#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.
I'll return with a brief postscript after the break.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.
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.
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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.
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.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.
- 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.
- During this time H5N1 has diversified into more than 100 distinct genotypes, with some displaying a predilection for spilling over into a wide range of mammals.
- While the known cases in the U.S. have been mild (so far), this virus has a history of producing severe, and often fatal illness. In recent years it has also become more neurotropic, further increasing the threat (see Cell: The Neuropathogenesis of HPAI H5Nx Viruses in Mammalian Species Including Humans).
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.
