared farm equipment, vehicles, or personnel may have played a role in virus spread. 
    The dispersal of virus between Farms 5, 7 and 9 could have been vectored by wild birds; as suggested by the fact that blackbirds found dead near Farm 7 were infected with a  virus closely related to the virus circulating in cattle in these farms. Alternatively, the birds at these premises could have been infected with virus shed by cattle. 
    Our phylogenomic analysis in affected cats (Farms 1, 2, 4, and 5) and the raccoon (Farm 8) combined with epidemiological information revealing the practice of feeding raw milk to cats in these farms indicate cattle-to-cat and cattle398 to-raccoon transmission. These observations indicate that complex pathways underlie the introduction and spread of HPAI H5N1 in dairy farms (Fig. 6), highlighting the need for efficient biosecurity practices and surveillance efforts in affected and non-affected farms.
    The spillover of HPAI H5N1 into dairy cattle and evidence for efficient mammal-to mammal transmission are unprecedented.
    This newly acquired viral property is concerning as it can lead to adaptation of the virus which may further enhance virus infectivity and transmissibility in other species, including humans. Therefore, it is imperative that robust and continuous surveillance and research efforts be established to monitor the circulation, spread, and adaptation of the HPAI H5N1 virus in this new host species.

              (Continue . . . ) 

    While there are no guarantees that H5N1 (regardless of genotype) will spark the next pandemic - or if it happened, how bad it would be - the evidence before us is increasingly hard to ignore.  
    • The H5N1 virus of today is a far cry from the HPAI H5 virus of even 4 years ago, having now spread across 90% of the globe, conquering both North and South America.
    Given the unpredictability of influenza - and the plethora of other threats out there - I might not bet good money on H5N1 sparking the next pandemic.

    But I wouldn't bet against it, either.